Mineralocorticoid Receptors in the Pathophysiology of Vascular Inflammation and Atherosclerosis.
Atherosclerosis is a chronic inflammatory disease of the vasculature that causes significant morbidity and mortality from myocardial infarction, stroke, and peripheral vascular disease. Landmark clinical trials revealed that mineralocorticoid receptor (MR) antagonists improve outcomes in cardiovascular patients. Conversely, enhanced MR activation by the hormone aldosterone is associated with increased risk of MI, stroke, and cardiovascular death. This review summarizes recent advances in our understanding of the role of aldosterone and the MR in the pathogenesis of vascular inflammation and atherosclerosis as it proceeds from risk factor-induced endothelial dysfunction and inflammation to plaque formation, progression, and ultimately rupture with thrombosis, the cause of acute ischemia. The role of the MR in converting cardiac risk factors into endothelial dysfunction, in enhancing leukocyte adhesion and infiltration into the vasculature, in promoting systemic inflammation and vascular oxidative stress, and in plaque destabilization and thrombosis are discussed. A greater understanding of the mechanisms by which the MR promotes atherosclerosis has substantial potential to identify novel treatment targets to improve cardiovascular health and decrease mortality.


Prevalence and correlates of obsessive-compulsive disorder and subthreshold obsessive-compulsive disorder among college students in Kerala, India.
There are scarce data on the prevalence of adult obsessive-compulsive disorder (OCD) in India. The aim was to study the point prevalence of OCD and subthreshold OCD and its psychosocial correlates among college students in the district of Ernakulam, Kerala, India. A cross-sectional survey of 5784 students of the age range of 18-25 years from 58 colleges was conducted. Students were self-administered the OCD subsection of the Clinical Interview Schedule-Revised, the Composite International Diagnostic Interview for obsessive-compulsive symptoms (OCSs), and other relevant instruments to identify OCD, subthreshold OCD, and related clinical measures. The point prevalence of OCD and subthreshold OCD was determined. Categorical variables were compared using Chi-square/Fisher's exact tests as necessary. Differences between means were compared using the ANOVA. The point prevalence of OCD was 3.3% (males = 3.5%; females = 3.2%). 8.5% students (males = 9.9%; females = 7.7%) fulfilled criteria of subthreshold OCD. Taboo thoughts (67.1%) and mental rituals (57.4%) were the most common symptoms in OCD subjects. Compared to those without obsessive-compulsive symptoms (OCSs), those with OCD and subthreshold OCD were more likely to have lifetime tobacco and alcohol use, psychological distress, suicidality, sexual abuse, and higher attention-deficit/hyperactivity disorder symptom scores. Subjects with subthreshold OCD were comparable to those with OCD except that OCD subjects had higher psychological distress scores and academic failures. OCD and subthreshold OCD are not uncommon in the community, both being associated with significant comorbidity. Hence, it is imperative that both are identified and treated in the community because of associated morbidity.


MRI capture of intermittent ventriculomegaly in a patient with ventriculo-peritoneal shunt.
Intermittent change in ventricular size in patients with ventriculo-peritoneal shunts is a recognised complication but definitive imaging evidence is rare. We report a 3 years old boy with a medullary astrocytoma and ventriculo-peritoneal shunt placement who demonstrated intermittent ventriculomegaly during a single MRI scan.


3D printing from transesophageal echocardiography for planning mitral paravalvular leak closure - feasibility study.
Transcatheter closure of paravalvular leak (PVL) is still a demanding procedure due to the complex anatomy of PVL channels and risk of interference between the implanted occluder and surrounding structures. Efforts are made to improve procedural outcomes in transcatheter structural heart interventions by establishing treatment strategy in advance with the use of 3D-printed physical models based on data obtained from cardiac computed tomography (CT) studies. In this feasibility study 3D printing of PVL models based on data recorded during transesophageal echocardiography (TEE) examinations was evaluated. 3D-TEE data of patients with significant PVL around mitral valve prostheses were used to prepare 3D models. QLab software was used to export DICOM images in Cartesian DICOM format of each PVL with the surrounding tissue. Image segmentation was performed in Slicer, a free, open-source software package used for imaging research. Models were printed to actual size with the Polyjet printer with a transparent, rigid material. We measured dimensions of PVLs both in TEE recordings and printed 3D models. The results were correlated with sizes of occluding devices used to close the defects. In 7 out of 8 patients, there was concordance between procedurally implanted occluders and pre-procedurally matched closing devices based on 3D-printed models. 3D-printing from 3D-TEE is technically feasible. Both shape and location of PVLs are preserved during model preparation and printing. It remains to be tested whether 3D printing would improve outcomes of percutaneous PVL closure.


Nucleotide sequence of mitochondrial CO I and ribosomal ITS II genes of Opisthorchis viverrini in northeast Thailand.
The mitochondrial cytochrome c oxidase subunit I (CO I) gene and the second internal transcribed spacer region (ITS II) gene of Opisthorchis viverrini were compared among O. viverrini from various areas in northeast Thailand. The nucleotide sequences of partial CO I gene (417 bp) of O. viverrini differed among O. viverrini originated from Ubon Ratana, Leongpleuy, Ban Phai, Maha Sarakham, and Chatturat. These intraspecific variations were classified into 5 patterns but no area-specific pattem was observed. Amino acid sequence deduced from the nucleotide sequences of these genes was identical. Nucleotide sequences of a region of the O. viverrini ITS II gene (296 bp) from different areas were identical. However, they were different from those of Clonorchis sinensis, Haplorchis taichui, H. pumilio, Fasciola gigantica, Echinostoma malayanum and Centrocestus sp..


Simvastatin-induced rhabdomyolysis and acute renal injury.
Simvastatin is one of the most commonly prescribed CoA reductase inhibitors. The safety profile of this drug has been widely discussed in the medical and consumer advocacy communities. Like other statins, simvastatin can cause a serious and potentially life-threatening complication: rhabdomyolysis. We describe a case of simvastatin-induced rhabdomyolysis complicated by acute renal failure requiring urgent hemodialysis. The relative safety of simvastatin compared to other HMG-CoA reductase inhibitors and the conditions that can potentiate its toxicity are discussed. The clinical features of rhabdomyolysis, and subsequent acute renal failure, and their treatment modalities are presented.


A case of calcific retropharyngeal tendinitis: the significance of an early diagnosis.
The clinical presentation of calcific retropharyngeal tendinitis, a rare entity, can mimic more serious disorders. We describe the case of a 35-year-old man who was referred to us for evaluation of a suspected retropharyngeal abscess. At presentation, the patient reported severe cervical pain and stiffness. He exhibited mild fever, torticollis, and a moderately elevated white blood count; no swelling of the retropharyngeal wall was observed. Based on the results of plain radiography and computed tomography (CT), we diagnosed the patient with calcific retropharyngeal tendinitis. He was treated with a 7-day course of a nonsteroidal anti-inflammatory drug and a 3-day course of a steroid, and he recovered well. We suggest that the true incidence of calcific retropharyngeal tendinitis is actually higher than what is generally believed because this diagnosis is frequently missed. Contrast-enhanced CT can aid in diagnosing calcific retropharyngeal tendinitis. CT should be performed in patients who present with nonspecific symptoms such as severe neck pain, sore throat, odynophagia, and mild fever.


Lipase degradation of plasticized polyvinyl chloride endotracheal tube surfaces to create nanoscale features.
Polyvinyl chloride (PVC) endotracheal tubes (ETTs) nanoetched with a fungal lipase have been shown to reduce bacterial growth and biofilm formation and could be an inexpensive solution to the complex problem of ventilator-associated pneumonia (VAP). Although bacterial growth and colonization on these nanoetched materials have been well characterized, little is known about the mechanism by which the fungal lipase degrades the PVC and, thus, alters its properties to minimize bacteria functions. This study used X-ray photoelectron spectroscopy (XPS) and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) to better describe the surface chemistry of both unetched and lipase nanoetched PVC ETT. ATR-FTIR analysis of the unetched and treated surfaces showed a similar presence of a plasticizer. This was confirmed by XPS analysis, which showed an increase of carbon and the presence of oxygen on both unetched and nanoetched surfaces. A quantitative comparison of the FTIR spectra revealed significant correlations (Pearson's correlation, R=0.997 [R2=0.994, P<0.001]) between the unetched and nanomodified PVC ETT spectra, demonstrating similar surface chemistry. This analysis showed no shifting or widening of the bands in the spectra and no significant changes in the intensity of the infrared peaks due to the degradation of the plasticizer by the fungal lipase. In contrast, results from this study did demonstrate significantly increased nanoscale surface features on the lipase etched compared to non-etched PVC ETTs. This led to a change in surface energetics, which altered ion adsorption to the ETTs. Thus, these results showed that PVC surfaces nanoetched with a 0.1% lipase solution for 48 hours have no significant change on surface chemistry but do significantly increase nanoscale surface roughness and alters ion adsorption, which suggests that the unique properties of these materials, including their previously reported ability to decrease bacterial adhesion and growth, are due to the changes in the degree of the nanoscale roughness, not changes in their surface chemistry.


Bergenin, Acting as an Agonist of PPARγ, Ameliorates Experimental Colitis in Mice through Improving Expression of SIRT1, and Therefore Inhibiting NF-κB-Mediated Macrophage Activation.
Bergenin, isolated from the herb of Saxifraga stolonifera Curt. (Hu-Er-Cao), has anti-inflammatory, antitussive and wound healing activities. The aim of the present study was to identify the effect of bergenin on experimental colitis, and explored the related mechanisms. Our results showed that oral administration of bergenin remarkably alleviated disease symptoms of mice with dextran sulfate sodium (DSS)-induced colitis, evidenced by reduced DAI scores, shortening of colon length, MPO activity and pathologic abnormalities in colons. Bergenin obviously inhibited the mRNA and protein expressions of IL-6 and TNF-α in colon tissues, but not that of mucosal barrier-associated proteins occludin, E-cadherin and MUC-2. In vitro, bergenin significantly inhibited the expressions of IL-6 and TNF-α as well as nuclear translocation and DNA binding activity of NF-κB-p65 in lipopolysaccharide (LPS)-stimulated peritoneal macrophages and RAW264.7 cells, which was almost reversed by addition of PPARγ antagonist GW9662 and siPPARγ. Subsequently, bergenin was identified as a PPARγ agonist. It could enter into macrophages, bind with PPARγ, promote nuclear translocation and transcriptional activity of PPARγ, and increase mRNA expressions of CD36, LPL and ap2. In addition, bergenin significantly up-regulated expression of SIRT1, inhibited acetylation of NF-κB-p65 and increased association NF-κB-p65 and IκBα. Finally, the correlation between activation of PPARγ and attenuation of colitis, inhibition of IL-6 and TNF-α expressions, NF-κB-p65 acetylation and nuclear translocation, and up-regulation of SIRT1 expression by bergenin was validated in mice with DSS-induced colitis and/or LPS-stimulated macrophages. In summary, bergenin could ameliorate colitis in mice through inhibiting the activation of macrophages via regulating PPARγ/SIRT1/NF-κB-p65 pathway. The findings can provide evidence for the further development of bergenin as an anti-UC drug, and offer a paradigm for the recognization of anti-UC mechanisms of compound with similar structure occurring in traditional Chinese medicines.


What is the evidence for the use of acupuncture as an intervention for symptom management in cancer supportive and palliative care: an integrative overview of reviews.
This study aims to systematically appraise the evidence for the use of acupuncture for symptom management in cancer and supportive care and to identify recommendations for clinical practice and future research. A systematic search was carried out to identify reviews of the use of acupuncture in cancer supportive and palliative care, using MEDLINE, EMBASE, CINAHL, Web of Science, Cochrane Library, British Nursing Index, Index to Theses, Dissertations and Theses (via Proquest) and NHS evidence. Search terms included: acupuncture, cancer and symptoms. Data were extracted for analysis. Reviews were assessed for quality using a five-item checklist but were not excluded from the review on grounds of quality, in order to include a comprehensive scope of the subject. Seventeen reviews were included in the review. Evidence was found for the use of acupuncture for treatment-related nausea and vomiting. Benefit was reported for other cancer-related symptoms, including pain, fatigue, hot flushes, xerostomia, dyspnoea and anxiety. Reviewers found a paucity of rigorous trials and heterogeneity of populations, interventions, controls and outcome measures, which challenge the process of systematic review and meta-analysis. Acupuncture should be considered for symptom management where there are limited treatment options, using current peer-reviewed guidelines and clinical reasoning. Much of the primary research reported in reviews is innovative and indicates potential benefit for people with cancer-related symptoms. The complexity of acupuncture as an intervention needs to be acknowledged in future research designs and when reviewing research findings. An iterative approach using adequate interventions, appropriate outcome measures and adherence to reporting standards is required to evaluate the efficacy of acupuncture in cancer supportive and palliative care.


[Routines for first prescription of oral contraceptives].
There is an increasing awareness about the risk of thromboembolic disease caused by combination oral contraceptives. This study assesses routines associated with prescription of an oral contraceptive, with an emphasis on venous thromboembolic disease. A questionnaire requesting information about medical history, examinations, and general routines when an oral contraceptive was prescribed for the first time was sent to general practitioners, public health nurses and midwives in two Norwegian counties in 2008. A slightly different questionnaire was distributed to a group of female medical students. They were requested to describe the queries, procedures and information they were subjected to when oral contraceptives was first prescribed for themselves. In total, 99-100% of the prescribers reported that they asked about smoking habits and venous thromboembolic disease in the family. 94% of the doctors and 100% of the public health nurses/midwives informed about the risk of venous thromboembolic disease (p=0.028). The students reported that they had been asked, examined and informed less often than that reported by health professionals. 54% of the physicians and 11% of the public health nurses /midwives most often prescribed third generation oral contraceptives (p < 0.001). Doctors, midwives and public health nurses seem to examine and inform their patients thoroughly about the risk of venous thromboembolic complications when prescribing combination oral contraceptives for the first time. Public health nurses and midwives seem to have a more rational prescription pattern of combined oral contraceptives than doctors.


Predictors of post-discharge seizures in children with traumatic brain injury.
In traumatic brain injury (TBI), hyperglycemia and hypothermia are thought to be associated with poor outcomes, but have not been systematically studied in children. Thus, our aim was to evaluate whether serum glucose and temperature at admission, among other clinical variables, were associated with need for post hospital-discharge seizure medication in children diagnosed with TBI. We performed a retrospective study of 1814 children who were diagnosed with TBI at a tertiary pediatric hospital. Serum glucose levels at admission and temperature at initial presentation, 12, and 24 h were collected. Ongoing seizure activity was defined as discharge prescription of a seizure-modifying medication. We identified 121 patients with need for continued seizure medications, and 80 patients expired. Independent predictors of prolonged seizures included serum glucose levels above 140 mg/dl (p < 0.003) and 199 mg/dl (p < 0.001), hypothermia (<35 °C), subdural hematoma (p < 0.001), midline shift (p < 0.001), and > 1% temperature change in the first 24 h (p < 0.001). Multivariate regression adjusting for GCS revealed that bilateral bleed (p = 0.008), body-temperature instability (p = 0.026), subdural hematoma (p < 0.001), and mechanism of injury (p = 0.007) were predictive of prolonged seizure activity. In summary, we conclude that body temperature may be playing a more significant role than glycemic control in propensity for ongoing seizure activity in children sustaining TBI.


Sonography of fetal midgut herniation: normal size criteria and correlation with crown-rump length.
Forty-eight fetuses were prospectively evaluated to (1) determine the normal size range of herniated midgut and (2) correlate sonographically the timing of midgut herniation with CRL. All fetuses of CRL 38 mm or less, and two of six fetuses with a CRL of 40 to 42 mm, demonstrated midgut herniation. No fetuses with a CRL greater than 44 mm had this finding. The cord containing midgut increased roughly from 4 to 7 mm, in maximum dimensions, for CRL of 19 to 41 mm. An anterior abdominal wall mass greater than 7 mm at any CRL, or of any size in a fetus of CRL greater than 44 mm, is suggestive of a fetal anomaly. Alternatively, a cord base "mass" within the 4 to 7 mm range for a CRL of 19 to 44 mm can be considered normal and not to require any follow-up.


Prediction of two-sample (99m)Tc-diethylene triamine pentaacetic acid plasma clearance from single-sample method.
To develop an equation to predict dual plasma sample method (DPSM) (99m)Tc-diethylene triamine pentaacetic acid ((99m)Tc-DTPA) plasma clearance from single plasma sample method (SPSM), and to clarify the condition in which DPSM can be substituted by SPSM in measurement of glomerular filtration rate (GFR). Patients with chronic kidney disease (CKD) were selected. Watson modified Christensen and Groth equation was used to calculate (99m)Tc-DTPA plasma clearance by SPSM (sGFR). The equation recommended by the Nephrourology Committee of the Society of Nuclear Medicine was used to calculate (99m)Tc-DTPA plasma clearance by DPSM (tGFR) in each patient. The difference between sGFR and tGFR was expressed as percent of the average of these two methods, and tGFR was predicted from sGFR. Plasma creatinine was measured by the kinetic picrate method, and GFR estimated by abbreviated modification of diet in renal disease (MDRD) equation (aGFR) and Cockcroft-Gault equation (cGFR) were evaluated as criteria in selection of DPSM and SPSM. Three hundred and sixty-nine patients with CKD were selected (208 male and 161 female). The average age and body weight were 51.4 +/- 15.5 years and 67.2 +/- 12.5 kg, respectively. The causes of CKD were glomerular disease, renal arterial stenosis, chronic tubulointerstitial disease, and other causes or causes unknown. The average tGFR was 62.9 +/- 36.5 ml/min/1.73 m2, ranging from 1-180 ml/min/1.73 m2. sGFR was significantly correlated with tGFR (r = 0.9194, p < 0.001), but widely scattered when tGFR <30 ml/min/1.73 m2; in contrast, then tGFR was > or =30 ml/min/1.73 m2, the difference was constant (-1.1%, 95% confidence interval -18.3%, 16.1%), and tGFR could be predicted from sGFR using the equation: predicted tGFR (ml/min/1.73 m2) = 7.4244 + 0.7318 x sGFR + 0.0022 x sGFR2 (n = 299, r2 = 0.9428, p < 0.001), and the difference decreased to 0.1%, 95% confidence interval (-15.8%, 16.0%). aGFR was better than cGFR in diagnosis of tGFR <30 ml/min/1.73 m2, the diagnostic sensitivity of a cut off value of aGFR = 45 ml/min/1.73 m2 was 91.8%, and recommended as a criterion in the selection of DPSM and SPSM. When GFR > or =30 ml/min/1.73 m2, tGFR can be predicted from sGFR, which will simplify the reference GFR measurement in clinical trials. sGFR becomes widely scattered when tGFR is less than 30 ml/min/1.73 m2. To obtain reliable reference GFR values, it is recommended that DPSM be used in clinical trials when aGFR is less than 45 ml/min/1.73 m2.


Guillaume des Moustiers' treatise on the armillary instrument (1264) and the practice of astronomical observation in medieval Europe.
This article is devoted to a thirteenth-century Latin text on how to construct, set up, and use a version of the so-called armillary instrument (instrumentum armillarum), which was first described in Ptolemy's Almagest as a tool for measuring ecliptic coordinates. Written in 1264 by Guillaume des Moustiers, bishop of Laon, this hitherto unstudied Tractatus super armillas survives in a single manuscript, where it is accompanied by a copious set of glosses. The text and its glosses jointly offer an unusually detailed account of the instrument's material aspects and methods of assembly. In addition, they reflect a keen awareness of the potential sources of error that may arise in the context of astronomical observation, while making suggestions on how these errors may be minimized or avoided. The Tractatus super armillas accordingly is a valuable source on the observational side of medieval European astronomy, which has often been minimized in modern historical accounts.


GAMMA: a tool for the rapid identification, classification and annotation of translated gene matches from sequencing data.
Tools used to identify genes in microbial sequences using a reference database generally report matches as a percent identity, which can be difficult to interpret in cases with <100% sequence identity, as changes to specific amino acids can have dramatic effects on protein function, such as when they occur in substrate binding regions or enzyme active sites, which in turn can have dramatic effects on phenotypes like antimicrobial resistance or virulence. Here, we present GAMMA, an open-source tool for Gene Allele Mutation Microbial Assessment, which uses protein coding-level identity to make gene calls from any gene database and generates a classification (e.g. mutant, truncation) and translated annotation (e.g. Y190S mutation, truncation at residue 110) for these calls. GAMMA accurately called antimicrobial resistance genes from a large set of genomes faster than three other tools. It can also be used with any gene database, as we demonstrated by identifying virulence genes in the same genome set. Because of its speed and flexibility, GAMMA can be used to rapidly find and annotate any gene matches of interest in microbial sequencing data. GAMMA is freely available as a Bioconda package (https://bioconda.github.io/recipes/gamma/README.html) and as a command line script (https://github.com/rastanton/GAMMA). Supplementary data are available at Bioinformatics online.


Residues in the GluN1 C-terminal domain control kinetics and pharmacology of GluN1/GluN3A N-methyl-d-aspartate receptors.
N-methyl-d-aspartate (NMDA) receptors assembled from GluN1 and GluN3 subunits are unique in that they form glycine-gated excitatory channels that are insensitive to glutamate and NMDA. Alternative splicing of the GluN1 subunit mRNA results in eight variants with regulated expression patterns and post-translational modifications. Here we investigate the role of residues in the GluN1 C-terminal alternatively spliced cassettes in receptor gating and modulation. We measured whole-cell currents from recombinant GluN1/GluN3A receptors expressed in HEK293 cells that differed in the sequence of their GluN1 C-terminal tail. We found that these residues controlled the level of steady-state activity and the degree to which activity was facilitated by zinc and protons. Further, we found that the phosphorylation status of sites specific to certain variants can also modulate channel activity. Based on these results we suggest that GluN1 C-terminal domain splicing may confer cell-specific and activity-dependent regulation onto the level and pharmacologic sensitivity of GluN1/GluN3A currents.


Telmisartan Inhibits Cell Proliferation and Tumor Growth of Esophageal Squamous Cell Carcinoma by Inducing S-Phase Arrest In Vitro and In Vivo.
Esophageal squamous cell carcinoma (ESCC) is the most common primary esophageal malignancy. Telmisartan, an angiotensin II type 1 (AT1) receptor blocker (ARB) and a widely used antihypertensive, has been shown to inhibit proliferation of various cancer types. This study evaluated the effects of telmisartan on human ESCC cell proliferation in vitro and in vivo and sought to identify the microRNAs (miRNAs) involved in these antitumor effects. We examined the effects of telmisartan on three human ESCC cell lines (KYSE150, KYSE180, and KYSE850). Telmisartan inhibited proliferation of these three cell lines by inducing S-phase arrest, which was accompanied by decreased expression of cyclin A2, cyclin-dependent kinase 2, and other cell cycle-related proteins. Additionally, telmisartan reduced levels of phosphorylated ErbB3 and thrombospondin-1 in KYSE180 cells. Furthermore, expression of miRNAs was remarkably altered by telmisartan in vitro. Telmisartan also inhibited tumor growth in vivo in a xenograft mouse model. In conclusion, telmisartan inhibited cell proliferation and tumor growth in ESCC cells by inducing cell-cycle arrest.


The cerebrospinal fluid and plasma concentrations of gamma-trace and beta2-microglobulin at various ages and in neurological disorders.
The concentrations of gamma-trace and beta2-microglobulin in cerebrospinal fluid (CSF) and plasma were determined in 64 individuals of various ages without signs of organic disorder in the central nervous system (CNS). A strong connection was found between the CSF level of gamma-trace and the age of the individual, with the CSF level of newborns being 3--4 times that of adults. A similar, but less marked, connection was found for the CSF level of beta2-microglobulin and the age of the individual. The plasma levels of the two proteins also varied with the age of the individual, but the variations were not as great as those of the CSF levels. The results strongly emphasize the necessity of using age-matched reference values when CSF and plasma levels of the proteins are to be evaluated in different groups of patients. Thirteen children and 98 adults with various neurological disorders were also examined. Significantly increased CSF levels of gamma-trace and beta2-microglobulin as well as increased plasma concentration of gamma-trace and CSF/plasma gradient of beta2-microglobulin were found in infectious disorders. Increased gamma-trace concentration in plasma and beta2-microglobulin concentration in CSF were seen in cerebrovascular disorders. The mechanisms which regulate the turnover of proteins in CSF are discussed.


[A study of blood serum proteins using spin probes in athletes during prolonged physical exercise].
Blood serum proteins were studied in walker athletes with the use of a new nitroxyl radical, 4-(phenylethynyl)-2,2,6,6-delta 3-dehydropiperidine-1-oxyl. Methodological aspects are described in detail. The immobilization parameter (IP), calculated from the electroparamagnetic resonance spectrum of the serum with a probe, reflected the distribution of the probe molecules between albumins and lipoproteins (LP), and changes in this parameter values in response to exercise were explained mainly by changed serum protein LP fraction. IP value was regarded as a characteristic of the body reserves connected with endurance phenomenon. The probe used in this work appeared to hold good promise for investigating the body conditions associated with reserve exhaustion, disturbed lipid metabolism, various stress reactions.


A spectral power analysis of driving behavior changes during the transition from nondistraction to distraction.
This article investigated and compared frequency domain and time domain characteristics of drivers' behaviors before and after the start of distracted driving. Data from an existing naturalistic driving study were used. Fast Fourier transform (FFT) was applied for the frequency domain analysis to explore drivers' behavior pattern changes between nondistracted (prestarting of visual-manual task) and distracted (poststarting of visual-manual task) driving periods. Average relative spectral power in a low frequency range (0-0.5 Hz) and the standard deviation in a 10-s time window of vehicle control variables (i.e., lane offset, yaw rate, and acceleration) were calculated and further compared. Sensitivity analyses were also applied to examine the reliability of the time and frequency domain analyses. Results of the mixed model analyses from the time and frequency domain analyses all showed significant degradation in lateral control performance after engaging in visual-manual tasks while driving. Results of the sensitivity analyses suggested that the frequency domain analysis was less sensitive to the frequency bandwidth, whereas the time domain analysis was more sensitive to the time intervals selected for variation calculations. Different time interval selections can result in significantly different standard deviation values, whereas average spectral power analysis on yaw rate in both low and high frequency bandwidths showed consistent results, that higher variation values were observed during distracted driving when compared to nondistracted driving. This study suggests that driver state detection needs to consider the behavior changes during the prestarting periods, instead of only focusing on periods with physical presence of distraction, such as cell phone use. Lateral control measures can be a better indicator of distraction detection than longitudinal controls. In addition, frequency domain analyses proved to be a more robust and consistent method in assessing driving performance compared to time domain analyses.


Potential Impact of Multi-Walled Carbon Nanotubes Exposure to the Seedling Stage of Selected Plant Species.
Phytotoxicity is a significant consideration in understanding the potential environmental impact of nanoparticles. Abundant experimental data have shown that multi-walled carbon nanotubes (MWNTs) are toxic to plants, but the potential impacts of exposure remain unclear. The objective of the present study was to evaluate possible phytotoxicity of MWNTs at 0, 20, 200, 1000, and 2000 mg/L with red spinach, lettuce, rice, cucumber, chili, lady's finger, and soybean, based on root and shoot growth, cell death, and electrolyte leakage at the seedling stage. After 15 days of hydroponic culture, the root and shoot lengths of red spinach, lettuce, and cucumber were significantly reduced following exposure to 1000 mg/L and 2000 mg/L MWNTs. Similar toxic effects occurred regarding cell death and electrolyte leakage. Red spinach and lettuce were most sensitive to MWNTs, followed by rice and cucumber. Very little or no toxic effects were observed for chili, lady's finger, and soybean.


Acute pancreatitis: current perspectives on diagnosis and management.
The last two decades have seen the emergence of significant evidence that has altered certain aspects of the management of acute pancreatitis. While most cases of acute pancreatitis are mild, the challenge remains in managing the severe cases and the complications associated with acute pancreatitis. Gallstones are still the most common cause with epidemiological trends indicating a rising incidence. The surgical management of acute gallstone pancreatitis has evolved. In this article, we revisit and review the methods in diagnosing acute pancreatitis. We present the evidence for the supportive management of the condition, and then discuss the management of acute gallstone pancreatitis. Based on the evidence, our local institutional pathways, and clinical experience, we have produced an outline to guide clinicians in the management of acute gallstone pancreatitis.


Repotrectinib (TPX-0005) Is a Next-Generation ROS1/TRK/ALK Inhibitor That Potently Inhibits ROS1/TRK/ALK Solvent- Front Mutations.
The use of tyrosine kinase inhibitors (TKI) with activity against ALK, ROS1, or TRKA-C can result in significant clinical benefit in patients with diverse tumors harboring ALK, ROS1, or NTRK1-3 rearrangements; however, resistance invariably develops. The emergence of on-target kinase domain mutations represents a major mechanism of acquired resistance. Solvent-front substitutions such as ALKG1202R, ROS1G2032R or ROS1D2033N, TRKAG595R, and TRKCG623R are among the most recalcitrant of these mechanisms. Repotrectinib (TPX-0005) is a rationally designed, low-molecular-weight, macrocyclic TKI that is selective and highly potent against ROS1, TRKA-C, and ALK. Importantly, repotrectinib exhibits activity against a variety of solvent-front substitutions in vitro and in vivo As clinical proof of concept, in an ongoing first-in-human phase I/II trial, repotrectinib achieved confirmed responses in patients with ROS1 or NTRK3 fusion-positive cancers who had relapsed on earlier-generation TKIs due to ROS1 or TRKC solvent-front substitution-mediated resistance.Significance: Repotrectinib (TPX-0005), a next-generation ROS1, pan-TRK, and ALK TKI, overcomes resistance due to acquired solvent-front mutations involving ROS1, NTRK1-3, and ALK Repotrectinib may represent an effective therapeutic option for patients with ROS1-, NTRK1-3-, or ALK-rearranged malignancies who have progressed on earlier-generation TKIs. Cancer Discov; 8(10); 1227-36. ©2018 AACR. This article is highlighted in the In This Issue feature, p. 1195.


Effect of MDP-Based Silane and Different Surface Conditioner Methods on Bonding of Resin Cements to Zirconium Framework.
To determine the shear bond strength (SBS) between zirconium framework and resin cements after different surface conditioner methods and after application of 10-methacryloyloxydecyl dihydrogen phosphate (MDP) based silane and a bonding agent mix. 128 disc-shaped zirconium-oxide specimens were prepared. Specimens were placed in autopolymerizing acrylic resin. The bonding surface of specimens was smoothed consecutively with 600-, 800-, and 1200-grit silicon carbide papers under water cooling. Eight groups were prepared: CJ, Co-Jet; N, Nd-YAG laser; E, Er-YAG laser; NS, Nd-YAG laser + silane; ES, Er-YAG laser + silane; CJB, Co-Jet + bonding agent; NSB, Nd-YAG laser + silane + bonding agent; ESB, Er-YAG laser + silane + bonding agent. SEM analysis was performed under 2000× magnification. Dual- and self-cured resin cements were bonded to specimens, and shear force was applied. Data were analyzed with one-way ANOVA and Tukey's multiple comparison test (p < 0.05). The SBS values differed from each other among the groups. While the CJB group showed the highest values, the N group showed the lowest. The treatment with MDP-based silane and bonding agent mix increased SBS values of each cement belonging to each group. SB values of dual-cure resin cement were higher than those of self-cure resin cements. Different surface conditioner methods exhibit an important effect on the SBS of resin cements to zirconium. The application of MDP-based silane and bonding agent mix enhanced SB values.


Fluorescent, Magnetic Multifunctional Carbon Dots for Selective Separation, Identification, and Eradication of Drug-Resistant Superbugs.
The emergence of drug-resistant superbugs remains a major burden to society. As the mortality rate caused by sepsis due to superbugs is more than 40%, accurate identification of blood infections during the early stage will have a huge significance in the clinical setting. Here, we report the synthesis of red/blue fluorescent carbon dot (CD)-attached magnetic nanoparticle-based multicolor multifunctional CD-based nanosystems, which can be used for selective separation and identification of superbugs from infected blood samples. The reported data show that multifunctional fluorescent magneto-CD nanoparticles are capable of isolating Methicillin-resistant Staphylococcus aureus (MRSA) and Salmonella DT104 superbug from whole blood samples, followed by accurate identification via multicolor fluorescence imaging. As multidrug-resistant (MDR) superbugs are resistant to antibiotics available in the market, this article also reports the design of antimicrobial peptide-conjugated multicolor fluorescent magneto-CDs for effective separation, accurate identification, and complete disinfection of MDR superbugs from infected blood. The reported data demonstrate that by combining pardaxin antimicrobial peptides, magnetic nanoparticles, and multicolor fluorescent CDs into a single system, multifunctional CDs represent a novel material for efficient separation, differentiation, and eradication of superbugs. This material shows great promise for use in clinical settings.


Detection of two isotypically different antibodies produced by a murine hybridoma.
A hybridoma, F31P46B, secreting monoclonal antibodies (mAbs) comprised of mu and gamma heavy chains in association with a single kappa light chain, has been characterized. This hybridoma was prepared by fusing splenocytes, derived from a BALB/c mouse immunized with Vibrio vulnificus and SP2/O-Ag-14 mouse myeloma cells. The specificity of this hybridoma was determined by ELISA screening on a large number of bacterial strains. Hybridoma cells of F31P46B were cloned by limiting dilution to an average cell density of 0.1 cells/well and repeated 3 times to ensure monoclonality. Isotyping of 7 subclones was then performed by Ouchterlony gel double diffusion, as well as a Bio-Rad isotyping kit, and both methods showed that both IgM and IgG2b were secreted. PAGE and immunoblotting showed the presence of mu, gamma, and kappa chains with respective molecular weights of 80, 50, and 25kDa. A series of fractions, collected from F31P46B ascites during Superose 12 gel chromatography, were tested by the two isotyping methods and each confirmed the presence of two immunoglobulin products. These data indicated that the hybridoma secreted two separate immunoglobulins, IgM/kappa and IgG2b/kappa.


In silico prediction of ADMET properties: how far have we come?
There have been considerable advances in the last few years in both the quantity and the quality of in silico ADMET property predictions. Most ADMET properties are now computable, and the accuracy of some of the software predictions for physicochemical properties in particular is close to that of measured data. There is, however, universal agreement that more good experimental ADMET data are needed for use in in silico model development, for models are only as good as the data on which they are based. Many data remain confidential but it is to be hoped that, with projects such as the Vitic toxicity database, being developed by Lhasa Limited, pharmaceutical companies will be prepared to release data to an 'honest broker' on a confidential basis, so that better in silico models can be developed. Incorporation of calculated ADMET properties into drug discovery and development is a multi-factorial problem and really needs a multi-factorial solution. Some progress is being made in this direction and it is hoped that within the foreseeable future software will be available for this purpose.


Assessment of severity of cardiac rejection in heterotopic heart transplantation using indium-111 antimyosin and magnetic resonance imaging.
Seven canine donor hearts in which atrial septal defect and tricuspid regurgitation had previously been produced were heterotopically transplanted into the recipients' chest cavities. Indium-111 antimyosin myocardial imaging of the excised heart was performed using a scinticamera. Magnetic resonance imaging was also performed and the T2 relaxation time calculated. Subsequently, these data were correlated with pathological findings, which indicated the degree of rejection. Indium-111 antimyosin uptake was high in moderate and severe rejection, but the T2 relaxation time was prolonged even in mild rejection. Thus indium-111 antimyosin uptake was specific, and the T2 relaxation time was sensitive, for detecting the severity and extent of cardiac rejection. Although ex vivo experimental results have been reported, these new methods allow characterisation and accurate evaluation of myocardial tissue undergoing cardiac rejection.


Immunofluorescence study in purpura pigmentosa chronica.
Purpura pigmentosa chronica comprises a group of vascular disorders of unknown etiology. In biopsied specimens obtained from 8 patients, we observed vascular changes such as fibrinoid degeneration and occlusive damage occasioned by a hyalinized substance as well as swollen endothelia in 3. However, in all biopsied specimens, direct immunofluorescence studies demonstrated depositions of C3 or C1q with or without immunoglobulins, and of fibrin in papillary vessels. These findings suggest the possibility that immunological processes are involved in producing the histopathologic features of this disorder.


Assessment of sensitivity to the anesthesia in a diabetic rat model.
Diabetes mellitus and glucose regulation are important in deciding on surgical intervention in pre-surgical assessments. In our study, we aimed to investigate the correlations between the induction time of anesthesia, glucose level, and weight in a diabetic rat model. Weight-matched adult male Wistar rats were grouped as control (n=8) and diabetic (n=8). In the latter group, diabetes was induced with a single intraperitoneal injection of 50 mg/kg streptozotosin. 72 hours after the injection, animals possessing a blood glucose concentration above 300 mg/kg were considered diabetic. The weights and blood glucose levels were observed for 7 days. In the end, 80 mg/kg ketamine and 12 mg/kg xylazine were administered to both groups, and the induction time of anesthesia was recorded. The success of anesthesia was confirmed with toe pinching by using a clamp. The Student's t- and Pearson's correlation tests were used for statistical analyses. The induction time of anesthesia was significantly reduced in the diabetic group compared to the controls (p<0.01). Diabetic animals weighed less than the control group (p<0.01). The correlation analysis in the diabetic group showed that the weight and blood glucose level of animals did not influence the induction time of anesthesia (respectively, p=0.80, r: 0.150; p=0.68, r: -0.300). A negative correlation between blood glucose concentration and weight was found in diabetics (p<0.05, r: -0.828). The dosage of anesthetic agents is important in the effectiveness of anesthesia, and surgical complications. Since our results indicate the susceptibility of diabetics to anesthesia, we suggest that the dose of anesthetics should be finely adjusted considering the presence of diabetes.


A rapid, sensitive method for the quantitation of N-acetyl-S-(2-hydroxyethyl)-L-cysteine in human urine using isotope-dilution HPLC-MS-MS.
Because of increasing concern about exposure to carcinogens and other toxicants, reliable methods for biological monitoring of potentially exposed populations must be developed. For biological monitoring to be useful, appropriate biomarkers of exposures to xenobiotics must be identified, and sensitive, specific methods for quantifying the targeted biomarker must be developed. We have developed a sensitive and selective method for the analysis of N-acetyl-S-(2-hydroxyethyl)-L-cysteine (HEMA), urinary metabolite of at least three different known human carcinogens (vinyl chloride, ethylene oxide, and ethylene dibromide). The method uses strong anion-exchange solid-phase extraction and isotope-dilution high-performance liquid chromatography-tandem mass spectrometry. Our method is simple and is not labor intensive; the preparation time per sample is less than 10 min. Because urine samples vary in both their concentration and ion strength, intersample variability in HEMA recovery during the extraction is large. To overcome this inherent limitation, we use the isotope-dilution technique, which allows a complete correction for the extraction recovery for each sample. The limit of detection of the method is 0.68 microgram/L in a 1-mL urine sample with a coefficient of variation of 22% (determined by replicate analyses at both 4 and 11 micrograms/L) and an accuracy indistinguishable from 100%. Preliminary analyses of urine from a population with no known overt exposure to the parent toxicants show a frequency of detection of approximately 75%, which indicates that this method has the sensitivity to detect urinary HEMA derived from environmental exposure. We are currently using this method to establish a reference range of background exposure to these toxicants in the U.S. population.


The type I BMP receptor ACVR1/ALK2 is required for chondrogenesis during development.
Bone morphogenetic proteins (BMPs) are crucial regulators of chondrogenesis. BMPs transduce their signals through three type I receptors: BMPR1A, BMPR1B, and ACVR1/ALK2. Fibrodysplasia ossificans progressiva (FOP), a rare disorder characterized by progressive ossification of connective tissue, is caused by an activating mutation in Acvr1 (the gene that encodes ACVR1/ALK2). However, there are few developmental defects associated with FOP. Thus, the role of ACVR1 in chondrogenesis during development is unknown. Here we report the phenotype of mice lacking ACVR1 in cartilage. Acvr1(CKO) mice are viable but exhibit defects in the development of cranial and axial structures. Mutants exhibit a shortened cranial base, and cervical vertebrae are hypoplastic. Acvr1(CKO) adult mice develop progressive kyphosis. These morphological defects were associated with decreased levels of Smad1/5 and p38 activation, and with reduced rates of chondrocyte proliferation in vertebral cartilage. We also tested whether ACVR1 exerts coordinated functions with BMPR1A and BMPR1B through analysis of double mutants. Acvr1/Bmpr1a and Acvr1/Bmpr1b mutant mice exhibited generalized perinatal lethal chondrodysplasia that was much more severe than in any of the corresponding mutant strains. These findings demonstrate that ACVR1 is required for chondrocyte proliferation and differentiation, particularly in craniofacial and axial elements, but exerts coordinated functions with both BMPR1A and BMPR1B throughout the developing endochondral skeleton.


Reinfection with Streptococcus suis analysed by whole genome sequencing.
A butcher with chronic dermatitis presented with a second episode of Streptococcus suis meningitis, 8 years after the first episode. To distinguish between reinfection and persistent carriage, we compared the two S. suis isolates using whole genome sequencing. We investigated whole genome sequences of the S. suis isolates by means of substitution rates and population structure of closely related strains in addition to available clinical information. Genome-wide analyses revealed an inserted region consisting of 12 genes in the first isolate and the calculated substitution rate between the isolates suggested infections were caused by highly similar, but unrelated strains. Continuous occupational exposure likely resulted in reinfection with S. suis in a butcher.


Hepatitis B virus infection and Schönlein-Henoch purpura.
Sch onlein -Henoch purpura developed in two children in association with hepatitis B virus (HBV) infection. The first child, an 8-year-old boy, first had a clinical picture of Sch onlein -Henoch purpura and then was found to have HBV-related chronic persistent hepatitis. In the second child, a 6-year-old girl, characteristic skin lesions, arthralgia, and proteinuria developed during acute hepatitis B. Immunofluorescence demonstrated IgA deposition in the renal glomeruli of the first patient. We suggest that evidence of HBV infection should be sought in patients with Sch onlein -Henoch purpura.


The Socio-Moral Image Database (SMID): A novel stimulus set for the study of social, moral and affective processes.
A major obstacle for the design of rigorous, reproducible studies in moral psychology is the lack of suitable stimulus sets. Here, we present the Socio-Moral Image Database (SMID), the largest standardized moral stimulus set assembled to date, containing 2,941 freely available photographic images, representing a wide range of morally (and affectively) positive, negative and neutral content. The SMID was validated with over 820,525 individual judgments from 2,716 participants, with normative ratings currently available for all images on affective valence and arousal, moral wrongness, and relevance to each of the five moral values posited by Moral Foundations Theory. We present a thorough analysis of the SMID regarding (1) inter-rater consensus, (2) rating precision, and (3) breadth and variability of moral content. Additionally, we provide recommendations for use aimed at efficient study design and reproducibility, and outline planned extensions to the database. We anticipate that the SMID will serve as a useful resource for psychological, neuroscientific and computational (e.g., natural language processing or computer vision) investigations of social, moral and affective processes. The SMID images, along with associated normative data and additional resources are available at https://osf.io/2rqad/.


What gender differences in cancer incidence changed during the last 10 years in central Italy?
We have investigated whether gender differences in cancer incidence have changed during the mid 1980s to late 1990s, and whether certain changes could be clues for gender-specific modifications in carcinogenic exposures. We used the incidence data from the Tuscany Cancer Registry and computed the standardized (on the European standard population) male-to-female incidence rate ratios (IRR) for two periods, 1986-87 and 1996-97, with corresponding 95% confidence intervals. Such statistics were calculated for two age groups, 0-59 years and 60 years and over. Among younger subjects there was a remarkable reduction in the IRR for smoking-related cancer sites such as oral cavity (IRR from 4.3 to 2.2), esophagus (IRR from 6.2 to 4.2), larynx (IRR from 13.3 to 5.7), and lung (IRR from 6.5 to 3.3). Less evident changes were observed among subjects aged 60 and over, eg for lung the IRR fell from 8.1 to 6.2. Most of the differences examined were probably due to changes in tobacco smoking which were different between genders during the last decade, with a decreasing prevalence of smokers among males and an increasing trend among females.


Effect of solvent and protonation/deprotonation on electrochemistry, spectroelectrochemistry and electron-transfer mechanisms of N-confused tetraarylporphyrins in nonaqueous media.
A series of N-confused free-base meso-substituted tetraarylporphyrins was investigated by electrochemistry and spectroelectrochemistry in nonaqueous media containing 0.1 M tetra-n-butylammonium perchlorate (TBAP) and added acid or base. The investigated compounds are represented as (XPh)4 NcpH2 , in which "Ncp" is the N-confused porphyrin macrocycle and X is a OCH3 , CH3 , H, or Cl substituent on the para position of each meso-phenyl ring of the macrocycle. Two distinct types of UV/Vis spectra are initially observed depending upon solvent, one corresponding to an inner-2H form and the other to an inner-3H form of the porphyrin. Both forms have an inverted pyrrole with a carbon inside the cavity and a nitrogen on the periphery of the π-system. Each porphyrin undergoes multiple irreversible reductions and oxidations. The first one-electron addition and first one-electron abstraction are located on the porphyrin π-ring system to give π-anion and π-cation radicals with a potential separation of 1.52 to 1.65 V between the two processes, but both electrogenerated products are unstable and undergo a rapid chemical reaction to give new electroactive species, which were characterized in the present study. The effect of the solvent and protonation/deprotonation reactions on the UV/Vis spectra, redox potentials and reduction/oxidation mechanisms is discussed with comparisons made to data and mechanisms for the structurally related free-base corroles and porphyrins.


Hormonal and nutritional regulation of postnatal hypothalamic development.
The hypothalamus is a key centre for regulation of vital physiological functions, such as appetite, stress responsiveness and reproduction. Development of the different hypothalamic nuclei and its major neuronal populations begins prenatally in both altricial and precocial species, with the fine tuning of neuronal connectivity and attainment of adult function established postnatally and maintained throughout adult life. The perinatal period is highly susceptible to environmental insults that, by disrupting critical developmental processes, can set the tone for the establishment of adult functionality. Here, we review the most recent knowledge regarding the major postnatal milestones in the development of metabolic, stress and reproductive hypothalamic circuitries, in the rodent, with a particular focus on perinatal programming of these circuitries by hormonal and nutritional influences. We also review the evidence for the continuous development of the hypothalamus in the adult brain, through changes in neurogenesis, synaptogenesis and epigenetic modifications. This degree of plasticity has encouraging implications for the ability of the hypothalamus to at least partially reverse the effects of perinatal mal-programming.


Resisting and tolerating P. falciparum in pregnancy under different malaria transmission intensities.
Resistance and tolerance to Plasmodium falciparum can determine the progression of malaria disease. However, quantitative evidence of tolerance is still limited. We investigated variations in the adverse impact of P. falciparum infections among African pregnant women under different intensities of malaria transmission. P. falciparum at delivery was assessed by microscopy, quantitative PCR (qPCR) and placental histology in 946 HIV-uninfected and 768 HIV-infected pregnant women from Benin, Gabon, Kenya and Mozambique. Resistance was defined by the proportion of submicroscopic infections and the levels of anti-parasite antibodies quantified by Luminex, and tolerance by the relationship of pregnancy outcomes with parasite densities at delivery. P. falciparum prevalence by qPCR in peripheral and/or placental blood of HIV-uninfected Mozambican, Gabonese and Beninese women at delivery was 6% (21/340), 11% (28/257) and 41% (143/349), respectively. The proportion of peripheral submicroscopic infections was higher in Benin (83%) than in Mozambique (60%) and Gabon (55%; P = 0.033). Past or chronic placental P. falciparum infection was associated with an increased risk of preterm birth in Mozambican newborns (OR = 7.05, 95% CI 1.79 to 27.82). Microscopic infections were associated with reductions in haemoglobin levels at delivery among Mozambican women (-1.17 g/dL, 95% CI -2.09 to -0.24) as well as with larger drops in haemoglobin levels from recruitment to delivery in Mozambican (-1.66 g/dL, 95% CI -2.68 to -0.64) and Gabonese (-0.91 g/dL, 95% CI -1.79 to -0.02) women. Doubling qPCR-peripheral parasite densities in Mozambican women were associated with decreases in haemoglobin levels at delivery (-0.16 g/dL, 95% CI -0.29 to -0.02) and increases in the drop of haemoglobin levels (-0.29 g/dL, 95% CI -0.44 to -0.14). Beninese women had higher anti-parasite IgGs than Mozambican women (P < 0.001). No difference was found in the proportion of submicroscopic infections nor in the adverse impact of P. falciparum infections in HIV-infected women from Kenya (P. falciparum prevalence by qPCR: 9%, 32/351) and Mozambique (4%, 15/417). The lowest levels of resistance and tolerance in pregnant women from areas of low malaria transmission were accompanied by the largest adverse impact of P. falciparum infections. Exposure-dependent mechanisms developed by pregnant women to resist the infection and minimise pathology can reduce malaria-related adverse outcomes. Distinguishing both types of defences is important to understand how reductions in transmission can affect malaria disease. ClinicalTrials.gov NCT00811421 . Registered 18 December 2008.


Effect of compound 48/80 on canine gastric mucosa.
The effect of compound 48/80 on the mucosal barrier of the canine Heidenhain pouch and mast cell content of gastric mucosa has been studied. 48/80 was administered in increasing doses (0.5--2.0 mg/kg) over 5 days. 0.5 mg/kg produced signs of systemic histamine release and stimulation of acid secretion by the pouch; these effects being most marked on the 1st day and absent on the 5th. Subsequent exposure of the mucosa to sodium taurocholate produced damage to the barrier similar to that in untreated animals. Histological examination revealed no evidence of mucosal mast cell degranulation by 48/80. The results suggest that the effects of 48/80 on gastric mucosa are mediated by systemic release of histamine and that local mast cells are resistant to its action.


A global view of suicidal behaviour.
Suicidal behaviour is a major public health problem. There is no one explanatory theory of suicidal behaviour, and various combinations of sociological and biological/medical interventions are required to reduce associated mortality and morbidity. The importance of primary prevention varies from community to community, and may have an impact at the population level. However, individual suicidal persons always require optimum assessment and management and that is usually provided by primary care and emergency physicians. This paper provides an overview of issues to be addressed in the assessment and management of suicidal patients.


Detection of the Vibration Signal from Human Vocal Folds Using a 94-GHz Millimeter-Wave Radar.
The detection of the vibration signal from human vocal folds provides essential information for studying human phonation and diagnosing voice disorders. Doppler radar technology has enabled the noncontact measurement of the human-vocal-fold vibration. However, existing systems must be placed in close proximity to the human throat and detailed information may be lost because of the low operating frequency. In this paper, a long-distance detection method, involving the use of a 94-GHz millimeter-wave radar sensor, is proposed for detecting the vibration signals from human vocal folds. An algorithm that combines empirical mode decomposition (EMD) and the auto-correlation function (ACF) method is proposed for detecting the signal. First, the EMD method is employed to suppress the noise of the radar-detected signal. Further, the ratio of the energy and entropy is used to detect voice activity in the radar-detected signal, following which, a short-time ACF is employed to extract the vibration signal of the human vocal folds from the processed signal. For validating the method and assessing the performance of the radar system, a vibration measurement sensor and microphone system are additionally employed for comparison. The experimental results obtained from the spectrograms, the vibration frequency of the vocal folds, and coherence analysis demonstrate that the proposed method can effectively detect the vibration of human vocal folds from a long detection distance.


Co-expression of different angiogenic factors in external auditory canal cholesteatoma.
Although external auditory canal cholesteatoma (EACC) was first described in 1850, its cause remains surprisingly unclear. Angiogenesis, the formation of new blood vessels, is essential to normal development and wound healing in adults. Abnormal regulation of angiogenesis has been implicated in the pathogenesis of several disorders. The aim of this study was to analyse angiogenesis regulator expression in EACC. Cryostat sections of 13 investigated EACC tissue samples and normal control tissue were immunostained for angiogenic hepatocyte growth factor (HGF)/scatter factor (SF), its c-Met receptor and vascular endothelial growth factor (VEGF) using a standard streptavidin-biotin complex procedure. Staining against von Willebrand factor (vWF) served as an endothelial marker. Statistical analysis was performed semiquantitatively. The assayed angiogenic factors were all present in the EACC tissue, and partly overexpressed. vWF was detected in the apical layers of the matrix epithelium. Positive immunoreactivity for c-Met and VEGF was detectable in all layers of the EACC epithelium; however, adjacent tissue did not express c-Met and VEGE. HGF/SF was predominantly expressed in the adjacent perimatrix tissue and fibroblasts in particular were stained positive. The presence of vWF in the apical part of the matrix depicted the attempt at angiogenesis in this part of the EACC. The detection of VEGF and c-Met in the epithelial part of the EACC implied that their origin may be epithelial, while HGF/SF may be secreted or stored in the adjacent mesenchymal EACC tissue. The angiogenic factors investigated seem to play an important role in establishing that EACC occurs by modulation of angiogenesis.


Hair loss in children in South-East Nigeria: common and uncommon cases.
The cosmetic importance of hair as a unique structure of the scalp is immense, such that once the loss of hair becomes an issue for a child, parents, in most cases, project their own concerns, often expressed as guilt. The clinical presentation of hair loss and scalp disorders in children varies widely, often ranging from subtle to disfiguring forms, and may be acquired or congenital. This variable pattern of hair loss is seen in all regions, possibly based on the ethnic origin of hair types. To determine the clinical aspects of hair loss based on clinical appearance, age of onset, duration of disease, and associated features, and to provide a guide for the evaluation of acquired hair loss and scalp disorders commonly occurring in childhood in south-east Nigeria. One hundred and thirteen children with hair loss and scalp disorders consulted the University of Nigeria Teaching Hospital Skin Clinic between February 2002 and March 2003. The data collected included age, sex, clinical presentation, associated symptoms, and family history. Laboratory tests [full blood count (FBC), thyroid function test (TFT), antinuclear antibody (ANA), urinalysis], microscopic examination, Wood's light examination, and histology were conducted for further confirmation where necessary. There were 71 males (62.8%) and 42 females (37.2%), aged between 3 months and 13 years. The presenting symptoms included scaly scalp, itchiness, and anxiety; some patients were asymptomatic. Hair loss and fear were the chief concerns of 89.6% and 51.3% of parents, respectively, who presented with their children. Commonly occurring diagnoses were tinea capitis (62; 54.9%), alopecia areata (43; 38.1%), psoriasis (5; 4.4%), and telogen effluvium (3; 2.7%). Seventeen patients with alopecia areata had atopic dermatitis and three had vitiligo. Commonly occurring hair loss in children in our region is mainly acquired, and the clinical course is related to the parent's attitude to treatment, particularly for tinea capitis.


Plant-bacteria associations are phylogenetically structured in the phyllosphere.
Determining whether and how global change will lead to novel interactions between hosts and microbes is an important issue in ecology and evolution. Understanding the contribution of host and microbial ecologies and evolutionary histories in driving their contemporary associations is an important step towards addressing this challenge and predicting the fitness consequences of novel associations. Using shotgun metagenomic and amplicon sequencing of bacterial communities from the leaf surfaces (phyllosphere) of trees, we investigated how phylogenetic relatedness among hosts and among their associated bacteria influences the distribution of bacteria among hosts. We also evaluated whether the functional traits of trees and bacteria explained these associations across multiple host species. We show that phylogenetically similar hosts tended to associate with the same bacteria and that phylogenetically similar bacteria tended to associate with the same host species. Phylogenetic interactions between tree and bacterial taxa also explained variation in their associations. The effect of host and symbiont evolutionary histories on bacterial distribution across hosts were observed across phylogenetic scales, but prominently explained variation among higher taxonomic categories of hosts and symbionts. These results suggest that ecological variation arising early in the plant and bacterial phylogenies have been particularly important for driving their contemporary associations. Variation in bacterial functional genes associated with the biosynthesis of aromatic amino acids and compounds and with cell motility were notably important in explaining bacterial community turnover among gymnosperm and angiosperm hosts. Overall, our results suggest an influence of host and bacterial traits and evolutionary histories in driving their contemporary associations.


Difficult decisions in times of constraint: criteria based resource allocation in the Vancouver Coastal Health Authority.
The aim of the project was to develop a plan to address a forecasted deficit of approximately $4.65 million for fiscal year 2010/11 in the Vancouver Communities division of the Vancouver Coastal Health Authority. For disinvestment opportunities identified beyond the forecasted deficit, a commitment was made to consider options for resource re-allocation within the Vancouver Communities division. A standard approach to program budgeting and marginal analysis (PBMA) was taken with a priority setting working committee and a broader advisory panel. An experienced, non-vested internal project manager worked closely with the two-member external research team throughout the process. Face to face evaluation interviews were held with 10 decision makers immediately following the process. The recommendations of the working committee included the implementation of 44 disinvestment initiatives with an annualized value of CAD $4.9 million, as well as consideration of possible investments if the realized savings match expectations. Overall, decision makers viewed the process favorably and the primary aim of addressing the deficit gap was met. A key challenge was the tight timeline which likely lead to less evidence informed decision making then one would hope for. Despite this, decision makers felt that better decisions were made then had the process not been in place. In the end, this project adds value in finding that PBMA can be used to cover a deficit and minimize opportunity cost through systematic application of criteria whilst ensuring process fairness through focusing on communication, transparency and decision maker engagement.


Flight speed and performance of the wandering albatross with respect to wind.
Albatrosses and other large seabirds use dynamic soaring to gain sufficient energy from the wind to travel large distances rapidly and with little apparent effort. The recent development of miniature bird-borne tracking devices now makes it possible to explore the physical and biological implications of this means of locomotion in detail. Here we use GPS tracking and concurrent reanalyzed wind speed data to model the flight performance of wandering albatrosses Diomedea exulans soaring over the Southern Ocean. We investigate the extent to which flight speed and performance of albatrosses is facilitated or constrained by wind conditions encountered during foraging trips. We derived simple equations to model observed albatross ground speed as a function of wind speed and relative wind direction. Ground speeds of the tracked birds in the along-wind direction varied primarily by wind-induced leeway, which averaged 0.51 (± 0.02) times the wind speed at a reference height of 5 m. By subtracting leeway velocity from ground velocity, we were able to estimate airspeed (the magnitude of the bird's velocity through the air). As wind speeds increased from 3 to 18 m/s, the airspeed of wandering albatrosses flying in an across-wind direction increased by 0.42 (± 0.04) times the wind speed (i.e. ~ 6 m/s). At low wind speeds, tracked birds increased their airspeed in upwind flight relative to that in downwind flight. At higher wind speeds they apparently limited their airspeeds to a maximum of around 20 m/s, probably to keep the forces on their wings in dynamic soaring well within tolerable limits. Upwind airspeeds were nearly constant and downwind leeway increased with wind speed. Birds therefore achieved their fastest upwind ground speeds (~ 9 m/s) at low wind speeds (~ 3 m/s). This study provides insights into which flight strategies are optimal for dynamic soaring. Our results are consistent with the prediction that the optimal range speed of albatrosses is higher in headwind than tailwind flight but only in wind speeds of up to ~ 7 m/s. Our models predict that wandering albatrosses have oval-shaped airspeed polars, with the fastest airspeeds ~ 20 m/s centered in the across-wind direction. This suggests that in upwind flight in high winds, albatrosses can increase their ground speed by tacking like sailboats.


Engineering a bifunctional copper site in the cupredoxin fold by loop-directed mutagenesis.
Copper sites in proteins are designed to perform either electron transfer or redox catalysis. Type 1 and CuA sites are electron transfer hubs bound to a rigid protein fold that prevents binding of exogenous ligands and side reactions. Here we report the engineering of two Type 1 sites by loop-directed mutagenesis within a CuA scaffold with unique electronic structures and functional features. A copper-thioether axial bond shorter than the copper-thiolate bond is responsible for the electronic structure features, in contrast to all other natural or chimeric sites where the copper thiolate bond is short. These sites display highly unusual features, such as: (1) a high reduction potential despite a strong interaction with the axial ligand, which we attribute to changes in the hydrogen bond network and (2) the ability to bind exogenous ligands such as imidazole and azide. This strategy widens the possibility of using natural protein scaffolds with functional features not present in nature.


Experimental urolithiasis in the bladder of rats.
Vesical foreign bodies readily lead to urolith formation but not in Brattleboro rats with diabetes insipidus. This experiment was designed to examine the roles of vesical foreign bodies, urine osmolality, and vesical infection in the formation of uroliths and associated reactive urothelial hyperplasia. ADH-deficient Brattleboro rats received surgical insertion of a silk suture in the bladder. Their bladders were infected with intravesical injection of urease positive P. vulgaris, while controls were similarly injected with sterile Ringer's sol. They received daily injections of either pitressin tannate in oil (1 U/kg body weight) or peanut oil. Urine flow rate, urine osmolality, urine culture, and gross and light microscopic examinations of the bladders were carried out at the end of 4th week. The results indicated that uroliths readily formed in the presence of all three factors; vesical foreign bodies, high urine osmolality, and infection, but not as readily in the presence of two or less of these three factors. The urothelial hyperplasia was prominent in infected bladders followed by non-infected bladder with high osmolar and low osmolar urine in this order.


Association between Sedentary Time and Cardiovascular Risk Factors in Korean Adults.
Sedentary behavior has been shown to have deleterious effects on cardiovascular outcomes. This study aimed to examine the association between sedentary time and cardiovascular risk factors in Korean adults. A cross-sectional study was performed using data from adults aged 19 years and above in the 2013 Korean National Health and Nutrition Examination Survey. Sedentary time was self-reported and categorized into quintiles. Cardiovascular risk factors, including blood pressure (BP), total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, low-density lipoprotein cholesterol, and fasting glucose levels, were categorized into dichotomous variables according to the Adult Treatment Panel III criteria. Multivariate logistic regression was performed with adjustment for various demographic and lifestyle variables, body mass index (BMI), waist circumference (WC), and moderate-to-vigorous physical activity. Complex sampling design was used, and survey weights and sample design variables were applied in analyses. A total of 3,301 individuals were included in the analyses, and mean sedentary time was 6.1 h/d. Prolonged sedentary time was significantly associated with high diastolic BP (top vs. bottom quintile: adjusted odds ratio [OR], 1.71; 95% confidence interval [CI], 1.09-2.68; Ptrend=0.03) and low HDL cholesterol level (top vs. bottom quintile: adjusted OR, 1.42; 95% CI, 1.02-1.98; Ptrend=0.02) after adjustment for BMI, WC, moderate-to-vigorous physical activity, and other variables. No significant associations were found between sedentary time and other cardiovascular risk factors. Prolonged sedentary time was significantly associated with high diastolic BP and low HDL cholesterol level in Korean adults. The associations were independent of general and abdominal obesity and moderate-to-vigorous physical activities.


Pulmonary abnormalities after cardiac surgery are better explained by atelectasis than by increased permeability oedema.
Cardiac surgery can be complicated by pulmonary abnormalities, but it is unclear how various manifestations interrelate. A prospective study in the intensive care unit was performed on 26 mechanically ventilated patients without cardiac failure within 3 h after elective cardiac surgery involving cardiopulmonary bypass. Oedema (extravascular lung water, EVLW) was measured by the thermal-dye technique and permeability by a dual radionuclide technique, yielding a pulmonary leak index (PLI). Radiographic, mechanical and gas exchange features were used to calculate the lung injury score (LIS), ranging between 0 and 4. Evidence for left lower lobe atelectasis was obtained from plain radiographs. The plasma colloid osmotic pressure (COP) was measured by an oncometer. The EVLW (normal, <7 ml/kg) was elevated in 36% of patients and the PLI (normal, <14.1 x 10(-3)/min) in 44%, but the variables did not interrelate directly. Patients with a supranormal EVLW had a lower COP than patients with normal EVLW. The duration of mechanical ventilation was prolonged in patients (20%) with EVLW > 10 ml/kg. There was no difference in EVLW and PLI in patients with LIS < 1 and LIS > 1 (31% of patients). In patients with radiographic evidence for atelectasis (46%), the positive end-expiratory pressure and inspiratory O2 fraction to maintain oxygenation were higher than in those without. After cardiac surgery, mild pulmonary oedema is relatively common, even in the absence of high filling pressures, and is mainly attributable to a low COP, irrespective of increased permeability in about one-half of patients. It may prolong mechanical ventilation at EVLW > 10 ml/kg. However, pulmonary radiographic and ventilatory abnormalities may result, at least in part, from atelectasis rather than increased permeability oedema.


A randomized controlled trial of double-versus single-gloving in vascular surgery.
With the increasing incidence of hepatitis B and HIV, and the increasing awareness of the risk and prevalence of hepatitis C, it is becoming even more necessary to adopt stricter policies to safeguard personnel and to reduce the risk of transmission. Previous studies have shown a need for eye protection, protective clothing and the use of double-gloving during operative or interventional procedures. The risk of infection is much less with unbroken skin and conversely more likely when hollow needles are used. Arguments against the routine use of double-gloving include the loss of dexterity and the discomfort incurred, and the potential loss of dexterity that might theoretically result in more rather than fewer needle-stick injuries.


Reduced TORC1 signaling abolishes mitochondrial dysfunctions and shortened chronological lifespan of Isc1p-deficient cells.
The target of rapamycin (TOR) is an important signaling pathway on a hierarchical network of interacting pathways regulating central biological processes, such as cell growth, stress response and aging. Several lines of evidence suggest a functional link between TOR signaling and sphingolipid metabolism. Here, we report that the TORC1-Sch9p pathway is activated in cells lacking Isc1p, the yeast orthologue of mammalian neutral sphingomyelinase 2. The deletion of TOR1 or SCH9 abolishes the premature aging, oxidative stress sensitivity and mitochondrial dysfunctions displayed by isc1Δ cells and this is correlated with the suppression of the autophagic flux defect exhibited by the mutant strain. The protective effect of TOR1 deletion, as opposed to that of SCH9 deletion, is not associated with the attenuation of Hog1p hyperphosphorylation, which was previously implicated in isc1Δ phenotypes. Our data support a model in which Isc1p regulates mitochondrial function and chronological lifespan in yeast through the TORC1-Sch9p pathway although Isc1p and TORC1 also seem to act through independent pathways, as isc1Δtor1Δ phenotypes are intermediate to those displayed by isc1Δ and tor1Δ cells. We also provide evidence that TORC1 downstream effectors, the type 2A protein phosphatase Sit4p and the AGC protein kinase Sch9p, integrate nutrient and stress signals from TORC1 with ceramide signaling derived from Isc1p to regulate mitochondrial function and lifespan in yeast. Overall, our results show that TORC1-Sch9p axis is deregulated in Isc1p-deficient cells, contributing to mitochondrial dysfunction, enhanced oxidative stress sensitivity and premature aging of isc1Δ cells.


Intraocular distribution of 70-kDa dextran after subconjunctival injection in mice.
To investigate the intraocular distribution kinetics of 70-kDa dextran after subconjunctival injection. The right eye of 15 mice received a single subconjunctival injection of a 1.5-microL solution of 0.25% 70-kDa tetramethylrhodamine-dextran (TMR-D). The distribution of fluorescent labeling in eye sections was examined by fluorescence microscopy at 0.25, 1, 4, 24, or 72 hours after the injection. The brightness and homogeneity of fluorescence in the sclera, choroid, and retina were scored near the injection site, on the side of the globe opposite the injection site, and adjacent to the optic nerve head. Fluorescence intensity within the sclera and choroid adjacent to the optic nerve was assessed quantitatively by imaging densitometry. TMR-D readily diffused transsclerally and dispersed throughout a large portion of the sclera, uvea, and cornea. Shortly after the injection, homogenous fluorescence was observed in the sclera and choroid on the same meridian as that of the injection site. This fluorescence gradually decreased in intensity with distance from the injection site. At the opposite meridian, fluorescence in the choroid was more intense than in the adjacent sclera and could be traced up to the ciliary muscle. TMR-D was also observed in the retinal and optic nerve vessels. The intensity of scleral and choroidal fluorescence adjacent to the optic nerve reached a maxima at 1 hour, and then decreased slowly, with half-lives of approximately 16 and 100 hours, respectively. Visible fluorescence was maintained at least until 72 hours in the sclera, choroid, iris, and cornea. Specific fluorescent labeling was never found in the contralateral eyes. Macromolecular 70-kDa dextran can be readily delivered to the mouse retina and uveal tissues by subconjunctival injection through transscleral diffusion, local hematogenous spread, and possibly movement through the uveoscleral outflow pathway. Subconjunctival injection may be a useful approach for delivering macromolecules to the retina and uvea.


Malignant interstitial (Leydig) cell tumour of the testis--a case report.
Interstitial (Leydig) cell tumour of the testis is an extremely uncommon tumour. We report one such tumour displaying histologic features of malignancy--large size capsular invasion and moderate nuclear pleomorphism in an adult male. The tumour also showed crystalloids of Reinke, confirming Leydig cell origin.


[Diabetes and alternative medicine: diabetic patients experiences with Ayur-Ved, "clinical ecology" and "cellular nutrition" methods].
In the last two years we discovered that three of our patients with type 1 diabetes mellitus (0.8%) suffered an unexpected worsening in their glycemic control due to a reduction of their insulin dosage in favour of some "alternative" diabetes treatments using herbs, vitamins, fantastic diets and trace elements prescribed by non-medical practitioners. The first patient, a 6.6 year old boy, was admitted to hospital because of a severe ketoacidosis with first degree coma as a result of his parents having reduced his insulin dosage by 77% and replacing the insulin with an ayurvedic herbal preparation (Bardana Actium Lapp). The second patient, a 10.4 year old boy, was admitted to hospital after his teachers noticed that he appeared tired, thinner and polyuric. During hospital admission for mild ketoacidosis the mother, reluctant at first, finally confessed that her son was under the care of a "clinical ecologist". Having identified several food allergies this "clinical ecologist" had placed the child on a spartan diet of bread, water and salt, and had reduced his insulin dosage by 68%. The third patient, a 21 year old male, upon transfer to the Adult Diabetic Center, reported that he had been under the care of a pranotherapist for several years. The pranotherapist had prescribed a cellular nutrition preparation (called "Madonna drops"), a meditation program and also a 50% reduction in his insulin dosage. During this period his HbAlc values had increased from 6.4% to 12%. Current orthodox diabetes treatments are considered unsatisfactory by many people and it is thus not surprising that they search for "miracle" cures. It is important, however, that hospital staff do not ridicule the patients or their parents for trying these alternative therapies. Nevertheless, it would be useful for staff to discuss in advance these "therapies" with patients, highlighting their ineffectiveness and strongly discouraging cures that call for a reduction or elimination of the insulin treatment.


Evaluation of a 3 year education and training program. For nursing personnel at a Swedish hospital.
An education and training program comprising 1) patient transfer technique, 2) physical fitness exercise, and 3) stress management was conducted during 3 consecutive years at a Swedish hospital. The present study was based on data from four sets of questionnaires, distributed to 348 female nursing personnel who participated in the entire program. The aim of the study was to evaluate the program. It was evident from the questionnaires that 90% of the subjects were positive about participating in the program and 88% expected that participation would lead to decreased musculoskeletal disorders. However, no decrease in the prevalence of musculoskeletal symptoms during the study time period was observed. One year after the cessation of the program, 93% of all nurses reported they mostly or always used the new patient transfer technique and 99% considered it to be useful.


Mandibular Overdentures Retained by Two Mini-Implants: A Seven-Year Retention and Satisfaction Study.
Patients with atrophic edentulous ridges generally have problems with retention, therapeutic satisfaction, and comfort with their complete dentures. An alternative treatment to assist in improving retention and stability involves the use of mini-implants. The aim of this study was to evaluate the retention of mandibular overdentures connected to two mini-implants and overall patient satisfaction with them. Seven patients with atrophic mandibular ridges (Type 4D Misch classification), aged 62 to 74 years old were rehabilitated with complete dentures. In each patient, two mini-implants measuring 15 or 13 mm in length and 1.8 mm in diameter were placed. After 15 days, overdentures were connected to the mini-implants with O-ring attachments. In each patient, retention of the overdentures was measured, and a survey of therapeutic satisfaction before and after connection to the mini-implants was administered. Prosthesis retention was measured with a digital dynamometer at 1 month, 6 months, and 2, 3, 5, and 7 years after mini-implant placement. Patient satisfaction was assessed with a survey. Data were analyzed with Student's t-test (satisfaction survey) and the Friedman test (retention measurements and satisfaction survey). The initial retention values (0.34 to 0.63 N without mini-implants) varied significantly (p ≤ 0.050). These values were less than the subsequent measurements of 3.92 to 9.64 N, taken after placement of the mini-implants and connecting them to the dentures. Satisfaction was good to very good over the 7-year observation period. Mucosa and peri-implant bone showed no pathological changes. In this limited sample size clinical study the results indicated that after connecting mandibular overdentures to two mini-implants, patient satisfaction significantly increased and retention significantly improved during the 7-year observation period.


Prevalence of IgG antibodies against West Nile virus in blood donors during the 2003 outbreak in Tunisia.
This study aimed to evaluate the prevalence of anti-West Nile virus (WNV) IgG among two populations of Tunisian blood donors living in areas where human outbreaks of WNV have occurred. Cohorts A (Monastir) and B (Mahdia) included 742 and 102 blood donors respectively. Sera were tested by IgG ELISA test and results were confirmed by PRNT test. WNV neutralizing antibodies were detected in 32 (4.3%) and in 14 (13.7%) sera in cohorts A and B respectively. The prevalence of anti-WNV IgG was significantly higher in cohort B than in cohort A (P<0.001) and was significantly lower in females than in males (P<0.001).


Relationship between daily rehabilitation time and functional gain in inpatient rehabilitation medicine of hospitalized older adults with subacute stroke.
Igarashi T, Hayashi S, Ogawa K, Matsui S, Nishimatsu T. Relationship between daily rehabilitation time and functional gain in inpatient rehabilitation medicine of hospitalized older adults with subacute stroke. Jpn J Compr Rehabil Sci 2022; 13: 56-63. Although there have been reports examining the relationship between daily rehabilitation time and functional gain, few have fully considered background factors such as severity of motor paralysis and comorbidities. This study aimed to examine the relationship between the daily rehabilitation time and improvement in functional status, longitudinally in hospitalized older adults with subacute stroke. From the results of the Functional Independence Measure (FIM), we calculated the FIM gain and FIM effectiveness, a measure that is less sensitive to the ceiling effect of FIM. Adjusted for covariates, multiple regression analysis was performed for daily rehabilitation time and FIM gain and effectiveness. This study enrolled 298 hospitalized older adults with subacute stroke (mean age, 78.1 ± 8.1 years, 112 females). The total scores of functional independence measure gain and effectiveness were 31.6 ± 22.5 points and 54.4 ± 35.2%, respectively. There was an association between FIM gain (total score) and total rehabilitation time (β = 0.29, p < 0.01) and between FIM effectiveness (total score) and total rehabilitation time (β = 0.22, p < 0.01). Although prognosis after stroke is poorer in older adults than in young adults, this study shows that increased daily rehabilitation time may improve functional status.


Intravenous gamma-globulin: clinical applications in pediatric care.
Intravenous gamma-globulin is being used with increasing frequency in the care of children. This article reviews the physiology of the immune system, the pharmacology of intravenous gamma-globulin, and presents four case studies. Administration guidelines, adverse reactions, and appropriate interventions are discussed. A table comparing four commonly used products is presented.


[Analysis of correlation factors for cervical intraepithelial neoplasia in married women in Beijing, China].
To investigate the characteristic of precancerous conditions of cervical intraepithelial neoplasia (CIN) and its related high-risk factors among the married women in Beijing, China. Based upon the method of cross-sectional survey, 6339 married women at reproductive age from 25 to 54 years old were selected randomly in a total of 137 communities of 12 districts or counties in Beijing from March 2007 to September 2008. The interview was carried out with unified questionnaires and gynecological examinations. And the cervical Pap smear was used for liquid-based cytological examination and the cervical secretion for detection of high-risk human papillomavirus (HPV) DNA. Furthermore, the women with abnormal cervical cytology received colposcopy and cervical biopsy. (1) Among 6, 339 study subjects, 374 cases had CIN and the prevalence rate was 5.9%; (2) For the cases with cervical cytology positive results, cervical biopsy showed an elevated level of abnormal cytology and an increased incidence of cervical lesions; (3) The peak age of CIN prevalence was 30 to 34 years old and there was a high grade of cervical neoplasia; (4) Among the population, the infection rate of high-risk HPV was 9.9% and the infection rate of high-risk HPV in positive cytological group (41.2%) was significantly higher than that in negative cytological group (6.6%); (5) The infection rate and DNA load of high-risk HPV increased following the severity grade of CIN. In Beijing, married women at 30 to 34 years old are the high-risk group in CIN incidence and the infection of high-risk HPV is an independent risk factor. Liquid-base cytology combined with high-risk HPV DNA test is a viable method to discover CIN in time and prevent the incidence of cervical cancer.


Open radical retropubic prostatectomy 2007: the true minimally invasive surgery for localized prostate cancer?
The introduction of robotic laparoscopic assisted prostatectomy at our institution and nationwide has been a great advancement and has caused us to focus and fine-tune our goal for improvements in prostate cancer outcomes whether the patient elects for robotic laparoscopic assisted prostatectomy or open minimally invasive radical retropubic prostatectomy. While these authors favor the open technique performed by highly skilled urologic surgical oncologists, the lessons we have learned to date suggest that it is the skill of the surgeon that determines outcome, regardless of whether or not the operation is performed by an open or robotic laparoscopic technique. The concepts we have articulated here are related to resection and avoidance of positive margins, limited intraoperative blood loss and pain control, which allow equivalence in these outcome areas, regardless of technique.


[Construction of expression vectors for efficient expression of soluble recombinant proteins].
The aim of the study is to construct two vectors for efficient expression of soluble recombinant proteins. The first vector was constructed by cloning the HisSUMO fragment into an expression vector pET30a(+) to fuse with the gene of interest (designated as HisSUMO Express). The second vector was constructed in the same way, but with a hydroxylamine cleavage site between HisSUMO and the gene of interest for an economic purpose (designated as HisSUMO Economic). The mouse fibroblast growth factor-21(mFGF-21), which was difficult to express in routine-used expression vectors, was taken as an example to test the vectors. The results showed that the mFGF-21 was expressed at high level in both vectors. The Sumo/mFGF-21 fusion protein accounted for more than 40% of the total bacterial protein. The fusion protein was purified with Ni-TNA column, and the HisSUMO was removed by cleavage of the fusion protein with either hydroxylamine solution or SUMO protease I. The concentration of the purified mFGF-21 mature protein was 54 mg/L and the recovery rate was 6%. The purified proteins derived from either hydroxylamine or SUMO protease I cleavage could stimulate glucose up-take by adipocytes. These results indicated that both HisSUMO Express and HisSUMO Economic were useful expression vectors for efficient expression of soluble recombinant proteins.


Processing of the Bacillus subtilis thrS leader mRNA is RNase E-dependent in Escherichia coli.
We have recently reported that processing occurs in the untranslated leader region of several members of a family of Gram-positive genes regulated by tRNA-mediated antitermination. We showed that cleavage at this site plays an important role in the induction of Bacillus subtilis thrS gene expression, following threonine starvation, by stabilising the downstream mRNA. Here we show that, when transferred on a plasmid, processing of the B. subtilis thrS leader can occur at the same site in Escherichia coli. Cleavage at this site is dependent on the E. coli endoribonuclease E, both in vivo and in vitro, suggesting that a functional homologue of RNase E is responsible for thrS processing in B. subtilis.


Are Functional Brain Alterations Present in Low Back Pain? A Systematic Review of EEG Studies.
This systematic review analyzed available literature on functional brain alterations in low back pain (LBP) measured with electroencephalography (EEG), as until now evidence thereof was unclear. Four electronic databases were systematically searched the 10th of March 2018, resulting in 12 included studies. Studies showed a risk of bias of 37.5 to 75% using the Newcastle-Ottawa Scale for case-control studies. Limited evidence reported higher amplitudes of balance-related potentials and early components of somatosensory evoked potentials (SEP) to noxious stimuli, and altered feedback-related negativity and P300 potentials during decision-making in chronic LBP (CLBP). These findings suggest postural strategies requiring a higher cortical attention-demand, increased sensory-discriminative processing of noxious input, and altered decision-making in CLBP. However, further research is warranted as these inferences were based on single studies. Moderate evidence for unaltered amplitude of late-phase SEPs to noxious stimuli and auditory evoked potentials in LBP implies that the affective-emotional processing of stimuli might be unaffected in LBP. Furthermore, moderate evidence indicated disturbed habituation of somatosensory stimuli in LBP. Most studies examined nonspecific or mixed CLBP populations, hence EEG-quantified brain activity in (sub)acute or recurrent LBP still needs to be explored. PERSPECTIVE: This review presents an overview of the current understanding of the functional LBP brain measured with EEG. The limited evidence in current research suggests altered cortical function regarding balance control, somatosensory processing, and decision making in LBP, and highlights opportunities for future EEG-research.


Pre-operative management of patients on drugs affecting blood coagulation.
The aim of the study is to present practical guidelines for the pre-operative management of patients taking commonly applied drugs that affect blood coagulation. In hospital practice it is the responsibility of an internist to evaluate the patient's condition before the patient undergoes surgery. Among the patients consulted by the internist prior to the surgery the number of patients taking the drugs affecting coagulation is on the increase. The surgery performed on these patients carries the increased risk of bleeding that may threaten health or even life of the patient.


Tongluo Xingnao effervescent tablet reverses memory deficit and reduces plaque load in APPswe/PS1dE9 mice.
Alzheimer's disease (AD) is the most common type of dementia. Amyloid-β (Aβ)-induced neurodegeneration is hypothesized to be the primary pathological mechanism of AD. Tongluo Xingnao effervescent tablets (TXET), based on the traditional Chinese formula Qionggui Tang, have been used to treat AD and other types of dementia in China for decades. In the present study, the effects of TXET on cognition deficit, amyloid-β production, amyloid precursor protein procession and β-secretase expression were investigated in the APPswe/PS1dE9 mouse model of AD. As expected, APPswe/PS1dE9 mice exhibited cognitive decline and higher levels of Aβ and plaques in the brain compared with normal mice; however, these changes were attenuated following TXET treatment. Levels of C-terminal fragment (CTF)-β protein were decreased following treatment with TXET; however, CTF-α levels were unaffected. Furthermore, TXET treatment did not decrease γ-secretase activity or levels of presenilin-1 (PS1), neprilysin or insulin-degrading enzyme. These results indicate that TXET may regulate Aβ metabolism by downregulating the expression of β-secretase. The results of the present study have laid the foundation for the development of a Chinese medicinal compound with a β-secretase inhibitor as the target for the treatment of AD.