Convex-probe Endobronchial Ultrasound: A Decade of Progress.
Ever since the invention of the flexible bronchoscope, perhaps no other innovation in the field of interventional pulmonology has caused so much excitement the world over, as the convex probe endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA). While it took over a decade from 1992 to 2004 for the radial EBUS to evolve into the commercial convex probe EBUS scope, another exciting decade has gone by with the technology being thoroughly researched and appraised. The current evidence suggests that EBUS-TBNA can replace mediastinoscopy as the first investigation in the mediastinal staging of lung cancer. The use of EBUS-TBNA has been extended to several other areas including the diagnosis of undefined mediastinal lymphadenopathy, evaluation of intra-parenchymal lesions and others. In fact, EBUS-TBNA is the preferred modality for accessing mediastinal lesions in contact with the airways. The procedure not only has a high diagnostic efficiency (80%-90% for most indications) but is also safe compared to alternative options, such as image-guided fine needle aspiration and mediastinoscopy in the diagnosis of mediastinal lymphadenopathy. Apart from the traditional use of EBUS to perform TBNA, the last decade has seen the evolution of its transoesophageal use, development of novel EBUS-TBNA needles to obtain better histological specimens and a smaller EBUS scope. This review summarises the developments made in this field over the years since its inception.


Different applications forms of green tea (Camellia sinensis (L.) Kuntze) for the treatment of periodontitis: a systematic review and meta-analysis.
Scaling and root planning (SRP) is the gold standard for non-surgical periodontal treatment. Green tea as a supporting alternative in non-surgical periodontal treatment has been suggested as a therapeutic option in the treatment of periodontitis. To analyse the comparative effectiveness of green tea (Camellia sinensis) in its different forms and applications for the treatment of periodontitis. We included randomized clinical trials evaluating green tea as an adjuvant therapeutic agent to scaling and root planning (SRP) in the treatment of periodontitis. For the meta-analysis, we calculated standardized mean difference (SMD) and 95%CI comparing green tea and control (only SRP). We subgrouped by types of application forms of green tea. The certainty of the evidence was assessed through GRADE. Nine studies were included. The follow-up time of treatments varied from 21 days to 6 months. The subgroup meta-analysis showed that the green tea as sachet reduced probing bleeding (SMD = -0.71; 95%CI) and the gingival index (SMD = -0.78; 95%CI) compared to SRP with very low certainty of evidence. The sachet (SMD = -0.29; 95%CI) and dentifrice (SMD = -1.31; 95%CI) reduced plaque index with very low certainty compared to the control. All forms of application of green tea showed very low certainty of evidence (SMD = -0.27; 95% CI) in reducing the probing depth, as well as for the loss of clinical insertion (SMD = -0.42; 95% CI) with low certainty of evidence. There was not a difference in the effectiveness of green tea isolated or in combination with SRP to reduce probing depth. Green tea adjunct to periodontal therapy showed very low certainty of effectiveness for the treatment of periodontal disease.


Danon disease: focusing on heart.
Danon disease is a rare X-linked dominant lysosomal disease due to the primary deficiency of lysosome-associated membrane protein 2 (LAMP2) gene. Cardiomyopathy, skeletal myopathy and mental retardation are the typical triad of Danon disease. More than 60 LAMP2 mutations have been reported. The molecular mechanism is defects in LAMP2 protein (due to LAMP2 mutation) which causes insidious glycogen accumulation in cardiac muscle cells and resulting in cardiac hypertrophy and electrophysiological abnormalities. However, there are significant differences between the male and female Danon disease patients with regard to clinical features and cardiac manifestations. The clinical symptoms are variable, from asymptomatic to sudden cardiac death. Wolff-Parkinson-White syndrome is more common in male than female patients. Hypertrophic cardiomyopathy is predominant in male patients, whereas the similar prevalence of hypertrophic and dilated cardiomyopathy in female patients. Male patients are diagnosed usually at teenage, whereas the diagnosis and events occurred approximately 15 years later in female than male patients. Heart transplantation is the reliable treatment once the occurrence of heart failure and should be considered as early as possible due to its rapid progression.


[Some reflections on the classification of African obstetric fistulas].
While the English-speaking world may have reached a consensus about Kees Waaldjik's classification of obstetric fistulas, no unanimity around this classification exists among French-speaking medical workers. The objective of this review is to propose a classification, based on long experience in the care of these women, by setting up a comparison with Waaldjik's. Our classification takes two criteria into account: (1) the environment of the fistula, that is: (a) fistula with a soft (relatively unscarred) vagina, b) fistula with vaginal sclerosis (bands or adhesions, vaginal stenosis or atresia), (c) vesicovaginal fistula associated with a (high or low) rectovaginal fistula or perineal lacerations (first, second or third degree); (2) the anatomical site of fistula, of which there are five types: (a) type I: fistula of the vesicovaginal wall, (b) type II: vesico-cervico-urethral fistula, with two major subgroups: type IIA (without destruction of the urethra) and type IIB (with destruction of the urethra), type IIA being subdivided in three subgroups: IIAa, IIAB and cIAI, (c) type III fistulae trigono-Neck utero-vaginal, (d) type IV: complex mixed fistula, (e) type V, high fistulas: the vesico-cervical-uterine fistula and classical vesicouterine. Our classification is simple, not simplistic, with some resemblance to that of Waaldjjik.


Introduction: importance of Mg in physiology and medicine and the need for ion selective electrodes.
Mg is a co-factor in more than 325 enzyme systems in cells and is the second most abundant intracellular cation after K. It is important in numerous physiologic and homeostatic functions such as hormone-receptor binding, gating of Ca2+ channels, transmembrane flux of ions, regulation of adenylate cyclase, Ca(2+)-Ca(2+) release, muscle contraction, cardiac excitability, neuronal activity, control of vasomotor tone and neurotransmitter release, to name a few. Serum total Mg measurements suggests this extracellular cation is often lowered in many hospitalized patients. It appears to be greatly depleted in normal food preparation and processing. Its daily intake has been declining steadily in the USA from where it was about 500 mg/day, at the turn of the century, to where it is now about 175-225 mg/day. Most mammals exhibit very similar levels of extracellular Mg, including humans. This might suggest that total Mg measurements on serum or plasma aren't sensitive blood variables or analytes to reflect what may be going on in the body at the cellular level. Mg exists in several forms in the blood, but the ionized, free Mg is probably the most physiologically important fraction, thus pointing to a need for sensitive, specific ion selective electrodes. Our studies, so far, suggest that ISE's can be designed which will work equally well on whole blood, serum and plasma to measure IMg2+ in healthy and diseased subjects.


Unexpected consequences of culling on the eradication of wildlife diseases: the role of virulence evolution.
The removal of individuals from an infected population (culling) is a common strategy used to eradicate wildlife diseases. The manipulation of host density can impose strong selective pressures on pathogen virulence by changing the ecological conditions, thus affecting the effectiveness of eradication programs. We present an analysis of the effect of virulence evolution on culling by extending a susceptible-infected model to the case of competing strains with superinfection. To assess both short- and long-term effects, we first carried out the analysis on an ecological timescale, with a two-strain competition model; then we explore the dynamics of a continuum of pathogenic strains on evolutionary timescales using a quantitative genetics approach (when infection and evolutionary processes occur on comparable timescales) and a game-theoretic approach (when evolutionary processes occur on a slower scale). We demonstrate that the competition among pathogenic variants in the presence of superinfection affects outcome of culling campaigns, since increased host mortality may select for less virulent strains able to establish in sparser populations. This can lead to the counterintuitive result that disease abundance and prevalence may even increase with culling, thus making the eradication of infections considerably less likely. This is particularly relevant in the case of zoonoses where higher prevalence and abundance of pathogens in wild reservoirs may increase the risk of spillover in livestock and humans.


Retrotransposon suicide: formation of Ty1 circles and autointegration via a central DNA flap.
Despite their evolutionary distance, the Saccharomyces cerevisiae retrotransposon Ty1 and retroviruses use similar strategies for replication, integration, and interactions with their hosts. Here we examine the formation of circular Ty1 DNA, which is comparable to the dead-end circular products that arise during retroviral infection. Appreciable levels of circular Ty1 DNA are present with one-long terminal repeat (LTR) circles and deleted circles comprising major classes, while two-LTR circles are enriched when integration is defective. One-LTR circles persist when homologous recombination pathways are blocked by mutation, suggesting that they result from reverse transcription. Ty1 autointegration events readily occur, and many are coincident with and dependent upon DNA flap structures that result from DNA synthesis initiated at the central polypurine tract. These results suggest that Ty1-specific mechanisms minimize copy number and raise the possibility that special DNA structures are a targeting determinant.


Genetic regulation of amphioxus somitogenesis informs the evolution of the vertebrate head mesoderm.
The evolution of vertebrates from an ancestral chordate was accompanied by the acquisition of a predatory lifestyle closely associated to the origin of a novel anterior structure, the highly specialized head. While the vertebrate head mesoderm is unsegmented, the paraxial mesoderm of the earliest divergent chordate clade, the cephalochordates (amphioxus), is fully segmented in somites. We have previously shown that fibroblast growth factor signalling controls the formation of the most anterior somites in amphioxus; therefore, unravelling the fibroblast growth factor signalling downstream effectors is of crucial importance to shed light on the evolutionary origin of vertebrate head muscles. By using a comparative RNA sequencing approach and genetic functional analyses, we show that several transcription factors, such as Six1/2, Pax3/7 and Zic, act in combination to ensure the formation of three different somite populations. Interestingly, these proteins are orthologous to key regulators of trunk, and not head, muscle formation in vertebrates. Contrary to prevailing thinking, our results suggest that the vertebrate head mesoderm is of visceral and not paraxial origin and support a multistep evolutionary scenario for the appearance of the unsegmented mesoderm of the vertebrates new 'head'.


DetPoseNet: Improving Multi-Person Pose Estimation via Coarse-Pose Filtering.
Human detection and pose estimation are essential for understanding human activities in images and videos. Mainstream multi-human pose estimation methods take a top-down approach, where human detection is first performed, then each detected person bounding box is fed into a pose estimation network. This top-down approach suffers from the early commitment of initial detections in crowded scenes and other cases with ambiguities or occlusions, leading to pose estimation failures. We propose the DetPoseNet, an end-to-end multi-human detection and pose estimation framework in a unified three-stage network. Our method consists of a coarse-pose proposal extraction sub-net, a coarse-pose based proposal filtering module, and a multi-scale pose refinement sub-net. The coarse-pose proposal sub-net extracts whole-body bounding boxes and body keypoint proposals in a single shot. The coarse-pose filtering step based on the person and keypoint proposals can effectively rule out unlikely detections, thus improving subsequent processing. The pose refinement sub-net performs cascaded pose estimation on each refined proposal region. Multi-scale supervision and multi-scale regression are used in the pose refinement sub-net to simultaneously strengthen context feature learning. Structure-aware loss and keypoint masking are applied to further improve the pose refinement robustness. Our framework is flexible to accept most existing top-down pose estimators as the role of the pose refinement sub-net in our approach. Experiments on COCO and OCHuman datasets demonstrate the effectiveness of the proposed framework. The proposed method is computationally efficient (5-6x speedup) in estimating multi-person poses with refined bounding boxes in sub-seconds.


Re-analysis of public genetic data reveals a rare X-chromosomal variant associated with type 2 diabetes.
The reanalysis of existing GWAS data represents a powerful and cost-effective opportunity to gain insights into the genetics of complex diseases. By reanalyzing publicly available type 2 diabetes (T2D) genome-wide association studies (GWAS) data for 70,127 subjects, we identify seven novel associated regions, five driven by common variants (LYPLAL1, NEUROG3, CAMKK2, ABO, and GIP genes), one by a low-frequency (EHMT2), and one driven by a rare variant in chromosome Xq23, rs146662057, associated with a twofold increased risk for T2D in males. rs146662057 is located within an active enhancer associated with the expression of Angiotensin II Receptor type 2 gene (AGTR2), a modulator of insulin sensitivity, and exhibits allelic specific activity in muscle cells. Beyond providing insights into the genetics and pathophysiology of T2D, these results also underscore the value of reanalyzing publicly available data using novel genetic resources and analytical approaches.


The role of visual feedback by a disclosing agent in plaque control.
The common prescription of disclosing agents for home use assumes a relationship between visual feedback from stained plaque and subsequent oral hygiene behaviour. A study of double crossover design showed that there was no significant difference in the improvement in plaque control between the group which received only individual oral hygiene education and another group which had the same oral hygiene education supplemented by the home use of a disclosing agent for 2 weeks. On receiving oral hygiene reinforcement and discontinuing use of the disclosing agent, there was a further significant improvement in plaque control after another 2 weeks. This again suggests that visual feedback from the disclosing agent did not play a critical role in patient motivation. It appears that oral hygiene education is still fundamental to the whole concept of prevention. The prescription of a disclosing agent for home use should not be considered mandatory. Thorough and repeated oral hygiene education seems to be the most important feature in patient motivation.


Metallothionein mRNA expression and cadmium tolerance in metal-stressed and reference populations of the springtail Orchesella cincta.
Metal contamination in soil ecosystems is a permanent and often strong selection pressure. The present study investigates metal tolerance in 17 Orchesella cincta (Collembola) populations from metal-contaminated and reference sites, and combines analyses at the phenotypic and molecular level. Metal tolerance was phenotypically assayed by measuring survival times of laboratory cultures during exposure to cadmium. Comparisons of survival curves showed that five out of eight metal-stressed populations tested evolved increased cadmium tolerance (Stolberg, Plombieres, Hoboken, Hygum and Gusum). In addition, the role of the metallothionein (MT) gene in cadmium tolerance of O. cincta was studied by means of quantitative RT-PCR. The constitutive and Cd-induced MT mRNA expression of the laboratory cultures was measured. Results show that the mean constitutive MT mRNA expression of populations from polluted sites was significantly higher than of populations from reference sites. However, no correlation between MT mRNA expression levels after laboratory exposure to cadmium and field cadmium concentrations was observed. Furthermore, no relation between survival rate during exposure to cadmium and MT mRNA expression was detected. Our results suggest that constitutive MT mRNA expression plays a role in early protection against cadmium toxicity, and indicate that mechanisms other then MT up-regulation are involved in tolerance to prolonged exposure to cadmium.


Irritable bowel syndrome and chronic pelvic pain.
The irritable bowel syndrome (IBS) is a common functional bowel disorder diagnosed by characteristic symptoms. It is often associated with gynecologic symptoms, especially chronic pelvic pain (CPP). IBS symptoms worsen during menstruation and are correlated with increased levels of various perimenstrual symptoms. Psychosocial factors including depression, somatization, substance abuse, and childhood abuse are similar in IBS and CPP. IBS predisposes women to undergo hysterectomy and negatively influences pain improvement postoperatively. Therefore, IBS should be considered in the differential diagnosis of CPP. Collaboration between gynecologists and gastroenterologists is needed in the care of women with CPP and IBS as well as in the conduct of additional research on the relationship of these two disorders.


Advances in point-of-care technologies for molecular diagnostics.
Advances in miniaturization, nanotechnology, and microfluidics, along with developments in cloud-connected point-of-care (POC) diagnostics technologies are pushing the frontiers of POC devices toward low-cost, user-friendly, and enhanced sensitivity molecular-level diagnostics. The combination of various bio-sensing platforms within smartphone-integrated electronic readers provides accurate on-site and on-time diagnostics based on various types of chemical and biological targets. Further, 3D printing technology shows a huge potential toward fabrication and improving the performance of POC devices. Integration of skin-like flexible sensors with wireless communication technology creates a unique opportunity for continuous, real-time monitoring of patients for both preventative healthcare and during disease outbreaks. Here, we review recent developments and advances in POC technologies and describe how these advances enhance the performance of POC platforms. Also, this review describes challenges, directions, and future trends on application of emerging technologies in POC diagnostics.


Optimal biliary access point and learning curve for endoscopic ultrasound-guided hepaticogastrostomy with transmural stenting.
Although endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS) with transmural stenting has increased for biliary decompression in patients with an inaccessible papilla, the optimal biliary access point and the learning curve of EUS-HGS have not been studied. We evaluated the optimal biliary access point and learning curve for technically successful EUS-HGS. 129 consecutive patients (male n = 81, 62.3%; malignant n = 113, 87.6%) who underwent EUS-HGS due to an inaccessible papilla were enrolled. EUS finding and procedure times according to each needle puncture attempt in EUS-HGS were prospectively measured. Learning curves of EUS-HGS were calculated for two main outcome measurements (procedure time and adverse events) by using the moving average method and cumulative sum (CUSUM) analysis, respectively. A total of 174 EUS-HGS attempts were performed in 129 patients. The mean number of needle punctures was 1.35 ± 0.57. Using the logistic regression model, bile duct diameter of the puncture site ⩽ 5 mm [odds ratio (OR) 3.7, 95% confidence interval (CI): 1.71-8.1, p < 0.01] and hepatic portion length [linear distance from the mural wall to the punctured bile duct wall on EUS; mean hepatic portion length was 27 mm (range 10-47 mm)] > 3 cm (OR 5.7, 95% CI: 2.7-12, p < 0.01) were associated with low technical success. Procedure time and adverse events were shorter after 24 cases, and stabilized at 33 cases of EUS-HGS, respectively. Our data suggest that a bile duct diameter > 5 mm and hepatic portion length 1 cm to ⩽ 3 cm on EUS may be suitable for successful EUS-HGS. In our learning curve analysis, over 33 cases might be required to achieve the plateau phase for successful EUS-HGS.


7 transformations of leadership.
Most developmental psychologists agree that what differentiates one leader from another is not so much philosophy of leadership, personality, or style of management. Rather, it's internal "action logic"--how a leader interprets the surroundings and reacts when his or her power or safety is challenged. Relatively few leaders, however, try to understand their action logic, and fewer still have explored the possibility of changing it. They should, because leaders who undertake this voyage of personal understanding and development can transform not only their own capabilities but also those of their companies. The authors draw on 25 years of consulting experience and collaboration with psychologist Susanne Cook-Greuter to present a typology of leadership based on the way managers personally make sense of the world around them. Rooke and Torbert classify leaders into seven distinct actionlogic categories: Opportunists, Diplomats, Experts, Achievers, Individualists, Strategists, and Alchemists-the first three associated with below-average performance, the latter four with medium to high performance. These leadership styles are not fixed, the authors say, and executives who are willing to work at developing themselves and becoming more self-aware can almost certainly move toward one of the more effective action logics. A Diplomat, for instance, can succeed through hard work and self-reflection at transforming himself into a Strategist. Few people may become Alchemists, but many will have the desire and potential to become Individualists and Strategists. Corporations that help their executives and leadership teams to examine their action logics can reap rich rewards.


Similarities between the secondary structure of satellite tobacco mosaic virus and tobamovirus RNAs.
The secondary structure of satellite tobacco mosaic virus (STMV) RNA was predicted using computer simulations of RNA folding. The analogies of structural elements in the 3' end untranslated regions (3'-UTR) of tobamoviral RNAs were analysed. In addition to the tRNA-like structure and pseudoknot stalk, which are found in all known RNAs of tobamoviruses and STMV, another region of stable consecutive pseudoknots was predicted in the 3'-UTR of STMV RNA. A similar pattern of repeated structural units, containing pseudoknot stalks and parts of the tRNA-like structure, was also found in odontoglossum ringspot virus (ORSV) RNA 3'-UTR. The predictions on the structure are supported by sequence comparisons which point to an important functional role of 3' terminal pseudoknots in STMV RNA as well as in other tobamoviral RNAs. The possible participation of pseudoknotted structures in the interactions with coat protein in STMV is discussed.


Nanomaterials under high-pressure.
The use of high-pressure for the study and elaboration of homogeneous nanostructures is critically reviewed. Size effects, the interaction between nanostructures and guest species or the interaction of the nanosystem with the pressure transmitting medium are emphasized. Phase diagrams and the possibilities opened by the combination of pressure and temperature for the elaboration of new nanomaterials is underlined through the examination of three different systems: nanocrystals, nano-cage materials which include fullerites and group-14 clathrates, and single wall nanotubes. This tutorial review is addressed to scientist seeking an introduction or a panoramic view of the study of nanomaterials under high-pressure.


Task selection and enriched environments: a functional upper extremity training program for stroke survivors.
Functional tasks using real-life objects in an enriched environment provide a multidimensional approach to treatment. Functional tasks are therapeutic for stroke survivors, because they require the simultaneous use of motor control, cognition, visual perception, sensation, and motor planning. Therapists utilizing functional tasks as treatment modalities must also be multidimensional in their implementation. This article provides a systematic approach to guide therapists in developing a functional upper extremity training program for stroke survivors.


The modifying effect of anesthetic technique on the metabolic and endocrine responses to anesthesia and surgery.
In spite of the fact that our knowledge on the release mechanisms of the surgical stress response is rather incomplete, several techniques are available to modulate the response. However, at present it appears that no technique is capable to effectively suppress all aspects of the injury response and the widespread use of the term "stress free anesthesia" in surgery is therefore not valid. However, continuous administration of local anesthetic agents in the epidural space is the most effective technique in so far as reduction of the stress response is concerned. The clinical implication of a variable reduction in the stress response to surgery by different anesthetic techniques remains largely unsettled, since only few controlled studies have been published on the clinical effects of pain relief and general anesthesia. However, a vast amount of data exist from controlled studies comparing regional anesthesia with local anesthetics and general anesthesia. The cumulative experience from these studies have demonstrated an advantageous effect on postoperative morbidity parameters such as blood loss, postoperative thromboembolic complications, pulmonary infective complications, gastrointestinal motility, postoperative hospital stay, etc. The most pronounced effect on morbidity in these studies is in procedures where regional anesthesia has also been demonstrated to be most effective on the surgical stress response. However, whether this is a causal relationship or a coincidental event, has not been finally answered.(ABSTRACT TRUNCATED AT 250 WORDS)


Immobilization of E. coli beta-galactosidase and its derivatives by polyacrylamide gel.
We have recently prepared some crosslinked derivatives of Escherichia coli beta-galactosidase by treating the enzyme with bisimidoesters. In this article, we report the results obtained when the native and these crosslinked derivatives are entrapped in polyacrylamide gel lattice. It was found that use of combination of three protective agents, viz., bovine serum albumin, cysteine, and lactose, during immobilization gave an increased yield of 190% in the case of DMA crosslinked preparation. In the case of native enzyme, the K(m), pH optimum, and temperature optimum were found to remain unchanged on immobilization. The DMA crosslinked preparation entrapped in polyacrylamide in the presence of BSA, lactose, and cysteine was found to be a significantly better catalyst and hydrolyzed 47% milk lactose as compared to 31% hydrolysis by entrapped native enzyme in 6 h.


Antipairing and strand transferase activities of E. coli helicase II (UvrD).
The product of the uvrD gene of Escherichia coli, UvrD (helicase II), is known to be involved in methyl-directed mismatch repair, transposon excision and uvrABC excision repair. In conjugational crosses, various uvrD mutants have been reported to result in higher, lower or unaffected recombination frequencies. In an attempt to clarify the role of UvrD in recombination, we have studied in vitro its effects on two key reactions driven by RecA, homologous pairing and strand exchange. We show here that UvrD efficiently prevents or reverses RecA-mediated homologous pairing. Unexpectedly, we also found that it can stimulate RecA-driven branch migration and even catalyze strand exchange in the absence of RecA. A possible in vivo role for these antagonistic activities is discussed.


Management and knowledge of enteral nutrition in intensive care units in a city in Belgium.
The administration of enteral nutrition in intensive care unit (ICU) patients is largely managed by nurses. However, the degree of knowledge, interest, and training in this field can differ considerably among nurses and among ICUs. Such differences may lead to variations in the way in which enteral nutrition is used. To investigate these issues, a questionnaire survey was sent to the nursing staffs of 5 ICUs in Belgium. The response rate was 68%. Although theoretical knowledge of enteral nutrition was globally poor, its advantages over parenteral nutrition were usually known. Responses to questions related to practical issues associated with enteral feeding showed more institution-specific answers than interindividual differences.


A Polynomial-Time Algorithm for Minimizing the Deep Coalescence Cost for Level-1 Species Networks.
Phylogenetic analyses commonly assume that the species history can be represented as a tree. However, in the presence of hybridization, the species history is more accurately captured as a network. Despite several advances in modeling phylogenetic networks, there is no known polynomial-time algorithm for parsimoniously reconciling gene trees with species networks while accounting for incomplete lineage sorting. To address this issue, we present a polynomial-time algorithm for the case of level-1 networks, in which no hybrid species is the direct ancestor of another hybrid species. This work enables more efficient reconciliation of gene trees with species networks, which in turn, enables more efficient reconstruction of species networks.


Estimated lifetime effective dose to hunters and their families in the three most contaminated counties in Sweden after the Chernobyl nuclear power plant accident in 1986 - A pilot study.
Hunters and their families were one of the most exposed subpopulations in Sweden after the Chernobyl nuclear power plant accident in 1986. In this pilot study we used existing registries and whole-body measurements to develop algorithms to calculate lifetime effective doses and collective doses to some hunters in Sweden. Ten hunters and their family members were randomly selected from each of the three most contaminated counties in Sweden (Västernorrland, Uppsala, Gävleborg) using the register for hunting weapons from the Police Authority in 1985. Hence, this design can be regarded as a closed cohort only including hunters and their family members living in these three counties at the time of the accident. Statistics Sweden matched these individuals (n = 85) with their dwelling coordinates onto the digital map produced by the Swedish Radiation Safety Authority after aerial measurements of 137Cs (kBq m-2). Internal effective doses were estimated using aggregated transfer factors from ground deposition to in-vivo body concentration for 134Cs and 137Cs in hunters (Bq kg-1). External effective doses were also calculated on the dwelling coordinate for 134Cs, 137Cs and short-lived nuclides in these three counties. Annual effective doses for external and internal doses were then cumulated up to a life expectancy of 80 years for men and 84 years for women, respectively. The total lifetime effective doses to the members of the hunter families in this cohort were on average 8.3 mSv in Västernorrland, 4.7 mSv in Uppsala and 4.1 mSv in Gävleborg. The effective dose to men were about 40% higher than in women. In all counties the internal dose was about 75% of the total lifetime effective dose. The collective dose for all hunters with family members, in total about 44,000 individuals, in these three counties could be approximated at about 256 manSv. This study shows it is possible to use register data to develop algorithms for calculating lifetime effective dose commitments for hunters with relatively accuracy.


Comparison of viral hepatitis-associated hepatocellular carcinoma due to HBV and HCV - cohort from liver clinics in Pakistan.
Hepatocellular carcinoma (HCC) is the first cause of death in cirrhotic patients, mostly due to viral hepatitis with HCV or HBV infection. This study was performed to estimate the true prevalence of viral hepatitis-related HCC and the demographic and clinical-pathological associations with the two virus types. This cross sectional observational study enrolled clinical data base of 188 HCC patients and variables included from baseline were age, sex, area of residence, clinical-pathological features such as underlying co-morbidity, presence or absence of liver cirrhosis, macrovascular involvement, tumor extension and metastasis, liver lobes involved, serum alpha-fetoprotein level, and hepatitis serologies. Overall prevalence of HCV- and HBV-related HCC was 66.0% and 34.0%, respectively. Patients with HCV were more likely to develop HCC at advanced age (52.4±11.9 vs. 40.7±12.09 years), with highly raised serum AFP levels (≥400ng/ml) 78.2% (HBV 67.1%), large tumor size (HCV-66% >5 cm, HBV-59.3%), and presence of portal vein thrombosis (8.06%, HBV 1.56%). A binominal multivariate analysis showed that HCV-HCC group were more likely to be cirrhotic (OR=0.245, 95%CI: 0.117, 0.516) and had more than two times higher rate of solitary macrovascular involvement (OR=2.533, 95%CI: 1.162, 5.521) as compared with HBV associated HCC. Statistically significant variations were observed from baseline to clinical-pathological characteristics in HCV vs HBV associated HCC. Our study suggests prompt and early screening for high risk patients so that the rate of progression of these chronic viral diseases to cirrhosis and cancer can be decreased.


Construction of a highly saturated genetic map and identification of quantitative trait loci for leaf traits in jujube.
Chinese jujube (Ziziphus jujuba Mill.), a member of the genus Ziziphus, which comes under the family Rhamnaceae, is the most important species in terms of its economic, ecological, and social benefits. To dissect the loci associated with important phenotypical traits and analyze their genetic and genomic information in jujube, a whole-genome resequencing (WGR) based highly saturated genetic map was constructed using an F1 hybrid population of 140 progeny individuals derived from the cross of 'JMS2' × 'Jiaocheng 5'. The average sequencing depth of the parents was 14.09× and that of the progeny was 2.62×, and the average comparison efficiency between the sample and the reference genome was 97.09%. Three sets of genetic maps were constructed for a female parent, a male parent, and integrated. A total of 8,684 markers, including 8,158 SNP and 526 InDel markers, were evenly distributed across all 12 linkage groups (LGs) in the integrated map, spanning 1,713.22 cM with an average marker interval of 0.2 cM. In terms of marker number and density, this is the most saturated genetic map of jujube to date, nearly doubling that of the best ones previously reported. Based on this genetic map and phenotype data from 2019 to 2021, 31 leaf trait QTLs were identified in the linkage groups (LG1, 15; LG3, 1; LG5, 8; LG7, 4; LG8, 1, and LG11, 2), including 17 major QTLs. There were 4, 8, 14, and 5 QTLs that contributed to leaf length, leaf width, leaf shape index, and leaf area, respectively. Six QTLs clusters were detected on LG1 (8.05 cM-9.52 cM; 13.12 cM-13.99 cM; 123.84 cM-126.09 cM), LG5 (50.58 cM-50.86 cM; 80.10 cM-81.76 cM) and LG11 (35.98 cM-48.62 cM). Eight candidate genes were identified within the QTLs cluster regions. Annotation information showed that 4 genes (LOC107418196, LOC107418241, LOC107417968, and LOC112492570) in these QTLs are related to cell division and cell wall integrity. This research will provide a valuable tool for further QTL analysis, candidate gene identification, map-based gene cloning, comparative mapping, and marker-assisted selection (MAS) in jujube.


Induction of the SOS response by IS1 transposase.
We find that IS1 transposase, like that of Tn10, can induce the SOS response when produced at high levels. Most of the activity (> 80%) requires IS1 ends in cis to the transposase gene and depends strictly on the presence of RecBCD function. This implies that processing of transposase-induced cleavages is responsible for generating the response. Induction of the SOS response during growth in a rich medium is seen only when cells approach stationary phase. The end-dependent induction is abolished by mutations in the ends of IS1 that eliminate transposition activity. IS1 ends in identical orientation on the same plasmid are inactive in transposition but stimulate SOS strongly. Even plasmids with a single end can stimulate SOS, probably as a consequence of plasmid dimer formation which places the ends in direct repeat orientation. These results imply that transposase-induced cleavages do not need inversely oriented ends. The system can therefore be used to dissociate cleavage activity from the other reactions of transposition. Induction of SOS by a series of short (67 to 114 bp) IS1-like elements was found to occur in a cyclical pattern as a function of length with a period of 10 to 11 bp. The frequency of cointegration promoted by these elements showed the same helix-phase dependence. These results suggest that transposase molecules bound to the ends of IS1 interact, and that this interaction is needed for the cleavages that initiate transposition.


Implants of polyanionic collagen matrix in bone defects of ovariectomized rats.
In recent years, there has been a great interest in the development of biomaterials that could be used in the repair of bone defects. Collagen matrix (CM) has the advantage that it can be modified chemically to improve its mechanical properties. The aim of the present study was to evaluate the effect of three-dimensional membranes of native or anionic (submitted to alkaline treatment for 48 or 96 h) collagen matrix on the consolidation of osteoporosis bone fractures resulting from the gonadal hormone alterations caused by ovariectomy in rats subjected to hormone replacement therapy. The animals received the implants 4 months after ovariectomy and were sacrificed 8 weeks after implantation of the membranes into 4-mm wide bone defects created in the distal third of the femur with a surgical bur. Macroscopic analysis revealed the absence of pathological alterations in the implanted areas, suggesting that the material was biocompatible. Microscopic analysis showed a lower amount of bone ingrowth in the areas receiving the native membrane compared to the bone defects filled with the anionic membranes. In ovariectomized animals receiving anionic membranes, a delay in bone regeneration was observed mainly in animals not subjected to hormone replacement therapy. We conclude that anionic membranes treated with alkaline solution for 48 and 96 h presented better results in terms of bone ingrowth.


Public health and the undergraduate medical curriculum: are we preparing physicians for the 21st century?
To investigate the adequacy of the undergraduate medical curriculum in Pakistan to address primary healthcare and public health needs of the community at national level. The cross-sectional study used standardised pilot-tested instruments from January 12 to July 14, 2010. Stratified purposive sampling technique was employed to include public and private-sector medical colleges in the study. A total of 174 faculty members were interviewed at 11 medical colleges. Data entry and analysis was done using SPSS 17.0. Of the 174 faculty members, 93 (53%) were male. The age of the respondents ranged between 26 and 68 years (Mean: 43 +/- 9 years). Of the participants, 64 (37%) had worked in a primary healthcare facility at some point in their career. Various aspects of maternal, newborn and child health are not covered by the medical curriculum as reported by the faculty members. There is disconnection between academia, primary healthcare providers, policymakers and the regulators. The primary healthcare providers have inadequate representation in the curriculum design. There is a need to re-direct financial resources, medical education, and medical practitioners with a focus on addressing the needs of the rural areas.


The evolution of patch selection in stochastic environments.
A null model for habitat patch selection in spatially heterogeneous environments is the ideal free distribution (IFD), which assumes individuals have complete knowledge about the environment and can freely disperse. Under equilibrium conditions, the IFD predicts that local population growth rates are zero in all occupied patches, sink patches are unoccupied, and the fraction of the population selecting a patch is proportional to the patch's carrying capacity. Individuals, however, often experience stochastic fluctuations in environmental conditions and cannot respond to these fluctuations instantaneously. An evolutionary stability analysis for fixed patch-selection strategies reveals that environmental uncertainty disrupts the classical IFD predictions: individuals playing the evolutionarily stable strategy may occupy sink patches, local growth rates are negative and typically unequal in all patches, and individuals prefer higher-quality patches less than predicted by their carrying capacities. Spatial correlations in environmental fluctuations can enhance or marginalize these trends. The analysis predicts that continually increasing environmental variation first selects for range expansion, then selects for persisting coupled sink populations, and ultimately leads to regional extinction. In contrast, continually increasing habitat degradation first selects for range contraction and may select for persisting coupled sink populations before regional extinction. These results highlight the combined roles of spatial and temporal heterogeneity on the evolution of habitat selection.


Efficient, Full Spectrum-Driven H2 Evolution Z-Scheme Co2P/CdS Photocatalysts with Co-S Bonds.
Exploring high-efficiency, low-cost, and stable photocatalysts that enable full solar spectrum including UV, visible, and near-infrared (NIR) light utilization for photocatalytic hydrogen generation still faces huge challenge. Herein, a Co2P/CdS Z-scheme photocatalyst without a noble metal is rationally fabricated to achieve ultrabroad UV-vis-NIR harvesting. Compared to Pt/CdS, CdS, and Co2P, the optimized Co2P/CdS exhibits much more outstanding performance with the H2 generation rates of 262.16, 66.98, and 3.93 mmol/g/h under solar, visible (780 nm > λ > 420 nm), and NIR (λ > 780 nm) light, respectively. Particularly, 10% Co2P/CdS displays a prominent apparent quantum efficiency value of 2.26% at 700 nm. The Z-scheme transform route can effectively enhance the separation of charge carriers in Co2P/CdS for UV-vis-driven HER, as confirmed by photoluminescence and photoelectrochemical measurements. More importantly, the Co-S bonds at the interface demonstrated by Fourier transform infrared, Raman (mapping), and X-ray photoelectron spectroscopy and density functional theory calculations can act as a "bridge" for charge transfer, thereby enhancing the full spectrum-driven H2 evolution. To the best of our knowledge, this is a rare research on full spectrum-driven photocatalytic HER without a noble metal.


Photonic crystal fiber in the polychaete worm Pherusa sp.
Setae of the polychaete worm Pherusa exhibit remarkably strong photonic effects, which arise from their two-dimensional-periodic internal structure of hexagonally packed cylindrical channels. The hexagonal order is limited to monocrystalline domains of different orientation, which results in an overall polycrystalline effect. A detailed experimental and theoretical investigation of this structure reveals that the internal photonic structure is carefully tuned with respect to its lattice constant in order to provide an optical response coinciding with the visible wavelength rage. A further optimization is observed for the packing fraction of cylindrical channels in order to maximize the width of photonic band gaps, and hence the reflectance of incident visible light.


Segmentation of CT Lung Images Using FCM with Active Contour and CNN Classifier.
Lung cancer is one of the unsafe diseases for human which reduces the patient life time. Generally, most of the lung cancers are identified after it has been spread into the lung parts and moreover it is difficult to find the lung cancer at the early stage. It requires radiologist and special doctors to find the tumoral tissue of the lung cancer. For this reason, the recommended work helps to segment the tumoral tissue of CT lung image in an effective way. The research work uses hybrid segmentation technique to separate the lung cancer cells to diagnose the lung tumour. It is a technique which combines active contour along with Fuzzy c means to diagnose the tumoral tissue. Further the segmented portion was trained by Convolutional Neural Network (CNN) in order to classify the segmented region as normal or abnormal. The evaluation of the proposed method was done by analyzing the results of test image with the ground truth image. Finally, the results of the implemented technique provided good accuracy, Peak signal to noise ratio (PSNR), Mean Square Error (MSE) value. In future the other techniques can be utilized to improve the details before segmentation. The proposed work provides 96.67 % accuracy. Hybrid segmentation technique involves several steps like preprocessing, binarization, thresholding, segmentation and feature extraction using GLCM.


Intron 1 inversion mutation among Turkish hemophilia A patients.
Hemophilia A is an X-linked bleeding disorder resulting mostly from heterogeneous point mutations in the factor VIII (F8) gene. Small/large gene deletions, insertions and gross gene rearrangements underlie the molecular pathogenesis of the disease. Two large inversion mutations due to intrachromosomal recombinations between inverted repeats found in intronic sequences and upstream regions of the F8 gene result in severe hemophilia A. The intron 1 inversion mutation is responsible for about 2% of the cases in various populations. Herein, we report the establishment of the long polymerase chain reaction (PCR) intron 1 inversion mutation detection in our laboratory and a similar frequency of 1-2% among Turkish patients.


The pharmacokinetics of enalapril in hospitalized patients with congestive heart failure.
The pharmacokinetics of the converting enzyme inhibitor, enalapril, were studied in an open, randomized, balanced crossover design in 12 hospitalized patients with stable, chronic congestive heart failure (CHF). Enalapril maleate is a prodrug requiring in vivo hepatic esterolysis to yield the active diacid inhibitor enalaprilat. CHF results in changes in regional blood flow that may affect the gastrointestinal absorption, hepatic hydrolysis and renal excretion of enalapril and enalaprilat. In order to evaluate the pharmacokinetics of enalapril in CHF, the following treatments were given: enalapril maleate 10 mg orally, enalapril maleate 5 mg intravenously and enalaprilat 5 mg intravenously. Each dose was followed by a 72 h period with frequent blood sampling and fractionated urine collection for the radioimmunoassay of enalaprilat, before and after sample hydrolysis. Mean absorption for the oral dose was 69%, hydrolysis 55%, bioavailability 38%, urinary recovery 77% and estimated first-pass effect 10%. The results were compared with available data in normal subjects. After oral administration of 10 mg enalapril maleate, the extent of absorption, the degree of hydrolysis and the bioavailability in CHF patients appear to be similar to those in normals with differences less than 10%. The rate of absorption and hydrolysis appear to be slightly slower in CHF. The serum concentrations of enalaprilat were consistently greater in CHF and maximal concentrations were reached at 6 h in CHF as compared to 4 h in normal subjects. We conclude that the presence of CHF does not appreciably alter the pharmacokinetic behaviour of enalapril. The observed differences may be associated with age as well as the disease state.


New insights on chromatin modifiers and histone post-translational modifications in renal cell tumours.
Renal cell tumours (RCTs) are the most common neoplasms affecting the kidney. They are clinically, pathologically and genetically heterogeneous, comprises four major histological subtypes [clear cell renal cell carcinoma (ccRCC), papillary renal cell carcinoma (pRCC) and chromophobe renal cell carcinoma (chRCC), which are malignant tumours, and oncocytoma, a benign tumour], as well as an increasing number of less common entities. Epigenetics has emerged as an important field in oncology due to the critical role it plays in neoplastic transformation and progression. Among epigenetic mechanisms, the modulation of chromatin packaging through covalent modifications is fundamental for gene transcription regulation and its deregulation is involved in carcinogenesis. Recently, deregulation of chromatin machinery in RCTs has increasingly acknowledged as an important mechanism for renal neoplastic transformation. The aim of this review is to summarize the most relevant alterations in histone post-translational modifications and chromatin modifiers, which have been implicated in renal tumorigenesis. The recognition of those modifications might provide new biomarkers for diagnosis and prognostication as well as novel targets for personalized therapeutic intervention.


Exploring Material Properties and Device Output Performance of a Miniaturized Flexible Thermoelectric Generator Using Scalable Synthesis of Bi2Se3 Nanoflakes.
Environmental heat-to-electric energy conversion presents a promising solution for powering sensors in wearable and portable devices. However, the availability of near-room temperature thermoelectric (TE) materials is highly limited, posing a significant challenge in this field. Bi2Se3, as a room-temperature TE material, has attracted much attention. Here, we demonstrate a large-scale synthesis of Bi2Se3 nanoflakes used for the microflexible TE generator. A high-performance micro-TE generator module, utilizing a flexible printed circuit, has been designed and fabricated through the process of screen printing. The TE generator configuration comprises five pairs of PN TE legs. The p-type TE leg utilizes commercially available Sb2Te3 powder, while the n-type TE leg employs Bi2Se3 nanoflakes synthesized in this study. For comparative purposes, we also incorporate commercially available Bi2Se3 powder as an alternative n-type TE leg. The optimal performance of the single-layer microflexible TE generator, employing Bi2Se3 nanoflakes as the active material, is achieved when operating at a temperature differential of 109.5 K, the open-circuit voltage (VOC) is 0.11 V, the short circuit current (ISC) is 0.34 mA, and the maximum output power (PMAX) is 9.5 μW, much higher than the generator consisting of commercial Bi2Se3 powder, which is expected to provide an energy supply for flexible electronic devices.


Synaptic plasticity in hippocampal CA1 neurons of mice lacking inositol-1,4,5-trisphosphate receptor-binding protein released with IP3 (IRBIT).
In hippocampal CA1 neurons of wild-type mice, a short tetanus (15 or 20 pulses at 100 Hz) or a standard tetanus (100 pulses at 100 Hz) to a naive input pathway induces long-term potentiation (LTP) of the responses. Low-frequency stimulation (LFS; 1000 pulses at 1 Hz) 60 min after the standard tetanus reverses LTP (depotentiation [DP]), while LFS applied 60 min prior to the standard tetanus suppresses LTP induction (LTP suppression). We investigated LTP, DP, and LTP suppression of both field excitatory postsynaptic potentials and population spikes in CA1 neurons of mice lacking the inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-binding protein released with IP3 (IRBIT). The mean magnitudes of LTP induced by short and standard tetanus were not different in mutant and wild-type mice. In contrast, DP and LTP suppression were attenuated in mutant mice, whereby the mean magnitude of responses after LFS or tetanus were significantly greater than in wild-type mice. These results suggest that, in hippocampal CA1 neurons, IRBIT is involved in DP and LTP suppression, but is not essential for LTP. The attenuation of DP and LTP suppression in mice lacking IRBIT indicates that this protein, released during or after priming stimulations, determines the direction of LTP expression after the delivery of subsequent stimulations.


[A Case Report on Subarachnoid Hemorrhage Secondary to Neurobrucellosis in a Patient with Cerebral Aneurysm].
Brucellosis is a multisystemic infection produced by a gram-negative bacillus that can develop a variety of clinical symptoms and complications. Involvement of the central nervous system is a challenging and dangerous consequence of systemic brucellosis. The neurobrucellosis clinical spectrum can be classified as central and peripheral. Meningitis, encephalitis, polyradiculoneuritis, cranial nerve involvement, depression, abscess and cerebrovascular events are some of the potential complications that may develop. The link between neurobrucellosis and cerebrovascular accident has been reported infrequently in the literature. In this report, a case of neurobrucellosis confirmed by cerebrospinal fluid agglutination test and who developed subarachnoid hemorrhage associated with cerebral aneurysm, which is a rare condition in its course was presented. Serum Rose Bengal test and serum Brucella standard tube agglutination (STA) tests were positive at a titer of 1/640 in a 38-year-old male patient who had complaints of fever, sweating, myalgia, arthralgia, weakness, head-neck-back pain and difficulty in walking for 14 days. On magnetic resonance imaging, Brucella sacroiliitis was identified. The patient's fever, head and neck pain continued and nuchal rigidity was found to be positive. Neurobrucellosis was diagnosed based on the cerebrospinal fluid (CSF) examination, which revealed a high white blood cell count, high protein, low glucose level, and STA in CSF at 1/640 titers. Imaging of the brain was conducted concurrently with cerebrospinal fluid analysis indicated subarachnoid hemorrhage caused by cerebral aneurysm rupture. In addition to the medical treatment, the aneurysm rupture was closed with surgical intervention. Three months of simultaneous triple antibiotic treatment were administered to the patient. In the third month of the treatment, the patient was completely cured and no longer had any problems. Although uncommon, subarachnoid hemorrhage due to aneurysm rupture is one of the cerebrovascular consequences of neurobrucellosis. In the process of differential diagnosis of cerebrovascular occurrences, particularly in areas where brucellosis is an endemic disease, it is important to keep in mind that neurobrucellosis can imitate a variety of diseases and cause cerebrovascular events.


A brief cognitive-behavioral approach to reducing anxiety sensitivity decreases pain-related anxiety.
Anxiety sensitivity (AS; fear of anxiety-related sensations) is a known risk factor for anxiety disorders and recently has been linked to pain disorders. The present study was guided by the hypothesis that a program designed to reduce AS levels might also result in a decrease in anxiety related to pain sensations. Female undergraduates, selected as either high or low in AS according to screening scores on the Anxiety Sensitivity Index (ASI), were randomly assigned to participate in 3 1-hour, small group sessions of either cognitive behavioral therapy (CBT; psycho-education, cognitive restructuring, and interoceptive exposure) or a non-specific treatment (NST). Immediately prior to and following the intervention, participants completed the 20-item Pain Anxiety Symptoms Scale (PASS-20). Consistent with hypothesis, results revealed a 3-way interaction between AS group, intervention condition, and time on PASS-20 total scores. Only participants with high pre-morbid levels of AS assigned to the CBT condition showed a significant reduction in scores on the PASS-20 from pre- to post-treatment. Implications for improving CBT approaches for pain disorders are discussed.


Matching diabetes treatment and lifestyle.
Strict glycaemic control reduces the likelihood of complications in patients with type 1 or type 2 diabetes mellitus. However, achieving such control as part of normal daily life can be difficult and may be further complicated by changes to daily routine. Here we highlight key ways of achieving good control without unduly restricting the patient's day-to-day activities. We also discuss the impact exercise, travel, changes in working patterns, and fasting can have on diabetic control and consider what practical advice healthcare professionals can offer to individuals facing such lifestyle changes.


Effects of TiO2 crystal structure on the luminescence quenching of [Ru(bpy)2(dppz)]2+-intercalated into DNA.
The intercalation of [Ru(bpy)2(dppz)]2+ labeled as Ru(II) (bpy=2,2'-bipyridine and dppz=dipyrido[3,2,-a:2',3'-c]phenazine) into herring sperm DNA leads to the formation of emissive Ru(II)-DNA dyads, which can be quenched by TiO2 nanoparticles (NPs) and sol-gel silica matrices at heterogeneous interfaces. The calcinations temperature exhibits a remarkable influence on the luminescence quenching of the Ru(II)-DNA dyads by TiO2 NPs. With increasing calcinations temperature in the range from 200 to 850°C, the anatase-to-rutile TiO2 crystal structure transformation increases the average particle size and hydrodynamic diameter of TiO2 and DNA@TiO2. The anatase TiO2 has the stronger ability to unbind the Ru(II)-DNA dyads than the rutile TiO2 at room temperature. The TiO2 NPs and sol-gel silica matrices can quench the luminescence of the Ru(II) complex intercalated into DNA by selectively capturing the negatively DNA and positively charged Ru(II) complex to unbind the dyads, respectively. This present results provide new insights into the luminescence quenching and competitive binding of dye-labeled DNA dyads by inorganic NPs.


Identification of a novel cell death receptor mediating IGFBP-3-induced anti-tumor effects in breast and prostate cancer.
Insulin-like growth factor-binding protein-3 (IGFBP-3), a major regulator of endocrine actions of IGFs, is a p53-regulated potent apoptotic factor and is significantly suppressed in a variety of cancers. Recent epidemiologic studies suggest that IGFBP-3 contributes to cancer risk protection in a variety of cancers, and a polymorphic variation of IGFBP-3 influences cancer risk, although other studies vary in their conclusions. Some antiproliferative actions of IGFBP-3 have been reported to be independent of IGFs, but the precise biochemical/molecular mechanisms of IGF-independent, antiproliferative actions of IGFBP-3 are largely unknown. Here we report a new cell death receptor, IGFBP-3R, that is a single-span membrane protein and binds specifically to IGFBP-3 but not other IGFBP species. Expression analysis of IGFBP-3 and IGFBP-3R indicates that the IGFBP-3/IGFBP-3R axis is impaired in breast and prostate cancer. We also provide evidence for anti-tumor effect of IGFBP-3R in vivo using prostate and breast cancer xenografts in athymic nude mice. Further in vitro studies demonstrate that IGFBP-3R mediates IGFBP-3-induced caspase-8-dependent apoptosis in various cancer cells. Knockdown of IGFBP-3R attenuated IGFBP-3-induced caspase activities and apoptosis, whereas overexpression of IGFBP-3R enhanced IGFBP-3 biological effects. IGFBP-3R physically interacts and activates caspase-8, and knockdown of caspase-8 expression or activity inhibited IGFBP-3/IGFBP-3R-induced apoptosis. Here, we propose that IGFBP-3R represents a novel cell death receptor and is essential for the IGFBP-3-induced apoptosis and tumor suppression. Thus, the IGFBP-3/IGFBP-3R axis may provide therapeutic and prognostic value for the treatment of cancer.


The effectiveness of a basic exercise intervention to improve strength and balance in women with osteoporosis.
To determine the effects of a simple exercise program on the balance and strength of postmenopausal women with osteoporosis. This program was based on low intensity strength and balance exercises, and was carried out with simple, readily available equipment. Sixty five women were randomly assigned to either the experimental group (EG; n=33, age: 57.4±4.8 years) or the control group (CG; n=32, age: 58.8±4.5 years). Participants in the EG underwent balance and strength training for 60 min, three times/week for 6 months. Each session consisted of warm-up exercises (10 min), balance training (20 min), strength training (20 min), and cooldown (10 min). Participants from the CG were asked not to modify their usual habits during the course of the study. Static balance was evaluated using the blind monopodal stance static balance test. In contrast, dynamic balance was assessed using the "8-foot up and go" test, whereas the strength of the upper and lower limbs was measured using the "arm curl" and "30 s chair stand" tests, respectively. All these variables were assessed at baseline and upon program completion. The EG showed significant improvements (P<0.001) in static balance (21%), dynamic balance (36%), and in the strength of the upper (80%) and lower (47%) limbs in comparison to the CG after the sixth month. Participants in the CG showed significantly lower values (P<0.001) in the four tests. In addition, a significant inverse relationship between static balance and the strength of the upper (r=-0.390; P=0.001) and lower (r=-0.317; P=0.01) limbs was found. The present study demonstrates that a physical exercise program based on balance and strength exercises, carried out with simple and readily available equipment, is capable of significantly improving the strength and balance of women with osteoporosis.


A review of devices used for photocuring resin-based composites.
Composite resin shrinks up to 5% by volume upon curing. This shrinkage and the associated contraction stress remain the two most significant clinical problems with curing resin composite restorations. Many patients continue to experience sensitivity following placement of direct composites and seating of indirect restorations utilizing resin cements. Unfortunately, some claims made by manufacturers or certain clinicians that promise to alleviate these problems are made from a marketing standpoint, with no refereed literature to support those claims. Even within the literature, contradictory results have been reported, perpetuating the confusion. It is of utmost importance that all practicing dentists be aware of the various types of curing systems available and the advantages and disadvantages of each system. It is the opinion of the author that no existing system will alleviate every problem. Until new composite systems are perfected, such as the cyclopolymerizable resins and expanding polymers, we will continue to have shrinkage and stress. Be aware of false claims, read and interpret the literature, and, most importantly, do what is best for your patients.


Simultaneous masking between electric and acoustic stimulation in cochlear implant users with residual low-frequency hearing.
Ipsilateral electric-acoustic stimulation (EAS) is becoming increasingly important in cochlear implant (CI) treatment. Improvements in electrode designs and surgical techniques have contributed to improved hearing preservation during implantation. Consequently, CI implantation criteria have been expanded toward people with significant residual low-frequency hearing, who may benefit from the combined use of both the electric and acoustic stimulation in the same ear. However, only few studies have investigated the mutual interaction between electric and acoustic stimulation modalities. This work characterizes the interaction between both stimulation modalities using psychophysical masking experiments and cone beam computer tomography (CBCT). Two psychophysical experiments for electric and acoustic masking were performed to measure the hearing threshold elevation of a probe stimulus in the presence of a masker stimulus. For electric masking, the probe stimulus was an acoustic tone while the masker stimulus was an electric pulse train. For acoustic masking, the probe stimulus was an electric pulse train and the masker stimulus was an acoustic tone. Five EAS users, implanted with a CI and ipsilateral residual low-frequency hearing, participated in the study. Masking was determined at different electrodes and different acoustic frequencies. CBCT scans were used to determine the individual place-pitch frequencies of the intracochlear electrode contacts by using the Stakhovskaya place-to-frequency transformation. This allows the characterization of masking as a function of the difference between electric and acoustic stimulation sites, which we term the electric-acoustic frequency difference (EAFD). The results demonstrate a significant elevation of detection thresholds for both experiments. In electric masking, acoustic-tone thresholds increased exponentially with decreasing EAFD. In contrast, for the acoustic masking experiment, threshold elevations were present regardless of the tested EAFDs. Based on the present findings, we conclude that there is an asymmetry between the electric and the acoustic masker modalities. These observations have implications for the design and fitting of EAS sound-coding strategies.


Looking through the right end of the telescope: creating a focused vision for a school of nursing.
The challenges facing nursing higher education necessitate that academic administrators have a focused vision for their schools of nursing. Nursing, like other areas of higher education, embraced the concept of strategic planning to set priorities, use resources wisely, and take advantage of available opportunities that were consistent with the strategic direction. While there has been a shift toward a less-structured approach to planning, nursing deans need tools to assess the environment, make rational decisions, set priorities, plan for change, and develop strategies to meet the short-term and long-term goals of the unit. Given the challenges facing nursing education and higher education, the need for a planning approach is critical. The case study in this article describes a flexible and creative approach to the planning process that helped the University of Virginia School of Nursing set priorities and achieve its goals.


Evidence-based treatments remain the best intervention for good long-term outcome of severe and enduring anorexia nervosa.
More research is needed about response to specialist treatments for severe and enduring anorexia nervosa. Current evidence suggests those with severe and enduring anorexia nervosa respond to evidence-based treatments and continue to recover over decades. In the absence of clear guidelines to the contrary and given our understanding of the superior efficacy of specialist treatments over more eclectic treatment choices, it is our responsibility to continue to train and supervise clinicians to deliver evidence-based treatments, irrespective of the variant of anorexia nervosa.


Case studies: orthopaedic surgery in adult patients with haemophilia A with inhibitors.
Whilst orthopaedic surgery in haemophilia patients without inhibitors is now relatively common in specialized centres, until recently there have been only a few sporadic instances of surgery having been undertaken on patients with inhibitors. The availability of recombinant activated factor VII (rFVIIa) for haemostatic cover during surgery allows procedures to be performed that previously may not have been considered possible. Complications associated with thrombosis are rare in haemophilia patients with inhibitors, but bleeding complications remain a concern. Globally, experience of performing orthopaedic surgery in these patients is increasing and many successful outcomes have been reported. However, more knowledge relating to the incidence and type of bleeding complications liable to be encountered, together with further information about appropriate rescue treatment, would be valuable. Data relating to long-term follow-up after surgery would be useful, as would a comparison of outcomes between haemophilia patients with and without inhibitors. Optimal dosing regimens for rFVIIa as surgical cover are still to be determined and further information is required relating to the cost effectiveness of rFVIIa in surgery. Further study should address these issues.


A review of the implantable cardioverter defibrillator trials.
Clinical ventricular tachycardia and ventricular fibrillation are associated with a high recurrence rate, and through the 1980s and the early 1990s a variety of therapies have been proposed including the implantable cardioverter defibrillator (ICD). Over the past decade it has been recognized that prospective randomized trials are imperative if the proper role for any therapy is to be defined. The Antiarrhythmic Versus Implantable Defibrillator (AVID) trial recently was concluded and helped define the role of the ICD in high-risk patients. Other trials are studying patients at high risk for sudden death who have not yet had a clinical event. The recently concluded Multicenter Automatic Defibrillator Implantation Trial and CABG Patch Trial helped determine the proper role of the ICD in various pre-event high-risk subsets. These trials are summarized in detail.


The impact of the Needlestick Safety and Prevention Act on home care and hospice organizations.
Administrators, managers, and clinicians need to be up-to-date on all aspects of the new Needlestick Safety and Prevention Act recently passed into law. This article gives the background and foundation needed to implement policies, procedures, and actions that will assure compliance with the law and increased worker safety.


Sensitization and subjective health complaints.
Why is it that some of us have more pain, more fatigue, and more gastrointestinal trouble than others? Is it possible that there are brain mechanisms and psychological mechanisms that make some people sensitized to specific complaints? In this concluding paper we review the historical and theoretical background, discuss the evidence and theoretical positions in the contributions, and draw some conclusions. Traditional psychosomatic models had less predictive value and less therapeutic importance than what was hoped for. The main problem with these models was the lack of a pathophysiological explanation for why psychological problems could be related to somatic disease. Sustained arousal or "allostatic load" offers more plausible and acceptable mechanisms for pathology, and, to some extent, for sensitization and illness. The combination of cognitive psychology and neurophysiology offers a model for somatic pathology, and, perhaps more important, also for the understanding of subjective complaints and illness.


Tobacco use among college students in Kerala, India.
Despite tobacco use among college students being a major health concern, data remain sparse from India. It is in this background that this study aimed to report the prevalence of tobacco use and its psychosocial correlates among college students in the State of Kerala, India. A total of 5784 students from 58 colleges from Ernakulam district, Kerala, selected by cluster random sampling and were provided with self-administered questionnaire. In addition to socio-demographic profile, the questionnaire incorporated alcohol, smoking, and substance involvement screening test (ASSIST, for assessing tobacco use and its severity, lifetime use of other substances); Kessler's scale (psychological distress) and Barkeley's scale (attention deficit hyperactivity disorder symptoms). Screening questions were used for assessing lifetime suicidality and sexual abuse. The lifetime prevalence of tobacco use was 8.6 per cent (21.5% males and 1.4% female). Among users, hazardous and dependent use defined using ASSIST scores was 63.3 and 2.9 per cent, respectively. Tobacco use was associated with older age, being male, urban residence, having a part-time job, use of alcohol and illicit drugs and academic failures. Although the prevalence of tobacco use in our study was relatively low, the proportionately higher rates of hazardous use and its association with the negative correlates suggest that more needs to be done to prevent its deleterious consequences.


Resveratrol prevents angiotensin II-induced hypertrophy of vascular smooth muscle cells through the transactivation of growth factor receptors.
We previously showed that augmented levels of endogenous angiotensin II (AngII) contribute to vascular smooth muscle cell (VSMC) hypertrophy through the transactivation of growth factor receptors in spontaneously hypertensive rats. Resveratrol (RV), a polyphenolic component of red wine, has also been shown to attenuate AngII-evoked VSMC hypertrophy; however, the molecular mechanism mediating this response is obscure. The present study was therefore undertaken to examine whether RV could prevent AngII-induced VSMC hypertrophy through the transactivation of growth factor receptor and associated signaling pathways. AngII treatment of VSMC enhanced the protein synthesis that was attenuated towards control levels by RV pretreatment as well as by the inhibitors of NADPH oxidase, c-Src, and growth factor receptors. Furthermore, RV pretreatment also inhibited enhanced levels of superoxide anion, NADPH oxidase activity, increased expression of NADPH oxidase subunits, and phosphorylation of c-Src, EGF-R, PDGE-R, ERK1/2, and AKT1/2. In conclusion, these results indicate that RV attenuates AngII-induced VSMC hypertrophy through the inhibition of enhanced oxidative stress and activation of c-Src, growth factor receptors, and MAPK/AKT signaling. We suggest that RV could be used as a therapeutic agent in the treatment of vascular complications associated with hypertension and hypertrophy.


Ground reaction force profiles from force platform gait analyses of clinically normal mesomorphic dogs at the trot.
Force platform analysis of gait provides ground reaction force information that can be used to study limbs with normal or abnormal function. When combined, the interrelated variables of ground reaction forces give a more thorough description of gait than when used individually. To describe the pattern of ground reaction forces in clinically normal, conditioned, mesomorphic dogs, we studied the data from platform gait analyses of 43 dogs. Mediolateral (Fx), craniocaudal (Fy), and vertical (Fz) forces were measured and recorded. Torque (Tz) around the vertical axis also was calculated. Mean stance times for forelimbs and hind limbs were 0.278 and 0.261 second, respectively. Among dogs, ground reaction forces were normalized and expressed as percentage of body weight (%bw). The vertical (Fz) peak, average force during stance phase, and force vs time impulses were 106.68, 60.82, and 17.2 %bw in forelimbs, and were 65.11, 35.3, and 9.33 %bw in hind limbs. The forelimb braking/propulsive (Fy) peaks were -16.74 and +6.73 %bw. In hind limbs, these peaks were -3.76 and +7.69 %bw. The usual mediolateral force (Fx) pattern found in forelimbs was laterally directed, with average peak magnitude of 6.69 %bw, whereas the hind limb patterns were variable.


Participatory Design of an Online Self-Management Tool for Users With Spinal Cord Injury: Qualitative Study.
Rehospitalization rates resulting from secondary conditions in persons with spinal cord injuries (SCI) are high. Self-management programs for many chronic conditions have been associated with decreases in hospital readmissions. However, in the SCI community, evidence suggests that satisfaction with traditional self-management programs is low. Users with SCI have indicated preference for programs that are online (rather than in-person), that target SCI-specific concerns, and are led by peers with SCI. There is currently no program with all of these features, which addresses self-management of secondary conditions after SCI. The aim of this study was to provide details of a participatory design (PD) process for an internet-mediated self-management program for users with SCI (called SCI & U) and illustrate how it has been used to define design constraints and solutions. Users were involved in development as codesigners, codevelopers, and key informants. Codesigners and codevelopers were recruited from consumer advocacy groups and worked with a core development team. Key informants were recruited from geographically distributed advocacy groups to form a product advisory council that met regularly with the core team. During meetings, codesigners and informants walked through stages of work that typify PD processes such as exploration, discovery, and prototyping. This paper details the process by analyzing 10 meetings that took place between August 2015 and May 2016. Meetings were recorded, transcribed, and subjected to an inductive thematic analysis; resulting themes were organized according to their relationship to PD stages. A total of 16 individuals participated in meeting discussions, including 7 researchers and 9 persons with SCI from 4 Canadian provinces. Themes of trust, expertise, and community emerged in every group discussion. The exploration stage revealed interest in online self-management resources coupled with concerns about information credibility. In general, participants indicated that they felt more confident with information received from trusted, in-person sources (eg, peers or health care professionals) than information found online. The discovery stage saw participants propose and discuss concepts to filter credible information and highlight community expertise, namely (1) a community-curated resource database, (2) online information navigators, and (3) group chats with peers. Several tools and techniques were collectively prototyped in an effort to foster trust and community; these are illustrated in the Results section. A PD process engaging users as codesigners, codevelopers, and informants can be used to identify design concerns and prototype online solutions to promote self-management after SCI. Future work will assess the usability of the collectively designed tools among a broad population of Canadians with SCI and the tools' impact on self-efficacy and health.


Cardiovascular and renal effects of low-dose atrial natriuretic peptide in compensated cirrhosis.
Patients with cirrhosis and ascites have high plasma levels of atrial natriuretic peptide (ANP). Pharmacological doses of this hormone usually worsen systemic hemodynamics of cirrhotic patients. We assessed whether ANP influences cardiovascular homeostasis and renal function in patients with compensated cirrhosis at plasma levels comparable to those observed in patients with cirrhosis and ascites. Radionuclide angiocardiography was performed in eight compensated cirrhotic patients during placebo (three periods of 15 min each) and ANP infusion (2, 4, and 6 pmol/kg.min for 15 min each), together with appropriate blood and urine sampling, to evaluate left ventricular diastolic, systolic, and stroke volume, heart rate, cardiac output, arterial pressure, peripheral vascular resistance, creatinine clearance, urinary sodium excretion, plasma renin activity, plasma aldosterone, norepinephrine and hematocrit. The infusion increased plasma ANP up to levels (52.03 +/- 2.29 pmol/L) comparable with those observed in 35 patients with ascites (46.42 +/- 1.57 pmol/ L). This increment was associated with significant reductions in left ventricular end diastolic volume, stroke volume, cardiac index (from 3.7 +/- 0.7 to 3.1 +/- 0.5 L/min.m2, p < 0.05) and mean arterial pressure (from 96.7 +/- 6.5 to 88.5 +/- 9.5 mmHg, p < 0.05), while heart rate and hematocrit significantly increased. Peripheral vascular resistance did not change. These hemodynamic effects occurred despite significant increases in plasma renin activity and norepinephrine. ANP also induced increases in creatinine clearance, urinary sodium excretion, and fractional sodium excretion. Low-dose ANP affected cardiovascular homeostasis and renal sodium handling in compensated cirrhosis, suggesting that this hormone may be involved in the pathophysiology of systemic hemodynamic and renal functional abnormalities of cirrhosis.


Proteomic profiling of salivary gland after nonviral gene transfer mediated by conventional plasmids and minicircles.
In this study, we compared gene transfer efficiency and host response to ultrasound-assisted, nonviral gene transfer with a conventional plasmid and a minicircle vector in the submandibular salivary glands of mice. Initially, we looked at gene transfer efficiency with equimolar amounts of the plasmid and minicircle vectors, corroborating an earlier report showing that minicircle is more efficient in the context of a physical method of gene transfer. We then sought to characterize the physiological response of the salivary gland to exogenous gene transfer using global proteomic profiling. Somewhat surprisingly, we found that sonoporation alone, without a gene transfer vector present, had virtually no effect on the salivary gland proteome. However, when a plasmid vector was used, we observed profound perturbations of the salivary gland proteome that compared in magnitude to that seen in a previous report after high doses of AAV. Finally, we found that gene transfer with a minicircle induces only minor proteomic alterations that were similar to sonoporation alone. Using mass spectrometry, we assigned protein IDs to 218 gel spots that differed between plasmid and minicircle. Bioinformatic analysis of these proteins demonstrated convergence on 68 known protein interaction pathways, most notably those associated with innate immunity, cellular stress, and morphogenesis.


In vivo evidence that 5-HT2C receptor antagonist but not agonist modulates cocaine-induced dopamine outflow in the rat nucleus accumbens and striatum.
During recent years, much attention has been devoted at investigating the modulatory role of central 5-HT(2C) receptors on dopamine (DA) neuron activity, and it has been proposed that these receptors modulate selectively DA exocytosis associated with increased firing of DA neurons. In the present study, using in vivo microdialysis in the nucleus accumbens (NAc) and the striatum of halothane-anesthetized rats, we addressed this hypothesis by assessing the ability of 5-HT(2C) agents to modulate the increase in DA outflow induced by haloperidol and cocaine, of which the effects on DA outflow are associated or not with an increase in DA neuron firing, respectively. The intraperitoneal administration of cocaine (10-30 mg/kg) induced a dose-dependent increase in DA extracellular levels in the NAc and the striatum. The effect of 15 mg/kg cocaine was potentiated by the mixed 5-HT(2C/2B) antagonist SB 206553 (5 mg/kg i.p.) and the selective 5-HT(2C) antagonist SB 242084 (1 mg/kg i.p.) in both brain regions. The mixed 5-HT(2C/2B) agonist, Ro 60-0175 (1 mg/kg i.p.), failed to affect cocaine-induced DA outflow, but reduced significantly the increase in DA outflow induced by the subcutaneous administration of 0.1 mg/kg haloperidol. The obtained results provide evidence that 5-HT(2C) receptors exert similar effects in both the NAc and the striatum, and they modulate DA exocytosis also when its increase occurs independently from an increase in DA neuron impulse activity. Furthermore, they show that 5-HT(2C) agonists, at variance with 5-HT(2C) antagonists, exert a preferential control on the impulse-stimulated release of DA.


C1 Transposterior Arch Lateral Mass Screws Combined With C2 Pedicle Screw and Rod Fixation for Pediatric Atlantoaxial Subluxation: A Minimal 10-Year Follow-up Outcome Analysis.
Although the short-term outcomes of the 1-step reduction and fixation technique using C1 transposterior arch lateral mass screws combined with C2 pedicle screw and rod fixation system for the treatment of pediatric atlantoaxial subluxation (AAS) have been satisfactory, its long-term outcomes and impact on spinal development are not well studied. This study was intended to assess the long-term reliability of this technique for pediatric AAS. A retrospective case series study was conducted to analyze the minimum 10-year follow-up outcomes from 7 pediatric patients with AAS who underwent atlantoaxial fusion using the aforementioned technique. Quality of life and cervical range of motion were both measured thoroughly. In addition, vertical growth within the fusion construct (C1-2), overall cervical alignment, and subaxial cervical spine degeneration were evaluated radiographically. The mean age of the 7 patients was 8.14 ± 2.41 (6-12) years at the time of surgery. The mean follow-up period was 11.00 ± 1.15 (10-13) years. No patients presented identifiable intervertebral disk degeneration or segmental instability in the subaxial cervical spine except for 1 patient who showed mild intervertebral disk degeneration. Vertical growth did continue within the atlantoaxial complex after surgery (11.90% ± 2.37%); however, there was a decrease in the percentage of vertical growth compared with the corresponding normal populations of the same age and sex. Moreover, there was a significant decrease in the range of cervical extension and rotation motion, and the overall cervical alignment straightened at the latest follow-up. The 1-step reduction and fixation technique is a relatively reliable surgical technique for pediatric AAS, which does not adversely affect the postoperative quality of life or the subaxial cervical degeneration. Nevertheless, certain limitations, such as decreased cervical range of motion and changes in cervical alignment, should be concerned.


Deep learning-based fast denoising of Monte Carlo dose calculation in carbon ion radiotherapy.
Plan verification is one of the important steps of quality assurance (QA) in carbon ion radiotherapy. Conventional methods of plan verification are based on phantom measurement, which is labor-intensive and time-consuming. Although the plan verification method based on Monte Carlo (MC) simulation provides a more accurate modeling of the physics, it is also time-consuming when simulating with a large number of particles. Therefore, how to ensure the accuracy of simulation results while reducing simulation time is the current difficulty and focus. The purpose of this work was to evaluate the feasibility of using deep learning-based MC denoising method to accelerate carbon-ion radiotherapy plan verification. Three models, including CycleGAN, 3DUNet and GhostUNet with Ghost module, were used to denoise the 1 × 106 carbon ions-based MC dose distribution to the accuracy of 1 × 108 carbon ions-based dose distribution. The CycleGAN's generator, 3DUNet and GhostUNet were all derived from the 3DUNet network. A total of 59 cases including 29 patients with head-and-neck cancers and 30 patients with lung cancers were collected, and 48 cases were randomly selected as the training set of the CycleGAN network and six cases as the test set. For the 3DUNet and GhostUNet models, the numbers of training set, validation set, and test set were 47, 6, and 6, respectively. Finally, the three models were evaluated qualitatively and quantitatively using RMSE and three-dimensional gamma analysis (3 mm, 3%). The three end-to-end trained models could be used for denoising the 1 × 106 carbon ions-based dose distribution, and their generalization was proved. The GhostUNet obtained the lowest RMSE value of 0.075, indicating the smallest difference between its denoised and 1 × 108 carbon ions-based dose distributions. The average gamma passing rate (GPR) between the GhostUNet denoising-based versus 1 × 108 carbon ions-based dose distributions was 99.1%, higher than that of the CycleGAN at 94.3% and the 3DUNet at 96.2%. Among the three models, the GhostUNet model had the fewest parameters (4.27 million) and the shortest training time (99 s per epoch) but achieved the best denoising results. The end-to-end deep network GhostUNet outperforms the CycleGAN, 3DUNet models in denoising MC dose distributions for carbon ion radiotherapy. The network requires less than 5 s to denoise a sample of MC simulation with few particles to obtain a qualitative and quantitative result comparable to the dose distribution simulated by MC with relatively large number particles, offering a significant reduction in computation time.


The Mental Capacity Act: a review of the current literature.
The Mental Capacity Act (MCA) is a piece of statutory legislation which is designed to empower and protect those who are assessed as being unable to make decisions for themselves. At the time of implementation, the legislation was described as visionary and it had the potential to change the lives of many. However, a post-legislative scrutiny report published in 2014 concluded that there is a lack of knowledge among professionals of the MCA, and so it is not embedded into daily clinical practice. This review of literature has identified four key themes: assessment, training, knowledge and empowerment. These appear to concur with the findings of the House of Lords report. The successful integration of the MCA into professionals' everyday practice is high on the political agenda, thus reinforcing the message that following the guidance set out in the MCA legislation is mandatory and not a choice. A shift in culture and improvement in knowledge and understanding of the MCA is required in order for it to be used in the correct manner for which it was designed.


"It was the missing piece": adolescent experiences of predictive genetic testing for adult-onset conditions.
Predictive genetic testing for adult-onset conditions, such as Huntington disease, is available to at-risk adults. Guidelines consistently recommend against such testing before adulthood unless there is associated medical benefit. Guidelines, and related commentary, cite a range of potential harms that might be associated with young people undergoing testing, yet evidence is limited. Clinical practice has forged ahead, with research demonstrating that some clinicians are making their own determinations about the best interests of individual young people and are providing testing in specific cases. For the first time, this study reports empirical evidence concerning the process and impacts of predictive testing in mature minors for adult-onset conditions where no medical benefit exists. First-hand accounts from nine young people have been documented. All were aged 16 or 17 years of age when tested. Six tested gene positive. Contrary to existing assumptions, the results convey a range of benefits and absence of harms flowing from testing. Some individuals reported considerable distress associated with institutional processes before testing. The results highlight that young people from families affected by genetic conditions might possess task-specific competence relating to decision making about predictive testing. Further research and longer-term follow-up is required to study the outcomes of testing in young people.


Age and sex prevalence of infectious dermatoses among primary school children in a rural South-Eastern Nigerian community.
Various dermatoses, due to their morbidity characteristics, have been shown to negatively impact on learning. The most epidemiologically important seem to be the infectious types because of their transmissibility and amenability to simple school-health measures. The aim of this study was to assess the prevalence and sex/age correlates of infectious dermatoses in a rural South-eastern Nigerian community. The pupils were proportionately recruited from the three primary schools based on school population. Stratified simple random sampling method was adopted and a table of random numbers was used to select required pupils from each arm. Clinical and laboratory examination was done to establish diagnoses of infectious skin disease. Data collected were analyzed using SPSS version 16. The 400 pupils consisted of 153 males and 247 females. Age range was between 6 and 12 years. The prevalence of infectious dermatoses was 72.3%. The five most prevalent clinical forms of infectious dermatoses, in order of decreasing prevalence, were tinea capitis (35.2%), scabies (10.5%), tinea corporis (5.8%), tinea pedis (5.5%), and impetigo (5.0%). More cases, generally, occurred among males than females (80.4% vs 67.2%)); while some specific clinical types, pediculosis and seborrheic dermatitis, exhibited predilection for females. Pyodermas and scabies were significantly more prevalent in the 7-9 age-group; while tinea capitis, tinea corporis, seborrheic dermatitis and pediculosis were more associated with ≥10 age-group. Infectious dermatoses were highly prevalent in the surveyed population. Many of the clinical types exhibited sex- and age-specificity.


[Determination and identification of acrylamide residues in poly-acrylamide by ultra-performance liquid chromatography-quadrupole electrostatic field orbitrap high-resolution mass spectrometry].
A new method for the direct determination of acrylamide residues in poly-acrylamide (PAM) by ultra-performance liquid chromatography (UPLC)-quadrupole electrostatic field orbitrap high-resolution mass spectrometry with the Hypercarb column was developed. With being diluted by water, the PAM sample was dissolved well by high-speed stirring. After filtering through a 0.22 μm aqueous phase microporous membrane, the sample was analyzed by high-resolution mass spectrometry directly. Chromatographic analysis was carried out using a Hypercarb column, distilled water and methanol applied as the mobile phases. In addition, the column temperature was strictly set at 20℃. The sample was determined in the mode of parallel reaction monitoring (PRM). Accurate mass-to-charge ratio extraction of the target compound ion and its fragment ion were utilized with elemental composition analysis and isotope distribution of the fragment ion to further improve the accuracy of qualitative and quantitative analysis. Meanwhile, the fragmentation pattern of acrylamide was acquired. The calibration curve showed a good linearity in the range of 2-50 μg/L with the correlation coefficient of 0.9998. The limit of detection (LOD) was 1.5 μg/kg, satisfying the detection demands. The recoveries of the acrylamide were in the range of 101.3%-107.1%. The relative standard deviations (RSD) were 3.1%-4.1%. The applications indicated that the mass percentages of AM in PAM were in the range of 0-0.43%. The proposed method is easy, fast, sensitive and suitable for the determination and confirmation of acrylamide residues in PAM.


EWSR1-fusion-negative, SMARCB1-deficient primary pulmonary myxoid sarcoma.
Primary pulmonary myxoid sarcoma (PPMS) is a recently defined rare neoplasm with histological and molecular similarity to extraskeletal myxoid chondrosarcoma. To date, 20 cases have been reported. A 48-year-old man presented with a huge mass filling the right hemithorax and extending into the tracheobronchial system. Histological findings were consistent with PPMS. Immunohistochemistry was positive for vimentin, CD10, and EMA, but other lineage-specific markers were negative. SMARCB1 (INI1) expression was lost in the tumour cells. FISH analysis (EWSR1, FUS, NR4A3, and SMARCB1) revealed no abnormalities. This case suggests SMARCB1 loss as a possible alternative molecular event driving EWSR1-negative PPMS.


Compassionate Off-Ramps: The Availability of Terminal Master's Degrees in US Medical Schools.
Medical students who underperform or find they are not a "good fit" for medicine have limited options. A terminal master's degree represents an exit alternative that recognizes students' completed coursework and acknowledges their commitment to the medical sciences. Although medical educators have called for the creation of such programs, termed "compassionate off-ramps," the prevalence of degree offerings in US programs is unknown. In the fall of 2020, a survey was sent to Student Affairs Deans at 141 LCME-accredited MD programs; 73 institutions responded (52%). Terminal master's degrees were offered by 19% of respondent institutions (n = 13). While 85% of those without a terminal master's (n = 48) endorsed degree benefits, only 36% (n = 21) had plans to create the degree. This study demonstrates that few US medical schools offer a terminal master's degree, leaving students who exit medicine with high levels of debt without an avenue for a degree to support employment or future academic pursuits. The authors identify implications for students, particularly those who are at a higher risk of failing Step 1, such as students who are underrepresented in medicine, socioeconomically disadvantaged, or who have a disability and are unaccommodated. Potential barriers to terminal master's program creation are identified and mitigating strategies are recommended.