The effect of temporary hemiepiphysiodesis in the treatment of skeleton immature posttraumatic genu angular deformity: a retrospective study of 27 cases.
The purpose of this study was to evaluate the effect, rate of angular correction, and complications of temporary hemiepiphysiodesis (TH) in the treatment of skeleton immature posttraumatic genu angular deformity. We retrospectively reviewed the records of 27 patients undergoing temporary hemiepiphysiodesis for the management of posttraumatic genu angular deformity. Based on the data from these patients, the rate of correction, effect of correction, length of the lower limbs, and complications were used as the outcome measures. Outcome measurements were obtained from a chart review of medical records that included information about clinical evaluations. Fifteen boys and 12 girls, with an average age of 6.3 years, were included in the study. The average follow-up was 3.8 years (range, 1.9 to 5.9 years) after surgery. Complete correction was obtained in 24 patients, while partial correction was obtained in 3 patients. The mean rate of angular correction was 8.41°/year in distal femur and 15.19°/year in proximal tibia. One patient had recurrence of genu valgum. No leg length discrepancy was found in our patients. Temporary hemiepiphysiodesis is a simple, effective, reliable, and reproducible method for the treatment of posttraumatic genu angular deformity, with fewer complications than osteotomy. Nevertheless, it is important to follow the rebound patient closely until skeletal maturity in our future work.


Comparative sensitivities of ThinPrep and Papanicolaou smear for adenocarcinoma in situ (AIS) and combined AIS/high-grade squamous intraepithelial lesion (HSIL): comparison with HSIL.
Despite the historic belief that cytologic screening offers little protection against cervical adenocarcinoma (CAC), there is emerging evidence that, by detecting the precursor lesion, adenocarcinoma in situ (AIS), cervical screening may reduce the incidence of CAC as it has for cervical squamous carcinoma. Because liquid-based cytology is fast replacing the conventional Papanicolaou smear (PS), it is important to establish that it is at least as effective in detecting AIS. The authors calculated the sensitivities of PS and ThinPrep (TP) for 100 women with histologic AIS (from 160 PS slides and 60 TP slides), for 94 women with AIS+high-grade squamous intraepithelial lesion (HSIL) (from 151 PS slides and 50 TP slides), and for 558 women with HSIL (from 788 PS slides and 383 TP slides). All smears were taken up to 36 months before the histologic diagnosis. In no category was there a significant difference between PS sensitivity and TP sensitivity. The HSIL category had a significantly higher overall sensitivity than the other categories. However, when sensitivity was defined as cytologic detection of high-grade disease, there was no difference between any of the categories. For the detection of a high-grade glandular lesion, the presence of a concurrent histologic HSIL was associated with reduced sensitivity for the detection of AIS. The current results indicated that it may prove possible for cervical screening, with either PS or TP, to reduce the incidence of CAC.


Comparison of preparation design and material thickness on microbial leakage through Cavit using a tooth model system.
Few studies have compared Cavit thickness and access design as factors in microbial leakage. The present study used an acrylic tooth model to measure leakage of Streptococcus mutans. Pilot studies confirming the sterility of Cavit showed it will inhibit microbial growth for 2 days. The experiments compared class I preparations where Cavit thickness was 4 mm with class II preparations where thickness was 2-3 mm. Accesses sealed with cotton pellets were compared with those without cotton. Results of the study showed no bacterial contamination in any of the class I samples (up to 14 days). Some class II samples showed contamination at day 1 (3 out of 14), with all contaminated at day 7 (14 of 14), yet only 1 contaminated at day 14 (1 out of 14). The results suggest that a 4-mm thickness of Cavit should prevent bacterial ingress for at least 2 weeks, but microbial leakage may occur if temporary thickness is less than 3 mm or in a complex access preparation.


FOXC1 regulates the functions of human basal-like breast cancer cells by activating NF-κB signaling.
Human basal-like breast cancer (BLBC) is an enigmatic and aggressive malignancy with a poor prognosis. There is an urgent need to identify therapeutic targets for BLBC, because current treatment modalities are limited and not effective. The forkhead box transcription factor FOXC1 has recently been identified as a critical functional biomarker for BLBC. However, how it orchestrates BLBC cells was not clear. Here we show that FOXC1 activates the transcription factor nuclear factor-κB (NF-κB) in BLBC cells by increasing p65/RelA protein stability. High NF-κB activity has been associated with estrogen receptor-negative breast cancer, particularly BLBC. The effect of FOXC1 on p65/RelA protein stability is mediated by increased expression of Pin1, a peptidyl-prolyl isomerase. FOXC1 requires NF-κB for its regulation of cell proliferation, migration and invasion. Notably, FOXC1 overexpression renders breast cancer cells more susceptible to pharmacological inhibition of NF-κB. These results suggest that BLBC cells may rely on FOXC1-driven NF-κB signaling. Interventions of this pathway may provide modalities for the treatment of BLBC.


Unraveling the aggregation propensity of human insulin C-peptide.
Over the last 20 years, proinsulin C-peptide emerged as an important player in various biological events. Much time and effort has been spent in exploring all functional features of C-peptide and recording its implications in Diabetes mellitus. Only a few studies, though, have addressed C-peptide oligomerization and link this procedure with Diabetes. The aim of our work was to examine the aggregation propensity of C-peptide, utilizing Transmission Electron Microscopy, Congo Red staining, ATR-FTIR, and X-ray fiber diffraction at a 10 mg ml-1 concentration. Our experimental work clearly shows that C-peptide self-assembles into amyloid-like fibrils and therefore, the aggregation propensity of C-peptide is a characteristic novel feature that should be related to physiological and also pathological conditions. © 2016 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 108: 1-8, 2017.


Studies on cell proliferation and tracer localization in the kidneys of guinea pigs with experimental autoimmune anti-tubular basement membrane nephritis.
The mitotic activity in kidneys of guinea pigs with experimental autoimmune anti-tubular basement membrane (TBM) nephritis was investigated using autoradiographic techniques to determine the uptake of [3H]thymidine by actively dividing cells. It was observed in these animals that cells of proximal tubules, distal tubules, cortical and medullary interstitium, medullary collecting ducts, and loops of Henle took up significantly greater amounts of [3H]thymidine when compared with normal animals. In addition, the behaviour of horseradish peroxidase (HRP) and goat anti-HRP IgG in extraglomerular sites in the kidneys of these animals was studied. Contrary to what was expected, these tracers appeared to be less concentrated in the tubules and interstitium of animals with anti-TBM disease, with tracer movement restricted in areas of disrupted TBM. The significance of these observations is discussed.


Fermentative production of enantiomerically pure S-1,2-propanediol from glucose by engineered E. coli strain.
The pure stereoisomers of 1,2-propanediol (1,2-PDO) could be used as starting materials to synthesize high value-added specialty chemicals and chiral pharmaceutical products. As the stereoisomers of 1,2-PDO cannot be obtained by traditional chemical synthesis processes, biotechnological processes have gained increasing attention. However, to our knowledge, the production of S-1,2-PDO directly from glucose has not been previously reported. In this study, we demonstrate a novel artificial pathway to convert L-lactic acid to S-1,2-PDO and its integration into the genome of Escherichia coli strain BW25113∆poxB with synchronous deletion of genes responsible for branch metabolic pathways from glucose. L-lactate production was increased by replacing the native D-lactate dehydrogenase with the L-lactate dehydrogenase from Bacillus coagulans. The methylglyoxal bypass pathway was blocked to avoid synthesis of a racemic mixture of D- and L-lactate and prevent the accumulation of methylglyoxal, a toxic intermediate. To further improve the yield of S-1,2-PDO, a novel cofactor regeneration system was introduced by combining pyruvate decarboxylase and acetaldehyde-CoA dehydrogenase II to simultaneously regenerate NADH and the CoA donor of acetyl-CoA for the lactate conversion pathway. Finally, 13.7 mM S-1,2-PDO with >99 % enantiomeric purity was directly produced from glucose by disrupting the major carbon-competing pathways and strengthening the lactate transformation pathway. This study demonstrates the first attempt to synthesize S-1,2-PDO by direct fermentation of glucose.


ABC5 International Consensus Conference on Advanced Breast Cancer, Lisbon, 16 November 2019: Commentary by the German panel of experts on the ABC5 voting results.
The Advanced Breast Cancer Fifth International Consensus Conference (ABC5) which focuses on the diagnosis and treatment of advanced breast cancer was held in Lisbon on November 14 - 16, 2019. The aim of the conference is to standardize the treatment of advanced breast cancer worldwide using evidence-based data and to ensure that patients with advanced breast disease anywhere in the world are treated appropriately and have access to the latest therapies. This year, the emphasis was on new developments and study results from patients with advanced breast cancer as well as precision medicine. The collaboration with patient advocates from all over the globe is also an important goal of the ABC Conference, which is why the international ABC panel also included a number of patient advocates. We present a commentary on the voting results of the ABC5 panelists in Lisbon by a working group of German breast cancer specialists together with the implications for routine clinical care in Germany. The commentary is based on the recommendations of the Breast Commission of the German Gynecological Oncology Working Group (AGO). This commentary is useful, it includes country-specific features for the ABC consensus.


Distribution of beryllium-7 (7Be) in the Black Sea in the summer of 2016.
The spatial distribution of 7Be activity in the surface layer of the Black Sea was studied using the data of field observations made during the 87th cruise of R/V Professor Vodyanitskii. Activity of 7Be varied spatially from 4.6 to 9.5 Bq m-3 (mean 7.5 ± 1.3 Bq m-3) where about 9% was found on suspended matter. The minimum values of activity were typical for samples taken in the shelf waters and the maximum-offshore. The influence of different factors on 7Be activity was analyzed. It was revealed that variation of both 7Be wet deposition on the sea surface and concentration of suspended matter were the most significant for spatiotemporal variability of 7Be activity in seawater during the study period. The estimates of 7Be distribution coefficient between dissolved and particulate forms were obtained. This coefficient varied from 1.5·105 to 2.4·105 L kg-1, averaged (1.9 ± 0.3)·105 L kg-1.


Elevated, non-proliferative temperatures change the profile of fermentation products in Corynebacterium glutamicum.
Although temperature is a crucial factor affecting enzymatic activity on biochemical and biofuel production, the reaction temperature for the generation of these products is usually set at the optimal growth temperature of the host strain, even under non-proliferative conditions. Given that the production of fermentation products only requires a fraction of the cell's metabolic pathways, the optimal temperatures for microbial growth and the fermentative production of a target compound may be different. Here, we investigated the effect of temperature on lactic and succinic acids production, and related enzymatic activities, in wild-type and succinic acid-overproducing strains of Corynebacterium glutamicum. Interestingly, fermentative production of lactic acid increased with the temperature in wild-type: production was 69% higher at 42.5 °C, a temperature that exceeded the upper limit for growth, than that at the optimal growth temperature (30 °C). Conversely, succinic acid production was decreased by 13% under the same conditions in wild-type. The specific activity of phosphoenolpyruvate carboxylase decreased with the increase in temperature. In contrast, the other glycolytic and reductive TCA cycle enzymes demonstrated increased or constant activity as the temperature was increased. When using a succinic acid over-producing strain, succinic acid production was increased by 34% at 42.5 °C. Our findings demonstrate that the profile of fermentation products is dependent upon temperature, which could be caused by the modulation of enzymatic activities. Moreover, we report that elevated temperatures, exceeding the upper limit for cell growth, can be used to increase the production of target compounds in C. glutamicum. KEY POINTS: • Lactate productivity was increased by temperature elevation. • Succinate productivity was increased by temperature elevation when lactate pathway was deleted. • Specific activity of phosphoenolpyruvate carboxylase was decreased by temperature elevation.


The effect of bone on dose distributions produced by the Fermi National Laboratory fast-neutron beam.
The dose distortion produced by bone during fast-neutron therapy was studied using a target-to-skin distance of 153 cm, with beams 10 x 10 field size at the surface of a phantom. Doses were measured using several muscle-equivalent ionization chambers in the phantom. Results showed that the dose was reduced by interposing bone-equivalent material between the point in question and the surface of the phantom.


Mathematical Modelling Highlights the Potential for Genetic Manipulation as an Adjuvant to Counter Efflux-Mediated MDR in Salmonella.
Bacteria have developed resistance to antibiotics by various mechanisms, notable amongst these is the use of permeation barriers and the expulsion of antibiotics via efflux pumps. The resistance-nodulation-division (RND) family of efflux pumps is found in Gram-negative bacteria and a major contributor to multidrug resistance (MDR). In particular, Salmonella encodes five RND efflux pump systems: AcrAB, AcrAD, AcrEF, MdsAB and MdtAB which have different substrate ranges including many antibiotics. We produce a spatial partial differential equation (PDE) model governing the diffusion and efflux of antibiotic in Salmonella, via these RND efflux pumps. Using parameter fitting techniques on experimental data, we are able to establish the behaviour of multiple wild-type and efflux mutant Salmonella strains, which enables us to produce efflux profiles for each individual efflux pump system. By combining the model with a gene regulatory network (GRN) model of efflux regulation, we simulate how the bacteria respond to their environment. Finally, performing a parameter sensitivity analysis, we look into various different targets to inhibit the efflux pumps. The model provides an in silico framework with which to test these potential adjuvants to counter MDR.


The effects of suspending medium viscosity on erythrocyte deformation and haemolysis in vitro.
Fresh adult human erythrocytes were suspended in isotonic pH adjusted solutions containing various concentrations of Dextran T.500. The cells were subjected to uniform hydrodynamic shear stress in a Ferranti Shirley Cone and Plate Viscosimeter. The amount of lysis incurred at any given combination of exposure parameters was markedly affected by the viscosity of the suspending medium. Optical diffraction patterns obtained whilst the cells were undergoing shear demonstrated that cellular deformation was also a function of viscosity. Consequently, the distorted shape of the stressed cell may play a crucial role in the haemolytic process.


Effectiveness and cost-effectiveness of a multicomponent intervention to implement a clinical practice guideline for systemic lupus erythematosus: protocol for a cluster-randomized controlled trial.
Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease with significant potential morbidity and mortality. Substantial gaps have been documented between the development and dissemination of clinical practice guidelines (CPG) and their implementation in practice. The aim of this study is to assess the effectiveness and cost-effectiveness of a multi-component knowledge transfer intervention to implement a CPG for the management of SLE (CPG-SLE). The study is an open, multicentre, controlled trial with random allocation by clusters to intervention or control. Clusters are four public university hospitals of the Canary Islands Health Service where rheumatologists are invited to participate. Patients diagnosed with SLE at least one year prior to recruitment are selected. Rheumatologists in intervention group receive a short educational group programme to both update their knowledge about SLE management according to CPG-SLE recommendations and to acquire knowledge and training on use of the patient-centred approach, a decision support tool embedded in the electronic clinical record and a quarterly feedback report containing information on management of SLE patients. Primary endpoint is change in self-perceived disease activity. Secondary endpoints are adherence of professionals to CPG-SLE recommendations, health-related quality of life, patient perception of their participation in decision making, attitudes of professionals towards shared decision making, knowledge of professionals about SLE and use of healthcare resources. Calculated sample size is 412 patients. Data will be collected from questionnaires and clinical records. Length of follow-up will be 18 months. Multilevel mixed models with repeated time measurements will be used to analyze changes in outcomes over time. Cost-effectiveness, from both social and healthcare services perspectives, will be analyzed by measuring effectiveness in terms of quality-adjusted life years gained. Deterministic and probabilistic sensitivity analyses are planned. Impact of CPGs in clinical practice could be improved by applying proven value interventions to implement them. The results of this ongoing trial are expected to generate important scientifically valid and reproducible information not only on clinical effectiveness but also on cost-effectiveness of a multi-component intervention for implementation of a CPG based on communication technologies for chronic patients in the hospital setting. ClinicalTrial.gov NCT03537638 . Registered on 25 May 2018.


Patch grafting the renal pelvis and ureteropelvic junction. A comparative study in pigs using lyophilized dura mater and free peritoneum.
Lyophilized dura mater (Lyodura) and autogenous free peritoneum were compared in the replacement of the partially resected renal pelvis and uretero-pelvic junction (UPJ) in the pig. The Lyodura and peritoneum grafts were both progressively resorbed, and replaced by fibroblasts which formed a mature scar lined by transitional epithelium, but without smooth muscle regeneration. Lyodura was found to be superior to free peritoneum with a longer time before resorption of the graft, less intense inflammatory reaction, absence of metaplastic bone formation, less risk of urine leak and greater ease of surgical manipulation.


Circulating CD4+CXCR5+ T cells contribute to proinflammatory responses in multiple ways in coronary artery disease.
Coronary artery disease (CAD) is a common subtype of cardiovascular disease. The major contributing event is atherosclerosis, which is a progressive inflammatory condition resulting in the thickening of the arterial wall and the formation of atheromatous plaques. Recent evidence suggests that circulating CD4+CXCR5+ T cells can contribute to inflammatory reactions. In this study, the frequency, phenotype, and function of circulating CD4+CXCR5+ T cells in CAD patients were examined. Data showed that circulating CD4+CXCR5+ T cells in CAD patients were enriched with a PD-1+CCR7- subset, which was previously identified as the most potent in B cell help. The CD4+CXCR5+ T cells in CAD patients also secreted significantly higher levels of IFN-γ, IL-17A, and IL-21 than those from healthy controls. Depleting the PD-1+ population significantly reduced the cytokine secretion. Interestingly, the CD4+CXCR5+PD-1- T cells significantly upregulated PD-1 following anti-CD3/CD28 or SEB stimulation. CD4+CXCR5+ T cells from CAD patients also demonstrated more potent capacity to stimulate B cell inflammation than those from healthy individuals. The phosphorylation of STAT1 and STAT3 were significantly higher in B cells incubated with CD4+CXCR5+ T cells from CAD than controls. The IL-6 and IFN-γ expression were also significantly higher in B cells incubated with CD4+CXCR5+ T cells from CAD. Together, this study demonstrated that CAD patients presented a highly activated CD4+CXCR5+ T cell subset that could contribute to proinflammatory responses in multiple ways. The possibility of using CD4+CXCR5+ T cells as a therapeutic target should therefore be examined in CAD patients.


Indices of hemodynamic and respiratory functions in premature infants at risk for the development of cerebral white matter injury.
To examine potential differences in clinical risk factors, including indices of hemodynamic and respiratory functions, of premature infants developing periventricular hemorrhagic infarction (PHI) or periventricular leukomalacia (PVL). Indices of hemodynamic stability and respiratory function were measured prospectively during the first week of life in a cohort of 100 premature infants with respiratory distress. Maternal history was retrospectively reviewed. These data were correlated with cranial ultrasonography using one-way ANOVA, Bonferroni multiple comparisons, and Wilcoxon rank sum tests. Longitudinal analysis was performed using Generalized Estimating Equations. Fifty-two infants with normal cranial ultrasound studies were compared to 12 with PHI and 9 with PVL. Infants developing PHI had significantly lower birth weights, lower Apgar scores, were more often male and multiple gestations, and required more vasopressor support than infants with normal ultrasound studies. Infants with PHI had significantly worse indices of respiratory function than either normal infants or those with PVL. PVL was significantly associated with maternal chorioamnionitis, whereas PHI was not. These data suggest that there are important differences in the pathogenesis of PHI and PVL. A clear understanding of these differences is required before future preventive strategies can be formulated.


Isolations of yellow fever virus from Haemagogus leucocelaenus in Rio Grande do Sul State, Brazil.
Following howling monkey (Alouatta caraya) deaths and yellow fever (YF) antigen detection by immunohistochemistry in the liver sample of a dead monkey in April and May 2001 in the municipalities of Garruchos and Santo Antônio das Missões, Rio Grande do Sul State, Brazil, epidemiological field investigations were initiated. Two strains of YF virus were isolated in suckling mice from 23 Haemagogus (Conopostegus) leucocelaenus Dyar & Shannon mosquitoes collected from the study sites. The YF virus was isolated from this species in the 1930s in Brazil and in the 1940s in Colombia. No human cases were reported during the current epizootic outbreak. The YF virus isolation and the absence of Hg. (Haemagogus) janthinomys Dyar from the area suggest that Hg. leucocelaenus may be a secondary YF vector and play an important role in the epidemiology of this disease in the Southern Cone.


Youth football injuries.
A paucity of literature exists on the subject of youth football with the majority of research concentrating on athletes of high-school age or older. Youth football participants include those athletes who compete in organised football prior to high school. Injury rate and severity for youth players is surprisingly low when compared with those competitors who have passed through puberty. As children mature they become bigger, faster and stronger, which is accompanied by an increased injury risk. Quarterbacks and running backs are injured almost five times more often than offensive linemen and linebackers. The knee is the most common site of injury followed by the ankle, wrist and hand. Fortunately, traumatic brain and cervical spine injuries are exceedingly rare. In this article, we review the youth football literature, identify the most common injuries by anatomical location, discuss the differential diagnoses and outline treatment options.


Intestinal injury caused by Eimeria spp. impairs the phosphotransfer network and gain weight in experimentally infected chicken chicks.
Parasitic infections caused by protozoan belonging to genus Eimeria are considered important for the poultry industry, due to their severe intestinal lesions and high mortality rates, causing significant economic losses. Although several mechanisms of coccidiosis pathogenesis are known, the effects of this infection on intestinal enzymes linked to adenosine triphosphate (ATP) metabolism, as creatine kinase (CK), adenylate kinase (AK), and pyruvate kinase (PK), remain unknown. Thus, the aim of this study was to evaluate whether coccidiosis impairs enzymes linked ATP metabolism in the intestine of chicken chicks. For this, 42 animals that were 2 days old were divided into two groups: uninfected (the negative control group) and experimentally infected on second day of life (the positive control group). On days 5, 10, and 15 post-infection (PI), fecal samples were collected for oocyst counts; intestinal tissue was collected in order to evaluate CK, AK, and PK activities, as well as parameters of the oxidative stress and histopathology. On days 10 and 15 PI, infected animals showed high counts of oocysts in fecal samples and intestinal lesions compared to the control group. Cytosolic CK activity was higher in infected animals on days 10 and 15 PI compared to the control group, while mitochondrial CK activity was lower on days 5, 10, and 15 PI. Also, AK activity was lower in infected animals on days 10 and 15 PI compared to control group, while no differences were observed between groups regarding PK activity. In relation to parameters of oxidative stress, intestinal lipid peroxidation and reactive oxygen species levels were higher in infected animals on days 10 and 15 PI compared to the control group, while non-protein thiol levels were lower on day 10 PI. On the 15th day, infected animals had lower body weight (P < 0.05). Based on this evidence, inhibition of mitochondrial CK activity causes an impairment of intestinal energetic homeostasis possibly through depletion on ATP levels, although the cytosolic CK activity acted as an attempt to restore the mitochondrial ATP levels through a feedback mechanism. Moreover, the impairment on energy metabolism appears to be mediated by excessive production of intestinal ROS, as well as oxidation of lipids and thiol groups.


Effects of lytS-L on the primary metabolism and butenyl-spinosyn biosynthesis in Saccharopolyspora pogona.
The LytTR family two-component system widely exists in bacterial cells and plays an important role in metabolic regulation. The lytS-L gene that encodes for a LytTR family sensor kinase was knocked out to study its influence on the growth, phenotype, and the biosynthesis of the insecticidal polyketide butenyl-spinosyn in Saccharopolyspora pogona NRRL 30141 (S. pogona). High performance liquid chromatography (HPLC) results showed that the butenyl-spinosyn yield of the lytS-L knockout mutant decreased by 58.9% compared with that of the parental strain. This is manifested by a weak toxicity of the mutant against the insect Helicoverpa assulta (H. armigera). Comparative proteomic analysis revealed the expression characteristics of the proteins in S. pogona and S. pogona-ΔlytS-L: a total of 14 proteins involved in energy metabolism were down-regulated, 9 proteins related to carbon metabolism such as glycolysis, and tricarboxylic acid cycle (TCA) were up-regulated, while 13 proteins involved in the biosynthesis of butenyl-spinosyn were down-regulated (fold change >1.2 or< 0.83). The qRT-PCR (Quantitative Real-time PCR) analysis illustrated that the changes in the expression levels of transcription and translation of the identified genes were consistent. This study explores the function of the two-component system of the LytTR family in S. pogona and shows that the lytS-L gene has an important influence on regulating primary metabolism and butenyl-spinosyn biosynthesis of S. pogona.


Effects of cocaine on rat pancreatic enzyme secretion and protein synthesis.
The effects of cocaine on amylase secretion and total protein synthesis was studied by use of vitro rat pancreatic tissue. In vitro, cocaine (2 or 10 mM) did not modify basal release of amylase; at a concentration of 2 mM, it reduced the secretory response to pancreozymin by 32% and that to urecholine by 68%. Incorporation of amino acids into total proteins was decreased by 15% by cocaine 2 mM and by 49.5% at 10 mM. Administered in vivo at a dose of 15 mg/kg intraperitoneally, cocaine was associated with decreased in protein synthesis 30, 90, and 180 min after its injection. These results indicate that cocaine can affect basic functions of the exocrine pancreas and reduce its response to secretagogues.


A phase I clinical trial of prolonged infusion of hydroxyurea in combination with hyperfractionated, accelerated, external radiation therapy in patients with advanced squamous cell cancer of the head and neck.
Preclinical data suggested that sustained inhibition of the anabolic enzyme, ribonucleotide reductase (RR), by hydroxyurea (HU) may be critical for the anticancer effects of the drug. A phase I trial of continuous infusion HU with concomitant hyperfractionated, accelerated radiation therapy (CHU-CHRT) was initiated to determine the maximum tolerated dose (MTD) and dose limiting toxicities (DLT) of HU in patients with locally advanced squamous cell carcinoma (SCC) of the head and neck. Patients were required to have histologically-documented and radiographically-staged locally advanced SCC of the hypopharynx (AJC stages II, III or IV), oropharynx (AJC stage IV), or oral cavity (AJC stage IV) not amenable to reasonable surgical resection. Eligible patients had adequate bone marrow, hepatic, and renal function and had to give informed consent. Concomitant, hyperfractionated, accelerated radiation therapy (CHRT) consisted of 1.2 Gy BID (6 hour minimum interfraction interval) on weekdays and 1.2 Gy delivered daily on the weekends to a total tumor dose of 74.4 Gy. Continuous infusion hydroxyurea (CHU) was administered at 0.25-0.375 mg/m2/min as a continuous intravenous infusion daily for 5 days with weekends days off for the duration of the radiation therapy. The dose of HU was increased by 0.125 mg/m2/min between dose levels until DLT was reached in 2/6 patients. If the primary had a complete clinical response and biopsies were negative, planned neck dissections were performed. Fifteen patients were enrolled and are evaluable. The initial dose level, 0.25 mg/m2/min was tolerated by 3/3 patients. At 0.375 mg/m2/min, 3/6 patients experienced grade 3-4 infections, with one patient having a non-fatal, subendocardial infarction. At 0.313 mg/m2/min, no patient experienced DLT. The MTD for CHU-CHRT was 0.313 mg/m2/min. The toxicities were primarily mucosal and a phase II study is in progress.


Role of stem cell derived exosomes in tumor biology.
Exosomes are nano-scale messengers loaded with bio-molecular cargo of RNA, DNA, and Proteins. As a master regulator of cellular signaling, stem cell (both normal, and cancer stem cells) secreted exosome orchestrate various autocrine and paracrine functions which alter tumor micro-environment, growth and progression. Exosomes secreted by one of the two important stem cell phenotypes in cancers a) Mesenchymal stem cells, and b) Cancer stem cells not only promote cancerous growth but also impart therapy resistance in cancer cells. In tumors, normal or mesenchymal stem cell (MSCs) derived exosomes (MSC-exo) modulate tumor hallmarks by delivering unique miRNA species to neighboring cells and help in tumor progression. Apart from regulating tumor cell fate, MSC-exo are also capable of inducing physiological processes, for example, angiogenesis, metastasis and so forth. Similarly, cancer stem cells (CSCs) derived exosomes (CSC-exo) contain stemness-specific proteins, self-renewal promoting regulatory miRNAs, and survival factors. CSC-exo specific cargo maintains tumor heterogeneity and alters tumor progression. In this review we critically discuss the importance of stem cell specific exosomes in tumor cell signaling pathways with their role in tumor biology.


Intranasal interferon-beta alleviates anxiety and depressive-like behaviors by modulating microglia polarization in an Alzheimer's disease model.
Alzheimer's disease (AD) patients frequently experience neuropsychiatric symptoms (NPS), which are linked to a lower quality of life and a faster rate of disease progression. A growing body of research indicates that several microglial phenotypes control the inflammatory response and are crucial in the pathophysiology of AD-related NPS. Given the crucial role played by inflammatory mediators produced by microglia in developing of NPS, interferon-beta (IFNβ), a cytokine with anti-inflammatory capabilities, maybe a successful treatment for NPS caused by AD. In this investigation, using a rat model of AD, we examined the impact of intranasal treatment of IFNβ on anxious/depressive-like behavior and microglial M1/M2 polarization. The rat hippocampus was bilaterally injected with lentiviruses harboring mutant human amyloid precursor protein. Rats were given recombinant IFNβ1a (68,000 IU/rat) via the intranasal route, starting on day 23 following viral infection and continuing until day 49. On days 47-49, the elevated plus maze, forced swim, and tail suspension tests were applied to measure anxiety- and depressive-like behavior. Additionally, qPCR was utilized to quantify the expression of M1 markers (CD68, CD86, and CD40) and M2 markers (Ym1, CD206, Arg1, GDNF, BDNF, and SOCS1). Our findings demonstrated that decreased M2 marker expression is accompanied by anxious/depressive-like behavior when the mutant human APP gene is overexpressed in the hippocampus. In the rat model of AD, IFNβ therapy reduces anxious/depressive-like behaviors, at least in part by polarizing microglia towards M2. Therefore, IFNβ may be a viable therapeutic drug for reducing NPS in the context of AD.


Site-specific nanoswitch circumventing immune resistance via activating TLR and inhibiting PD-L1/PD-1 axis.
Immunotherapy has fundamentally altered cancer treatment; however, its effectiveness is clinically hampered by insufficient intratumoral T lymphocyte infiltration and failed T lymphocyte priming. Additionally, inducing cancer-specific immune responses while sparing normal cells remains challenging. Herein, we developed a redox-activatable polymeric nanoswitch (c-N@IM/JQ) that remained 'off' status in circulation but rapidly switched 'on' after entering the tumor. Toll-like receptor (TLR) 7/8 agonist (imidazoquinoline, IMQ) and bromodomain and extraterminal inhibitor (JQ1) are locked in c-N@IM/JQ with a redox-cleavable linker (switch off). Upon systemic administration, c-N@IM/JQ with c-RGD peptide modification preferentially accumulated at tumor sites and responded to the high glutathione levels to release native IMQ for fully mobilizing T lymphocyte army, and JQ1 for removing the programmed death ligand (PD-L)-1 protection on tumor cells (switch on). These strengthened T lymphocyte armies are easily accessible to these de-protected tumor cells, revitalizing the immune response against tumors.


Working toward evidence-based guidelines for cost-of-care conversations between patients and physicians: A systematic review of the literature.
As healthcare costs continue to rise, so does the importance of having cost-of-care conversations during medical office visits, especially for patients from vulnerable populations and patients with high-cost illnesses such as cancer. Such conversations remain relatively rare, however, even though physicians and patients say they want to have them. Furthermore, there is a lack of evidence-based guidelines for encouraging cost conversations and improving their quality. The purpose of this project was to conduct a systematic review of the cost-of-care conversations literature, focusing on empirical studies to characterize the state of the literature and provide a foundation for developing evidence-based guidelines for these important conversations. We searched seven electronic databases and identified an initial list of 1,986 records, 54 of which met inclusion criteria. We reviewed those articles to identify study purpose, use of theory, conceptual and operational definitions of cost conversations, sample characteristics, research methods, variables relevant to cost conversations, and relevant study findings. Results revealed that this literature (a) consists overwhelmingly of cross-sectional survey research set in the United States, (b) defines cost conversations chiefly as those focused on healthcare or medication costs (either in general or out-of-pocket), (c) is focused primarily on establishing incidence/frequency of cost conversations but also considers patient/provider desire for, attitudes/beliefs toward, and perceived barriers to cost conversations, and (d) lacks theoretical guidance. There were very few findings that could provide actionable evidence to guide quality conversations about reducing cost of care. We offer observations and recommendations for the next steps in cost conversations research so that patients and physicians can work together to promote quality care at affordable costs.


Corrective exercise-based therapy for adolescent idiopathic scoliosis: Systematic review and meta-analysis.
to analyze the efficacy of Corrective exercise-based therapy in the improvement of deformity and quality of life in adolescent idiopathic scoliosis. PubMed Medline, Scopus, Web of Science (WOS), Physiotherapy Evidence Database, CINAHL Complete and SciELO, until June 2021. Randomized controlled trials was selected, including participants diagnosed with adolescent idiopathic scoliosis, in which the experimental group received Corrective exercise-based therapy. Two authors independently searched the scientific literature in the data sources, extracted the data and assessed the risk of bias. A pairwise meta-analysis using the random-effects model was performed. Eight randomized controlled trials providing data from 279 adolescent idiopathic scoliosis patients were included. Seven randomized controlled trials including 236 patients showed moderate-quality evidence for a medium effect (SMD = -0.52, 95% CI -0.96 to -0.1), favoring corrective exercise-based therapy for spinal deformity reduction. Corrective exercise-based therapy was better than no intervention (SMD = -0.59, 95% CI -1.18 to -0.01) but similar to other intervention (SMD = -0.2, 95% CI -0.67 to 0.27), and a medium effect was found (SMD = -0.51, 95% CI -0.89 to -0.13) when corrective exercise-based therapy was used with other therapies. Four studies including 151 patients showed low-quality evidence of a large effect of Corrective exercise-based therapy on Scoliosis Research Society measurement (SRS-22) total score improvement (SMD = 1.16, 95% CI 0.36 to 1.95). In mild and moderate adolescent idiopathic scoliosis patients, corrective exercise-based therapy could be used to reduce spinal deformity and to improve quality of life as isolated treatment or as coadjuvant treatment combined with other therapeutic resources.


The relationship between inspiratory lung function parameters and airway hyper-responsiveness in subjects with mild to moderate COPD.
The aim of this study was to evaluate the effects of increasing doses of inhaled histamine on the forced expiratory volume in one second (FEV1), inspiratory lung function parameters (ILPs) and dyspnea in subjects with mild to moderate chronic obstructive pulmonary disease (COPD) METHODS: Thirty-nine (27 males and 12 females) stable COPD patients (GOLD stages I and II) inhaled a maximum of six sequential doses of histamine according to ERS standards until one of these provocative doses produced a 20% decrease in FEV1 (PD20). The effects on the FEV1, the forced inspiratory volume in one second (FIV1), inspiratory capacity (IC), forced inspiratory flow at 50% of the vital capacity (FIF50), peak inspiratory flow (PIF) and dyspnea score by a visual analogue scale (VAS) were measured and investigated after each dose step After each dose of histamine, declines in all of the lung function parameters were detected; the largest decrease was observed in the FEV1. At the PD20 endpoint, more FEV1 responders than ILP responders were found. Among the ILPs, the FIV1 and IC best predicted which patients would reach the PD20 endpoint. No significant correlations were found between any of the lung function parameters and the VAS results In COPD patients, the FEV1 and ILPs declined after each dose of inhaled histamine. FEV1 was more sensitive to histamine than the ILPs. Of the ILPs, FIV1 and IC were the best predictors of reaching the PD20 endpoint. No statistically significant correlations were found between the lung function parameters and the degree of dyspnea.


Comparison of clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea.
This study is aimed to investigate the differences in the clinical features and surgical outcomes between hypopnea- and apnea-predominant obstructive sleep apnea (OSA). Cohort study. Single tertiary care centre. This study included 190 patients with OSA who underwent multilevel upper airway surgery between September 2012 and September 2021. The patients were divided into two groups according to the proportion of each respiratory event: hypopnea-predominant (n = 102) and apnea-predominant (n = 88). The primary outcome measure was the percentage improvement in the apnea-hypopnea index (AHI) from baseline AHI after surgery. The apnea-predominant group included more male patients and had higher AHI, respiratory disturbance index (RDI) and oxygen desaturation index (ODI) than the hypopnea-predominant group. Both groups showed significant improvements in AHI, apnea index, RDI, supine AHI, REM AHI, non-REM AHI, ODI, lowest O2 saturation and Epworth Sleepiness Scale scores following the surgery. Notably, hypopnea index increased after surgery in the apnea-predominant OSA group. Although the improvement in the absolute value of AHI by surgery was significantly greater in the apnea-predominant group than in the hypopnea-predominant group, the two groups showed no significant difference in the percentage improvement in AHI from baseline AHI. Patients with apnea-predominant OSA had more severe disease than those with hypopnea-predominant OSA; however, surgical outcomes, as evaluated by percentage AHI improvement, were comparable between the two groups. In addition, multilevel upper airway surgery may induce the transition from apnea to hypopnea in patients with apnea-predominant OSA.


TIPE3 hypermethylation correlates with worse prognosis and promotes tumor progression in nasopharyngeal carcinoma.
Increasing evidence recognizes that DNA methylation abnormalities play critical roles in cancer development. Our previous genome-wide methylation profile showed that tumor necrosis factor-alpha-induced protein 8 like 3 (TIPE3) was hypermethylated in nasopharyngeal carcinoma (NPC). However, the relationship between TIPE3 methylation and its mRNA expression, as well as its biological roles in NPC are unknown. Bisulfite pyrosequencing and quantitative RT-PCR were performed to quantify the TIPE3 methylation and expression levels. Kaplan-Meier curves and Cox regression analysis were used to estimate the correlation between TIPE3 methylation levels and survival in two patient cohorts collected from two hospitals (n = 441). The MTT, colony formation, Transwell migration and invasion assays, and xenograft tumor growth and lung metastatic colonization models were used to identify the functions of TIPE3 on NPC cells. We found that TIPE3 CpG island (CGI) was hypermethylated and its mRNA levels were downregulated in many cancers, including NPC. TIPE3 downregulation was associated with its CGI hypermethylation. Furthermore, NPC patients with high TIPE3 CGI methylation levels had poorer clinical outcomes than those with low methylation levels. The TIPE3 CGI methylation level was an independent prognostic factor. Moreover, restoring TIPE3 expression significantly inhibited NPC cell proliferation, migration and invasion in vitro, and suppressed tumor growth and lung metastatic colonization in vivo, while silencing TIPE3 acted in an opposite way. TIPE3 downregulation correlates with its CGI hypermethylation in several solid cancers. TIPE3 acts as a tumor suppressor in NPC, providing a further insight into NPC progression and representing a potential prognostic biomarker for NPC.


Long-term successful arthroscopic repair of large and massive rotator cuff tears with a functional and degradable reinforcement device.
Rotator cuff repair is a procedure with varying outcomes, and there has been subsequent interest in devices that reinforce the repair and enhance structural and functional outcomes. The objective of this study was to determine these outcomes for arthroscopic repair of large and massive rotator cuff tears augmented with a synthetic absorbable mesh designed specifically for reinforcement of tendon repair by imaging and clinical assessments. Consecutive arthroscopic repairs were performed on 18 patients with large to massive rotator cuff tears by use of a poly-l-lactic acid synthetic patch as a reinforcement device and fixation with 4 sutures. Patients were assessed preoperatively and at 6 months, 12 months, and a mean of 42 months after surgery by the American Shoulder and Elbow Surgeons (ASES) shoulder score to evaluate clinical performance and at 12 months by ultrasound to assess structural repair. Ultrasound showed that 15 of 18 patients had intact rotator cuff repair at 12 months; at 42 months, an additional patient had a failed repair. Patients showed improvement in the ASES shoulder score from 25 preoperatively to 71 at 12 months and 70 at 42 months after surgery. Patients with intact rotator cuff (n = 14) at 42 months had an ASES shoulder score of 82. The poly-l-lactic acid bioabsorbable patch designed specifically to reinforce the surgical repair of tendons supported successful repair of large to massive rotator cuff tears in 83% of patients at 12 months after surgery and 78% of patients at 42 months after surgery, with substantial functional improvement.


Effects of a Chinese herbal preparation on vascular cells in culture: mechanisms of cardiovascular protection.
1. The use of traditional Chinese medicinal herbs or their pharmaceutical products for disease prevention and management is becoming increasingly popular in Western countries. Mixtures of various Chinese herbs have been used for the treatment of syndromes clinically overlapping Western cardiovascular syndromes. One modern preparation, known as the 'Cardiotonic Pill' (CP), is a pharmaceutical product derived mainly from a medicinal herb, Salvia miltiorrhiza bunge, and recently widely used in Chinese hospitals for the prevention and management of ischaemic cardiovascular diseases. Although the CP is believed to confer an extensive range of benefits, little is known about the physiological actions of this medicine, particularly at the cellular and molecular levels. Therefore, the aim of the present study was to explore possible cellular mechanisms of the CP on the cardiovascular system. 2. Cultured human vascular endothelial cells (EC) and vascular smooth muscle cells (VSMC) were exposed to the CP at various concentrations for periods ranging from hours to days. Cellular DNA synthesis was determined by a [(3)H]-thymidine incorporation assay, proliferation and death were assessed by investigations of cell numbers and apoptosis, whereas the expression of extracellular adhesion molecules was analysed by flow-cytometry and Western blotting. 3. The CP extract at concentrations of less than 200 microg/mL was not associated with cell damage. At doses beyond the therapeutic range (10-20 microg/mL), the CP appeared to exert a mild inhibitory effect on DNA synthesis and proliferation of EC in serum-enriched cultures. The CP significantly attenuated tumour necrosis factor-alpha-induced expression of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in a dose-dependent manner, with 50 and 100 microg/mL CP producing decreases in the expression of ICAM-1 of 26-32% and 32-44%, respectively, and of VCAM-1 of approximately 23% and 27-42%, respectively. The CP did not affect apoptosis in EC under conditions of serum-deprivation. 4. In VSMC, the CP significantly inhibited platelet-derived growth factor BB-induced DNA synthesis and cell proliferation in a dose-dependent manner. The CP did not affect VSMC expression of adhesion molecules. 5. We conclude that the CP inhibits expression of ICAM-1 and VCAM-1 in EC and proliferation of VSMC in a manner that has potentially beneficial therapeutic effects.


The mechanism of oxidation of nitroalkanes by horseradish peroxidase.
Horseradish peroxidase catalyzes the anaerobic oxidation of 2-nitropropane (probably as the nitronate R-) by H2O2 via Compounds I and II to form R-R. The oxidation rate is stimulated 10-fold by O2 and the products become acetone and NO-2. The aerobic oxidation of R- is a free radical chain reaction which is initiated by peroxidase and propagated by R because (a) R-R, reasonably, must arise as 2R leads to R-R, (b) over 90% of the enzyme-initiated reaction occurs free in solution, and (c) the Km value for R- is independent of the type of initiator. We present a scheme for initiation, propagation, and termination which explains product structure, the effects of resorcinol, CN-, ascorbate, superoxide dismutase, and catalase, as well as the ping-pong reaction kinetics. We used methanenitronate to investigate the locus of electron transfer from R- into the heme moiety of the enzyme because this donor reacts with Compound II to form an isoporphyrin, which then rearranges to a modified enzyme in which the ferriheme contains the nitromethyl group in covalent linkage at a methine carbon. The modified enzyme is 30-50% as active catalytically as the native enzyme. We argue that reduction of Compound II by R- occurs at the methine carbon by two competing pathways, namely, direct one electron transfer and, at about one-half the frequency, homolytic cleavage of a covalent heme-substrate adduct (isoporphyrin).


Acute hepatic failure due to hepatosplenic B-cell non-Hodgkin's lymphoma in a patient infected with hepatitis C virus.
We report a 75-year-old Japanese man infected with hepatitis C virus (HCV) who died of acute hepatic failure due to the hepatic infiltration of B-cell non-Hodgkin's lymphoma (NHL) cells. He suddenly developed jaundice, fatigue, fever, and hepatosplenomegaly during the course of chronic infection with HCV. Postmortem liver necropsy revealed extensive infiltration of lymphoma cells into the liver. Although the association between HCV infection and NHL has recently become a matter of concern, we believe this to be the first reported case of acute hepatic failure caused by hepatic involvement of non-Hodgkin's lymphoma in an HCV-infected patient.


The structure and distribution of external sense organs in newly hatched and mature earthworms.
Fully mature adult Eisenia foetida sensory buds are abundant on the prostomium and the first segment. In subsequent segments they are restricted to the anterior half where they form a single row aligned with the setae and encircling the worm. In the more posterior regions of the worm the buds are widely separated and fewer. The surface of each bud is a raised circular or oval area from which 15 to 100 so-called sensory hairs arise, being cylindrical and apparently flexible. The number of these projections decreases toward the posterior end of the worm. In worms newly emerged from egg cocoons, the general pattern of distribution and external form of sensory buds resembles that of adults, but the buds are much fewer and smaller than in adults. Although these worms emerge with their definitive adult number of segments, new buds and additional sensory projections are formed during post hatching development.


Validation of supra-pubic ultrasonography for preoperative prostate volume measurement in sub-Saharan Africa.
Advances in urological techniques in sub-Saharan Africa need to be supported with practical ancillary diagnostics. This study aimed at determining the accuracy of suprapubic ultrasonography (SPUS) relative to transrectal ultrasonography (TRUS), the current gold standard, in estimating preoperative prostate volume in a sub-Saharan African hospital. Cross-sectional study of prospectively enrolled patients with severe lower urinary tract symptoms and histologically confirmed benign prostatic hyperplasia. The volume of the prostate was estimated using two modalities, SPUS and TRUS. Open prostatectomy was performed on all patients, and the mass of the enucleated prostate adenoma was measured directly. Fifty patients were enrolled, with a mean age of 69 years. The mean prostate volume as determined by TRUS, SPUS, and direct measurement of enucleated prostatic tissue was 96.0, 95.9 and 83.5 mL, respectively. Prostate volume determined by SPUS correlated strongly with the TRUS measurement (ρ = 0.98, P < 0.001). The mean difference between the volume estimates by TRUS and SPUS was 0.09 mL [95% CI -2.07 to 1.89, P = 0.93], with upper and lower limits of agreement of -13.8 and +13.6 mL, respectively. Sensitivity, specificity, positive and negative predictive value for SPUS relative to TRUS for classifying patients according to the indication for TURP (prostate volume ≤80 mL) versus open prostatectomy (>80 mL) were 95% or higher. The volume of the enucleated adenoma was less than the volume estimated by ultrasonography by approximately 12.5 mL. SPUS is accurate relative to TRUS in assessing preoperative volume of the prostate and can be used in the African context to assign patients to open prostatectomy or TURP.


Advances in contrast-enhanced MR angiography of the renal arteries.
Renal artery stenosis (RAS) is a potentially curable cause of renovascular hypertension (RVH) and is caused by either atherosclerosis or fibromuscular dysplasia in the vast majority of patients. Although intra-arterial digital subtraction angiography is still considered the standard of reference test for the anatomic diagnosis of RAS, MR angiography and functional renal MR imaging are promising alternatives that also allow for functional characterization of RAS. This article provides an overview of these techniques and discusses their relative merits and shortcomings. Because missing RVH may have serious consequences the most important requirement for an alternative test is that it has high sensitivity. An unresolved issue is the prediction of functional recovery after therapy.


Basic determinants of child linear growth outcomes in sub-Saharan Africa: a cross-sectional survey analysis of positive deviants in poor households.
Childhood malnutrition is a significant public health problem confronting countries across the globe. Although there is evidence of a downward trend in undernutrition globally, sub-Saharan Africa did not experience significant improvement in the past decades. This study investigated the basic determinants of linear growth among children living in poor households. We analysed a nationally representative sample of children aged 0-59 months (N = 24,264). The study countries were Ghana, Kenya, the Democratic Republic of Congo (DRC), Nigeria, and Mozambique. The child's height-for-age Z-scores (HAZ), categorised into HAZ > - 2 standard deviations (SD) (not stunted) and HAZ < - 2 SD (stunted) was the outcome variable of interest. We used logistic regression as our analytical strategy. In DRC, Ghana, Kenya and Nigeria, maternal years of schooling was associated with positive linear growth among children living in poor households. In Ghana and DRC, four antenatal visits had a positive effect on better linear growth, while in Nigeria, healthy maternal body mass index (kg/m2) had a positive effect on child's linear growth. The putative socio-demographic determinants investigated in our study can promote the linear growth of children living in poor households. Interventions aimed at fostering linear growth among children living in poverty should focus on enhancing these factors.


Transitory neurological findings in a population of at risk infants.
Two-hundred fifty infants with high and no risk history transitory neurological findings (TNF) were examined during the first year of life. The neurological situation and the developmental progress were reconsidered in these children at 2.5-4.5 and 5-7 years of age. TNF were diagnosed mainly during the first two trimesters. Hyperirritability and asymmetries resolved to about 70% during the first half of the first year of life. In contrast, isolated central hypotonia resolved over a much longer period. No correlations of distinct types of TNF could be found with VLBW and LBW-infants, with fullterm infants, with birthweights, nor with risk factors. Children who developed spastic CP presented permanent hypertonia beside other specific neurological symptoms during the second half of the first year of life. Children with lasting non-spastic handicaps showed permanent hypotonia combined with other neurological abnormalities and symptoms of psychomotor retardation, which evolved also during the second half of the first year. From these results the question arises: which parts of TNF are essentially neurobiological findings indicating processes of transformation of the sensory motor system from non-intentional fetal to intentional motor behaviour of early infancy. TNF, then, should not longer be looked at as symptoms of pathological value only.


Application of Visible-to-UV Photon Upconversion to Photoredox Catalysis: The Activation of Aryl Bromides.
The activation of aryl-Br bonds was achieved by sequential combination of a triplet-triplet annihilation process of the organic dyes, butane-2,3-dione and 2,5-diphenyloxazole, with a single-electron-transfer activation of aryl bromides. The photophysical and chemical steps were studied by time-resolved transient fluorescence and absorption spectroscopy with a pulsed laser, quenching experiments, and DFT calculations.


Decolorization and degradation of azo dye--Reactive Violet 5R by an acclimatized indigenous bacterial mixed cultures-SB4 isolated from anthropogenic dye contaminated soil.
Azo dyes an important group of synthetic compounds are recalcitrant xenobiotics. Conventional technologies are unsuccessful to efficiently remove these compounds from contaminated environment. However, consorted metabolic functioning of innate microbial communities is a promising approach for bioremediation of polluted environment. Bacterial mixed cultures SB4 proficient in complete decolorization of azo dye - Reactive Violet 5R was developed through culture enrichment technique. Bacterial community composition based on 16S rRNA gene analysis revealed that mixed cultures SB4 composed of six bacterial strains namely Bacillus sp. V1DMK, Lysinibacillus sp. V3DMK, Bacillus sp. V5DMK, Bacillus sp. V7DMK, Ochrobacterium sp. V10DMK, Bacillus sp. V12DMK. SB4 grew well in minimal medium containing low amount of glucose and yeast extract (YE) (1 g/L) and decolorized 200mg/L of RV5 within 18 h under static condition. Mixed cultures SB4 decolorized wide range of azo dyes and maximum rate of decolorization was observed at 37 °C and pH 7.0. Decolorization efficiency was found to be unaltered under high RV5 and salt concentration where 1500 mg/L of RV5 was decolorized in presence of 20 g/L NaCl. We propose the asymmetric cleavage of RV5 and Fourier transformed infrared (FTIR), NMR and gas chromatography-mass spectrometry (GC-MS) confirmed the formation of four intermediatory compounds 1-diazo-2-naphthol, 4-hydroxybenzenesulphonic acid, 2-naphthol and benzenesulphonic acid.


Optimization of the production of triabin, a novel thrombin inhibitor, in High Five™ insect cells infected with a recombinant baculovirus.
The isolation of a new type of thrombin inhibitor, called triabin, from the saliva of the hematophagous bug Triatoma pallidipennis, has recently been described. In the in vitro platelet aggregation inhibition assay triabin has a similar potency as the thrombin inhibitor hirudin now in phase III clinical trials. However, in another in vitro assay using a low molecular weight substrate for thrombin, triabin does not inhibit thrombin completely even at 6 fold higher molar doses in comparison with hirudin. This means that triabin has a novel mode of action towards thrombin making triabin into an interesting candidate as a therapeutic agent. Recently it has been shown that a recombinant baculovirus can be efficiently used for the triabin production in insect cells and that the yields in adherent cultures of High Five™ cells (approx. 20 mg l-1) were about 7 fold higher than in adherent cultures of Sf9 cells (approx. 3 mg l- 1). To optimize the triabin yield from the baculovirus/insect cell expression system, experiments were performed with suspension adapted cultures of High Five™ cells to investigate the effects of the state of the host cell, of the multiplicity of infection, of the cell density at the time of infection and of supplementation of the medium with nutrients and oxygen. Triabin yields of up to 200 mg l-1, as determined by an activity assay, could finally be obtained here.


Propofol exerts hippocampal neuron protective effects via up-regulation of metallothionein-3.
Propofol is an intravenous anesthetic with neuroprotective effects against cerebral ischemia or hypoxia injury. However, the underlying mechanisms remain obscure. Recent years emerging evidence has demonstrated that metallothionein-3 (MT-3), a growth inhibitory factor that exists mainly in the central nervous system, exhibited neuroprotective effect in vivo. Here, we used a model of hypoxia/re-oxygenation (H/R) injury to examine the hippocampal neuroprotective effect of propofol, and explored the role of MT-3 in this action. H/R resulted in reduced cell viability and increased cell death in hippocampal neuron culture, as indicated by MTT assay and lactate dehydrogenase (LDH) release assay, respectively. Pretreatment of propofol at different concentrations (50, 150, and 250 μmol/L) reversed H/R-induced neurotoxicity and increased MT-3 mRNA and protein expressions. Moreover, propofol failed to exert neuroprotective effect when MT-3 was silenced by the transfection with the specific siRNA, suggesting that MT-3 was the crucial mediator for propofol's neuroprotective effect against H/R. In conclusion, our findings showed that propofol is neuroprotective in H/R model on hippocampal neuron cells and that it may act by up-regulation of MT-3.


Low-Power Light Guiding and Localization in Optoplasmonic Chains Obtained by Directed Self-Assembly.
Optoplasmonic structures contain plasmonic components embedded in a defined photonic environment to create synergistic interactions between photonic and plasmonic components. Here, we show that chains of optical microspheres containing gold nanoparticles in their evanescent field combine the light guiding properties of a microsphere chain with the light localizing properties of a plasmonic nanoantenna. We implement these materials through template guided self-assembly and investigate their fundamental electromagnetic working principles through combination of electromagnetic simulations and experimental characterization. We demonstrate that optoplasmonic chains implemented by directed self-assembly achieve a significant reduction in guiding losses when compared with conventional plasmonic waveguides and, at the same time, retain the light localizing properties of plasmonic antennas at pre-defined locations. The results reinforce the potential of optoplasmonic structures for realizing low-loss optical interconnects with high bandwidth.


Cortical thinning trajectories across disease stages and cognitive impairment in amyotrophic lateral sclerosis.
Cortical neuron degenerative process underlying upper motor neuron involvement in amyotrophic lateral sclerosis (ALS) spreads to extra-motor regions as disease progresses. This is associated with cognitive and behavioural worsening in more severe disease stages. However, the clinical variability of ALS patients might reflect different cortical involvement in extra-motor areas. To investigate cortical thinning across disease stages in ALS patients accounting for their cognitive/behavioural impairment. Thirty-six ALS patients (17 with cognitive/behavioural impairment, ALSimp) and 26 healthy controls underwent structural 3T magnetic resonance imaging. Cortical thickness was measured with a region-wise approach. The King's Clinical Staging System was used to determine disease stages. The Jonckheere-Terpstra test tested for trends in cortical thinning and cognitive involvement across disease stages. Significant trends toward cortical atrophy across disease stages were found in bilateral frontal and cingular cortex, left temporal gyrus and right occipital gyrus of ALS patients, consistently with cognitive impairment in phonemic fluency, language, verbal episodic memory and social cognition. Sub-group analyses revealed that ALSimp had specific thinning in the right fronto-temporal insular cortex related to more pronounced cognitive involvement. Looking at ALS patients irrespective of their cognitive phenotype, motor and extra-motor cortical involvement is consistent with neuropathological studies of disease dissemination. Segregating patients according to their cognitive status, a distinctive trajectory of cortical thinning emerged for ALSimp patients, suggesting a specific course distinct to that of the classic ALS phenotype.


The effect of partial thyroidectomy for Graves' disease on serum long-acting thyroid stimulator protector (LATS-P).
The effect of partial thyroidectomy on serum LATS-P has been investigated in twenty-one consecutive patients. Before surgery, LATS-P was detectable in seventeen (81%) but 1 year after operation only five (24%) had activity. The activity did not fall immediately after surgery but declined progressively throughout the year. In no patient was an increase in activity demonstrated; nor did LATS-P appear in those patients who did not have activity before operation.


Decreased cell replication and polyamine content in insulin-producing cells after exposure to human interleukin 1 beta.
Interleukin 1 (IL-1) has been suggested to cause the islet B cell destruction occurring during the development of insulin-dependent diabetes mellitus. One mechanism by which B cell loss can be compensated for is via de novo formation of new cells through replication. In the present study the replicatory activity of cells in isolated rat pancreatic islets and in the insulin-producing cell line RINm5F has been assessed by [3H]thymidine incorporation methods after exposure to 1-25 U/ml of human recombinant IL-1 beta (rIL-1 beta). In the rat islets [3H]thymidine incorporation was decreased by 20% 5 h after exposure to 25 U/ml rIL-1 beta. A similar inhibition was also observed in islets exposed to 2.5 and 12.5 U/ml rIL-1 beta. In the RINm5F cells there was a dose-dependent inhibition of the cell replication to approximately 50% of the controls in cells exposed to 25 U/ml rIL-1 beta for 48 h. This was also accompanied by an increased cell death, as measured by trypan blue inclusion (controls 13% and rIL-1 beta treated cells 25%). The insulin content of the RINm5F cells was reduced by about 40% after a 48-h exposure to 25 U/ml rIL-1 beta. When the exposure of the RINm5F cells to rIL-1 beta was decreased to 24 h there was no increased cell death, but a reduced replicatory activity was still observed. rIL-1 beta decreased the cellular content of the polyamines spermidine and spermine.(ABSTRACT TRUNCATED AT 250 WORDS)


The neurophysiology of unmyelinated tactile afferents.
CT (C tactile) afferents are a distinct type of unmyelinated, low-threshold mechanoreceptive units existing in the hairy but not glabrous skin of humans and other mammals. Evidence from patients lacking myelinated tactile afferents indicates that signaling in these fibers activate the insular cortex. Since this system is poor in encoding discriminative aspects of touch, but well-suited to encoding slow, gentle touch, CT fibers in hairy skin may be part of a system for processing pleasant and socially relevant aspects of touch. CT fiber activation may also have a role in pain inhibition. This review outlines the growing evidence for unique properties and pathways of CT afferents.


Associations between hemorrhoids and other diagnoses.
The risk factors and mechanisms that contribute to the occurrence of hemorrhoids are not well understood. The study of the comorbid occurrences of hemorrhoids with other diagnoses in identical patients may point to a common underlying pathophysiology. The present study was undertaken to determine which diagnoses are associated with the occurrence of hemorrhoids. A case-control study compared the occurrence of comorbid diseases in case subjects with hemorrhoids with that of control subjects without hemorrhoids. The case population comprised all patients with hemorrhoids (International Classification of Diseases codes 455.0-455.9), who were discharged from hospitals of the U.S. Department of Veterans Affairs between 1986 and 1996. In a multiple logistic regression analysis, the occurrence of hemorrhoids served as outcome variable, and age, gender, ethnicity, and the comorbid occurrence of other diagnoses served as predictor variables. A total of 96,314 individual patients with hemorrhoids and the same number of control subjects were identified. In a chart review of a random sample of 100 cases, the diagnosis of hemorrhoids could be confirmed in 97 percent of all instances checked. The variety of diagnoses associated with hemorrhoids could be broken down into five large categories: 1) diseases associated with diarrhea (odds ratio, 1.30; 95 percent confidence interval, 1.27-1.33); 2) spinal cord injuries (odds ratio, 1.17; 95 percent confidence interval, 1.09-1.26); 3) constipation and related diseases (odds ratio, 1.48; 95 percent confidence interval, 1.43-1.54); 4) various types of anorectal diseases (odds ratio, 4.71; 95 percent confidence interval, 4.44-5.0); and 5) conditions that could be considered manifestations or sequelae of the hemorrhoidal disease itself (odds ratio, 3.41; 95 percent confidence interval, 3.30-3.51). The types and spectrum of comorbid diagnoses associated with hemorrhoids suggest that an increased tone of the anal sphincter constitutes a common pathophysiologic mechanism for the development of hemorrhoids.


Liposarcoma of spermatic cord.
Liposarcoma of the spermatic cord is a rare tumor. Most are of a low-grade malignancy, and treatment is wide local excision with radical orchiectomy. At present there is no clear indication for chemotherapy. Because recurrence, especially local recurrence, is a possibility, periodic followup is necessary. Local recurrences are treated with repeat wide local excision and radiotherapy.


Wilms tumor in adolescence.
A review of the literature reveals that Wilms tumor is rare in adolescence. At the time of diagnosis 78 per cent of children are less than 5 years old. Of 17 cases of Wilms tumor seen at the Ontario Cancer Foundation Clinic in Kingston from 1973 to 1975, 3 children were between 16 and 17 years old. Of 316 cases registered in Ontario with the Ontario Cancer Treatment and Research Foundation only 5 were in the 15 to 19-year age group. The possibility of Wilms tumor in patients beyond the usual age group is not considered as a differential diagnosis because of its relative rarity. Patients may present with features suggestive of neuroblastoma, renal cell carcinoma, hydronephrosis, cholecystitis, appendicitis and twisted ovarian cyst as seen in our 3 patients. In comparison, a review of 84 reported cases of renal cell carcinoma in children from 1934 to 1974 showed 5 cases in the 15 to 18-year age group.


Near-death experiences in cardiac arrest survivors.
Near-death experiences (NDEs) have become the focus of much interest in the last 30 years or so. Such experiences can occur both when individuals are objectively near to death and also when they simply believe themselves to be. The experience typically involves a number of different components including a feeling of peace and well-being, out-of-body experiences (OBEs), entering a region of darkness, seeing a brilliant light, and entering another realm. NDEs are known to have long-lasting transformational effects upon those who experience them. An overview is presented of the various theoretical approaches that have been adopted in attempts to account for the NDE. Spiritual theories assume that consciousness can become detached from the neural substrate of the brain and that the NDE may provide a glimpse of an afterlife. Psychological theories include the proposal that the NDE is a dissociative defense mechanism that occurs in times of extreme danger or, less plausibly, that the NDE reflects memories of being born. Finally, a wide range of organic theories of the NDE has been put forward including those based upon cerebral hypoxia, anoxia, and hypercarbia; endorphins and other neurotransmitters; and abnormal activity in the temporal lobes. Finally, the results of studies of NDEs in cardiac arrest survivors are reviewed and the implications of these results for our understanding of mind-brain relationships are discussed.


Effects of sensory stimulation on respiratory cardiac cycle variability in humans.
The effects of the phase of respiration on the response of respiratory cardiac cycle variability to sensory stimulation were studied in five healthy young male subjects. Transcutaneous electrical stimulation of the ulnar nerve or hand-grip exercise was applied during inspiration or expiration. Although both electrical stimulation and hand-grip exercise depressed respiratory cardiac cycle variability, the nature of the depression differed according to where in the respiration cycle the stimuli were applied. The amplitude of respiratory cardiac cycle variation was significantly decreased when either stimulus was applied during expiration (P < 0.05), and was unchanged when applied during inspiration (P > 0.05). These findings would suggest that cardiac vagal efferent activity was effectively inhibited by sensory stimulation during expiration, but was not inhibited by such stimulation during inspiration. This mechanism may account, in part, for the known suppression of respiratory cardiac cycle variability during exercise.


Attenuation of ischemic renal injury with fructose 1,6-diphosphate.
Fructose 1,6-diphosphate (FDP) has been shown to attenuate tissue injury associated with ischemia and shock by enhancing the anaerobic carbohydrate utilization and by inhibiting oxygen-free-radical generation by the neutrophils. Previously, we have reported that FDP prevents ischemic renal failure if administered prior to the ischemic insult. The present study was designed to determine whether this agent could prevent renal damage when administered during the postischemic reperfusion period. Rats were subjected to 30 min of bilateral renal artery occlusion and infused with FDP (350 mg/kg body wt) beginning 10 min after release of the renal artery clamps. Control rats received an equal volume of glucose/saline solution. A third group of rats were sham operated. Twenty-four hours after injury, BUN, creatinine, and fractional sodium excretion values were less in FDP-treated rats than in control rats (P less than 0.001, P less than 0.005, and P less than 0.001, respectively) and not different from values observed in sham-operated rats. Inulin clearance was greater (P less than 0.001) in FDP-treated rats than in control rats (665 +/- 38 microliters/min/g kidney wt). Renal histology was also better preserved in the FDP-treated group. These data suggest that FDP infused after the initiation of an acute ischemic insult provides significant, but not complete, functional and histologic protection from renal damage.


Tertiary Enamide-Triggered SEAr: Domino Allylation and Enamine-Type Addition.
Two unprecedented domino reactions are described, starting from ketospiro-enesulfonamides. By treatment with ZrCl4 and allylsilane, an intramolecular electrophilic aromatic substitution and subsequent allylation is observed. By treatment with TiCl4 and allylsilane, a double enamine-type reaction takes place, thus creating simultaneously four contiguous stereogenic centers diastereoselectively.


Effects of changes in infusion rate versus glucose concentration on absorption in infant miniature pig small intestine.
The effect of changes in the rate of infusion versus glucose concentration on glucose, water, and sodium absorption was studied in 20 infant miniature pigs using the single-pass small intestinal perfusion technique. During infusions of glucose loads of up to 75.0 mumol/min, glucose absorption increased similarly whether rate of infusion or glucose concentration was increased. Beyond 75.0 mumol/min, glucose absorption was not altered by changes in infusion rate, but was enhanced by increases in glucose concentration (slope of rate vs. concentration, p less than 0.0001). Net water and sodium absorption were similar in the two groups except for a decrease at the highest glucose concentration (rate vs. concentration at 187.5 mumol/min, p less than 0.05). A glucose concentration of 112.5 mM resulted in maximal glucose, water, and sodium absorption.


The "brain drain" of health care workers: causes, solutions and the example of Jamaica.
Despite much media attention being given to the physician shortage in Canada in recent years, this shortage pales in comparison to that seen in many middle- and low-income countries. A major cause of the shortage in these countries is the migration of health care workers from developing to developed nations, a phenomenon known as the "brain drain". The loss of these workers is having devastating impacts globally, particularly in Sub-Saharan Africa and the Caribbean. Causes of the "brain drain" are numerous and include poor working conditions in poorer countries and active recruitment by richer countries. Jamaica has been one of the countries in the Caribbean hardest hit by mass migration of health care workers. The multiple dimensions of Jamaica's health worker "brain drain" illustrate both the complexity of the issues reviewed in this commentary, and the net loss for low- and middle-income countries. Creative and sustainable solutions to the problem are actively being sought globally, but will require commitment and support from all nations as well as from international funding bodies if meaningful impacts on health are to be realized.


[Acute pulmonary embolism in the emergency department: What do the guidelines say?]
The therapeutic strategy of acute pulmonary embolism (PE) is based on risk stratification of early mortality in the emergency department. Anticoagulant therapy should be given to all PE patients as early as possible, and direct oral anticoagulants are expected to replace vitamin K antagonists in the majority of cases. The use of a reperfusion strategy should always be considered in patients with high-risk PE defined as PE with clinical hemodynamic instability. Surgical or percutaneous embolectomy is an alternative in case of contraindication to thrombolytic therapy in these patients. Intermediate-risk PEs defined by a sPESI score of≥1 warrant hospitalization, and continuous care monitoring for patients presenting with elevated biomarkers and right ventricular dysfunction. Low risk PEs (sPESI=0) could be managed on an outpatient basis, provided that a care pathway had been defined beforehand.


Combination treatment with platycodin D and osthole inhibits cell proliferation and invasion in mammary carcinoma cell lines.
In this study, two invasive mammary carcinoma cells (MDA-MB-231 and 4T1) were utilized to evaluate the inhibitory activities of platycodin D, osthole, and the two in combination. The anti-proliferative effect was tested using the MTT and BrdU assay, and the combination of 15μM osthole and 75μM platycodin D was used for subsequent analyses. The anti-invasive effect was evaluated by the transwell assay. The results showed that the combination treatment reduced both cell proliferation and invasion. Western blot and real-time PCR revealed that the platycodin D-osthole combination significantly decreased TβRII, Smad2, Smad3 and Smad4 gene or protein expressions, as well as effectively blocked TGF-β-induced phosphorylation of Smad2 and Smad3. Thus, this study demonstrates that the anti-cancer effects of the platycodin D-osthole combination in breast cancer cells involve proliferation inhibition and invasion blockade, both of which may be mediated by perturbations in the TGF-β/Smads pathway.


Effect of two sonochemical procedures on achieving to different morphologies of lead(II) coordination polymer nano-structures.
Micro and nano-structures of a lead(II) coordination polymer, [Pb2(2-Me-8-Hq)2(MeOH)2]n (1), [2-Me-8-HqH=2-methyl-8-hydroxyquinoline], were synthesized by two sonochemical methods. These new micro and nano-structures were characterized by scanning electron microscopy, X-ray powder diffraction, IR spectroscopy and elemental analyses. Compound 1 was structurally characterized by single-crystal X-ray diffraction and consists of primary dimeric unit of [Pb2(2-Me-8-Hq)2(MeOH)2]. Self assembly between the dimmeric units of [Pb2(2-Me-8-Hq)2(MeOH)2] from Pb-O bonds results in formation of a one-dimensional lead(II) coordination polymer. The Pb(II)-ion in compound 1 has PbO6N1 coordination sphere with a stereo-chemically 'active' electron lone pair on the metals. By a reversible solid-state structural transformation, we successfully prepared [Pb2(2-Me-8-Hq)2]n (2) by thermal desolvation of 1. Thermal stability of compound 1 was studied by thermo gravimetric and differential thermal analyses. In addition nano-structure of PbO was prepared from calcination process of compound 1 at 873 K.


Fire disaster caused by LPG tanker explosion at Lice in Diyarbakır (Turkey): July 21, 2014.
A disaster can be defined as a situation where the affected society cannot overcome its own resources. Our aim was to present the case of a fire disaster caused by a liquefied petroleum gas (LPG) tanker-based explosion on the Diyarbakır-Bingöl road in Lice to determine the various kinds of challenges and patient groups that an emergency department faces and to discuss more effective interventions for similar disasters. This is a retrospective cross-sectional study. To find out the factors that affected mortality, we investigated the patient conditions presented at the time of admission. Among 69 patients included in the study, 62 were male (89.9%) and seven were female (10.1%). The average age of patients was 32.10±14.01 years, and the burn percentage was 51.1±32.2. One patient died during the first response, and a total of 34 patients (49.3%) died during the patient follow-up. Factors statistically related to mortality were determined to be inclusion in the severe burn group, presence of inhalation injuries, use of central venous catheter on patients, application of fasciotomy, presence of a tracheostomy opening, use of endotracheal intubation and sedoanalgesia, and transfer to centers outside the city (p-values <0.001, <0.001, <0.001, <0.001, <0.001, <0.001, 0.001, and 0.003, respectively). In conclusion, although fire disasters caused by LPG tanker explosions are rare, the frequency of such disasters will increase with the increase in LPG use. The factors affecting mortality should be determined to decrease mortality. We recommend that all personnel members who engage in work related to LPG from production to use, in addition to rescue and first-response personnel, be trained comprehensively and that advanced technological fire equipment be used to prevent such disasters.


A systematic review on the effectiveness of school and community-based injury prevention programmes on risk behaviour and injury risk in 8-12 year old children.
To review existing literature on the effectiveness of community-based and school-based physical activity related injury prevention programmes implemented to increase safety behaviour and decrease injury risk in 8-12 year old children, considering the methodological quality of the studies. A systematic review with quality assessment. A systematic search was performed using the CINAHL, Cochrane, EMBASE, PubMed and Sportdiscus databases. Inclusion criteria included the following: children aged 8-12 years; school- or community-based injury prevention programmes; an outcome defined as number of injuries, injury incidence or safety behaviour; published in an English language journal. Methodological quality was assessed for all included studies. The search yielded 5377 records, of which 11 were included in the review; four studies were considered as being of high quality. The focus of studies that were included was on the use of safety devices (8), pedestrian safety (2) and physical activity-related injury prevention (1). For safety device use, short term effects of school- and community-based interventions are promising for 8-12 year olds. Results regarding sustainability of the effect are inconsistent. A mediating effect on the distribution of safety devices was observed. Both financial and non-financial barriers seemed to prevent participants from purchasing a safety device. The short term effects for school- and community-based interventions using safety devices for 8-12 year olds are promising. More high quality research is, however warranted, preferably shifting focus from safety behaviour change to actual physical activity injury reduction.


A spatio-temporal network for video semantic segmentation in surgical videos.
Semantic segmentation in surgical videos has applications in intra-operative guidance, post-operative analytics and surgical education. Models need to provide accurate predictions since temporally inconsistent identification of anatomy can hinder patient safety. We propose a novel architecture for modelling temporal relationships in videos to address these issues. We developed a temporal segmentation model that includes a static encoder and a spatio-temporal decoder. The encoder processes individual frames whilst the decoder learns spatio-temporal relationships from frame sequences. The decoder can be used with any suitable encoder to improve temporal consistency. Model performance was evaluated on the CholecSeg8k dataset and a private dataset of robotic Partial Nephrectomy procedures. Mean Intersection over Union improved by 1.30% and 4.27% respectively for each dataset when the temporal decoder was applied. Our model also displayed improvements in temporal consistency up to 7.23%. This work demonstrates an advance in video segmentation of surgical scenes with potential applications in surgery with a view to improve patient outcomes. The proposed decoder can extend state-of-the-art static models, and it is shown that it can improve per-frame segmentation output and video temporal consistency.


Prognostic value of the QRS duration in patients with heart failure: a subgroup analysis from 24 centers of Val-HeFT.
This study investigated whether QRS duration (QRS D) is a prognostic indicator in patients with heart failure (New York Heart Association [NYHA] classes II-IV). This subgroup analysis included 248 patients with heart failure recruited in the German centers of the Valsartan Heart Failure Trial (Val-HeFT). Mean age was 60 years, mean NYHA class was 2.3, and mean left ventricular ejection fraction (EF) was 27.9%. Electrocardiograms were recorded and analyzed at the beginning of the study, at 2 weeks, 4 months, 1 year, and 2 years. The mean observation period for mortality was 25 months. Patients > or = 65 years and patients with an EF <20% had a significantly longer QRS D (P = .02; P = .0005). NYHA class, etiology of heart failure, therapy with angiotensin-converting enzyme inhibitors, amiodarone or beta-blockers, implanted defibrillator, and atrial fibrillation had no significant influence on QRS D. Total mortality was 9%: 14 patients died suddenly, 7 from heart failure, 2 from noncardiac causes. Kaplan-Meier plots show significantly different survival rates for patients with QRS D <120 ms, QRS D 120-159 ms, or QRS D > or = 160 ms (P = .0085). Multivariate analysis showed that QRS D was the only independent risk factor for all-cause mortality (P = .008). NYHA class, EF, atrial fibrillation, age, and gender failed to qualify as independent prognostic factors. QRS duration in the surface electrocardiogram is an easily obtainable parameter with a significant prognostic impact in patients with congestive heart failure and a reduced EF. In this German subgroup of Val-HeFT patients, it was an independent predictor of all-cause mortality.


Outcomes in preterm infants who received a lipid emulsion with fish oil: An observational study.
100% soybean oil emulsions (SO100) are associated with poor docosahexaenoic acid (DHA) and arachidonic acid (ARA) status in extremely low birth weight (ELBW) infants. A multi-oil emulsion with 15% fish oil (FO15) contains more DHA and ARA than SO100. This study compares clinical outcomes, namely growth and fatty acids, in ELBW infants who received S0100 or FO15. This observational study included ELBW infants born between 2014 and 2019 who received SO100 or FO15 for >7 days. Gas chromatography/mass spectrometry was used to measure erythrocyte fatty acids. The mean ± SD gestational age was 27 ± 3 and 26 ± 2 weeks for SO100 (n = 43) and FO15 (n = 43), respectively (P = 0.2). DHA (-0.3 ± 0.10% per week, P = 0.026, for FO15 vs -0.2 ± 0.05% per week, P < 0.001, for SO100) and ARA (-0.8 ± 0.21% per week for FO15 vs -0.9 ± 0.17% per week for SO100; P < 0.001 for both) declined in both groups with no difference between groups (P interaction > 0.7 for both). After controlling for days to reach full feeds, the mean difference in weight z score trajectories was similar (Est = -0.08; 95% CI, -0.82 to 0.04; P = 0.2), and SO100 was associated with a nonsignificant increased odds for cholestasis (odds ratio, 3.1; 95% CI, 0.96-10.2; P = 0.059). There was no difference in other clinical comorbidities. In comparison with ELBW infants who received SO100, infants who received FO15 still demonstrated a decline in DHA and ARA. Growth and other clinical outcomes were unchanged.


Hepatic immune complex elimination studied with FITC-labelled antigen.
Fluorescein isothiocyanate (FITC)-labelled model antigens (Ags) were used to form soluble IgG immune complexes (ICs) in vitro. The Ag and IC preparations were found to be excellent alternatives to isotope-tagged preparations for the study of plasma clearance after intravenous injection in rats. Ag and IC were eliminated from the blood at the same rate. By direct fluorescence microscopy the FITC-labelled IgG ICs could easily be detected in hepatic non-parenchymal liver cells 30 min after intravenous injection, whereas uncomplexed Ag was apparently taken up by the liver to a much lesser extent.


The Utility of Increased Constraint in Primary Total Knee Arthroplasty for Obese Patients.
Total knee arthroplasty (TKA) for obese patient entails more preoperative comorbidities and complications, and shorter longevity. This article is a retrospective review comparing longevity of the constrained implant with a standard prosthesis. Patient-specific data, Knee Society Scores, complications, and revisions were recorded and compared. No statistical differences were found. The constrained condylar knee for obese patients improves the intramedullary alignment of the prosthesis and supports the surrounding soft tissues. The clinical results are similar to a standard implant in the nonobese with similar longevity at midterm follow-up.


Leptomeningeal Carcinomatosis: Molecular Landscape, Current Management, and Emerging Therapies.
Leptomeningeal carcinomatosis is a devastating consequence of late-stage cancer, and despite multimodal treatment, remains rapidly fatal. Definitive diagnosis requires identification of malignant cells in the cerebrospinal fluid (CSF), or frank disease on MRI. Therapy is generally palliative and consists primarily of radiotherapy and/or chemotherapy, which is administered intrathecally or systemically. Immunotherapies and novel experimental therapies have emerged as promising options for decreasing patient morbidity and mortality. In this review, the authors discuss a refined view of the molecular pathophysiology of leptomeningeal carcinomatosis, current approaches to disease management, and emerging therapies.


Evolution of the MHC class I genes of a New World primate from ancestral homologues of human non-classical genes.
The products of the classical human major histocompatibility complex (MHC) class I genes (HLA-A, -B, -C) are highly polymorphic molecules that bind peptides and present them to T lymphocytes. The non-polymorphic, non-classical MHC class I gene products (HLA-E, -F, -G) are not restricting elements for the majority of T lymphocytes. The evolutionary relationship of the non-classical and classical MHC class I genes is unclear. Here we present the cloning and sequencing of the MHC class I genes of a New World primate, the cotton-top tamarin (Saguinus oedipus). The expressed MHC class I genes of this species are more closely related to the human non-classical HLA-G gene than they are to genes of the human classical HLA-A, -B, and -C loci. These observations imply that classical and non-classical genes do not necessarily constitute mutually exclusive groups over evolutionary time.


Unemployment, Nonstandard Employment, and Fertility: Insights From Japan's "Lost 20 Years".
In this study, we examine relationships of unemployment and nonstandard employment with fertility. We focus on Japan, a country characterized by a prolonged economic downturn, significant increases in both unemployment and nonstandard employment, a strong link between marriage and childbearing, and pronounced gender differences in economic roles and opportunities. Analyses of retrospective employment, marriage, and fertility data for the period 1990-2006 indicate that changing employment circumstances for men are associated with lower levels of marriage, while changes in women's employment are associated with higher levels of marital fertility. The latter association outweighs the former, and results of counterfactual standardization analyses indicate that Japan's total fertility rate would have been 10 % to 20 % lower than the observed rate after 1995 if aggregate- and individual-level employment conditions had remained unchanged from the 1980s. We discuss the implications of these results in light of ongoing policy efforts to promote family formation and research on temporal and regional variation in men's and women's roles within the family.


A miniaturized microstrip antenna with tunable double band-notched characteristics for UWB applications.
This paper proposes the step-by-step design procedure for obtaining independent dual band-notch performance, which provides a valuable method for designing tunable dual band-notched UWB antenna. The proposed antenna consists of the semicircle ring-like radiating patch with an elliptical-shaped slot and double split ring resonators on the top surface of the substrate and defected ground structure (DGS) on the bottom surface of the substrate. The operating frequencies ranged from 1.3 to 11.6 GHz (S11 < - 10 dB). By loading varactor diodes at the gap of the resonators structure and changing the varactor diode's reverse bias voltage(0-30 V), a wider band-notched tuning range from 2.47-4.19 to 4.32-5.96 GHz can be achieved, which covers the whole WiMAX band and WLAN band. The experimental results agree well with the simulated results. The notched gain at notched frequency points is about - 5.3 dBi and - 5 dBi, demonstrating that the narrow-band interference signal could be efficiently suppressed. The security of UWB communication systems can be further enhanced. Meanwhile, the selection of varactor diode and DC bias circuit are fully considered. Hence, the accuracy of the experiment results and antenna operating performance have been improved. Furthermore, the proposed antenna only has an electrical size of 0.26λ*0.19λ at 1.3 GHz. Compared to the related reported antennas, the proposed antenna has achieved a simpler structure, low profile, compact size, tunable dual band-notched characteristics, extensive independent tunable range, and good band-notched performance simultaneously, to the best of our knowledge. The proposed antenna is believed to have a valuable prospect in UWB communication, Wireless Body Area Network, Industry Science Medicine, mobile communication applications, etc.