Comparably improved health-related quality of life after total arterial revascularization versus conventional coronary surgery--Copenhagen arterial revascularization randomized patency and outcome trial.
We compared health-related quality of life up to 11 months after coronary artery bypass grafting using total arterial revascularization versus conventional coronary surgery. In this randomized single-center trial, 161 patients underwent total arterial revascularization using single or bilateral internal thoracic artery (ITA) and radial artery grafts versus 170 patients conventionally revascularized using left ITA and saphenous vein grafts. Preoperatively, and at 3 and 11 months, postoperatively, patients filled in the generic questionnaire Short Form-36 (SF-36). The mean age was 59±8 years and 39 were women (12%). Median EuroSCORE (European System for Cardiac Risk Evaluation) was 2 (interquartile range 1-4). More than 90% of patients filled in the questionnaire at all three time points. Preoperatively, all scores were lower (P<0.001) than for a sample of the general Danish population. On all scales of the SF-36, there was statistically significant improvement at 3 and 11 months in both groups. For 'social functioning', the improvement following total arterial revascularization was significantly higher than following conventional revascularization (P=0.01). For total arterial revascularization, there were also not statistically significant improvements for 'physical component summary' (P=0.09), 'bodily pain' (P=0.07) and 'vitality' (P=0.08). Health-related quality of life up to 1 year after total arterial revascularization is equal or slightly better than results after conventional coronary surgery.


Estimated continuous cardiac output based on pulse wave transit time in off-pump coronary artery bypass grafting: a comparison with transpulmonary thermodilution.
To evaluate the accuracy of estimated continuous cardiac output (esCCO) based on pulse wave transit time in comparison with cardiac output (CO) assessed by transpulmonary thermodilution (TPTD) in off-pump coronary artery bypass grafting (OPCAB). We calibrated the esCCO system with non-invasive (Part 1) and invasive (Part 2) blood pressure and compared with TPTD measurements. We performed parallel measurements of CO with both techniques and assessed the accuracy and precision of individual CO values and agreement of trends of changes perioperatively (Part 1) and postoperatively (Part 2). A Bland-Altman analysis revealed a bias between non-invasive esCCO and TPTD of 0.9 L/min and limits of agreement of ±2.8 L/min. Intraoperative bias was 1.2 L/min with limits of agreement of ±2.9 L/min and percentage error (PE) of 64 %. Postoperatively, bias was 0.4 L/min, limits of agreement of ±2.3 L/min and PE of 41 %. A Bland-Altman analysis of invasive esCCO and TPTD after OPCAB found bias of 0.3 L/min with limits of agreement of ±2.1 L/min and PE of 40 %. A 4-quadrant plot analysis of non-invasive esCCO versus TPTD revealed overall, intraoperative and postoperative concordance rate of 76, 65, and 89 %, respectively. The analysis of trending ability of invasive esCCO after OPCAB revealed concordance rate of 73 %. During OPCAB, esCCO demonstrated poor accuracy, precision and trending ability compared to TPTD. Postoperatively, non-invasive esCCO showed better agreement with TPTD. However, invasive calibration of esCCO did not improve the accuracy and precision and the trending ability of method.


Determinants of rate of change in functional disability: An application of latent growth curve modeling.
Our aim was to identify disablement factors, including predisposing, intra-individual, and extra-individual factors, which predict the rate of change in general functional disability (GFD) in older adults. This study utilized the Taiwan Longitudinal Study on Aging Survey in 1996-2007 (N=3,186). Multiple-indicator latent growth curve modeling was used to examine how 12 disablement factors predicted the rate of change in GFD. GFD trajectories were modeled using Nagi's functional limitations, activities of daily living, and instrumental activities of daily living. Greater age (B=.025), female gender (B=.114), and greater numbers of comorbidities (B=.038) were associated with faster increase in GFD. Education (B=-.005) and participation in physically active leisure time activities (B=-.031) were associated with slower increase in GFD. Our findings add to the understanding of how disablement factors contribute to the rate of change in GFD. Predisposing factors played the main role. However, the factors we found to be associated with the rate of change in GFD in older adults were slightly different from the factors reported in the literature. Decreasing the number of comorbidities and increasing the level of physically active leisure time activity should be considered priorities for preventing disability as people age.


Fetal plasma renin and renin substrate in mid-trimester pregnancy.
Blood samples were obtained by fetoscopy from 30 fetuses in the middle trimester of pregnancy. The results indicate that high concentrations of renin and relatively low levels of renin substrate are present in the fetus early in pregnancy. These values are similar to those previously demonstrated in the full-term fetus.


[Isolated cervical intramedullary metastasis from breast cancer. Value of magnetic resonance imaging].
A metastasis from a breast carcinoma developed in the cervical cord. The localisation and nature of the lesion were easily diagnosed by a contrast MRI study with Gadolinium DTPA.


Utilizing Social Determinants of Health to Elicit Perceived Control Beliefs About Physical Activity Among African Americans.
This qualitative study explored African Americans' perceived behavioral control (PBC) beliefs about how social determinants of health (SDoH) impact their physical activity behavior. Thirty semi-structured interviews were conducted with African Americans aged 30-50 in Oklahoma. Interviews were audio recorded, transcribed, coded, and analyzed for themes by two independent coders. Economic stability themes represented beliefs that financial status facilitates physical activity, yet, employment duties impede physical activity. SES barriers to physical activity did not emerge within this relatively high SES sample. Neighborhood and built environment themes represented beliefs that accessibility facilitates physical activity, while inclement weather impedes physical activity. Although not a part of the question path, motivation emerged as a theme and represented beliefs about how motivation impacts physically active behavior in the absence of other SDoH barriers. This research can inform interventions developed to promote physical activity among African American adults in the central US.


Systemic drug photosensitivity-Culprits, impact and investigation in 122 patients.
Systemic drugs are a potentially reversible cause of photosensitivity. We explore prevalence, impact, phototest findings and culprit drugs. Retrospective review of patients was diagnosed with drug-induced photosensitivity in a specialist photoinvestigation centre (2000-2016), using data recorded in standardized pro forma. Patients underwent detailed clinical evaluation. Monochromator phototesting was performed to 300 ± 5 nm, 320 ± 10 nm, 330 ± 10 nm, 350 ± 20 nm, 370 ± 20 nm, 400 ± 20 nm, 500 ± 20nm and 600 ± 20 nm. Broadband UVA and solar-simulated radiation (SSR) testing were performed, and photopatch testing and laboratory tests examined for other causes of photosensitivity. DLQI was evaluated. Prevalence of drug-induced photosensitivity was 5.4% (122/2243) patients presenting with photosensitivity. Patients with drug-induced photosensitivity were 52.5% female; median 62 years (range 11-86); phototype I (17.2%), II (39.3%), III (26.2%), IV (6.5%), V (4.1%). Fifty-five (45.1%) patients had reduced erythemal thresholds on monochromator phototesting: 83.6%% to UVA alone, 14.5% to both UVA and UVB, 1.8% to UVA and visible light; 61.4% (n = 75) showed abnormal response to broadband UVR. Drugs implicated: quinine (11.5%), diuretics (10.7%; thiazide 9.8%), antifungals (9.8%), proton-pump-inhibitors (9.8%), angiotensin-converting enzyme inhibitors (7.4%), anti-inflammatory drugs (6.6%), statins (5.7%), selective serotonin reuptake inhibitors (4.9%), calcium channel antagonists (3.3%), anti-epileptics (3.3%), tricyclic antidepressants (3.3%), beta-blockers (2.5%), antibiotics (2.5%), others (≤1.6% cases each). Emerging culprits included azathioprine (2.5%) and biologics (TNF-α inhibitors, denosumab; 2.5%). Median DLQI was 11 (range 2-27) for the past year. Classically described photosensitizing drugs such as thiazides and quinine remain common offenders, while emerging culprits include biologics such as TNF-a inhibitors and proton-pump-inhibitors. There is very large impact on life quality; identification facilitates measures including drug cessation and implementation of appropriate photoprotection.


Investigation of the clinical significance and pathological features of lanthanum deposition in the gastric mucosa.
There are often specific endoscopic findings caused by deposition of lanthanum (La) in the gastric mucosa of patients taking lanthanum carbonate (LaC), a novel phosphate binder for patients on hemodialysis. We conducted a retrospective study to investigate the clinical significance of La deposition in the gastric mucosa, and the association between endoscopic features and histologic findings in the same population. We compared background factors in patients taking LaC with and without La deposition in their gastroscopic biopsy specimen. We also investigated the relationship between gastric endoscopic biopsy specimens with La deposition and the concurrent endoscopic images. There was a significant difference in the total dose of LaC between the La-positive and La-negative groups (990 g [180-3150 g] vs. 480 g [225-1328 g]; p = 0.013). In 27 biopsy specimens with specific whitish mucosa, 10 showed mild histiocytic infiltration and 17 showed severe infiltration. In contrast, among 24 specimens with non-whitish mucosa, 5 showed no histiocytic infiltration, 10 showed mild infiltration, and 9 showed severe infiltration. There was a significant relationship between endoscopic features and the degree of histiocytic infiltration (p = 0.026). We demonstrated that La deposition in the gastric mucosa depended on the total dose of LaC and was not affected by background factors. The specific endoscopic features of La deposition are associated with the infiltration of histiocytes, which represents the body's normal response to foreign bodies. Trial registry The protocol was registered in the University Hospital Medical Information Network Clinical Trial Registry (UMIN000038929, https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000044393 ).


Myostatin/activin pathway antagonism: molecular basis and therapeutic potential.
Muscle wasting is associated with a wide range of catabolic diseases. This debilitating loss of muscle mass and functional capacity reduces the quality of life and increases the risks of morbidity and mortality. Major progress has been made in understanding the biochemical mechanisms and signaling pathways regulating muscle protein balance under normal conditions and the enhanced protein loss in atrophying muscles. It is now clear that activation of myostatin/activin signaling is critical in triggering the accelerated muscle catabolism that causes muscle loss in multiple disease states. Binding of myostatin and activin to the ActRIIB receptor complex on muscle cell membrane leads to activation of Smad2/3-mediated transcription, which in turn stimulates FoxO-dependent transcription and enhanced muscle protein breakdown via ubiquitin-proteasome system and autophagy. In addition, Smad activation inhibits muscle protein synthesis by suppressing Akt signaling. Pharmacological blockade of the myostatin/activin-ActRIIB pathway has been shown to prevent or reverse the loss of muscle mass and strength in various disease models including cancer cachexia and renal failure. Moreover, it can markedly prolong the lifespan of animals with cancer-associated muscle loss. Furthermore, inhibiting myostatin/activin actions also improves insulin sensitivity, reduces excessive adiposity, attenuates systemic inflammation, and accelerates bone fracture healing in disease models. Based on these exciting advances, the potential therapeutic benefits of myostatin/activin antagonism are now being tested in multiple clinical settings. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.


Comparison of recombinant adenovirus and synthetic peptide for DC-based melanoma vaccination.
Optimal strategies for antigen-specific melanoma vaccination are currently being defined in experimental mouse models. Using a single H2-K(b)-binding peptide epitope derived from the melanosomal enzyme tyrosinase-related protein 2 (TRP2) in C57BL/6 mice, we show that adenovirus-transduced dendritic cells (DC) are clearly superior to peptide-pulsed DC for the induction of CD8+ T cells and antimelanoma immunity. Vaccine efficacy strictly depended on the presence of linked CD4+ T-cell help during the priming but not the effector phase of the immune response. These results provide important information for the translation of melanoma vaccine strategy in future clinical applications.


Medical center supports patient advocacy.
At Hurley Medical Center, patient advocates enjoy an amiable relationship with administrators and are considered a valuable management information resource.


When stable RNA becomes unstable: the degradation of ribosomes in bacteria and beyond.
This review takes a comparative look at the various scenarios where ribosomes are degraded in bacteria and eukaryotes with emphasis on studies involving Escherichia coli and Saccharomyces cerevisiae. While the molecular mechanisms of degradation in bacteria and yeast appear somewhat different, we argue that the underlying causes of ribosome degradation are remarkably similar. In both model organisms during ribosomal assembly, partially formed pre-ribosomal particles can be degraded by at least two different sequentially-acting quality control pathways and fully assembled but functionally faulty ribosomes can be degraded in a separate quality control pathway. In addition, ribosomes that are both structurally- and functionally-sound can be degraded as an adaptive measure to stress.


The CD40 ligand, gp39, is defective in activated T cells from patients with X-linked hyper-IgM syndrome.
The prominent role of the CD40 receptor in B cell responses led us to investigate the role of the gp39-CD40 interaction in a group of primary immunodeficient patients with defective antibody production. Here we report that patients with hyper-IgM syndrome (HIM) have a defective gp39-CD40 interaction. B cells from HIM patients express functional CD40, but their T cells do not bind CD40-Ig. These patients expressed normal levels of gp39 mRNA, but these mRNAs encode defective gp39 proteins owing to mutations in the extracellular domain of gp39. Soluble recombinant forms of gp39 containing these mutations were unable to bind CD40 and drive normal B cell proliferation. The gene encoding gp39 was mapped to Xq26, the X chromosome region where the gene responsible for HIM had previously been mapped. These data suggest that a defect in gp39 is the basis of X-linked HIM.


Gastrinoma with multiple liver metastases: effectiveness of dacarbazine (DTIC) therapy.
Gastrinoma when associated with liver metastasis results in markedly reduced survival. However, a standard chemotherapeutic protocol for patients with unresectable tumors has not been established. We treated two patients with gastrinoma with multiple liver metastases with intravenous administration of 5-dimethyltriazenoimidazole-4-carboxamide (DTIC; dacarbazine) at a dose of 200 mg/body for 5 consecutive days. The first patient showed a marked decrease in serum gastrin levels, from 338 000 pg/ml to 22 900 pg/ml (normal range, >220pg/ml), as well as a decrease in the size and number of peripancreatic and liver tumors, after four courses of DTIC. An additional nine courses of the treatment were given, and the peripancreatic tumor was resected. The patient has been in good overall condition for more than 3(1/2) years. The second patient was treated with a total of ten courses of DTIC. Serum gastrin levels did not increase and the hepatic tumor did not change in size for more than 4 years. DTIC was effective in controlling the clinical and biochemical manifestations of gastrinoma associated with liver metastasis without serious side effects. As the toxity of DTIC is minimal, (e.g., nausea and vomiting) DTIC therapy should be considered useful for islet cell carcinomas with multiple metastases.


The introductory placebo washout: a retrospective evaluation.
We examined the effects of the "introductory placebo washout" technique by reanalyzing the results of a recent trial of an experimental antidepressant. At the beginning, all patients were placed on placebo in a single-blind design. Patients who were rated as placebo responders with the physician-administered Hamilton Rating Scale for Depression (HRSD) were excluded from the trial. In spite of this technique, an alternative measure of depression indicated that many patients with a positive response to placebo had been entered in the trial. In the reanalysis, elimination of these "hidden placebo responders" did not lower the final placebo response rate and actually diminished the differences observed at the end of the study between the active treatment and placebo groups. These data suggest that the introductory placebo washout may have unpredictable, possibly confounding effects on patient samples in trials of antidepressant agents.


Identification of the high-molecular-mass mitochondrial oxaloacetate keto-enol tautomerase as inactive aconitase.
The homogeneous bovine heart mitochondrial high-molecular-mass oxaloacetate keto-enol tautomerase [(1988) Biochim. Biophys. Acta 936, 10-19] is shown to be an iron-sulfur protein as revealed by the enzyme spectral properties and direct chemical determination of non-heme iron and acid-labile sulfur. The protein is capable of catalysing the aconitase reaction after treatment with ferrous ions under anaerobic conditions. Treatment of the 'activated' protein with N-ethylmaleimide results in the simultaneous irreversible loss of the oxaloacetate keto-enol tautomerase and aconitase activities. The effects of some substrates and inhibitors on both activities show that the same catalytic site is involved in the oxaloacetate tautomerase and aconitase reactions. It is concluded that the protein previously described as a 80 kDa oxaloacetate keto-enol tautomerase is inactive aconitase.


Laminar organization of peptide-like immunoreactivity in the anuran optic tectum.
Peptide, 5-hydroxytryptamine (5-HT)-, tyrosine hydroxylase (TOH)-, and glial fibrillary acidic protein (GFAP)-like immunoreactivity was studied in the optic tectum of Rana pipiens. Peroxidase-antiperoxidase and indirect immunofluorescence single- and double-labeling methods were used to compare differential laminar distribution of each of these substances. Substance P (SP), leucine-enkephalin (LENK), cholecystokinin octapeptide (CCK8), bombesin (BOM), avian pancreatic polypeptide (APP), and possibly neurotensin display unique individual patterns of laminar distribution of processes and cell bodies throughout the tectum. A correlative analysis of the topographical distribution of SP, LENK, BOM, and APP on the basis of double-labeled sections shows a precise laminar segregation of these substances. Vasoactive intestinal peptide-, beta-endorphin-, and ranatensinlike immunoreactivity is consistently absent from our material. 5HT- and TOH-like immunoreactivity discloses a reticular array of fibers without clear evidence of laminar organization. This peptide-like laminar organization is particularly elaborate throughout the superficial neuropil of the optic tectum, the major retinorecipient zone. The pattern of lamination demonstrated in the present study differs in several important features from that previously described on the basis of several histological methods. The cells of origin of processes (axons and/or dendrites) in the superficial tectal neuropil may be either intrinsic or extrinsic to the tectum. Special reference is made to conflicting evidence regarding the possibility of a retinal contribution to peptide-like tectal lamination.


Paternal high-fat diet alters triglyceride metabolism-related gene expression in liver and white adipose tissue of male mouse offspring.
Obesity is a major public health problem, and its prevalence is progressively increasing worldwide. In addition, accumulating evidence suggests that diverse nutritional and metabolic disturbances including obesity can be transmitted from parents to offspring via transgenerational epigenetic inheritance. The previous reports have shown that paternal obesity has profound impacts on the development and metabolic health of their progeny. However, little information is available concerning the effects of paternal high-fat diet (HFD) exposure on triglyceride metabolism in the offspring. Therefore, we investigated the effects of paternal HFD on triglyceride metabolism and related gene expression in male mouse offspring. We found that paternal HFD exposure significantly increased the body weight, liver and epididymal white adipose tissue (eWAT) weights, and liver triglyceride content in male offspring, despite consuming control diet. In addition, paternal HFD exposure had induced changes in the mRNA expression of genes involved in lipid and triglyceride metabolism in the liver and eWAT. These findings indicate transgenerational inheritance from the paternal metabolic disturbance of triglyceride and support the effects of paternal lifestyle choices on offspring development and health later in life.


Heme oxygenase: function, multiplicity, regulatory mechanisms, and clinical applications.
In biological systems oxidation of heme is carried out by two isozymes of the microsomal heme oxygenase, HO-1 and HO-2. HO-1 is the commonly known heme oxygenase, the activity of which can be induced by up to 100-fold in response to a wide variety of stimuli (metals, heme, hormones, etc.). HO-2 was only recently discovered, and the isozyme appears to be uninducible. The two forms are products of two different genes and differ in their tissue expression. The primary structure of HO-1 and an HO-2 fragment of 91 amino acid residues show only 58% homology, but share a region with 100% secondary structure homology. This region is believed to be the catalytic site. Most likely, HO-1 gene is regulated in the same manner as metallothione in the gene. HO-1 has a heat shock regulatory element, and possibly many promoter elements, which bind to respective inducers and cause transcription of the gene. In vivo induction of HO-1 activity in the liver is accompanied by decreases in the total P-450 levels and, in a reconstituted system, cytochrome P-450b heme can be quantitatively converted to biliverdin by HO-1 and HO-2. The enzyme activity is inhibited in vivo for extended periods subsequent to binding of Zn- and Sn- protoporphyrins. This property appears useful for the suppression of bilirubin production. The metalloporphyrins, however, are not innocuous and cause major disruptions in cellular metabolism. In this review recent findings on heme oxygenase are highlighted.


Investigation of the mechanism of copy number variations involving the α-globin gene cluster on chromosome 16: two case reports and literature review.
Thalassemia is one of the most common single-gene disorder worldwide. An important genetic cause of thalassemia is copy number variations (CNVs) in the α-globin gene cluster. However, there is no unified summary and discussion on the detailed information and mechanisms of these CNVs. In this study, two novel CNVs, a tandem duplication (αααα159) and deletion (--259), were identified in two Chinese families with thalassemia patients, according to the results of hematologic analysis, routine genetic testing for thalassemia, multiplex ligation-dependent probe amplification (MLPA), next-generation sequencing (NGS) and other molecular methods. Co-inherited with βCD41-42 mutation and --SEA deletion separately, αααα159 and --259 resulted in a patient with β-thalassemia intermedia and a lethal fetus with Hb Bart's hydrops fetalis syndrome, respectively. Next, a literature review was performed to summarize all known CNVs involving the α-globin gene cluster. The molecular structure characteristics of these CNVs were analyzed and the possible mechanism was explored. It is the first time to analyze the generation mechanism of genome arrangements in the α-globin gene cluster systematically.


Central auditory processing. I. Ear dominance--a perceptual or an attentional asymmetry?
The phenomenon of ear dominance for pitch described by Efron and Yund has been attributed by them to an asymmetry of sensory origin in the binaural integration of dichotic tone pairs. An explanation of this phenomenon in terms of an attentional bias is rejected on the basis of two experiments where the possibility of such bias was excluded. These and other experiments indicate that a simple explanation of this ear dominance in terms of a hemispheric specialization in the processing of tonal stimuli also must be rejected.


Plasma Levels of High Sensitivity Cardiac Troponin T in Adults with Repaired Tetralogy of Fallot.
Detectable low circulating level of cardiac troponin T (cTnT) may reflect subclinical myocardial injury. We tested the hypothesis that circulating levels of hs-cTnT are altered in adults with repaired tetralogy of Fallot (TOF) and associated with ventricular volume load and function. Eighty-eight TOF patients and 48 controls were studied. Plasma hs-cTnT levels were determined using a highly sensitive assay (hs-cTnT). The right (RV) and left ventricular (LV) volumes and ejection fraction (EF) were measured using 3D echocardiography and, in 52 patients, cardiac magnetic resonance (CMR). The median (interquartile range) for male and female patients were 4.87 (3.83-6.62) ng/L and 3.11 (1.00-3.87) ng/L, respectively. Thirty percent of female but none of the male patients had increased hs-cTnT levels. Female patients with elevated hs-cTnT levels, compared to those without, had greater RV end-diastolic and end-systolic volumes and LV systolic dyssynchrony index (all p < 0.05). For patient cohort only, hs-cTnT levels correlated positively with CMR-derived RV end-diastolic volume and negatively with echocardiography-derived LV and RV EF (all p < 0.05). Multiple linear regression identified sex and RV EF as significant correlates of log-transformed hs-cTnT levels. Increased hs-cTnT levels occur in 30% of female patients after TOF repair, and are associated with greater RV volumes and worse RV EF.


Renal lesions following administration of calcitonin. A consideration on the morphological similarities to IgA nephropathy.
In previous papers angiolysis of mesenteric arteries and mesangiolytic changes of renal arteries following administration of a vast amount of Na2EDTA were reported. In this study the effect of the calcium depressor calcitonin is investigated experimentally in the kidney. Long-term observation over 6 months demonstrates early stages of mesangiolysis in the renal glomeruli, morphological changes of the basement membrane and mesangial cell proliferation. Moreover, paramesangial dense deposits, probably consisting of IgA were visualized. The variable intensities of the lesions in different glomeruli and segments are very similar to those observed in IgA nephropathy.


Common origin of inferior mesenteric and accessory renal artery.
Arteriography performed in the preoperative evaluation of a patient with horseshoe kidney and renal calculi revealed a common origin of the inferior mesenteric artery and an anomalous left lower polar renal artery. The origin of the anomaly and its clinical significance are reviewed.


Vascular endothelial growth factor-D is a survival factor for human breast carcinoma cells.
Vascular endothelial growth factor-D (VEGF-D) stimulates growth of vascular and lymphatic endothelial cells by signaling through the tyrosine kinase receptors KDR (VEGFR-2) and Flt-4 (VEGFR-3). In the present study, we examined the effects of VEGF-D on apoptosis in human MCF-7 and MDA-MB-231 breast carcinoma cells. Because VEGF-D was not expressed constitutively in vitro, stable VEGF-D transfectants were produced. The VEGF-D-expressing MCF-7 and MDA-MB-231 lines displayed resistance to apoptosis induced by hypoxia, staurosporin and cycloheximide. Increased Bcl-2 expression, decreased homogenous caspase activities and inhibition of poly(ADP-ribose) polymerase cleavage were associated with inhibition of apoptosis in VEGF-D-expressing clones. Also, caspase-3 activation was suppressed in the VEGF-D expressing MDA-MB-231 clone. The antiapoptotic effect of VEGF-D in vitro was recapitulated in vivo using VEGF-D-expressing MDA-MB-231 xenografts. The lack of VEGFR-2 protein expression by Western blot and ineffectiveness of a neutralizing VEGFR-2 antibody in eliminating the antiapoptotic effects of VEGF-D suggest a different and yet unknown signaling mechanism. Our findings indicate that VEGF-D has a novel function as a survival factor of breast carcinoma cells in addition to its established functions as an angiogenic and lymphangiogenic factor.


The exodus of German dermatologists and their contributions to their adopted countries.
This study reviews the establishment of dermatology in Germany, the exodus of German dermatologists during the Third Reich, and their contribution to dermatology in the United States and European countries.


Evaluation of relative active tectonics by using geomorphic indices of the Bamo anticline, Zagros Fold-Thrust Belt, Kurdistan Region of Iraq.
The Mountain Front Flexure forms a prominent morphotectonic structures along the Zagros Fold-Thrust Belt (ZFTB). It consists of several segments that defines tectonic salients and recessions within the belt. These segments are separated by strike-slip faults, including Khanaqin fault, which forms the boundary between the Kirkuk embayment and Lurestan Arc. The Bamo anticline is a complex N-S trending structure located above the Khanaqin fault zone, and it is thought to manifest active deformation in the Zagros Fold-Thrust Belt and along the fault. This study examines the state of active tectonics along the Bamo anticline through quantitative analyses of the evolved landscape using geomorphic indices. For that reason, six indices have been chosen for the analysis, such as stream length-gradient index (SL), drainage basin asymmetry (AF), hypsometric integral and hypsometric curve (HI & HC), ratio of valley-floor width to valley height (VF), basin shape (BS), and mountain front sinuosity (Smf). Each index's results were categorized into three classes, and the results from the first five indices, excluding Smf, were integrated to get the index of relative active tectonics (IRAT). This index was then compared with the results of Smf to assess the relative active tectonics (RAT) along the anticline. The results of the IRAT, classified into four classes from very high to low tectonic activity, reveal that no area is classified as class 1 (very high activity). However, 38% and 56% of the region are categorized as classes 2 (high activity) and 3 (moderate activity), respectively. Furthermore, the remaining 6% of the research area exhibits class 4 (low activity). The Smf values for the Northern, Middle, and Southern segments of the anticline are 1.12, 1.18, and 1.27, respectively. Consequently, based on the Smf data, all mountain fronts are classified as class 2 (moderate tectonic activity.


Polymorphisms in DNA repair and apoptosis-related genes and clinical outcomes of patients with non-small cell lung cancer treated with first-line paclitaxel-cisplatin chemotherapy.
This study was conducted to analyze a comprehensive panel of single nucleotide polymorphisms (SNPs) in genes in DNA repair and apoptosis pathways and determine the relationship between polymorphisms and treatment outcomes of patients with non-small cell lung cancer (NSCLC) treated with first-line paclitaxel-cisplatin chemotherapy. Three hundred eighty two patients with NSCLC were enrolled. Seventy-four SNPs in 48 genes (42 SNPs in 27 DNA repair pathway genes and 32 SNPs in 21 apoptotic pathway genes) were genotyped and their associations with chemotherapy response and overall survival (OS) were analyzed. Among SNPs in DNA repair genes, BRCA1 rs799917 was significantly associated with both chemotherapy response and OS. XRCC1 rs25487 exhibited a significant association with chemotherapy response and ERCC2 rs1052555 with OS. Four SNPs in apoptotic genes (TNFRSF1B rs1061624, BCL2 rs2279115, BIRC5 rs9904341, and CASP8 rs3769818) were significantly associated with OS, but not with response to chemotherapy. When the six SNPs which were associated with OS in individual analysis were combined, OS decreased as the number of bad genotypes increased (P(trend) = 2 × 10(-6)). Patients with 3, and 4-6 bad genotypes had significantly worse OS compared with those carrying 0-2 bad genotypes (adjusted hazard ratio [aHR] = 1.54, 95% CI = 1.14-2.08, P = 0.005; aHR = 2.10, 95% CI = 1.55-2.85, P = 2 × 10(-6), respectively). In conclusion, these findings suggest that the six SNPs identified, particularly their combined genotypes, could be used as biomarkers predicting chemotherapy response and survival of NSCLC patients treated with first-line paclitaxel-cisplatin chemotherapy.


A Comparison of Perineal Myocutaneous Flaps Following Abdominoperineal Excision of the Rectum for Anorectal Pathology.
Flap-based reconstruction following abdominoperineal resection has been used to address the resultant soft tissue defect and reduce postoperative wound complications. Vertical rectus abdominis myocutaneous flaps have been the traditional choice, but locoregional flaps have attracted attention in minimally invasive resection because they avoid additional abdominal dissection. However, few data exist comparing flap types. To compare outcomes for different types of perineal reconstruction in patients undergoing abdominoperineal resection exclusively for anorectal pathology. This was a retrospective comparative study. This study was conducted at a large, tertiary referral institution. Following Institutional Review Board approval, prospectively maintained clinical and financial databases were interrogated and cross-referenced for patients undergoing proctectomy or abdominoperineal resection with flap reconstruction from 2007 to 2018. Patients with primary gynecological or urological pathology were excluded. The primary outcome was flap complication rate. Secondary outcomes included perineal hernia rate, donor site complications, emergency department consult after discharge, readmission <90 days, and length of stay. Data were analyzed using univariate and multivariate techniques. A total of 135 patients (79 female, median age 58 years) were included: 68 rectus, 52 gluteal, and 15 gracilis flap reconstructions. Median follow-up was 46 months. Rates of both major and minor flap complications were similar for rectus and gluteal flaps, even when controlling for differences between groups via multivariate analysis ( p > 0.9), including extent of resection and use of mesh. For all flaps, American Society of Anesthesiology score ≥3 was the only independent predictor of major, but not minor, flap complications. For rectus and gluteal flaps, smoking, female sex, and American Society of Anesthesiology score ≥3 were independent predictors of major flap complications ( p < 0.05). This study was limited by its retrospective nature and potential selection bias associated with flap choice; it was also impossible to quantify defect size. Gluteal flaps have similar complication rates to rectus flaps and may be considered for patients who are otherwise suitable for minimally invasive abdominoperineal resection. See Video Abstract at http://links.lww.com/DCR/B866 .Una comparación de los colgajos miocutáneos perineales después de la escisión abdominoperineal del recto para patología anorectal. La reconstrucción con colgajo después de la resección abdominoperineal se ha utilizado para abordar el defecto de tejido blando resultante y reducir las complicaciones postoperatorias de la herida. Los colgajos miocutáneos verticales del recto abdominal han sido la elección tradicional, pero los colgajos locorregionales han atraído la atención en la resección mínimamente invasiva porque evitan la disección abdominal adicional. Sin embargo, existen pocos datos que comparen los tipos de colgajos.


The Hip-Hop club scene: Gender, grinding and sex.
Hip-Hop culture is a key social medium through which many young men and women from communities of colour in the USA construct their gender. In this study, we focused on the Hip-Hop club scene in New York City with the intention of unpacking narratives of gender dynamics from the perspective of young men and women, and how these relate to their sexual experiences. We conducted a three-year ethnographic study that included ethnographic observations of Hip-Hop clubs and their social scene, and in-depth interviews with young men and young women aged 15-21. This paper describes how young people negotiate gender relations on the dance floor of Hip-Hop clubs. The Hip-Hop club scene represents a context or setting where young men's masculinities are contested by the social environment, where women challenge hypermasculine privilege and where young people can set the stage for what happens next in their sexual and emotional interactions. Hip-Hop culture therefore provides a window into the gender and sexual scripts of many urban minority youth. A fuller understanding of these patterns can offer key insights into the social construction of sexual risk, as well as the possibilities for sexual health promotion, among young people in urban minority populations.


Coumarin glucosides from Cruciata taurica.
Two new coumarin glycosides (1 and 2) along with two known coumarin glucosides, daphnin (3) and daphnetin glucoside (4) were isolated from the aerial parts of Cruciata taurica. The structures of the new compounds were elucidated by spectral methods and chemical means as 7-O-(6' -acetoxy-beta-D-glucopyranosyl)-8-hydroxycoumarin (1) and 7-O-[6 '-O-(3'',4''-dihydroxycinnamoyl)-beta-D-glucopyranosyl]-8-hydroxycoumarin (2). The phylogenetic significance of coumarins in C. taurica was discussed.


Commuting by car: weight gain among physically active adults.
Prolonged sitting, including time spent sitting in cars, is detrimentally associated with health outcomes. This study examined whether commuting by car was associated with adults' weight gain over 4 years. Among 822 adult residents of Adelaide, Australia, weight change was ascertained from self-reported weight at baseline (2003-2004) and at follow-up (2007-2008). Using time spent for car commuting and work status at baseline, participants were categorized as non-car commuters, occasional car commuters, and daily car commuters. Multilevel linear regression (conducted in 2012) examined associations of weight change with car-commuting category, adjusting for potential confounding variables, for the whole sample, and among those who were physically inactive or active (≥150 minutes/week) in their leisure time. For the overall sample, adjusted mean weight gain (95% CI) over 4 years was 1.26 (0.64, 1.89) kg for non-car commuters; 1.53 (0.69, 2.37) kg for occasional car commuters; and 2.18 (1.44, 2.92) kg for daily car commuters (p for trend=0.090). Stratified analyses found a stronger association for those with sufficient leisure-time physical activity. For non-car commuters with sufficient leisure-time physical activity, the adjusted mean weight gain was 0.46 (-0.43, 1.35) kg, which was not significantly greater than 0. Over 4 years, those who used cars daily for commuting tended to gain more weight than those who did not commute by car. This relationship was pronounced among those who were physically active during leisure time. Reducing sedentary time may prevent weight gain among physically active adults.


Algoriphagus shivajiensis sp. nov., isolated from Cochin back water, India.
Novel orange-pigmented, Gram-negative, rod-shaped, non-motile bacteria, designated strains NIO-S3(T) and NIO-S4, were isolated from a water sample collected from Cochin back waters, Thanneermukkom and Arookutty, Kerala, India. Both strains were positive for oxidase and catalase activities, and hydrolyzed gelatin and Tween 40. The predominant fatty acids were iso-C15:0, anteiso-C15:0, iso-C17:0 3OH, C16:1ω7c/C16:1ω6c (summed feature 3) and iso-C17:1ω9c/C16:0 10-methyl (summed feature 9), whereas MK-7 was the major respiratory quinone, and phosphatidylethanolamine, two unidentified phospholipids and one unidentified lipid were the only polar lipids. The DNA G+C content of the two strains was 43.7 and 43.6mol%, respectively. The 16S rRNA gene sequence analysis indicated that they were members of the genus Algoriphagus and closely related to Algoriphagus olei CC-Hsuan-617(T), Algoriphagus aquatilis A8-7(T), Algoriphagus aquaeductus LMG 24398(T) and Algoriphagus mannitolivorans DSM 15301(T), with pairwise sequence similarities of 96.8, 96.6, 96.2 and 96.2%, respectively. DNA-DNA hybridization between strains NIO-S3(T) and NIO-S4 showed a relatedness of 89%. Based on data from the current polyphasic study, the strains are proposed as a novel species of the genus Algoriphagus, for which the name Algoriphagus shivajiensis sp. nov. is proposed. The type strain of A. shivajiensis is NIO-S3(T) (=JCM 17885(T)=MTCC 11066(T)).


[An activity inspired by escape games to engage reflective posture in Ifsi].
In order to encourage first year nursing students to adopt a reflective posture, an educational activity inspired by escape games was proposed in distance learning. This initiative highlights a better knowledge of oneself and a consideration for others, precursor elements in the personal development of the student, in his rise in competences, and to initiate the construction of his professional nursing identity.


Identifying transcriptional targets.
Identifying the targets of transcription factors is important for understanding cellular processes. We review how targets have previously been isolated and outline new technologies that are being developed to identify novel direct targets, including chromatin immunoprecipitation combined with microarray screening and bioinformatic approaches.


An outbreak of Enterobacter cloacae associated with contamination of a blood gas machine.
Over a 3-month period, five cases of Enterobacter cloacae bacteraemia occurred on our neonatal unit. In at least three of these, isolation of the organism coincided with clinical deterioration and evidence of sepsis. In one case, the same strain was isolated from an abscess on the neonate's forearm. The isolates had identical sensitivity patterns being resistant to all beta-lactams tested except imipenem. The extended time course of the infections made cross-infection an unlikely explanation. Moreover, close questioning of the staff and observation of their practices with regard to blood culture collection, failed to reveal any likely mechanism for pseudobacteraemia. On extensive investigation of the environment to try to identify a potential source of the organism, a strain of Enterobacter cloacae, was isolated from the probe of the blood gas machine and the probe cover. No other environmental samples were found to harbour the organism. Subsequent typing procedures showed the blood gas isolate to be indistinguishable from the clinical isolates. Five neonates were successfully treated with imipenem and gentamicin. The exact mechanism whereby these bacteraemias occurred remains obscure. In one case, the baby had positive blood cultures within 2 h of being on the unit and contamination of the blood culture bottle by the doctor taking the culture was suspected. Most of the episodes, however, appeared clinically to be genuine septicaemias. When vigorous infection control procedures were instituted to prevent staff acquisition of the organism from the machine, cases on the unit ceased.


Exploratory Factor Analysis of the Social Communication Disorder Screener.
Currently, there are no existing measures to screen for or diagnose Social (Pragmatic) Communication Disorder (SPCD). We conducted an exploratory factor analysis (EFA) of the Social Communication Disorder Screener (SCDS), a 14-item, parent-report measure based on the DSM-5 diagnostic criteria for SPCD. This EFA examined the internal consistency and factor structure of the SCDS for a sample of 500 parents of children, ages 5-18 years, representative of the U.S. census. Results yielded a correlated three-factor solution with good internal consistency reliability. Findings supported the presence of three subscale as well as the derivation of a total composite score reflecting overall verbal and non-verbal communication and limitations across contexts. Clinical and research implications are discussed.


Ubiquitination of BST-2 protein by HIV-1 Vpu protein does not require lysine, serine, or threonine residues within the BST-2 cytoplasmic domain.
The cellular protein BST-2/CD317/Tetherin has been shown to inhibit the release of HIV-1 and other enveloped viruses from infected cells. The HIV-1 accessory protein Vpu binds to both BST-2 and βTrCP, a substrate-recognition subunit for the SCF (Skip1-Cullin1-F-box protein) E3 ubiquitin ligase complex. This interaction leads to both the degradation of BST-2 and the enhancement of viral egress. Recently BST-2 was shown to be ubiquitinated in this process. Here we have confirmed the Vpu- and βTrCP-dependent multi/polyubiquitination of BST-2. Ubiquitinated BST-2 accumulated in cells treated with a lysosomal inhibitor but not a proteasomal inhibitor. Additionally, we observed that a BST-2 mutant deleted for its cytosolically exposed lysine residues is also ubiquitinated. Subsequent experiments suggested that Vpu promotes BST-2 ubiquitination upon amino acid residues bearing hydroxyl- but not thiol-bearing side chains. However, a BST-2 mutant bearing substitutions for its cytoplasmically exposed Ser, Thr, and Lys residues was still down-regulated, ubiquitinated, and degraded in a Vpu-dependent manner. Our results suggest that Vpu may target either the BST-2 cytoplasmic Tyr residues or the NH(2) terminus itself for ubiquitination.


Effectiveness of Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy With Versus Without Extreme Septal Hypertrophy.
Data on the effectiveness of alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM) and extreme septal hypertrophy (ESH) are lacking. This study aimed to compare the effectiveness of ASA in patients with vs without ESH. Clinical profiles of 17 patients with ESH and 256 patients without ESH were compared. Baseline pressure gradient and limiting symptoms were comparable between patients with and without ESH. At median 1.1 years of follow-up after ASA, pressure gradient was 48.5 ± 40.4 mm Hg in the ESH group and 40.9 ± 35.2 mm Hg in the non-ESH (N-ESH) group (P=.33). Patients with New York Heart Association class III/IV represented 5.9% of the ESH group and 16.9% of the N-ESH group (P=.39). Patients with Canadian Cardiovascular Society class III/IV represented 5.9% of the ESH group and 10.2% of the N-ESH group (P=.87). The effectiveness of ASA seems comparable between patients with and without ESH.


Diversity of tailed phages in Baltic Sea sediment: large number of siphoviruses with extremely long tails.
We present the first attempt at quantitative analysis of morphological diversity of tailed viruses obtained from marine sediments without ultracentrifugation or enrichment on specific host strains. Sandy mud samples were collected in the Gulf of Gdańsk in the spring, autumn and winter. VLPs were analyzed by transmission electron microscopy. The distribution of three groups of tailed phages was similar in all seasons (Siphoviridae: 52% on average; Myoviridae: 42%; Podoviridae: 6%). 19% of siphoviruses had prolate heads. Interestingly, 11% of siphoviral particles had tails longer than 300 nm, and 6% longer than 600 nm.


Positive intravenous secretin test in patients with achlorhydria-related hypergastrinemia.
The intravenous secretin test is widely used to distinguish gastrinoma (Zollinger-Ellison syndrome) from other causes of fasting hypergastrinemia. We report 2 patients with fasting hypergastrinemia and a rise of greater than 200 pg/ml in serum gastrin concentration after intravenous injection of 2 CU/kg body wt of pure natural secretin. Both patients had pentagastrin-fast achlorhydria. Thus, the intravenous secretin test may be positive in patients with achlorhydria-related hypergastrinemia. Gastric acid secretion should be measured in hypergastrinemic patients before embarking on a secretin test.


Geometric method for measuring body surface area: a height-weight formula validated in infants, children, and adults.
Estimates of body surface area were made based on measurement of 81 subjects, ranging from premature infants to adults. SA was calculated geometrically for each subject from 34 body measurements, and the values obtained compared with those based on previously published formulas and graphs. The most widely used formula, that of Du Bois and Du Bois, increasingly underestimated SA as values fell below 0.7 m2; the disparity was greatest in the newborn infant (7.96%). Closer agreement was obtained with the equations and nomograms of Body, Brody, Faber and Melcher, and Sendroy and Cecchini, although minor deviations were noted in some age ranges. The formula SA (m2) = weight (kg)0.5378 X height (cm)0.3964 X 0.024265, derived from the measured data by multiple regression analysis, gave a good fit for all values of SA from less than 0.2 m2 to greater than 2.0 m2 (r = 0.998). This formula was used to construct nomograms for estimation of SA in infants, children, and adults from height (length) and weight.


Integrating UAV data for assessing the ecological response of Spartina alterniflora towards inundation and salinity gradients in coastal wetland.
The overwhelming spread of Spartina alterniflora (smooth cordgrass) has put many native plant communities and coastal environments at risk. A better understanding of how S. alterniflora responds to inundation and salinity gradients will help manage the invasion of this species. However, current spatial quantitative analyses are insufficient. Thus, unmanned aerial vehicles (UAVs) and field sampling data were integrated to assess the ecological response of S. alterniflora to inundation and salinity gradients. This study aimed to determine the optimum ecological range of flooding and saline for S. alterniflora in Dafeng Milu National Nature Reserve in Jiangsu, China. Our results showed that the optimum ecological amplitude of S. alterniflora to flooding depth was [-0.07 m, 0.82 m] and the optimum mean growing point was 0.38 m. Furthermore, the optimum flooding time was [0 h,11.87 h], and the optimum mean growing point was 4.13 h. Our analyses also showed that soil salinity had significant effects on the growth of S. alterniflora. The optimum ecological amplitude of S. alterniflora to soil salinity was [13.77 g/kg, 22.57 g/kg], and the optimum mean growing point was 18.19 g/kg. This is the first spatially quantitative analysis to study the eco-hydrological mechanism driving both the aboveground biomass and height of S. alterniflora over the intertidal zone to the best of our knowledge. Determining the optimal ecological range for flooding and salt will provide a scientific basis for measures to establish the ecological control of S. alterniflora and to predict the expansion of S. alterniflora in response to rising sea levels.


Gestational Glucose Intolerance and Birth Weight-Related Complications.
To evaluate the risks of large-for-gestational-age birth weight (LGA) and birth weight-related complications in pregnant individuals with gestational glucose intolerance, an abnormal screening glucose loading test result without meeting gestational diabetes mellitus (GDM) criteria. In a retrospective cohort study of 46,989 individuals with singleton pregnancies who delivered after 28 weeks of gestation, those with glucose loading test results less than 140 mg/dL were classified as having normal glucose tolerance. Those with glucose loading test results of 140 mg/dL or higher and fewer than two abnormal values on a 3-hour 100-g oral glucose tolerance test (OGTT) were classified as having gestational glucose intolerance. Those with two or more abnormal OGTT values were classified as having GDM. We hypothesized that gestational glucose intolerance would be associated with higher odds of LGA (birth weight greater than the 90th percentile for gestational age and sex). We used generalized estimating equations to examine the odds of LGA in pregnant individuals with gestational glucose intolerance compared with those with normal glucose tolerance, after adjustment for age, body mass index, parity, health insurance, race and ethnicity, and marital status. In addition, we investigated differences in birth weight-related adverse pregnancy outcomes. Large for gestational age was present in 7.8% of 39,685 pregnant individuals with normal glucose tolerance, 9.5% of 4,155 pregnant individuals with gestational glucose intolerance and normal OGTT, 14.5% of 1,438 pregnant individuals with gestational glucose intolerance and one abnormal OGTT value, and 16.0% of 1,711 pregnant individuals with GDM. The adjusted odds of LGA were higher in pregnant individuals with gestational glucose intolerance than in those with normal glucose tolerance overall (adjusted odds ratio [aOR] 1.35, 95% CI 1.23-1.49, P <.001). When compared separately with pregnant individuals with normal glucose tolerance, those with either gestational glucose intolerance subtype had higher adjusted LGA odds (gestational glucose intolerance with normal OGTT aOR 1.21, 95% CI 1.08-1.35, P <.001; gestational glucose intolerance with one abnormal OGTT value aOR 1.77, 95% CI 1.52-2.08, P <.001). The odds of birth weight-related adverse outcomes (including cesarean delivery, severe perineal lacerations, and shoulder dystocia or clavicular fracture) were higher in pregnant individuals with gestational glucose intolerance with one abnormal OGTT value than in those with normal glucose tolerance. Gestational glucose intolerance in pregnancy is associated with birth weight-related adverse pregnancy outcomes. Glucose lowering should be investigated as a strategy for lowering the risk of these outcomes in this group.


Influence of the application time on the penetration of different dental adhesives and a fissure sealant into artificial subsurface lesions in bovine enamel.
Sealing of approximal enamel lesions by infiltration with low viscous resins seems to be a promising approach in non-operative dentistry and should bear advantages compared to remineralization or invasive treatment. The aim of this in vitro study was to evaluate the penetration ability of five dental adhesives and a fissure sealant into initial enamel lesions for an application time of either 15 s or 30 s. In each of 54 specimens of bovine enamel, three windows were demineralized for 14 days. Subsequently, two windows were etched with phosphoric acid for 5s in order to degrade the surface layer, whereas one window served as untreated control. The specimens were randomly divided into six groups and a fissure sealant as well as five different adhesives were applied onto the subsurface lesions and allowed to penetrate for either 15 or 30 s. Overlying material was wiped away and the resins were light cured. To visualize the penetrated resins and the remaining pore structures, the specimens were infiltrated with a low viscous fluorescent resin and studied using a Confocal Laser Scanning Microscope (CLSM). For Helioseal, Heliobond, Resulcin Monobond, and Excite an application time of 30s resulted in significantly higher (p < 0.05; t-test) penetration depths (47-105 microm) compared to 15s (29-49 microm). Helioseal, Heliobond, Resulcin Monobond, and Excite are suitable for sealing artificial subsurface enamel lesions in vitro. After an application time of 30 s a significant deeper penetration could be observed for these materials.


A New Day 4 Grading System to Assess Embryo Quality in Frozen Embryo Transfer Cycles.
To present a new day 4 (D4) embryo grading system to assess embryos in frozen-thawed embryo transfer (FET) cycles. A new grading system (grades A-E) was developed from the 2011 ESHRE Istanbul Consensus for D4 embryos in FET cycles. Embryos with complete compaction were classified as grade A; those with partial compaction were assigned as grade B; and those without compaction were classified as grades C, D, and E according to their different blastomere number ratio (BNR; number of embryo blastomeres on D4/number of embryo blastomeres on D3, D4/D3). Embryos with a BNR of ≥ 1.5 were defined as grade C, those with a BNR of ≥ 1.2 and < 1.5 were defined as grade D, and those with a BNR of ≥ 1.0 and < 1.2 were defined as grade E. Using this proposed grading model, 5460 embryos with known implantation data were retrospectively analyzed after D4 transfer in FET cycles. The transferred embryos exhibited a similar declining trend in implantation and live birth rates from the top grade A to the lowest grade E. The in vitro fertilization group showed increased implantation rates of grade B and E embryos compared with the intracytoplasmic sperm injection group (grade B: 41.99%, 34.63%, χ2 = 5.84, p < 0.05 and grade E: 18.98%, 14.08, χ2 = 75.62, p < 0.01). Receiver-operating characteristic analysis revealed that our proposed model predicted the implantation outcomes and live birth rates of all embryos (area under the curve = 0.65; 95% confidence interval [CI],0.63-0.66; p < 0.01 and AUC = 0.73; 95%CI, 0.65-0.84; p < 0.001, respectively). This study demonstrates that the new grading system provided by us can be a useful tool for assisting embryo selection via changes in embryo morphology. D4 embryo transfer provides a simple and applicable method for FET cycles in daily practice.


Metataxanomic, bioactivity and microbiome analysis of Red Sea marine sponges from Egypt.
Red Sea marine sponges (phylum Porifera) and associated microorganisms harbor a wide range of microorganisms, which are considered an essential source of bioactive products. In this study, we screened both the crude extracts of Red Sea marine sponges and their associated bacterial extract for antimicrobial activity and antiviral activity. Molecular characterization of bioactive producers was performed using16S rRNA sequencing, in addition to metagenomic analysis of three representative sponges utilizing the 16S rRNA gene V3-V4 region sequencing in two different seasons. Twelve samples were collected from five different sponge species by scuba diving, and all the crude extracts of sponges showed antimicrobial activity except Negombata corticata. Moreover, 84 out of 110 bacterial isolates extracts demonstrated antimicrobial activity against at least one tested microorganism. These results revealed the bioactivity and biodiversity of the Red Sea marine invertebrates-associated bacteria. It was found that the bioactive isolates belong to several bacterial groups. The bacterial communities of Negombata magnifica, Negombata corticata, and Siphonochalina siphonella were shown with great diversity and differences in the bacterial percentage, diversity, and unique community composition at different seasons in each sponge species. Unique microenvironment for each sponge species may be linked to the production of specific bioactive product.


BI 1291583: a novel selective inhibitor of cathepsin C with superior in vivo profile for the treatment of bronchiectasis.
Airway inflammation in chronic inflammatory lung diseases (e.g. bronchiectasis) is partly mediated by neutrophil-derived serine protease (NSP)/antiprotease imbalance. NSPs are activated during neutrophil myelopoiesis in bone marrow by cathepsin C (CatC; DPP1). CatC is therefore an attractive target to reduce NSP activity in the lungs of patients with bronchiectasis, restoring the protease/antiprotease balance. We report results from the preclinical pharmacological assessment of the novel CatC inhibitor BI 1291583. Binding kinetics of BI 1291583 to human CatC were determined by surface plasmon resonance. In vitro inhibition of human CatC activity was determined by CatC-specific fluorescent assay, and selectivity was assessed against related cathepsins and unrelated proteases. Inhibition of NSP neutrophil elastase (NE) production was assessed in a human neutrophil progenitor cell line. In vivo inhibition of NE and NSP proteinase 3 (PR3) in bronchoalveolar lavage fluid (BALF) neutrophils after lipopolysaccharide (LPS) challenge and distribution of BI 1291583 was determined in a mouse model. BI 1291583 bound human CatC in a covalent, reversible manner, selectively and fully inhibiting CatC enzymatic activity. This inhibition translated to concentration-dependent inhibition of NE activation in U937 cells and dose-dependent, almost-complete inhibition of NE and PR3 activity in BALF neutrophils in an in vivo LPS-challenge model in mice. BI 1291583 exhibited up to 100 times the exposure in the target tissue bone marrow compared with plasma. BI 1291583-mediated inhibition of CatC is expected to restore the protease-antiprotease balance in the lungs of patients with chronic airway inflammatory diseases such as bronchiectasis.


Estimation of the rate of osteogenesis by tetracycline double labeling in intertrochanteric fractures of the femur in different age groups and its correlation with radiological grading of osteoporosis.
Our aim was to estimate the rate of osteogenesis by using tetracycline double labeling and to correlate it with the radiological grading of osteoporosis in patients of intertrochanteric fracture of the femur in different age groups. Thirty-two cases of intertrochanteric fracture of the femur of either sex, without any associated osteopenic conditions, who were admitted for surgery constituted the clinical material. The cases were divided into three age groups: group I, <45 years; group II, 45-60 years; and group III, >60 years. Osteoporosis was graded in all groups on plain X-rays by Singh's index (SI) and metacarpal index (MI). The patients were labeled with a single large dose (1.5 g) of tetracycline orally on day 1 and day 8. An iliac crest bone biopsy specimen was obtained from each of the patients during surgical intervention. Thin undecalcified sections were made by the hand grinding technique. The sections were studied under UV light for presence of fluorescence, and rate of osteogenesis (mineral appositional rate, MAR) was calculated for each of the groups. Only 7 patients were found to have radiological osteoporosis (by Singh's index). The average MI and MAR were found to be 46.5% and 1.48 microm/day, respectively. The single-dose labeling schedule has shown good fluorescent bands, comparable to the conventional dose schedule. No correlation was found between Singh's index and metacarpal index in group I and III, whereas in group II it was significant. There is no significant correlation between the rate of new bone formation and the radiological grading of osteoporosis.


The asymmetric synthesis and in vitro characterization of succinyl mercaptoalcohol and mercaptoketone inhibitors of matrix metalloproteinases.
A series of succinyl based mercaptoketones and diastereomeric mercaptoalcohols were prepared and evaluated in vitro as inhibitors of the matrix metalloproteinases collagenase-1 (MMP-1), stromelysin (MMP-3), and gelatinase-B (MMP-9).


Ultrasound-Guided Dorsolateral Approach for Quadratus Lumborum Block in Rabbits (Oryctolagus cuniculus): A Prospective, Randomized, Blinded, Cadaveric Study Comparing Four Different Injectate Volumes.
Ultrasound-guided (US-guided) loco-regional anesthesia can provide significant analgesia and anesthetic-sparing effects when used in rabbits. The aims of this study were to investigate the thoraco-lumbar anatomy of the rabbits, particularly the quadratus lumborum (QL) muscle, to design an appropriate US-guided quadratus lumborum block (QLB) specific for rabbits, and to define the most adequate volume of injectate required to consistently cover the ventral branches of T11 to L3 without affecting the pelvic limb innervation (L4, L5 and L6). Sixteen adult rabbit cadavers were included in the study. After randomization, four different volumes of injectate (0.1 mL/kg, 0.2 mL/kg, 0.3 mL/kg and 0.4 mL/kg) were tested, with these volumes additionally randomized to two sites of injection (right or left QL fascia). An ultrasound-guided QLB was performed with a solution of lidocaine, iodinated contrast and tissue dye (in a proportion of 3:1:1 volume, respectively), with subsequent computed tomography (CT) and anatomical dissection, to evaluate the spread of the injectate. In all but one case, the US-guided QLB performed with a dorsolateral approach using 0.3 mL/kg was adequate, while a dose of 0.4 mL/kg consistently reached the targeted nerves but also extended to L4 and caudally. This may suggest that an injectate volume of 0.3 mL/kg may be the most appropriate to produce adequate spread while not affecting pelvic limb innervation.


[Portal hypertension. Choice of therapy for children under 10 years: shunt or palliative surgery?].
Over the last 17 years, 65 cases of portal hypertension have been treated. Major surgery (shunt or disconnection) was performed in 22 children, 7 of these operations being conducted over the last two years by employing two recently developed techniques (Warren's selective distal splenorenal shunt, and Sugiura's wide azygoportal disconnection).


Microvascular Barrier Protection by microRNA-183 via FoxO1 Repression: A Pathway Disturbed in Neuropathy and Complex Regional Pain Syndrome.
Blood nerve barrier disruption and edema are common in neuropathic pain as well as in complex regional pain syndrome (CRPS). MicroRNAs (miRNA) are epigenetic multitarget switches controlling neuronal and non-neuronal cells in pain. The miR-183 complex attenuates hyperexcitability in nociceptors, but additional non-neuronal effects via transcription factors could contribute as well. This study explored exosomal miR-183 in CRPS and murine neuropathy, its effect on the microvascular barrier via transcription factor FoxO1 and tight junction protein claudin-5, and its antihyperalgesic potential. Sciatic miR-183 decreased after CCI. Substitution with perineural miR-183 mimic attenuated mechanical hypersensitivity and restored blood nerve barrier function. In vitro, serum from CCI mice und CRPS patients weakened the microvascular barrier of murine cerebellar endothelial cells, increased active FoxO1 and reduced claudin-5, concomitant with a lack of exosomal miR-183 in CRPS patients. Cellular stress also compromised the microvascular barrier which was rescued either by miR-183 mimic via FoxO1 repression or by prior silencing of Foxo1. PERSPECTIVE: Low miR-183 leading to barrier impairment via FoxO1 and subsequent claudin-5 suppression is a new aspect in the pathophysiology of CRPS and neuropathic pain. This pathway might help untangle the wide symptomatic range of CRPS and nurture further research into miRNA mimics or FoxO1 inhibitors.


Effect of lysine modification on the secondary structure of ovalbumin.
In order to determine the effect of chemical modification of the epsilon-amino groups on the secondary structure of ovalbumin, we prepared six acetylated (17, 36, 54, 70, 82, and 98%) and four succinylated derivatives (25, 50, 72, and 97%) of the protein. Native ovalbumin and the acylated derivatives were homogeneous as revealed by the electrophoretic pattern. The UV-absorption and fluorescence spectra changed progressively with the extent of modification. However, circular dichroic (CD) studies indicated that acylation of 15 of the 20 lysine residues had little effect on the secondary structure of ovalbumin. Acylation of the remaining five lysine residues resulted in a fairly severe change in the secondary structure. The alpha-helical content decreased from about 31% in the native state to 16.5% in the 97% succinylated ovalbumin and to 21.5% in the 98% acetylated derivative. A comparison of these data with the spectral and hydrodynamic data of Qasim and Salahuddin (1978) suggested that the secondary structure of ovalbumin is more resistant to acylation than is the tertiary structure and, thus, the tertiary and the secondary structures are, to some extent, mutually independent. Raising the pH to 11.2 did not alter the secondary structure of ovalbumin and increasing the ionic strength by more than 20-fold did not reverse the loss of helical structure in 97% succinylated protein. These two observations suggest that the change in secondary structure upon maximal acylation may not only involve electrostatic effects, but also certain other factors, such as steric hindrance due to the entering bulky groups.


[Extension of the length of terms of temporary work incapacity, set by the Medical Expert Commission for Evaluation of Work Capacity, in the case of patients with malignant tumors].
The results of granting temporary disability payments for longer periods were followed in 549 patients with malignant tumors at various sites. It was found that 76-82% of stage I-IIa (T1-2N0M0) cancer patients resume working; working ability is limited in 14-18%. Two-thirds of them need another 2-3 months to complete treatment. To allow such patients to stay out of work is essential for prevention of disability from malignant tumors.


[1,2-Bis(di-phenyl-phosphan-yl)ethane-κ2 P,P]chlorido-(isonicotinamide-κN)palladium(II) nitrate aceto-nitrile monosolvate.
The PdII central atom in the title complex, [PdCl(C26H24P2)(C6H6N2O)]NO3·CH3CN or [PdCl(dppe)(INAM)]NO3·CH3CN, where dppe is 1,2-bis-(di-phenyl-phosphan-yl)ethane and INAM is isonicotinamide, exists in a slightly distorted square-planar environment defined by the two P atoms of the dppe ligand, a chloride ligand and the N atom of the isonicotinamide pyridyl ring. The crystal packing in the structure is held together by hydrogen bonds between the amide of the INAM ligand and the nitrate ions that complete the outer coordination sphere. A mol-ecule of aceto-nitrile is also found in the asymmetric unit of the title complex.


Rapamycin restores p14, p15 and p57 expression and inhibits the mTOR/p70S6K pathway in acute lymphoblastic leukemia cells.
The aim of the present study was to investigate the effects of rapamycin and its underlying mechanisms on acute lymphoblastic leukemia (ALL) cells. We found that the p14, p15, and p57 genes were not expressed in ALL cell lines (Molt-4 and Nalm-6) and adult ALL patients, whereas mTOR, 4E-BP1, and p70S6K were highly expressed. In Molt-4 and Nalm-6 cells exposed to rapamycin, cell viability decreased and the cell cycle was arrested at the G1/S phase. Rapamycin restored p14, p15, and p57 gene expression through demethylation of the promoters of these genes. As expected, rapamycin also increased p14 and p15 protein expression in both Molt-4 and Nalm-6 cells, as well as p57 protein expression in Nalm-6 cells. Rapamycin additionally decreased mTOR and p70S6K mRNA levels, as well as p70S6K and p-p70S6K protein levels. However, depletion of mTOR by siRNA did not alter the expression and promoter methylation states of p14, p15, and p57. These results indicate that the inhibitory effect of rapamycin may be due mainly to increased p14, p15, and p57 expression via promoter demethylation and decreased mTOR and p70S6K expression in ALL cell lines. These results suggest a potential role for rapamycin in the treatment of adult ALL.


Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing.
The current study tested the hypothesis that conditioned pain modulation is mediated by the release of endogenous opioids with a placebo-controlled (sugar pill) study of naltrexone (50 mg) in 33 healthy volunteers over two counter-balanced sessions. Pain modulation consisted of rating of heat pain (palm) during concurrent cold water immersion (foot). Compared to baseline heat pain ratings, concurrent foot immersion lowered pain intensity ratings, which suggests an inhibitory effect, was reduced with naltrexone, suggesting at least partial dependence of inhibition on endogenous opioids. An exploratory analysis revealed that individual differences in catastrophizing moderated the effects of naltrexone; endogenous opioid blockade abolished modulation in subjects lower in catastrophizing while modulation was unaffected by naltrexone among high catastrophizers. The results suggest a role of endogenous opioids in endogenous analgesia, but hint that multiple systems might contribute to conditioned pain modulation, and that these systems might be differentially activated as a function of individual differences in responses to pain.


Investigation of the effects of substitution levels, assay methods and length of adaptation to experimental diets on determined metabolisable energy value of maize, barley and soya bean meal.
1. Two experiments were carried out to investigate the influence of substitution levels, assay methods and adaptation length of broilers to experimental diets on metabolisable energy of corn and barley (Experiment 1) and soya bean meal (Experiment 2). In each experiment, the test feedstuffs proportionately replaced the reference diet at the rates of 150, 300 or 450 g/kg. Each treatment had 8 or 7 replicate cages containing three birds per cage. Broiler chickens were adapted to experimental diets for either 7 or 4 d prior to excreta collection on d 20 and 21.2. Metabolisable energy was determined using the difference method at each substitution level and the regression method, using the 4 combinations of the substitution levels.3. In Experiment 1, AME and AMEn were lower (P < 0.01) for barley than for maize, irrespective of the assay method and there was a trend for an adaptation × cereal grains interaction (P < 0.10) for AME determined by the difference regression method. For maize, AME and AMEn calculated using regression or the difference method were not significantly different, whereas barley AME and AMEn values were greater (P < 0.01) when derived using regression analysis.4. In Experiment 2, there was no significant adaptation length × substitution levels interaction. The AME and AMEn values were lowest (P < 0.01) at 150 g/kg SBM inclusion level when calculated using the difference method. On the other hand, AME and AMEn values determined by the regression method were not influenced by substitution levels.5. It was concluded that the influence of substitution levels on assayed metabolisable energy is feedstuff-dependent and that the regression method produced more consistent metabolisable energy values in a feedstuff-independent manner.


Fetal sex-related dysregulation in testosterone production and their receptor expression in the human placenta with preeclampsia.
To determine the effects of fetal sex on aromatase and androgen receptor (AR) expression in the placenta of normal and preeclamptic pregnancies. Placentae from preeclamptic (five female and six male fetuses) and healthy pregnancies (seven female and seven male fetuses) were examined by immunofluorescence, western blotting and quantitative reverse transcriptase PCR. Placental AR levels were significantly higher (P<0.05) in placentae of both male and female fetuses compared with their respective sexes in normal pregnancies. The placental aromatase levels varied depending on fetal sex. If the fetus was female, aromatase levels were substantially higher (P<0.05) in preeclamptic than in normal placentae. If the fetus was male, the aromatase levels were significantly lower (P<0.05) in preeclamptic than in normal placentae. Placental aromatase levels were significantly higher (P<0.05) in male- than in female-bearing normal placentae. Dysregulation in androgen production and signaling in preeclamptic placentae may contribute to placental abnormalities, increasing the frequency of maternal-fetal complications associated with preeclampsia.


In situ generation of micrometer-sized tumor cell-derived vesicles as autologous cancer vaccines for boosting systemic immune responses.
Cancer vaccine, which can promote tumor-specific immunostimulation, is one of the most important immunotherapeutic strategies and holds tremendous potential for cancer treatment/prevention. Here, we prepare a series of nanoparticles composed of doxorubicin- and tyrosine kinase inhibitor-loaded and hyaluronic acid-coated dendritic polymers (termed HDDT nanoparticles) and find that the HDDT nanoparticles can convert various cancer cells to micrometer-sized vesicles (1.6-3.2 μm; termed HMVs) with ~100% cell-to-HMV conversion efficiency. We confirm in two tumor-bearing mouse models that the nanoparticles can restrain tumor growth, induce robust immunogenic cell death, and convert the primary tumor into an antigen depot by producing HMVs in situ to serve as personalized vaccines for cancer immunotherapy. Furthermore, the HDDT-healed mice show a strong immune memory effect and the HDDT treatment can realize long-term protection against tumor rechallenge. Collectively, the present work provides a general strategy for the preparation of tumor-associated antigen-containing vesicles and the development of personalized cancer vaccines.


The amino acid sequence of the CCGG recognizing DNA methyltransferase M.BsuFI: implications for the analysis of sequence recognition by cytosine DNA methyltransferases.
The Bacillus subtilis FI DNA methyltransferase (M.BsuFI) modifies the outer cytosine of the DNA sequence CCGG, causing resistance against R.BsuFI and R.MspI restriction. The M.BsuFI gene was cloned and expressed in B.subtilis and Escherichia coli. As derived from the nucleotide sequence, the M.BsuFI protein has 409 amino acids, corresponding to a molecular mass of 46,918 daltons. Including these data we have compared the nucleotide and amino acid sequences of different CCGG recognizing enzymes. These analyses showed that M.BsuFI is highly related to two other CCGG specific methyltransferases, M.MspI and M.HpaII, which were isolated from Gram-negative bacteria. Between M.BsuFI and M.MspI the sequence similarity is particularly significant in a region, which has been postulated to contain the target recognition domains (TRDs) of cytosine-specific DNA methyltransferases. Apparently M.BsuFI and M.MspI, derived from phylogenetic distant organisms, use highly conserved structural elements for the recognition of the CCGG target sequence. In contrast the very same region of M.HpaII is quite different from those of M.BsuFI and M.MspI. We attribute this difference to the different targeting of methylation within the sequence CCGG, where M.HpaII methylates the inner, M.BsuFI/M.MspI the outer cytosine. Also the CCGG recognizing TRD of the multispecific B.subtilis phage SPR Mtase is distinct from that of the host enzyme, possibly indicating different requirements for TRDs operative in mono- and multispecific enzymes.


Intracortical inhibition and facilitation with unilateral dominant, unilateral nondominant and bilateral movement tasks in left- and right-handed adults.
To investigate intracortical inhibition and facilitation in response to unilateral dominant, nondominant and bilateral biceps activation and short-term upper extremity training in right- and left-handed adults. Paired-pulse transcranial magnetic stimulation was used to measure intracortical excitability in motor dominant and nondominant cortices of 26 nondisabled adults. Neural facilitation and inhibition were measured in each hemisphere during unilateral dominant, nondominant and bilateral arm activation and after training in each condition. No differences were seen between right- and left-handed subjects. Intracortical facilitation and decreased inhibition were seen in each hemisphere with unilateral activation/training of contralateral muscles and bilateral muscle activation/training. Persistent intracortical inhibition was seen in each hemisphere with ipsilateral muscle activation/training. Inhibition was greater in the nondominant hemisphere during dominant hemisphere activation (dominant arm contraction). Strongly dominant individuals show no difference in intracortical responses given handedness. Intracortical activity with unilateral and bilateral arm activation and short-term training differs based on hemispheric dominance, with the motor dominant hemisphere exerting a larger inhibitory influence over the nondominant hemisphere. Bilateral activation and training have a disinhibitory effect in both dominant and nondominant hemispheres.


Buspirone: chemical profile of a new class of anxioselective agents.
Buspirone is a lipophilic, dibasic heterocyclic with no structural resemblance to other anxiolytic or antipsychotic agents. Neurochemical binding studies suggest that buspirone has both dopamine agonist and antagonist properties. Structural comparisons with (+)-butaclamol indicate that buspirone possesses features required for binding at the postsynaptic dopamine receptor site. This is consonant with the drug's biologic properties, but does not define a mechanism for its anxioselective action. The transient antipsychotic effect associated with peak blood levels of buspirone in rats was consistent with such an effect, predicted by [3H]spiperone binding studies. The low (20 mg) anxioselective dose, acting in concert with extensive metabolism in humans, produces low blood levels of the parent drug, suggesting that buspirone's effect is exerted through interactions with a high-affinity, low-threshold receptor system.


Herpes simplex virus 1 UL41 protein abrogates the antiviral activity of hZAP by degrading its mRNA.
The zinc finger antiviral protein (ZAP) is a host restriction factor that inhibits the replication of various viruses by degradation of certain viral mRNA. However, previous study demonstrated that ectopic expression of rat ZAP did not suppress the replication of herpes simplex virus type 1 (HSV-1), an archetypal member of the alphaherpesvirus subfamily, and the molecular mechanism underneath is still illusive. Human ZAP (hZAP) does not suppress the replication of herpes simplex virus 1, and HSV-1 UL41 protein was identified as an antagonist of hZAP by degrading its mRNA. Infection of wild-type (WT), but not UL41-null mutant (R2621) virus, diminished the accumulation of hZAP to abrogate its antiviral activity. Moreover, ectopic expression of hZAP inhibited the replication of R2621 but not WT HSV-1. HSV-1 UL41 was shown for the first time to evade the antiviral function of hZAP via its RNase activity.


Third report of Allochaetophoridae Reck, 1959 (Acari: Trombidiformes) based on the description of a new species from Iran.
A new mite species Allochaetophora iranica sp. nov. (Tetranychoidea: Allochaetophoridae), is described and illustrated based on females and deutonymphs collected from Phragmites australis (Poaceae) in Iran (Kerman Province). This is the third report of the family Allochaetophoridae for the world and first report of it from Asia.


Model-free idealization: Adaptive integrated approach for idealization of ion-channel currents.
Single-channel electrophysiological recordings provide insights into transmembrane ion permeation and channel gating mechanisms. The first step in the analysis of the recorded currents involves an "idealization" process, in which noisy raw data are classified into two discrete levels corresponding to the open and closed states of channels. This provides valuable information on the gating kinetics of ion channels. However, the idealization step is often challenging in cases of currents with poor signal-to-noise ratios and baseline drifts, especially when the gating model of the target channel is not identified. We report herein on a highly robust model-free idealization method for achieving this goal. The algorithm, called adaptive integrated approach for idealization of ion-channel currents (AI2), is composed of Kalman filter and Gaussian mixture model clustering and functions without user input. AI2 automatically determines the noise reduction setting based on the degree of separation between the open and closed levels. We validated the method on pseudo-channel-current datasets that contain either computed or experimentally recorded noise. We also investigated the relationship between the noise reduction parameter of the Kalman filter and the cutoff frequency of the low-pass filter. The AI2 algorithm was then tested on actual experimental data for biological channels including gramicidin A, a voltage-gated sodium channel, and other unidentified channels. We compared the idealization results with those obtained by the conventional methods, including the 50%-threshold-crossing method.


Successful Transplantation of a Liver from a Donor with HELLP Syndrome Undergoing Hypothermic Oxygenated Machine Perfusion (HOPE) Prior to Implantation.
BACKGROUND Liver transplantation (LT) has become the treatment of choice for patients with end-stage liver disease (ESLD). The organ shortage forced clinicians to use livers from donors with certain risk factors, so-called extended-criteria donor (ECD) organs. Hypothermic oxygenated machine perfusion (HOPE) is an alternative to conventional static cold storage and reduces early allograft injury in ECD organs. In this article we present the case of a 45-year-old man with hepatitis B virus (HBV)-associated cirrhosis and hepatocellular carcinoma (HCC) who underwent successful liver transplantation supported by pretransplant hypothermic oxygenated machine perfusion (HOPE) from a 34-year-old extended-criteria donor (ECD) with hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome. CASE REPORT Liver transplantation was scheduled for a 45-year-old man with hepatocellular carcinoma (HCC) due to hepatitis B virus-induced liver cirrhosis. The organ donor was a 34-year-old woman who had developed intracerebral hemorrhage and brain death due to HELLP syndrome after delivery. Compared to the day of admission to the intensive care unit, a decrease in the donor's transaminases was observed prior to organ procurement. Before transplantation, HOPE was conducted after regular back-table preparation of the graft. LT was performed according to the standard surgical techniques and a standardized immunosuppressive regimen was conducted. In the post-transplant period, transaminases peaked directly after the operation and normalized after 1 week. No major surgical complications occurred. The patient was discharged after a 24-day hospital stay with normal liver function. CONCLUSIONS This case report supports the benefits of using HOPE in ECD organs and it should be considered in livers of donors with HELLP syndrome to improve post-transplant outcome.


Confidence limits, error bars and method comparison in molecular modeling. Part 2: comparing methods.
The calculation of error bars for quantities of interest in computational chemistry comes in two forms: (1) Determining the confidence of a prediction, for instance of the property of a molecule; (2) Assessing uncertainty in measuring the difference between properties, for instance between performance metrics of two or more computational approaches. While a former paper in this series concentrated on the first of these, this second paper focuses on comparison, i.e. how do we calculate differences in methods in an accurate and statistically valid manner. Described within are classical statistical approaches for comparing widely used metrics such as enrichment, area under the curve and Pearson's product-moment coefficient, as well as generic measures. These are considered of over single and multiple sets of data and for two or more methods that evince either independent or correlated behavior. General issues concerning significance testing and confidence limits from a Bayesian perspective are discussed, along with size-of-effect aspects of evaluation.


The role of dietitians in residential aged care: How do cooks and chefs perceive their contribution?
This study aimed to explore how dietitians could work with cooks and chefs to contribute to best practice. Data from interviews and focus groups comprising 38 chefs, cooks and food service managers were analysed. Inductive line-by-line coding of transcripts was conducted within a critical realist framework. Coding was completed independently by two authors before reaching consensus on themes. Four main themes emerged: (i) knowledge sharing; (ii) communication; (iii) collaboration; and (iv) accessibility. Participants praised dietitians' knowledge and expertise, but some raised concerns about inconsistency in the advice they received. Dietitians working in residential aged care are ideally positioned to act as advocates for residents and food services. However, findings suggest that experiences of working with dietitians are mixed. Aged care menu guidelines and quality measures could assist, not only in promoting a consistent approach to dietetic advice, but also a system for benchmarking satisfaction and best practice.


Spatial plasticity of the auditory cortex in single-sided deafness.
To evaluate spatial plasticity of the auditory cortex in single-sided deafness (SSD). Cross-sectional study comparing a cohort with adult-onset, idiopathic SSD to a cohort with normal hearing. Demographic, audiometric, magnetoencephalographic imaging, and magnetic resonance imaging data were collected for 13 SSD adult subjects and 13 normal-hearing controls. Locations of peak activation corresponding to the M100 response in auditory cortices ipsilateral and contralateral to tonal stimuli (0.5 kHz and 4 kHz) were extracted from advanced biomagnetic source imaging analyses. Spatial extent of frequency representation across the 0.5 kHz to 4 kHz zone was computed for the two hemispheres. Spatial separation distance between peak locations for 0.5 kHz and 4 kHz stimuli in SSD showed increased activation spread distance in the hemisphere contralateral to the only hearing ear and decreased distance in the ipsilateral hemisphere. In contrast, normal hearing controls had nearly the same activation spread distance in the two hemispheres for ipsilateral and contralateral inputs. The difference between interhemispheric activation spread distance in SSD is significantly increased to 6.5 mm, when compared to 1.7 mm in normal controls (P < .05). Loss of unilateral peripheral input in SSD is associated with spatial reorganization of the auditory cortex in both hemispheres. This change in central auditory functional organization may in turn lead to higher order hearing deficits that rely on interhemispheric processing. Hearing optimization in the only hearing ear may require remediation of both spatial and temporal central auditory changes in SSD. NA Laryngoscope, 126:2785-2791, 2016.


Validation of the electronic Visual Analogue Scale of Anxiety.
Currently, the use of electronic scales is increasing rapidly, which is not surprising considering its accuracy, the ease of use and the increased compliance. The value of Visual Analogue Scales as a mean to objectify subjective variables has long been recognised. The current study aimed to validate the electronic Visual Analogue Scale of Anxiety (eVAAS). Seventy-one subjects, control subjects (n=46) and Panic Disorder patients (n=25), filled out the paper VAAS and the eVAAS in a randomised order. Panic was provoked using 35% CO(2) inhalation allowing us to include maximal scores in our analyses. The correlation between eVAAS and pVAAS was very strong and highly significant (r=0.98, p<0.001). pVAAS scores were slightly higher than eVAAS scores (p<0.001), but this difference is clinically unimportant. The VAAS established on a tablet PC is a useful and valid measure of anxiety and holds intrinsic benefits for anxiety assessment.


[Preventive intervention during the planning of a new factory: contribution of an occupational medicine service on installation of a ceramic dye-producing plant].
The control during the planning of a factory is a sort of prevention. For instance, we suggested industrial hygiene standards for a new chemical plant, which have been into account. According to our suggestions they set up a closed factory process, a dust and fumes filtering plant and the water recycle. After some controls outside the factory, lead and dust concentrations were below the maximum allowed levels (30 and 5 mg/Nmc).


Stem length in revision total knee arthroplasty.
Stems are intramedullary extensions of either the femoral or tibial component of a total knee arthroplasty (TKA) designed to increase the mechanical stability to decrease the risk of aseptic loosening. Biomechanical studies have shown that TKA stems increase the mechanical stability by transferring load over a larger area and thereby reduce strain at the bone-component interface [1-4]. The length of a revision TKA stem is determined by the patient's anatomy and the intended fixation, namely fully cemented or press-fit cortical contact. The advantages and disadvantages of various stem lengths must be weighed against the needs of the patient to achieve an optimal outcome.


Discovery of Mitochondrial Ribosomes.
In this introductory chapter, I will briefly describe how I came to discover the mammalian mitoribosome and will add a few notes on my contribution to the field.


Clinical outcomes of laparo-endoscopic single-site surgery radical nephrectomy.
The conventional laparoscopic surgery is now paving way to the new technologies including robotic and laparoscopic single-site surgery (LESS). We present our updated experience on LESS radical nephrectomy (LESS-RN). The data from patients undergoing LESS-RN in our two institutions were reviewed along with various clinical and pathological parameters. Between 2008 and 2011, 42 LESS-RN were performed (right = 22, left = 20) with mean (range) age and BMI of 63.7 (33-86) years and 25.1 (18-38.6) kg/m(2), respectively. In addition to the instruments in the single port, one extra 3-mm needlescopic instrument was required in 19 patients (right = 17, left = 2). In three patients, two additional 5-mm trocars and instruments were required. None required open conversion. The recorded adverse events include one bowel injury (intraoperative closure without the need for stoma), one postoperative bleeding requiring blood transfusion, one prolonged ileus, and one deep venous thrombosis. The resected specimens revealed pT1a (n = 3), pT1b (n = 33), pT2a (n = 4), and pT3b (n = 2) tumors. The finding of pT3b was incidental rather than planned procedure. None of the patients had positive margins. LESS-RN has proven to be feasible and safe. Beyond cosmesis, further advantages of this approach need to be addressed by randomized trials.


Farnesol-DMPC phase behaviour: a (2)H-NMR study.
Involved in a number of diverse metabolic and functional contexts, farnesol is a central component of the mevalonate pathway, post-translationally attaches to proteins, and affects a number of other membrane-associated events. Despite farnesol's biological implications, a detailed analysis of how farnesol affects the physical properties and phase behaviour of lipid membranes is lacking. As (2)H-NMR spectra are sensitive to molecular motions and acyl chain orientation, they can be used to measure the degree of molecular order present in the system. Also, since the (2)H-NMR spectra of fluid and gel phase lipids are very different, they are sensitive probes of membrane phase equilibrium and can be used to determine fluid-gel phase boundaries. In this study, dimyristoyl phosphatidylcholine-d(54) (DMPC-d(54)) bilayers containing varying concentrations of trans-trans farnesol (2.5-20.0 mol%) are investigated over a range of temperatures (8-30 degrees C). Analysis of these spectra has led to the construction of a farnesol-DMPC-d(54) temperature-composition plot. We show that increasing concentrations of farnesol induce a decrease in the fluid-gel phase transition temperature and promote fluid-gel coexistence. Interestingly, farnesol does not seem to affect the quadrupolar splittings (Delta v(Q)) in the fluid phase, i.e., the organization of farnesol within the bilayer and its interaction with phospholipids does not appreciably influence acyl chain order in the fluid phase.


A desolvation model for trifluoroethanol-induced aggregation of enhanced green fluorescent protein.
Studies of amyloid disease-associated proteins in aqueous solutions containing 2,2,2-trifluoroethanol (TFE) have shown that the formation of structural intermediates is often correlated with enhanced protein aggregation. Here, enhanced green fluorescent protein (EGFP) is used as a model protein system to investigate the causal relationship between TFE-induced structural transitions and aggregation. Using circular dichroism spectroscopy, light scattering measurements, and transmission electron microscopy imaging, we demonstrate that population of a partially α-helical, monomeric intermediate is roughly correlated with the growth of β-sheet-rich, flexible fibrils for acid-denatured EGFP. By fitting our circular dichroism data to a model in which TFE-water mixtures are assumed to be ideal solutions, we show that increasing entropic costs of protein solvation in TFE-water mixtures may both cause the population of the intermediate state and increase aggregate production. Tertiary structure and electrostatic repulsion also impede aggregation. We conclude that initiation of EGFP aggregation in TFE likely involves overcoming of multiple protective factors, rather than stabilization of aggregation-prone structural elements.