Phototoxicity of phenothiazinium dyes against methicillin-resistant Staphylococcus aureus and multi-drug resistant Escherichia coli.
Photodynamic inactivation (PDI) has been investigated to cope with the increasing incidence of multidrug-resistant (MDR) pathogens. Here we studied the PDI mediated by methylene blue (MB) and toluidine blue O (TBO) in clinical methicillin-resistant Staphylococcus aureus and MDR Escherichia coli, together with their corresponding American Type Culture Collection (ATCC) strains. Effect of photosensitizer concentration (12.5, 25, 50 μg/ml) and laser irradiation time (10, 20 and 30 min) on lethal photosensitization was investigated. TBO was more effective. TBO at 50 μg/ml, 46.8 J cm⁻², exhibited 0.7 log killing for MDR E. coli and 1.7 log killing for E. coli (ATCC 25922); 3.1 log killing for MRSA, and 4.2 log killing for S. aureus (ATCC 25923). MB at 50 μg/ml, 163.8 J cm⁻², only exhibited 2.2 log killing in MRSA and 3.1 log killing in S. aureus (ATCC 25923). MB (50 μg/ml, 163.8 J cm⁻²) induced 0.2 log killing for MDR E. coli and 0.3 log killing for E. coli (ATCC 25922). After TBO-PDI, MDR isolates were more susceptible to some antibiotics than control groups. Our studied clinical isolates were more resistant to PDI-mediated killing than their ATCC reference strains. Thus, TBO/MB-mediated PDI in other MDR isolates deserves further investigation.


Contrasting demography of two Patagonian shrubs under different conditions of sheep grazing and resource supply.
Two shrub species, dominant in western Patagonia, Argentina, exhibited different demographic behaviors under the effect of sheep grazing and of manipulated resource levels. Senecio filaginoides showed an increase in cover under increasing grazing pressures; the rise was explained by an increasing number of individuals and not by larger plants; this trend was reversed when no grazing took place. Mulinum spinosum showed a slight decrease in cover and density at increasing grazing pressures, and no change in plant size. In a field experiment in which water was added (30 mm in early summer) and the dominant grasses removed, both factors substantially augmented the number of 1-year-old seedlings of Senecio recruited; the only noticeable response of Mulinum was an increase in seedling emergence because of grass removal. Six years after this last treatment, Senecio exhibited a ten fold increase in density, and its population structure showed a peak in younger classes; Mulinum remained unaffected. In seedling surveys conducted within an exclsure and in its surroundings, the emergence of Senecio was similar in these areas in the two years of the study, whereas the emergence of Mulinum was higher inside the exclosure for one of the years. The emergence of Senecio in the wetter year was 3 times larger than in the drier one. Grazing did not affect first-year survival of any species; the major source of seedlign death in this case, as well as in the manipulative experiment, was desiccation during summer drought. We conclude that the contrasting responses of the two species to grazing are mostly due to the greater ability of Senecio to benefit from any increase in resources, including those not used by grazed plants. The difference might also be due to a reduction in the seed availability of Mulinum caused by sheep preference for its fruits. The dissimilar abilities of the two shrubs to employ the resources freed by grazing would derive more from their contrasting demographic potential (i.e. the ability to rapidly increase biomass/m2) than from a difference in their niche overlap with palatable species.


[The effect of transversus abdominis plane block for pediatric patients receiving bone graft to the alveolar cleft].
Transversus abdominis plane block (TAP block) is useful for lower abdominal operations. Recently, ultrasound guided nerve block has been performed with ultrasound scanning. We investigated the effectiveness of TAP block in 64 pediatric patients (aged 5-12 years, F/M = 21/43) receiving bone graft from the ilium to the alveolar cleft. We compared the dosages for postoperative analgesics between the groups of TAP block and non-TAP block. In the TAP block group, the frequency of using the postoperative analgesics was lower compared with non TAP block group (P < 0.05). We concluded that TAP block was effective in pediatric patients receiving bone graft to the alveolar cleft.


Effects of leptin treatment and Western diet on wheel running in selectively bred high runner mice.
The role of leptin in regulating physical activity is varied. The behavioral effects of leptin signaling depend on the type of activity and the animal's physiological state. We used mice from lines selectively bred for high voluntary wheel running to further study how leptin regulates volitional exercise. Mice from four replicate high runner (HR) lines typically run ~3-fold more revolutions per day than those from four non-selected control (C) lines. HR mice have altered dopamine function and differences from C in brain regions known to be important in leptin-mediated behavior. Furthermore, male HR mice have been found to dramatically increase running when administered Western diet, an effect possibly mediated through leptin signaling. Male mice from generation 61 (representing three HR lines and one C line) were allowed wheel access at 24 days of age and given either Western diet (high in fat and with added sucrose) or standard chow. After four weeks, Western diet significantly increased circulating leptin, insulin, C-peptide, gastric inhibitory polypeptide, and inflammatory hormone resistin concentrations in HR mice (C mice not measured). Western diet increased running in HR mice, but did not significantly affect running in C mice. During the fifth week, all mice received two days of intra-peritoneal sham injections (physiological saline) followed by three days of murine recombinant leptin injections, and then another six days of sham injections. Leptin treatment significantly decreased caloric intake (adjusted for body mass) and body mass in all groups. Wheel running significantly increased with leptin injections in HR mice (fed Western or standard diet), but was unaffected in C mice. Whether Western diet and leptin treatment stimulate wheel running in HR mice through the same physiological pathways awaits future study. These results have implications for understanding the neural and endocrine systems that control locomotor activity, food consumption, and body weight, and how they may vary with genetic background.


Externalizing disorders in adolescence mediate the effects of maternal depression on substance use disorders.
Maternal depression has been linked to increased risk of substance use disorders (SUDs) in offspring. Cross-sectional studies have identified relationships among maternal depression, externalizing disorders and SUDs, but no longitudinal examination of causality has been undertaken. In order to address this gap in the literature, depression and externalizing disorders at or prior to age 15 were tested as mediators of the relationship between maternal depression and SUDs diagnosed between ages 16 and 20 in a sample of 702 Australian youth (363 women) using path models. Mothers' and fathers' substance diagnoses and earlier onset of substance abuse in youth were controlled for in all analyses. Consistent with previous work, maternal depression predicted SUDs between ages 16 and 20. An indirect effect of maternal depression through youth externalizing disorders diagnosed by age 16 was detected for alcohol and cannabis use disorders, but not drug disorders. Early adolescent depression was not a mediator of the relationship between maternal depression and any of the substance outcomes measured. To our knowledge, this study is the first to examine depression and externalizing disorders in early adolescence as mediators of the effect of maternal depression on psychopathology in later adolescence. Further work is needed to understand how family environment and genetic factors may explain the mediation by externalizing disorders.


Oral Cancer Early Detection--a Pressing Need for Continuing Education in Jordan.
To identify deficiencies in the knowledge of general medical (GMPs) and dental practitioners (GDPs) regarding early detection of oral cancer, to compare differences between subgroups, and to identify educational needs for continuing education courses on this subject. 165 GDPs and 165 GMPs were directly interviewed to assess their knowledge about oral cancer using a pre-tested survey. Knowledge scores were generated from correct responses of participants to factual questions about oral cancer. Few participants (15.2% of GDPs and 12.8% of GMPs) reported that they attended any continuing education courses on oral cancer during their professional career. Most participants (81.6% of GDPs and 86.3% of GMPs) admitted that their knowledge about oral cancer was not up to date and that they would need to attend continuing education courses on oral cancer if available. A few significant differences were identified between groups regarding knowledge about risk factors, clinical presentations and diagnostic techniques but the overall knowledge scores showed no significant difference between GMPs and GDPs. The present study identified several deficiencies in the knowledge of GMPs and GDPs regarding risk factors, clinical presentations, and diagnostic techniques of oral cancer. Interventions to correct these defects through properly designed continuing education courses are required.


Evaluation of postsurgical recurrence in Crohn's disease: a new indication for capsule endoscopy?
Recurrence after surgery to treat Crohn's disease is frequent and unpredictable. The efficacy of postsurgery capsule endoscopy in detecting recurrence in patients with Crohn's disease is yet to be confirmed. To assess the safety, accuracy, and therapeutic impact of capsule endoscopy in these patients. Crohn's disease recurrence at the neoileum (Rutgeers score) was assessed in the patients by colonoscopy and capsule endoscopy. The M2A Patency Capsule (Given Imaging, Yoqneam, Israel) was administered 1 week before capsule endoscopy. Capsule endoscopy was performed within 2 weeks of colonoscopy. Investigators were blinded to the results of each technique. Patient comfort during the procedures was recorded. Twenty-four patients with Crohn's disease with ileocolonic anastomosis were prospectively included. All patients were asymptomatic and did not receive any prophylactic treatment. Neoileum recurrence. A colonoscopy was performed in all patients, although the neoileum could not be reached in 3 of them. M2A Patency Capsule excretion was delayed in 2 patients; thus capsule endoscopy was given only to 22 patients. Recurrence was visualized with colonoscopy in 6 patients and with capsule endoscopy in 5. Ten additional recurrences were visualized only with capsule endoscopy. Moreover, proximal involvement was detected in 13 patients. Therapeutic management was modified in 16 patients. All patients preferred capsule endoscopy. Capsule endoscopy is more effective in the evaluation of recurrence after surgery for Crohn's disease and is better tolerated than colonoscopy. This is of significant therapeutic relevance.


Mesangial proliferative glomerulonephritis in familial Mediterranean fever patient with E148Q mutation: the first case report.
Familial Mediterranean fever (FMF) is an autosomal recessive hereditary disease characterized by recurrent attacks of fever, usually accompanied by sterile polyserositis. Although amyloidosis is the most common renal involvement, non-amyloid renal lesions, such as glomerulonephritis, have been described in patients with FMF. In this report, we present the first case of an FMF patient with heterozygous mutation of E148Q, mesangial proliferative glomerulonephritis, and no amyloidosis. While the association of mutation E148Q with renal involvement is still obscure, colchicine treatment is useful in mesangial proliferative glomerulonephritis with FMF.


Analysis of survival in patients with pulmonary atresia and intact ventricular septum treated surgically.
The epidemiology of 98 children who underwent surgical intervention for pulmonary atresia and intact ventricular septum is presented. Sixty-one (62.2%) of the children died. Survival time from the date of the first operation ranged from 0 to 17.76 years. Analysis of the survivors revealed that an estimate of the probability of surviving for two years is 47% (95% confidence limits of 37%, 57%). An estimate of the median survival time is 1.43 years. In a Cox proportional hazards model, using survival time in days as the outcome variable (n = 73, using complete data), operative weight at first operation (P = 0.0019), right/left ventricular pressure ratio (P = 0.0185), and absence of ventriculo-coronary arterial connections (P = 0.0362) were identified as significant predictors of survival.


Identifying priority areas for freshwater supply conservation integrating multi-scale freshwater flows.
Identifying priority areas for conservation is an effective measurement for the sustainable provision of ecosystem services (ESs) under threats globally. Although many approaches have been developed to identify conservation priority areas by combining supply and demand of ESs, the integration of ESs flows into the identification still need further exploration. For ESs like freshwater supply services, the processes of freshwater flows across multiple scales are crucial. This study aimed to propose a new study framework to identify priority areas for freshwater supply conservation by integrating the multi-scale (i.e., sub-watershed, tributary, and mainstream) freshwater flows, using the Yangtze River Delta as the study area. The results suggested that spatial mismatches between the supply and demand of freshwater supply services existed at different scales. There were approximately 129, 58, and 55 pairs of freshwater flows in sub-watersheds, tributaries, and mainstreams, respectively, which transported 5.98 × 1010 m3, 2.07 × 1010 m3 and 2.50 × 1010 m3 of freshwater. The results of multi-scale freshwater flows were integrated into conservation target goals, and the identified priority areas for freshwater supply conservation were selected at three scales. The priority areas selected at the sub-watershed scale were the largest. Compared with the traditional method of identifying priority areas without considering freshwater flows, the priority areas identified in this study included both sites with a high supply capacity and sites with a relatively low supply capacity, as they were significant for meeting the local freshwater demand. The increasing understanding of freshwater flows and the integration of the flows for the identification of priority areas for freshwater supply conservation are important for the development of more practical and rational policies or ecological management for the sustainable conservation of ESs.


An overview of infection control in dental practice.
Although it is not possible to cover all of the ramifications of infection control in prosthodontics, currently available information may be summarized as follows: 1. All dental disciplines must be concerned with the dangers involved in the spread of certain infectious diseases. 2. Prosthodontists and their ancillary personnel may be exposed to certain diseases predominantly found in adult patients, such as hepatitis B and tuberculosis. 3. Dentists must ensure that at least six basic infection control procedures are observed when treating patients. 4. Additional control procedures should be observed in the fabrication and handling of impressions and dental prosthesis. 5. Dental offices and commercial laboratories should work closely together to coordinate control of potential cross-infection between the two disciplines. The control of infectious diseases in prosthodontics is not difficult. It requires the expenditure of a little time, a little money, and most important, a great deal of discipline. The rewards are well worth the additional effort and could even be lifesaving.


Overall survival in women with breast cancer: the influence of pepsinogen C gene polymorphism.
We aimed to study the role of an insertion/deletion polymorphism in the Pepsinogen C (PGC) gene in the clinical outcome of 172 breast cancer patients. The six polymorphic alleles were amplified using PCR. Our results indicate that patients carrying the allele 6 present a higher 5-year survival mean (83.4% of 6 allele carriers were alive at 5 years vs. only 68.6% of noncarriers, p=0.001), suggesting a role for this polymorphism in the outcome of breast cancer patients. We hypothesize that PGC polymorphism can be a predictive biomarker in breast cancer, contributing to an individual profile of great interest in clinical oncology.


Duodenal G- and D-cell changes following corticosteroid administration. Immunocytochemical long-term study in guinea pigs.
Prednisolone administration in guinea pigs for 20 days induces significant hypergastrinemia and duodenal G-cell hyperplasia. Hypergastrinemia and duodenal G-cell hyperplasia are less prominent following 40 days of prednisolone administration and this could be partly attributed to the duodenal D-cell increased activity, which represents an adaptive response to the alterations of gastric secretory functions induced by corticosteroids.


Influence of saturation deficit and temperature on Ixodes ricinus tick questing activity in a Lyme borreliosis-endemic area (Switzerland).
Questing Ixodes ricinus ticks were sampled monthly in a periurban mixed forest at Neuchâtel, Switzerland, in 1996, 1997, and 1998. A total of 5,530 I. ricinus nymphs and 1,385 adults were collected. The emergence of questing tick populations in spring varied among years in relation to the air temperature. The monthly variation in questing nymph density was negatively correlated with the saturation deficit; there was a strong decrease in tick numbers in late spring and summer as soon as the saturation deficit increased. A variation in tick density in relation to the saturation deficit was also observed between years; the tick density was high when the saturation deficit was low during spring and summer (1997) and was low when the saturation deficit was high (1998). During the 3-year study period, marked climatic differences among years highlighted the influence of temperature and saturation deficit on the phenology of ticks.


Coronary collateral circulation behaviour and myocardial viability in chronic total occlusion treated with coronary angioplasty.
We explored the role of microcirculation integrity following the chronic occlusion of an infarct-related artery to assess the behaviour of collateral circulation during and after reperfusion by coronary angioplasty Eighteen patients with a proximally occluded left anterior descending artery and firm evidence of intercoronary collateral circulation were studied with selective coronary angiography and selective intracoronary myocardial contrast echocardiography, before coronary angioplasty, and at 5 and 15 min and 12 h later. Myocardial enhancement during myocardial contrast echocardiography was evaluated with a semiquantitative score (0-3), which was correlated to basal and 6 months' regional left ventricular wall motion results. 16/18 procedures were successfully performed; four patients with an inadequate acoustic window were excluded. Restenosis was evident at the 6 months' follow-up in two patients. Basal myocardial contrast echocardiography indicated that 81/192 segments from the left anterior descending coronary artery and 90/192 from the right coronary artery were perfused; no perfusion was observed in 21 segments either before or after coronary angioplasty. After coronary angioplasty, the angiographic intercoronary collateral circulation immediately disappeared, and myocardial contrast echocardiography revealed that there was a progressive reduction of segments perfused by the right coronary artery and an increase in segments perfused by the left anterior descending coronary artery. Regional left ventricular wall motion analysis demonstrated that there was abnormal motion in 51/192 segments. There was no improvement in segments with score 0 and abnormal motion after 6 months (100% sensitivity), but 16/17 segments with score 3 did show an improvement (98% specificity). The predictive value of intermediate scores (1-2) in detecting long-term improvement, was only 43%. These data show that the adaptive mechanism observed in the behaviour of epicardial and microvascular circulation after reperfusion of a chronic occluded infarct-related artery can vary. In addition, this study clearly shows that microvascular integrity detected by myocardial contrast echocardiography can provide myocardial viability.


Left coronary cusp ablation for elimination of left ventricular summit premature ventricular complex.
We first reported that epicardial LAVA in the LV summit can be mapped and PVC was completely eliminated by RF ablation above the left coronary cusp using single catheter technique.


Treatment planning of implants in posterior quadrants.
Differences in anatomy and biomechanics make treatment of posterior quadrants with dental implants substantially different to that of anterior areas. Without implants, when posterior teeth were lost, treatment options included a long span fixed partial denture or a removable prosthesis, especially when no terminal abutment was available. Today, with the use of implants, options are available that allow preservation of unrestored teeth.(1) When teeth are missing, implant supported restorations can be considered the treatment of choice from the perspective of occlusal support, preservation of adjacent teeth and avoidance of a removable partial denture.


Analysis and genetic manipulation of Shigella virulence determinants for vaccine development.
Shigellosis is a major public health problem in developing countries. Current epidemics of Shigella dysenteriae serotype 1 strains are particularly serious and are characterized by high mortality rates. A high proportion of the isolates are resistant to many of the antibiotics currently in use in these countries, a feature which seriously compromises clinical treatment of the infections. Efficacious vaccines are thus urgently needed. Basic studies on Shigella virulence factors, infections in laboratory models, and host responses has led to the development of several strategies for the production of vaccines. All of these are live oral vaccines involving bacteria capable of at least limited survival in the animal intestine and of carrying selected antigens to the mucosal immune system. One type of vaccine involves non-pathogenic shigellae, attenuated either by introduction of a requirement for aromatic amino acids (aroD) or by loss of the large plasmid that specifies bacterial invasion of the mucosal epithelium. S. dysenteriae 1 strains under development as vaccines need to be engineered to eliminate high level Shiga toxin production, and a rapid and effective method to achieve this was recently elaborated. The second type of vaccine is represented by hybrid strains consisting of a carrier organism, such as an attenuated Salmonella or an Escherichia coli K-12 strain carrying the Shigella invasion plasmid, and the selected foreign antigen that it produces, in all cases so far the Shigella O antigen polysaccharide.


Effect of statins on pulmonary function in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis of randomized controlled trials.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease, and its treatment is still controversial. Statins have been proven to have anti-inflammatory and immunomodulatory effects, but their effectiveness in the treatment of COPD is still unclear. We conducted this meta-analysis to more accurately evaluate the therapeutic effect of statins on COPD patients. Randomized controlled studies published in PubMed, Cochrane Library, Embase, Wiley Online Library, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang databases from inception to July 2022 were retrieved to evaluate the effect of statins on COPD patients. Two evaluators conducted literature screening based on inclusion and exclusion criteria, and conducted a bias risk assessment on them. Meta analysis was conducted using Stata17.0 statistical software. A total of 1,463 patients from 10 studies were included. After statin treatment, the percentage of predicted forced expiratory volume in the first second (FEV1%pred) of COPD patients was improved [weighted mean difference (WMD): 7.89; 95% confidence interval (CI): 7.19-8.60; P<0.05], and the level of the inflammatory factor C-reactive protein (CRP) decreased (WMD: -0.63; 95% CI: -1.84, 0.58; P<0.05). The 6-minute walking distance (6MWD) of patients in the statin treatment group demonstrated a significant benefit (WMD: 26.27; 95% CI: 24.02-28.51; P<0.05). Compared to the placebo control group, statins significantly reduced COPD Assessment Test (CAT) (WMD: -2.45; 95% CI: -3.62, -1.27). Preliminary evidence suggests that statins may have a certain effect on improving lung function, reducing inflammatory factor levels, and improving clinical symptoms in COPD patients. However, due to the quality and quantity limitations of the included studies, these results need to be further verified through a larger, higher quality randomized controlled trial (RCT).


Leukaemic transformation of engrafted bone marrow cells.
Recurrent leukaemia following bone marrow transplantation is most often due to the regrowth of original host leukaemia cells, but may also be due to the malignant transformation of normal donor marrow cells after transplantation into a leukaemia patient. We report the ninth case of malignant change in cells of donor origin in a 12-year-old boy who was originally diagnosed as having Ph1+ CML. He remained Ph1+ during lymphoid blast crisis. After transplantation with marrow from a cytogenetically normal sister, he relapsed to Ph1- ALL in the female donor cells. The marrow showed a mixed karyotype of 46,XX/46,XX,inv(9)(p12q12). It would appear that, haematologically, the patient showed different manifestations of the same disease state. Cytogenetically, however, the pre- and post-transplant leukaemias were different.


Combined effect of obesity and low physical performance on the incidence of hypertension in Chinese community-dwelling older population.
The combination of having a low physical performance and obesity results in a vicious cycle, but the effect of this combination on the incidence of hypertension is still unknown. This article aims to examine the effect of obesity and low physical performance on the incidence of hypertension in older adults. The sample was comprised of 349 Chinese community-dwelling participants (199 women; mean age 66.30 ± 5.78 years) without hypertension at baseline. Obesity was defined as having a body mass index (BMI) greater than or equal to 28 kg/m2. Participants scoring in the top 20% on the Timed Up and Go Test (TUGT) or in the slowest 20% of the 4-m walking test were defined as having a low physical performance. The outcome was new onset hypertension at the 1-year follow-up. We found that 89 (25.5%) of the 349 participants without hypertension at baseline had developed hypertension at their 1-year follow-up. After multivariate adjustments, it was found that the incidence of hypertension was associated with the combination of obesity and having a low physical performance (OR = 7.30, 95% CI = 1.36-39.11), but not solely with obesity (OR = 1.40, 95% CI = 0.68-2.88) or solely with low physical performance (OR = 0.98, 95% CI = 0.29-3.27). Hence, although obesity and low physical performance did not independently affect the incidence of hypertension after one year, the combination of the two can significantly increase the incidence of hypertension in Chinese community-dwelling older adults.


Increased insulin circulating levels induced by canatoxin in rats.
Canatoxin, a proteic neurotoxin from Canavalia ensiformis seeds, raises circulating insulin levels and induces hypoglycemia in rats. The hyperinsulinemia produced by canatoxin (6 micrograms kg-1, 20 min; 108% of increase in female rats) was both time and dose dependent and lasted only about 30 min, while the fall in blood glucose levels (around 30%) was long lasting. The hyperinsulinemic response to canatoxin was greater in females (+108 +/- 18%) than males (+43 +/- 8%), but no difference was noted in the hypoglycemia. Pretreatment of rats with either naloxone, naltrexone, atropine or hexamethonium abolished both the hyperinsulinemia and the hypoglycemia. These data suggest that these phenomena are influenced by opioids and depend on parasympathetic stimulation.


Global tracking in human gliomas: a comparison with established tracking methods.
Global tracking (GT) is a recently published fibre tractography (FT) method that takes simultaneously all fibres into account during their reconstruction. The purpose of this study was to compare this new method with fibre assignment by continuous tracking (FACT) and probabilistic tractography (PT) for the detection of the corticospinal tract (CST) in patients with gliomas. Tractography of the CST was performed in 17 patients with eight low grade and nine anaplastic astrocytomas located in the motor cortex or the corticospinal tract. Diffusions metrics as fractional anisotropy (FA), mean (MD), axial (AD) and radial diffusivity (RD) were obtained. The methods were additionally applied on a physical phantom to assess their accuracy. PT was successful in all (100 %), GT in 16 (94 %) and FACT in 15 patients (88 %). The case where GT and FACT, both, missed the CST showed the highest AD and RD, whereas the one where FACT algorithm, alone, was not successfully showed the lowest AD and RD of the group. FA was reduced on the pathologic side (FApath 0.35 ± 0.16 (mean ± SD) versus FAcontralateral 0.51 ± 0.15, pcorr < 0.03). RD was increased on the pathologic side (RDpath 0.67 ± 0.29 × 10(-3) mm(2)/s versus RDcontralateral 0.46 ± 0.08 × 10(-3) mm(2)/s, pcorr < 0.03). In the phantom measurement, only GT did not detect false positive fibres at fibre crossings. PT performed well even in areas of increased diffusivities indicating a severe oedema or disintegration of tissue. FACT was also susceptible to a decrease of diffusivities and to a susceptibility artefact, where GT was robust.


Geographic differences in the use of Veterans Administration hospitals.
This study contrasts the determinants of community hospital utilization with Veterans Administration (VA) hospital utilization using traditional planning variables. The comparisons had some expected and some unanticipated findings. Regional differences in non-VA hospital admissions and bed days are fairly well explained by measures of medical need, provider supply, community alternatives, and sociodemographic characteristics (other than those used as proxies for case mix). However, regional variations in the VA are explained less well by the same classes of variables and the unexplained differences between the two systems do not correspond geographically. This suggests that the two systems have different reasons for regional variation. Further, contrary to expectation, when other predictors are held constant, excess bed capacity in the area does not correlate with lower VA utilization. The study is important as the VA comes under increasing pressure to contain costs. It may well be that the rational planning model attributed to the public sector is less likely to overcome maldistribution than the private sector 'invisible hand'. Policy analysts need to give more attention to the political, bureaucratic determinants of resource allocation before changing eligibility criteria or merging the two systems.


Area-level deprivation and preterm birth: results from a national, commercially-insured population.
Area-level deprivation is associated with multiple adverse birth outcomes. Few studies have examined the mediating pathways through which area-level deprivation affects these outcomes. The objective of this study was to investigate the association between area-level deprivation and preterm birth, and examine the mediating effects of maternal medical, behavioural, and psychosocial factors. We conducted a retrospective cohort study using national, commercial health insurance claims data from 2011, obtained from the Health Care Cost Institute. Area-level deprivation was derived from principal components methods using ZIP code-level data. Multilevel structural equation modeling was used to examine mediating effects. In total, 138,487 women with a live singleton birth residing in 14,577 ZIP codes throughout the United States were included. Overall, 5.7% of women had a preterm birth. In fully adjusted generalized estimation equation models, compared to women in the lowest quartile of area-level deprivation, odds of preterm birth increased by 9.6% among women in the second highest quartile (odds ratio (OR) 1.096; 95% confidence interval (CI) 1.021, 1.176), by 11.3% in the third highest quartile (OR 1.113; 95% CI 1.035, 1.195), and by 24.9% in the highest quartile (OR 1.249; 95% CI 1.165, 1.339). Hypertension and infection moderately mediated this association. Even among commercially-insured women, area-level deprivation was associated with increased risk of preterm birth. Similar to individual socioeconomic status, area-level deprivation does not have a threshold effect. Implementation of policies to reduce area-level deprivation, and the screening and treatment of maternal mediators may be associated with a lower risk of preterm birth.


The outlook for linkage research in psychiatric disorders.
Analysis of the distribution of diagnoses in families (segregation analysis) has not, so far, advanced us toward the goal of resolving the inheritance of the major psychiatric disorders. Recent advances in genetics, particularly the development of new molecular genetic linkage methods, have made it, at least theoretically, feasible to scan the entire human genome, so that in a properly designed and executed set of studies it will be possible to demonstrate whether there exists single locus transmission for a particular disorder, and to map the locus. We present here an analysis of feasibility of moderate-sized pedigrees (approximately 15 persons, two generations) and affected-sib-pair sets in such studies. Eight to ten moderate-sized pedigrees are sufficient to perform definitive mapping under the tested conditions, of recessive or additive inheritance, low penetrance of the heterozygote, and a genetically homogeneous disorder. The affected-sib-pair method required 25 pairs of sibs to detect linkage under such conditions in a recessive model, and 45 in a dominant model. When there is genetic heterogeneity, moderate-sized pedigrees are much less useful, but the affected-sib-pair method retains considerable power.


Coconut shell biochar application in liquid-solid microextraction of triazine herbicides from multi-media environmental samples.
A rapid, fast, widely applicable liquid-solid microextraction and purification method of triazine herbicides (TRZHs) in muti-media samples using salting-out assisted liquid-liquid extraction (SALLE) combined with self-assembled monolithic spin columns-solid phase micro extraction (MSC-SPME) was developed. Environmentally friendly coconut shell biochar (CSB) was used as the adsorbents of MSC-SPME. Ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was the separation and determination method. The adsorption kinetics and isotherms were investigated to indicate the interaction between CSB and TRZHs. Several parameters influencing the liquid-solid microextraction efficiency, such as sample pH, salting-out solution volume and pH, sample loading speed, elution speed, elution ratio and volume of eluent were systematically investigated with the aid of orthogonal design. The whole extraction process was operated within 10 min. Under the optimum extraction and determination conditions, good linearities for three TRZHs were obtained in a range of 0.10-200.00 ng mL-1, with linear coefficients (R2) greater than 0.999. The limits of detection (LODs) and limits of quantification (LOQs) were in the range of 6.99-11.00 ng L-1 and 23.33-36.68 ng L-1, respectively. The recoveries of the three TRZHs in multi-media environmental samples were ranged from 69.00% to 124.72%, with relative standard deviations (RSDs) lower than 0.43%. This SALLE-MSC-SPME-UPLC-MS/MS method was successfully applied to the determination of TRZHs in environmental and food samples and exhibited the advantages of high efficiency and sensitivity, low cost, and environmental friendliness. Compared with the methods published before, CSB-MSC was green, rapid, easy-operated, and reduced the whole cost of the experiment; SALLE combined MSC-SPME eliminated the matrix references effectively; what's more, the SALLE-MSC-SPME-UPLC-MS/MS method could be applied to various sample without complicated sample pretreatment procedure.


Three-dimensional finite element analysis of strength, stability, and stress distribution in orthodontic anchorage: a conical, self-drilling miniscrew implant system.
The aims of this study were to analyze the stress distribution and displacement patterns that develop in an orthodontic miniscrew implant and its surrounding osseous structures for 2 implant materials under horizontal and torsional loading, with no ossseointegration. A numeric approach was adopted. The finite element method was used to determine the stress and displacement of the various components at a given time after miniscrew implant application, when, due to viscoelastic relaxation effects, the only remaining stress field was from the application of the orthodontic load. Stress distribution was not significantly different between the 2 types of implant material. Increased stress values were located at the necks of the implants and the surrounding cortical bone. Bending of the titanium miniscrew was observed in the neck region under horizontal traction. The differences between the values of stress and displacement we obtained for the 2 types of miniscrew were too small to be clinically significant. Optimization of the miniscrew implant composed of the titanium alloy might be achieved by increasing the bulk (quantity) of the material in the neck region. The miniscrew implant can be immediately loaded and used for group movement of teeth.


Serving on a Board of Nursing: Pursuing Justice, Mercy, and Humility.
What is it like to serve on a State Board of Nursing (BON)? How does one deal with the weight of the responsibility, the discomfort of inexperience in the role, and integrate personal faith with the professional expectations of administering justice and discipline? The author defines the patients cared for in the BON role and the balance of discipline with care for nurses.


Pyoderma gangrenosum after colectomy for inflammatory bowel disease. Case report.
Pyoderma gangrenosum appeared parastomally after proctocolectomy and ileostomy for ulcerative colitis in two patients. The cases are described and diagnosis and treatment are discussed.


Spatially restricted microRNA directs leaf polarity through ARGONAUTE1.
Gene regulation by RNA interference requires the functions of the PAZ domain protein Argonaute. In plants, mutations in ARGONAUTE1 (AGO1) are associated with distinctive developmental defects that suggest a role for microRNA (miRNA) in organ polarity. Potential targets of miRNA regulation are the homeodomain/leucine zipper genes PHABULOSA (PHB) and PHAVOLUTA (PHV). These genes are expressed in a polar fashion in leaf primordia and are required for adaxial cell fate. Here we show that a 21-nucleotide miRNA that directs cleavage of PHB/PHV messenger RNA accumulates first in the embryonic meristem, and then in the abaxial domain of the developing leaf. miRNA distribution is disrupted by mutations in AGO1, indicating that AGO1 affects the regulation of miRNA. In addition, interactions between homeodomain/leucine zipper genes and an allelic series of ago1 indicate that miRNA acts as a signal to specify leaf polarity.


Lymphocyte targeting with 111In-labelled monoclonal antibodies.
In vitro tests were conducted using human T and B cell lines, as well as whole blood, to establish the usefulness of 2 murine monoclonal antibodies (MAbs), an anti-CD5 (Pan T) and a Pan B, for potential radioimmunolocalization and therapy. Both MAbs showed specificity for the cell line in question as tested by indirect immunofluorescence and radioimmunoassay. Assays carried out on whole blood showed 40-70% of the added activity of 111In-labelled Pan B antibody binding to B cells and 20-24% of 111In-Pan T antibody binding to T cells. The amount of internalised 111In-labelled Pan B was 6% of total amount at 24 hr indicating a slow internalisation process. These results should allow for in vivo targeting of normal and neoplastic B and T cells.


Cloning of the murine cDNA encoding VDJP, a protein homologous to the large subunit of replication factor C and bacterial DNA ligases.
A putative full-length 1.7-kb cDNA, encoding a murine protein that specifically binds to the nonamer portion of the V(D)J recombinational signal sequence (RSS) element, has been cloned. By its sequence analysis, this cDNA is identical to a portion of the 4.5-kb murine replication factor C large-subunit-encoding cDNA. By Northern blot analysis, the 1.7-kb mRNA species is observed in murine immature B cells but not in non-lymphoid cells and tissues, while the 4.5-kb replication factor C-encoding cDNA is expressed in all cell types. The deduced VDJP amino-acid sequence includes a region of homology with bacterial DNA ligases at the C terminus of each of the proteins. VDJP has been synthesized as a fusion protein in bacteria, and the purified protein has been previously shown to mediate the joining of DNA fragments in a V(D)J RSS-dependent fashion (Guilliams et al., Biochem. Biophys. Res. Commun. 202 (1994) 1134-1141).


Fertility-related considerations in endometriosis.
Endometriosis and infertility often present together but the exact cause-effect mechanism of this association is unknown. Though there are several proposed mechanisms regarding the pathophysiology of endometriosis-related infertility, no one theory is universally accepted. Surgical exploration is gold standard for diagnosis but imaging modalities especially specialized ultrasonography and magnetic resonance imaging can highlight disease burden and aid in planning for surgical excision. Overall, medical therapy is ineffective for endometriosis-related infertility; however, surgery may be fertility enhancing in women with minimal stage disease and in women with large endometriomas. Assisted reproductive technology may be required with endometriosis-related infertility. Medically induced superovulation with intrauterine insemination is typically the first line; however, women with advanced disease may need a more aggressive form of treatment with in vitro fertilization.


Ultrasensitive photoelectrochemical microcystin-LR immunosensor using carboxyl-functionalized graphene oxide enhanced gold nanoclusters for signal amplification.
An ultrasensitive photoelectrochemical (PEC) immunosensor based on gold nanoclusters (AuNCs) with 11-mercaptoundecanoic acid (MUA) ligands was fabricated for determination of microcystin-LR (MC-LR). The PEC immunosensor was developed by loading the monoclonal MC-LR antibody (Ab) to the MUA-AuNCs modified gold electrodes. After different measurement conditions being optimized, silver nanoparticles (AgNPs), gold nanorods (AuNRs), graphene oxide (GO) and carboxyl-functionalized graphene oxide (cGO) were introduced into MUA-AuNCs to enhance the sensing properties. The experimental result revealed that the sensitivity of PEC immunosensors was enhanced by both their photoelectrochemical properties and antibody loading properties with dependent relationship, which was different from the enhancement strategy of PEC sensors based on redox reactions. Among different hybrid nanocomposites, MUA-AuNCs/cGO not only improved the photoelectrochemical properties, but also loaded more antibodies for sensing, which resulted in best sensing performance. Thus, a universal method was proposed to enhance the sensing performance of PEC immunosensors based on impedance changes. Finally, MUA-AuNCs/cGO based PEC immunosensors exhibited a wide linear range of 0.001 nM-1000 nM with low detection limit of 0.011 pM (S/N = 3) for MC-LR determination. Meanwhile, the designed PEC immunosensors showed high selectivity, reproducibility and specificity, which provided the promising applications in aquatic environment.


[Friedrich Theodor Althoff (1859-1908) and the German universities around 1900].
Usually the diplomat Wilhelm von Humboldt (1767-1835) is regarded as the creator of German supremacy in academic, especially medical education. Actually this role was played by the "bureaucrat" Friedrich Althoff (1839-1909), who directed German education from 1882 to 1907. His greatest accomplishment was the selection of the best professors.


Reactivity of Diphenylberyllium as a Brønsted Base and Its Synthetic Application.
Diphenylberyllium [Be3 Ph6 ] is shown here to react cleanly as a Brønsted base with a vast variety of protic compounds. Through the addition of the simple molecules tBuOH, HNPh2 and HPPh2 , as well as the more complex 1,3-bis-(2,6-diisopropylphenyl)imidazolinium chloride, one or two phenyl groups in diphenylberyllium were protonated. As a result, the long-postulated structures of [Be3 (OtBu)6 ] and [Be(μ-NPh2 )Ph]2 have finally been verified and shown to be static in solution. Additionally [Be(μ-PPh2 )(HPPh2 )Ph]2 was generated, which is only the second beryllium-phospanide to be prepared; the stark differences between its behaviour and that of the analogous amide were also examined. The first crystalline example of a beryllium Grignard reagent with a non-bulky aryl group has also been prepared; it is stabilised with an N-heterocyclic carbene.


Mapping the body: tracing the personal and the political dimensions of HIV/AIDS in Khayelitsha, South Africa.
This article offers an analysis of the body-mapping dimension of the 'treatment literacy' initiatives of the Treatment Action Campaign (TAC), an HIV/AIDS-focused social movement in South Africa. It situates body mapping within the politics of HIV/AIDS activism in South Africa. The alliance between activists and biomedical practitioners is explored and the emphasis on the 'science of HIV' in TAC treatment literacy considered alongside the foregrounding of social realities, such as poverty and inequality. The article argues that the education activities of the TAC illustrate 'context-sensitive' science, rather than following a linear model of 'public understanding of science'. The personal accounts published alongside the first body maps are explored to illustrate an evident re-socialisation of biological organs and an emphasis on the relationality of bodies. The bounded bodies and the activist emphasis on body politics become ways to counteract fears of the virulence of the illness.


Inhibition of (Na+ + K+)-ATPase by ouabain: involvement of calcium and membrane proteins.
Treatment of plasma membrane isolated from murine plasmocytoma MOPC 173 with an EDTA-containing buffer resulted in a 300-fold increase in sensitivity of (Na+ + K+)-stimulated Mg2+-ATPase to ouabain. This phenomenon was associated with the solubilization by EDTA of phospholipid free proteins (approx. 30 000-34 000 daltons) from the cytoplasmic face of the plasma membrane and with removal of about 90% of the membrane bound Ca2+. The recovery of the original resistance to ouabain required specifically Ca2+ and was associated with a binding of the solubilized proteins to the membrane.


Exploring outdoor activity limitation (OAL) factors among older adults using interpretable machine learning.
The occurrence of outdoor activity limitation (OAL) among older adults is influenced by multidimensional and confounding factors associated with aging. The aim of this study was to apply interpretable machine learning (ML) to develop models for multidimensional aging constraints on OAL and identify the most predictive constraints and dimensions across multidimensional aging data. This study involved 6794 community-dwelling participants older than 65 from the National Health and Aging Trends Study (NHATS). Predictors included related to six dimensions: sociodemographics, health condition, physical capacity, neurological manifestation, daily living habits and abilities, and environmental conditions. Multidimensional interpretable machine learning models were assembled for model construction and analysis. The multidimensional model demonstrated the best predictive performance (AUC: 0.918) compared to the six sub-dimensional models. Among the six dimensions, physical capacity had the most remarkable prediction (AUC: physical capacity: 0.895, daily habits and abilities: 0.828, physical health: 0.826, neurological performance: 0.789, sociodemographic: 0.773, and environment condition: 0.623). The top-ranked predictors were SPPB score, lifting ability, leg strength, free kneeling, laundry mode, self-rated health, age, attitude toward outdoor recreation, standing time on one foot with eyes open, and fear of falling. Reversible and variable factors, which are higher in the set of high-contribution constraints, should be prioritized as the main contributing group in terms of interventions. The integration of potentially reversible factors, such as neurological performance in addition to physical function into ML models, yields a more accurate assessment of OAL risk, which provides insights for targeted, sequential interventions for older adults with OAL.


Thyroid Bethesda Atypia of Undetermined Significance or Follicular Lesion of Undetermined Significance (AUS/FLUS): A Heterogenous Group.
The Bethesda system of reporting thyroid cytopathology (BSRTC) was introduced in 2007. The third category of atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) poses difficulties for the pathologist, and different papers have been published varying the risks of malignancy. (1) Evaluation of the cytological features of thyroid lesions according to BSRTC. (2) After resection, correlation with histopathological report to evaluate the risk of malignancy (ROM) and the risk of neoplasm (RON). (3) Division of category III into six subgroups based on cytological findings and assessment of ROM and RON. A total of 282 patients with diagnosed thyroid lesions underwent fine-needle sampling under ultrasound guidance. Smears were prepared and stained with May-Grunwald-Giemsa stain and Papanicolaou stain. Of 282 cases, there were 9 cases (3.1%) of category I, 157 cases (55.8%) of category II, 24 cases (8.5%) of category III, 20 cases (7.1%) of category IV, 14 cases (4.8%) of category V, and 58 cases (20.7%) of category VI. The RON was 60, 17.1, 63.1, 77.7, 91.7, and 98.2% and the ROM was 60, 14.3, 26.3, 38.9, 91.7, and 96.3% in categories I, II, III, IV, V, and VI, respectively. The RON was 0, 75, 50, 100, 66.6, and 100% and the ROM was 0, 25, 50, 100, 16.6, and 0% in subgroups 1, 2, 3, 4, 5, and 6, respectively. We have proposed a system of subgrouping AUS/FLUS that may help to dispel the confusion generated by an AUS/FLUS report, and provide with a more exact and reproducible diagnostic and prognostic tool.


Synthesis of Disaccharide Nucleosides Utilizing the Temporary Protection of the 2',3'-cis-Diol of Ribonucleosides by a Boronic Ester.
Disaccharide nucleosides are an important class of natural compounds that have a variety of biological activities. In this study, we report on the synthesis of disaccharide nucleosides utilizing the temporary protection of the 2',3'-cis-diol of ribonucleosides, such as adenosine, guanosine, uridine, 5-metyluridine, 5-fluorouridine and cytidine, by a boronic ester. The temporary protection of the above ribonucleosides permits the regioselective O-glycosylation of the 5'-hydroxyl group with thioglycosides using a p-toluenesulfenyl chloride (p-TolSCl)/silver triflate (AgOTf) promoter system to afford the corresponding disaccharide nucleosides in fairly good chemical yields. The formation of a boronic ester prepared from uridine and 4-(trifluoromethyl)phenylboronic acid was examined by ¹H, 11B and 19F NMR spectroscopy.


Response of the human testis to long-term estrogen treatment: morphology of Sertoli cells, Leydig cells and spermatogonial stem cells.
The present investigation is concerned with the morphological changes observed in human testicular tissue following prolonged estrogen administration. Testicular material obtained from 11 transsexual patients who had been submitted to long-term estrogen treatment prior to sex-reversal surgery was studied by means of light- and electron microscopy. The testes of all patients examined present a more or less uniform appearance: There are narrow seminiferous cords surrounded by an extensively thickened lamina propria. They contain Sertoli cells and spermatogonia exclusively. There is no evidence of typical Leydig cells. The persisting spermatogonia show the characteristic features of pale type-A spermatogonia, whereas dark type-A spermatogonia are almost completely eliminated from the epithelium. In view of the fact that spermatogonia that survived radiotherapy and treatment with various noxious agents have recently been regarded as the stem cells of the human testis, it is suggested that also the majority of those spermatogonial types that are less sensitive to disturbances of the endocrine balance may consist of stem cells. The present results, therefore, corroborate the concept that the stem cells of the human testis may be derived from pale type-A spermatogonia or the variants of this cell type. Sertoli cells display two types of ovoid nuclei. In contrast to untreated material the nuclei lie adjacent to the basal lamina, and organelles and telolysosomes are confined to the apical cytoplasm. The apico-basal differentiation of mature cells, therefore, is not observed. Moreover, typical organelles and inclusions of mature cells are absent, as are the junctional specializations. Thus, Sertoli cells have transformed into immature cells, resembling precursors prior to puberty. Fibroblast-like cells in the interstitial tissue, which display strongly lobulated nuclei, a well-developed smooth endoplasmic reticulum, lipid droplets, and numerous inclusions are assumed to represent dedifferentiated Leydig cells. Since after estrogen treatment serum testosterone and gonadotropin levels are known to be reduced, it appears that the morphological changes correlate well with the endocrine status.


Comparison of isolated outer hair cells from five mammalian species.
Live outer hair cells were isolated from guinea pig, chinchilla, rat, mouse, and gerbil. The organ of Corti from selected turns of the cochlea was briefly incubated with collagenase and outer hair cells were separated from the tissue by micromanipulation under microscopic observation. Morphological criteria for cell viability were: cylindrical cell shape without swelling or distortion of the membrane; location of the nucleus in its normal position near the base of the cell; cytoplasm devoid of Brownian motion and granulation. Both yield and quality (as judged by these morphological criteria) of isolated hair cells varied with the species and the turn from which the isolation was attempted. Consistently high yields and cells of good morphology were obtained from guinea pigs and chinchillas. Fewer cells were obtained from rats and mice, and their quality was less consistent. Gerbils gave the poorest yield and quality of outer hair cells. In all species, the preparation was more successful from the apical than from the basal turn. The length of apical hair cells varied almost 4-fold from 60 to 80 microns in guinea pig and chinchilla to 20 to 40 microns in the other species, while their diameter only varied 1.5-fold from 7 (mouse) to 10 microns (chinchilla). Outer hair cells could be maintained in vitro in good condition for several hours. Typical early signs of degeneration were increased Brownian motion and granulation in the cytoplasm, upward movement of the nucleus, or distortion of cell shape. Degeneration was always accompanied by a shortening along the long axis.


Changes in surgical principles as a result of modern, effective, perioperative treatments
Oncology has evolved to a great extent over the last quarter of century. The significant success is multifactorial, including primary and secondary prevention, the development of diagnostics, new methods of chemo-and radiotherapy, and the integration of basic research results into practice. From the point of view of surgery, the establishing and widespread practical application of the principles of preoperative oncotherapy played a major role in this development. Between 1997 and 2005, 44 patients with gastric cancer and 102 patients with borderline resectable or irresectable esophageal cancer received perioperative treatment at the Department of Surgery of the University of Pecs. The response rate was above 50% in both groups and complete pathological remission was achieved in 3 patients with gastric cancer and 17 patients with esophageal cancer. Based on our own experience and literature data, the development of seven new principles in surgical oncology were observed as the result of a very successful preoperative oncologic treatment. The desired free resection margin was reduced to the millimeter dimension in many cancer cases. Thus so-called organ-preserving procedures were made possible. Regarding the prognosis, the stage after the treatment became determinant. Complete histopathological remission could also be achievable in patients with oligometastases. In the case of a complete remission, the watch and wait tactics emerged as an option. Along the preoperative treatment of resectable colorectal liver metastases, there is no need to strive for complete remission. The treatment order of the primary tumor and its metastases can be reversed. Based on the improving results of oncology treatments, a reduction in surgical activity in the treatment of cancer patients is expected.


Effect of preoperative chemotherapy on survival of patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.
To determine the effect of preoperative chemotherapy on survival in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes. We retrospectively analyzed 55 consecutive patients who received radical nephroureterectomy with or without preoperative chemotherapy for upper urinary tract urothelial carcinoma clinically involving regional lymph nodes at a single institution between January 1991 and December 2013. Median follow up was 18 months (range 2-193). Of 55 patients, 24 (43.6%) received preoperative chemotherapy (study group) and 31 (56.4%) underwent primary surgery (control group). Preoperative chemotherapy consisted of two to four cycles (median 3) of cisplatin-containing regimens. The fraction of patients with lower pathological T stage and N stage than clinical T stage and N stage was higher in the study group (29.2% and 54.2%) compared with the control group (3.2% and 16.1%; P = 0.013 and 0.010, respectively). The 5-year overall survival rate was significantly higher in the study group than in the control group (44.0% vs 12.9%, log-rank, P = 0.003). In multivariate analysis incorporating age at diagnosis, Eastern Cooperative Oncology Group Performance Status, clinical N stage and the number of removed lymph nodes, preoperative chemotherapy was a predictor of better overall survival (P = 0.047, HR 0.47, 95% CI 0.22-0.99). Preoperative chemotherapy might provide better survival outcomes in patients with upper urinary tract urothelial carcinoma clinically involving regional lymph nodes.


Rapid reviews: A critical perspective.
The high scientific uncertainty of many far-reaching and serious political decisions during the "coronavirus crisis" underpins the enormous importance of having evidence syntheses that are quickly available and at the same time reliable. As these requirements can only be insufficiently fulfilled by systematic reviews due to the high amount of time required, abbreviated evidence syntheses in the form of rapid reviews are becoming increasingly popular. This commentary aims to enhance methodological and methodical discussions and research about abbreviated evidence syntheses. A selective literature search and evaluation focussing on research dealing with rapid reviews. In rapid reviews, a wide variety of methods can be used to speed up the process of literature search and evaluation, while at the same time maintaining the principles of methodological quality and transparent reporting. But do rapid reviews currently keep what they promise? We discuss the increasing trend towards rapid reviews, giving the currently available evidence on the topic some critical reflection. Following this discussion, we will finally derive demands that go beyond the topic of rapid reviews alone.


Neck dissection of level IIb: is it really necessary?
To determine whether resection of level IIb is necessary in elective or therapeutic neck dissections. Prospective case series. Level IIb nodes were analyzed for micrometastases as separate specimens in 160 neck dissections on 148 patients with squamous cell carcinoma of the head and neck. In 106 elective neck dissections (N0 necks) from upper aerodigestive tract (UADT) and skin/parotid squamous carcinoma primaries, level IIb was involved in 4.5% and 33%, respectively. In 54 therapeutic neck dissections (N+ necks) from UADT and skin/parotid squamous carcinoma primaries, level IIb was involved in 25% and 71%, respectively. Apart from skin/parotid squamous carcinoma primaries, level IIb was never involved unless level IIa was also involved. Level IIb nodes can be left in situ in UADT primary carcinomas in nontonsillar N0 necks without significantly compromising regional clearance of micrometastases.


Response of submerged macrophytes and leaf biofilms to the decline phase of Microcystis aeruginosa: Antioxidant response, ultrastructure, microbial properties, and potential mechanism.
Decaying cyanobacterial blooms carry a potential risk for submerged macrophyte and periphyton biofilms in aquatic environments. This study comprehensively studied the responses in growth, oxidative response, detoxification pathway, and ultrastructure characteristics of aquatic plants to Microcystis aeruginosa (M. aeruginosa) exudates and extracts released during the decline phase. Particular emphasis was placed on the variation of extracellular polymeric substances (EPS) and quorum-sensing signaling molecules. The results showed that superoxide dismutase, peroxidase, and glutathione S-transferase were significantly induced as antioxidant response, and the malondialdehyde content increased. Increased content of MC-LR (1.129 μg L-1) and NH4+-N (1.35 mg L-1) were found in the decline phase of M. aeruginosa, which played a vital role in the damage to submerged plants. In addition, a change in the amount of osmiophilic granules and a variation of organelles and membranes was observed. A broad distribution of α-d-glucopyranose polysaccharides was dominant and aggregated into clusters in biofilm EPS in response to exposure to decaying M. aeruginosa. Furthermore, exposure to exudates and extracts changed the abundance and structure of the microbial biofilm community. Increased contents of N-acylated-L-homoserine lactone signal molecule might result in a variation of biofilm EPS production in response to decaying M. aeruginosa. These results expand the understanding of how submerged macrophyte and periphyton biofilms respond to environmental stress caused by exudates and extracts of decaying M. aeruginosa.


High pressure laminates reinforced with electrospun cellulose acetate nanofibers.
In the work, the non-woven cellulose acetate (CA) nanofiber mats were prepared via electrospinning, and CA nanofiber were incorporated into the core layer of the high-pressure laminates (HPLs). When the concentration of CA was 16 wt%, SEM images demonstrated that the morphology of the CA nanofiber mat was the best, with an average diameter of 654±246 nm. When CA nanofiber mats were incorporated into the core layer of HPLs, the mechanical properties of the resulted HPLs composites were significantly improved. Specifically, the tensile strength and elongation at break of the nanofiber mats reinforced HPLs composites increased remarkably to 40.8 ±1.1 MPa and 27.9 ± 0.9 %, respectively, which were nearly 6 times and 4.4 times higher than those of the pure HPLs. Furthermore, the incorporation of the CA nanofiber mats also significantly improved the flame retardancy of the HPLs, which was revealed from the thermogravimetric analysis (TGA) results.


Clinicopathological significance of PI3K, Akt and survivin expression in gastric cancer.
Gastric cancer is the second leading cause of cancer-related deaths worldwide, and is characterized by invasion and metastasis. Increasing attention is being focused on discovering molecular markers for diagnosis and prognosis. Our objective was to evaluate PI3K, Akt and survivin protein expression in gastric cancer, and their correlations with clinicohistological features and prognosis in patients with gastric cancer. Tissue samples were obtained from 70 patients with gastric cancer patients and 20 patients with normal gastric mucosa. The protein levels of PI3K, Akt and survivin were evaluated by immunohistochemistry. Statistical analyses were performed to establish the correlations between their expressions and patients' clinicopathologic characteristics. The positive expression rates of PI3K, Akt and survivin were significantly higher in the gastric cancer tissues compared to normal gastric mucosa (P<0.05). Expression levels of PI3K, Akt and survivin proteins were significantly correlated with TNM stage, differentiation grade, lymph node metastasis and metastases to other organs (P<0.05). Cooperative relationships were identified between PI3K and Akt, and PI3K and survivin (P<0.01), suggesting the involvement of the PI3K/Akt/survivin signaling pathway in the tumorigenesis of gastric cancer. Protein expression of PI3K, Akt and survivin were significantly associated with the development, progression and metastasis of gastric cancer and may have value as diagnostic and prognostic markers in gastric cancer.


Impact of muscle tension dysphonia on tonal pitch target implementation in vietnamese female teachers.
Muscle tension dysphonia (MTD) is a voice disorder with deteriorated vocal quality, particularly pitch problems. Because pitch is mainly controlled by the laryngeal muscles, and because MTD is characterized by increased laryngeal muscle tension, we hypothesized that it may result in problems in pitch target implementation in tonal languages. We examined tonal samples of 42 Vietnamese female primary school teachers diagnosed with MTD and compared them with 30 vocally healthy female teachers who spoke the same dialect. Tonal data were analyzed using Computerized Speech Lab (CSL-4300B) for Windows. From tonal sampling bases, fundamental frequency (F0) was measured at target points specified by contour examination. Parameters representing pitch movement including time, size, and speed of movement were measured for the falling tone and rising tone. We found that F0 at target points in MTD group was lowered in most tones, especially tones with extensive F0 variation. In MTD group, target F0 of the broken tone in isolation was 37.5 Hz lower (P<0.01) and target F0 of rising tone in isolation was 46 Hz lower (P<0.01) than in control group. In MTD group, speed of pitch fall of the falling tone in isolation was faster than control group by 2.2 semitones/second (st/s) (P<0.05) and speed of pitch rise in the rising tone in isolation was slower than control group by 7.2 st/s (P<0.01). These results demonstrate that MTD is associated with problems in tonal pitch variation.


Polyacrylamide gel electrophoresis of human erythrocyte membrane enzymes solubilized with triton X-100.
Human erythrocyte ghosts were solubilized in a low ionic strength medium containing 1% Triton X-100 and subjected to electrophoresis in polyacrylamide gels containing Triton X-100. Five major bands were stained with Coomassie Blue, all except one band being heterogenous when re-electrophoresed in gels containing sodium dodecyl sulphate. It was possible to detect acetylcholinesterase, non-specific esterase, ATPase, alkaline phosphatase, 5'-nucleotidase, glyceraldehyde-3-phosphate dehydrogenase, lactate dehydrogenase, and aldolase activities on the Triton-containing polyacrylamide gels. Two of the enzymes, ATPase and 5'-nucleotidase, showed substantial inhibition by Triton X-100 in quantitative studies. This appears to be a useful method for studying membrane enzymes in normal and pathological red cells.


Tenofovir substitution in Namibia based on an analysis of the antiretroviral dispensing database.
In the management of HIV infection, tenofovir is preferred to its predecessors - zidovudine and stavudine - in the antiretroviral therapy (ART) nucleoside backbone. Tenofovir's (TDF) preference is based on its safety profile. Nevertheless, TDF causes adverse reactions, some of which warrant its substitution for patients. The rate of TDF-substitution is suggestive of the rate of occurrence of TDF-related adverse reactions. However, the rate of substitution of TDF with another nucleoside reverse transcriptase inhibitor (NRTI) in Namibia was unknown. The objective of this review was to measure the rate of TDF's substitution for the period of January 1, 2008 to November 30, 2011, and to compare the gender difference in the rates of TDF's substitution. We accessed antiretroviral medicine dispensing records from the national antiretroviral dispensing database (NDB). We selected patients who were started on a TDF-containing conventional ART regimen - 2NRTI+1NNRT. We used the initial and current ART regimens to identify records of TDF's substitution with another NRTI. A total of 84,741 patients were initiated on ART (Jan-1-2008 to Nov-30-2011). A total of 52,612 patient-records were excluded from the analysis because they did not meet the criteria for inclusion. Of the 32,129 included records, 59.4% (n=19 096) and 40.6% (n=13 033) were for female and male patients, respectively. Of these, 1.2% (n=380) of the patients had their TDF substituted with another NRTI. Of the females and males, respectively, 1.1% (95% CI: 0.9-1.3; n=210) and 1.3% (95% CI: 1.1-1.5; n=170) had TDF substituted with another NRTI. No gender difference was observed (p-value = 0.11). The percentage of patients for whom TDF was substituted with another NRTI, possibly due to TDF-related adverse reactions, was within the current published limits. However, 1.2% is likely not a true representation of the percentage of patients who experience adverse events because some patients could have been maintained on TDF even in the presence of adverse events. Further investigation is required to determine the clinical reasons for TDF's withdrawal.


Clinical Implication of EGF A61G Polymorphism in the Risk of Non Small Cell Lung Adenocarcinoma Patients: A Case Control Study.
The epidermal growth factor (EGF) plays important roles in non-small cell lung cancer (NSCLC) susceptibility and functional polymorphism in the EGF (+61A/G) gene has been linked to increased risk of NSCLC. This study aimed to evaluate the role of the EGF +61A/G polymorphism in risk of NSCLC adenocarcinoma (ADC) occurrence and survival in an Indian population. This case- control study included 100 histopathologically confirmed NSCLC (ADC) patients and 100 healthy controls. EGF (A61G) was genotyped by AS-PCR to elucidate putative associations with clinical outcomes. The association of the polymorphism with the survival of NSCLC patients was estimated by Kaplan-Meier curves. It was found that EGF 61AG heterozygous and GG homozygous genotype is significantly associated with increased risk of NSCLC (ADC) occurrence compared to AA genotype, [OR 2.61 (1.31-5.18) and 3.25 (1.31-8.06), RR 1.51(1.15-2.0) and 1.72 (1.08-2.73) and RD 23.2 (6.90-39.5) and 28.53(7.0-50.1) for heterozygous AG (p=0.005) and homozygous GG (p=0.009)]. Patients homozygous for the G allele exhibited a significantly poor overall survival. The median survival time for patients with EGF 61 AA, AG, and GG genotypes was 10.5, 7.4, and 7.1 months (p=0.02), respectively. NSCLC (ADC) patients with GG + AG exhibited 7.3 months median survival compared to the AA genotype (p=0.009). The present study revealed that the EGF A61G genotype may be a novel independent prognostic marker to identify patients at higher risk of occurrence and an unfavourable clinical outcome.


Clinical utility of three-dimensional contrast-enhanced ultrasound in the differentiation between noninvasive and invasive neoplasms of urinary bladder.
The purpose of this study was to evaluate the effectiveness of three-dimensional contrast-enhanced ultrasound in differentiating invasive and noninvasive neoplasms of urinary bladder. A total of 60 lesions in 60 consecutive patients with bladder tumors received three dimensional ultrasonography, low acoustic power contrast enhanced ultrasonography and low acoustic power three-dimensional contrast-enhanced ultrasound examination. The IU22 ultrasound scanner and a volume transducer were used and the ultrasound contrast agent was SonoVue. The contrast-specific sonographic imaging modes were PI (pulse inversion) and PM (power modulation). The three dimensional ultrasonography, contrast enhanced ultrasonography, and three-dimensional contrast-enhanced ultrasound images were independently reviewed by two readers who were not in the images acquisition. Images were analyzed off-site. A level of confidence in the diagnosis of tumor invasion of the muscle layer was assigned on a 5° scale. Receiver operating characteristic analysis was used to assess overall confidence in the diagnosis of muscle invasion by tumor. Kappa values were used to assess inter-readers agreement. Histologic diagnosis was obtained for all patients. Final pathologic staging revealed 44 noninvasive tumors and 16 invasive tumors. Three-dimensional contrast-enhanced ultrasound depicted all 16 muscle-invasive tumors. The diagnostic performance of three-dimensional contrast-enhanced ultrasound was better than those of three dimensional ultrasonography and contrast enhanced ultrasonography. The receiver operating characteristic curves were 0.976 and 0.967 for three-dimensional contrast-enhanced ultrasound, those for three dimensional ultrasonography were 0.881 and 0.869, those for contrast enhanced ultrasonography were 0.927 and 0.929. The kappa values in the three dimensional ultrasonography, contrast enhanced ultrasonography and three-dimensional contrast-enhanced ultrasound for inter-reader agreements were 0.717, 0.794 and 0.914. Three-dimensional contrast-enhanced ultrasound imaging, with contrast-enhanced spatial visualization is clinical useful for differentiating invasive and noninvasive neoplasms of urinary bladder objectively.


Acousto-optic, point receiver hydrophone probe for operation up to 100 MHz.
This work describes the results of initial evaluation of a wideband acousto-optic hydrophone probe designed to operate as point receiver in the frequency range up to 100 MHz. The hydrophone was implemented as a tapered fiber optic (FO) probe sensor with a tip diameter of approximately 7 microm. Such small physical dimensions of the sensor eliminate the need for spatial averaging corrections so that true pressure-time (p-t) waveforms can be faithfully recorded. The theoretical considerations that predicted the FO probe sensitivity to be equal to 4.3 mV/MPa are presented along with a brief description of the manufacturing process. The calibration results that verified the theoretically predicted sensitivity are also presented along with a brief description of the improvements being currently implemented to increase this sensitivity level by approximately 20 dB. The results of preliminary measurements indicate that the fiber optic probes will exhibit a uniform frequency response and a zero phase shift in the frequency range considered. These features might be very useful in rapid complex calibration i.e. determining both magnitude and phase response of other hydrophones by the substitution method. Also, because of their robust design and linearity, these fiber optic hydrophones could also meet the challenges posed by high intensity focused ultrasound (HIFU) and other therapeutic applications. Overall, the outcome of this work shows that when fully developed, the FO probes will be well suited for high frequency measurements of ultrasound fields and will be able to complement the data collected by the current finite aperture piezoelectric PVDF hydrophones.


N-terminal labeling of proteins using initiator tRNA.
Methodology based on tRNA mediated protein engineering is described for the introduction of fluorophores and other labels at the N-terminus of proteins produced in cell-free translation systems. One method for low-level (trace) N-terminal labeling is based on the use of an Escherichia coli initiator tRNA(fMet) misaminoacylated with methionine modified at the alpha-amino group. In addition to the normal formyl group, the protein translational machinery incorporates the fluorophore BODIPY-FL and the affinity tag biotin at an N-terminal end of the nascent protein. A second method for higher N-terminal labeling uses a chemically aminoacylated amber initiator suppressor tRNA and a DNA template which contains a complementary amber (UAG) codon instead of the normal initiation (AUG) codon. This more versatile approach is demonstrated using a variety of N-terminal markers including fluorescein, biotin, PC-biotin, and a novel dual marker conjugate (Biotin/BODIPY-FL).


Characterization of soluble PD-L1 in pleural effusions of mesothelioma patients: potential implications in the immune response and prognosis.
Programmed death-ligand 1 (PD-L1) protein plays a central role in the antitumor immune response, and appears to be a predictor of prognosis and efficacy for PD-L1 and programmed death 1 (PD-1) blockade therapy. The immunoregulatory role and prognostic impact of PD-L1 soluble form (sPD-L1) have been investigated in biological fluids of patients with different tumors. In malignant pleural mesothelioma (MPM), circulating sPD-L1 has been recently reported in patients' sera, but no data are available in pleural effusions (PE). In our study, we evaluated the baseline expression levels of sPD-L1 in PE from 84 MPM patients and correlated them with PD-L1-status in matched tumors and patients' overall survival (OS). sPD-L1 in PE was determined by ELISA and tumor PD-L1 by immunohistochemistry. Association of sPD-L1 with OS was estimated using the Cox regression model. We observed that sPD-L1 was variably expressed in all the PE and tended to be higher (by 30%) in patients with PD-L1-positive tumors (cut-off ≥ 1% stained cells) as compared to patients with PD-L1-negative tumors (geometric mean ratio = 1.28, P value = 0.288). sPD-L1 levels were significantly higher than those of sPD-1 (P value = 0.001) regardless of the MPM histotypes and they were positively correlated (r = 0.50, P value < 0.001). Moreover, high PE sPD-L1 concentrations were associated with a trend towards increased OS (hazard ratio 0.79, 95% CL 0.62-1.01, P value = 0.062). Our study documents the presence of sPD-L1 in PE of MPM patients, and suggests its possible biological and prognostic role in MPM.


Long term follow-up of composite non-vascularized toe phalanx transfers for aphalangia.
The results of 21 non-vascularized toe phalanx transfers in 13 patients were reviewed radiologically with respect to function, physeal patency, growth and donor site morbidity at a mean follow-up of 7.4 (range 2.9-13.6) years. Physeal patency was maintained in 4 of 18 surviving transfers. The length of the transferred phalanx averaged 75% of the contralateral comparable toe phalanx and 44% of the contralateral digit proximal phalanx. Most patients had good or simple use of the hand with active joint motion. There was universal shortening of the donor toe with hypoplasia of the middle and distal phalanges. This review suggests that transfer of a non-vascularized toe phalanx provides a reliable but limited means for increasing length of a digit, stabilizing soft tissue "nubbins" and improving function. Longer follow-up has shown more modest gains in growth than in some previous reports.


Augmented Reality Integration in Manikin-Based Simulations: Bringing Basic Science to the Critical Care Bedside with Limited Augmented Reality Resources.
Immersive simulation and augmented reality (AR) are powerful educational tools in high-risk medical professions. Basic science AR, such as anatomic holograms, are gaining popularity. Many educators want to adopt AR and integrate basic science review in high-risk clinical decision-making but cannot afford it. In this project, we designed three AR integrated manikin-based simulations (ARI-MBS) by combining critical care scenarios with commercially available AR programs. Using a single headset and limited equipment, we technically integrated AR into MBS in a way that both students and faculty found rewarding. We present our design, so that others may replicate it. The online version contains supplementary material available at 10.1007/s40670-023-01821-z.


A calculator program to determine k and V from measured serum drug concentrations by a two point curve fitting method.
A calculator program is presented which determines k and V from two drugs levels or k from an assumed V and one drug level during maintenance dosing with any of four dosing schedules: intermittent, fixed interval; intermittent, two fixed intervals; intermittent, non-uniform dose, non-uniform interval; continuous intravenous infusion/sustained release. A loading dose and or one additional level taken before maintenance dosing begins can be taken into account for additional flexibility. Steady state concentrations are projected when dosage regimen and pharmacokinetic parameters are known.


Effects of DNA methylation on topoisomerase I and II cleavage activities.
DNA methylation is deregulated during oncogenesis. Since several major anti-cancer drugs act on topoisomerases, we investigated the effects of cytosine methylation on topoisomerase cleavage activities. Both topoisomerase I and II cleavage patterns were modified by CpG methylation in c-myc gene DNA fragments. Topoisomerase II changes, mainly cleavage reduction, occurred for methylation sites within 7 base pairs from the topoisomerase II breaks and were different for VM-26 and azatoxin. For topoisomerase I, cleavage enhancement as well as suppression were observed. Using synthetic methylated oligonucleotides, we show that hemimethylation is sufficient to alter topoisomerase I activity. Cytosine methylation on the scissile strand within the topoisomerase I consensus sequence had strong effects. Cleavage was stimulated by methylation at position -4 and was strongly inhibited by methylation at position -3 (with position -1 being the enzyme-linked nucleotide). This inhibitory effect was attributed to the presence of a methyl group in the major groove, since the transition uracil to thymine also inhibited cleavage. Altogether these results suggest an interaction of topoisomerase I with the DNA major grove at positions -3 and -4. In addition, DNA methylation may have profound effects on the activity of topoisomerases and may alter the distribution of cleavage sites produced by anticancer drugs in chromatin.


Current diagnosis and management of unusual pancreatic tumors.
The finding of a solid or cystic mass in the pancreas is becoming more common secondary to the increasing use of cross-sectional imaging and the improved sensitivity of such studies for the detection of pancreatic abnormalities. Because of the aggressive natural history of pancreatic cancer, this has caused concern that all pancreatic abnormalities may be cancer as well as confusion over proper diagnostic and treatment algorithms. This review provides an overview of the natural history, diagnostic considerations, and treatment recommendations for the less common tumors of the pancreas which can be misinterpreted as pancreatic cancer including: solid pseudopapillary tumors (SPT), acinar cell carcinoma (ACC), lymphoplasmacytic sclerosing pancreatitis (LPSP), primary pancreatic lymphoma (PPL), and metastatic renal cell carcinoma to the pancreas. A Medline search was conducted to identify studies investigating the clinicopathologic features, molecular genetics, pathogenesis, diagnosis, and treatment of SPT, ACC, LPSP, PPL, and pancreatic metastases. It is often possible to obtain an accurate pretreatment diagnosis for these unusual pancreatic tumors and to successfully differentiate them from the more common pancreatic malignancies.


Researchers successfully engineer endovascular probes for brain recording at a microscopic scale.
A neural probe capable of recording single-cell resolution was implanted using an endovascular approach through micrometer-scale vasculature. Overall, this, among other developments, are enabling safer and more specific targeting of neurologic conditions, but their overall ethical implications remain to be further discussed.


Evaluation of procedures for typing of group B Streptococcus: a retrospective study.
This study evaluates two procedures for typing of Streptococcus agalactiae (group B streptococci; GBS) isolates, using retrospective typing data from the period 2010 to 2014 with a commercial latex agglutination test (latex test) and the Lancefield precipitation test (LP test). Furthermore, the genotype distribution of phenotypically non-typable (NT) GBS isolates is presented. We also raise the awareness, that the difference in typing results obtained by phenotypical methods and genotype based methods may have implications on vaccine surveillance in case a GBS vaccine is introduced. A total of 616 clinical GBS isolates from 2010 to 2014 were tested with both a latex test and the LP test. Among these, 66 isolates were genotyped by PCR, including 41 isolates that were phenotypically NT. The latex test provided a serotype for 83.8% of the isolates (95% CI [80.7-86.6]) compared to 87.5% (95% CI [84.6-90.0]) obtained by the LP method. The two assays provided identical capsular identification for all sero-typeable isolates (excluding NT isolates). The PCR assay provided a genotype designation to the 41 isolates defined as phenotypically NT isolates. We found that the latex test showed a slightly lower identification percentage than the LP test. Our recommendation is to use the latex agglutination as the routine primary assay for GBS surveillance, and then use the more labour intensive precipitation test on the NT isolates to increase the serotyping rate. A genotype could be assigned to all the phenotypically NT isolates, however, as a consequence genotyping will overestimate the coverage from possible future capsular polysaccharide based GBS vaccines.


[Dependence of serum hormones (T, FSH, LH) on morphometric testicular findings after chemo- and radiotherapy in patients with malignant testicular tumors].
Correlations which exist between morphometric parameters of remaining testicular tissue, on the one hand, and serum hormones on the other (testosterone = T, follicle-stimulating hormone = FSH, luteinising hormone = LH), depending on therapeutic action taken on patients for malignant testicular tumours, seem to suggest that decline in epithelial thickness together with increase in wall thickness leads to rise in FSH. No unambiguous relations, on the other hand, were found to exist between testosterone or luteotrophic hormone and morphometric findings. Hence, FSH seems to characterise the severity of damage to germ epithelium and thus the degree of impairment to spermatogenesis. FSH may be accepted as a criterion for fertility disorders in sexually active men.


Psychological risk factors and the course of depression and anxiety disorders: A review of 15 years NESDA research.
The Netherlands Study of Depression and Anxiety (NESDA; Nbaseline=2981) is an ongoing longitudinal, multi-site, naturalistic, cohort study examining the etiology, course, and consequences of depression and anxiety. In this article we synthesize and evaluate fifteen years of NESDA research on prominent psychological risk factors for the onset, persistence, recurrence, and comorbidity of affective disorders. A narrative review of 62 NESDA articles examining the specificity and predictive value of neuroticism, behavioral inhibition, repetitive negative thinking, experiential avoidance, cognitive reactivity, locus of control, (implicit) self-esteem, (implicit) disorder-specific self-associations, and attentional bias for the course of affective disorders. All self-reported risk factors showed cross-sectional relationships with singular and comorbid affective disorders, and prospective relationships with the development and chronicity of depression and anxiety disorders. High neuroticism, low self-esteem, and negative repetitive thinking showed most prominent transdiagnostic relationships, whereas cognitive reactivity showed most pronounced depression-specific associations. Implicit self-esteem showed predictive validity for the persistence and recurrence of anxiety and depression over and above self-reported risk factors. Automatic approach-avoidance behavior and attentional bias for negative, positive, or threat words showed no relationship with affective disorders. NESDA identified both (a) transdiagnostic factors (e.g., neuroticism, low implicit self-esteem, repetitive negative thinking) that may help explain the comorbidity between affective disorders and overlap in symptoms, and (b) indications for disorder-specific risk factors (e.g., cognitive responsivity) which support the relevance of distinct disorder categories and disorder-specific mechanisms. Thus, the results point to the relevance of both transdiagnostic and disorder-specific targets for therapeutic interventions.


Trypanosoma brucei brucei infection in goats. Response of peripheral blood lymphocytes to mitogen stimulation.
The in vitro proliferative response of peripheral blood lymphocytes from Trypanosoma b. brucei infected goats to mitogens was studied during the course of infection. An inverse correlation was observed between the number of lymphocytes and their capacity to respond to concanavalin A, phytohemagglutinin and pokeweed mitogen. Lymphocyte responsiveness to mitogens was reduced during a period of increased lymphocyte counts. During this period of time only few trypanosomes were detectable in the peripheral blood. Later in the infection, when lymphocytes decreased, mitogen responsiveness and parasitemia increased.


Skepticism about the paranormal: legitimate and illegitimate.
With the growth of belief in the paranormal, skepticism can play a vital role in the scientific appraisal of claims. There are two forms: the first, hardly legitimate, is negative or total skepticism. It is nihilistic and dogmatic, and essentially self-defeating and self-contradictory. The second, a legitimate form, is selective skepticism. Here skepticism operates as a methodological principle of inquiry, testing hypotheses and theories in the light of evidence, but always open to new departures in thought. Skepticism has been applied historically to epistemology, metaphysics, religion, and ethics. The paranormal field has been full of fraud. Here the skeptic insists upon replicable experiments by neutral or skeptical observers before he will accept a claim as confirmed.


Social support as a moderator between depressive symptoms and quality of life outcomes of breast cancer survivors.
To examine the unique relationships among demographic variables, depressive symptoms scoring ≥16 on the Center for Epidemiological Studies-Depression (CES-D), social support and quality of life (QOL) in breast cancer survivors, and whether social support moderated the effects of depressive symptoms on the outcome of QOL. Specifically, this study aimed to probe more deeply into the nature of causal mechanisms of moderation. A model based, descriptive cross-sectional research design was conducted. A total of 150 breast cancer survivors were recruited from two teaching hospitals in Taiwan. All participants completed the CES-D, Interpersonal Support Evaluation List, and the Medical Outcomes Study 36-Item Short Form Health Questionnaire. The moderation models and moderating hypotheses were tested and confirmed by applying structural equations and hierarchical regression analyses. Approximately 35% of the participants had depressive symptoms. Findings indicated social support as a moderator of effects of depressive symptoms on QOL. Social support significantly moderated depressive symptoms on QOL. Testing for moderating effects provides helpful information regarding the role of social support in buffering the relationship between depressive symptoms and QOL. The moderating effects of social support are adequate in the management of nursing care for breast cancer patients, particularly in the early phase of treatment or in cases of newly diagnosed patients who may not know how to manage their health conditions. These findings may aid in the development of social support interventions to enhance social support for breast cancer survivors.


Undetected for a century: Palaearctic Agrilus ribesi Schaefer (Coleoptera: Buprestidae) on currant in North America, with adult morphology, larval biology and DNA barcode.
We report the Eurasian species Agrilus ribesi Schaefer, 1946, for the first time from North America and propose that the damage to currants (Ribes spp.) in Ontario prior to 1940 and ascribed to A. cuprescens were caused by this species. We provide morphological diagnostic characters for A. ribesi and closely related A. cuprescens and we complement this information with DNA barcodes from four alien Agrilus species established in North America (i.e., A. ribesi Schaefer, A. cuprescens (Ménétriés), A. planipennis Fairmaire and A. sulcicollis Lacordaire) to enable DNA-based identification of these invasive species. Additionally, published information on A. ribesi is summarized and new data are provided on the host plants and biology of larva in North America. The distribution of A. ribesi is mapped, both in its native Palaearctic region and in Canada and the USA, together with the range of its potential host plants in North America. A. ribesi was recovered as a sister-species of A. cuprescens on the neighbor joining DNA barcoding tree and low genetic variability of North American populations may indicate a single introduction to North America for each of these species.


Genome-Wide Analysis of Microsatellites in Alternaria arborescens and Elucidation of the Function of Polyketide Synthase (PksJ).
Microsatellites or simple sequence repeats (SSRs) have been the most widely applied class of molecular markers used in genetic studies, having applications in genetic conservation, population studies, as well as diagnostics of fungi. Mining and analysis of SSRs of the whole genome sequence have been carried out in this study for the fungus Alternaria arborescens causing early blight of tomato and well known for producing mycotoxins like alternariol (AOH), alternariol monomethyl ether (AME), etc. A total of 4097 microsatellites were identified in A. Arborescens genome. Contig 1 was identified as the most SSR-rich region which was further analyzed to correlate the presence of SSRs with different biological processes. A total of 246 putative genes were predicted in this study and KEGG pathway analysis of 155 predicted genes indicated that SSRs can be linked with important metabolic pathways, molecular functioning, signal transduction, and cellular processes. The prediction of fungal mycotoxin inducer gene Polyketide synthase (PksJ) linked with SSR in this study may be a potential candidate participating in oncogenic signal transduction in human. Our study is the first report of PksJ gene in A. arborescens, a precursor of AOH and AME.


The Effect of Repositioning Maneuver Applied with the TRV Chair on Residual Dizziness after Benign Paroxysmal Positional Vertigo.
This study aims to investigate the effect of TRV chair on residual dizziness (RD) after idiopathic posterior semicircular canal benign paroxysmal positional vertigo (BPPV) successfully treated with canalith repositioning maneuver (CRM). Prospective case-control study. Hospital. Thirty-three patients with posterior canal BPPV were included in the study. These patients were divided into two identical groups. CRM was applied to the first group with a TRV chair (TRV group) and manually to the second group (manual group). Dizziness Handicap Inventory (DHI), Beck Anxiety Inventory (BAI), and video head impulse test were applied to the patients. Patients in both groups were asked to report the RD developed after successful CRM daily by visual analog scale (VAS). The TRV group's first-day RD rate was 94.1% with VAS, and the RD duration was 2.47 ± 1.77 (0-7) days. The manual group's first-day RD rate was 100%, and the RD duration was 3.38 ± 1.70 (1-7) days. There was no difference between the groups in terms of RD duration ( p > 0.05). Mean RD severity and severity in the first 3 days were lower in the TRV group compared with the manual group ( p < 0.05). There was no difference between the groups on other days ( p > 0.05). In addition, there was a positive correlation between RD and DHI and BPPV duration ( p < 0.05). RD is a multifactorial symptom associated with how the repositioning maneuver is performed, BPPV duration, and DHI. Performing the repositioning maneuver with the TRV chair can reduce the severity of RD.


Obesity care strategies in primary care practices.
We evaluated pediatric obesity clinics for internal referrals developed at 5 primary care offices. Clinics developed site-specific strategies: 1 group approach and 4 clinics providing individualized care only. Clinicians reported patient/family motivation as an important referral consideration and compliance as the greatest challenge and perceive clinics to have provided some help.