Poroid adnexal skin tumors with YAP1 fusions exhibit similar histopathologic features: A series of six YAP1-rearranged adnexal skin tumors.
Adnexal skin tumors are diagnostically challenging with few known molecular signatures. Recently, however, YAP1-MAML2 and YAP1-NUTM1 fusions were identified in poroid adnexal skin tumors. Herein, we subjected eight poroid adnexal skin tumors (three poromas and five porocarcinomas) to fusion gene analysis by whole transcriptome sequencing and next-generation DNA sequencing analysis. YAP1 fusions were identified in six cases. YAP1-NUTM1 fusions were identified in two poromas and three porocarcinomas. A single case of porocarcinoma harbored a YAP1-MAML2 fusion. Two cases were negative for gene fusion. All cases that harbored YAP1-NUTM1 fusions showed nuclear protein in testis (NUT) expression by immunohistochemistry, with NUT being negative in the YAP1-MAML2-positive case. In this case series, we provide a detailed histopathologic description of six YAP1-fused poroid skin tumors, which we show harbor reproducible histopathologic features, to include broad, bulbous tumor tongues with admixtures of basaloid, poroid cells punctuated by squamatized cuticles and ductules, with uniform tumor nuclei featuring frequent grooves and pseudonuclear inclusions. Awareness of the characteristic histopathologic features of YAP1-fused poroid adnexal skin tumor is a step toward a more reproducible classification of adnexal skin tumors as well as a step toward targeted therapy for metastatic and/or unresectable examples of this poroid group of neoplasms.


[Iron deficiency anemia and its importance in gastroenterology clinical practise].
Iron deficiency anemia (IDA) is a universal problem involving individuals of all ages and both sexes and is a common cause of referral to medical departments. This anemia is one of the most common types of anemia. IDA impairs growth and intellectual development in children and adolescent. In women IDA is most common in reproductive period because of menstrual and pregnancy iron losses. IDA affects roughly 10-30% of all pregnancies and, among others morbidities, may contribute of developing postpartum depression. Among other adult patient, chronic occult gastrointestinal bleeding is the leading cause of IDA. Approximately, one third of patients with anemia have iron deficiency and up to two thirds of patients with IDA have serious gastrointestinal lesions detected with esophagogastroduodenoscopy and colonoscopy, including 10-15% with malignancy. However, in practice not all anemic patients undergo appropriate diagnostic tests to detect iron deficiency. Furthermore, a substantial proportion of patients with IDA do not undergo endoscopic evaluation. The approach to its investigation and subsequent therapy depends upon a comprehensive understanding of iron metabolism and heme synthesis. Once diagnosis of iron deficiency or IDA is established, evaluation for the cause of anemia must be appropriate performed and treatment must include corrective replenishment of body stores.


[Secretin stimulated magnetic resonance cholangiopancreatography in diseases of the biliary and pancreatic ducts].
MRCP has replaced ERCP as the diagnostic tool in diseases in the biliary and pancreatic ducts. Secretin increases the secretion to ducts, and this has been reported to improve MRCP image quality. We report our experience with S-MRCP in our first 20 patients. Secretin was given intravenously and images were obtained every minute for 10 minutes. These images were compared with MRCP images taken before and after secretin stimulation. New information was yielded in 18 cases, i.e. information not observed in previous radiological examinations. In diagnostics of dysfunction of the sphincter of Oddi, the method may be useful, given the functional aspect of the procedure where increased pressure in the ducts may lead to pain. It may further improve the diagnostics of pancreatic cancer versus pancreatitis, in pancreas divisum and sclerosing cholangitis. The method is also valuable for clarifying whether there is injury to the pancreatic duct after blunt abdominal trauma. Surgical common bile duct injuries may be better assessed than with any other method. In difficult pancreatic and biliary investigations, S-MRCP seems to be a useful and complication-free supplement to existing diagnostic methods.


Abcd2 is a strong modifier of the metabolic impairments in peritoneal macrophages of ABCD1-deficient mice.
The inherited peroxisomal disorder X-linked adrenoleukodystrophy (X-ALD), associated with neurodegeneration and inflammatory cerebral demyelination, is caused by mutations in the ABCD1 gene encoding the peroxisomal ATP-binding cassette (ABC) transporter ABCD1 (ALDP). ABCD1 transports CoA-esters of very long-chain fatty acids (VLCFA) into peroxisomes for degradation by β-oxidation; thus, ABCD1 deficiency results in VLCFA accumulation. The closest homologue, ABCD2 (ALDRP), when overexpressed, compensates for ABCD1 deficiency in X-ALD fibroblasts and in Abcd1-deficient mice. Microglia/macrophages have emerged as important players in the progression of neuroinflammation. Human monocytes, lacking significant expression of ABCD2, display severely impaired VLCFA metabolism in X-ALD. Here, we used thioglycollate-elicited primary mouse peritoneal macrophages (MPMΦ) from Abcd1 and Abcd2 single- and double-deficient mice to establish how these mutations affect VLCFA metabolism. By quantitative RT-PCR, Abcd2 mRNA was about half as abundant as Abcd1 mRNA in wild-type and similarly abundant in Abcd1-deficient MPMΦ. VLCFA (C26∶0) accumulated about twofold in Abcd1-deficient MPMΦ compared with wild-type controls, as measured by gas chromatography-mass spectrometry. In Abcd2-deficient macrophages VLCFA levels were normal. However, upon Abcd1/Abcd2 double-deficiency, VLCFA accumulation was markedly increased (sixfold) compared with Abcd1-deficient MPMΦ. Elovl1 mRNA, encoding the rate-limiting enzyme for elongation of VLCFA, was equally abundant across all genotypes. Peroxisomal β-oxidation of C26∶0 amounted to 62% of wild-type activity in Abcd1-deficient MPMΦ and was significantly more impaired (29% residual activity) upon Abcd1/Abcd2 double-deficiency. Single Abcd2 deficiency did not significantly compromise β-oxidation of C26∶0. Thus, the striking accumulation of VLCFA in double-deficient MPMΦ compared with single Abcd1 deficiency was due to the loss of ABCD2-mediated, compensatory transport of VLCFA into peroxisomes. We propose that moderate endogenous expression of Abcd2 in Abcd1-deficient murine macrophages prevents the severe metabolic phenotype observed in human X-ALD monocytes, which lack appreciable expression of ABCD2. This supports upregulation of ABCD2 as a therapeutic concept in X-ALD.


Tactile Sensing for Minimally Invasive Surgery: Conventional Methods and Potential Emerging Tactile Technologies.
As opposed to open surgery procedures, minimally invasive surgery (MIS) utilizes small skin incisions to insert a camera and surgical instruments. MIS has numerous advantages such as reduced postoperative pain, shorter hospital stay, faster recovery time, and reduced learning curve for surgical trainees. MIS comprises surgical approaches, including laparoscopic surgery, endoscopic surgery, and robotic-assisted surgery. Despite the advantages that MIS provides to patients and surgeons, it remains limited by the lost sense of touch due to the indirect contact with tissues under operation, especially in robotic-assisted surgery. Surgeons, without haptic feedback, could unintentionally apply excessive forces that may cause tissue damage. Therefore, incorporating tactile sensation into MIS tools has become an interesting research topic. Designing, fabricating, and integrating force sensors onto different locations on the surgical tools are currently under development by several companies and research groups. In this context, electrical force sensing modality, including piezoelectric, resistive, and capacitive sensors, is the most conventionally considered approach to measure the grasping force, manipulation force, torque, and tissue compliance. For instance, piezoelectric sensors exhibit high sensitivity and accuracy, but the drawbacks of thermal sensitivity and the inability to detect static loads constrain their adoption in MIS tools. Optical-based tactile sensing is another conventional approach that facilitates electrically passive force sensing compatible with magnetic resonance imaging. Estimations of applied loadings are calculated from the induced changes in the intensity, wavelength, or phase of light transmitted through optical fibers. Nonetheless, new emerging technologies are also evoking a high potential of contributions to the field of smart surgical tools. The recent development of flexible, highly sensitive tactile microfluidic-based sensors has become an emerging field in tactile sensing, which contributed to wearable electronics and smart-skin applications. Another emerging technology is imaging-based tactile sensing that achieved superior multi-axial force measurements by implementing image sensors with high pixel densities and frame rates to track visual changes on a sensing surface. This article aims to review the literature on MIS tactile sensing technologies in terms of working principles, design requirements, and specifications. Moreover, this work highlights and discusses the promising potential of a few emerging technologies towards establishing low-cost, high-performance MIS force sensing.


Modification of small bowel mechanosensitivity by intestinal fat.
Lipids may exacerbate symptoms induced by gut stimuli. To determine the mechanism whereby fat exerts this effect. Twenty four healthy subjects were studied during fasting. We measured perception (0-6 scale) in response to jejunal balloon distension and transmucosal electrical nerve stimulation; phasic stimuli (one minute) were randomly applied at five minute intervals during intestinal infusion (2 ml/min) of saline and then Intralipid 2 kcal/min (high fat; n=8 subjects), Intralipid 0.5 kcal/min (low fat; n=8), or saline (n=8). Intestinal lipids increased the perception of jejunal distension regardless of concentration (by 53% with high fat, 49% with low fat, and 17% with saline; p<0.05 for both fat loads). This effect could not be attributed to changes in intestinal compliance as intraballoon pressures remained unchanged during lipid infusion (2% change; NS). Sensitisation induced by lipids seemed to be specifically related to intestinal mechanoreceptors because electrical stimulation, which non-specifically activates gut afferents, was perceived equally during saline and lipid administration (10%, 11%, and 15% change during high fat, low fat, and saline, respectively; NS). Physiological amounts of lipids heighten intestinal sensitivity by modulating intestinal mechanoreceptor response.


[Determination of total and inorganic phosphorus in the presence of organic phosphoric acid esters and proteins].
Total phosphorus was estimated after mineralization of a sample, containing organic phosphoesters and proteins; a method is based on the formation of phosphomolybdenovanadium complex at acid pH. The analyses for inorganic phosphorus were carried our together with estimation if some labile phosphoesters (glucose-I-phosphate, ADP, ATP), which was possible due to low acidity of the medium (0.24 N HC1O4), small concentrations of reagents (3.2 mg/ml of molybdate, 0.08 mg/ml vanadate), addition of sodium citrate to neutralize the excess of molybdenovanadium acid and extraction of the colored complex with butyl or isobutyl alcohol. Optical density was measured at two wave lengths (340 nm and 390 nm) which enabled to estimate from 0.5 to 80 microng of phosphrorus in a sample.


Mitral valve surgery with surgical embolectomy for mitral valve endocarditis complicated by septic coronary embolism.
Acute myocardial infarction (AMI) complicated by septic coronary embolism due to active infective endocarditis is rare but usually fatal. We report a case of successful mitral valve surgery with surgical embolectomy in a 27-year-old man with an AMI complicated by septic coronary embolism due to mitral valve endocarditis. A chest radiograph revealed cardiomegaly and marked pulmonary edema. A transthoracic echocardiogram disclosed severe mitral regurgitation with highly mobile vegetations and hypokinesia of the left ventricular apex. The electrocardiographic findings of ST segment elevation in leads V2-4 and elevated cardiac enzyme levels were strongly suggestive of an acute anterolateral AMI. Nevertheless, emergent cardiac surgery was needed without selective coronary angiography because of intractable heart failure and life-threatening ventricular tachyarrhythmia requiring cardiopulmonary resuscitation. A total occlusion of the distal left anterior descending artery caused by embolic vegetation and thrombus, which was incidentally detected intraoperatively, was successfully recanalized by surgical embolectomy and thrombectomy using a direct coronary incision. The mitral valve endocarditis was managed with wide debridement and mechanical valve replacement. Three years after the surgery a follow-up echocardiogram showed no abnormalities of the regional wall, motion in the left ventricle and the patient is living an active life without any complications.


Quantification of Renal Sympathetic Vasomotion as a Novel End Point for Renal Denervation.
Renal sympathetic denervation, a potentially revolutionary interventional treatment for hypertension, faces an existential problem due to the inability to confirm successful ablation of the targeted renal sympathetic nerves. Based on the observation that renal sympathetic nerve activity exerts rhythmic, baroreflex-driven, and vasoconstrictive control of the renal vasculature, we developed a novel technique for identifying rhythmic sympathetic vascular control using a time-varying, 2-component Windkessel model of the renal circulation. This technology was tested in 2 different animal models of renal denervation; 10 rabbits underwent chronic, surgical renal denervation, and 9 pigs underwent acute, functional renal denervation via intrathecal administration of ropivacaine. Both methods of renal denervation reduced negative admittance gain, negative phase shift renal vascular control at known sympathetic vasomotor frequencies, consistent with a reduction in vasoconstrictive, baroreflex-driven renal sympathetic vasomotion. Classic measures like mean renal blood flow and mean renal vascular resistance were not significantly affected in either model of renal denervation. Renal sympathetic vasomotion monitoring could provide intraprocedural feedback for interventionists performing renal denervation and serve more broadly as a platform technology for the evaluation and treatment of diseases affecting the sympathetic nervous system.


Changes in soft drinks purchased by British households associated with the UK soft drinks industry levy: a controlled interrupted time series analysis.
To determine changes in household purchases of drinks 1 year after implementation of the UK soft drinks industry levy (SDIL). Controlled interrupted time series. Households reporting their purchasing to a market research company (average weekly n=22 091), March 2014 to March 2019. A two-tiered tax levied on soft drinks manufacturers, announced in March 2016 and implemented in April 2018. Drinks with ≥8 g sugar/100 mL (high tier) are taxed at £0.24/L, drinks with ≥5 to <8 g sugar/100 mL (low tier) are taxed at £0.18/L. Absolute and relative differences in the volume of, and amount of sugar in, soft drinks categories, all soft drinks combined, alcohol and confectionery purchased per household per week 1 year after implementation. In March 2019, compared with the counterfactual, purchased volume of high tier drinks decreased by 140.8 mL (95% CI 104.3 to 177.3 mL) per household per week, equivalent to 37.8% (28.0% to 47.6%), and sugar purchased in these drinks decreased by 16.2 g (13.5 to 18.8 g), or 42.6% (35.6% to 49.6%). Purchases of low tier drinks decreased by 170.5 mL (154.5 to 186.5 mL) or 85.8% (77.8% to 93.9%), with an 11.5 g (9.1 to 13.9 g) reduction in sugar in these drinks, equivalent to 87.8% (69.2% to 106.4%). When all soft drinks were combined irrespective of levy tier or eligibility, the volume of drinks purchased increased by 188.8 mL (30.7 to 346.9 mL) per household per week, or 2.6% (0.4% to 4.7%), but sugar decreased by 8.0 g (2.4 to 13.6 g), or 2.7% (0.8% to 4.5%). Purchases of confectionery and alcoholic drinks did not increase. Compared with trends before the SDIL was announced, 1 year after implementation, volume of all soft drinks purchased combined increased by 189 mL, or 2.6% per household per week. The amount of sugar in those drinks was 8 g, or 2.7%, lower per household per week. Further studies should determine whether and how apparently small effect sizes translate into health outcomes. ISRCTN18042742.


Oxidative stress impairs IKCa- and SKCa-mediated vasodilatation in mesenteric arteries from diabetic rats.
To investigate the role of oxidative stress in impaired intermediate-conductance Ca(2+)-activated potassium channels (IKCa)- and small-conductance Ca(2+)-activated potassium channels (SKCa)-mediated relaxation in diabetic resistance arteries. Rat diabetic model was induced by a high fat and high glucose diet and streptozotocin (STZ) injection. Endothelial function of mesenteric arteries was assessed with the use of wire myography. The expression levels of IKCa and SKCa in cultured human umbilical vein endothelial cells (HUVECs) treated with H2O2 and/or antioxidant alpha lipoic acid (ALA) were measured using Western blotting. IKCa- and SKCa-mediated vasodilatation in response to acetylcholine was impaired in the third-order mesenteric arterioles of diabetic rats. In cultured HUVECs, H2O2 significantly decreased the protein expression of IKCa and SKCa. ALA alleviated the impairment of both vasodilatation function of the mesenteric arterioles ex vivo and enhanced the expression of IKCa and SKCa challenged with H2O2 in cultured HUVECs. Our data demonstrated for the first time that impaired IKCa- and SKCa-mediated vasodilatation in diabetes was induced, at least in part, by oxidative stress via down-regulation of IKCa and SKCa channels.


On the realization of an analytic high-resolution EEG.
The analytic solution of the harmonic downward continuation of the scalp potential field in an N-shell heterogeneous, but isotropic, spherical volume conductor model has been derived. The objective of this paper was to investigate the realization of a so-called "high-resolution electroencephalogram (EEG)": by enhancing the poor spatial resolution of EEG recordings. To this end, the forward problem for a dipolar source arbitrarily located at the source point Q = Q(rs, phi s, theta s) has been determined in a compact matrix notation. It is possible to transfer the potential field given on the outer surface of a spherically shaped volume conductor to an arbitrary inner surface (e.g., to the cortical surface) under consideration of the electrical and geometrical properties of the model. For the application of the proposed method to real-world problems, the coefficients of the series expansion describing the cortical potential distribution are determined by minimizing the squared curvature of the scalp potential field integrated over the scalp surface. Simulation results for distributed sources show that the proposed method is superior to the surface Laplacian method for interelectrode distances below 2.5 cm.


CD41 T cell recovery during suppression of HIV replication: an international comparison of the immunological efficacy of antiretroviral therapy in North America, Asia and Africa.
Even among HIV-infected patients who fully suppress plasma HIV RNA replication on antiretroviral therapy, genetic (e.g. CCL3L1 copy number), viral (e.g. tropism) and environmental (e.g. chronic exposure to microbial antigens) factors influence CD4 recovery. These factors differ markedly around the world and therefore the expected CD4 recovery during HIV RNA suppression may differ globally. We evaluated HIV-infected adults from North America, West Africa, East Africa, Southern Africa and Asia starting non-nucleoside reverse transcriptase inhibitorbased regimens containing efavirenz or nevirapine, who achieved at least one HIV RNA level <500/ml in the first year of therapy and observed CD4 changes during HIV RNA suppression. We used a piecewise linear regression to estimate the influence of region of residence on CD4 recovery, adjusting for socio-demographic and clinical characteristics. We observed 28 217 patients from 105 cohorts over 37 825 person-years. After adjustment, patients from East Africa showed diminished CD4 recovery as compared with other regions. Three years after antiretroviral therapy initiation, the mean CD4 count for a prototypical patient with a pre-therapy CD4 count of 150/ml was 529/ml [95% confidence interval (CI): 517–541] in North America, 494/ml (95% CI: 429–559) in West Africa, 515/ml (95% CI: 508–522) in Southern Africa, 503/ml (95% CI: 478–528) in Asia and 437/ml (95% CI: 425–449) in East Africa. CD4 recovery during HIV RNA suppression is diminished in East Africa as compared with other regions of the world, and observed differences are large enough to potentially influence clinical outcomes. Epidemiological analyses on a global scale can identify macroscopic effects unobservable at the clinical, national or individual regional level.


Magnetic control of the pair creation in spatially localized supercritical fields.
We examine the impact of a perpendicular magnetic field on the creation mechanism of electron-positron pairs in a supercritical static electric field, where both fields are localized along the direction of the electric field. In the case where the spatial extent of the magnetic field exceeds that of the electric field, quantum field theoretical simulations based on the Dirac equation predict a suppression of pair creation even if the electric field is supercritical. Furthermore, an arbitrarily small magnetic field outside the interaction zone can bring the creation process even to a complete halt, if it is sufficiently extended. The mechanism for this magnetically induced complete shutoff can be associated with a reopening of the mass gap and the emergence of electrically dressed Landau levels.


[Hematophagous activity of Anopheles vestitipennis Dyar & Knab, 1906 (Diptera: Culicidae)].
The hematophagic activity of Anopheles vestitipennis Dyar and Knab, 1906, was studied in a rural locality during the dry and rain seasons, through inside and outside home collects with human bait at a schedule form 19:00 to 07:00 hours. The species showed preference by inside home food (endophagic) in both seasons. There was 2 maximum activity peaks inside of the buildings, from 23:00 to 24:00 hours and from 02:00 to 03:00 hours (the first one agrees with the peak occurring outside). During the dry season the activity peak outside occurred from 24:00 to 01:00 hours; while inside occurred from 02:00 to 03:00 hours.


Identification of ricin in crude and purified extracts from castor beans using on-target tryptic digestion and MALDI mass spectrometry.
Ricin is a toxic protein produced in the seeds of the castor bean plant. The toxicity of the protein and the ease in which it can be extracted from the seeds makes it a potential biological warfare agent. There has been extensive work in the development of analytical techniques that can identify the protein robustly and rapidly. On-target tryptic digestion and MALDI MS was used to distinguish ricin from bovine serum albumin and three other type 2 ribsome-inactivating proteins (RIPs), abrin, agglutinin (RCA(120)), and viscumin, using the peptide mass fingerprint. The sequence coverage obtained was enhanced using methanol-assisted tryptic digestion and was particularly useful for the detection of these toxins in complex matrixes. When used in conjunction with intact protein MALDI mass measurement, a positive identification of ricin (or any of the other RIPs) was achieved including confirmation of the integrity of the disulfide bond between the A and B chains. This applicability of this methodology was demonstrated by the identification of ricin in a typical "crude white powder" that may be illicitly produced in a clandestine lab. The analysis on the solubilized sample using this method can be undertaken in around an hour with minimal sample preparation.


Smoking-Cessation Assistance: Before and After Stage 1 Meaningful Use Implementation.
Brief smoking-cessation interventions in primary care settings are effective, but delivery of these services remains low. The Centers for Medicare and Medicaid Services' Meaningful Use (MU) of Electronic Health Record (EHR) Incentive Program could increase rates of smoking assessment and cessation assistance among vulnerable populations. This study examined whether smoking status assessment, cessation assistance, and odds of being a current smoker changed after Stage 1 MU implementation. EHR data were extracted from 26 community health centers with an EHR in place by June 15, 2009. AORs were computed for each binary outcome (smoking status assessment, counseling given, smoking-cessation medications ordered/discussed, current smoking status), comparing 2010 (pre-MU), 2012 (MU preparation), and 2014 (MU fully implemented) for pregnant and non-pregnant patients. Non-pregnant patients had decreased odds of current smoking over time; odds for all other outcomes increased except for medication orders from 2010 to 2012. Among pregnant patients, odds of assessment and counseling increased across all years. Odds of discussing or ordering of cessation medications increased from 2010 compared with the other 2 study years; however, medication orders alone did not change over time, and current smoking only decreased from 2010 to 2012. Compared with non-pregnant patients, a lower percentage of pregnant patients were provided counseling. Findings suggest that incentives for MU of EHRs increase the odds of smoking assessment and cessation assistance, which could lead to decreased smoking rates among vulnerable populations. Continued efforts for provision of cessation assistance among pregnant patients is warranted.


The use of MRI scanning to triage patients.
The rise in the incidence of prostate cancer is mainly attributed to the increasing use of the serum prostate-specific antigen (PSA) blood test as a screening tool. Regardless of doubts over its sensitivity and specificity, PSA remain a key mechanism in the diagnosis and management of prostate cancer. The Department of Health (DH) in the UK recommends urgent specialist referral for patients presenting with age-elevated PSA. This national guideline, known as the National Cancer Wait Times (NCWT) system, aims at monitoring the process of referral, investigation and management of new suspicious prostate cancer cases. The use of transrectal ultrasound (TRUS) guided prostate biopsy is the gold-standard specialist investigation for prostate cancer. However, there is growing interest in the use of imaging techniques like magnetic resonance imaging (MRI) as first-line specialist investigation for suspicious prostate cancer.


Maternal and infant characteristics in abuse: a case control study.
Eighty-six abused children identified by two Children's Aid Societies in Hamilton-Wentworth County, Ontario, were compared with 86 controls born in the same hospital. Three factors were significantly more common in the abused group: (1) low socioeconomic status of the mother, (2) younger age at time of delivery, and (3) indication of a psychosocial problem recorded in the medical chart. The failure to find significant differences between abused children and controls in birthweight, Apgar score, and prematurity contrasts with earlier investigations of infant characteristics and child abuse.


Down-regulation of GPR137 expression inhibits proliferation of colon cancer cells.
G protein-coupled receptors (GPRs) are highly related to oncogenesis and cancer metastasis. G protein-coupled receptor 137 (GPR137) was initially reported as a novel orphan GPR about 10 years ago. Some orphan GPRs have been implicated in human cancers. The aim of this study is to investigate the role of GPR137 in human colon cancer. Expression levels of GRP137 were analyzed in different colon cancer cell lines by quantitative polymerase chain reaction and western blot analysis. Lentivirus-mediated short hairpin RNA was specifically designed to knock down GPR137 expression in colon cancer cells. Cell viability was measured by methylthiazoletetrazolium and colony formation assays. In addition, cell cycle characteristic was investigated by flow cytometry. GRP137 expression was observed in all seven colon cancer cell lines at different levels. The mRNA and protein levels of GPR137 were down-regulated in both HCT116 and RKO cells after lentivirus infection. Lentivirus-mediated silencing of GPR137 reduced the proliferation rate and colonies numbers. Knockdown of GPR137 in both cell lines led to cell cycle arrest in the G0/G1 phase. These results indicated that GPR137 plays an important role in colon cancer cell proliferation. A better understanding of GPR137's effects on signal transduction pathways in colon cancer cells may provide insights into the novel gene therapy of colon cancer.


[Disorders of energy metabolism in the rat brain under extreme exposures: a new method for assessing the energy state of the brain].
We propose a new method to evaluate energy state of the brain based on vital assay for phosphate metabolites and intracellular pH in the brain. A proposed Z-index describes a set of correlations between phosphates involved in brain energy metabolism assayed in vivo by magnetic resonance spectroscopy on 31P nuclei. We tried to use Z-index as a quantitative test for disturbed energy metabolism. Potentialities of Z-index for evaluating rat brain energy state after extreme influences (gamma [correction of X-] irradiation and postoperative shock of the brain cortex) have been demonstrated.


Using ABC narrative recording to identify the function of problem behavior: a pilot study.
Many professionals report using ABC narrative recording to identify the function of problem behavior in children with developmental disabilities, but research has not established whether their analyses yield valid results. Thus, the purpose of this study was to examine whether the function identified by expert reviewers using ABC narrative recordings would match the one identified by a functional analysis (FA) and the Questions About Behavioral Function (QABF) scale in four children with developmental disabilities. The functions identified by all twelve experts using the ABC narrative recordings matched at least one of the functions identified by the FA for three of four participants. The experts' analyses also agreed with the informant-based assessment at a statistically significant level for two of three participants with a conclusive QABF. Altogether, the results suggest that ABC narrative recording may be useful to generate hypotheses to identify the function of problem behavior, but that more research is needed before recommending its use as a standalone functional behavior assessment.


Options for coronary translocation and other considerations in aortic root translocation (Bex-Nikaidoh procedure).
The surgical options for patients with transposition of the great arteries (TGA), ventricular septal defect (VSD), and left ventricular outflow tract obstruction include intracardiac baffling with the right ventricle to pulmonary artery (PA) conduit (Rastelli procedure), "reparation a l'etage ventriculaire" or aortic root translocation (Bex-Nikaidoh procedure). The Bex-Nikaidoh procedure allows a more normal, anatomically aligned left ventricular outflow tract. However, the operation is technically demanding, and coronary translocation remains one of the major challenges for successful root translocation. All patients who underwent aortic root translocation in a single institute over a period of 2 years from January 2015 to December 2017 were included in the study. Surgical technique and early outcomes are described with specific focus on the different observed coronary artery patterns and surgical strategies for translocation. Fourteen patients underwent aortic root translocation. The coronary artery patterns observed could be categorized into four different patterns based on the size of the pulmonary annulus and the relative position of the PA relative to the aorta. Successful translocation of the coronary arteries was achieved in every patient. Mean follow-up was 18.42 ± 9.22 months. There was no mortality and no reoperation during the follow-up period. The Bex-Nikaidoh procedure is a promising surgical option for TGA, VSD, and pulmonary stenosis. Good outcomes are achievable despite wide variations in anatomy using a tailored approach for coronary translocation.


[Giardiasis and cryptosporidiosis in children institutionalized at daycare centers in the state of São Paulo].
Two cross-sectional studies were conducted, in 2002 (N=379) and 2003 (N=397), to estimate the prevalence of intestinal parasites among children at five municipal daycare centers in Botucatu, State of São Paulo. Socioeconomic, sanitary and educational data were collected and parasitological tests were performed on feces. Giardia duodenalis presented prevalence of 23.7% (2002) and 21.4% (2003) followed by Cryptosporidium sp with 15.5% (2002) and 3.7% (2003).


[Completion technology of pelvic surgery accompanying with cystectomy in elderly and senile patients].
Results of treatment of 204 elderly and senile patients who underwent cystprostatectomy or anterior pelvic exenteration are analyzed. A comparative analysis of two groups of patients whose operation ended with the traditional drainage through the anterior abdominal wall (n = 100), and bilateral perineal drainage (n = 104) is presented. Bilateral perineal drainage after operations on the pelvic organs, accompanied by cystectomy and extended lymphadenectomy in conjunction with the restoration of the peritoneum lateral pelvic walls, improves postoperative recovery of intestinal peristalsis, promotes an earlier reduction in the intensity of pain and morbidity in the early postoperative period. Perineal installation of drains is a simple in design and safe procedure. We recommend bilateral perineal drainage after operations on the pelvic organs, accompanied by cystectomy and extended lymphadenectomy.


Economic evaluation of the new oral anticoagulants for the prevention of thromboembolic events: a cost-minimization analysis.
Randomized clinical trials have shown that the new oral anticoagulants have at least similar impact regarding reduction of thromboembolic events, compared with warfarin, with similar or improved safety profiles. There is little data on real costs within clinical practice. Our aim here was to perform economic analysis on these strategies from the perspective of Brazilian society and the public healthcare system. Cost-minimization analysis; anticoagulation clinic of Hospital Municipal Odilon Behrens, Belo Horizonte, MG, Brazil. Patients at the anticoagulation clinic were recruited between August and October 2011, with minimum follow-up of four weeks. Operational and non-operational costs were calculated and corrected to 2015. This study included 633 patients (59% women) of median age 62 years (interquartile range -49-73). The mean length of follow-up was 64 ± 28 days. The average cost per patient per month was $ 54.26 (US dollars). Direct costs accounted for 32.5% of the total cost. Of these, 69.5% were related to healthcare professionals. With regards to indirect costs, 52.4% were related to absence from work and 47.6% to transportation. Apixaban, dabigatran and rivaroxaban were being sold to Brazilian public institutions, on average, for $ 49.87, $ 51.40 and $ 52.16 per patient per month, respectively, which was lower than the costs relating to warfarin treatment. In the Brazilian context, from the perspective of society and the public healthcare system, the cumulative costs per patient using warfarin with follow-up in anticoagulation clinics is currently higher than the strategy of prescribing the new oral anticoagulants.


Individualized Treatment of Tinnitus during Sleep Using Combined Tinnitus Signal and Music.
Tinnitus is a widely seen otological symptom that interferes with daily activities and causes discomfort. Tinnitus treatments can be classified into 4 main groups: pharmacological treatments, cognitive and behavioral therapy, psychological treatments, and combined treatment approaches made up of at least 2 of these 3 treatment methods. The aim of this study was to assess whether it would be possible to develop an individualized treatment method of tinnitus by application of a combined tinnitus signal and music during sleep. Forty-three ears of 30 patients who had subjective tinnitus were included. The patients were evaluated using Tinnitus Handicap Inventory, Visual Analogue Scale, and Beck Depression Inventory. The psychoacoustic parameters of tinnitus, such as tinnitus frequency and loudness, and minimal masking levels, were determined. The patients were asked to select musical melodies that they liked. The tinnitus frequency of each patient was taken as the central frequency according to ANSI 2004. All sound files were prepared as stereo channels, with 16-bit resolution and 44,100 Hz sampling rate. The root mean square power value of the music and the band noise's average root mean square power value were equalized with the "Amplification" command, and 70% of the music and 30% of wide/narrow-band noise were mixed as a stereo channel by the "Mix Paste" command. The patients were instructed to listen to that individualized music/narrow-band noise (tinnitus signal) for 2 h during sleep for a duration of 6 months. Tinnitus frequencies of the patients measured prior to treatment and at the second, fourth, and sixth months of follow-up were not significantly different. A statistically significant decrease was seen in tinnitus loudness, minimal masking levels, and residual inhibition during the follow-up. Tinnitus Handicap Inventory scores decreased significantly during follow-up, and the number of patients who complained of tinnitus decreased (p < 0.05). The Visual Analogue Scale scores significantly decreased during follow-up (p < 0.05). Beck Depression Inventory scores decreased significantly during follow-up (p < 0.05). Stimulation of the auditory and limbic systems during sleep by the tinnitus signal combined with individualized musical melodies seems an alternative, effective, and cheap method in the treatment of tinnitus.


Short-term effects of corticosteroid therapy on cardiac and skeletal muscles in muscular dystrophies.
Duchenne muscular dystrophy (DMD) is the most common muscular dystrophy of childhood. It leads to progressive deterioration in cardiac and skeletal muscles. Corticosteroids are considered an effective therapy. This study aimed to evaluate the role of short-term prednisone therapy in improving left ventricular (LV) systolic function, LV mass (LVM), and motor power in cases of muscular dystrophies. Twenty-five cases of muscular dystrophy including 17 cases of DMD, 3 cases of Becker muscular dystrophies, and 5 cases of female patients with DMD-like phenotype were included in the study. The diagnosis of 12 patients was confirmed by muscle biopsy with immunohistochemistry; the patients were subjected to motor assessment, measurement of creatine kinase level, and echocardiographic examination before and after prednisone therapy. Transthoracic echocardiographic assessment of the LV systolic function (fractional shortening) was done. Myocardial performance index and LVM were calculated. Intermittent dosage of prednisone was administered 5 mg/kg per day on 2 consecutive days weekly for 3 months. Fractional shortening improved on prednisone therapy (P = 0.009) and LVM increased (P = 0.012); improvement in walking was detected in 77% of the patients, climbing stairs improved in 88.9%, Gower sign improved in 70%, and rising from chair improved in 60%. Prednisone had no effect on the patients with marked motor impairment (on wheelchair). The creatine kinase level was significantly lower after steroid therapy (P = 0.04). Three months of intermittent prednisone therapy could improve cardiac and skeletal muscle function in congenital muscular dystrophy.


Hormone receptors in breast cancer. Analytic accuracy of contemporary assays.
When powders of human breast carcinomas were assayed by an unselected group of laboratories, there was 90% to 98% concurrence in estrogen and progesterone receptor results. While these results demonstrate room for improvement in assay technique, it is clear that the variability due to the analysis does not exceed the variability of the clinical course and the clinical assessment of the conditions of patients with breast cancer.


Parent-Metabolite Pharmacokinetic Modeling and Pharmacodynamics of Veliparib (ABT-888), a PARP Inhibitor, in Patients With BRCA 1/2-Mutated Cancer or PARP-Sensitive Tumor Types.
Veliparib (ABT-888) is a novel oral poly-ADP-ribose polymerase (PARP) inhibitor that is being developed for the treatment of hematologic malignancies and solid tumors. Although the pharmacokinetics of veliparib have been studied in combination with cytotoxic agents, limited information exists regarding the pharmacokinetics (PK) of chronically dosed single-agent veliparib in patients with either BRCA 1/2-mutated cancer or PARP-sensitive tumors. The objectives of the current analysis were to characterize the population pharmacokinetics of veliparib and its primary, active metabolite, M8, and to evaluate the relationship between veliparib and M8 concentrations and poly-ADP-ribose (PAR) level observed in peripheral blood mononuclear cells (PBMCs). Seventy-one subjects contributed with veliparib plasma concentrations, M8 plasma concentrations, and PAR levels in PBMCs. Veliparib and M8 concentrations were modeled simultaneously using a population PK approach. A 2-compartment model with delayed first-order absorption and the elimination parameterized as renal (CLR /F) and nonrenal clearance (CLNR /F) adequately described veliparib pharmacokinetics. The pharmacokinetics of the M8 metabolite was described with a 2-compartment model. Creatinine clearance(CLCR ) and lean body mass (LBM) were identified as significant predictors of veliparib CLR /F and central volume of distribution, respectively. For a typical subject (LBM, 48 kg; CLCR , 95 mL/min), total clearance (CLR /F + CLNR /F), and central and peripheral volume of distribution for veliparib were estimated as 17.3 L/h, 98.7 L, and 48.3 L, respectively. At least 50% inhibition of PAR levels in PBMCs was observed at dose levels ranging from 50 to 500 mg.


[A trial of using augmentin (amoxicillin/clavulanate) in surgical practice].
The experience with the use of augmentin (amoxycillin/clavulane) in abdominal surgery for prophylaxis of postoperative purulent complications was analyzed. The drug was used in 44 patients after relatively pure operations, 37 of them having various risk factors. In 2 patients (4.5 per cent) of that group postoperative pyoinflammatory complications were recorded. For comparison the results of the prophylactic use of cefoperazone, cefamandole or ceftazidime in the group of 78 patients after relatively pure operations on the abdominal cavity organs were analyzed. Postoperative complications in the latter group amounted to 7.4 per cent (4 patients). The results of the treatment of patients in two groups after contaminated operations were also compared. The patients of one group (41 patients) were treated prophylactically with augmentin in a dose of 1200 mg intraoperatively followed by the drug use in a dose of 600 mg thrice daily for 1 to 2 days after the operation. Postoperative pyoinflammatory complications were recorded in 4 patients of that group (9.7 per cent). 78 patients of the other group were treated prophylactically with ceftazidime or cefoperazone in a dose of 2 g and metronidazole intraoperatively or cefoperazone in a dose of 2 g twice daily and metronidazole in a dose of 500 mg twice daily for 1 to 2 days after the operation. Postoperative infectious complications were recorded in 8 patients of that group (10 per cent). In the group of patients with acute cholecystitis treated with ciprofloxacin in a dose of 400 mg in combination, with metronidazole before the operation and for 1 to 2 days after the operation postoperative complications were recorded in 4 patients (17 per cent).


Renal cortical ceramide patterns during ischemic and toxic injury: assessments by HPLC-mass spectrometry.
Ceramides are a class of signaling molecules that can acutely accumulate in tissues as part of a "stress response." They are classically measured by the diacylglycerol kinase assay, which, in general, measures total ceramide rather than individual moieties within the diverse ceramide family. The present study was undertaken to 1) adapt current HPLC-mass spectrometry technology for measuring individual renal ceramides, and 2) use this technique to more fully characterize the nature of the renal ceramide "stress" reaction. Renal cortical tissues were obtained from CD-1 mice under control conditions and 2 or 18 h after renal injury (ischemia-reperfusion and glycerol-mediated myohemoglobinuria). C24, C22, and C16 ceramides were identified in normal renal cortex, constituting 70, 10, and 20% of the total ceramide pool, respectively. Within each of these families, heterogeneity was apparent because of differing degrees of unsaturation (0-3 double bonds) in the constituent fatty acid of ceramide. Renal injury dramatically changed ceramide profiles: 1) total ceramide increased by approximately 300%; 2) although all ceramides participated in this reaction, they did so to differing degrees; 3) this caused pronounced changes in ceramide distribution patterns; 4) injury induced a striking shift toward unsaturated (vs. saturated) fatty acids within the C22 and C24 (but not the C16) ceramide pools; and 5) the extent of these qualitative changes differed according to the etiology of the initiating renal damage. Thus we conclude that ceramide stress response involves major qualitative (and not simply quantitative) changes in ceramide expression that are partially disease dependent. These findings underscore the fact that simply measuring total renal ceramide content (e.g., by diacylglycerol kinase assay) substantially oversimplifies the nature and, hence, the potential implications of the ceramide stress reaction.


The oral disposition index calculated from a meal tolerance test is a crucial indicator for evaluating differential normalization of postprandial glucose and triglyceride excursions in morbidly obese patients after laparoscopic sleeve gastrectomy.
To determine the normalization of postprandial blood glucose (PG) and triglyceride (TG) excursions in 30 morbidly obese patients with or without diabetes mellitus (DM) 1-year after they underwent a laparoscopic sleeve gastrectomy (LSG) vs. their pre-surgery data, we administered the 75-g oral glucose tolerance test (OGTT) and a meal tolerance test (MTT) using a 75-g glucose-equivalent carbohydrate- and fat-containing meal. The results were as follows; (i) Postoperative body-weight reduction was associated with DM remission and reduced multiple cardiometabolic risks. (ii) OGTT data showing postprandial hyper-insulinemic hypoglycemia in many post-surgery patients were associated with overdiagnosis of improved glucose tolerance. However, postoperative MTT data without hypoglycemia showed no improvement in the glucose tolerance vs. pre-surgery data. (iii) The disposition index (DI) i.e., [Matsuda index] × (Glucose-induced insulin secretion) was progressively worsened from normal glucose tolerance to DM patients after LSG. These post-surgery DI values measured by the MTT were correlated with 2h-plasma glucose levels and were not normalized in DM patients. (iv) The baseline, 2h-TG, and an increase in 2h-TG values above baseline were correlated with the insulin resistance index, DI, or HbA1c; These TG values were normalized post-LSG. In conclusion, the glucose tolerance curve measured by the MTT was not normalized in T2DM patients, which was associated with impaired normalization of the DI values in those patients 1-year after the LSG. However, the baseline TG and a fat-induced 2h-TG values were normalized postoperatively. The MTT can be used to assess normalization in postprandial glucose and TG excursions after LSG.


Association of soluble HLA-G with acute rejection episodes and early development of bronchiolitis obliterans in lung transplantation.
Lung transplantation has evolved into a life-saving therapy for select patients with end-stage lung diseases. However, long-term survival remains limited because of bronchiolitis obliterans syndrome (BOS). Soluble HLA-G, a mediator of adaptive immunity that modulates regulatory T cells and certain classes of effector T cells, may be a useful marker of survival free of BOS. We conducted a retrospective, single-center, pilot review of 38 lung transplant recipients who underwent collection of serum and bronchoalveolar lavage fluid 3, 6 and 12 months after transplantation, and compared soluble HLA-G concentrations in each to the presence of type A rejection and lymphocytic bronchiolitis in the first 12 months and to the presence of BOS at 24 months after transplantation. Lung soluble HLA-G concentrations were directly related to the presence of type A rejection but not to lymphocytic bronchiolitis. Our data demonstrate that soluble HLA-G concentrations in bronchoalveolar lavage but not in serum correlates with the number of acute rejection episodes in the first 12 months after lung transplantation, and thus may be a reactive marker of rejection.


Prevalence and predictors of harmful khat use among university students in ethiopia.
Comprehensive assessment of harmful khat use is lacking because often researchers rely on a simple tool for studying it. The aim of this study was to determine the prevalence and predictors of harmful khat use among Ethiopian university students by developing a comprehensive scale based on Alcohol Use Identification Test, Severity of Dependency Syndrome scale, and International Classification of Diseases definition of harmful substance use. Logistic regression was performed to identify predictors of harmful khat use. One in five current khat user students were identified as harmful khat users [20.6% (95% CI: 14.3-22.3)]. Harmful khat use in this study was strongly associated with chewing at commercial places [adjusted odds ratio (AOR) = 2.32 (95% CI: 1.01-5.33)], and having non-student friends accompanying the khat-chewing ceremony [AOR = 3.77 (95% CI: 1.09-13.03). Students who started chewing khat at the age of 20 years or later [AOR = 0.19 (95% CI: 0.07-0.55)] and those who preferred to study in the library [AOR = 0.31(95% CI: 0.12-0.81)] were less likely to be harmful khat users. The university authorities, in addition to provision of student guidance on substance-use prevention, need to work in collaboration with the surrounding community and responsible public authorities in order to reduce harmful use of khat by their students.


Revisiting the roles and responsibilities of speech-language therapists in South African schools.
The role of speech-language therapists (SLTs) in schools in South Africa needs to be revisited based on the changing educational needs in the country. This article builds on a paper by Kathard et al. (2011), which discussed the changing needs of the country with regard to the role of SLTs working in schools. South African policy changes indicated a shift from supporting the child to supporting the teacher, but also place more emphasis on the support of all learners in literacy in an effort to address past inequities. This paper addresses several of the questions that emerged from Kathard et al. and explores the collaborative roles played by SLTs on four levels in the education context. Collaboration at the learner level (level 1) focuses on prevention and support, whereas collaboration at the teacher level (level 2) is described in terms of training, mentoring, monitoring and consultation. Collaboration can also occur at the district level (level 3), where the focus is mainly on the development and implementation of support programmes for teachers in areas of literacy and numeracy. Collaboration at the level of national and provincial education (level 4) is key to all other roles, as it impacts on policy. This last level is the platform to advocate for the employment of SLTs in schools. Such new roles and responsibilities have important implications for the preparation of future SLTs. Suggestions for curricular review and professional development are discussed. It is proposed that SASLHA responds to the changes by developing a position statement on the roles and responsibilities of SLTs in schools.


Connexin 36 expression is required for electrical coupling between mouse rods and cones.
Rod-cone gap junctions mediate the so-called "secondary rod pathway", one of three routes that convey rod photoreceptor signals across the retina. Connexin 36 (Cx36) is expressed at these gap junctions, but an unidentified connexin protein also seems to be expressed. Cx36 knockout mice have been used extensively in the quest to dissect the roles in vision of all three pathways, with the assumption, never directly tested, that rod-cone electrical coupling is abolished by deletion of this connexin isoform. We previously showed that when wild type mouse cones couple to rods, their apparent dynamic range is extended toward lower light intensities, with the appearance of large responses to dim flashes (up to several mV) originating in rods. Here we recorded from the cones of Cx36del[LacZ]/del[LacZ] mice and found that dim flashes of the same intensity evoked at most small sub-millivolt responses. Moreover, these residual responses originated in the cones themselves, since: (i) their spectral preference matched that of the recorded cone and not of rods, (ii) their time-to-peak was shorter than in coupled wild type cones, (iii) a pharmacological block of gap junctions did not reduce their amplitude. Taken together, our data show that rod signals are indeed absent in the cones of Cx36 knockout mice. This study is the first direct demonstration that Cx36 is crucial for the assembly of functional rod-cone gap junctional channels, implying that its genetic deletion is a reliable experimental approach to eliminate rod-cone coupling.


Health Care Costs Following COVID-19 Hospitalization Prior to Vaccine Availability.
Postacute sequelae of coronavirus (PASC) disease of 2019 (COVID-19) include morbidity and mortality, but little is known of the impact on medical expenditures. This study measures patients' health care costs after COVID hospitalization before vaccinations. The Merative MarketScan database is used to track trends in medical expenditures for commercially insured patients hospitalized for COVID-19 (case subjects) compared with COVID-19 patients not hospitalized (control subjects) using a propensity score matching model. Medical expenditures were estimated from 30-, 60-, and 120-day clean periods after an initial COVID-19 encounter through the end of 2020. Average total medical expenditures were 96% higher for individuals hospitalized for COVID-19 starting 30 days after initial COVID-19 encounter and almost 70% higher 120 days after based on the propensity score matching. The average spending differential was $11,242 30 days after and $4959 120 days after. This effect is highest for inpatient admissions and services 60 days after at $56,862 and lowest among pharmaceuticals 120 days after at $329. The magnitude of the difference is greater for those with hypertension or diabetes where total expenditures is $14,958 30 days after, and $5962 120 days after compared with those without these chronic conditions. The results suggest both health and economic implications for COVID-19 hospitalization and supports the use of vaccinations to help mitigate these implications. PASC includes increased health care costs for hospitalized patients, particularly for those with chronic conditions. Preventing COVID-19 hospitalization has economic value in terms of reduced medical spending in addition to health benefits associated with reduced morbidity and mortality.


Effect of Salvia miltiorrhiza hydrophilic extract on antioxidant enzymes in diabetic patients with chronic heart disease: a randomized controlled trial.
To investigate whether Salvia miltiorrhiza hydrophilic extract (SMHE) has the ability to ameliorate oxidative stress in diabetic patients with chronic heart disease (CHD), 62 patients with CHD were recruited. These patients were assigned randomly into two groups: (1) placebo group receiving hypoglycemic therapy; (2) treatment group receiving hypoglycemic therapy plus SMHE. The biological markers related to oxidative stress were measured to determine the effect of treatment. Thirty patients in the placebo group and 24 patients in the treatment group were followed to completion in this study. Overall, the malondialdehyde (MDA) level at day 30 in the treatment group was significantly lower than in the placebo group. However, no significant difference in the serum antioxidant enzymes activities was observed between the groups. At day 60, the serum glutathione (GSH) level, superoxide dismutase (SOD), Paraoxonase (PONase) and glutathione reductase (GSSG-R) activities increased markedly in the treatment group compared with the placebo group. There was no significant difference in the level of lipid profile between the two groups. This study indicated that SMHE clearly reduced oxidative stress in diabetic patients with CHD.


Ecdysteroid control of cell proliferation during optic lobe neurogenesis in the moth Manduca sexta.
Cell proliferation within the optic lobe anlagen is dependent on ecdysteroids during metamorphosis of the moth Manduca sexta. We use cultured tissues to show that ecdysteroids must be maintained above a sharp threshold concentration to sustain proliferation. Proliferation can be turned on and off repeatedly simply by shifting the ecdysteroid concentration to above or below this threshold. In subthreshold hormone, cells arrest in the G2 phase of the cell cycle. Ecdysteroid control of proliferation is distinguished from differentiative and maturational responses to ecdysteroids by requiring tonic exposure to the hormone and lower levels of 20-hydroxyecdysone, and by being sensitive to either 20-hydroxyecdysone or its precursor, ecdysone. These characteristics allow optic lobe development to be divided into two ecdysteroid-dependent phases. Initially, moderate levels of ecdysteroid stimulate proliferation. Later, high levels of 20-hydroxyecdysone trigger a wave of apoptosis within the anlage that marks completion of its proliferative phase.


Integrated Risk Assessment and Management Methods Are Necessary for Effective Implementation of Natural Hazards Policy.
A transdisciplinary, integrated risk assessment and risk management process is particularly beneficial to the development of policies addressing risk from natural hazards. Strategies based on isolated risk assessment and management processes, guided by traditional "predict, then act" methods for decision making, may induce major regret if future conditions diverge from predictions. Analytic methods designed to identify robust solutions-those that perform satisfactorily over a broader range of future conditions-are more suitable for management of natural hazards risks, for at least three major reasons discussed within. Such approaches benefit from co-production of knowledge to collaboratively produce adaptive, robust policies through an iterative process of dialogue between analysts, decisionmakers, and other stakeholders: exploring tradeoffs, searching for futures in which current plans are likely to fail, and developing adaptive management strategies responsive to evolving future conditions. The process leads to more effective adoption of risk management policies by ensuring greater feasibility of solutions, exploring a wide range of plausible future conditions, generating buy-in, and giving a voice to actors with a diversity of perspectives. The second half of the article presents Louisiana's coastal master planning process as an exemplary model of participatory planning and integrated risk assessment and management. Louisiana planners have adopted a decision framework that incorporates insights from modern methods for decision making under deep uncertainty to effectively address the deep uncertainties and complexities characteristic of a variety of natural hazards and long-range planning problems.


GROWSCREEN-Rhizo is a novel phenotyping robot enabling simultaneous measurements of root and shoot growth for plants grown in soil-filled rhizotrons.
Root systems play an essential role in ensuring plant productivity. Experiments conducted in controlled environments and simulation models suggest that root geometry and responses of root architecture to environmental factors should be studied as a priority. However, compared with aboveground plant organs, roots are not easily accessible by non-invasive analyses and field research is still based almost completely on manual, destructive methods. Contributing to reducing the gap between laboratory and field experiments, we present a novel phenotyping system (GROWSCREEN-Rhizo), which is capable of automatically imaging roots and shoots of plants grown in soil-filled rhizotrons (up to a volume of ~18L) with a throughput of 60 rhizotrons per hour. Analysis of plants grown in this setup is restricted to a certain plant size (up to a shoot height of 80cm and root-system depth of 90cm). We performed validation experiments using six different species and for barley and maize, we studied the effect of moderate soil compaction, which is a relevant factor in the field. First, we found that the portion of root systems that is visible through the rhizotrons' transparent plate is representative of the total root system. The percentage of visible roots decreases with increasing average root diameter of the plant species studied and depends, to some extent, on environmental conditions. Second, we could measure relatively minor changes in root-system architecture induced by a moderate increase in soil compaction. Taken together, these findings demonstrate the good potential of this methodology to characterise root geometry and temporal growth responses with relatively high spatial accuracy and resolution for both monocotyledonous and dicotyledonous species. Our prototype will allow the design of high-throughput screening methodologies simulating environmental scenarios that are relevant in the field and will support breeding efforts towards improved resource use efficiency and stability of crop yields.


Management of Delayed Skin Necrosis Following Hyaluronic Acid Filler Injection Using Pulsed Hyaluronidase.
Facial fillers are minimally invasive aesthetic procedures performed for facial rejuvenation and contouring all over the world. Fillers even in the most experienced hands can lead to fatal complications such as vascular complications that need to be managed immediately with the help of hyaluronidase protocols mentioned in literature. In this case report, a patient was asymptomatic with no signs of vascular occlusion such as blanching or poor capillary refill for 48 h. He came after more than 48 h of the filler injection with complaints of pulsating pain in the right infraorbital and nasolabial area. We noticed necrosed microvesicles in the infraorbital artery territory with signs of impending skin necrosis extending from right infraorbital region up to the nasolabial fold (slightly medial to it). He was treated immediately with three pulsed doses of 500 units higher dilation of 10 ml each every hour (reconstitution carried out using 3mL normal saline). The skin color improved with decreased pain, and the next day (after 14 hours) we injected 500 units of hyaluronidase in higher dilution of 10mL as slight redness was still present. Skin redness, swelling, and pain disappeared the following day. Skin was completely healed and by 15 days we noticed slight post-inflammatory hyperpigmentation, which was easily managed with Q-switched laser and creams. We hereby report a case of delayed skin necrosis (>48 h) following filler injections in the cheek area, in the infraorbital artery vascular territory, which was successfully managed with pulsed dose of hyaluronidase.


Decline in incidence of hospitalisation for acute myocardial infarction in the Netherlands from 1995 to 2000.
To study the change in incidence of hospitalisation for a first acute myocardial infarction (AMI) in the Netherlands from 1995 to 2000. Patients hospitalised with their first AMI in the Netherlands in 1995 and 2000 were identified through linkage of the national hospital discharge register and the population register. 21,565 patients hospitalised for their first AMI in 1995 and 19,058 patients hospitalised for their first AMI in 2000 were identified. In both years, the age specific incidence of hospitalisation for a first AMI was higher in men than in women and increased with age (up to 90 years). In both men and women, the age standardised incidence was lower in 2000 than in 1995, a decline of 19% (95% confidence interval 17% to 21%) and 17% (95% confidence interval 14% to 19%), respectively. Our study provides the first nationwide incidence estimates of first AMI in the Netherlands. From 1995 to 2000, the risk of AMI declined considerably.


Promoting self-management and adherence during prophylaxis: evidence-based recommendations for haemophilia professionals.
Throughout life, a patient with severe haemophilia is confronted with many treatment-related challenges. Insight into self-management and non-adherence could improve the quality of care for these patients. The aim of this study was to provide an overview of the current evidence on self-management and adherence to prophylaxis in haemophilia. Based on series of studies and published literature, aspects of treatment were explored: learning and performing self-infusion, achieving self-management skills in adolescence, adherence issues and coping with haemophilia. Evidence-based and age-group-specific recommendations for haemophilia professionals were formulated. Nearly, all severe haemophilia patients and parents were able to perform self-infusion and the quality level of infusion skills was acceptable. Learning self-infusion was generally initiated before the onset of puberty and full self-management was obtained 10 years later. Adherence was defined using a Delphi consensus procedure and was determined by skipping, dosing and timing of infusions. Adherence levels varied according to age, with highest levels in children (1-12 years) and the lowest among 25-40 years. Adherence to prophylaxis was acceptable (43%), yet 57% of the population struggled with prophylaxis. Qualitative research showed that the position of prophylaxis in life is the main driver of adherence. This position is influenced by acceptance and self-management skills. Regarding coping with haemophilia, the majority of patients used a problem-focused approach. Self-management and adherence to prophylaxis vary during the life span. Acceptance of the disease and self-management skills were important aspects that may require tailored professional support.


[Methodological design for the National Survey Violence Against Women in Mexico].
To describe the methodology, the research designs used, the estimation and sample selection, variable definitions, collection instruments, and operative design and analytical procedures for the National Survey Violence Against Women in Mexico. A complex (two-step) cross-sectional study was designed and the qualitative design was carried out using in-depth interviews and participant observation in health care units. We obtained for the quantitative study a total of 26 240 interviews in women users of health services and 2 636 questionnaires for health workers; the survey is representative of the 32 Mexican states. For the qualitative study 26 in-depth interviews were conducted with female users and 60 interviews with health workers in the States of Quintana Roo, Coahuila and the Federal District.


Patella Fracture Identified Using Point-of-care Ultrasound.
A 49-year-old female fell from standing. Her right knee extended into the air. She had acute right knee pain preventing weight-bearing. Her knee was most comfortable fully-extended. She could not flex it due to pain, nor extend it against resistance. Tenderness and a horizontal defect were noted over the anterior knee. Bedside ultrasound demonstrated a horizontally-fractured patella (confirmed on X-ray) with intact femoral and patellar tendons. She was put in a knee immobilizer and underwent surgery, with return to full function and activities. Ultrasound can identify patella fractures and help with early evaluation, management, and specialty referral, as well as ordering more-focused imaging. In one study, POCUS (point-of-care ultrasound) for patella fracture had 95% sensitivity, 63% specificity, 86% positive predictive value, and 83% negative predictive value. The dynamic nature of ultrasound allows a ruptured patella (87% sensitivity) or quadriceps tendon (100% sensitivity) to be excluded with high certainty.


Online Information About Periviable Birth: Quality Assessment.
Over 20,000 parents in the United States face the challenge of participating in decisions about whether to use life support for their infants born on the cusp of viability every year. Clinicians must help families grasp complex medical information about their baby's immediate prognosis as well as the risk for significant long-term morbidity. Patients faced with this decision want supplemental information and frequently seek medical information on the Internet. Empirical evidence about the quality of websites is lacking. We sought to evaluate the quality of online information available about periviable birth and treatment options for infants born at the cusp of viability. We read a counseling script to 20 pregnant participants that included information typically provided by perinatal and neonatal providers when periviable birth is imminent. The women were then asked to list terms they would use to search the Internet if they wanted additional information. Using these search terms, two reviewers evaluated the content of websites obtained via a Google search. We used two metrics to assess the quality of websites. The first was the DISCERN instrument, a validated questionnaire designed to assess the quality of patient-targeted health information for treatment choices. The second metric was the Essential Content Tool (ECT), a tool designed to address key components of counseling around periviable birth as outlined by professional organizations. DISCERN scores were classified as low quality if scores were 2, fair quality if scores were 3, and high quality if scores were 4 or higher. Scores of 6 or higher on the ECT were considered high quality. Interreviewer agreement was assessed by calculated kappa statistic. A total of 97 websites were reviewed. Over half (57/97, 59%) were for-profit sites, news stories, or personal blogs; 28% (27/97) were government or medical sites; and 13% (13/97) were nonprofit or advocacy sites. The majority of sites scored poorly in DISCERN questions designed to assess the reliability of information presented as well as data regarding treatment choices. Only 7% (7/97) of the websites were high quality as defined by the DISCERN tool. The majority of sites did not address the essential content defined by the ECT. Importantly, only 18% of websites (17/97) indicated that there are often a number of reasonable approaches to newborn care when faced with periviable birth. Agreement was strong, with kappa ranging from .72 to .91. Most information about periviable birth found on the Internet using common search strategies is of low quality. News stories highlighting positive outcomes are disproportionately represented. Few websites discuss comfort care or how treatment decisions impact quality of life.


Worry and rumination in older adults: Differentiating the processes.
This study examined the factor structure of the adapted Ruminative Response Scale in a large Australian older adult sample. Previously, the factor structure has only been explored in small UK sample and thus remains tentative. A further objective was to explore overlapping and distinct characteristics of worry, brooding and reflection in relation to coping behaviour which has not previously been examined in older adults. A total of 138 older adults aged between 65 and 97 years (M = 77, SD = 7.9) completed a number of instruments to measure worry, rumination, anxiety and coping behaviour. A three-factor structure comprised of worry, brooding and reflection emerged. However, no unique relationship was found between the rumination components (brooding and reflection) and worry and coping pathways. The factor structure supports the idea that worry, brooding and reflection are distinguishable constructs in the elderly. However, the lack of differential associations between the rumination components and worry in relation to coping strategies provided evidence that rumination and worry are part of the same theoretical construct of repetitive thought. The implications of these findings for the management of anxiety and depression in the elderly are discussed.


The systems biology of uric acid transporters: the role of remote sensing and signaling.
Uric acid homeostasis in the body is mediated by a number of SLC and ABC transporters in the kidney and intestine, including several multispecific 'drug' transporters (e.g., OAT1, OAT3, and ABCG2). Optimization of uric acid levels can be viewed as a 'systems biology' problem. Here, we consider uric acid transporters from a systems physiology perspective using the framework of the 'Remote Sensing and Signaling Hypothesis.' This hypothesis explains how SLC and ABC 'drug' and other transporters mediate interorgan and interorganismal communication (e.g., gut microbiome and host) via small molecules (e.g., metabolites, antioxidants signaling molecules) through transporters expressed in tissues lining body fluid compartments (e.g., blood, urine, cerebrospinal fluid). The list of uric acid transporters includes: SLC2A9, ABCG2, URAT1 (SLC22A12), OAT1 (SLC22A6), OAT3 (SLC22A8), OAT4 (SLC22A11), OAT10 (SLC22A13), NPT1 (SLC17A1), NPT4 (SLC17A3), MRP2 (ABCC2), MRP4 (ABCC4). Normally, SLC2A9, - along with URAT1, OAT1 and OAT3, - appear to be the main transporters regulating renal urate handling, while ABCG2 appears to regulate intestinal transport. In chronic kidney disease (CKD), intestinal ABCG2 becomes much more important, suggesting remote organ communication between the injured kidney and the intestine. The remote sensing and signaling hypothesis provides a useful systems-level framework for understanding the complex interplay of uric acid transporters expressed in different tissues involved in optimizing uric acid levels under normal and diseased (e.g., CKD, gut microflora dysbiosis) conditions.


[Effect of extract of ginkgo biloba leaves on proliferation of SCs cultured in vitro].
To investigate the effect of extract of ginkgo biloba leaves (EGb50) on the proliferation of SCs cultured in vitro. The SCs were isolated from 3-day-old SD rats' sciatic nerves by the method of enzyme gradation digestion (n=20) and the purified 2nd passage of SCs were divided into 2 groups: the experimental group, in which SCs were cultured in FBS-DMEM medium with EGb50 (terminal concentration: 50 microg/mL); the control group, in which SCs were cultured in the FBS-DMEM medium without EGb50. The absorbance (A) value was detected by the 2, 3-bis- (2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide (XTT) method 1, 3, 5, 7 and 9 days after culture, then the growth curves was drawn. Cell cycle was detected by flow cytometry (FCM). Disintegration per minute (DPM) of SCs was detected by the method of 3H-thymine nucleoside (3H-TdR) 2 and 3 days after culture and nerve growth factor (NGF) synthesis in SCs culture media was detected by ELISA method. Most SCs were spindle-shaped with a purity above 90%. XTT detection showed that A value of SCs in the control group was gradually increased 3 days after culture, reached the peak 5 days after culture and gradually decreased from then; the A value in the experimental group experienced the similar changes, but it was higher than that in the control group at each time point (P < 0.01). 3H-TdR showed that the DPM of the experimental group was 1 961.78 +/- 231.13 and 4 601.51 +/- 605.08 at 2 and 3 days after culture, while for the control group, the A value was 1347.15 +/- 121.57 and 3740.42 +/- 158.73 at the same time point, indicating a significant difference between two groups (P < 0.01). FCM observation indicated that the SCs proliferation index of the experimental group and the control group was 18.6% +/- 3.2% and 9.7% +/- 2.9%, indicating a significant difference between two groups (P < 0.01). ELISA observation showed that the NGF concentration in the experimental and the control group was (0.0656 +/- 0.0039) ng/mL and (0.0386 +/- 0.0036) ng/mL, indicating a significant difference (P < 0.01). EGb50 is capable of enhancing the proliferation of SCs cultured in vitro, which may be one of the important mechanisms to promote peripheral nerve regeneration.


Effect of selected modified atmosphere packaging on Campylobacter survival in raw poultry.
Most current research on Campylobacter has focused on preharvest or processing plant cross-contamination. Little is known about the effect of storage environment on the survival of Campylobacter on raw poultry. We evaluated the effects of modified storage atmosphere and freezing on the survival of naturally occurring Campylobacter on raw poultry. Broiler carcasses (n = 560) were collected as they exited the chiller in 2 commercial processing plants and were sampled for the detection of Campylobacter, Escherichia coli, psychrophiles, and total aerobes at 0 and 14 d of refrigerated (2°C) storage. Gases evaluated were air, 100% O(2), 100% CO(2), and a standard poultry modified atmosphere packaging mixture (5% O(2) + 10% CO(2) + 85% N). Freezing was included as a control group. All carcasses were sampled by the whole-carcass rinse method. The rinse fluid was recovered and pooled from 5 individual rinses, and serial dilutions were made for examination of Campylobacter (42°C, 48 h), E. coli (37°C, 24 h), psychrophiles (plate count agar, 4°C, 7 d), and total aerobic bacterial populations (plate count agar, 37°C, 24 h). Campylobacter counts for all treatments were reduced during the 14-d storage period but the 100% O(2) treatment caused a significantly (P < 0.05) greater reduction than the other gas treatments. For the psychrophiles, storage in air resulted in the greatest growth after 14 d, with reduced psychrophilic growth allowed by either O(2) or the modified atmosphere packaging mixture (not different from each other). Of the treatments evaluated, CO(2) allowed the least growth of psychrophiles. Proliferation of E. coli and aerobes was the greatest when packaged in air after 14 d, whereas CO(2) packaging resulted in the least growth. These data suggest that storage under O(2) may reduce Campylobacter recovery and slow psychrophile and aerobe recovery following storage.


An Investigation of Dynamic Cerebral Autoregulation in Adolescent Concussion.
Although cerebrovascular impairments are believed to contribute to concussion symptoms, little information exists regarding brain vasomotor control in adolescent concussion, particularly autoregulatory control that forms a fundamental response mechanism during changes in blood pressure. This research tested the hypothesis that adolescent concussion is marked by impaired dynamic cerebral autoregulation. Nineteen concussed adolescents (15 ± 2 yr, 13 females) and 18 healthy controls (15 ± 2 yr, 9 females) completed two sit-to-stand trials. Brachial artery blood pressure and cerebral blood flow velocity in the right middle cerebral artery were measured continuously. Dynamic rate of regulation was calculated as the rate of change in cerebrovascular resistance relative to the change in arterial blood pressure. The concussed adolescents were followed through their rehabilitation for up to 12 wk. At the first visit, the concussed adolescents demonstrated reduced rate of regulation compared with the healthy controls (0.12 ± 0.04 vs 0.19 ± 0.06 s, P ≤ 0.001). At the concussed adolescents final visit, after symptom resolution, the rate of regulation improved to levels that were not different from the healthy controls (n = 9; 0.15 ± 0.08 vs 0.19 ± 0.06 s, P= 0.06). Two distinct groups were observed at the final visit with some individuals experiencing recovery of dynamic cerebral autoregulation and others showing no marked change from the initial visit. Adolescents demonstrate an impairment in dynamic cerebral autoregulation after concussion that improves along with clinical symptoms in some individuals and remains impaired in others despite symptom resolution.


An epidemic of depression or the medicalization of distress?
The syndrome of major depression is widely regarded as a specific mental illness that has increased to the point where it will be second in the International Burden of Disease ranking by 2020. This article examines the assumption that major depression is a specific illness, that it is rapidly increasing, and that a medical response is justified. I argue that major depression is not a natural entity and does not identify a homogenous group of patients. The apparent increase in major depression results from: confusing those who are ill with those who share their symptoms; the surveying of symptoms out of context; the benefits that accrue from such a diagnosis to drug companies, researchers, and clinicians; and changing social constructions around sadness and distress. Standardized medical treatment of all these individuals is neither possible nor desirable. The major depression category should be replaced by a clinical staging strategy that acknowledges the continuous distribution of depressive symptoms. Trials that test social and lifestyle treatments as well as drugs and cognitive behavioral therapy across different levels of severity, chronicity, and symptom patterns might lead to the development of a coherent evidence-based stepped treatment model.


[Study on the effect of extraction behaviour of molybdenum (V) thiocyanate complex in the dimethyl sulfoxide and water system by spectrophotometry].
In this paper the effect of petroleum sulfoxide-carbon tetrachloride used as extractant on the extraction behaviour of molybdenum (V) thiocyanate complex at different concentration of dimethyl sulfoxide and water system is studied by spectrophotometry. The mixture ratio of extraction is directly calculated using spectrophotometric data. Functional relation of mixture ratio and concentration of thiocyanate in mixed solution is discussed. By increasing the percent of volume of dimethyl sulfoxide in mixed solution, the effects of mixture ratio and percentage of extraction were studied. The experimental results were explained. It shows that the extraction system of MoO (SCN)3 has an application value.


Minimum important change values for pain and disability: which is the best to identify a meaningful response in patients with chronic nonspecific low back pain?
To examine the association between different minimum important change (MIC) values for pain and disability and a successful response in global perception of improvement in patients with chronic nonspecific low back pain (CNLBP). A prospective cohort study was conducted. At baseline, all participants completed a sociodemographic and clinical questionnaire, the Numeric Pain Rating Scale and the Quebec Back Pain Disability Scale (QBPDS). After a physiotherapy program, the Global Perceived Effect Scale (GPES) was completed together with pain and disability measures. The association of the different literature MIC values for pain and disability with a successful response on the GPES was analyzed using logistic regression models. The discrimination power, sensitivity, specificity and predictive values were computed. A total of 183 patients with CNLBP participated in this study. A reduction of 30% on the QBPDS (OR = 7.8; area under the curve = 0.73; sensitivity = 0.72; specificity = 0.76) most accurately identified patients who perceived a global improvement on the GPES. Composite criteria using both pain and disability MIC values presented high odds ratios and specificity values, but failed to identify patients who perceived a meaningful improvement. A 30% reduction on the QBPDS is recommended to identify patients with CNLBP who achieve a clinical improvement with physiotherapy treatment.


Multifactorial analysis of biliary infection after percutaneous transhepatic biliary drainage treatment of malignant biliary obstruction.
The symptoms of patients with malignant biliary obstruction (MBO) could be effectively alleviated with percutaneous transhepatic biliary drainage (PTBD). Postoperative infections were considered as challenging issues for clinicians. In this study, the risk factors of biliary infection in patients after PTBD were analyzed. From July 2003 to September 2010, 694 patients with MBO received PTBD treatment. Bile specimens were also collected during PTBD. All relevant information and results were collected, including gender, age, obstruction time, types of primary tumor, sites of obstruction, drainage style, tumor stage, hemoglobin, phenotype of peripheral blood monocyte (Treg), total bilirubin, direct bilirubin, albumin, Child-Pugh score, and results of bile bacterial culture. For the 694 patients involved in this study, 485 were male and 209 were female, with a mean age of 62 years (ranged 38-78 years). For the bile culture, 57.1% patients (396/649) were negative and 42.9% patients showed positive (298/694), and then 342 strains of microorganism were identified. The risk factors of biliary system infection after PTBD included: age (χ2 = 4.621, P = 0.032), site of obstruction (χ2 = 17.450, P < 0.001), drainage style (χ2 = 14.452, P < 0.001), tumor stage (χ2 = 4.741, P = 0.029), hemoglobin (χ2 = 3.914, P = 0.048), Child-Pugh score (χ2 = 5.491, P = 0.019), phenotype of peripheral blood monocyte (Treg) (χ2 = 5.015, P = 0.025), and results of bile bacterial culture (χ2 = 65.381, P < 0.001). Multivariate analysis suggested that high-risk factors were drainage style, Child-Pugh score, and results of bile culture. The risk factors of biliary infection after PTBD included: age, site of obstruction, drainage style, tumor stage, hemoglobin, Child-Pugh score, phenotype of peripheral blood monocyte (Treg), and results of bile culture. It was further concluded that drainage style, Child-Pugh score, and results of bile culture were independent risk factors.


cGMP activates a pH-sensitive leak K+ current in the presumed cholinergic neuron of basal forebrain.
In an earlier study, we demonstrated that nitric oxide (NO) causes the long-lasting membrane hyperpolarization in the presumed basal forebrain cholinergic (BFC) neurons by cGMP-PKG-dependent activation of leak K+ currents in slice preparations. In the present study, we investigated the ionic mechanisms underlying the long-lasting membrane hyperpolarization with special interest in the pH sensitivity because 8-Br-cGMP-induced K+ current displayed Goldman-Hodgkin-Katz rectification characteristic of TWIK-related acid-sensitive K+ (TASK) channels. When examined with the ramp command pulse depolarizing from -130 to -40 mV, the presumed BFC neurons displayed a pH-sensitive leak K+ current that was larger in response to pH decrease from 8.3 to 7.3 than in response to pH decrease from 7.3 to 6.3. This K+ current was similar to TASK1 current in its pH sensitivity, whereas it was highly sensitive to Ba(2+), unlike TASK1 current. The 8-Br-cGMP-induced K+ currents in the presumed BFC neurons were almost completely inhibited by lowering external pH to 6.3 as well as by bath application of 100 microM Ba(2+), consistent with the nature of the leak K+ current expressed in the presumed BFC neurons. After 8-Br-cGMP application, the K+ current obtained by pH decrease from 7.3 to 6.3 was larger than that obtained by pH decrease from pH 8.3 to 7.3, contrary to the case seen in the control condition. These observations strongly suggest that 8-Br-cGMP activates a pH- and Ba(2+)-sensitive leak K+ current expressed in the presumed BFC neurons by modulating its pH sensitivity.


Microgastrinae (Hymenoptera: Braconidae) of Reunion Island: a catalogue of the local species, including 18 new taxa and a key to species.
Microgastrine wasps (Hymenoptera: Braconidae) are primary parasitoids of Lepidoptera. Some of them parasitise major economic pests and have been largely used for biocontrol programs. We revise here the fauna of Reunion Island: 34 species were recorded, belonging to 13 genera. One genus and 18 species are newly described: Dodogaster gen. nov, Apanteles minatchy sp. nov., A. pashmina sp. nov., A. romei sp. nov., Cotesia xavieri sp. nov., Dolichogenidea ashoka sp. nov., D. broadi sp. nov., D. lumba sp. nov., D. uru sp. nov., D. villemantae sp. nov., Distatrix yunae sp. nov., Dodogaster grangeri sp. nov., Exoryza safranum sp. nov., Glyptapanteles chidra sp. nov., Nyereria ganges sp. nov., N. mayurus sp. nov., Parapanteles covino sp. nov., P. darignac sp. nov. and Wilkinsonellus narangahus sp. nov.. On the remaining 16 species, 12 are new distribution records. Finally, Glyptapanteles antsirabensis (Granger) comb. nov., G. ficus (Granger) comb. nov., G. subandinus (Blanchard) comb. nov., and Venanides curticornis (Granger) comb. nov. are reassigned from the traditionally defined Apanteles genus to these respective genera. A key to all genera and species is provided.


Feasibility of Transfer Learning from Finger PPG to In-Ear PPG.
The success of deep learning methods has enabled many modern wearable health applications, but has also highlighted the critical caveat of their extremely data hungry nature. While the widely explored wrist and finger photoplethysmography (PPG) sites are less affected, given the large available databases, this issue is prohibitive to exploring the full potential of novel recording locations such as in-ear wearables. To this end, we assess the feasibility of transfer learning from finger PPG to in-ear PPG in the context of deep learning for respiratory monitoring. This is achieved by introducing an encoder-decoder framework which is set up to extract respiratory waveforms from PPG, whereby simultaneously recorded gold standard respiratory waveforms (capnography, impedance pneumography and air flow) are used as a training reference. Next, the data augmentation and training pipeline is examined for both training on finger PPG and the subsequent fine tuning on in-ear PPG. The results indicate that, through training on two large finger PPG data sets (95 subjects) and then retraining on our own small in-ear PPG data set (6 subjects), the model achieves lower and more consistent test error for the prediction of the respiratory waveforms, compared to training on the small in-ear data set alone. This conclusively demonstrates the feasibility of transfer learning from finger PPG to in-ear PPG, leading to better generalisation across a wide range of respiratory rates.


Tissue lesions caused by microplanar beams of synchrotron-generated X-rays in Drosophila melanogaster.
To examine tissue lesions caused by microplanar beams of synchrotron-generated X-rays in Drosophila melanogaster using stereomicroscopy, light and electron microscopy. Pupae were irradiated by 25-microm wide, 1.175 mm-high parallel microplanes at 100 microm on-centre intervals, at 20, 24, 32, 36, 48 or 72 h of development, with absorbed doses per microplane between 75 and 3,000 Gy. Transverse or longitudinal irradiation with in-slice absorbed doses of 75 or 375 Gy caused no recognizable effects. All pupae irradiated at or after 48 h developed normally. Conversely, the development to adulthood was delayed in 90% of pupae irradiated at 24h with doses of 750 Gy. However, neither those pupae nor adults that hatched after pupal irradiation at 48 and 72 h displayed morphological changes. Pupae exposed at 48 h of development to 3,000 Gy developed into adults with sharply delimited lesions in the irradiated microplanes of the compound eye or the cuticle of wings and abdomen. Post-mitotic eukaryotic cells can survive radiation doses of 3,000 Gy largely undamaged, even at the beginning of the terminal morphogenesis. The extremely sharp delimitation between damaged tissue microplanes and adjacent intact tissues may be relevant for future perspectives of radiosurgery.


Safety data and withdrawal of hepatotoxic drugs.
The occurrence of drug induced liver injury (DILI) is the most common reason of post-marketing withdrawals. DILI in humans is difficult to predict using in vitro cytotoxicity screening and animal studies. A review of hepatotoxicity data was performed with the aim of identifying relevant factors that could have predicted the occurrence of serious DILI. The drugs withdrawn from the market due to hepatotoxicity in Europe and/or in USA either by marketing authorization holders or by Regulatory agencies from 1997 to 2016 were selected. The liver safety data and the withdrawal decisions were identified from a search within the European medicine agency (EMA) website, the Food and drug administration (FDA) orange book and PubMed®. From 1997 to 2016, eight drugs were withdrawn from the market for hepatotoxicity reason: tolcapone, troglitazone, trovafloxacin, bromfenac, nefazodone, ximelagatran, lumiracoxib and sitaxentan. The safety data suggest that while liver test abnormalities have been detected during clinical trials, other relevant factors leading to the discontinuation of these drugs have been identified: lack of predictability of animal models, inappropriate liver function test, non-compliance with drug treatment, less attention paid to rare adverse drug reactions, unpredictable occurrence and irreversible outcome of liver toxicity. Several relevant factors may contribute to an inadequate risk management leading to the discontinuation of the drugs. Preclinical safety data are not sufficient to allow early prediction of DILI in humans and post-marketing safety monitoring and signal detection still should be used to identify potential serious cases of DILI. However, it seems that changes in Pharmacovigilance legislation with a closer management of drug safety may have contributed to the improvement of the risk minimization.


Compressed-Sensing Accelerated 3-Dimensional Magnetic Resonance Cholangiopancreatography: Application in Suspected Pancreatic Diseases.
The aims of this study were to prospectively evaluate image quality, duct visibility, and diagnostic performance in duct-related pathologies of compressed-sensing (CS) accelerated 3-dimensional (3D) magnetic resonance cholangiopancreatography (MRCP) prototype protocols and compare these with those of conventional 3D MRCP protocol in patients with suspected pancreatic diseases. The institutional review board approved this prospective study and all patients provided written informed consent. A total of 80 patients (47 men and 33 women; median age, 57 years; age range, 24-87 years) underwent 3D MRCP at 3.0 T. Three protocols were performed in each patient in random order: CS breath-hold (BH) protocol, CS navigator-triggered (NT) protocol, and conventional NT protocol. The acquisition time of each protocol was recorded. Image quality and duct visibility were independently rated in random order on a 5-point scale by 2 radiologists, who were blinded to the protocols. Receiver operating characteristic curves were generated, and area under the curve (Az value) was used to compare the diagnostic performance of each protocol in duct-related pathologies. Acquisition time was 17 seconds for the CS-BH and 134.1 ± 33.5 seconds for the CS-NT protocol, both being significantly shorter than the conventional NT protocol (364.7 ± 78.4 seconds; both P < 0.01). The CS-BH MRCP protocol showed significantly less artifacts compared with the CS-NT and conventional NT protocols (both P < 0.01). Visualization of bile ducts was comparable in all 3 protocols, whereas CS-NT and conventional NT MRCP depicted pancreatic duct better than CS-BH MRCP did (for proximal, middle, and distal segment; all P < 0.05). Compressed-sensing-NT MRCP had the highest diagnostic performance for detecting ductal anomalies, long-segment duct stenosis, abnormal branch ducts, and communication between cystic lesion and pancreatic duct (mean Az value, 0.943-0.983). Compressed-sensing MRCP is feasible in patients with suspected pancreatic diseases. Compressed-sensing-NT MRCP demonstrated superior diagnostic accuracy for duct-related pathologies.


Bone speed of sound, bone turnover and IGF-I in adolescent synchronized swimmers.
This pilot study compared bone speed of sound (SOS), bone turnover and insulin-like growth factor 1 (IGF-1) between 20 Caucasian, postmenarcheal, adolescent synchronized swimmers (SS) and 20 aged- and maturity-matched nonswimmers (NS). Daily dietary intake and physical activity levels were also assessed. Bone SOS was measured by quantitative ultrasound. Blood samples were analyzed for osteocalcin, cross-linked N-teleopeptide of type I collagen (NTx), IGF-I and 25-OH vitamin D. Although no differences in bone SOS or turnover markers were observed between groups, the lower IGF-1 and vitamin D intake found in synchronized swimmers, in combination with their higher strenuous activity levels, should be further explored.