Association between the use of muscle-building supplements and DNA damage in resistance training practitioners.
Little is known about the relationship between the supplements used for sport and safety, especially regarding the induction of genotoxicity. Therefore, more knowledge about a DNA damage possibly caused using sport supplements is necessary. The aim of this study was to investigate the potential association between the use of muscle-building supplements and DNA damage in resistance training practitioners. Muscle-building supplements were classified into three categories based on evidence of efficacy and safety: Strong Evidence to Support Efficacy and Apparently Safe (SESEAS); Limited or Mixed Evidence to Support Efficacy (LMESE), and Little to No Evidence to Support Efficacy and/or Safety (LNESES). DNA damage was evaluated by the comet assay (DNA damage index and frequency) and buccal micronucleus by the cytome assay (micronuclei and nuclear buds). In the sequence, the adjusted analysis of covariance was performed. This study included 307 individuals ages 37.99 ± 13.95 y (52.1% men), of which 157 consumed supplements. The results of the comet assay revealed that participants who used supplements had higher DNA damage indexes (P = 0.018) and damage frequency (P = 0.045) than those who reported using no supplements. Moreover, the comet assay also indicated that the participants who used supplements classified into the SESEAS category presented the highest DNA damage index (P = 0.025) and frequency (P = 0.044) compared with those who used no supplements. However, we found no significant difference in the micronuclei and nuclear buds in the evaluated groups (P > 0.05). Supplement use is not associated with permanent damage, suggesting that SESEAS supplements are safe for consumption.


Ground state isomerization of a model green fluorescent protein chromophore.
The relationship between ground state cis-trans isomerization and protonation state is explored for a model green fluorescent protein chromophore, 4-hydroxybenzylidene-1,2-dimethylimidazolinone (HBDI). We find that the protonation state has only a modest effect on the free energy differences between cis and trans isomers and on the activation energies for isomerization. Specifically, the experimental free energy differences are 3.3, 8.8, and 9.6 kJ/mol for cationic, neutral, and anionic forms of HBDI, respectively, and the activation energies are 48.9, 54.8, and 54.8 kJ/mol for cationic, neutral, and anionic forms, respectively. Furthermore, these activation energies are much smaller than might be expected based on comparison with similar systems. These results suggest that there may be a sub-population of the chromophore, which is nearly equally accessible to all three protonation states, through which thermal isomerization may proceed.


Approving the use of animals in medical education.
Animals have been and will continue to be used in educational programs, but some concerns about the responsibility for assuring their proper care and humane use need to be discussed. Research animals have been regulated and monitored quite successfully by Institutional Animal Care and Use Committees (IACUC). These Committees are extending their responsibilities to cover animals used in educational programs. Three common roles of these IACUCs are described, including oversight, investigative and training responsibilities. Guidelines developed for faculty using animals at the University of Florida are presented and discussed.


Prognostic significance of MR identified EMVI, tumour deposits, mesorectal nodes and pelvic side wall disease in locally advanced rectal cancer.
To study the prognostic significance of MRI identified tumour deposits (TD), extramural vascular invasion (EMVI), lymph node metastases (LNM) and pelvic sidewall (PSW) disease in rectal cancer. This IRB approved study was conducted on patients with stage IIA-IIIC rectal adenocarcinoma treated with neoadjuvant long course chemoradiotherapy (LCCRT) and total mesorectal excision (TME) type of surgery between 2012-2018. A radiologist blinded to outcome reviewed staging and restaging magnetic resonance imaging (MRI) for TD, EMVI, LNM and PSW. The agreement between four radiologists was studied and we obtained outcome data from a prospectively maintained database. The prognostic significance of imaging findings was assessed. A total of 297 (186 males) patients with a mean age of 47.3 (SD14.4) years were included in the study. The majority had T3 (n = 206) or T4 (n = 59) stage disease. The mean duration of follow-up was 49.3 ± 25 months (6.6-101 months). 5-year overall (OS) and disease-free survival (DFS) was 84% and 74%, respectively. Staging and restaging MRI had EMVI in 49.5% and 31.3%; TD in 47.5% and 31.6%; LNM in 61.1% and 38.1% and PSW in 11.4% and 6.1%. OS was adversely affected by EMVI, TD and PSW with the adjusted HR (aHR) of 3.32, 3.31, 3.27 for staging MRI and 2.99, 3.1, 2.81 for restaging MRI, respectively, p < 0.05. DFS was affected by EMVI (aHR = 1.85, 2.33) and TD (aHR = 1.83, 2.19), p < 0.05. Persistence of these findings after LCCRT led to worst outcome. Intra- and interobserver agreement for EMVI, TD and LN was 0.789, 0.734, 0.406 and 0.449, 0.354, 0.376, respectively, p < 0.001. MRI identified that TD, EMVI and PSW disease are independent poor prognostic indicators in rectal cancer patients. Interobserver agreement for these findings was moderate to fair.


Identifying key roles and responsibilities of peer workers in behavioral health services: A scoping review.
The roles and responsibilities of peer workers (PWs) are not well articulated. This scoping review aims to systematically identify and describe the roles of PWs in outpatient, community based mental health and substance use services, and compare their roles and responsibilities across these service settings METHODS: The scoping review was a priori developed and implemented according to the Joanna Briggs Institute methodology, which includes stating the review objectives, conducting a three-step search method, and charting the results. Forty-four peer reviewed manuscripts were included in the review. PWs were used more often in mental health (n = 27) than substance use (n = 10) programs. Peers adopted a wide range of skills. Across program contexts, peers were frequently used as a source of informal support or mentorship and care coordination. Mental health programs often used peers to deliver manualized interventions, while substance use programs more frequently leveraged PWs to facilitate service linkage and engagement. Roles of peers differed between substance use and mental health programs, reflecting significant diversity in how peers are being integrated into the behavioral health workforce. Peer certification programs must balance consistency with the wide range of skills required of this workforce.


Genetic and pharmacological mouse models of chronic melanocortin activation show enhanced baroreflex control of heart rate.
The central melanocortin system is an important regulator of energy homeostasis and cardiovascular functions. Although the acute effects of melanocortins on central blood pressure regulation are well-established, their long-term effects on autonomic balance and baroreflex function remain largely unexplored. Here we investigated the impact of chronic melanocortin activation on cardiovascular and autonomic nervous system functions by studying α- and γ-MSH overexpressing (MSH-OE) mice and, as pharmacological model, mice treated with the stable α-MSH analogue melonotan-II (MT-II, 0.3 mg/kg/day for 7 days, i.p.). Mean arterial pressure (MAP) and heart rate (HR) were measured in conscious mice by radiotelemetry. MSH-OE mice did not differ from their wild-type littermates in terms of MAP, but displayed reduced HR under physiological baseline conditions. To evaluate the relative activities of sympathetic and parasympathetic nervous systems, we applied autonomic receptor blockers and found an enhanced HR response to atropine in MSH-OE mice, indicating increased cardiac vagal activity. The compensatory increase in HR after drug-evoked vasodilatation was also augmented in MSH-OE mice. Exposure to a high-sodium diet (8% NaCl) markedly reduced HR in MSH-OE mice without concomitant changes in blood pressure, suggesting improved reflex regulation of HR. Chronic treatment with MT-II did not change 24-h MAP or HR regardless of the acute pressor and tachycardic actions of MT-II. Consistent with the finding in MSH-OE mice, MT-II-treated mice showed an enhanced HR response to vasodilatation. These observations suggest that chronic melanocortin activation may provide cardioprotective regulation by enhancing vagal nerve activity and baroreflex control of heart rate.


Dose modulation: a new concept of antibiotic therapy in the critically ill patient?
Considerable evidence has shown that adequate antibiotic therapy is of utmost importance in the critically ill septic patient. However, antibiotic concentration may be insufficient early in infection course. We propose the concept of dose modulation, meaning front-line variability of antibiotic dose, according to patient and microorganism characteristics, followed by its reduction after clinical response and patient recovery. Therefore, dose modulation means concentrating the largest weight of antibiotics at the front-end, when the microbial load is higher and the pharmacokinetic changes poses the highest risk of underdosing and nibbling off antibiotic dose, when the sepsis syndrome is improving, guided by pharmacokinetic and pharmacodynamic data.


Neuroblastoma presenting as hip pain and skull prominence in a child.
Neuroblastoma is a common cancer in children especially those under 5-years old, however they can have varied presentations that may make diagnosis difficult. Neuroblastoma is not usually high on a clinician's differential for a child's gait dysfunction. We describe a case of a 6-year-old female who presented to the Emergency Department for new onset right hip pain. She had associated gait disturbance and pain with ambulation as well as a new lump on her right parietal skull. An MRI of the brain, lumbar spine, and pelvis revealed the diagnosis of a left adrenal neuroblastoma that had metastasized to the femur, the lumbar spine, and the skull. This case shows the importance of early suspicion of malignancy in a patient with seemingly disparate symptoms to ensure early intervention.


Integrative properties of retinal ganglion cell electrical responsiveness depend on neurotrophic support and genotype in the mouse.
Early stages of glaucoma and optic neuropathies are thought to show inner retina remodeling and functional changes of retinal ganglion cells (RGCs) before they die. To assess RGC functional plasticity, we investigated the contrast-gain control properties of the pattern electroretinogram (PERG), a sensitive measure of RGC function, as an index of spatio-temporal integration occurring in the inner retina circuitry subserving PERG generators. We studied the integrative properties of the PERG in mice exposed to different conditions of neurotrophic support. We also investigated the effect of genotypic differences among mouse strains with different susceptibility to glaucoma (C57BL/6J, DBA/2J, DBA/2.Gpnmb(+)). Results show that the integrative properties of the PERG recorded in the standard C57BL/6J inbred mouse strain are impaired after deficit of neurotrophic support and partially restored after exogenous neurotrophic administration. Changes in PERG amplitude, latency, and contrast-dependent responses differ between mouse strains with different susceptibility to glaucoma. Results represent a proof of concept that the PERG could be used as a tool for in-vivo monitoring of RGC functional plasticity before RGC death, the effect of neuroactive treatments, as well as for high-throughput tool for phenotypic screening of different mouse genotypes.


Rivaroxaban versus warfarin in Japanese patients with nonvalvular atrial fibrillation in relation to the CHADS2 score: a subgroup analysis of the J-ROCKET AF trial.
Results from a trial of rivaroxaban versus warfarin in 1280 Japanese patients with atrial fibrillation (J-ROCKET AF) revealed that rivaroxaban was noninferior to warfarin with respect to the principal safety outcome. In this subanalysis, we investigated the safety and efficacy of rivaroxaban and warfarin in relation to patients' CHADS2 scores. The mean CHADS2 score was 3.25, and the most frequent scores were 3 and 4. No statistically significant interactions were observed between principal safety outcome event rates and CHADS2 scores with respect to treatment groups (P value for interaction = .700). Irrespective of stratification into moderate- and high-risk groups based on CHADS2 scores of 2 and 3 or more, respectively, no differences in principal safety outcome event rates were observed between rivaroxaban- and warfarin-treated patients (moderate-risk group: hazard ratio [HR], 1.06; 95% confidence interval [CI], .58-1.95; high-risk group: HR, 1.11; 95% CI, .86-1.45; P value for interaction = .488). The primary efficacy end point rate in the rivaroxaban-treated group was numerically lower than in the warfarin-treated group, regardless of risk group stratification (moderate-risk group: HR, .46; 95% CI, .09-2.37; high-risk group: HR, .49; 95% CI, .22-1.11; P value for interaction = .935). This subanalysis indicated that the safety and efficacy of rivaroxaban compared with warfarin were similar, regardless of CHADS2 score.


Tissue eosinophil proliferation and maturation in schistosome-infected mice and hamsters.
Extramedullary eosinophilopoiesis is described as a regular pathological feature of murine and cricetine schistosome infections. Using the Dominici staining technique, colonies of developing eosinophils were commonly found in certain tissue sites of dense oviposition, particularly in the liver, and in associated lymphoreticular tissues. The relationship of these observations to the role of eosinophilic leukocytes in schistosomiasis is discussed.


The role of mitochondrial respiration in salinity tolerance.
NaCl is the most abundant salt in salinity-affected land. The ability of plants to sift the water table, limit NaCl uptake, compartmentalise Na⁺/Cl⁻ ions and prevent negative ionic and osmotic effects on cell function, are the foundations of salinity tolerance mechanisms. In this review, we show that although the quantitative response of respiratory rate to changes in salt concentration is complex, the properties of respiratory processes are crucial for tolerance during ion exclusion and tissue tolerance. We consider whole-plant gas exchange and carbon balance analysis alongside the salt responses of mitochondrial properties and genetic studies manipulating respiratory processes. We showcase the importance of efficient ATP generation, dampened reactive oxygen species and mitochondrial osmolytes for salinity tolerance in plants.


Risk-adjusted econometric model to estimate postoperative costs: an additional instrument for monitoring performance after major lung resection.
The objectives of this study were to develop a risk-adjusted model to estimate individual postoperative costs after major lung resection and to use it for internal economic audit. Variable and fixed hospital costs were collected for 679 consecutive patients who underwent major lung resection from January 2000 through October 2006 at our unit. Several preoperative variables were used to develop a risk-adjusted econometric model from all patients operated on during the period 2000 through 2003 by a stepwise multiple regression analysis (validated by bootstrap). The model was then used to estimate the postoperative costs in the patients operated on during the 3 subsequent periods (years 2004, 2005, and 2006). Observed and predicted costs were then compared within each period by the Wilcoxon signed rank test. Multiple regression and bootstrap analysis yielded the following model predicting postoperative cost: 11,078 + 1340.3X (age > 70 years) + 1927.8X cardiac comorbidity - 95X ppoFEV1%. No differences between predicted and observed costs were noted in the first 2 periods analyzed (year 2004, $6188.40 vs $6241.40, P = .3; year 2005, $6308.60 vs $6483.60, P = .4), whereas in the most recent period (2006) observed costs were significantly lower than the predicted ones ($3457.30 vs $6162.70, P < .0001). Greater precision in predicting outcome and costs after therapy may assist clinicians in the optimization of clinical pathways and allocation of resources. Our economic model may be used as a methodologic template for economic audit in our specialty and complement more traditional outcome measures in the assessment of performance.


Contemporary management of atrial fibrillation.
The incidence of atrial fibrillation approximately doubled for every 10-year increment in age in the Framingham Heart Study cohort; thus physicians will be faced with an increasing patient population with atrial fibrillation. Hypertension is observed to be the most common associated risk factor in both sexes. The management of patients with atrial fibrillation is evolving as a result of a number of published studies. Calcium channel blockers and beta-blockers are emerging as the preferred choices for rate control rather than digoxin. Low-dose anticoagulation therapy has shown beneficial effects not only in primary prevention, but also for secondary prevention of thromboembolism. Thus, patients who cannot be successfully cardioverted should be anticoagulated if there are no contraindications (Table 3) and if they do not fall into the low-risk group--defined as patients under the age of 65 without risk factors (hypertension, diabetes, previous stroke). Patients not eligible for anticoagulation should be on aspirin therapy. Patients with lone atrial fibrillation are not at higher risk for thromboembolism than the general population; therefore, they can be managed without anticoagulation or antiplatelet therapy. Antiarrhythmic treatment should be approached cautiously; amiodarone in low doses is the most effective and safe treatment, but this remains controversial.


A review on control and fault-tolerant control systems of AC/DC microgrids.
Microgrids (MG) treat local energy supply issues effectively and from a point of view of the distribution grid, may be a power supply or virtual load. Despite holding a myriad of benefits, MGs also bear a set of challenges, including a higher fault rate. Currently, many articles focus on control techniques; however, little has been written about the techniques of control, hierarchical control, and fault-tolerant control (FTC) applied to MGs, which is the motive of this bibliographic revision on control systems. A brief comparison of the different approaches in the field of present-day research is carried out primarily addressing hierarchical control and fault tolerance. The objective of this investigation is to attract the interest of researchers to the field of control and fault tolerance applied to MGs, such as: modeling, testbed, benchmark systems, control and hierarchical control strategies, fault diagnosis and FTC.


Aneurysm diameter and proximal aortic neck diameter influence clinical outcome of endovascular abdominal aortic repair: a 4-year EUROSTAR experience.
Our objective was to evaluate the effect of preoperative aneurysm and aortic neck diameter on clinical outcome after infrarenal abdominal endovascular aneurysm repair (EVAR). Data of patients in the European Collaborators Registry on Stent-Graft Techniques for Abdominal Aortic Aneurysm Repair (EUROSTAR) registry base who underwent EVAR with Talent stent grafts were analyzed. Patient characteristics and clinical outcomes were compared among four groups defined by preoperative abdominal aortic aneurysm (AAA) and proximal aortic neck diameter: A, AAA < or =60 mm and neck < or =26 mm; B, AAA >60 mm and neck < or =26 mm; C, AAA < or =60 mm and neck >26 mm; and D, AAA >60 mm and neck >26 mm. Over a 7-year period, 1,317 patients underwent EVAR. Patients in groups B and D were significantly older and had a higher American Society of Anesthesiologists score compared with groups A and C (p=0.002 and 0.003, respectively). Mortality rate was highest in group D (p=0.002), as were rupture and conversion rates (p=0.015 and 0.037, respectively). This study demonstrates that patients with an AAA >60 mm and a proximal aortic neck >26 mm have worse clinical outcome after EVAR.


Neural injury biomarkers of novel shellfish toxins, spirolides: a pilot study using immunochemical and transcriptional analysis.
In 1991, routine biotoxin monitoring of bivalve molluscs at aquaculture sites along the eastern shore of Nova Scotia, Canada revealed a group of novel seafood toxins called spirolides, whose origin was the dinoflagellate Alexandrium ostenfeldii. Result from this preliminary study in rodents demonstrates a highly toxic lethal response in rats and mice after intraperitoneal injections of lipophilic extracts. To elucidate the modes of action and toxicologic pathology, brain and internal organs were examined by histology and various biomarkers of neural injury were monitored by immunohistochemistry (IH) and/or transcriptional analysis. The histological and transcriptional data showed that the effects of spirolides are species dependent for mice and rats. Histopathology showed that in the mouse brain, the hippocampus and brain stem appeared to be the major target regions but no histological changes were observed in the rat. Transcriptional analysis in the mouse brain showed no alterations in the biomarkers whereas in the rat brain there were major changes in the markers of neuronal injury. These biomarkers included the early injury markers HSP-72, c-jun and c-fos which are essential for converting stimuli into intracellular changes within neurons. The potential effects of spirolides were also evaluated with respect to different subtypes of the acetylcholine receptors (AChRs) since earlier reports showed these as putative targets. Both the muscarinic and nicotinic AChRs were found to be upregulated. Hence, transcriptional and immunohistochemical analysis does provide insight to the molecular mechanisms of this novel group of shellfish toxins. No histological changes were observed in other tissues.


Recreational motor vehicle use and facial trauma.
The use of recreational motorized vehicles (RMVs), including all-terrain vehicles (ATVs), snowmobiles, and go-carts, has increased in recent decades. Because RMVs are lightly regulated, there are numerous safety concerns. This analysis examines a nationally representative resource to estimate the incidence of craniofacial trauma secondary to RMV accidents, evaluating injury and demographic patterns. The Consumer Product Safety Commission's National Electronic Injury Surveillance System was examined for facial trauma resulting in emergency department (ED) visits stemming from the use of ATVs, motorbikes/scooters, snowmobiles, and utility vehicles. Characteristics including demographics, anatomic sites, mechanism, and location of injury were evaluated, as well as details regarding helmet and alcohol use. There were 1,464 entries extrapolating to an estimated 61,312 ED visits over a 5-year period for facial trauma from RMV use. From 2009 to 2013, there was a 28% reduction in ED visits. The majority of patients were male, and the median age was 17 years. Lacerations (45.1%), contusions/abrasions (26.7%), and fractures (24%) were the most frequent injuries. Among fractures, the most common types were nasal (29%), followed by mandible (20%) and orbital (8%) fractures. All-terrain vehicles (62%) were the most common vehicles. Alcohol consumption resulted in a higher rate of facial fractures (48.5% vs. 22.8%). As there is a significant potential for injury, familiarity with injury patterns associated with RMVs is useful in the management of facial trauma. Recreational motorized vehicles facial trauma results in tens of thousands of ED visits annually. This data reinforces the importance of pursuing further efforts to raise public awareness and improve safety measures.


General and efficient synthesis of arylamino- and alkylamino-substituted diphenylporphyrins and tetraphenylporphyrins via palladium-catalyzed multiple amination reactions.
A series of arylamino- and alkylamino-substituted diphenylporphyrins and tetraphenylporphyrins were efficiently synthesized by reactions of brominated porphyrin precursors with amines via palladium-catalyzed amination. The multiple amination reactions are general and suitable for a variety of amines, affording the desired aminoporphyrins in good to excellent yields. Examples include aromatic and aliphatic amines, primary and secondary amines, electron-rich, -neutral, and -poor amines as well as heteroaromatic amines and imines.


[Colonoscopic diagnosis and treatment of intestinal invagination in children].
1. The possibilities of diagnostics and treatment of an intestinal invagination in children by the help of a colonileoscopy are discussed. 2. Clinico-endoscopical comparisons of ileocaecal invaginations in children and their connections with the sphincteric function of the Bauhin's ileocaecal valve are made.


Artificial Intelligence-Enabled De Novo Design of Novel Compounds that Are Synthesizable.
Development of computer-aided de novo design methods to discover novel compounds in a speedy manner to treat human diseases has been of interest to drug discovery scientists for the past three decades. In the beginning, the efforts were mostly concentrated to generate molecules that fit the active site of the target protein by sequential building of a molecule atom-by-atom and/or group-by-group while exploring all possible conformations to optimize binding interactions with the target protein. In recent years, deep learning approaches are applied to generate molecules that are iteratively optimized against a binding hypothesis (to optimize potency) and predictive models of drug-likeness (to optimize properties). Synthesizability of molecules generated by these de novo methods remains a challenge. This review will focus on the recent development of synthetic planning methods that are suitable for enhancing synthesizability of molecules designed by de novo methods.


Immuno-oncology in GI tumours: Clinical evidence and emerging trials of PD-1/PD-L1 antagonists.
The use of immune checkpoint inhibitors constitutes an emerging therapeutic field for the therapy of gastrointestinal (GI) malignancies following the recent FDA approvals of PD-1 inhibitors for esophago-gastric adenocarcinoma, hepatocellular carcinoma and for microsatellite-instable tumors, which are mainly colorectal cancers. This paper reviews the clinical evidence end of 2017 and discusses the clinical development programs of atezolizumab, avelumab, durvalumab, nivolumab and pembrolizumab in GI-tract cancers. Since 2014, these antagonists of the PD-1/PD-L1 axis have gained approval for use in numerous other tumors. Phase II trials and phase I expansion cohorts demonstrate clinical activity in patients with oesophageal, gastric, colorectal, anal and hepatic cancer. Signals of outstanding efficacy are particularly observed in biomarker selected populations and for certain combination regimen. Comprehensive phase III development programs have been initiated in oesophageal and gastric cancer, with randomized trials ongoing in hepatocellular and colorectal cancer as well.


Determinants of heat stress and strain in electrical utilities workers across North America as assessed by means of an exploratory questionnaire.
Previous field studies monitoring small groups of participants showed that heat stress in the electrical utilities industry may be detrimental to worker health and safety. Our aim in this study was to characterize heat stress and strain in electrical utilities workers across North America. A total of 428 workers in the power generation, transmission, and distribution industry across 16 U.S. states and 3 Canadian Provinces completed a two-part on-line questionnaire anonymously. The first part comprised 13 general questions on the employee's workplace location, role in the organization, years of experience, general duties, average work shift duration, and other job-related information. It also included two questions on self-reported heat stress. The second part consisted of the "Heat Strain Score Index" (HSSI), a validated questionnaire which evaluates heat stress at the workplace as "safe level" (score ≤13.5: worker experiences no/low heat strain), "caution level" (score 13.6 to 18.0: moderate risk for heat strain), and "danger level" (score >18.0: high risk for heat strain). In addition to the survey, we obtained meteorological data from weather stations in proximity (12.3 ± 12.2 km) to the work locations. Based on the HSSI, 32.9%, 22.3%, and 44.4% of the responders' workplaces were diagnosed as "safe level," "caution level," and "danger level," respectively. The HSSI varied significantly depending on the occupation from 4.9 ± 3.2 in contact center workforce to 19.1 ± 5.4 in mechanics (p < 0.001), and demonstrated moderate linear relationships with summertime (June, July, August) midday air temperature (r = 0.317, p < 0.001) and outdoor midday Wet-Bulb Globe Temperature (r = 0.322, p < 0.001). The highest HSSI was observed in mechanics, machine operators in line installations, line workers, electricians, and meter-readers. We conclude that electrical utilities workers experience instances of severe environmental heat stress resulting in elevated levels of heat strain, particularly when performing physically demanding tasks (e.g., manually climbing utility poles, installing lines).


Characterization of chromatin-condensing proteins during spermiogenesis in a neogastropod mollusc (Murex brandaris).
During the process of chromatin condensation in the spermiogenesis of the neogastropod mollusc Murex brandaris, the nuclear protein complement undergoes a complex series of changes. These changes lead to the appearance of three small protamines in the ripe sperm nuclei. We have characterized this system electrophoretically and at the compositional level, as well as through the analysis of crossreactions with antibodies elicited against a specific spermatozoan protamine. Our results indicate that the complex pattern of chromatin condensation during spermiogenesis in this species (M. brandaris) may be modulated by a series of post-translational (and intranuclear) modifications of DNA-interacting proteins, such as precursors to the sperm protamines. The amino acid composition of each sperm protamine is remarkably simple (lys + arg + gly > or = 96 mol%). This system of spermiogenic/spermatozoal proteins in the neogastropod M. brandaris clearly differs from that in patellogastropods and archaeogastropods, and it may be helpful in understanding evolutionary changes in the chromatin condensation pattern during the spermiogenesis of gastropod molluscs.


Understanding how cystic fibrosis mutations disrupt CFTR function: from single molecules to animal models.
Defective epithelial ion transport is the hallmark of the life-limiting genetic disease cystic fibrosis (CF). This abnormality is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR), the ATP-binding cassette transporter that functions as a ligand-gated anion channel. Since the identification of the CFTR gene, almost 2000 disease-causing mutations associated with a spectrum of clinical phenotypes have been reported, but the majority remain poorly characterised. Studies of a small number of mutations including the most common, F508del-CFTR, have identified six general mechanisms of CFTR dysfunction. Here, we review selectively progress to understand how CF mutations disrupt CFTR processing, stability and function. We explore CFTR structure and function to explain the molecular mechanisms of CFTR dysfunction and highlight new knowledge of disease pathophysiology emerging from large animal models of CF. Understanding CFTR dysfunction is crucial to the development of transformational therapies for CF patients.


Variation in the nucleotide sequence of a prolamin gene family in wild rice.
Variation in the DNA sequence of the 10 kDa prolamin gene family within the wild rice species Oryza rufipogon was probed using the direct sequencing of PCR-amplified genes. A comparison of the nucleotide and deduced amino-acid sequences of eight Asian strains of O. rufipogon and one strain of the related African species O. longistaminata is presented.


Host-directed therapies for malaria: possible applications and lessons from other indications.
Host-directed therapies (HDT) are rapidly advancing as a new and clinically relevant strategy to treat infectious disease. The application of HDT can be broadly used to (i) inhibit host factors essential for pathogen development, including host protein kinases, (ii) control detrimental immune signalling, resulting from excessive release of cytokines, chemokines and extracellular vesicles and (iii) strengthen host defence mechanisms, such as tight junctions in the endothelium. For malaria and other eukaryotic parasite-causing diseases, HDTs could provide a novel avenue to combat the growing resistance seen across all antimicrobials and provide protection against the severe forms of disease through modulation of the host immune response.


Microwave-assisted extraction followed by capillary electrophoresis-amperometric detection for the determination of antioxidant constituents in Folium Eriobotryae.
A method based on capillary electrophoresis-amperometric detection has been developed for the determination of catechin, rutin, kaempferol, gentistic acid, and quercetin in Folium Eriobotryae with the aid of microwave-assisted solvent extraction. The effects of the acidity and the concentration of the running buffer, separation voltage, injection time, detection potential, and irradiation time were investigated to acquire the optimum analysis conditions. The detection electrode was a 300-mum-diameter carbon disc electrode at a detection potential of +0.90 V. The five analytes could be well separated within 12 min in a 40-cm length fused-silica capillary at a separation voltage of 12 kV in a 50-mM borate buffer (pH 9.0). The relation between peak current and analyte concentration was linear over about three orders of magnitude with detection limits (S/N=3) ranging from 2.1 to 4.5 microM for all the analytes.


[Reconstruction of the proximal femur with the MUTARS® system].
In the proximal femur a modular tumor prosthesis can be used today for reconstruction after resection of primary malignant bone tumors, metastatic lesions, and in revision surgery. The MUTARS® Münster system offers a high modularity and the possibility of combining it with the hip and knee revision system. Technical innovations, like hexagonal press fit bone anchorage, fine adjustment of rotation, silver coating of the surface of the prosthesis, and functional reconstruction with the help of a Trevira tube, guarantee a very good long-term survival of the prostheses and protection against the main complications such as aseptic loosening, deep infection, and instability.


Effect of sheath material and reaction overpressure on Ag extrusions into the TiO2 insulation coating of Bi-2212 round wire.
In order to develop a high current density in coils, Bi-2212 wires must be electrically discrete in tight winding packs. It is vital to use an insulating layer that is thin, fulfils the dielectric requirements, and can survive the heat treatment whose maximum temperature reaches 890 °C. A thin (20-30 µm) ceramic coating could be better as the insulating layer compared to alumino-silicate braided fiber insulation, which is about 100 μm thick and reacts with the Ag sheath during heat treatment, degrading the critical current density (Jc). At present, TiO2 seems to be the most viable ceramic material for such a thin insulation because it is chemically compatible with Ag and Bi-2212 and its sintering temperature is lower than the maximum temperature used for the Bi-2212 heat treatment. However, recent tests of a large Bi-2212 coil insulated only with TiO2 showed severe electrical shorting between the wires after over pressure heat treatment (OPHT). The origin of the shorting was frequent silver extrusions that penetrated the porous TiO2 layer and electrically connected adjacent Bi-2212 wires. To understand the mechanism of this unexpected behaviour, we investigated the effect of sheath material and hydrostatic pressure on the formation of Ag extrusions. We found that Ag extrusions occur only when TiO2-insulated Ag-0.2%Mg sheathed wire (Ag(Mg) wire) undergoes OPHT at 50 bar. No Ag extrusions were observed when the TiO2-insulated Ag(Mg) wire was processed at 1 bar. The TiO2-insulated wires sheathed with pure Ag that underwent 50 bar OPHT were also free from Ag extrusions. A key finding is that the Ag extrusions emanating from the Ag(Mg) sheath actually contain no MgO, suggesting that local depletion of MgO facilitates local, heterogeneous deformation of the sheath under hydrostatic overpressure. Our study also suggests that predensifying the Ag(Mg) wire before insulating it with TiO2 and doing the final OPHT can potentially prevent Ag extrusion.


A 'cheap' optimal control approach to estimate muscle forces in musculoskeletal systems.
This paper shows a new method to estimate the muscle forces in musculoskeletal systems based on the inverse dynamics of a multi-body system associated optimal control. The redundant actuator problem is solved by minimizing a time-integral cost function, augmented with a torque-tracking error function, and muscle dynamics is considered through differential constraints. The method is compared to a previously implemented human posture control problem, solved using a Forward Dynamics Optimal Control approach and to classical static optimization, with two different objective functions. The new method provides very similar muscle force patterns when compared to the forward dynamics solution, but the computational cost is much smaller and the numerical robustness is increased. The results achieved suggest that this method is more accurate for the muscle force predictions when compared to static optimization, and can be used as a numerically 'cheap' alternative to the forward dynamics and optimal control in some applications.


Antigenicity, storage, and aging: physiologic autoantibodies to cell membrane and serum proteins and the senescent cell antigen.
Normal human serum contains autoantibodies to a wide range of cellular and serum proteins. IgG autoantibodies to cell membrane proteins spectrin, syndein (Band 2.1), Band 3 degradation products, and the senescent cell antigen are among them. Physiologic autoantibodies to the senescent cell antigen, a approximately 62 000 dalton glycopeptide derived from Band 3, initiate removal of senescent, damaged, and stored cells in vivo. The senescent cell antigen is one of the two Band 3 degradation products (Mr approximately 66 000 and 62 000) observed in freshly prepared ghosts. Since the senescent cell antigen is observed on red cells aged in situ, data suggest that Band 3 undergoes proteolysis in situ. IgG eluted from blood stored for transfusion binds to the senescent cell antigen. The amount of IgG on red cells increases during storage suggesting accumulation of the senescent cell antigen. Autoantibodies to other cell and serum proteins are discussed as possible regulators of homeostasis. The effect of age on physiologic autoantibodies is reviewed.


Identifying surgeon and institutional drivers of cost in total shoulder arthroplasty: a multicenter study.
Despite rapid increases in the demand for total shoulder arthroplasty, data describing cost trends are scarce. We aim to (1) describe variation in the cost of shoulder arthroplasty performed by different surgeons at multiple hospitals and (2) determine the driving factors of such variation. A standardized, highly accurate cost accounting method, time-driven activity-based costing, was used to determine the cost of 1571 shoulder arthroplasties performed by 12 surgeons at 4 high-volume institutions between 2016 and 2018. Costs were broken down into supply costs (including implant price and consumables) and personnel costs, including physician fees. Cost parameters were compared with total cost for surgical episodes and case volume. Across 4 institutions and 12 surgeons, surgeon volume and hospital volume did not correlate with episode-of-care cost. Average cost per case of each institution varied by factors of 1.6 (P = .47) and 1.7 (P = .06) for anatomic total shoulder arthroplasty (TSA) and reverse total shoulder arthroplasty (RSA), respectively. Implant (56% and 62%, respectively) and personnel costs from check-in through the operating room (21% and 17%, respectively) represented the highest percentages of cost and highly correlated with the cost of the episode of care for TSA and RSA. Variation in episode-of-care total costs for both TSA and RSA had no association with hospital or surgeon case volume at 4 high-volume institutions but was driven primarily by variation in implant and personnel costs through the operating room. This analysis does not address medium- or long-term costs.


Mapping of the Gastrointestinal Short Form Questionnaire (GSF-Q) into EQ-5D-3L and SF-6D in patients with gastroesophageal reflux disease.
The short, self-administered Gastroesophageal Reflux Disease (GERD) Symptom Frequency Questionnaire (GSFQ) is a specific Quality of Life (QoL) instrument which measures the impact of GERD symptoms on QoL. This study aims to map the specific scores in GSFQ into two generic instruments: SF-6D and EQ-5D-3 L, in order to obtain utility estimates derived from the GERD condition. A national representative sample of GERD patients was selected, stratified by gender, age (< 45, ≥45 years) and GERD severity (0-I, II-IV Savary-Miller score) for validation purposes. Age, gender, BMI, GERD diagnose, GERD severity, associated comorbidities and risk factors were recorded. GSFQ, SF-6D, EQ-5D-3 L, and the HRQoL Visual Analogue Scale (VAS) were answered by patients. Several mapping methods were estimated, regression using dummy variables, and linear, quadratic and cubic regression using optimal factor scores. The use of a GERD aggregated summary severity derived from the GSFQ was dimed the best predictor. Overall Mean Absolute Error (MAE), overall Mean Absolute Percentage Error (MAPE) were used as goodness-of-fit (GOF) indexes to compare models. A total of 3405 patients were recruited by 490 clinicians. Mean age was 49 (±14.4) years and 49.8% were women. Reported comorbidities were clustered in 6 antecedents and 15 concomitant pathologies. Aggregation of levels for the frequency of symptoms items was found more suitable for estimation. Regression weights were found to follow a monotonous progressive pattern. Overall MAE ranged from 0.092 to 0.094 for SF-6D utility prediction and from 0.008 to 0.08 for EQ-5D-3 L, while MAPE values ranged from 27.9 to 29% for SF-6D and from 36.8 to 38.4% for EQ-5D-3 L. Cubic regression GOF demonstrated a better fit. It is possible to translate specific GSFQ scores assessing GERD condition into generic SF-6D and EQ-5D-3 L utility values. Although regression using dummy variables is a suitable mapping procedure, other alternative mapping methods convey better fit, in particular cubic regression.


Circulating and cardiac levels of apelin, the novel ligand of the orphan receptor APJ, in patients with heart failure.
The orphan receptor APJ and its recently identified endogenous ligand, apelin, are expressed in the heart. However, their importance in the human cardiovascular system is not known. This study shows that apelin-like immunoreactivity is abundantly present in healthy human heart and plasma. Gel filtration HPLC analysis revealed that atrial and plasma levels of high molecular weight apelin, possibly proapelin, were markedly higher than those of mature apelin-36 itself. As assessed by quantitative RT-PCR analysis, left ventricular apelin mRNA levels were increased 4.7-fold in chronic heart failure (CHF) due to coronary heart disease (p<0.01) and 3.3-fold due to idiopathic dilated cardiomyopathy (p<0.05), whereas atrial apelin mRNA levels were unchanged. Atrial and plasma apelin-like immunoreactivity as well as atrial and ventricular APJ receptor mRNA levels were significantly decreased in CHF. Our results suggest that a new cardiac regulatory peptide, apelin, and APJ receptor may contribute to the pathophysiology of human CHF.


Late Longitudinal Comparison of Endovascular and Open Popliteal Aneurysm Repairs.
We sought to define suitable anatomy predicting durable exclusion of popliteal artery aneurysms (PAAs) and define optimal patient selection criteria for endovascular repair (ER). Seventy-five PAAs were repaired in 66 patients (64 male and 2 female) over the past 13 years. Fifty-two aneurysms (69%) were treated with open surgical exclusion and/or bypass using autologous vein (69%) or polytetrafluorethylene (31%) conduit. Extended bypass targets required inflow from the common femoral artery in 15% of limbs and outflow via a tibial artery in 31%. Since May 2001, ER was considered in patients with high medical risk, limited vessel tortuosity, absence of significant occlusive disease (ankle-brachial index > 0.9), and PAA not involving below knee segments. Interventions were performed via antegrade femoral access in 23 limbs (31%) using commercially available endografts. Device diameters ranged between 7 and 13 mm, with a median of 2 devices per PAA, and mean treatment length was 22 cm (range, 5-36 cm). All patients were followed with duplex ultrasound surveillance and were prescribed clopidogrel and/or aspirin. Patients treated endovascularly were older (82 vs. 70 years old, P = 0.01), but had shorter length of stay (2 vs. 12 days, P = 0.01) and lower complication rates (8% vs. 17%, P = 0.02). Mean surveillance interval was 39 months with similar 4-year survival (67.9% open and 73.7% endovascular). Primary and secondary patencies were 67.2%, 67.2% after ER and 65.5%, 78.4% for open at 4 years, respectively. Four of 6 endovascular failures were thrombosis within 4 months of intervention and had conversions to open repair (OR). Secondary interventions were required after 48.1% of endovascular and 54.1% of ORs. Three limbs were lost in the series (2 open and 1 endovascular). Similar outcomes can be expected after endovascular and open PAA repair with adherence to specific anatomic and technical selection requisites.


Validity of dual-energy x-ray absorptiometry for estimation of visceral adipose tissue and visceral adipose tissue change after surgery-induced weight loss in women with severe obesity.
Reliable and simple methods to quantify visceral adipose tissue (VAT) and VAT changes are needed. This study investigated the validity of dual-energy x-ray absorptiometry (DXA) compared with magnetic resonance imaging (MRI) for estimating VAT cross sectionally and longitudinally after surgery-induced weight loss in women with severe obesity. Women with obesity (n = 36; mean age 43 [SD 10] years; 89% White) with DXA and MRI before bariatric surgery (T0) at 12 (T12) and 24 months (T24) post surgery were included. CoreScan (GE Healthcare, Chicago, Illinois) estimated VAT from 20% of the distance between the top of the iliac crest and the base of the skull. MRI VAT (total VAT) was measured from the base of the heart to the sacrum/coccyx on a whole-body scan. Mean DXA VAT was 45% of MRI VAT at T0, 46% at T12, and 68% at T24. DXA underestimated change in MRI VAT between T0 and T12 by 26.1% (0.81 kg, p = 0.03) and by 71.7% (0.43 kg, p < 0.001) between T12 and T24. The relationship between DXA VAT and MRI VAT differed between T12 and T24 (p value for interaction = 0.03). CoreScan lacks validity for comparing VAT across individuals or for estimating the size of changes within individuals; however, within the limits of measurement error, it may provide a useful indicator of whether some VAT change has occurred within an individual.


Differentiation between various effects of cytotoxic fractions of lymphocyte culture medium.
This paper describes the partial characterization of supernatants derived from mitogen stimulated lymphocytes by ammonium sulfate precipitation, ultrafiltration on Hollow-Fiber beakers and gelchromatography. Fractions from these purification procedures were tested on FL-target cells and the following target cell alterations were measured: RNA- and protein synthesis, 3H-TdR incorporation, cell number and lysis of target cells. Target cell alterations of control fractions from supernatants of non-stimulated lymphocytes, from culture medium and from FCS were compared to the effects of fractions from activated lymphocytes. 3H-TdR incorporation was not only inhibited by the fractions of activated lymphocyte cultures but also by fractions of various controls. Inhibition of 3H-TdR incorporation disappeared when control fractions were serially diluted. Only fractions of supernatant from activated lymphocytes could lyse target cells. It were the same fractions which still inhibited 3H-TdR incorporation of target cells after serial dilution and which showed stimulating effects on RNA synthesis. MW of fractions which were differentiated from control fractions with respect to target cell lysis were: 90,000, 45,000 and lower than 20,000 d.


Orbital subperiosteal abscess and blindness complicating a minimally displaced zygomatic complex fracture.
A case of orbital subperiosteal abscess (SPA) complicating a minimally displaced zygomatic complex (ZMC) fracture is reported and the aetiology and management of this potentially life-threatening condition is discussed. The value of CT scanning in staging orbital infection and determining the site of the abscess and involved paranasal sinuses is emphasised. The correct interpretation of a lateral skull radiograph with the patient brow up may have lead to earlier diagnosis and treatment.


Molecular mechanism of 1,1-dichloroethylene toxicity: excreted metabolites reveal different pathways of reactive intermediates.
The excretion and biotransformation of [14C] 1,1-dichloroethylene (vinylidene chloride, VDC) after administration of a single oral dose has been investigated in female rats. Seventy-two hours after a dose of 0.5, 5.0, and 50.0 mg/kg, 1.26, 9.70, 16.47%, respectively, are exhaled as unchanged VDC, and 13.64, 11.35, 6.13% as 14CO2. The main pathway of elimination is through renal excretion with 43.55, 53.88, 42.11% of the administered radioactivity. Through the biliary system, 15.74, 14.54, 7.65% of the activity are eliminated. The isolation of the main metabolites of VDC from 24 h urine is accomplished through the combined application of solvent extraction, ion exchange chromatography and thin layer chromatography. Then gas chromatography and mass spectrometry are used for their identification. Three metabolites have been identified: thiodiglycolic acid, N-acetyl-S-(2-carboxymethyl)cysteine and methyl-thio-acetylaminoethanol. In addition, three smaller unidentified radioactive peaks have been found. Thiodiglycolic acid is the main metabolite in VDC metabolism. The simultaneous formation of an ethanolamine- and a cysteine-conjugation product points to different reaction pathways of the postulated intermediate reactive epoxide; ethanolamine probably originates from membrane lipids, which react with VDC-epoxide and/or its derivatives. This pathway could explain, in part, the parenchyma damaging effect of VDC.


Experience of diagnosis and treatment of traumatic bronchial rupture in children in a single clinical center.
To examine the diagnosis and treatment of traumatic bronchial rupture in children at the Children's Hospital of Chongqing Medical University, Chongqing, China. The diagnosis and treatment of eight cases of traumatic bronchial rupture were analyzed retrospectively from January 2014 to December 2019 in our hospital. Diagnosis of the eight patients was clear after a chest CT with three-dimensional reconstruction techniques and fiberoptic bronchoscopy; six of the patients had a delay in diagnosis of at least 2 weeks. Among the patients, six had left bronchus rupture, and the other two had right bronchus rupture. All eight patients received surgery; seven patients received a bronchial end-to-end valgus anastomosis, and one received right middle lobe lobectomy. There were no deaths in this group, and all patients were cured and discharged. Follow-up was conducted for 3 months to 2 years; the patients who received surgery showed mild bronchostenosis within 2 weeks after the trauma, and the other six patients showed moderate bronchostenosis upon CT examination. Being alert to bronchial rupture after trauma in children is helpful for diagnosis. Chest CT with three-dimensional reconstruction techniques and fiberoptic bronchoscopy are the most valuable diagnostic methods. The patients can show excellent results if the operation for a continuous valgus anastomosis of the posterior wall and interrupted end-to-end valgus anastomosis of the anterior wall on the ruptured side is performed in the early stage of traumatic bronchial rupture.


CaO2 based Fenton-like reaction at neutral pH: Accelerated reduction of ferric species and production of superoxide radicals.
One challenge in H2O2 based Fenton-like reaction is to break through the limitation of slow reduction of ferric species (FeIII). Present work describes a dramatic acceleration of Fenton-like reaction at neutral pH by using calcium peroxide (CaO2) as a source of hydrogen peroxide (H2O2) and EDTA as a chelating agent of ferric ions. In an optimized condition, phenol degradation in the H2O2 system displayed an initial latent time of 60 min, while phenol can be degraded immediately and removed completely in 30 min in the CaO2 system. Visual MINTEQ analyses indicated Fe-EDTA- was the active species in the reaction. The contribution of 1O2 in CaO2 system was excluded by the poor selectivity in phenol conversion and the comparable 1O2-TEMP EPR signals in both CaO2 and H2O2 systems. Kinetic analyses using chloroform as the probe of O2·- suggested the high production rate of O2·-, which is four orders of magnitude higher than that in H2O2 system. The mechanism of the accelerated CaO2 based Fenton-like reactions was featured by that two electrons coming from CaO2 can be utilized to promote reduction of FeIII: an inner sphere electron transfer takes place to reduce FeIII-EDTA and produce O2·-, and subsequently O2·- provides an electron to reduce another FeIII-EDTA. The revealed intrinsic reducibility in CaO2 based Fenton-like reaction represents a new strategy to break through the well-known rate limiting step of FeIII reduction in Fenton-like reaction and facilitate the removal of organic pollutants at neutral pHs, and also indicates a promising source of O2·- for diverse applications.


Icotinib, a potent and specific EGFR tyrosine kinase inhibitor, inhibits growth of squamous cell carcinoma cell line A431 through negatively regulating AKT signaling.
Icotinib is a potent and specific epidermal growth factor receptor tyrosine kinase inhibitor. In this study, we reported that icotinib had the antitumor activity on human squamous cell carcinoma cell line A431 in vitro. Meanwhile, adhesion to fibronectin and expression of integrin α3 and β1 were significantly reduced in a dose-dependent manner after the treatment of icotinib. Moreover, icotinib induced cell cycle arrested and affected expression of various cell cycle related proteins in squamous cancer cell line A431, whereas it did not cause apoptosis. Furthermore, icotinib remarkably down-regulated phosphorylation of protein kinase B (AKT) though blocking the interaction between 3-phosphoinositide-dependent protein kinase-1 (PDK1) and AKT in A431 cells. Taken together, it is shown that the small molecular compound, icotinib, has an anti-squamous cell carcinoma activity in vitro and its antitumor mechanism is associated with the blockage of the interaction between PDK1 and AKT. These results provide a novel strategy for anti-squamous cell carcinoma therapy.


Registration of colorectal cancer in Scotland: an assessment of data accuracy based on review of medical records.
Colorectal cancer accounts for a substantial burden of morbidity and mortality in the population. While the need for reliable incidence data may be self-evident, the quality of cancer registration data has rarely been assessed. In Scotland during 1993, the medical records of a random sample of cancer registrations attributed to the year 1990 were sought. The sample contained 238 registrations of colorectal cancer, 217 (91%) of which had relevant medical records available for review. Registration details were reabstracted from available records and compared with data in the registry. Discrepancies in identifying items of data (surname, forename, sex and date of birth) were recorded in eight cases (3.7%, 95% confidence intervals 1.2-6.2%). None would have disturbed record linkage. Discrepancy rates of 3.7% (1.2-6.3%) in postcode of residence at the time of diagnosis (excluding differences arising through boundary changes), 8.3% (4.6-12.0%) in 'anniversary date' (excluding differences of 30 days or less), 2.8% (0.6-5.0%) in histological verification status and 13.5% (8.9-18.1%) in morphology code (excluding 'inferred' morphology codes) were recorded. Twelve cases (5.5%, 2.5-8.6%) were deemed not to warrant site codes for cancer of the colon (ICD-9 153) or rectum (ICD-9 154). In many respects, therefore, the data held about registrations of colorectal cancer in Scotland appear to show a high level of accuracy. Completeness of case ascertainment has still to be formally assessed.


Promotion of BST2 expression by the transcription factor IRF6 affects the progression of endometriosis.
Endometriosis (EM) is a benign, multifactorial, immune-mediated inflammatory disease that is characterized by persistent activation of the NF-κB signaling pathway and some features of malignancies, such as proliferation and lymphangiogenesis. To date, the pathogenesis of EM is still unclear. In this study, we investigated whether BST2 plays a role in the development of EM. Bioinformatic analysis was performed with data from public databases to identify potential candidate targets for drug treatment. Experiments were conducted at the cell, tissue, and mouse EM model levels to characterize the aberrant expression patterns, molecular mechanisms, biological behaviors of endometriosis as well as treatment outcomes. BST2 was significantly upregulated in ectopic endometrial tissues and cells compared with control samples. Functional studies indicated that BST2 promoted proliferation, migration, and lymphangiogenesis and inhibited apoptosis in vitro and in vivo. The transcription factor (TF) IRF6 induced high BST2 expression by directly binding the BST2 promoter. The underlying mechanism by which BST2 functions in EM was closely related to the canonical NF-κB signaling pathway. New lymphatic vessels may serve as a channel for the infiltration of immune cells into the endometriotic microenvironment; these immune cells further produce the proinflammatory cytokine IL-1β, which in turn further activates the NF-κB pathway to promote lymphangiogenesis in endometriosis. Taken together, our findings provide novel insight into the mechanism by which BST2 participates in a feedback loop with the NF-κB signaling pathway and reveal a novel biomarker and potential therapeutic target for endometriosis.


Diameter measurement of optical nanofibers using a composite photonic crystal cavity.
We demonstrate a method for making precise measurements of the diameter of a tapered optical fiber with a sub-wavelength diameter waist (an optical nanofiber). The essence of the method is to create a composite photonic crystal cavity by mounting a defect-mode grating on an optical nanofiber. The resultant cavity has a resonance wavelength that is sensitive to the nanofiber's diameter, allowing the diameter to be inferred from optical measurements. This method offers a precise, nondestructive, and in situ way to characterize the nanofiber diameter.


Neurochemical effects of ethylhexyl nitrate in rats.
Rats injected i.p. with 100 mg ethylhexyl nitrate/kg body wt excreted 0.3% of the dose in the urine within 24 h. No urinary nitrite was found within 5 postinjection hours while an output of 26.9 +/- 15.8 micrograms nitrite/h X kg body wt. was detected between 5-24 h. Cerebral glutathione concentration was below the control level after 1 day but returned to control value after 3 and 7 days postinjection. Brain acetylcholine esterase activity was marginally decreased after 1 day while RNA and succinate dehydrogenase assay excluded major structural damage. It seems that the mechanism of clinical symptoms experienced by exposed workers are comparable to those exposed to dynamite and are largely functional.


Radiofrequency Coblation-Assisted Resection of Skull Base Neoplasms Using an Endoscopic Endonasal Approach.
We describe our early experiences with resecting skull base tumors using a radiofrequency ablation-assisted endoscopic endonasal approach. Ninety-seven patients with skull base tumors who were admitted to the Otorhinolaryngology department at Shanghai Jiaotong University Affiliated Shanghai Sixth People's Hospital between January 2014 and December 2016 were operated on using a radiofrequency ablation-assisted endoscopic endonasal approach. Complete resection was achieved in all patients. This paper describes the operative technique and presents the degree of resection, complications, and early clinical outcomes. We investigated the safety and feasibility of the technique and assessed preliminary treatment outcomes. No patients experienced a new neurological deficit, cerebrospinal fluid leak, or meningitis after surgery. No deaths related to skull base tumors were observed during the follow-up period (14-50 months). The volume of intraoperative blood loss was 100-1,200 mL (median 350 mL), the duration of operation was 40-510 min (median 180 min), and the hospital stay was 6-65 days (median 18). Our limited experience indicates that this technique is feasible and safe for complete resection of some skull base tumors in selected cases and in the future will have an increasing role to play in endoscopic sinonasal and skull base tumor dissection.


Assessment of concentration, bioaccumulation and sources of polycyclic aromatic hydrocarbons in zooplankton of Chabahar Bay.
The amounts and sources of polycyclic aromatic hydrocarbons (PAHs) and their bioaccumulation factors (BAFs) in the zooplankton community of Chabahar Bay were investigated. The highest amounts of total PAHs (tPAHs) in the water and zooplankton samples were 62.2ngL(-1) and 1478.6ngg(-1) dry weights, in near the Shahid Beheshti Port and desalination, respectively. The greatest amount of BAF (51,780) was obtained in the entry of Bay, and it was related to the phenanthrene accumulation. Using molecular ratio, the results showed that the major input source of PAH compounds in zooplankton of Chabahar Bay was pyrolytic (fuel) source.


Measurements of the branching fractions and bounds on the charge asymmetries of charmless three-body charged B decays.
We present measurements of branching fractions and charge asymmetries for charmless B-meson decays to three-body final states of charged pions and kaons. The analysis uses 81.8 fb(-1) of data collected at the Upsilon(4S) resonance with the BABAR detector at the SLAC PEP-II asymmetric B Factory. We measure the branching fractions B(B+-->pi(+)pi(-)pi(+))=(10.9+/-3.3+/-1.6)x10(-6), B(B+-->K+pi(-)pi(+))=(59.1+/-3.8+/-3.2)x10(-6), and B(B+-->K+K-K+)=(29.6+/-2.1+/-1.6)x10(-6) and provide 90% C.L. upper limits for other decays. We observe no charge asymmetries for these modes.


Role of dynamin 2 in the disassembly of focal adhesions.
Dynamin 2 (DNM2) is involved in endocytosis and intracellular membrane trafficking through its function in vesicle formation from distinct membrane compartments. During the last decade, several studies pointed out an important role of DNM2-dependent trafficking in turnover of focal adhesions which represent a physical link between the extracellular matrix and the intracellular actin cytoskeleton, and a platform for several signalling pathways. Here, we review the involvement of DNM2 in structural and functional aspects of the focal adhesion sites. Mutations in the DNM2 gene cause two hereditary neuromuscular disorders: dominant centronuclear myopathy and Charcot-Marie-Tooth peripheral neuropathy. Potential impairment of focal adhesions as a pathophysiological hypothesis in DNM2-related human diseases is discussed.


Endovascular Management of a Basilar Artery Pseudoaneurysm After Iatrogenic Injury During Endoscopic Third Ventriculostomy: Case Report.
Endoscopic third ventriculostomy (ETV) is a well-established neurosurgical procedure. However, it carries risks of intraoperative complications, among which major vascular injury is the most dangerous. Reportedly, prominent bleeding during ETV has been noted in <1% of cases. Herein, we describe a case of a 34-year-old woman with occlusive hydrocephalus caused by a quadrigeminal cistern arachnoid cyst, who developed a pseudoaneurysm after injury of the basilar artery apex during ETV. Complete obliteration of the pseudoaneurysm with endovascular balloon-assisted coiling was done on the first postoperative day, and the patient demonstrated gradual recovery, but approximately 4 weeks later, she suffered massive rebleeding, seemingly due to rupture of the weak pseudoaneurysm wall, which resulted in her death. Careful evaluation of sagittal T2-weighted magnetic resonance images before ETV may be invaluable for assessment of the basilar artery position in relation to the third ventricle floor. In addition, use of a blunt surgical instrument (instead of a sharp one or cautery) for fenestration may be safer for prevention of arterial injury. Finally, special care should be applied in cases with an opaque third ventricle floor and inability to visualize the basilar artery during ETV.


Near field and far field plasmonic enhancements with bilayers of different dimensions AgNPs@DLC for improved current density in silicon solar.
The effect of a bilayer of different dimension silver nanoparticles (Ag NPs) on light trapping in silicon solar cells is investigated. Here, we report on the improved performance of silicon solar cells by integrating two layers of silver nanoparticles of different sizes. We experimentally examine the plasmonic near-field and far-field effects of bilayer Ag NPs embedded within an anti-reflective DLC layer on silicon solar cells' optical and electrical characteristics. Field-Emission Scanning Electron Microscopy drove the two-dimensional differences in the size of Ag NPs. The surface plasmon resonance of the two-dimensional nanoparticles was estimated from the absorption optical spectra. External quantum efficiency measurements showed that near-field or far-field plasmonic effects altered with the Ag NPs size. The development of far fields was confirmed by measuring the solar cell performance under AM 1.5 G illumination. The impact of the far-field in the cell containing two layers of Ag NPs, which outer layer is larger dimensions NPs, improves the current density up to 38.4 mA/cm2 (by 70% compared to the bare reference cell).


Local tissue concentrations of cefazolin during total joint arthroplasty: a systematic review.
Periprosthetic joint infections (PJI) following joint arthroplasty are now the leading cause of reoperation and are associated with serious morbidity to the patient, often requiring several staged operations and a prolonged course of parenteral antibiotics. Prophylactic administration of intravenous antibiotics before skin incision is arguably the most important measure to prevent PJI; however, the dose effectiveness of cefazolin in target tissue is not well known. We aimed to identify parameters affecting local tissue concentration (LTC) of cefazolin. We performed a literature search using the following keywords: "orthopaedics," "orthopedic," "arthroplasty" and "cefazolin." We included studies that measured LTC of cefazolin from samples obtained during either a total knee or total hip arthroplasty. Of the 332 records screened, we included 10 studies that described LTC of cefazolin. The included studies evaluated dosing (n = 7), procedure type (n = 3), body mass index (n = 1) and tourniquet utilization (n = 1). Few studies have measured LTC levels of antibiotics (or levels of cefazolin) to validate current recommendations for antibiotic prophylaxis in orthopedic surgery. With infection as the leading reason for early reoperation or revision surgery, the parameters affecting LTC during orthopedic procedures need to be further assessed.


Pathophysiology of fibroid disease: angiogenesis and regulation of smooth muscle proliferation.
Uterine fibroids are the most common tumours presenting in women. The pathophysiology of fibroids is poorly understood, but disordered angiogenesis and altered smooth muscle cell proliferation are believed to play a role. In this review, current knowledge of both of these processes will be summarized. Differences between 'normal' adjacent myometrium and fibroid tumours within the same uterus are outlined. Exploiting these differences represents one of the best opportunities for the development of medical treatments that target fibroid tissue selectively.


Structural Classification of CDR-H3 in Single-Domain VHH Antibodies.
The immune systems protect vertebrates from foreign molecules or antigens, and antibodies are important mediators of this system. The sequences and structural features of antibodies vary depending on species. Many of antibodies from vertebrates, including camelids, have both heavy and light chain variable domains, but camelids also have antibodies that lack the light chains. In antibodies that lack light chains, the C-terminal variable region is called the VHH domain. Antibodies recognize antigens through six complementarity-determining regions (CDRs). The third CDR of the heavy chain (CDR-H3) is at the center of the antigen-binding site and is diverse in terms of sequence and structure. Due to the importance of antibodies in basic science as well as in medical applications, there have been many studies of CDR-H3s of antibodies that possess both light and heavy chains. However, nature of CDR-H3s of single-domain VHH antibodies is less well studied. In this chapter, we describe current knowledge of sequence-structure-function correlations of single-domain VHH antibodies with emphasis on CDR-H3. Based on the 370 crystal structures in the Protein Data Bank, we also attempt structural classification of CDR-H3 in single-domain VHH antibodies and discuss lessons learned from the ever-increasing number of the structures.


Effect of hydrocarbons and other parameters on hydrocarbon-utilizing Pichia angusta MTCC-225.
Pichia angusta MTCC-225, a catalase-positive yeast that utilizes methanol and lighter hydrocarbons, is the subject of this investigation. An orthogonal experimental design L16 was used to investigate the effects of methanol, a gas mixture, zero air, temperature, agitation, and salts solution on hydrocarbon utilizing P. angusta. QUALITEK-4 Software was used for automatic design and analysis of the experimental results. Among the various parameters tested, agitation contributed the highest influence (56.5%). Zero air, methanol concentration, and gas mixture showed a moderate influence on the growth of P. angusta. Methanol concentration and gas mixture showed a 10.91 and 10.12% influence, respectively, on yeast growth. Zero air played an important role, with a 15.19% influence on the utilization of hydrocarbon.


Postoperative evaluation of palatoplasty using the modified Kaplan method.
Bilateral buccal mucosal flaps were used for a pushback operation of the nasal mucosa as well as the oral mucosa. Two flaps from the buccal mucosal areas were inserted into the nasal mucosal raw surface at the hard and soft palatal border to achieve nasal mucosal pushback. Forty-four children with cleft palates were retrospectively studied to investigate the velopharyngeal function, articulation, and craniofacial morphology following primary palatoplasty using the modified Kaplan method. 72.7% showed good velopharyngeal function. Articulation disorders were found in 26 of the 44 subjects (59.1%). A craniofacial morphological analysis revealed no major changes in the SNA (sella-nasion point A angle) and SNB (sella-nasion point B angle) and no cases of a marked loss of maxillary mandibular balance. In addition, no significant differences were observed in the maxillary length and width. The results of these palatoplasties by the modified Kaplan method indicated that the use of bilateral buccal mucosal flaps for the pushback of the nasal mucosa was effective in preventing the contraction of the maxillary and mandibular corpal lengths.


The AAA-type ATPases Pex1p and Pex6p and their role in peroxisomal matrix protein import in Saccharomyces cerevisiae.
The recognition of the conserved ATP-binding domains of Pex1p, p97 and NSF led to the discovery of the family of AAA-type ATPases. The biogenesis of peroxisomes critically depends on the function of two AAA-type ATPases, namely Pex1p and Pex6p, which provide the energy for import of peroxisomal matrix proteins. Peroxisomal matrix proteins are synthesized on free ribosomes in the cytosol and guided to the peroxisomal membrane by specific soluble receptors. At the membrane, the cargo-loaded receptors bind to a docking complex and the receptor-docking complex assembly is thought to form a dynamic pore which enables the transition of the cargo into the organellar lumen. The import cycle is completed by ubiquitination- and ATP-dependent dislocation of the receptor from the membrane to the cytosol, which is performed by the AAA-peroxins. Receptor ubiquitination and dislocation are the only energy-dependent steps in peroxisomal protein import. The export-driven import model suggests that the AAA-peroxins might function as motor proteins in peroxisomal import by coupling ATP-dependent removal of the peroxisomal import receptor and cargo translocation into the organelle.


Use of a biomarker in exposure-response analysis to support dose selection for fingolimod.
Fingolimod 0.5 mg q.d. (once daily) has been approved for the treatment of patients with relapsing and remitting forms of multiple sclerosis (RRMS). Fingolimod at two doses (0.5 and 1.25 mg) showed superior effectiveness in the frequency of relapse with little difference between the two dose groups. At the same time, fingolimod manifests a number of dose-dependent adverse events. Given the safety concerns and similar effect size at both dose groups, it was reasonable to raise the question whether doses even lower than 0.5 mg would produce sufficient effectiveness. Therefore, our analysis focused on estimating the effect size of the primary endpoint at doses lower than 0.5 mg via exposure-response analysis. Specifically, we aim to show how biomarker data can be used as a bridge in exposure-response analysis to estimate the clinical endpoint response at certain doses when the direct relationship between exposure and the clinical endpoint can not be quantified reliably.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e67; doi:10.1038/psp.2013.44; published online 21 August 2013.


Introduction of unsaturation into the N-n-alkyl chain of the nicotinic receptor antagonists, NONI and NDNI: effect on affinity and selectivity.
N-n-octylnicotinium iodide (NONI) and N-n-decylnicotinium iodide (NDNI) are selective nicotinic receptor (nAChR) antagonists mediating nicotine-evoked striatal dopamine (DA) release, and inhibiting [3H]nicotine binding, respectively. This study evaluated effects of introducing unsaturation into the N-n-alkyl chains of NONI and NDNI on inhibition of [3H]nicotine and [3H]methyllycaconitine binding (alpha4beta2* and alpha7* nAChRs, respectively), (86)Rb+ efflux and [3H]DA release (agonist or antagonist effects at alpha4beta2* and alpha6beta2*-containing nAChRs, respectively). In the NONI series, introduction of a C3-cis- (NONB3c), C3-trans- (NONB3t), C7-double-bond (NONB7e), or C3-triple-bond (NONB3y) afforded a 4-fold to 250-fold increased affinity for [3H]nicotine binding sites compared with NONI. NONB7e and NONB3y inhibited nicotine-evoked 86Rb+ efflux, indicating alpha4beta2* antagonism. NONI analogs exhibited a 3-fold to 8-fold greater potency inhibiting nicotine-evoked [3H]DA overflow compared with NONI (IC50 = 0.62 microM; Imax = 89%), with no change in Imax, except for NONB3y (Imax = 50%). In the NDNI series, introduction of a C4-cis- (NDNB4c), C4-trans-double-bond (NDNB4t), or C3-triple-bond (NDNB3y) afforded a 4-fold to 80-fold decreased affinity for [3H]nicotine binding sites compared with NDNI, whereas introduction of a C9 double-bond (NDNB9e) did not alter affinity. NDNB3y and NDNB4t inhibited nicotine-evoked 86Rb+ efflux, indicating antagonism at alpha4beta2* nAChRs. Although NDNI had no effect, NDNB4t and NDNB9e potently inhibited nicotine-evoked [3H]DA overflow (IC50 = 0.02-0.14 microM, Imax = 90%), as did NDNB4c (IC50 = 0.08 microM; Imax = 50%), whereas NDNB3y showed no inhibition. None of the analogs had significant affinity for alpha7* nAChRs. Thus, unsaturated NONI analogs had enhanced affinity at alpha4beta2*- and alpha6beta2*-containing nAChRs, however a general reduction of affinity at alpha4beta2* and an uncovering of antagonist effects at alpha6beta2*-containing nAChRs were observed with unsaturated NDNI analogs.


Femoral-tibial bypass for calcific arterial disease.
Overt calcification of the recipient artery and outflow bed has been regarded as a poor prognostic factor for femoral-distal arterial bypass patency and subsequent wound healing. In order to determine the short- and long-term limb salvage and graft patency rates achieved in these patients, the records of 35 patients undergoing 38 attempted femoral-tibial bypasses to a calcified recipient artery were reviewed. Two patients were unreconstructable at the time of surgery. Thirty-one of the 36 operations (86 percent) were performed using in situ saphenous vein bypass techniques, 3 were performed with polytetrafluoroethylene (PTFE), 1 with a composite sequential, and 1 with a composite vein graft. Immediate limb salvage was achieved in 31 of 36 limbs (86 percent). Five early below-knee amputations (14 percent) were required, two due to graft thromboses and three due to progressive foot necrosis despite patent grafts. One patient (3 percent) died secondary to sepsis. Three-year primary graft patency and limb salvage rates did not differ significantly from bypasses to noncalcified vessels. Femoral-distal bypass in the presence of overt calcific arterial disease may be successfully accomplished and offers an excellent prognosis for long-term graft patency and limb salvage.


Negative impact of non-evidence-based information received by women taking antidepressants during pregnancy from health care providers and others.
The use of antidepressants by women during pregnancy continues to be a controversial subject, with conflicting information regarding the safety of this group of drugs. We sought (1) to determine the impact of information, advice, and comments women received from health care providers, family, and media about use of antidepressants during pregnancy, and (2) to compare experiences regarding the psychosocial impact of women who continued and discontinued antidepressant therapy during pregnancy. Women who had taken an antidepressant at some point during pregnancy were interviewed. The responses of women who continued antidepressant therapy throughout pregnancy were compared with those of women who discontinued therapy at some point in the pregnancy. A questionnaire with questions pertaining to information women had received from various individuals regarding the use of an antidepressant while pregnant was administered to both groups. Ninety-four interviews were completed; 78 were with women who continued antidepressant therapy throughout pregnancy, and 16 were with women who discontinued therapy. The small number of women in the discontinuation group was a result of many women declining to participate. More than one half of the women who continued the medication throughout pregnancy had frequently considered discontinuing, despite reassurance that continuation would cause no harm to their baby. Negative information was recalled far more often than reassuring information. Information from friends, family, and health care providers can have a negative impact on decision-making regarding pharmacotherapy for depression during pregnancy. Health care providers should be cognizant of this when counselling patients who require antidepressant therapy during pregnancy.


Biallelic loss of function NEK3 mutations deacetylate α-tubulin and downregulate NUP205 that predispose individuals to cilia-related abnormal cardiac left-right patterning.
Defective left-right (LR) organization involving abnormalities in cilia ultrastructure causes laterality disorders including situs inversus (SI) and heterotaxy (Htx) with the prevalence approximately 1/10,000 births. In this study, we describe two unrelated family trios with abnormal cardiac LR patterning. Through whole-exome sequencing (WES), we identified compound heterozygous mutations (c.805-1G >C; p. Ile269GlnfsTer8/c.1117dupA; p.Thr373AsnfsTer19) (c.29T>C; p.Ile10Thr/c.356A>G; p.His119Arg) of NEK3, encoding a NIMA (never in mitosis A)-related kinase, in two affected individuals, respectively. Protein levels of NEK3 were abrogated in Patient-1 with biallelic loss-of function (LoF) NEK3 mutations that causes premature stop codon. Subsequence transcriptome analysis revealed that NNMT (nicotinamide N-methyltransferase) and SIRT2 (sirtuin2) was upregulated by NEK3 knockdown in human retinal pigment epithelial (RPE) cells in vitro, which associates α-tubulin deacetylation by western blot and immunofluorescence. Transmission electron microscopy (TEM) analysis further identified defective ciliary ultrastructure in Patient-1. Furthermore, inner ring components of nuclear pore complex (NPC) including nucleoporin (NUP)205, NUP188, and NUP155 were significantly downregulated in NEK3-silenced cells. In conclusion, we identified biallelic mutations of NEK3 predispose individual to abnormal cardiac left-right patterning via SIRT2-mediated α-tubulin deacetylation and downregulation of inner ring nucleoporins. Our study suggested that NEK3 could be a candidate gene for human ciliopathies.


3-substituted 2-phenylimidazo[2,1-b]benzothiazoles: synthesis, anticancer activity, and inhibition of tubulin polymerization.
A new series of 3-substituted 2-phenylimidazo[2,1-b]benzothiazoles (3 a-h) were synthesized by C-arylation of 2-arylimidazo[2,1-b]benzothiazoles using palladium acetate as catalyst, and the resulting compounds were evaluated for their anticancer activity. Compounds 3 a, 3 e, and 3 h exhibited good antiproliferative activity, with GI50 values in the range of 0.19-83.1 μM. Compound 3 h showed potent anticancer efficacy against 60 human cancer cell lines, with a mean GI50 value of 0.88 μM. This compound also induced cell-cycle arrest in the G2/M phase and inhibited tubulin polymerization followed by activation of caspase-3 and apoptosis. A high-throughput tubulin polymerization assay showed that the level of inhibition for compound 3 h is similar to that of combretastatin A-4. Molecular modeling studies provided a molecular basis for the favorable binding of compounds 3 a, 3 e, and 3 h to the colchicine binding pocket of tubulin.


Nanotechnology-based biomaterials for orthopaedic applications: Recent advances and future prospects.
Bioimplant engineering aims to mature biological alternatives to restore, retain, or modify damaged tissues and/or the functionality of organs. Remarkable advancements in modern material technology have helped the diversity of materials for orthopaedic implant application. As such, nanomaterials can simulate the surface properties of natural tissues, especially with respect to surface topography, surface chemistry, surface energy, and surface wettability. The novel properties of nanomaterials also encourage their use for improving the growth of different tissues. The present review lays the foundation for nanotechnology-driven biomaterials through revelation of fundamental design considerations to determine the performance of an orthopaedic implant in terms of success or failure, their antimicrobial/antibacterial activities, and response to cell adhesion, proliferation, and differentiation. In this context, the nano-functionalization of biomaterial surface has been widely investigated to improve cell adhesion, proliferation, differentiation, and migration for implants with high antimicrobial activity. The potential use of nanomaterials (in terms of nanostructured surface or functional nanocoating over implant surface) can resolve several issues (e.g., corrosion resistance and bacterial adhesion) pertaining to conventional metallic or non-metallic implants, especially for optimization of implant techniques. The future trends of orthopaedic biomaterials (e.g., porous structures, smart biomaterials, and 3D implants) are promising to achieve the desired properties and structure of an implant with stimuli-responsive behaviour. The major challenges in commercialization of nanotechnology-derived biomaterials are finally addressed to help overcome the limitations of pre-existing orthopaedic biomaterials in terms of key variables, e.g., quality, treatment cost, implant life, and pain relief.


The effects of a daycare reform on health in childhood - Evidence from Sweden.
This paper studies the impact of a daycare reform on children's mental and physical health development in Sweden. The reform effectively reduced daycare fees by a significant amount and went along with an expansion of supply. We draw on a unique set of comprehensive individual-level healthcare register data over the period 1999-2008. By exploiting variation in reform exposure by birth cohort, we estimate short and medium-run effects on child health at different ages. We find a significant reduction in mental disorders in the medium-run for children affected by the reform. The reform leads to strong and immediate increases in probabilities of diagnosis with physical health conditions that fade out as children get older. Sub-sample analyses indicate that the reform effects are strongly associated with children from disadvantaged backgrounds. An analysis of healthcare utilization shows that affected children have more overall medical visits at younger ages but fewer sickness-related visits in primary school than non-affected children.


Interfacial Lattice-Strain-Driven Generation of Oxygen Vacancies in an Aerobic-Annealed TiO2 (B) Electrode.
Oxygen vacancies play crucial roles in defining physical and chemical properties of materials to enhance the performances in electronics, solar cells, catalysis, sensors, and energy conversion and storage. Conventional approaches to incorporate oxygen defects mainly rely on reducing the oxygen partial pressure for the removal of product to change the equilibrium position. However, directly affecting reactants to shift the reaction toward generating oxygen vacancies is lacking and to fill this blank in synthetic methodology is very challenging. Here, a strategy is demonstrated to create oxygen vacancies through making the reaction energetically more favorable via applying interfacial strain on reactants by coating, using TiO2 (B) as a model system. Geometrical phase analysis and density functional theory simulations verify that the formation energy of oxygen vacancies is largely decreased under external strain. Benefiting from these, the obtained oxygen-deficient TiO2 (B) exhibits impressively high level of capacitive charge storage, e.g., ≈53% at 0.5 mV s-1 , far surpassing the ≈31% of the unmodified counterpart. Meanwhile, the modified electrode shows significantly enhanced rate capability delivering a capacity of 112 mAh g-1 at 20 C (≈6.7 A g-1 ), ≈30% higher than air-annealed TiO2 and comparable to vacuum-calcined TiO2 . This work heralds a new paradigm of mechanical manipulation of materials through interfacial control for rational defect engineering.


Malnutrition in Relation to Muscle Mass, Muscle Quality, and Muscle Strength in Hospitalized Older Adults.
Muscle quality is an essential muscle metric, which can be assessed by measuring intermuscular adipose tissue (IMAT) and skeletal muscle radiodensity (SMD) via computed tomography (CT) images. We aimed to explore the associations of Global Leadership Initiative on Malnutrition (GLIM)-defined malnutrition with muscle mass, muscle quality, and muscle strength in hospitalized older adults. A cross-sectional study. Hospitalized older patients. Malnutrition was defined by the GLIM criteria after screening by the Mini Nutrition Assessment-Short Form (MNA-SF). Chest CT images were used to segment skeletal muscle area (SMA) and IMAT, and to measure SMD. Skeletal muscle index (SMI) was calculated by SMA (cm2)/body height squared (m2). Handgrip strength (HGS) was measured using a digital dynameter. Univariate and multivariate logistic regression models were performed to calculate odds ratios (ORs) and 95% CIs. We included 1135 patients. The MNA-SF score is positively associated with SMI, SMD, and HGS, but negatively associated with IMAT. Compared to patients with normal nutrition, patients with malnutrition had significantly lower SMD and HGS in both men and women. Women with malnutrition had significantly higher IMAT than women with normal nutrition, whereas men with malnutrition had significantly lower SMI than men with normal nutrition. After adjustment for confounders, SMI (adjusted OR 0.95, 95% CI 0.93, 0.98), SMD (adjusted OR 0.94, 95% CI 0.93, 0.98), and HGS (adjusted OR 0.91, 95% CI 0.89, 0.94) were significantly and negatively associated with malnutrition. IMAT appeared to be positively associated with malnutrition, but the result was not statistically significant (adjusted OR 1.03, 95% CI 1.00, 1.07). Our study provides new evidence regarding the association between handgrip strength and malnutrition in older inpatients. Moreover, a small association of chest CT--derived muscle quality and mass with malnutrition is identified.


S-100a0 protein stimulates the basal (Mg2+-activated) adenylate cyclase activity associated with skeletal muscle membranes.
S-100a0 protein, the alpha alpha isoform of the S-100 family, stimulates basal (Mg2+-activated) adenylate cyclase (AC) activity associated with the sarcolemma, longitudinal tubules and terminal cisternae of rat skeletal muscle cells. The stimulatory effect of S-100a0 on AC activity is maximal around 5 microM S-100a0 and half-maximal around 0.2 microM S-100a0. Also, the stimulatory effect is greatest on the AC activity associated with the terminal cisternae than on the other membrane fractions studied. These data are discussed in relation to the subcellular localization of S-100a0 in muscle cells.


Whitepaper: Training in Diagnostic and Interventional Breast Radiology.
Breast imaging represents an integral part of radiology and is subject to strict quality controls. Regarding this, precise diagnostics including multimodal assessment by mammography, sonography, and MRI, including image-guided biopsy and localization procedures, is often decisive and must be performed by experts with profound knowledge and skills in all of these procedures.However, due to numerous restructurings, breast imaging has been shifted more and more towards large, specialized centers, resulting in less patient exposition and training opportunities for radiologists in smaller sites. The following whitepaper summarizes the current circumstances and discusses opinions of the participating societies. Under the leadership of the German Roentgen Society (DRG) and with the participation of the DRG's AG Mammadiagnostik, the CAFRAD (Chefarztforum Radiologie), the KLR (Konferenz der Lehrstuhlinhaber für Radiologie e. V.), the DRG's Forum Junge Radiologie (FJR) and the Berufsverband der Deutschen Radiologen e. V. (BDR), possible solutions were discussed and consented for a structured training in breast radiology in the future. In addition to the teaching provided at the primary workplace, qualified training should be ensured through flexible, multi-institutional, interdisciplinary, and cross-sectoral collaboration. Furthermore, the integration of online case collections and close cooperation with certified breast cancer centers and mammography screening units is recommended. It is indispensible that online courses and case collections adhere to the standards of the national societies and include a maximum of one third of the required cases. In order to provide training in breast radiology at a high professional level, a paradigm shift with closer cooperation of all participants is necessary. This includes close collaboration of the breast imaging societies with the federal medical associations to establish new teaching concepts like e-learning in the training schedule of radiologists. · Breast diagnostics is an integral part of radiology training.. · Due to recent restructurings, smaller training centers have difficulties in meeting the case numbers demanded by the Specialist Training Regulations (WBO). Improved integration of the new structures and their adaptation to the needs of education are necessary to guarantee standardized high-quality training of young radiologists.. · The integration of certified case collections enables quality-assured training, even across regions in online-based formats. In accordance with the "blended learning principle", up to one-third of the required number of patient studies can be substituted with cases from a certified case collection.. · Legally secured short- and medium-term internships may complement training in radiology.. · Sauer ST, Bley TA, Wenkel E et al. Whitepaper: Training in Diagnostic and Interventional Breast Radiology. Fortschr Röntgenstr 2023; 195: 699 - 706.


Clinical, neurophysiological and pathological findings of HNPP patients with 17p12 deletion: a single-centre experience.
Classic clinical manifestations of HNPP are characterized by recurrent painless mononeuropathies, but a minority of patients present with an atypical clinical pattern, including CMT-like neuropathy, acute or chronic inflammatory demyelinating neuropathy-like polyneuropathy, and carpal tunnel syndrome. Electrophysiological examination plays a central role in the diagnosis of HNPP, disclosing a non-uniform conduction slowing, more pronounced at entrapment sites. We report clinical, electrophysiological and pathological findings from 73 patients with HNPP, coming from 53 unrelated families, followed at our Institute of Neurology over a 20-year period. Typical presentation with recurrent multiple mononeuropathies was observed in 28/64 (44%) patients. In the remaining 36/64 (56%), we observed an atypical clinical presentation, characterized by generalized weakness and cramps, chronic ulnar neuropathy, carpal tunnel syndrome, chronic sensory polyneuropathy, Guillain-Barrè-like presentation, and CMT-like presentation. Nine patients were asymptomatic for neuropathic symptoms. Nerve conduction studies showed in all cases a sensori-motor demyelinating polyneuropathy with conduction abnormalities preferentially localized at common entrapment sites. When performed, sural nerve biopsy disclosed the focal thickening of the myelin sheath in all patients. About half of the patients with HNPP from our cohort showed an atypical clinical presentation. Neurophysiological examination represents the main tool for a proper diagnosis.


Rhinosinusitis in morbidity registrations in Dutch General Practice: a retro-spective case-control study.
There is only limited accurate data on the epidemiology of rhinosinusitis in primary care. This study was conducted to assess the incidence of acute and chronic rhinosinusitis by analysing data from two Dutch general practice registration projects. Several patient characteristics and diseases are related to the diagnosis rhinosinusitis. The Continuous Morbidity Registration (CMR) and the Transitionproject (TP) are used to analyse the data on rhinosinusitis in primary practice. Both registries use codes to register diagnoses. In the CMR 3244 patients are registered with rhinosinusitis and in the TP 5424 CMR: The absolute incidence of (acute) rhinosinusitis is 5191 (18.8 per 1000 patient years). Regarding an odds ratio of 5.58, having nasal polyps is strongest related to rhinosinusitis compared to the other evaluated comorbidities. A separate code for chronic rhinosinusitis exists, but is not in use. TP: Acute and chronic rhinosinusitis are coded as one diagnosis. The incidence of rhinosinusitis is 5574 or 28.7 per 1000 patient years. Patients who visit their general practitioner with "symptoms/complaints of sinus", allergic rhinitis and "other diseases of the respiratory system" have the highest chances to be diagnosed with rhinosinusitis. Medication is prescribed in 90.6 % of the cases. Rhinosinusitis is a common diagnosis in primary practice. In the used registries no difference could be made between acute and chronic rhinosinusitis, but they give insight in comorbidity and interventions taken by the GP in case of rhinosinusitis.