Foot Oligodactyly as the Main Dysplasia in Children.
Introduction Foot oligodactyly is usually associated with fibular insufficiency or cleft foot syndrome. A foot with a reduced number of rays may occasionally have an isolated dysplasia. Methods We reviewed the clinical notes and X-rays of six children with oligodactyly, having a normal development of the tibia and fibula. Clinical evaluation recorded the plantigrade or deviated foot, appropriate shoe wear, and aesthetic presentation of barefoot children. Radiological examination revealed missing or hypoplastic bones in the foot, the presence of other deformities, and leg length discrepancy (LLD) of the affected limb. Results On clinical evaluation, all children except one had a plantigrade foot with normal shoe wear; the lesion was not spotted in three of them unless informed of the presence of the dysplasia. Radiological examination in four of them revealed the absence or hypoplasia of the navicular, with a normal shape of the first metatarsal. Calcaneocuboid joints were normal in five of them; LLD was the main problem in three children. The girl with bilateral oligodactyly presented as a normal child. Conclusion Oligodactyly may present as an isolated dysplasia. LLD in these patients, which is less severe than in children with fibular or tibial insufficiency, is the main issue that requires surgical management in later life. Prenatal diagnosis of oligodactyly as an isolated dysplasia is an important feature for appropriate counseling of parents.


Evidence-based care through clinical practice.
This article describes how a working group examined ways to overcome difficulties with applying research findings to clinical practice. The group developed a ward-based distance learning package to assist in developing staff skills and ultimately enhance patient health care. The package has implications for all registered nurses in all nursing contexts.


Ginsenoside Rg5 Inhibits Succinate-Associated Lipolysis in Adipose Tissue and Prevents Muscle Insulin Resistance.
Endoplasmic reticulum (ER) stress, inflammation, and lipolysis occur simultaneously in adipose dysfunction and contribute to insulin resistance. This study was designed to investigate whether ginsenoside Rg5 could ameliorate adipose dysfunction and prevent muscle insulin resistance. Short-term high-fat diet (HFD) feeding induced hypoxia with ER stress in adipose tissue, leading to succinate accumulation due to the reversal of succinate dehydrogenase (SDH) activity. Rg5 treatment reduced cellular energy charge, suppressed ER stress and then prevented succinate accumulation in adipose tissue. Succinate promoted IL-1β production through NLRP3 inflammasome activation and then increased cAMP accumulation by impairing PDE3B expression, leading to increased lipolysis. Ginsenoside Rg5 treatment suppressed NLRP3 inflammasome activation, preserved PDE3B expression and then reduced cAMP accumulation, contributing to inhibition of lipolysis. Adipose lipolysis increased FFAs trafficking from adipose tissue to muscle. Rg5 reduced diacylglycerol (DAG) and ceramides accumulation, inhibited protein kinase Cθ translocation, and prevented insulin resistance in muscle. In conclusion, succinate accumulation in hypoxic adipose tissue acts as a metabolic signaling to link ER stress, inflammation and cAMP/PKA activation, contributing to lipolysis and insulin resistance. These findings establish a previously unrecognized role of ginsenosides in the regulation of lipid and glucose homeostasis and suggest that adipose succinate-associated NLRP3 inflammasome activation might be targeted therapeutically to prevent lipolysis and insulin resistance.


Managing stress and anxiety through qigong exercise in healthy adults: a systematic review and meta-analysis of randomized controlled trials.
An increasing number of studies have documented the effectiveness of qigong exercise in helping people reduce psychological stress and anxiety, but there is a scarcity of systematic reviews evaluating evidence from randomized controlled trials (RCTs) conducted among healthy subjects. Thirteen databases were searched for RCTs from their inception through June 2013. Effects of qigong exercise were pooled across trials. Standardized mean differences (SMDs) were calculated for the pooled effects. Heterogeneity was assessed using the I2 test. The risk of bias was assessed using the Cochrane criteria. Seven RCTs met the inclusion criteria. Two RCTs suggested that qigong exercise immediately relieved anxiety among healthy adults, compared to lecture attendance and structured movements only. Four RCTs suggested qigong exercise relieved anxiety (pooled SMD = -0.75; 95% CI, -1.11 to -0.40), and three RCTs suggested that qigong exercise reduced stress (pooled SMD = -0.88; 95% CI, -1.22 to -0.55) among healthy subjects following one to three months of qigong practice, compared to wait-list controls. The available evidence suggests that qigong exercise reduces stress and anxiety in healthy adults. However, given the limited number of RCTs and their methodological flaws, further rigorously designed RCTs are needed.


Age-related pattern of body density and body composition in Japanese males and females, 11 and 18 years of age.
The age-related pattern of body density and body composition in Japanese males (n = 266) and females (n = 318), 11.00 to 18.99 years of age was studied. Body density (BD) as well as height, body weight, and seven skinfold thicknesses were measured. Percentage fat (%Fat) was calculated using the age- and sex-specific equation of Lohman. Fat mass (FM), fat-free mass (FFM), and the body mass index (BMI) were calculated. The trend for BD in males was lowest at 11 years (1.0530 g/ml) and increased to 1.0695 g/ml at 14 years, and then decreased slightly at 15 to 17 years. In female, BD decreased from 1.0530 g/ml at 13 years to 1.0424 g/ml at 17 years. Mean %Fat was highest in males at 11 years (15.8%), and lowest at 14 years (10.1%). The highest mean %Fat in females occurred at 16 years (22.8%), and the lowest at age 11 years (15.2%). Overall, only 6.8% of males and 3.1% of females were classified as obese. Between 11 and 18 years, FFM of males differed by 20.7 kg or 67.9%, whereas females showed a difference of only 10.8 kg or 34.7%. Consequently, age effects explained approximately 60% of the male variance of FFM but only 26% in females. Body density of each sex and age group in this study did not differ significantly from previous Japanese studies, and the pooled BD data for 1,457 Japanese including the present study are reported as a reference.


Malignant rhabdoid tumor of the liver. A distinct clinicopathologic entity.
A malignant rhabdoid tumor occurring as a primary hepatic neoplasm in a six-month-old white infant is reported. It was treated by an attempt at total resection involving right hepatic lobectomy and by chemotherapy with cis-platinum, VP-16, and Adriamycin. Despite this, recurrence of the tumor resulted in the girl's death within three months. The neoplasm showed typical light microscopic features of malignant rhabdoid tumor as well as filamentous cytoplasmic inclusions by electron microscopic examination and staining for both cytokeratin and vimentin by immunohistochemistry. The classic clinicopathologic features of this tumor support the concept that malignant rhabdoid tumors similar to those of the kidney may occur in extrarenal sites.


The Impact of Total Hip Arthroplasty Surgical Approach on Short-Term Postoperative and Patient-Reported Outcomes.
Background While multiple studies have compared outcomes between the direct anterior approach (DAA) and posterolateral (PL) total hip arthroplasty (THA), the debate over the optimal approach remains. Proponents of the DAA suggest that its muscle-sparing properties and unrestricted rehabilitation facilitate a more rapid return to function. The majority of studies demonstrate that patient-reported outcomes (PROs) are similar between approaches beyond the one-year timeframe, but results are mixed when evaluating earlier time points. The purpose of this study was to compare clinical outcomes and PROs between DAA and PL THAs at six weeks postoperatively. Methods A retrospective review of 749 primary THAs (151 PL, 598 DAA) from March 2020 to November 2022 was performed. All surgeries were performed by one of the five board-certified and fellowship-trained orthopedic surgeons. All patients completed Patient Reported Outcomes Measurement Information System-Physical Function (PROMIS-PF) questionnaires preoperatively and at six weeks postoperatively. A univariate comparison of clinical outcomes (length of stay (LOS), home discharge rate, 90-day ED returns, and readmissions) and six-week PROMIS-PF scores between approaches was performed. Multivariate analysis was performed to evaluate the effect of the approach on outcomes after adjusting for baseline differences between groups. Results Patients undergoing DAA THA experienced significantly shorter average LOS (0.71 vs. 1.36 days, p<0.001), higher rates of home discharge (99.0 vs. 92.1%, p<0.001), and lower rates of 90-day readmissions (0.7 vs. 6.0%, p<0.001) than those undergoing the PL approach. At six weeks postoperatively, DAA patients achieved higher average PROMIS-PF scores (42.2 vs. 39.9, p=0.001). After adjusting for the Charlson Comorbidity Index and baseline physical function, the DAA was significantly associated with shorter LOS (β=-0.52, p<0.001), increased odds of home discharge (OR=5.70, p=0.001), reduced risk of 90-day readmission (OR=0.14, p=0.001), and higher PROMIS-PF scores at six weeks postoperatively (β=1.37, p=0.045). Conclusion In comparison to patients undergoing PL THA, those treated using the DAA experienced improved clinical and PROs over the six-week postoperative period. While both approaches resulted in satisfactory outcomes, these results support the assertion that DAA THA may result in more rapid recovery and return to function.


Suitability of small bronchoscopic tumour specimens for lung cancer genotyping.
Biomarker-driven clinical trials in advanced non-small cell lung cancer (NSCLC) usually accept biopsy specimens only, as cytology specimens are supposed to be more challenging due to low neoplastic cell content and suboptimal DNA quantity. We aimed to evaluate 2 aspects of bronchoscopic biopsy and cytology specimens: (1) the proportion of neoplastic cells and quantity of DNA extracted, and (2) the detection limit of the Scorpion amplification refractory mutation system on endoscopic samples obtained in daily clinical practice. We screened 679 patients with advanced-stage NSCLC for the presence of an activating EGFR mutation according to the guidelines of the European Society of Medical Oncology. Their diagnostic tumour tissue samples were characterized. A dilution experiment was performed to determine the minimal proportion of neoplastic cells for a reliable test result. Surgical biopsies, bronchoscopic forceps biopsy samples and needle aspiration cytology specimens exhibited a median tumour cell proportion of 70 versus 30 versus 20% and a DNA quantity of 2,500 versus 1,610 versus 1,440 ng, respectively. The overall EGFR mutation rate was 11%, with no differences between different sample types. Dilution experiments showed that the detection limit depends on the type of mutation. A neoplastic cell content of at least 10 and 25% for exon 19 deletions and exon 21 L858R point mutation, respectively, was required for a true negative result. Bronchoscopic forceps biopsy and needle aspiration cytology specimens are suitable for accurate EGFR mutation analysis using single-gene quantitative real-time polymerase chain reaction. Technologies with a better analytical sensitivity are evolving and should consider these endoscopic tumour specimens.


Q methodology.
Q methodology is more than just a technique for assessing attitudes. It is an approach which has subjectivity as its central focus and aims to allow researchers to present the views and perspectives of different people without insisting on the 'superior', more 'objective' status of the researcher's own construction of reality ( 1 ). It is a way of examining the world from the internal standpoint of an individual.


Safety and efficacy of single-balloon enteroscopy in management of gastrointestinal bleeding in patients with a left ventricular assist device.
Background and study aims Left ventricular assist devices (LVADs) are currently the standard of care in treatment of patients with end-stage heart failure waiting for heart transplant as well as destination therapy for non-transplant candidates. However, patients with LVADs are at increased risk of gastrointestinal bleeding due to the device's unique effects on hemodynamics. A major source of gastrointestinal bleeding in these patients are gastrointestinal angioectasias located within the small bowel that can only be reached with deep enteroscopy. The goal of our study was to determine the safety and efficacy of single-balloon enteroscopy (SBE) in treating gastrointestinal bleeding in patients with LVADs. Patients and methods We present a retrospective case series performed on patients with LVADs who underwent SBE to treat episodes of gastrointestinal bleeding. All procedures were performed at Emory University Hospital by a single endoscopist. Patient demographics, diagnosis and treatment of gastrointestinal bleeding, episodes of re-bleeding, and procedure-related complications were examined. Results A total of 27 SBE procedures performed in 14 patients were reviewed. SBE was performed in an antegrade approach in 89 % (24/27) of cases. Deep intubation was achieved in all antegrade procedures, with the distal jejunum reached in 79 % (19/24) of cases. The diagnostic yield was 78 %. There were no reported complications associated with the procedures. Conclusions SBE is a safe and effective modality to manage gastrointestinal bleeding in patients with LVADs.


The present status of vaccination against coccidioidomycosis in man.
Vaccines of killed whole cells of Coccidioides immitis have been injected intramuscularly in 97 human subjects to determine the safety and tolerable dose of vaccine and certain immunologic responses. Seventy-eight individuals received the whole killed spherule preparation; 18 received killed mycelial vaccine. The maximum tolerable dose of spherule vaccine was approximately 5 mg. Systemic effects were slight though in two prior coccidioidin reactors a moderate febrile illness and sbustantial antibody production followed vaccination with killed spherules. The vaccines irregularly induced antibody or delayed hypersensitivity to coccidioidin or spherule antigen. Greater antigenic mass perhaps as a soluble preparation may be needed for consistent immunologic stimulation though the spherule vaccine may be protective despite absence of detectable antibody or sensitivity to coccidioidin.


Proteinuria in an African HIV-infected patient: effects of telmisartan.
Kidney disease remains a major comorbidity of HIV infection especially in subjects of African ethnicity. HIV-associated renal disease with overt proteinuria has been associated with poorer outcomes and increased mortality. Telmisartan, an angiotensin II receptor blocker partial agonist of the PPAR-? approved for the treatment of hypertension, seems to exert a nephro-protective effect independent of blood pressure reduction in the general population. But data are lacking in HIV-positive patients with proteinuria. A case is described of an HIV-positive African patient with severe proteinuria treated with telmisartan. This therapy allowed proteinuria to be improved. This case shows for the first time that therapy with telmisartan has renoprotective effects also in an African HIV-infected patient.


Shaping of the root canal using Er:YAG laser irradiation.
The purpose of the present study was to investigate the degree of Er:YAG laser irradiation at the apical area in vitro. Since the laser was developed, advancement of laser treatment has been seen in various fields. However, few reports exist on shaping of the root canal using Er:YAG laser irradiation. Six single-rooted human teeth were used. The working length of root canals was set at 6.5 mm, and they were enlarged to apical file size #25. An Er:YAG laser and cone-shaped irradiation tips (R135T and R200T) were used. Laser irradiation conditions were 30 m J, 20 pps, and water flow of 5 mL/min. Samples were irradiated three times for 10 sec each using each tip. To evaluate the cutting degree of horizontal area of the root canal, the laser-irradiated surfaces were observed using microfocus X-ray computed tomographic photography before and after every irradiation. The samples were observed under a scanning electron microscope. Measurement of pixels in an area was performed by image-editing software (Adobe Photoshop 7.0). Statistical analysis was performed using StatView (version 5.0). One-way ANOVA and the Tukey-Kramer tests were used; p<0.05 indicated statistical significance. When root canals were irradiated with R200T for 10 sec (p<0.05), a large amount of evaporation (0.12 ± 1.07 mm(2)) was acquired in their cut area compared with the other irradiation conditions. In scanning electron microscopic observation, there was no smear layer and the dentinal tubules were open. When the distance between the tip and root dentin was adjacent, the shaping of root dentin by Er:YAG laser irradiation was definitely observed.


Architecture of fiber network: from understanding to engineering of molecular gels.
A new approach of engineering of molecular gels was established on the basis of a nucleation-initiated network formation mechanism. A variety of gel network structures can be obtained by regulating the starting temperature of the sol-gel transition. This enables us to tune the network from the spherulitic domains pattern to the extensively interconnected fibrillar network. As the consequence of fibrous network structure turning, desirable rheological and other in-use properties of the materials can be obtained accordingly. This approach of micro-/nanostructural fabrication may open up a new route for micro-/nanofunctional materials engineering in general.


How changing quality management influenced PGME accreditation: a focus on decentralization and quality improvement.
Evaluating the quality of postgraduate medical education (PGME) programs through accreditation is common practice worldwide. Accreditation is shaped by educational quality and quality management. An appropriate accreditation design is important, as it may drive improvements in training. Moreover, accreditors determine whether a PGME program passes the assessment, which may have major consequences, such as starting, continuing or discontinuing PGME. However, there is limited evidence for the benefits of different choices in accreditation design. Therefore, this study aims to explain how changing views on educational quality and quality management have impacted the design of the PGME accreditation system in the Netherlands. To determine the historical development of the Dutch PGME accreditation system, we conducted a document analysis of accreditation documents spanning the past 50 years and a vision document outlining the future system. A template analysis technique was used to identify the main elements of the system. Four themes in the Dutch PGME accreditation system were identified: (1) objectives of accreditation, (2) PGME quality domains, (3) quality management approaches and (4) actors' responsibilities. Major shifts have taken place regarding decentralization, residency performance and physician practice outcomes, and quality improvement. Decentralization of the responsibilities of the accreditor was absent in 1966, but this has been slowly changing since 1999. In the future system, there will be nearly a maximum degree of decentralization. A focus on outcomes and quality improvement has been introduced in the current system. The number of formal documents striving for quality assurance has increased enormously over the past 50 years, which has led to increased bureaucracy. The future system needs to decrease the number of standards to focus on measurable outcomes and to strive for quality improvement. The challenge for accreditors is to find the right balance between trusting and controlling medical professionals. Their choices will be reflected in the accreditation design. The four themes could enhance international comparisons and encourage better choices in the design of accreditation systems.


A Feedback Regulatory Loop Containing McdR and WhiB2 Controls Cell Division and DNA Repair in Mycobacteria.
Cell division must be coordinated with DNA repair, which is strictly regulated in response to different drugs and environmental stresses in bacteria. However, the mechanisms by which mycobacteria orchestrate these two processes remain largely uncharacterized. Here, we report a regulatory loop between two essential mycobacterial regulators, McdR (Rv1830) and WhiB2, in coordinating the processes of cell division and DNA repair. McdR inhibits cell division-associated whiB2 expression by binding to the AATnACAnnnnTGTnATT motif in the promoter region. Furthermore, McdR overexpression simultaneously activates imuAB and dnaE2 expression to promote error-prone DNA repair, which facilitates genetic adaptation to stress conditions. Through a feedback mechanism, WhiB2 activates mcdR expression by binding to the cGACACGc motif in the promoter region. Importantly, analyses of mutations in clinical Mycobacterium tuberculosis strains indicate that disruption of this McdR-WhiB2 feedback regulatory loop influences expression of both cell growth- and DNA repair-associated genes, which further supports the contribution of McdR-WhiB2 regulatory loop in regulating mycobacterial cell growth and drug resistance. This highly conserved feedback regulatory loop provides fresh insight into the link between mycobacterial cell growth control and stress responses. IMPORTANCE Drug-resistant M. tuberculosis poses a threat to the control and prevention of tuberculosis (TB) worldwide. Thus, there is a need to identify the mechanisms enabling M. tuberculosis to adapt and grow under drug-induced stress. Rv1830 has been shown to be associated with drug resistance in M. tuberculosis, but its mechanisms have not yet been elucidated. Here, we reveal a regulatory role of Rv1830, which coordinates cell division and DNA repair in mycobacteria, and rename it McdR (mycobacterial cell division regulator). An increase in McdR levels represses the expression of cell division-associated whiB2 but activates the DNA repair-associated, error-prone enzymes ImuA/B and DnaE2, which in turn facilitates adaptation to stress responses and drug resistance. Furthermore, WhiB2 activates the transcription of mcdR to form a conserved regulatory loop. These data provide new insights into the mechanisms controlling mycobacterial cell growth and stress responses.


[Infection by Bordetella pertussis and bordetella parapertussis in cases of suspected whooping cough (2011-2015) in Mar del Plata, Argentina].
. To classify the study population in the Argentinian National Health Surveillance System framework, determine the proportion of infection by Bordetella pertussis and Bordetella parapertussis, and identify factors associated with the cases of suspected whooping cough attended to in the city of Mar del Plata and its outskirts during the period 2011- 2015. An observational and descriptive study was carried out. Clinical cases with suspicion of whooping cough were diagnosed by laboratory. The laboratory studies consisted of culture, PCR, and serology using the ELISA technique. A total of 572 cases were evaluated. The female sex was the most frequent (51.9%). The most frequent age range was 2 to 17 moths (51.1%; 290/568), which was also the group with the most confirmed cases. Only 47.8% (155/324) of the population studied had complete vaccination for their age. Whooping cough due to B. pertussis was confirmed in 15.5% (89/572) of cases and one case with B. parapertussis. Those cases that had contact with a coughing relative were significantly associated with the confirmation of Bordetella spp. by the laboratory (odds ratio: 3.3; 95% confidence interval: 1.9-5.4). The results show the need to suspect whooping cough and diagnose it early in children, adolescents, and adults in order to better control the disease. Likewise, continuing prevention and containment measures are fundamental in decreasing the circulation of the causal agent.


[A case of transitional cell carcinoma of the bladder with heterotopic bone formation].
A 85-year-old woman consulted our clinic due to asymptomatic macrohematuria on January 6, 1987. In the cystoscopic examination, solitary and pedunculated bladder tumor was revealed. This tumor was located on the retrotrigonal region near the right ureteral orifice. On January 20, transurethral resection of bladder tumor was planned but the base of the tumor was stony hard, so complete resection was not performed. On February 10, transurethral resection of bladder was performed repeatedly. At that time, the cystoscopic finding showed that the tumor size had increased and transurethral bladder ultrasonography showed invasion into the deep muscular layer. On February 17, total cystectomy and ileal conduit was done. Histological examination revealed poorly differentiated TCC with osteoid, bone and cartilage. This patient was discharged in good condition on March 27. Heterotopic bone formation in the bladder tumor is rare. Ten cases were collected from the literature. We report a case of heterotopic bone formation and discuss the mechanism of the etiology.


Reverse engineering morphogenesis through Bayesian optimization of physics-based models.
Morphogenetic programs direct the cell signaling and nonlinear mechanical interactions between multiple cell types and tissue layers to define organ shape and size. A key challenge for systems and synthetic biology is determining optimal combinations of intra- and inter-cellular interactions to predict an organ's shape, size, and function. Physics-based mechanistic models that define the subcellular force distribution facilitate this, but it is extremely challenging to calibrate parameters in these models from data. To solve this inverse problem, we created a Bayesian optimization framework to determine the optimal cellular force distribution such that the predicted organ shapes match the desired organ shapes observed within the experimental imaging data. This integrative framework employs Gaussian Process Regression (GPR), a non-parametric kernel-based probabilistic machine learning modeling paradigm, to learn the mapping functions relating to the morphogenetic programs that generate and maintain the final organ shape. We calibrated and tested the method on cross-sections of Drosophila wing imaginal discs, a highly informative model organ system, to study mechanisms that regulate epithelial processes that range from development to cancer. As a specific test case, the parameter estimation framework successfully infers the underlying changes in core parameters needed to match simulation data with time series imaging data of wing discs perturbed with collagenase. Unexpectedly, the framework also identifies multiple distinct parameter sets that generate shapes similar to wild-type organ shapes. This platform enables an efficient, global sensitivity analysis to support the necessity of both actomyosin contractility and basal ECM stiffness to generate and maintain the curved shape of the wing imaginal disc. The optimization framework, combined with fixed tissue imaging, identified that Piezo, a mechanosensitive ion channel, impacts fold formation by regulating the apical-basal balance of actomyosin contractility and elasticity of ECM. This framework is extensible toward reverse-engineering the morphogenesis of any organ system and can be utilized in real-time control of complex multicellular systems.


[PET--new ways inside the body].
Using positron-emitting short-lived radionuclide tracers, a wide range of substances can now be labelled without their biological properties being affected. Positron emission tomography (PET) enables the distribution and metabolism of the labelled substance to be studied in different organs. By providing quantitative, locational, functional and biochemical information difficult to obtain by other means, PET opens up new possibilities, both diagnostic, pathophysiological and therapeutic, in a broad spectrum of medical practice. The development of the technique is described, with particular reference to its use at Uppsala.


Robust Multicontrast MRI Spleen Segmentation for Splenomegaly Using Multi-Atlas Segmentation.
Magnetic resonance imaging (MRI) is an essential imaging modality in noninvasive splenomegaly diagnosis. However, it is challenging to achieve spleen volume measurement from three-dimensional MRI given the diverse structural variations of human abdomens as well as the wide variety of clinical MRI acquisition schemes. Multi-atlas segmentation (MAS) approaches have been widely used and validated to handle heterogeneous anatomical scenarios. In this paper, we propose to use MAS for clinical MRI spleen segmentation for splenomegaly. First, an automated segmentation method using the selective and iterative method for performance level estimation (SIMPLE) atlas selection is used to address the concerns of inhomogeneity for clinical splenomegaly MRI. Then, to further control outliers, semiautomated craniocaudal spleen length-based SIMPLE atlas selection (L-SIMPLE) is proposed to integrate a spatial prior in a Bayesian fashion and guide iterative atlas selection. Last, a graph cuts refinement is employed to achieve the final segmentation from the probability maps from MAS. A clinical cohort of 55 MRI volumes (28 T1 weighted and 27 T2 weighted) was used to evaluate both automated and semiautomated methods. The results demonstrated that both methods achieved median Dice , and outliers were alleviated by the L-SIMPLE (≍1 min manual efforts per scan), which achieved 0.97 Pearson correlation of volume measurements with the manual segmentation. In this paper, spleen segmentation on MRI splenomegaly using MAS has been performed.


Advances in the anatomic study of the interscapular region of the cat.
New clinical oriented approaches are supported by the integration of advanced imaging techniques, e.g. computed tomography and magnetic resonance, with gross anatomy imaging. The interscapular region of the cat is a typical site of a highly invasive infiltrative pathology, i.e. Feline Injection-Site Sarcoma. Even if chemotherapy and radiotherapy have been considered as pre-surgical therapies, extensive surgery is still the recommended treatment. Evidence suggested that the relationships between muscles, infiltrative mass and adjacent musculoskeletal structures could change according to the forelimb positions: a fact to be duly considered while planning the surgical approach. Anatomic and tomographic atlases provide only images of the interscapular region from cats positioned with their forelimbs extended cranially, which means that, they do not record musculoskeletal modifications due to the forelimb movements. Aim of this study was to provide detailed images of the changes occurring in the musculoskeletal structures of the interscapular region of cats according to their forelimb position by comparing cross-sectional gross anatomy, computed tomography and magnetic resonance imaging. We provide an atlas of normal cross-sectional anatomy, computed tomography and magnetic resonance imaging of the interscapular region of the cat, from the fifth cervical vertebra to the fifth thoracic vertebra. We compare and couple the slices obtained both in flexed and extended forelimb positioning with the animal maintained in sternal recumbency. This study shows a new and dynamic way to investigate the interscapular region of the cat and provides anatomical references for in vivo computed tomography and magnetic resonance imaging, considering changes in the muscular form according to the forelimb positioning. We believe that an in-depth anatomical knowledge of the interscapular region may be helpful to approach the study of any pathology located there and, in particular, to set up an appropriate therapy for the feline injection-site sarcoma.


Topical sevoflurane and healing of a post-operative surgical site superinfected by multi-drug-resistant Pseudomonas aeruginosa and susceptible Staphylococcus aureus in an immunocompromised patient.
Infections caused by multi-drug-resistant organisms are too common and represent a therapeutic challenge. Topical application of sevoflurane may be useful for the treatment of cutaneous infections, as this general anesthetic has antimicrobial properties in vitro. A 43-year-old male patient received a liver transplant because of cirrhosis caused by hepatitis C. The surgical site was infected initially by multi-drug-resistant Pseudomonas aeruginosa that was susceptible to colistin, but parenteral administration of this antibiotic led to deterioration of renal function and was discontinued. The incision did not heal with daily lavage and debridement and was superinfected with Staphylococcus aureus. The off-label use of liquid sevoflurane in the form of site irrigations was followed by healing and closure of the site. This healing could be attributable to the mixed effect of three possible actions of sevoflurane: Direct antimicrobial effect, local analgesic effect that improved the quality of the dressings, and a direct vasodilator effect that, in theory, increased the supply of nutrients to the incision bed. The use of liquid sevoflurane on sites infected by microorganisms resistant to conventional antibiotics appears to be an attractive therapeutic option that deserves future research.


Delusional development in child autism at the onset of puberty: vicissitudes of psychic dimensionality between disintegration and development.
Although the psychogenetic hypotheses on child autism have been superseded, psychoanalysis can still reflect on the relational exchange and its sensory aspects in concomitance with the mental development of these patients. Without making generalizations as regards the pathogenesis, but considering the specific features of each autistic child, it may be possible to achieve an integration of those islands of competence that make up these patients' limited personal heritage. Such integration may be reached through the analysis of representational, emotional and relational transformations. The first part of this article describes the case of an autistic child in treatment from the age of four on a four-times-weekly basis who, during puberty, developed severe formal thought disorders together with delusional and hallucinatory formations. The second part develops some post-Jungian theoretical contributions, such as the concept of self as nothingness and the idea of the unsaturated archetype, so as to evaluate the function of some a-priori concepts in support of the analyst's position. These concepts are considered in relation to Bion's model of transformation, and to the formulations on dimensional awareness, especially on the shift from a two-dimensionality to three-dimensionality view, as well as to the rhythm of the object's presence and absence.


Electronic Characteristics, Stability and Water Oxidation Selectivity of High-Index BiVO4 Facets for Photocatalytic Application: A First Principle Study.
Some high-index facets of BiVO4, such as (012), (210), (115), (511), (121), (132) and (231), exhibit much better photocatalytic performance than conventional (010) and (110) surfaces for water splitting. However, the detailed mechanisms and stability of improved photocatalytic performance for these high-index BiVO4 surfaces are still not clear, which is important for designing photocatalysts with high efficiency. Here, based on first principle calculation, we carried out a systematic theoretical research on BiVO4 with different surfaces, especially high-index facets. The results show that all of the high-index facets in our calculated systems show an n-type behavior, and the band edge positions indicate that all of the high-index facets have enough ability to produce O2 without external bias. Electronic structures, band alignments and formation enthalpy indicate that (012), (115) and (132) could be equivalent to (210), (511) and (231), respectively, in the calculation. Oxidation and reduction potential show that only (132)/(231) is stable without strongly oxidative conditions, and the Gibbs free energy indicates that (012)/(210), (115)/(511), (121) and (132)/(231) have lower overpotential than (010) and (110). Our calculation is able to unveil insights into the effects of the surface, including electronic structures, overpotential and stability during the reaction process.


Centaurin beta1 down-regulates nucleotide-binding oligomerization domains 1- and 2-dependent NF-kappaB activation.
Centaurin beta1 (CENTB1), a GTPase-activating protein, is a member of the ADP-ribosylation factor family encoded by a gene located on the short arm of human chromosome 17. A yeast two-hybrid screen first suggested a direct interaction between CENTB1 and NOD2. Co-immunoprecipitation experiments confirmed direct interaction between CENTB1 and NOD2 and demonstrated similar interaction between CENTB1 and NOD1. We also demonstrate that endogenous CENTB1 interacts with endogenous NOD2 and NOD1 in SW480 and HT-29 intestinal epithelial cells. CENTB1 partially co-localized with NOD2 and NOD1 proteins in the cytoplasm of mammalian cells. CENTB1 expression in epithelial cells was highly induced by tumor necrosis factor alpha, interleukin 1beta, and the NOD1 and NOD2 ligands (gamma-d-glutamyl-meso-diaminopimelic acid and muramyl dipeptide, respectively). In addition, CENTB1 mRNA level is increased in the inflamed mucosa of patients with inflammatory bowel disease. Functionally, CENTB1 overexpression inhibited NOD1- and NOD2-dependent activation of NF-kappaB, whereas small inhibitory RNA against CENTB1 increased NF-kappaB activation following NOD1- or NOD2-mediated recognition of the bacterial components gamma-d-glutamyl-meso-diaminopimelic acid and muramyl dipeptide, respectively. In contrast, CENTB1 had no effect on NF-kappaB activation induced by Toll-like receptors. In conclusion, CENTB1 selectively down-regulates NF-kappaB activation via NODs pathways, creating a "feedback" loop and suggesting a novel role of CENTB1 in innate immune responses to bacteria and inflammatory responses.


Three-dimensional visualization system for ophthalmic microscopes using visible light and near-infrared illumination.
In this paper, we describe a three-dimensional visualization system for ophthalmic microscopes that is aimed at microsurgery without the eyepieces. A three-dimensional visualization system for ophthalmic microscopes using the mixed illumination, which consists of visible light and near-infrared illumination, is established in order to acquire more exact information of object and reduce the amount of light irradiated to the patients, and its usage in microsurgery without eyepieces is herein described. A custom-designed stereoscopic three-dimensional display which is manufactured for the convenience of the surgeons during the long-time surgery, is connected directly to the camera of the ophthalmic microscope in order to eliminate the discomfort of eyepieces to the surgeon and signal delay between the camera, mounted on the microscope, and display device for surgeon. The main features of the established system are the signal delay-free for surgeon and the low level of illumination for patient. In particular, it could significantly reduce the amount of light irradiated on a patient's eye via NIR illumination. Upon comparison with the conventional system during clinical ophthalmology trials, this system is confirmed to require almost the same operation time and reduced discomfort and eyestrain during long periods of observation.


MRI features of growth hormone deficiency in children with short stature caused by pituitary lesions.
We verified the advantages of using magnetic resonance imaging (MRI) for improving the diagnostic quality of growth hormone deficiency (GHD) in children with short stature caused by pituitary lesions. Clinical data obtained from 577 GHD patients with short stature caused by pituitary lesions were retrospectively analyzed. There were 354 cases (61.3%) with anterior pituitary dysplasia; 45 cases (7.8%) of pituitary stalk interruption syndrome (PSIS); 15 cases (2.6%) of pituitary hyperplasia due to primary hypothyroidism; 38 cases (6.6%) of Rathke cleft cyst; 68 cases (11.8%) of empty sella syndrome; 16 cases (2.8%) of pituitary invasion from Langerhans cell histiocytosis; 2 cases (0.3%) of sellar regional arachnoid cyst and 39 cases (6.8%) of craniopharyngioma. MRI results showed that the height of anterior pituitary in patients was less than normal. Location, size and signals of posterior pituitary and pituitary stalk were normal in anterior pituitary dysplasia. In all cases pituitary hyperplasia was caused by hypothyroidism. MRI results showed that anterior pituitary was enlarged, and we detected upward apophysis and obvious homogeneous enhancement. There were no pituitary stalk interruption and abnormal signal. We also observed that after hormone replacement therapy the size of pituitary gland was reduced. Anterior pituitary atrophy was observed in Rathke cleft cyst, empty sella syndrome, sellar regional arachnoid cyst and craniopharyngioma. The microstructure of hypophysis and sellar region was studied with MRI. We detected pituitary lesions, and the characteristics of various pituitary diseases of GHD in children with short stature. It was concluded that in children with GHD caused by pituitary lesions, MRI was an excellent method for early diagnosis. This method offers clinical practicability and we believe it can be used for differential diagnosis and to monitor the therapeutic effects.


"Usual" interstitial pneumonia with autoimmune features: a prospective study on a cohort of idiopathic pulmonary fibrosis patients.
The classification interstitial pneumonia with autoimmune features (IPAF) includes patients with interstitial lung disease (ILD) associated with autoimmune characteristics insufficient to reach classification criteria for a specific autoimmune disease (SAD). These criteria are divided into three domains: clinical, serological and morphological. The latter domain does not include the usual interstitial pneumonia (UIP) pattern, which is deemed not to be significantly associated with SAD. Therefore, the enrolment of these patients is more difficult, requiring at least one item from both of the other domains. The objective of this study is to evaluate the rate of progression towards SAD of a cohort of UIP patients satisfying only one IPAF domain (we called this group "UIPAF") compared with classic idiopathic pulmonary fibrosis (IPF). We prospectively enrolled IPF patients with radiologic and/or histologic UIP pattern, followed jointly by rheumatologists and pulmonologists from January 2017 to January 2021, with a minimum follow-up of 12 months. We enrolled 190 IPF patients, 38 (20%) of whom were classified as UIPAF. IPF and UIPAF patients were similar for general characteristics, severity and prognosis, at presentation and at annual check-up. However, 28.9% of UIPAF patients progressed towards SAD, compared with 2% of IPF patients (χ2=30.4, p≤0.0001). The association between a single clinical or serological domain of IPAF and UIP pattern is predictive for the development of a SAD if compared with isolated UIP. ILD can be the first manifestation of SAD, even with a UIP pattern, therefore, the morphological domain of IPAF criteria could be removed.


Who experiences unmet need for mental health services and what other barriers to accessing health care do they face? Findings from Australia and Canada.
To examine factors associated with unmet need for mental health services and links with barriers to access to care more broadly. The Commonwealth Fund International Health Policy Surveys from 2013 and 2016 were used to explore factors associated with unmet need for adults who experienced emotional distress for 1320 respondents in Australia and 2284 in Canada. Over one in five adults in Australia (21%) and in Canada (25%) experienced emotional distress, just over half said they received professional help (51% in Australia, 59% in Canada). The majority of those who did not get help indicated did not want to see a professional (37% in Australia, 30% in Canada). For those who did seek help, the factors associated with not receiving care included lower income, higher out-of-pocket health care costs, and poorer health. When compared with people with met needs, those with unmet needs for mental health services were more likely to also experience affordability, medication, and trust-related access barriers (AOR range 2.41 to 7.49 for the two countries, P < 0.01). Including unmet needs for mental health services as part of regular reporting on access to care may bring attention to access barriers for people with mental health conditions.


The nucleotide sequence of phenylalanine tRNA and 5S RNA from Rhodospirillum rubrum.
The complete nucleotide sequence of tRNAPhe and 5S RNA from the photosynthetic bacterium Rhodospirillum rubrum has been elucidated. A combination of in vitro and in vivo labelling techniques was used. The tRNAPhe sequence is 76 nucleotides long, 7 of which are modified. The primary structure is typically prokaryotic and is most similar to the tRNAPhe of Escherichia coli and Anacystis nidulans (14 differences of 76 positions). The 5S ribosomal RNA sequence is 120 nucleotides long and again typical of other prokaryotic 5S RNAs. The invariable GAAC sequence is found starting at position 45. When aligned with other prokaryotic 5S RNA sequences, a surprising amount of nucleotide substitution is noted in the prokaryotic loop region of the R. rubrum 5S RNA. However, nucleotide complementarity is maintained reinforcing the hypothesis that this loop is an important aspect of prokaryotic 5S RNA secondary structure. The 5S and tRNAPhe are the first complete RNA sequences available from the photosynthetic bacteria.


Effects of repulsive interaction on the electric double layer of an imidazolium-based ionic liquid by molecular dynamics simulation.
The effects of repulsive interaction on the electric double layer (EDL) and differential capacitance (Cd) of an ionic liquid (IL) 1-butyl-3-methyl-imidazolium hexafluorophosphate (BMIM(+)/PF6(-)) on the graphite electrode were studied by molecular dynamics (MD) simulations. The strength of repulsive interaction was studied by manually tuning the parameter lambda (λ) with λ = 1.00 for normal Lennard-Jones interaction and smaller λ for stronger repulsion between IL and the electrode. When λ changes from 1.00 to 0.25, the dependence of Cd on potential (Cd-U) curves at different repulsions is asymmetrically camel-shaped with higher Cd at the negative polarization than that at the positive due to the thinner effective thickness of EDL from the specific adsorption of BMIM(+). Such a trend is opposite in the case of λ = 0.05. Apart from that, the maximum of Cd at the negative polarization monotonically decreases with increasing repulsion. On the other hand, the maximum of Cd at the positive polarization first increases with increasing repulsion, due to the more effective screening of PF6(-) by weakening the specific adsorption of BMIM(+) as λ changes from 1.00 to 0.75, and then it decreases with increasing repulsion.


Divergent roles of Rad4 and Rad23 homologs in Metarhizium robertsii's resistance to solar ultraviolet damage.
The anti-ultraviolet (UV) role of a Rad4-Rad23-Rad33 complex in budding yeast relies on nucleotide excision repair (NER), which is mechanistically distinct from photorepair of DNA lesions generated under solar UV irradiation but remains poorly known in filamentous fungi. Here, two nucleus-specific Rad4 paralogs (Rad4A and Rad4B) and nucleocytoplasmic shuttling Rad23 ortholog are functionally characterized by multiple analyses of their null mutants in Metarhizium robertsii, an entomopathogenic fungus lacking Rad33. Rad4A was proven to interact with Rad23 and contribute significantly more to conidial UVB resistance (90%) than Rad23 (65%). Despite no other biological function, Rad4A exhibited a very high activity in photoreactivation of UVB-impaired/inactivated conidia by 5-h light exposure due to its interaction with Rad10, an anti-UV protein clarified previously to have acquired a similar photoreactivation activity through its interaction with a photolyase in M. robertsii. The NER activity of Rad4A or Rad23 was revealed by lower reactivation rates of moderately impaired conidia after 24-h dark incubation but hardly observable at the end of 12-h dark incubation, suggesting an infeasibility of its NER activity in the field where nighttime is too short. Aside from a remarkable contribution to conidial UVB resistance, Rad23 had pleiotropic effect in radial growth, aerial conidiation, antioxidant response, and cell wall integrity but no photoreactivation activity. However, Rad4B proved redundant in function. The high photoreactivation activity of Rad4A unveils its essentiality for M. robertsii's fitness to solar UV irradiation and is distinct from the yeast homolog's anti-UV role depending on NER. IMPORTANCE Resilience of solar ultraviolet (UV)-impaired cells is crucial for the application of fungal insecticides based on formulated conidia. Anti-UV roles of Rad4, Rad23, and Rad33 rely upon nucleotide excision repair (NER) of DNA lesions in budding yeast. Among two Rad4 paralogs and Rad23 ortholog characterized in Metarhizium robertsii lacking Rad33, Rad4A contributes to conidial UVB resistance more than Rad23, which interacts with Rad4A rather than functionally redundant Rad4B. Rad4A acquires a high activity in photoreactivation of conidia severely impaired or inactivated by UVB irradiation through its interaction with Rad10, another anti-UV protein previously proven to interact with a photorepair-required photolyase. The NER activity of either Rad4A or Rad23 is seemingly extant but unfeasible under field conditions. Rad23 has pleiotropic effect in the asexual cycle in vitro but no photoreactivation activity. Therefore, the strong anti-UV role of Rad4A depends on photoreactivation, unveiling a scenario distinct from the yeast homolog's NER-reliant anti-UV role.


The protective effects of naproxen against interleukin-1β (IL-1β)- induced damage in human umbilical vein endothelial cells (HUVECs).
Non-steroidal anti-inflammatory drugs (NSAIDs) are one of the most widely used medications in the world. Naproxen is an NSAID with relatively low selectivity for cyclooxygenase-2 (COX-2), thereby having decreased risk for cardiovascular (CV) events. However, it is unclear whether naproxen might provide protection against atherosclerosis, an underlying cause of numerous cardiovascular diseases (CVDs). In the present study, we exposed human umbilical vein endothelial cells to interleukin-1β (IL-1β), a key cytokine involved in atherogenesis, with or without naproxen. Our findings indicate that naproxen could protect against IL-1β-induced damage by improving cell viability and preventing cell death. Additionally, naproxen suppressed the expression of the cytokines IL-6, IL-12, and tumor necrosis factor-α (TNF-α), and downregulated the expression of vascular endothelial growth factor (VEGF) and tissue factor (TF) induced by IL-1β. Importantly, naproxen also inhibited the attachment of monocytes to endothelial cells, which was achieved through Krüppel-like factor 6 (KLF6)-mediated reduced expression of intracellular adhesion molecule-1 (ICAM-1) and E-selectin. These findings suggest that naproxen may aid in the prevention of atherosclerosis by exerting cardioprotective effects beyond low COX-2-selectivity.


Delayed thrombocytopenia following abciximab therapy.
Inhibitors of glycoprotein (GP) IIb/IIIa are currently approved for the treatment of acute coronary syndromes and during performance of percutaneous coronary interventions (PCIs). More than 500 000 patients annually undergo PCIs in the USA alone. Of these, 35% are receiving GPIIb/IIIa inhibitors. Currently, three different intravenous GPIIb/IIIa inhibitors are commercially available. Profound thrombocytopenia occurs almost exclusively with abciximab. Usually thrombocytopenia develops within 24 hours following abciximab administration. This paper describes three patients who developed delayed profound thrombocytopenia, occurring five days following abciximab therapy. These cases of thrombocytopenia were self-limited and reversible. Absence of serious bleeding complications was noted. The pathophysiology, differential diagnosis, natural history and management of the coronary patients with abciximab-induced thrombocytopenia are discussed.


Induction of asynchronous replication of polyoma DNA in rat cells by ultraviolet irradiation and the effects of various inhibitors.
The ability of various DNA damaging agents to induce asynchronous replication of polyoma DNA (APR) in rat cells carrying integrated copies of these DNA sequences may provide a useful model for understanding mechanisms of gene amplification. The present study has explored in detail the ability of UV irradiation to induce APR in the polyoma transformed rat fibroblast cell line H3. We have found that the optimum condition for induction of APR was obtained by irradiating the H3 cells with UV-C (wavelength, 254 nm) at 1-2 J/m2. Irradiation with UV-B (270-360 nm) was much less effective, and no induction of APR was obtained with even high doses of UV-A (345-440 nm). This action spectrum provides evidence that the critical target for induction of APR is DNA. We found that when normal rat fibroblasts were irradiated with UV-C and then fused to H3 cells, this also led to induction of APR. These results provide evidence that the induction of APR by UV-C is mediated by a trans-acting factor. The induction of APR by UV-C was inhibited by high doses of cycloheximide or actinomycin D, suggesting that the production of this trans-acting factor requires de novo protein and RNA synthesis. On the other hand, low doses of cycloheximide or actinomycin D alone were able to induce APR, perhaps by blocking the synthesis of cellular factors that normally inhibit APR. Thus, induction of APR by UV-C provides a useful system for identifying cellular factors that might mediate or prevent the asynchronous replication of various DNA sequences.


Inspiratory Muscle Training Effects on Cycling During Acute Hypoxic Exposure.
Hypoxic environments increase the physiological demands of exercise. Inspiratory muscle training can reduce the demands of exhaustive exercise in this environment. This study examined the impact of inspiratory muscle training on moderate intensity hypoxic cycling exercise. There were 17 healthy adult men who undertook 4 wk of inspiratory muscle training (N = 8) or 4 wk of sham inspiratory muscle training (N = 9). Subjects completed four fixed intensity (100 W) and duration (10 min) cycle ergometry tests. Two were undertaken breathing normoxic ambient air and two breathing a hypoxic gas mixture (14.6% oxygen, balance nitrogen). One normoxic and hypoxic test occurred before, and one after, inspiratory muscle training. Inspiratory muscle training increased maximal inspiratory mouth pressure by 21 ± 16 cmH2O. Arterial oxygen saturation and its ratio to minute ventilation also increased after inspiratory muscle training during hypoxic exercise from 83 ± 4% to 86 ± 3% (approximately 3%) and 2.95 ± 0.48 to 3.52 ± 0.54% · L · min-1(approximately 21%), respectively. In addition, minute ventilation and carbon dioxide output fell by 12-13% after inspiratory muscle training during hypoxic exercise. Inspiratory muscle training reduced the physiological demand of moderate intensity exercise during acute hypoxic, but not normoxic, exercise. It may therefore be of benefit in adults exercising in a hypoxic environment.Lomax M, Massey HC, House JR. Inspiratory muscle training effects on cycling during acute hypoxic exposure. Aerosp Med Hum Perform. 2017; 88(6):544-549.


How birds direct impulse to minimize the energetic cost of foraging flight.
Birds frequently hop and fly between tree branches to forage. To determine the mechanical energy trade-offs of their bimodal locomotion, we rewarded four Pacific parrotlets with a seed for flying voluntarily between instrumented perches inside a new aerodynamic force platform. By integrating direct measurements of both leg and wing forces with kinematics in a bimodal long jump and flight model, we discovered that parrotlets direct their leg impulse to minimize the mechanical energy needed to forage over different distances and inclinations. The bimodal locomotion model further shows how even a small lift contribution from a single proto-wingbeat would have significantly lengthened the long jump of foraging arboreal dinosaurs. These avian bimodal locomotion strategies can also help robots traverse cluttered environments more effectively.


Arterial calcifications, arterial stiffness, and cardiovascular risk in end-stage renal disease.
To test the predictive values of and independent contributions to cardiovascular and all-cause mortality of various arterial parameters exploring characteristics of the arterial wall at different sites, we studied prospectively 110 stable end-stage renal disease patients on hemodialysis. These parameters involved carotid diameter, carotid intima-media thickness, carotid compliance, carotid distensibility, carotid incremental elastic modulus, aortic diameter, aortic pulse wave velocity, and the presence of arterial calcifications measured at the sites of the carotid artery, abdominal aorta, iliofemoral axis, and legs. The presence of calcifications was analyzed semiquantitatively as a score (0 to 4) according to the number of arterial sites with calcifications. During a follow-up of 53+/-21 months (mean+/-SD), 25 cardiovascular and 14 noncardiovascular deaths occurred. In univariate analysis, the carotid incremental elastic modulus was the most closely related to prognosis. Risk of death increased with the number of vascular sites involved by calcifications. Moreover, information (in terms of prediction) given by carotid elastic incremental modulus was additive to the presence and extent of vascular calcification-related prediction value. Adjusted hazard ratios of all-cause and cardiovascular mortality for an increase of 1 unit in calcification score were 1.9 (95% confidence interval [CI], 1.4 to 2.6) and 2.6 (95% CI, 1.5 to 4.4), respectively (P<0.001 for both). Adjusted hazard ratios of all-cause and cardiovascular mortality for a 1-SD increase in carotid incremental elastic modulus were 1.6 (95% CI, 1.2 to 2.2) and 1.7 (95% CI, 1.2 to 2.4), respectively (P<0.01 for both). The results of this study showed that the presence and extent of vascular calcifications were strong predictors of cardiovascular and all-cause mortality. Carotid incremental elastic modulus gave additional predictive value.


Preparation and evaluation of topical microemulsion system containing metronidazole for remission in rosacea.
The aim of this study was to prepare a topical water-in-oil type microemulsion containing metronidazole and to compare its effectiveness with a commercial gel product in the treatment of rosacea. A pseudo-ternary phase diagram (K(m)=2:1) was constructed using lecithin/butanol/isopropyl myristate/water. The microemulsion was chosen from the microemulsion region in the phase diagram. The formulation was a water-in-oil type microemulsion (droplet size: 11.6 nm, viscosity: 457.3 mPa·s, conductivity: 1.5 µs/cm, turbidity: 6.89 NTU) and the addition of the metronidazole did not alter the properties of the system. The release experiment showed that the release rate of metronidazole from the commercial gel product was higher than that of the microemulsion. Stability experiments showed that the metronidazole microemulsion remained stable for at least 6 months; none of the characteristic properties of the microemulsion had changed, the system retained its clarity and there was no sign that crystallization of metronidazole has occurred. Microemulsion was compared to a gel product in a randomized, double-blind, baseline-controlled, split-face clinical trial for the treatment of patients. After the 6-week treatment period there was a statistically significant difference in reduction of the main symptoms of rosacea. Of the patients treated with the microemulsion, 17% experienced complete relief from inflammatory lesions, and 50% from erythema. The microemulsion resulted in complete relief in 38% of the patients with telangiectasia while the commercial product did not provide any relief of telangiectasia symptoms. In conclusion, the microemulsion containing metronidazole was found to be more effective in reducing the symptoms of rosacea compared to the commercial gel product.


Asymmetry of the Brain: Development and Implications.
Although the left and right hemispheres of our brains develop with a high degree of symmetry at both the anatomical and functional levels, it has become clear that subtle structural differences exist between the two sides and that each is dominant in processing specific cognitive tasks. As the result of evolutionary conservation or convergence, lateralization of the brain is found in both vertebrates and invertebrates, suggesting that it provides significant fitness for animal life. This widespread feature of hemispheric specialization has allowed the emergence of model systems to study its development and, in some cases, to link anatomical asymmetries to brain function and behavior. Here, we present some of what is known about brain asymmetry in humans and model organisms as well as what is known about the impact of environmental and genetic factors on brain asymmetry development. We specifically highlight the progress made in understanding the development of epithalamic asymmetries in zebrafish and how this model provides an exciting opportunity to address brain asymmetry at different levels of complexity.


Effects of domain knowledge, working memory capacity, and age on cognitive performance: an investigation of the knowledge-is-power hypothesis.
Domain knowledge facilitates performance in many cognitive tasks. However, very little is known about the interplay between domain knowledge and factors that are believed to reflect general, and relatively stable, characteristics of the individual. The primary goal of this study was to investigate the interplay between domain knowledge and one such factor: working memory capacity. Adults from wide ranges of working memory capacity, age, and knowledge about the game of baseball listened to, and then answered questions about, simulated radio broadcasts of baseball games. There was a strong facilitative effect of preexisting knowledge of baseball on memory performance, particularly for information judged to be directly relevant to the baseball games. However, there was a positive effect of working memory capacity on memory performance as well, and there was no indication that domain knowledge attenuated this effect. That is, working memory capacity contributed to memory performance even at high levels of domain knowledge. Similarly, there was no evidence that domain knowledge attenuated age-related differences (favoring young adults) in memory performance. We discuss implications of the results for understanding proficiency in cognitive domains from an individual-differences perspective.


Which patients benefit most from laparoscopic ventral hernia repair? A comparative study.
To establish which patients suffering ventral hernia benefit the most from laparoscopic approach. From January 2005 to October 2008, 126 patients underwent surgery due to incisional hernia at our University Hospital. Patients were assigned to laparoscopic surgery (n=60) or conventional surgery (n=66) at the surgeon's discretion. Patients were subdivided according to the greater diameter of the defect: (G1, defect <5 cm; G2, defect 5 to 15 cm; and G3, defect >15 cm). Data on patient demographic, clinical, and perioperative variables were collected prospectively. Groups were comparable in terms of sex, body mass index, American Society of Anesthesiologists score, size of defect, and proportion of primary repairs. Four patients were converted to open surgery. Mean hospital stay in the group with the smaller hernias (G1 was 3.16 d laparoscopic surgery vs. 2.87 d conventional surgery, P>0.05). Hospital stay for patients who underwent laparoscopy was shorter in G3 (4.25 d Lap vs. 12.6 d Open; P=0.02). Patients with very large incisional hernias are those who benefit the most from laparoscopic treatment.


Pathogens and host DNA in Ixodes ricinus nymphal ticks from a German forest.
Unfed nymphs of Ixodes ricinus were collected from vegetation in a forest on the outskirts of Berlin, Germany and were analyzed for host and pathogen DNA. Pathogens were detected in 47% of the ticks. Borrelia afzelii was the commonest pathogen detected, followed by Rickettsia helvetica. Other pathogens included B. valaisiana, B. garinii, B. burgdorferi sensu stricto, Anaplasma phagocytophilum, and a relapsing fever-like Borrelia. Most of the host DNA detected was of rodent origin and was associated with infection by B. afzelii, R. helvetica, and A. phagocytophilum. Bird DNA was associated with B. valaisiana and B. garinii, and ruminant DNA with A. phagocytophilum. B. afzelii was also found in two ticks that contained bird DNA.


Novel antibody to a carbonic anhydrase: patent evaluation of WO2011138279A1.
A novel antibody against human carbonic anhydrase XII (CA XII) was developed and characterized. Its specificity for the human CA XII isoform was assessed and its ability to inhibit CA XII was found about 40 times higher than acetazolamide, a well-known CA sulfonamide inhibitor. The antibody was shown to decrease cell proliferation in cultured A549 lung carcinoma cells, making it an interesting molecule for targeting and treating some forms of CA XII overexpressing tumors. The possibility of conjugating this antibody with fluorescent markers for diagnostic purposes or with toxins or anticancer drugs for treating purposes makes it an interesting molecule for developing new combined approaches for cancer treatment.


[Role of human telomerase reverse transcriptase in apoptosis of human umbilical vein endothelial cells induced by trichostatin A].
The aim of this study was designed to investigate the effect of TSA on human umbilical vein endothelial cells and to reveal its possible mechanisms and relationship between apoptosis and activity of telomerase reverse transcriptase. sulforhodamine B method was employed to determine the growth rate of umbilical vein endothelial cells. The cell apoptotic rate was measured by flow cytometry (FCM). The hTERT and p21(Waf1) mRNA expression before and after TSA treatment were detected by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). The quantitative of hTERT protein expression in cells were detected by flow cytometry. After transfection, the cell telomerase activity was detected by PCR and telomeric repeat amplification protocol assay (PCR-TRAP-ELISA) and early apoptosis was measured by Annexin V/PI stain and flow cytometry. After being treated with TSA, the proliferation of umbilical vein endothelial cells was inhibited. Slight apoptosis and cell cycle arrest were detected. However, the same concentration of TSA induced serious apoptosis in HeLa cells. Up-regulation of hTERT mRNA expression was observed within 48 h after TSA treatment, but the change of p21(Waf1) expression was not significant. The umbilical vein endothelial cells hTERT protein expression level was increased within 24 h. After transfection of the dominant negative, wild type and control hTERT plasmid, a significant difference of telomerase activity in these cells was observed by PCR-TRAP-ELISA assay. WT-hTERT-transfected cells were more resistant to apoptosis induced by trichostatin A. Human umbilical vein endothelial cells could be resistant to apoptosis induced by high concentrate TSA, and hTERT might play an important role in this process.


Experience with captopril treatment.
Experience with the use of foreign (Capoten Lopirin; Squibb) and Hungarian (Tensiomin; EGIS) captopril preparations is reported. It was found that the first dose of captopril resulted in a larger blood pressure decrease in hypertensive patients with a high blood renin level. A linear correlation was observed between the blood renin level before treatment and the captopril induced blood pressure decrease following the first dose. Captopril monotherapy lowered the blood pressure effectively without significant pulse rate change in patients whose blood pressure was difficult to influence with combined treatment containing no captopril. This paper reports on the area of indications and side-effects of the drug.


Clonidine abolishes the adverse effects on apoptosis and behaviour after neonatal ketamine exposure in mice.
An increasing amount of both experimental and epidemiological data indicates that neonatal anaesthesia causes disruption of normal brain development in rodents and primates, as manifested by acute increased apoptosis and long-lasting altered behaviour and learning. It is necessary to seek strategies that avoid the possible adverse effects after anaesthesia. Our purpose is to show that increased apoptosis and behavioural alterations after ketamine exposure during this period may be prevented by clonidine, a compound already used by paediatric anaesthetists for sedation. To investigate the protective properties of clonidine pre-treatment, five groups of 10-day-old mice were injected with either ketamine 50 mg/kg, clonidine 40 μg/kg, ketamine 50 mg/kg 30 min after 10 μg/kg clonidine, ketamine 50 mg/kg 30 min after 40 μg/kg clonidine or saline (control). Apoptosis was measured 24 h after treatment using Flouro-Jade staining. Spontaneous activity in a novel environment was tested at an age of 55 days. Pre-treatment with 40 μg/kg clonidine, but not 10 μg/kg clonidine, 30 min before ketamine exposure abolished ketamine-induced apoptosis and the behavioural changes observed in the young adult mice. The mice exposed to clonidine alone showed no differences from the saline-treated (control) mice. The administration of clonidine eliminated the adverse effects of ketamine in this mouse model, suggesting a possible strategy for protection. Alone, clonidine did not cause any adverse effects in these tests.


Women experiencing the intergenerationality of conjugal violence.
to analyze the family relationship, in childhood and adolescence, of women who experience conjugal violence. qualitative study. Interviews were held with 19 women, who were experiencing conjugal violence, and who were resident in a community in Salvador, Bahia, Brazil. The project was approved by the Research Ethics Committee (N. 42/2011). the data was organized using the Discourse of the Collective Subject, identifying the summary central ideas: they witnessed violence between their parents; they suffered repercussions from the violence between their parents: they were angry about the mother's submission to her partner; and they reproduced the conjugal violence. The discourse showed that the women witnessed, in childhood and adolescence, violence between their parents, and were injured both physically and psychologically. As a result of the mother's submission, feelings of anger arose in the children. However, in the adult phase of their own lives, they noticed that their conjugal life resembled that of their parents, reproducing the violence. investment is necessary in strategies designed to break inter-generational violence, and the health professionals are important in this process, as it is a phenomenon with repercussions in health. Because they work in the Family Health Strategy, which focuses on the prevention of harm and illness, health promotion and interdepartmentality, the nurses are essential in the process of preventing and confronting this phenomenon.


Leukocyte depletion does not affect the in vitro healing ability of platelet rich plasma.
The clinical use of platelet-rich plasma (PRP) containing or deprived of leukocytes remains a subject of debate and a controversial issue. It is not yet clear whether leukocyte content has a positive or negative effect on tissue healing processes. Several studies, conducted mainly in the orthopedic field, support the use of leukocyte-poor (LP) PRP, whereas other studies have not identified any significant differences between the use of LP and leukocyte-rich PRP. In the present study, the role of leukocytes contained in PRP was assessed to verify their in vitro effect on fibroblasts and endothelial cells, which have a leading role in the biological processes associated with wound healing (including angiogenesis and matrix remodeling). The original sample of PRP was divided into two aliquots, one of which remained unaltered, while the other was deprived of leukocytes. The two aliquots were used in in vitro tests in order to verify the effects of leukocytes on proliferation, wound healing and tube formation, and in molecular analyses of growth factor and enzyme content. The present results highlighted a substantial overlap between the two formulations. This may be explained by similar levels of growth factors (vascular endothelial growth factor, thrombospondin-1, interferon-γ, platelet-derived growth factor-BB, -AA and -B, tumor growth factor-β1, fibroblast growth factor 7 and tumor necrosis factor-α) and enzymes (gelatinases and plasminogen activators) in the two formulations. These results support the hypothesis that the ability of the PRP to affect the in vitro biological response of endothelial cells and fibroblasts does not rely on the presence of leukocytes.


A spurious markedly increased serum estradiol level due to an IgA lambda.
To alert physicians about the potential for erroneous laboratory determinations of hormone levels and emphasize the need to assess the overall clinical situation as well. We present a case report of a woman with a dramatically increased serum estradiol (E(2)) level on radioimmunoassay and review the studies that led to the conclusion that this laboratory finding did not reflect her true estrogen status. In a 41-year-old woman, an unnecessary surgical procedure was performed because of a falsely increased serum E(2) level and a unilateral ovarian mass. The markedly increased serum E(2) measured by radioimmunoassay was found to be attributable to an IgA lambda that bound to the 125 I-labeled tracer of the assay. When repeatedly abnormal hormone levels and the clinical picture seem discrepant, use of a different assay method should be considered.


Permeation, metabolism and site of action concentration of nicotinic acid derivatives in human skin. Correlation with topical pharmacological effect.
A novel methodology for establishing a pharmacological dose-effect relationship of methyl nicotinate, hexyl nicotinate and nicotinic acid acting as peripheral vasodilators in the skin following topical application is investigated. This methodology involves the estimation of the unbound drug concentration in the aqueous compartment at the site of action in tissue, termed C(*), which was evaluated as the pertinent concentration responsible for the pharmacological effect. Blood capillaries next to the epidermis-dermis boundary were postulated to be the relevant site of action. C(*) was estimated from drug transport parameters for different layers of human cadaver skin determined in vitro. Immunohistochemical studies showed that the plane of separation of skin achieved by heat treatment was between the basal cells of the epidermis and the lamina lucida, confirming the integrity of the epidermis and the dermis used in the experiments. The permeation rate for epidermis increased drastically with increasing lipophilicity of the drug. Dermis permeability was roughly the same for all three compounds. The epidermis represented the major transport barrier in vitro for methyl nicotinate and nicotinic acid but not for hexyl nicotinate. The esters were metabolised to nicotinic acid during tissue permeation to an extent that was rather limited for the epidermis but very pronounced for the dermis. Nonspecific alpha-naphthylacetate-esterase activity was predominantly located in the dermis, which was in agreement with the metabolism results. The drugs were applied each at three different concentrations in vivo to the ventral forearm of healthy human volunteers and vasodilation was evaluated based on skin erythema which was quantified by measuring colour change of reflected light. Area under the curve of the change of colour co-ordinates as a function of time was used as a measure of pharmacological effect. The pharmacological effect of all three drugs was comparable when similar C(*) values were considered, even though the concentrations applied to the skin differed by orders of magnitude. The effect showed a strong positive dependence on C(*). Methyl and hexyl nicotinate showed identical, nearly sigmoidal effect/C(*)-profiles, while the profile for nicotinic acid was linear, suggesting a possible difference in the intrinsic pharmacological potency between the esters and the acid. These results demonstrate the validity of C(*) as the relevant drug concentration for the cutaneous pharmacological effect of the topically applied drugs and underline the usefulness of the presented methodology for establishing dose-response relationships in dermal therapy and expressing bioavailability.


Phylogenomic Insights into Animal Evolution.
Animals make up only a small fraction of the eukaryotic tree of life, yet, from our vantage point as members of the animal kingdom, the evolution of the bewildering diversity of animal forms is endlessly fascinating. In the century following the publication of Darwin's Origin of Species, hypotheses regarding the evolution of the major branches of the animal kingdom - their relationships to each other and the evolution of their body plans - was based on a consideration of the morphological and developmental characteristics of the different animal groups. This morphology-based approach had many successes but important aspects of the evolutionary tree remained disputed. In the past three decades, molecular data, most obviously primary sequences of DNA and proteins, have provided an estimate of animal phylogeny largely independent of the morphological evolution we would ultimately like to understand. The molecular tree that has evolved over the past three decades has drastically altered our view of animal phylogeny and many aspects of the tree are no longer contentious. The focus of molecular studies on relationships between animal groups means, however, that the discipline has become somewhat divorced from the underlying biology and from the morphological characteristics whose evolution we aim to understand. Here, we consider what we currently know of animal phylogeny; what aspects we are still uncertain about and what our improved understanding of animal phylogeny can tell us about the evolution of the great diversity of animal life.


The Effectiveness of Physical Agents for Lower-Limb Soft Tissue Injuries: A Systematic Review.
Study Design Systematic review. Background Soft tissue injuries to the lower limb bring a substantial health and economic burden to society. Physical agents are commonly used to treat these injuries. However, the effectiveness of many such physical agents is not clearly established in the literature. Objective To evaluate the effectiveness and safety of physical agents for soft tissue injuries of the lower limb. Methods We searched 5 databases from 1990 to 2015 for randomized controlled trials (RCTs), cohort studies, and case-control studies. Paired reviewers independently screened the retrieved literature and appraised relevant studies using the Scottish Intercollegiate Guidelines Network criteria. Studies with a high risk of bias were excluded. We synthesized low-risk-of-bias studies according to principles of best-evidence synthesis. Results We screened 10261 articles. Of 43 RCTs identified, 20 had a high risk of bias and were excluded from the analysis, and 23 RCTs had a low risk of bias and were included in the analysis. The available higher-quality evidence suggests that patients with persistent plantar fasciitis may benefit from ultrasound or foot orthoses, while those with persistent midportion Achilles tendinopathy may benefit from shockwave therapy. However, the current evidence does not support the use of shockwave therapy for recent plantar fasciitis, low-Dye taping for persistent plantar fasciitis, low-level laser therapy for recent ankle sprains, or splints for persistent midportion Achilles tendinopathy. Finally, evidence on the effectiveness of the following interventions is not established in the current literature: (1) shockwave therapy for persistent plantar fasciitis, (2) cryotherapy or assistive devices for recent ankle sprains, (3) braces for persistent midportion Achilles tendinopathy, and (4) taping or electric muscle stimulation for patellofemoral pain syndrome. Conclusion Almost half the identified RCTs that evaluated the effectiveness of physical agents for the management of lower-limb soft tissue injuries had a high risk of bias. High-quality RCTs are still needed to assess the effectiveness of physical agents for managing the broad range of lower-limb soft tissue injuries. The effectiveness of most interventions remains unclear. Level of Evidence Therapy, 1a. Protocol registered July 10, 2014 with PROSPERO (CRD42014010621). J Orthop Sports Phys Ther 2016;46(7):523-554. Epub 6 Jun 2016. doi:10.2519/jospt.2016.6521.


Are dose calculations during dose optimization in brachytherapy necessary?
We consider the problem of anatomy based dose optimization in brachytherapy. A calculation method for some objective functions and their derivatives is proposed which significantly reduces the number of required operations. The optimization in some cases, ignoring a preprocessing step, is independent of the number of sampling points. The idea is that some of the objectives and their derivatives used for dose optimization do not require the explicit calculation of dose values. Dose optimization with the new modified computation method for the objectives and derivatives is, depending on the number of sampling points, up to 100 times faster than the conventional method with dose calculation.


Identification of gustatory-olfactory flavor mixtures: effects of linguistic labeling.
Two experiments, using different ranges and numbers of stimuli, examined how linguistic labels affect the identification of flavor mixtures containing different proportions of sucrose (gustatory flavorant) and citral (olfactory flavorant). Both experiments asked subjects to identify each stimulus as having either "mostly sugar" or "mostly citrus." In one condition, no labels preceded the flavor stimuli. In another condition, each flavor stimulus followed a label, either SUGAR or CITRUS, which, the subjects were informed, usually though not always named the stronger flavor component; that is, the labels were probabilistically valid. The results of both experiments showed that the labels systematically modified the identification responses: Subjects responded "sugar" or "citrus" more often when the flavor stimulus followed the corresponding label, SUGAR or CITRUS. But the labels hardly affected overall accuracy of identification. Accuracy was possibly limited, however, by both the confusability of the flavor stimuli per se and the way that confusability could limit the opportunity to discern the probabilistic associations between labels and individual flavor stimuli. We describe the results in terms of a decision-theoretic model, in which labels induce shifts in response criteria governing the identification responses, or possibly effect changes in the sensory representations of the flavorants themselves.


On the biosynthetic origin of carminic acid.
The chemical composition of the scale insect Dactylopius coccus was analyzed with the aim to discover new possible intermediates in the biosynthesis of carminic acid. UPLC-DAD/HRMS analyses of fresh and dried insects resulted in the identification of three novel carminic acid analogues and the verification of several previously described intermediates. Structural elucidation revealed that the three novel compounds were desoxyerythrolaccin-O-glucosyl (DE-O-Glcp), 5,6-didehydroxyerythrolaccin 3-O-β-D-glucopyranoside (DDE-3-O-Glcp), and flavokermesic acid anthrone (FKA). The finding of FKA in D. coccus provides solid evidence of a polyketide, rather than a shikimate, origin of coccid pigments. Based on the newly identified compounds, we present a detailed biosynthetic scheme that accounts for the formation of carminic acid (CA) in D. coccus and all described coccid pigments which share a flavokermesic acid (FK) core. Detection of coccid pigment intermediates in members of the Planococcus (mealybugs) and Pseudaulacaspis genera shows that the ability to form these pigments is taxonomically more widely spread than previously documented. The shared core-FK-biosynthetic pathway and wider taxonomic distribution suggests a common evolutionary origin for the trait in all coccid dye producing insect species.


Development and validation of a solid-phase extraction gas chromatography-mass spectrometry method for the simultaneous quantification of methadone, heroin, cocaine and metabolites in sweat.
A sensitive and specific method is presented to simultaneously quantify methadone, heroin, cocaine and metabolites in sweat. Drugs were eluted from sweat patches with sodium acetate buffer, followed by SPE and quantification by GC/MS with electron impact ionization and selected ion monitoring. Daily calibration for anhydroecgonine methyl ester, ecgonine methyl ester, cocaine, benzoylecgonine (BE), codeine, morphine, 6-acetylcodeine, 6-acetylmorphine (6AM), heroin (5-1000 ng/patch) and methadone (10-1000 ng/patch) achieved determination coefficients of >0.995, and calibrators quantified to within +/-20% of the target concentrations. Extended calibration curves (1000-10,000 ng/patch) were constructed for methadone, cocaine, BE and 6AM by modifying injection techniques. Within (N = 5) and between-run (N = 20) imprecisions were calculated at six control levels across the dynamic ranges with coefficients of variation of <6.5%. Accuracies at these concentrations were +/-11.9% of target. Heroin hydrolysis during specimen processing was <11%. This novel assay offers effective monitoring of drug exposure during drug treatment, workplace and criminal justice monitoring programs.


Kinetics-mediate fabrication of multi-model bioimaging lanthanide nanoplates with controllable surface roughness for blood brain barrier transportation.
Effective delivery of imaging agents or therapeutics to the brain has remained elusive due to the poor blood-brain barrier (BBB) permeability, resulting in the apparent risks of inefficient diagnosis and therapeutic agents for brain disease. Herein, we report on the surface roughness mediated BBB transportation for the first time. The lanthanide-based core/shell/shell structured NaYF4:Yb,Er@NaGdF4:Yb@NaNdF4:Yb nanoplates with controllable surface roughness and multi-model bioimaging features were synthesized and used to evaluate the surface roughness dependent BBB permeability without any surface bio-functionalization. By controlling the kinetics of the shell coating process, the hexagon-disc, multi-petals and six-petals nanoplates with different surface roughness can be obtained. Comparing with the NPs with less Ra and receptor-conjugated NPs, the obtained six-petals nanoplates with highest roughness exhibit excellent performance in BBB transportation and tumor targeting, which lay solid foundation for the diagnosis and the therapy of brain tumor.


"Familiarity-based stimulus generalization of conditioned suppression": Correction to Robinson, Whitt, and Jones (2017).
Reports an error in "Familiarity-based stimulus generalization of conditioned suppression" by Jasper Robinson, Emma J. Whitt and Peter M. Jones (Journal of Experimental Psychology: Animal Learning and Cognition, 2017[Apr], Vol 43[2], 159-170). The article was incorrectly published under American Psychological Association copyright. The authors should have retained copyright of this article under the Creative Commons Attribution License. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2017-15338-002.) We report that stimulus novelty/familiarity is able to modulate stimulus generalization and discuss the theoretical implications of novelty/familiarity coding. Rats in Skinner boxes received clicker → shock pairings before generalization testing to a tone. Before clicker training, different groups of rats received preexposure treatments designed to systematically modulate the clicker and the tone's novelty and familiarity. Rats whose preexposure matched novelty/familiarity (i.e., either both or neither clicker and tone were preexposed) showed enhanced suppression to the tone relative to rats whose preexposure mixed novelty/familiarity (i.e., only clicker or tone was preexposed). This was not the result of sensory preconditioning to clicker and tone. (PsycINFO Database Record


Factors involved in the decision to perform a selective versus nonselective fusion of Lenke 1B and 1C (King-Moe II) curves in adolescent idiopathic scoliosis.
A retrospective evaluation of 203 adolescent idiopathic scoliosis patients with Lenke 1B or 1C (King-Moe II) type curves. To evaluate the incidence of inclusion of the lumbar curve in the treatment of this type of deformity as well as radiographic factors associated with lumbar curve fusion. In patients with structural thoracic curves and compensatory lumbar curves, many authors have recommended fusing only the thoracic curve (selective thoracic fusion). Studies have shown that correction of the thoracic curve results in spontaneous correction of the unfused lumbar curve; however, in some cases, truncal decompensation develops. Though there have been various attempts to define more accurately what type of curve pattern should undergo selective fusion, controversy continues in this area. Measurements were obtained from the preoperative standing posteroanterior and side-bending radiographs of 203 patients with Lenke Type 1B or 1C curves from five sites of the DePuy AcroMed Harms Study Group. Patients were divided into two groups depending on their most distal vertebra instrumented: the "selective thoracic fusion" group included patients who were fused to L1 or above and the "nonselective fusion" group included patients fused to L2 or below. A statistical comparison was conducted to identify variables associated with the choice for a nonselective fusion. The incidence of fusion of the lumbar curve ranged from 6% to 33% at the different patient care sites. Factors associated with nonselective fusion included larger preoperative lumbar curve magnitude (42 +/- 10 degrees vs. 37 +/- 7 degrees, P < 0.01), greater displacement of the lumbar apical vertebra from the central sacral vertical line, (3.1 +/- 1.4 cm vs. 2.2 +/- 0.8 cm, P < 0.01), and a smaller thoracic to lumbar curve magnitude ratio (1.31 +/- 0.29 vs. 1.44 +/- 0.30, P = 0.01). The characteristics of the compensatory "nonstructural" lumbar curve played a significant role in the surgical decision-making process and varied substantially among members of the study group. Side-bending correction of the lumbar curve to <25 degrees (defining these as Lenke 1, nonstructural lumbar curves) was not sufficientcriteria to perform a selective fusion in some of these cases. The substantial variation in the frequency of fusing the lumbar curve (6% to 33%) confirms that controversy remains about when surgeons feel the lumbar curve can be spared in Lenke 1B and 1C curves. Site-specific analysis revealed that the radiographic features significantly associated with a selective fusion varied according to the site at which the patient was treated. The rate of selective fusion was 92% for the 1B type curves compared to 68% for the 1C curves.


The influence of the type of dietary fat on postprandial fat oxidation rates: monounsaturated (olive oil) vs saturated fat (cream).
To compare postprandial whole-body fat oxidation rates in humans, following high-fat (43% of total energy) mixed breakfast meals, of fixed energy and macronutrient composition, rich in either monounsaturated fat (MUFA) from extra virgin olive oil or saturated fat (SFA) from cream. Paired comparison of resting metabolic rate (RMR), thermic effect of a meal and substrate oxidation rates following consumption of isocaloric breakfast meals, differing only in the type of fat, administered in random order 1-2 weeks apart. Fourteen male volunteers, body mass index (BMI) in the range 20-32 kg/m(2), aged 24-49 y and resident in Melbourne, Australia, were recruited by advertisement in the local media or by personal contact. Body size and composition was determined by anthropometry and dual energy X-ray absorptiometry (DEXA). Indirect calorimetry was used to measure RMR, thermic effect of a meal, post-meal total energy expenditure and substrate oxidation rate. Blood pressure and pulse rates were measured with an automated oscillometric system. Fasting and 2 h postprandial glucose and insulin concentrations and the fasting lipid profile were also determined. In the 5 h following the MUFA breakfast, there was a significantly greater postprandial fat oxidation rate (3.08+/-4.58 g/5 h, P=0.017), and lower postprandial carbohydrate oxidation rate (P=0.025), than after the SFA breakfast. Thermic effect of a meal was significantly higher (55 kJ/5 h, P=0.034) after the MUFA breakfast, in subjects with a high waist circumference (HWC > or = 99 cm) than those with a low waist circumference (LWC<99 cm). This difference was not detected following the SFA breakfast (P=0.910). If postprandial fat oxidation rates are higher after high MUFA, rather than SFA meals, then a simple change to the type of dietary fat consumed might have beneficial effects in curbing weight gain in men consuming a relatively high-fat diet. This may be particularly evident in men with a large waist circumference.


Meteorological effects of environmental controls.
The solution of the continuity equation in practical applications is examined, and the values needed for approximate solutions are indicated. Models are adequate for investigating what could happen, but are less satisfactory for predicting what will happen. An example is given in relation to the distribution of SO2 over Connecticut. More knowledge is needed about atmospheric chemistry before better predictions can be expected. The effect of particulates on atmospheric opacity is reviewed.


Very early spondyloarthritis: where the inflammation in the sacroiliac joints starts.
Involvement of the sacroiliac joints (SIJ) is a major and characteristic feature of the spondyloarthritides (SpA). In early ankylosing spondylitis and undifferentiated SpA (uSpA) sacroiliitis is the most common early clinical finding and the presumed first manifestation of the disease. Magnetic resonance imaging has proved useful for visualising inflammation in the SIJ in adults and children. Recently, initial localisation of the inflammation in the SIJ has been described in some detail, but it has not been completely defined to date--either in imaging or in histopathological studies. This is mainly owing to the lack of data in very early disease and the lack of follow up studies. Here we present a patient with early disease, which may augment our understanding of this stage of SpA.


Pinus massoniana bark extract selectively induces apoptosis in human hepatoma cells, possibly through caspase-dependent pathways.
Pinus massoniana bark extract (PMBE) is a mixture of flavonoids, whose antioxidant and apoptosis-inducing properties have been confirmed in vitro. In this study, the apoptotic effect and mechanism of PMBE in HepG2 human hepatoma cells were evaluated. PMBE exerted dose- and time-dependent cell growth inhibition on HepG2 cells, and selectively induced apoptosis without impact on normal liver L-02 cells. Apoptosis induced by PMBE in HepG2 cells was also confirmed by annexin-V/PI staining, transmission electron microscopy and sub-G1 phase accumulation. Moreover, PMBE also slightly blocked the cell cycle in the G2/M and S phases in HepG2 cells. The investigation of the mechanism by which PMBE induced apoptosis in HepG2 cells indicated that activation of extrinsic and intrinsic caspase, inhibition of NF-kappaB activation and decrease of the antiapoptotic protein Bcl-2 and the intact Bid protein were involved. Furthermore, the antitumor activity of PBME was demonstrated in vivo by a 42.88-69.94% reduction rate of tumor weight in H22 tumor-implanted mice. Taken together, these data indicate that PMBE selectively induces apoptosis in HepG2 cells through caspase-dependent pathways, and inhibits tumor growth in vivo, making it a potential candidate for anticancer therapeutics.


An intelligent nanodevice based on the synergistic effect of telomerase-triggered photodynamic therapy and gene-silencing for precise cancer cell therapy.
The development of intelligent and precise cancer therapy systems that enable accurate diagnosis and specific elimination of cancer cells while protecting normal cells to improve the safety and effectiveness of the treatment is still a challenge. Herein, we report a novel activatable nanodevice for precise cancer therapy. The nanodevice is constructed by adsorbing a DNA duplex probe onto MnO2 nanosheets. After cellular uptake, the DNA duplex probe undergoes telomerase-triggered conformation switching, resulting in a Ce6 "turn-on" signal for the identification of cancer cells. Furthermore, Deoxyribozyme (DNAzyme) is activated to catalyse the cleavage of survivin mRNA, actualizing a precise synergistic therapy in cancer cells involving photodynamic therapy and gene-silencing. The MnO2 nanosheets provide Mn2+ for the DNAzyme and relieve hypoxia to improve the efficiency of the photodynamic therapy. Live cell studies reveal that this nanodevice can diagnose cancer cells and specifically eliminate them without harming normal cells, so making the treatment safer and more effective. The developed DNA-MnO2 nanodevice provides a valuable and general platform for precise cancer therapy.