Factors impacting length of stay and survival in patients with advanced gynecologic malignancies and malignant bowel obstruction.
Malignant bowel obstruction in patients with gynecologic malignancies can impose a large symptomatic burden. The objectives of this study were to identify factors associated with shorter length of hospital stay and overall survival in gynecologic oncology patients with malignant bowel obstructions. A retrospective chart review was performed from December 2014 to March 2019 on patients admitted to a tertiary care center with a malignant bowel obstruction and advanced gynecologic malignancy. Data collection included patient and tumor characteristics, malignant bowel obstruction management (such as conservative management with bowel rest, nasogastric tube, pharmacotherapy or active intervention with surgery, chemotherapy, radiation, total parenteral nutrition or interventional stents), length of hospital stay, and survival outcomes. Statistical analysis included comparisons with Student's t-test and χ2 test, multivariable analysis, and survival analysis. A total of 107 patients with gynecologic cancer with malignant bowel obstruction were included. The majority of patients (63%, n=67) had ovarian cancer. The median length of hospital stay was 12 days (range 1-23), with a median overall survival after malignant bowel obstruction diagnosis of 7 months (range 0.1-64.1). Patients with active interventions had a longer length of stay compared with those with conservative management (13 vs 6 days, p<0.001). However, patients who received multiple active interventions had increased overall survival (9.1 vs 2.9 months, p=0.049). Patients who received multimodal treatment for malignant bowel obstruction had an increased length of stay and improvement in survival of over 6 months. This emphasizes the importance of a multidisciplinary approach to actively manage malignant bowel obstruction in advanced gynecologic cancer.


Significance of serum laminin P1 values in patients with transitional cell carcinoma of the bladder.
The goal of this study was to investigate the relation between serum laminin P1 expression and the grade, stage, size, and multiplicity of the tumors to elucidate the potential role of laminin as a diagnostic and prognostic factor in transitional cell carcinoma (TCC) of the bladder. Serum concentration of laminin P1 was measured by radioimmunoassay in 38 patients with TCC of the bladder and compared with the serum laminin P1 values obtained from 34 healthy control subjects. Patients were grouped according to their tumor stage, grade, size, and multiplicity to compare the serum laminin P1 values. The mean serum laminin P1 level in the patient group was statistically higher than the controls (P = 1.3 x 10(-8); with the destruction of basement membrane (stages pT1 or greater), a significant increase in the serum value was observed (P = 0.00023). Laminin level was found to be positively related to the tumor size and number; however, no correlation was observed with the grade. In tumors invading the lamina propria and beyond, the sensitivity of laminin P1 was 78.9% and specificity was 97.1%. The positive and negative predictive values of laminin P1 were 93.7% and 89.5%, respectively. The patients whose serum laminin P1 levels were above the upper limit of normal (1.6863 U/mL) were found to have a higher recurrence rate (72%) than the patients who had lower serum values in the control cystoscopies performed 3 months after the first admission (P < 0.01). Serum laminin P1 seems to be a valuable adjunctive marker to predict tumor invasion and recurrence. This warrants further research.


Prevalence and Associated Factors of Depressive Symptoms Among Patients With Chronic Low Back Pain: A Cross-Sectional Study.
Background: Few studies have focused on depressive symptoms among patients with chronic low back pain in China. The aim of this cross-sectional study was to assess the prevalence and associated factors of depressive symptoms in patients with chronic low back pain. Methods: From May to August 2021, 1,172 patients with chronic low back pain were recruited in China. Depressive symptoms were assessed through the Patient Health Questionnaire. Associations of demographic characteristics, clinical characters and social-psychological factors with depressive symptoms were investigated among patients with chronic low back pain. Results: The prevalence of depressive symptoms was 25.00%. Logistic regression analysis found that duration of pain in 1-5 years (1-3 years: OR = 2.91, 95%CI: 1.65-5.14, 3-5 years: OR = 3.09, 95%CI: 1.55-6.15) and more severe pain (OR = 1.13, 95%CI: 1.10-1.17) were associated with higher risks of depressive symptoms. Better family function (good family function: OR = 0.25, 95%CI: 0.15-0.41, moderate family dysfunction: OR = 0.47, 95%CI: 0.29-0.77) and higher pain self-efficacy (OR = 0.94, 95%CI: 0.93-0.95) were associated with lower risks of depressive symptoms. Conclusion: Patients with chronic low back pain have a high prevalence of depressive symptoms in China. Duration of pain, pain severity, family function and pain self-efficacy were predictors of depressive symptoms among chronic low back pain patients in China. Early identification of the associated factors may be helpful for the timely management of depressive symptoms.


Heme oxygenase-1 inhibits rat and human breast cancer cell proliferation: mutual cross inhibition with indoleamine 2,3-dioxygenase.
Heme oxygenase-1 (HO-1) is the rate limiting enzyme of heme catabolism whereas indoleamine 2,3 dioxygenase (IDO) catabolizes tryptophan through the kynurenine pathway. We analyzed the expression and biological effects of these enzymes in rat and human breast cancer cell lines. We show that rat (NMU and 13762) but not human cells (MCF-7 and T47D) express HO-1. When overexpressed, we found this enzyme to have anti-proliferative and proapoptotic effects by antioxidant mechanisms in these four cell lines. We show that IDO is expressed by rat and human breast cancer cells. IDO inhibition with 1-MT and siRNA leads to diminished proliferation in rat cells. In contrast, HO-1 negative human cell lines increase proliferation upon IDO inhibition. Since we also demonstrate that IDO inhibits the anti-proliferative HO-1, we propose that IDO has opposite effects on proliferation depending on the coexpression or not of HO-1. We also describe that HO-1 inhibits IDO at the post-translational level through heme starvation. In vivo, we show that rat normal breast expresses HO-1 and IDO. In contrast, N-nitrosomethylurea-induced breast adenocarcinomas only express IDO. In conclusion, we show that HO-1/IDO cross-regulation modulates apoptosis and proliferation in rat and human breast cancer cells.


Characterizing Current Attitudes and Practices for Human Subject Safety in Studies Involving Pupil Dilation.
Standards in pupil dilation practices regarding the safety of human subjects are not present in vision research despite the potential for significant adverse effects. We developed two surveys to examine current practices around pupil dilation among vision researchers and individuals associated with oversight of human subjects research. While both groups note an absence of adverse events associated with pupil dilation, vision researcher practices differed with informed consent use and measures taken to minimize complications. For Institutional Review Boards, general risk assumption associated with dilation was not unanimous and there was a lack of specific guidance available to researchers for minimizing risk. These results uncover the need for standardized practices regarding pupil dilation in human subjects research.


PFGE: a tool for examination of heterogeneity between the bacterial spot-causing xanthomonads of tomato plants in Bulgaria.
Pulsed-field gel electrophoresis (PFGE) is a highly discriminative molecular typing method that is used for epidemiological studies and investigation of outbreaks caused by different pathogens, including phytopathogenic Xanthomonas species. Bacterial spot (BS) is the most common and one of the most destructive diseases of tomato and pepper plants in Bulgaria. Several Xanthomonas species are known to cause BS, but the global distribution and genetic diversity of these species are not well understood. A collection of 100 BS-causing strains, isolated during the period of 1985-2012 from different tomato cultivars and weeds associated with tomato production areas from 11 geographic regions in Bulgaria, were screened for genetic diversity by genomic DNA restriction with rare-cutting endonucleases (XbaI and SpeI) subsequently resolved by PFGE. Two haplotypes for Xanthomonas vesicatoria and one haplotype for Xanthomonas gardneri strains were found.


Halothane induced disorder of red cell membranes of subjects susceptible to malignant hyperthermia.
Membrane fluidity of red blood cells drawn from malignant hyperthermic pigs and humans was studied using spin-probes and electron paramagnetic resonance technique. The order parameter and rotational correlation time were determined with 12-doxylstearate and 16-doxylstearate, respectively. It was found that halothane decreased both parameters, but that the decrease of these parameters in subjects susceptible to malignant hyperthermia was much greater than that in normal subjects. The differences were most pronounced at 3 mM halothane. A possibility of using blood for a non-invasive screening for malignant hyperthermia is discussed.


From Histoanatomy to Sonography in Myofascial Pain Syndrome: A EURO-MUSCULUS/USPRM Approach.
Myofascial pain is a common clinical condition, whereby accurate physical examination is usually considered as the cornerstone to identify/diagnose the "trigger point complex," that is, the characteristic finding of this syndrome. Considering the emerging role of ultrasound examination as the natural extension of physical assessment for musculoskeletal disorders, we briefly revise the histological/anatomical features of trigger points and propose a standardized, multistep sonographic approach to myofascial pain. We also imply that the integrated clinical-ultrasound evaluation could be considered as a potential tool to discriminate different phases/subsets of this challenging pathology.


Scaffold-Free Spheroids with Two-Dimensional Heteronano-Layers (2DHNL) Enabling Stem Cell and Osteogenic Factor Codelivery for Bone Repair.
Scaffold-free spheroids offer great potential as a direct supply of cells for bottom-up bone tissue engineering. However, the building of functional spheroids with both cells and bioactive signals remains challenging. Here, we engineered functional spheroids with mesenchymal stem cells (MSCs) and two-dimensional heteronano-layers (2DHNL) that consisted of black phosphorus (BP) and graphene oxide (GO) to create a 3D cell-instructive microenvironment for large defect bone repair. The effects of the engineered 2D materials on the proliferation, osteogenic differentiation of stem cells was evaluated in an in vitro 3D spheroidal microenvironment. Excellent in vivo support of osteogenesis of MSCs, neovascularization, and bone regeneration was achieved after transplanting these engineered spheroids into critical-sized rat calvarial defects. Further loading of osteogenic factor dexamethasone (DEX) on the 2DHNL showed outstanding in vivo osteogenic induction and bone regrowth without prior in vitro culture in osteogenic medium. The shortened overall culture time would be advantageous for clinical translation. These functional spheroids impregnated with engineered 2DHNL enabling stem cell and osteogenic factor codelivery could be promising functional building blocks to provide cells and differential clues in an all-in-one system to create large tissues for time-effective in vivo bone repair.


Characterization and Validation of the LT-SYS Copper Assay on a Roche Cobas 8000 c502 Analyzer.
Validation of the LT-SYS quantitative in vitro copper assay on a Roche Cobas 8000 c502 analyzer and comparison with a BIOMED assay on a Roche Cobas Mira analyzer. Imprecision and bias were quantified at different concentration levels (serum and plasma) over a 20-day period. Linearity was assessed covering a range from 4.08 µmol/L to 33.8 µmol/L. Limit of blank (LoB) and limit of detection (LoD) were established based on a total of 120 blank and low-level samples. The method comparison was based on 58 plasma samples. Within-run imprecision ranged from 0.7% to 1.2% and within-laboratory imprecision from 1.4% to 3.3%. Relative bias for the 2 serum pools with known target values was less than 2.5%. The assay did not deviate from linearity over the tested measuring range. LoB and LoD were 0.12 µmol/L and 0.23 µmol/L, respectively. The method comparison revealed an average deviation of 11.5% (2.016 µmol/L), and the linear regression fit was y = 1.464 + 0.795x. The LT-SYS copper assay characterized in this study showed a fully acceptable performance with good degrees of imprecision and bias, no deviation from linearity in the relevant measuring rangem, and very low LoB and LoD.


Posterolateral Approach With Buttress Plates and Cannulated Screw Fixation for Large Posterior Malleolus Fractures.
The present study retrospectively reviewed the clinical efficacy of open reduction and internal fixation with buttress plates and cannulated screws via a posterolateral approach for the treatment of large posterior malleolus fractures. From July 2009 to April 2012, 34 patients (15 males and 19 females; mean age 41.2 years) with posterior malleolus fractures involving >25% of the distal articular tibia, were treated by cannulated screw and buttress plate fixation. All the patients were followed for ≥24 months. The outcome measures included the radiographic appearance of the reduction and bone union and the Baird-Jackson score. The average operation time was 105.6 (range 78 to 145) minutes. Radiologic examination showed all fractures achieved anatomic reduction and primary bone union at a mean of 3.8 (range 3 to 7) months after surgery. After an average follow-up period of 32.7 (range 24 to 44) months, no displacement, loosening, or breakage of internal fixation was observed. However, mild posttraumatic arthritis was present in 3 patients. According to the Baird-Jackson scoring system, the outcomes were rated as excellent in 11 cases, good in 17, fair in 5, and poor in only 1 case, for an excellent and good rate of 82.3%. An association analysis indicated age and injury mechanism might be factors influencing the intraoperative and postoperative outcomes. A posterolateral approach with buttress plate and cannulated screw internal fixation could be an effective technique for reduction and fixation of large posterior malleolus fragments.


Late-Stage Melanoma in New York State: Associations with Socioeconomic Factors and Healthcare Access at the County Level.
A diagnosis of late-stage melanoma is associated with significant mortality. From a public health perspective, the knowledge of geographic disparities in late-stage diagnoses can inform efforts to facilitate the diagnosis of the earlier stage, highly curable melanomas. We conducted a county-level analysis of melanoma in New York state to identify communities that may benefit from pilot health interventions to reduce the burden of late-stage melanoma. From 1995 to 2016, late-stage melanoma incidence increased from 1.5 to 2.8 cases per 100,000 in New York state. We found statistically significant associations between decreased county-level health system access (including physician density and resident educational status) and increased county incidence and proportion of late-stage disease among diagnosed cases (P < 0.001 for both). Increased county-level socioeconomic status, including measures of resident wealth and medical insurance status, was positively associated with greater late-stage incidence (P < 0.001). However, decreased county-level socioeconomic status was positively associated with a greater proportion of late-stage disease among cases at diagnosis (P = 0.009). Counties with reduced access to physician services and lower socioeconomic status may be suitable for pilot interventions promoting the recognition and diagnosis of early-stage melanomas to reduce late-stage diagnoses and associated mortality.


Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer.
Head and neck cancer is the sixth most common cancer across the globe. This is generally associated with tobacco and alcohol consumption. Cancer in the pharynx majorly arises through human papillomavirus (HPV) infection, thus classifying head and neck squamous cell carcinoma (HNSCC) into HPV-positive and HPV-negative HNSCCs. Aberrant, mesenchymal-epithelial transition factor (c-MET) signal transduction favors HNSCC progression by stimulating proliferation, motility, invasiveness, morphogenesis, and angiogenesis. c-MET upregulation can be found in the majority of head and neck squamous cell carcinomas. c-MET pathway acts on several downstream effectors including phospholipase C gamma (PLCγ), cellular Src kinase (c-Src), phosphotidylinsitol-3-OH kinase (PI3K), alpha serine/threonine-protein kinase (Akt), mitogen-activated protein kinase (MAPK), and wingless-related integration site (Wnt) pathways. c-MET also establishes a crosstalk pathway with epidermal growth factor receptor (EGFR) and contributes towards chemoresistance in HNSCC. In recent years, the signaling communications of c-MET/HGF in metabolic dysregulation, tumor-microenvironment and immune modulation in HNSCC have emerged. Several clinical trials have been established against c-MET/ hepatocyte growth factor (HGF) signaling network to bring up targeted and effective therapeutic strategies against HNSCC. In this review, we discuss the molecular mechanism(s) and current understanding of c-MET/HGF signaling and its effect on HNSCC.


Simultaneous occurrence of dysaesthetic peno/scroto-dynia and stomatodynia.
The 'dynias' are a group of chronic focal pain syndromes with a predilection for orocervical or urogenital regions. Only exceptionally do they involve both sites in the same patient. Here, we report a case of simultaneous occurrence of dysaesthetic peno/scroto dynia and stomatodynia.


Ketorolac trometamol topical formulations: release behaviour, physical characterization, skin permeation, efficacy and gastric safety.
The objective of this study was to improve systemic delivery of the highly analgesic ketorolac trometamol (ketorolac tromethamine) via the transdermal route, through cost-effective topical formulations, to avoid most of the problems associated with ketorolac trometamol therapy. In-vitro release behaviour of the drug from different microemulsion and emulgel formulations was evaluated. E2 emulgel (based on isopropyl myristate as penetration enhancer) and E7 emulgel (based on Brij 92 as penetration enhancer) were evaluated for their physical properties, rat skin permeation, in-vivo analgesic effect (hot-plate test and the paw pressure test), acute and chronic anti-inflammatory activity and gastric safety. Isopropyl myristate and the synergistic effect of the two known penetration enhancers (propylene glycol and Brij 92) significantly modulated drug permeation and may be a promising approach for the transdermal delivery of ketorolac trometamol and other drugs. Selected in-vivo tested formulae (E2 and E7) caused significantly less ulcer score and less gastric erosion compared with oral ketorolac trometamol. E7 showed significantly higher analgesic and anti-inflammatory activity compared with E2 with no significant difference compared with oral ketorolac trometamol. The developed ketorolac trometamol E7 emulgel appeared promising for dermal and transdermal delivery of ketorolac trometamol, which would circumvent most of the problems associated with drug therapy.


Modelling of Protein Kinase Signaling Pathways in Melanoma and Other Cancers.
Melanoma is a highly aggressive tumor with a strong dependence on intracellular signaling pathways. Almost half of all melanomas are driven by mutations in the v-Raf murine sarcoma viral oncogene homolog B (BRAF) with BRAFV600E being the most prevalent mutation. Recently developed targeted treatment directed against mutant BRAF and downstream mitogen-activated protein kinase (MAPK) MAP2K1 (also termed MEK1) have improved overall survival of melanoma patients. However, the MAPK signaling pathway is far more complex than a single chain of consecutively activated MAPK enzymes and it contains nested-, inherent feedback mechanisms, crosstalk with other signaling pathways, epigenetic regulatory mechanisms, and interacting small non-coding RNAs. A more complete understanding of this pathway is needed to better understand melanoma development and mechanisms of treatment resistance. Network reconstruction, analysis, and modelling under the systems biology paradigm have been used recently in different malignant tumors including melanoma to analyze and integrate 'omics' data, formulate mechanistic hypotheses on tumorigenesis, assess and personalize anticancer therapy, and propose new drug targets. Here we review the current knowledge of network modelling approaches in cancer with a special emphasis on melanoma.


The evolution, evolvability and engineering of gene regulatory DNA.
Mutations in non-coding regulatory DNA sequences can alter gene expression, organismal phenotype and fitness1-3. Constructing complete fitness landscapes, in which DNA sequences are mapped to fitness, is a long-standing goal in biology, but has remained elusive because it is challenging to generalize reliably to vast sequence spaces4-6. Here we build sequence-to-expression models that capture fitness landscapes and use them to decipher principles of regulatory evolution. Using millions of randomly sampled promoter DNA sequences and their measured expression levels in the yeast Saccharomyces cerevisiae, we learn deep neural network models that generalize with excellent prediction performance, and enable sequence design for expression engineering. Using our models, we study expression divergence under genetic drift and strong-selection weak-mutation regimes to find that regulatory evolution is rapid and subject to diminishing returns epistasis; that conflicting expression objectives in different environments constrain expression adaptation; and that stabilizing selection on gene expression leads to the moderation of regulatory complexity. We present an approach for using such models to detect signatures of selection on expression from natural variation in regulatory sequences and use it to discover an instance of convergent regulatory evolution. We assess mutational robustness, finding that regulatory mutation effect sizes follow a power law, characterize regulatory evolvability, visualize promoter fitness landscapes, discover evolvability archetypes and illustrate the mutational robustness of natural regulatory sequence populations. Our work provides a general framework for designing regulatory sequences and addressing fundamental questions in regulatory evolution.


Estimate of undetected severe acute respiratory coronavirus virus 2 (SARS-CoV-2) infection in acute-care hospital settings using an individual-based microsimulation model.
Current guidance states that asymptomatic screening for severe acute respiratory coronavirus virus 2 (SARS-CoV-2) prior to admission to an acute-care setting is at the facility's discretion. This study's objective was to estimate the number of undetected cases of SARS-CoV-2 admitted as inpatients under 4 testing approaches and varying assumptions. Individual-based microsimulation of 104 North Carolina acute-care hospitals. All simulated inpatient admissions to acute-care hospitals from December 15, 2021, to January 13, 2022 [ie, during the SARS-COV-2 ο (omicron) variant surge]. We simulated (1) only testing symptomatic patients, (2) 1-stage antigen testing with no confirmatory polymerase chain reaction (PCR) test, (3) 1-stage antigen testing with a confirmatory PCR for negative results, and (4) serial antigen screening (ie, repeat antigen test 2 days after a negative result). Over 1 month, there were 77,980 admissions: 13.7% for COVID-19, 4.3% with but not for COVID-19, and 82.0% for non-COVID-19 indications without current infection. Without asymptomatic screening, 1,089 (credible interval [CI], 946-1,253) total SARS-CoV-2 infections (7.72%) went undetected. With 1-stage antigen screening, 734 (CI, 638-845) asymptomatic infections (67.4%) were detected, with 1,277 false positives. With combined antigen and PCR screening, 1,007 (CI, 875-1,159) asymptomatic infections (92.5%) were detected, with 5,578 false positives. A serial antigen testing policy detected 973 (CI, 845-1,120) asymptomatic infections (89.4%), with 2,529 false positives. Serial antigen testing identified >85% of asymptomatic infections and resulted in fewer false positives with less cost per identified infection compared to combined antigen plus PCR testing.


Development of Enzymes Involved in Photosynthetic Carbon Assimilation in Greening Seedlings of Maize (Zea mays).
Upon illumination of dark-grown maize seedlings (5 days old) with incandescent light, there occurred a nearly simultaneous increase, after a certain lag period, in the activities of enzymes engaged in the C(4) pathway and the Calvin-Benson cycle. The light-induced biosynthesis of chlorophyll (a and b) precedes the increase in enzyme activities and proceeds without lag phase. A diphasic feature in the elevation of enzyme activities as a function of the intensities of light provided was observed; the increase in enzyme activities was enhanced by light intensities greater than 10(3) ergs per square centimeter per second in comparison with light of lower intensities. Under light intensities greater than 10(3) ergs per square centimeter per second, the simultaneous addition of levulinic acid, which inhibited chlorophyll formation, markedly reduced the increase of enzyme activities. However, neither the diphasic light effect nor the inhibitory effect of levulinic acid was observed with ribulose-1,5-bisphosphate carboxylase. The enzyme activities in the dark-grown maize seedlings were enhanced by a brief irradiation with the red light and the red light effect was reversed by the following far red light treatment. The red light-induced increase in the enzyme activities did not accompany chlorophyll synthesis, and was completely inhibited by cycloheximide, indicating that enzyme synthesis rather than activation might be involved. Light may play a dual role in enzyme induction; one is as an energy source through the photosystems at high intensities and the other is presumably as a signal mediated by phytochrome at low intensities.


Interphase Effect on the Macro Nonlinear Mechanical Behavior of Cement-Based Solidified Sand Mixture.
This paper investigates the interphase effect on the macro nonlinear mechanical behavior of cement-based solidified sand mixture (CBSSM) using a finite element numerical simulation method. CBSSM is a multiphase composite whose main components are soil, cement, sand and water, often found in soft soil foundation reinforcement. The emergence of this composite material can reduce the cost of soft soil foundation reinforcement and weaken silt pollution. Simplifying the CBSSM into a three-phase structure can efficiently excavate the interphase effects, that is, the sand phase with higher strength, the cement-based solidified soil phase (CBSS) with moderate strength, and the interphase with weaker strength. The interphase between aggregate and CBSS in the mixture exhibits the weak properties due to high porosity but gets little attention. In order to clarify the mechanical relationship between interphase and CBSSM, a bilinear Cohesive Model (CM) was selected for the interphase, which can phenomenologically model damage behaviors such as damage nucleation, initiation and propagation. Firstly, carry out the unconfined compression experiments on the CBSSM with different artificial gradations and then gain the nonlinear stress-strain curves. Secondly, take the Monte Carlo method to establish the numerical models of CBSSM with different gradations, which can generate geometric models containing randomly distributed and non-overlapping sand aggregates in Python by code. Then, import the CBSSM geometric models into the finite element platform Abaqus and implement the same boundary conditions as the test. Fit experimental nonlinear stress-strain curves and verify the reliability of numerical models. Finally, analyze the interphase damage effect on the macroscopic mechanical properties of CBSSM by the most reliable numerical model. The results show that there is an obviously interphase effect on CBSSM mechanical behavior, and the interphase with greater strength and stiffness ensures the macro load capacity and service life of the CBSSM; a growth in the interphase number can also adversely affect the durability of CBSSM, which provides a favorable reference for the engineering practice.


The cardioprotective association of average alcohol consumption and ischaemic heart disease: a systematic review and meta-analysis.
Most, but not all, epidemiological studies suggest a cardioprotective association for low to moderate average alcohol consumption. The objective was to quantify the dose-response relationship between average alcohol consumption and ischaemic heart disease (IHD) stratified by sex and IHD end-point (mortality versus morbidity). A systematic search of published studies using electronic databases (1980-2010) identified 44 observational studies (case-control or cohort) reporting a relative risk measure for average alcohol intake in relation to IHD risk. Generalized least-squares trend models were used to derive the best-fitting dose-response curves in stratified continuous meta-analyses. Categorical meta-analyses were used to verify uncertainty for low to moderate levels of consumption in comparison to long-term abstainers. The analyses used 38,627 IHD events (mortality or morbidity) among 957,684 participants. Differential risk curves were found by sex and end-point. Although some form of a cardioprotective association was confirmed in all strata, substantial heterogeneity across studies remained unexplained and confidence intervals were relatively wide, in particular for average consumption of one to two drinks/day. A cardioprotective association between alcohol use and ischaemic heart disease cannot be assumed for all drinkers, even at low levels of intake. More evidence on the overall benefit-risk ratio of average alcohol consumption in relation to ischaemic heart disease and other diseases is needed in order to inform the general public or physicians about safe or low-risk drinking levels.


Differences in peripheral noradrenergic function among actively drinking and abstinent alcohol-dependent individuals.
We examined whether excessive alcohol consumption was related to changes in plasma levels of noradrenaline (NA) and whether these changes recover following abstinence. We also explored whether there were differences in NA levels between Type I and Type II alcoholics and controls during active drinking and abstinence. Plasma concentrations of NA were determined in (1) 27 Caucasian men with alcohol dependence who were regularly drinking (active drinkers) within 24 hours of hospitalization, (2) 29 Caucasian alcohol-dependent men who were in remission (abstinent for a minimum of three months), and (3) 28 race- and gender-matched healthy controls. NA concentrations were significantly higher in actively drinking alcohol-dependent subjects compared to those in remission and controls. While Type I and Type II alcoholic individuals differed across clinical measures, NA levels were similar in the two subtypes. Both subtypes showed an elevation in NA levels during active drinking compared to controls, but NA levels did not differ between the two subtypes and controls during remission. The findings indicate that chronic exposure to alcohol may lead to disturbances in NA activity that may manifest in early abstinence. However, the changes in NA activity appears to normalize after a longer period of abstinence. Alterations in NA activity do not seem to be specific for Type I or Type II subtypes of alcoholism.


Curative surgery for multiple hepatocellular carcinomas after lenvatinib plus transarterial chemoembolization: a case report.
Surgical therapy following lenvatinib (LEN) plus transarterial chemoembolization (TACE) is a useful therapeutic option for intermediate-stage hepatocellular carcinoma (HCC). A 66-year-old man with a history of hepatitis C was detected four masses in the caudate lobe and segment 6/7 of the liver, with a maximum lesion diameter of 14 cm by computed tomography. The patient was diagnosed with intermediate-stage HCC and received LEN plus TACE. After resuming LEN for 8 weeks, computed tomography showed weakened stained areas of the tumors, and no new lesions. Thus, the patient was evaluated as having a partial response in the modified Response Evaluation Criteria in Solid Tumors. The patient underwent hepatic caudate lobectomy, partial hepatectomy of S6/7, and S6 microwave coagulation therapy for radical resection. The patient is currently alive and recurrence-free at 12 months postoperatively. In patients with multiple HCC lesions, hepatic resection combined with local therapy might be an effective treatment option.


[DHEA: an unknown star].
To clarify the physiological function of dehydroepiandrosterone (DHEA), the most abundant steroid in human plasma, which remains poorly understood. To analyse the beneficial effects of a supplementation in order to alleviate its decrease in ageing and improve well-being. DHEA (and its sulfate) acts on peripheral tissues as an androgenic and estrogenic precursor. It is also considered as a neurosteroid. DHEA administration in several pathological animal models is promising, especially in metabolic diseases such as obesity and insulin resistance. It appears like a factor of immunomodulation and facilitates cognitive acquisition. In humans there is little evidence that DHEA may be useful in characterized pathologies apart from adrenal insufficiency. An interesting effect was also noted in severe systemic lupus erythematosus. The effects on cognitive and neuropsychiatric diseases such as midlife dysthymia are not yet convincing. Prospective studies of supplementation versus placebo indicate inconstant improvement in well-being in the post-menopausal state. DHEA is not a panacea against ageing despite there being a well-established aging-related decrease of DHEA. Contrary to some assertions there are no proven relations between cardiovascular or cancer risk. Until now adrenal insufficiency has been the only well-documented indication of an oral DHEA supplementation. However, DHEA may be a good way for androgen supplementation in menopausal men. Further investigations are needed to better know the anti-inflammatory and immunomodulation properties of DHEA. At the least, prospective studies on large populations are necessary to assess the true benefits and dangers of DHEA in prevention of ageing.


Somatotopic representation of facial muscles within the facial nucleus of the mouse. A study using the retrograde horseradish peroxidase and cell degeneration techniques.
The somatotopic representation of facial muscles within the facial nucleus was investigated by means of the retrograde horseradish peroxidase and cell degeneration techniques in the mouse. The nasolabial muscle is represented in the dorsolateral, lateral, and dorsal intermediate subnucleus; the mentalis muscle, in the ventral intermediate subnucleus; the platysma, in the dorsomedial part of the dorsal intermediate subnucleus and along the lateral border of the dorsomedial and ventromedial subnucleus; the orbicularis oculi and frontalis muscle, in the dorsal portions of the dorsolateral, dorsal intermediate, and dorsomedial subnucleus; the rostral and caudal auricular muscles, in the dorsomedial and ventromedial subnucleus, respectively; and the caudal belly of the digastric muscle, in the suprafacial nucleus. The present study shows that the facial muscles are represented in an orderly fashion in seven subnuclei of the facial nucleus, as in other animal species.


Reflections of medical students regarding the care of geriatric patients in the continuing care retirement community.
There is growing recognition that students training to provide care for older adults need to be trained in all settings where older adults receive care, including retirement communities. The purpose of this study was to allow medical students to see older patients living and participating in activities in the long-term care setting and examine the effects that this experience had on the students. Medical students were assigned to write an open-ended reflection paper about a community health experience. Forty-eight students wrote their reflection papers on their experience in a continuing care retirement facility. Three independent reviewers examined these reflective narratives for common themes. After analyzing the students' narratives, 6 themes emerged: (1) The initial exposure to dementia, (2) confronting death and dying, (3) the diversity of care and services for the elderly, (4) the cost of care for the elderly, (5) seniors can lead active lives if given the opportunity, and (6) the rewards of the health care team-patient relationship. The students' reflective narratives provide valuable insights into how medical students view retirement communities, the physician's role in the care of geriatric patients, the importance of interdisciplinary health care, the cost of care for elderly patients, and their views on dementia and dying. Through this experience, students received valuable lessons about taking care of older adults in the community that their interactions with patients in the hospital and ambulatory medical offices had not provided.


Care of Patients With HIV Infection: Diagnosis and Monitoring.
Appropriate screening for HIV infection is the cornerstone of HIV-related care. There have been several recent changes in testing technology and screening recommendations. The US Preventive Services Task Force recommends universal HIV screening at least once for adolescents and adults ages 15 to 65 years, and additional screening for patients at higher risk, although evidence is insufficient to determine optimum rescreening intervals. All pregnant women should be screened for HIV infection in the first trimester, and pregnant women at high risk should be screened again in the third trimester. The Centers for Disease Control and Prevention recommends use of an algorithm using fourth-generation tests for screening; this decreases the window period between infection and detection to as few as 14 days, thereby reducing the number of false-negative results. Home HIV testing kits, which require follow-up confirmatory testing, also are available. Clinicians should be aware of HIV-specific laws in their states, including those criminalizing HIV exposure and transmission. Thorough medical and laboratory evaluations are essential at initiation of care for patients with HIV infection, along with appropriate follow-up monitoring, as recommended in various guidelines.


Sulforaphane inhibits platelet-derived growth factor-induced vascular smooth muscle cell proliferation by targeting mTOR/p70S6kinase signaling independent of Nrf2 activation.
Activation of nuclear factor erythroid 2-related factor 2 (Nrf2, a transcription factor) and/or inhibition of mammalian target of rapamycin (mTOR) are implicated in the suppression of vascular smooth muscle cell (VSMC) proliferation. The present study has examined the likely regulatory effects of sulforaphane (SFN, an antioxidant) on Nrf2 activation and platelet-derived growth factor (PDGF)-induced mTOR signaling in VSMCs. Using human aortic VSMCs, nuclear extraction and siRNA-mediated downregulation studies were performed to determine the role of Nrf2 on SFN regulation of PDGF-induced proliferative signaling. Immunoprecipitation and/or immunoblot studies were carried out to determine how SFN regulates PDGF-induced mTOR/p70S6K/S6 versus ERK and Akt signaling. Immunohistochemical analysis was performed to determine SFN regulation of S6 phosphorylation in the injured mouse femoral artery. SFN (5μM) inhibits PDGF-induced activation of mTOR without affecting mTOR association with raptor in VSMCs. While SFN inhibits PDGF-induced phosphorylation of p70S6K and 4E-BP1 (downstream targets of mTOR), it does not affect ERK or Akt phosphorylation. In addition, SFN diminishes exaggerated phosphorylation of S6 ribosomal protein (a downstream target of p70S6K) in VSMCs in vitro and in the neointimal layer of injured artery in vivo. Although SFN promotes Nrf2 accumulation to upregulate cytoprotective genes (e.g., heme oxygenase-1 and thioredoxin-1), downregulation of endogenous Nrf2 by target-specific siRNA reveals an Nrf2-independent effect for SFN-mediated inhibition of mTOR/p70S6K/S6 signaling and suppression of VSMC proliferation. Strategies that utilize local delivery of SFN at the lesion site may limit restenosis after angioplasty by targeting mTOR/p70S6K/S6 axis in VSMCs independent of Nrf2 activation.


Reaction mechanism and kinetic modeling of DEET degradation by flow-through anodic fenton treatment (FAFT).
The previously developed batch anodic Fenton treatment (AFT) technology has been successfully applied to degrade various pesticides in aqueous solution. The goal of this work is the development of a flow-through AFT system (FAFT) which is critical to bringing this technology into practical general use in the field. For this purpose, the degradation of DEET (N,N-diethyl-3-methylbenzamide), an insect repellent, and nine model amides was studied. Oxidation products of these compounds in FAFT were identified by GC/MS, and the results revealed that various -OH additions (most likely on the aromatic ring), quinone/keto product formation, and dimerization/bimolecular disproportionation are the major reaction pathways. This proposed overall reaction mechanism was then combined with the basic Fenton's mechanism to model the kinetics of various active species in FAFT including DEET, Fe2+, H2O2, and total iron under different reaction conditions. In addition, both initial and steady-state hydroxyl radical concentrations were measured in FAFT using benzoic acid as a chemical probe; the measured *OH concentrations were best-fitted exponentially. On the basis of the obtained [*OH] trend and the mass balance of the FAFT system, a simple FAFT model was developed to fit all of the degradation data of DEET and the model amides.


Gli1 Defines a Subset of Fibro-adipogenic Progenitors that Promote Skeletal Muscle Regeneration With Less Fat Accumulation.
Skeletal muscle has remarkable regenerative ability after injury. Mesenchymal fibro-adipogenic progenitors (FAPs) are necessary, active participants during this repair process, but the molecular signatures of these cells and their functional relevance remain largely unexplored. Here, using a lineage tracing mouse model (Gli1-CreER Tomato), we demonstrate that Gli1 marks a small subset of muscle-resident FAPs with elevated Hedgehog (Hh) signaling. Upon notexin muscle injury, these cells preferentially and rapidly expanded within FAPs. Ablation of Gli1+ cells using a DTA mouse model drastically reduced fibroblastic colony-forming unit (CFU-F) colonies generated by muscle cells and impaired muscle repair at 28 days. Pharmacologic manipulation revealed that Gli1+ FAPs rely on Hh signaling to increase the size of regenerating myofiber. Sorted Gli1+ FAPs displayed superior clonogenicity and reduced adipogenic differentiation ability in culture compared to sorted Gli1- FAPs. In a glycerol injury model, Gli1+ FAPs were less likely to give rise to muscle adipocytes compared to other FAPs. Further cell ablation and Hh activator/inhibitor treatments demonstrated their dual actions in enhancing myogenesis and reducing adipogenesis after injury. Examining single-cell RNA-sequencing dataset of FAPs from normal mice indicated that Gli1+ FAPs with increased Hh signaling provide trophic signals to myogenic cells while restrict their own adipogenic differentiation. Collectively, our findings identified a subpopulation of FAPs that play an essential role in skeletal muscle repair. © 2021 American Society for Bone and Mineral Research (ASBMR).


[Histological statistics of malignant urogenital tumors].
A statistic survey was carried out on the histology of the 465 malignant tumors at our urological department during the last 10 years. The most frequent tumors were bladder tumor (50%), prostatic tumor (17%) and renal tumor (15%). Histological typing and grading were tabulated for each tumors.


A Study Comparing Cost-Effectiveness of Combination Therapy for Preventing Opportunistic Infections Among Human Immunodeficiency Virus-Infected Adults on Antiretroviral Therapy.
India is going through an epidemiologic and demographic transition made possible by increased investment in health sector and sustained development. The country has more than 2 million people infected with human immunodeficiency virus (HIV). Information on cost-effectiveness of competing interventions is a useful contributor to decisions concerning allocation and prioritization of healthcare resources. This paper aims to study the cost, health outcomes as measured by disability-adjusted life-years (DALYs), and cost-effectiveness per DALY averted of prophylaxis for tuberculosis, diarrhea, and mouth ulcers in HIV-infected adults. Data were analyzed on 375 HIV-infected persons enrolled at the ART Centre in New Delhi between April 2004 and April 2006. Using estimates of the age of onset of HIV infection, cost of medicines, and antiretroviral regimen followed, we used standard methods to calculate the cost per DALY as a measure of cost-effectiveness. Sensitivity analysis was conducted to determine the robustness of cost-effectiveness results by making reasonable changes in underlying assumptions. The results revealed that the incremental cost-effectiveness ratio for tuberculosis prophylaxis was ₹4821.48 ($78.86) per DALY averted compared with no prophylaxis, followed by diarrhea (₹8299.08, $135.74) and mouth ulcers (₹20 058.14, $328.07). The estimates are less than the per capita gross domestic product of India, indicating that the current treatments are highly cost-effective. This will help policymakers understand the best opportunities to improve population health and help researchers to develop more standardized methods in the area, thus improving quality and comparability across cost per DALY studies.


Does massive intraabdominal free gas require surgical intervention?
We describe a rare case of an 81-year-old man who presented with severe epigastralgia. A chest radiograph showed massive free gas bilaterally in the diaphragmatic spaces. Computed tomography (CT) scan also showed massive free gas in the peritoneal cavity with portal venous gas. We used a wait-and-see approach and carefully considered surgery again when the time was appropriate. The patient received conservative therapy with fasting, an intravenous infusion of antibiotics, and nasogastric intubation. The patient soon recovered and was able to start eating meals 4 d after treatment; thus, surgical intervention was avoided. Thereafter, colonoscopy examination showed pneumatosis cystoides intestinalis in the ascending colon. On retrospective review, CT scan demonstrated sporadic air-filled cysts in the ascending colon. The present case taught us a lesson: the presence of massive intraabdominal free gas with portal venous gas does not necessarily require surgical intervention. Pneumatosis cystoides intestinalis should be considered as a potential causative factor of free gas with portal venous gas when making the differential diagnosis.


Evidence supporting the use of physical modalities in the treatment of upper extremity musculoskeletal conditions.
To evaluate recent trials and reviews of physical modalities and conservative treatments for selected upper extremity musculoskeletal conditions for evidence supporting their use. Recent evidence suggests that many localized tendinopathies are related more to degenerative than inflammatory processes. With this realization, there is increased emphasis on finding new modalities to treat tendinopathies and other localized musculoskeletal conditions that rely on other than anti-inflammatory mechanisms. Although there is good evidence to support the short-term benefits of corticosteroid injections, convincing evidence in support of other conservative treatments and modalities is generally lacking. Extracorpal shock wave therapy may have significant clinical benefit for calcific tendinitis; however, it requires intravenous sedation in most cases and does not appear to be effective in lateral epicondylitis. The most consistent positive treatment effects for rotator cuff tendinitis were achieved by ultrasound-guided subacromial corticosteroid injection as well as manual therapy in conjunction with therapeutic exercise. Although there is evidence supporting the use of several different physical modalities and conservative treatments for upper extremity musculoskeletal conditions, there is a strong need for larger, higher quality randomized controlled trials. Although most studies are able to demonstrate short-term benefits, there is a lack of high-quality data demonstrating that these conservative treatments have long-term benefits, particularly, with regard to functional outcomes.


Three-Dimensional Culture Reduces Cell Size By Increasing Vesicle Excretion.
Our previous study has shown that three-dimensional (3D) culture decreases mesenchymal stem cell (MSC) size, leading to enhanced trafficking ability and reduced lung vascular obstructions. However, the underlying mechanisms are unclear. In this study, we proposed that 3D culture reduces MSC size by increasing vesicle excretion. Scanning electron microscope showed that 3D culture markedly increased the amount of membrane-bound vesicles on the cell surface. In consistence, tunable resistive pulse sensing quantifying analysis of vesicles in the culture medium indicated that there were higher levels of vesicles in the 3D culture MSC medium. 3D culture significantly lowered the level of actin polymerization (F-actin), suggestive of lowering actin skeleton tension may facilitate vesicle excretion. Indeed, treatment of MSCs with Cytochalasin D or functional blockade of integrin β1 caused increased vesicle secretion and decreased cell sizes. Thus, our results suggest that 3D culture reduces MSC size by increasing vesicle excretion which is likely mediated by lowering cytoskeleton tension. Stem Cells 2018;36:286-292.


Drosophila crumbs is required to inhibit light-induced photoreceptor degeneration.
Mutations in the human transmembrane protein CRB1 are associated with severe forms of retinal dystrophy, retinitis pigmentosa 12 (RP12), and Leber's congenital amaurosis (LCA). The Drosophila homolog, crumbs, is required for polarity and adhesion in embryonic epithelia and for correct formation of adherens junctions and proper morphogenesis of photoreceptor cells. Here, we show that mutations in Drosophila crumbs result in progressive, light-induced retinal degeneration. Degeneration is prevented by expression of p35, an inhibitor of apoptosis, or by reduction of rhodopsin levels through a vitamin A-deficient diet. In the dark, rhabdomeres survive but exhibit morphogenetic defects. We demonstrate that it is the extracellular portion of the Crumbs protein that is essential to suppress light-induced programmed cell death, while proper morphogenesis depends on the intracellular part. We conclude that human and Drosophila Crumbs proteins are functionally conserved to prevent light-dependent photoreceptor degeneration. This experimental system is now ideally suited to study the genetic and molecular basis of RP12- and LCA-related retinal degeneration.


The Rise and Fall of Dopamine: A Two-Stage Model of the Development and Entrenchment of Anorexia Nervosa.
Dopamine has long been implicated as a critical neural substrate mediating anorexia nervosa (AN). Despite nearly 50 years of research, the putative direction of change in dopamine function remains unclear and no consensus on the mechanistic role of dopamine in AN has been achieved. We hypothesize two stages in AN- corresponding to initial development and entrenchment- characterized by opposite changes in dopamine. First, caloric restriction, particularly when combined with exercise, triggers an escalating spiral of increasing dopamine that facilitates the behavioral plasticity necessary to establish and reinforce weight-loss behaviors. Second, chronic self-starvation reverses this escalation to reduce or impair dopamine which, in turn, confers behavioral inflexibility and entrenchment of now established AN behaviors. This pattern of enhanced, followed by impaired dopamine might be a common path to many behavioral disorders characterized by reinforcement learning and subsequent behavioral inflexibility. If correct, our hypothesis has significant clinical and research implications for AN and other disorders, such as addiction and obesity.


Early prediction of treatment response in rheumatoid arthritis by quantitative macrophage PET.
To determine whether macrophage positron emission tomography (PET)/computed tomography (CT) imaging using (R)-[11C]PK11195 at 0 and 2 weeks is associated with clinical response at 13 weeks in patients with early rheumatoid arthritis (RA). Whole-body (R)-[11C]PK11195 PET/CT scans were performed at baseline and after 2 weeks of COBRA-light (combination therapy of methotrexate and prednisone) treatment in 35 patients with clinically active early RA. Clinical assessment (Disease Activity Score of 44 joints (DAS44)) was performed at 0, 2 and 13 weeks of treatment. PET/CT scans were assessed visually by two blinded, experienced readers, and by calculating standardised uptake values (SUVs) for shoulders, elbows, hips, knees, and hand and feet joints. Clinical and PET variables were compared using (multivariate) linear regression. 18 males and 17 females were included (baseline DAS44=3.2 ± 1.0). 171 out of 1470 joints were visually PET positive at baseline, decreasing to 100 joints after 2 weeks. In general, small feet joints showed the highest uptake at baseline, and the largest decrease after 2 weeks (Δ0-2). Neither baseline nor Δ0-2 PET measures correlated with DAS44 at 13 weeks. However, at 2 weeks, average SUV of the feet significantly correlated with DAS44 at 13 weeks (R2=0.14, p=0.04). In a multivariable model, DAS44 and average SUV of the feet at 2 weeks showed substantial combined predictive value (combined R2=0.297, p<0.01). Quantitative macrophage PET assessment of feet joints, together with DAS44, after 2 weeks of COBRA light treatment in patients with early RA correlates with clinical response after 3 months of treatment.


Sumatriptan-naproxen migraine efficacy in allodynic patients: early intervention.
This study evaluated the effectiveness of a single fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg (sumatriptan-naproxen) using a very early treatment paradigm in migraine patients whose attacks were historically accompanied by cutaneous allodynia. Evidence suggests that allodynic migraineurs may demonstrate a better response when treated prior to developing central sensitization, and that these patients are treated more effectively with a compound of sumatriptan and naproxen sodium than either drug alone. This study targeted patients who have accompanying allodynia using a very early treatment paradigm where treatment was initiated while symptoms were still mild. This was an open-label prospective, outpatient study of adult migraineurs who had screened positive for cutaneous allodynia and typically experienced moderate to severe pain preceded by an identifiable mild pain phase. Patients were treated with sumatriptan-naproxen using a very early intervention paradigm in 4 test migraines over 12 weeks where dosage occurred within 30 minutes of symptom onset. Data from diaries and questionnaires were used to evaluate the primary endpoints of sustained pain-free response at 24 hours post dose (using no second dose of study drug and no other rescue drugs), and overall satisfaction with sumatriptan-naproxen. Forty allodynic migraineurs enrolled in this study and reported a total of 160 migraines. Of these migraines, 78 (49%) achieved sustained pain-free at 24 hours and 94 (59%) were reported as pain-free at 2 hours. The number of patients who rated their Overall Satisfaction following treatment with sumatriptan-naproxen as "Satisfied" (satisfied or very satisfied) was 32 (80%) after the first migraine and 25 (63%) after 3 or more migraines. In this open-label study, allodynic patients reported that their migraine attacks responded well and they achieved a high degree of satisfaction following treatment with a fixed-dose tablet of sumatriptan 85 mg/naproxen sodium 500 mg administered in a very early treatment paradigm.


An evaluation of bioequivalence of two 7-day 17beta-estradiol transdermal delivery systems by anatomical site.
An open-label, randomized, crossover study was conducted to assess the bioequivalence of two 7-day transdermal 17beta-estradiol delivery systems following application to the buttock in 42 postmenopausal women. The systems tested were a generic Estradiol Transdermal System (Mylan Pharmaceuticals, Inc.) and Climara (Berlex Laboratories, Inc.), the reference product. Each system was labeled to deliver 17beta-estradiol 0.1 mg/day and was applied for 7 days. Serial serum samples were assayed for estradiol, estrone, and estrone sulfate using validated assays. The bioequivalence confidence intervals for the ratio of log-transformed 17beta-estradiol Cmax values for the Estradiol Transdermal System and Climara were outside the interval of 0.80 to 1.25, indicating that the products were not bioequivalent. Application site reactions and skin irritation were more common with the Estradiol Transdermal System than with Climara. The odds of patch lifting or detachment were 6.95 times higher with the Estradiol Transdermal System than with Climara. Because these two transdermal delivery systems had been previously shown to be bioequivalent after application to the abdomen, the findings of this study suggest that bioequivalence at one anatomical site is not indicative of bioequivalence at another.


Unusual binding of ethidium to a deoxyoligonucleotide containing a B-Z junction.
Equilibrium binding studies are reported that describe the interaction of the simple intercalator ethidium with a hexadecadeoxynucleotide (BZ-1) that contains a stable B-Z junction. The transition of BZ-1 from its low-salt right-handed form to its high-salt hybrid form containing the junction between left- and right-handed DNA was found to greatly facilitate ethidium binding. Ethidium binding to all conformational forms of BZ-1 was found to be complex and highly cooperative, a result that indicates an unusually robust conformational mobility in the molecule. Binding results were quantitatively analyzed by using an allosteric model that provides a description of energetics of the conformational transitions in BZ-1, in addition to estimates of the binding constants for ethidium binding to the different conformations. These results provide a quantitative description of a structurally specific intercalator-DNA interaction.


Hybrids of Polymeric Capsules, Lipids, and Nanoparticles: Thermodynamics and Temperature Rise at the Nanoscale and Emerging Applications.
The importance of thermodynamics does not need to be emphasized. Indeed, elevated temperature processes govern not only industrial scale production but also self-assembly, chemical reaction, interaction between molecules, etc. Not surprisingly, biological processes typically take place at a specific temperature. Here, we look at possibilities to raise the localized temperature by a laser around noble-metal nanoparticles incorporated into shells of layer-by-layer polyelectrolyte microcapsules-freely suspended delivery vehicles in an aqueous solution, developed in the Department of Interfaces, Max Planck Institute of Colloids and Interfaces, headed by Helmuth Möhwald. Understanding the mechanisms of localized temperature rise is essential, that is why we analyze the influence of incident intensity, nanoparticle size, their distribution and aggregation state, as well as thermodynamics at the nanoscale. This leads us to scrutinize "global" (used for thermal encapsulation) versus "local" (used for release of encapsulated materials) temperature rise. Similar analysis is extended to planar polymeric coatings, the lipid membrane system of vesicles and cells, on which nanoparticles are adsorbed. Insights are provided into the mechanisms of physicochemical and biological effects, the nature of which has always been profoundly, interactively, and engagingly discussed in the Department of Interfaces. This analysis is combined with recent developments providing outlook and highlighting a broad range of emerging applications.


Symptomatic reinfarctation of a previously silent myocardial region four months after successful reperfusion--a case report.
Coronary collateral circulation helps to preserve myocardial perfusion distal to severely stenotic or totally obstructed coronary arteries. The presence or absence of angina pectoris and the state of myocardial function depend on the extent of collateralization and its functional contribution to myocardial blood flow. Clinical and experimental observations have suggested that newly developed collaterals usually remain even after successful revascularizaton. The authors present a case of a patient with extensive intercoronary collaterals and hibernating myocardium after an acute inferior wall myocardial infarction who underwent successful percutaneous transluminal coronary angioplasty of a totally obstructed, dominant right coronary artery and then experienced extensive reinfarction following reocclusion 4 months later. This case demonstrates failure of extensive collaterals to prevent acute myocardial infarction.


Theoretical Study on the Spectroscopic Properties and Photodissociation Mechanism of Dibromocarbene.
Detailed calculations on the electronic states of dibromocarbene (CBr2) herein are presented. First, the spectroscopic properties of the electronic states including geometry parameters, harmonic vibrational frequencies and transition energies of the lowest electronic states of the neutral radical were calculated in detail using the internally contracted multireference configuration interaction methods including Davidson correction (icMRCI+Q) with correlation consistent basis sets of aug-cc-pVXZ (X = T, Q, 5). Second, as CBr2 including two Br atoms, the Spin-Orbit Coupling (SOC) effect on the spectroscopic parameters and the one-dimensional cuts of the potential energy surface (PESs) of the lowest three states were studied. The barrier to linearity and dissociation of the singlet state were discussed. Third, the one-dimensional cuts along with the vertical transition energy (VTE), the oscillator strength, and so on of the electronic states related to the several lowest dissociation limits of CBr2 were calculated at the icMRCI+Q/aug-cc-pVTZ level. Based on the computed results of the electronic states of the radical, the photodissociation mechanism in the UV region were discussed in detail. The ab initio calculations are compared with the previous theoretical and experimental data and are in good agreement. The present work will provide a comprehensive understanding on the electronic structures and dissociation dynamics for the electronic states of the CBr2 radical.


Complete mitochondrial DNA genome of Pseudobagrus brevicaudatus (Siluriformes: Bagridae).
The complete mitochondrial genome of Pseudobagrus brevicaudatus (Siluriformes: Bagridae) was sequenced in this study. The total length of the mitogenome is 16,533 bp, with the base composition of 31.6% A, 26.8% T, 15.0%G, 26.6% C. The gene order and genes were the same as that found in other previously reported catfishes, including 13 protein-coding genes, 22 transfer RNA genes, 2 ribosomal RNA genes, and 1 non-coding control region. Except for ND6 gene and 8 tRNA genes, all other mitochondrial genes were encoded on the heavy strand. This complete mitogenome data provides the basis for taxonomic and conservation research of this and closely related species.


Quality of life of family caregivers of cancer patients in Singapore and globally.
Family caregivers of cancer patients often suffer from impaired quality of life (QOL) due to stress arising from the responsibility of caregiving. Most research on such QOL impairments was conducted in Western populations. Thus, this exploratory study sought to (a) examine the QOL levels of family caregivers of cancer patients in an Asian population in Singapore, in relation to caregivers from other countries within and outside of Asia; and (b) investigate the association between sociodemographic factors and QOL impairments in family caregivers in Singapore. A total of 258 family caregivers of cancer patients who were receiving outpatient treatment completed the Caregiver Quality of Life Index-Cancer (CQOLC) and a sociodemographic survey. We compared the published CQOLC total scores from Turkey, Iran, Taiwan, South Korea, the United Kingdom, the United States and Canada with the Singapore dataset and examined the demographic relationships. Caregivers in Singapore and Asia had lower CQOLC total scores than their Western counterparts. Caregivers who were male, of Chinese ethnicity, had parental relationships with their care recipient, or cared for advanced-stage cancer patients were found to have impaired QOL. The findings of this study highlight possible areas in which support can be provided for family caregivers of cancer patients, and underscore the need to reconcile cultural diversity, values, societal expectations and demographic characteristics in Singapore.


Urinary protein and essential hypertension in black and in white people.
The objectives of this work were to examine the association between urinary protein and blood pressure and to compare the pattern of urinary protein excretion with essential hypertension in people of European origin (whites) and in people of African or African-Caribbean origin (blacks) living in southwest London, United Kingdom. In the groups as a whole, there were no significant differences in total urinary protein excretion between blacks and whites (geometric means [95% CI]: 94.0 [85.9 to 102.9] mg/24h for the blacks [n=151] and 102.1 [96.1 to 108.4] mg/24h for the whites [n= 219]). There were also no significant differences between blacks and whites in urinary albumin (6.5 [4.9 to 8.5] mg/24h for the blacks [n=97] and 7.1 [5.6 to 9.0] mg/24h for the whites [n=123]). In both groups, those with essential hypertension displayed a significantly raised urinary protein excretion (1.21-fold higher for the blacks and 1.19-fold higher for the whites) and albumin excretion (1.69-fold higher for the blacks and 2.40-fold higher for the whites). Urinary transferrin excretion measured in a subgroup of 67 subjects was also raised in those with essential hypertension (3.22-fold higher in the blacks and 2.76-fold higher in the whites). Examination of urinary proteins by SDS-PAGE did not identify any pattern consistent with a reduction in renal tubular protein reabsorption in those with essential hypertension. These results suggest that the increase in protein excretion in essential hypertension could be due, at least in part, to an increase in glomerular protein ultrafiltration.


Cloning, expression profiling, and acetylation identification of alpha-tubulin N-acetyltransferase 1 from Bombyx mori.
Alpha-tubulin N-acetyltransferase 1 (ATAT1) is an acetyltransferase specific to α-tubulin and performs important functions in many cellular processes. Bombyx mori is an economic insect and also known as a model lepidoptera insect. In this study, we cloned a B. mori ATAT1 gene (BmATAT1) (Gen Bank accession number: XP_004932777.1). BmATAT1 contained an open reading frame (ORF) of 1,065 bp encoding 355 amino acids (aa). Expression profiling of BmATAT1 protein showed that the expression levels of BmATAT1 at different developmental stages and different tissues in fifth-instar larvae differ. BmATAT1 was highly expressed at the egg stage and in the head of the fifth-instar larvae. Subcellular localization showed that BmATAT1 was distributed in the cytoplasm and nucleus. Furthermore, BmATAT1 may lead to time-dependent induction of cell cycle arrest in the G2/M phase by flow cytometry analysis. Interestingly, using site-specific mutation, immunoprecipitation, and Western blotting, we further found a BmATAT1 acetylated site at K156, suggesting that this acetyltransferase could be regulated by acetylation itself.


Cdk5 protein inhibition and Aβ42 increase BACE1 protein level in primary neurons by a post-transcriptional mechanism: implications of CDK5 as a therapeutic target for Alzheimer disease.
The β-secretase enzyme BACE1 initiates production of the amyloid-β (Aβ) peptide that comprises plaques in Alzheimer disease (AD) brain. BACE1 levels are increased in AD, potentially accelerating Aβ generation, but the mechanisms of BACE1 elevation are not fully understood. Cdk5/p25 has been implicated in neurodegeneration and BACE1 regulation, suggesting therapeutic Cdk5 inhibition for AD. In addition, caspase 3 has been implicated in BACE1 elevation. Here, we show that the Cdk5 level and p25:p35 ratio were elevated and correlated with BACE1 level in brains of AD patients and 5XFAD transgenic mice. Mouse primary cortical neurons treated with Aβ42 oligomers had increased BACE1 level and p25:p35 ratio. Surprisingly, the Aβ42-induced BACE1 elevation was not blocked by Cdk5 inhibitors CP68130 and roscovitine, and instead the BACE1 level was increased greater than with Aβ42 treatment alone. Moreover, Cdk5 inhibitors alone elevated BACE1 in a time- and dose-dependent manner that coincided with increased caspase 3 cleavage and decreased Cdk5 level. Caspase 3 inhibitor benzyloxycarbonyl-VAD failed to prevent the Aβ42-induced BACE1 increase. Further experiments suggested that the Aβ42-induced BACE1 elevation was the result of a post-transcriptional mechanism. We conclude that Aβ42 may increase the BACE1 level independently of either Cdk5 or caspase 3 and that Cdk5 inhibition for AD may cause BACE1 elevation, a potentially negative therapeutic outcome.


The use of a CT scan to predict the feasibility of decompression of the first segment of the facial nerve via the transattical approach.
Total surgical decompression of the facial nerve can be offered to patients severely affected by Bell's palsy whether via the transattical or middle fossa approach. We prefer, when feasible, the transattical approach because it does not violate the cranial vault. The purpose of this study was to find the anatomical parameter of the temporal bone, measured by means of computed tomography (CT scan) and to decide which of these approaches should be offered. Sixty temporal bones were studied by CT scan, and then dissected in order to perform total facial nerve decompression via the transattical approach. Correlation between the two studies was established. Results suggest that measurement by CT scan of the attical area in the axial plane (AAA) may determine those patients for whom the transattical approach to facial nerve decompression should be undertaken.


Postpartum headache after epidural anaesthesia: Who to blame?
Epidural analgesia is considered the preferred analgesic choice during labour. Post dural puncture headache (PDPH) is considered a potential complication of this analgesic technique and is a frequently hypothesis for any headache occurring after delivery. It is essential that anaesthetists and obstetricians are familiar with other possible differential diagnosis for postpartum headache (PPH). 37-year-old female presented after delivery with intense occipital pulsatile headache associated with neck radiation, nausea and vomiting, hemodynamically stable and normal neurologic physical examination. Abnormalities in thyroid hormone levels were found. CT-scan findings suggested pituitary apoplexy. There are many differential diagnoses for PPH and some are rarely considered, such as pituitary apoplexy. It is essential to differentiate signs and symptoms of each diagnosis, since many of them overlap. Not all postpartum headaches are PDPH and the first suspected diagnosis may not always be accurate.


A robust and selective method for the quantification of glycosylphosphatidylinositols in biological samples.
We have developed an assay for the quantification of glycosylphosphatidylinositol (GPI)-anchored glycoconjugates. The method is based on nitrous acid deamination and sodium borodeuteride reduction of the glucosamine residue, common to all GPI structures, to yield [1-2H]-2,5-anhydromannitol. Following acid methanolysis and trimethylsilyl derivatization, detection is by selected ion monitoring gas chromatography-mass spectrometry. The unnatural inositol isomer scyllo-inositol is used as an internal standard and the [1-2H]-2,5-anhydromannitol trimethylsilyl derivative is detected by following a characteristic electron-impact fragment ion at m/z 273. This method is more selective for GPIs than assays based on measuring myo-inositol content, which are often confounded by contaminating inositol-phospholipids. We show that the method can be applied to measure total GPI content in crude total lipid extracts and even in whole trypanosome ghosts. The method was applied to whole cell lysates of wild-type, GPI-deficient, and glycosaminoglycan-deficient CHO cells. The data revealed that proteoglycans did not interfere with total glucosamine estimates but that there are background levels of non-GPI and nonproteoglycan glucosamine-containing material in CHO cells.


Comparison and evaluation of mitotic figures in oral epithelial dysplasia using crystal violet and Feulgen stain.
Routine staining procedures often pose a problem in differentiating a mitotic cell from an apoptotic cell, deteriorating the reliability of histology grading. Although various new methods have been recommended for identifying mitotic figures (MFs) in tissues, the time factor and cost makes them less feasible. Thus, an attempt was made to evaluate the efficacy of crystal violet and Feulgen reaction in identifying MFs and also to see for any variation in the number of MFs in various grades of Epithelial dysplasia. 1. Using crystal violet and Feulgen stain in the identification and counting of MFs on diagnosed cases of epithelial dysplasia and thereby to evaluate their efficacy. 2. To evaluate the variation in the number of MFs in various grades of epithelial dysplasia. The study sample includes retrieval of 30 formalin fixed paraffin embedded tissue sections diagnosed for different grades of epithelial dysplasia (WHO grading system, 2005) from the archives, Department of Oral Pathology, MSRDC, Bengaluru. Ten tissue sections each of mild, moderate and severe epithelial dysplasia were stained with H&E, Feulgen and 1% crystal violet stains and the number of MFs were counted. Five cases of cervical carcinoma were taken as control. Stained sections were compared, and data obtained was statistically analyzed using the Kruskal-Wallis test. A significant increase in the number of MFs (p = 0.02) was observed in Feulgen stained sections as compared to H&E stain. Feulgen stain can be considered as a simple, reliable, cost-effective and reproducible method of staining MFs.


Inhalational Anesthesia for Near-fatal Pediatric Asthma Complicated by Malignant Hyperthermia.
Acute severe asthma is a commonly encountered condition in the pediatric emergency room and the pediatric intensive care unit (PICU). Its treatment involves the use of bronchodilatory agents acting on different receptors, steroids to reduce ongoing inflammation, and non-invasive or invasive mechanical ventilation to offload the increased work of breathing from the respiratory muscles. Patients refractory to these therapies may require the use of inhaled anesthetic agents and extracorporeal gas exchange (ECMO) for life-threatening asthma exacerbations. Depending on institutional protocols, the use of these therapies may vary. The use of inhaled anesthetic agents for asthma management in the PICU is infrequent and is limited to centers with specialized equipment. Commonly encountered side effects include hypotension, arrhythmias, and delirium. Malignant hyperthermia (MH) is a well-known but infrequent side effect of inhaled anesthetic use, depolarizing muscle agents, and has not been described in the PICU following the use of anesthetics for pediatric asthma.


Dinosaur bonebed amber from an original swamp forest soil.
Dinosaur bonebeds with amber content, yet scarce, offer a superior wealth and quality of data on ancient terrestrial ecosystems. However, the preserved palaeodiversity and/or taphonomic characteristics of these exceptional localities had hitherto limited their palaeobiological potential. Here, we describe the amber from the Lower Cretaceous dinosaur bonebed of Ariño (Teruel, Spain) using a multidisciplinary approach. Amber is found in both a root layer with amber strictly in situ and a litter layer mainly composed of aerial pieces unusually rich in bioinclusions, encompassing 11 insect orders, arachnids, and a few plant and vertebrate remains, including a feather. Additional palaeontological data-charophytes, palynomorphs, ostracods- are provided. Ariño arguably represents the most prolific and palaeobiologically diverse locality in which fossiliferous amber and a dinosaur bonebed have been found in association, and the only one known where the vast majority of the palaeontological assemblage suffered no or low-grade pre-burial transport. This has unlocked unprecedentedly complete and reliable palaeoecological data out of two complementary windows of preservation-the bonebed and the amber-from the same site.


Chelation therapy for metal intoxication: comments from a thermodynamic viewpoint.
Chelation therapy plays a prominent role in the clinical treatment of metal intoxication. In this paper the principal causes of metal toxicity are exposed, and the chemical and biomedical requisites of a chelating agent are sketched. The chelating agents currently in use for scavenging toxic metal ions from humans belong to few categories: those characterized by coordinating mercapto groups, by oxygen groups, poliaminocarboxylic acids, and dithiocarbamates. Considering that the complex formation equilibria have been studied for less than 50% of chelators in use, some reflections on the utility of stability constants are presented, together with an evaluation of ligands under the stability profile. The competition between endogenous and toxic target metal ions for the same chelating agent is furthermore examined. A thorough examination of stability constant databases has allowed to select, for each toxic metal, the ligands distinguished by the best pMe values. Even though this selection does not consider the biomedical requisites of a chelating agent, it gives a clear picture both of the pMe values that can be attained, and of the most appropriate chelators for each metal ion.


Photoreceptor Pigment for Blue Light in Neurospora crassa.
Irradiating the mycelium of Neurospora crassa with moderate intensities of blue light causes a reversible photoreduction of a b-type cytochrome. The action spectrum for the photoreduction of cytochrome b is very similar to the absorption spectrum of flavin pigments. Prolonged irradiation of the mycelium with strong blue light irreversibly bleaches flavin-like pigments and as these pigments are bleached the photoresponse of cytochrome b is lost. We conclude from these and other data that a flavin is the photoreceptor pigment for the photoreduction of cytochrome b. The close similarity between the action spectrum for the photoreduction of cytochrome b and action spectra for a number of physiological photoresponses suggests that this photoreceptor pigment controls a wide variety of photobiological processes in a wide diversity of organisms.


Serum Metabolomic Analysis of Radiation-Induced Lung Injury in Rats.
Radiation-induced lung injury is a common complication of radiotherapy for lung cancer, breast cancer, esophageal cancer, and thymoma. This study aims to illustrate biomarkers of radiation-induced lung injury and its potential mechanism through the study of metabolomic alterations in serum of Sprague-Dawley rats with different radiation doses. Serum from 0, 10, or 20 Gy irradiated rats were collected and subjected to gas chromatography-mass spectrometry. The result showed that there were 23 dysregulated metabolites between the 10 Gy irradiation group and the 0 Gy control group, whereas 36 preferential metabolites were found between the 20 Gy irradiated rat serum and the control groups. Among them, there were 19 common differential metabolites in the 2 irradiation groups, including 3 downregulated (benzyl thiocyanate, carbazole, and N-formyl-L-methionine) and 16 upregulated metabolites. We further analyzed the metabolic pathways of different metabolites; the results showed that there were 3 significant enrichment pathways in the 10 Gy vs 0 Gy group and 7 significant enrichment pathways in the 20 Gy vs 0 Gy group. Among them, taurine and hypotaurine metabolism, riboflavin metabolism, and glyoxylate and dicarboxylate metabolism were the common metabolic enrichment pathways of the 10 Gy vs 0 Gy group and the 20 Gy vs 0 Gy group.


Process evaluation of a cluster randomised controlled trial to improve bronchiolitis management - a PREDICT mixed-methods study.
Bronchiolitis is the most common reason for hospitalisation in infants. All international bronchiolitis guidelines recommend supportive care, yet considerable variation in practice continues with infants receiving non-evidence based therapies. We developed six targeted, theory-informed interventions; clinical leads, stakeholder meeting, train-the-trainer, education delivery, other educational materials, and audit and feedback. A cluster randomised controlled trial (cRCT) found the interventions to be effective in reducing use of five non-evidence based therapies in infants with bronchiolitis. This process evaluation paper aims to determine whether the interventions were implemented as planned (fidelity), explore end-users' perceptions of the interventions and evaluate cRCT outcome data with intervention fidelity data. A pre-specified mixed-methods process evaluation was conducted alongside the cRCT, guided by frameworks for process evaluation of cRCTs and complex interventions. Quantitative data on the fidelity, dose and reach of interventions were collected from the 13 intervention hospitals during the study and analysed using descriptive statistics. Qualitative data identifying perception and acceptability of interventions were collected from 42 intervention hospital clinical leads on study completion and analysed using thematic analysis. The cRCT found targeted, theory-informed interventions improved bronchiolitis management by 14.1%. The process evaluation data found variability in how the intervention was delivered at the cluster and individual level. Total fidelity scores ranged from 55 to 98% across intervention hospitals (mean = 78%; SD = 13%). Fidelity scores were highest for use of clinical leads (mean = 98%; SD = 7%), and lowest for use of other educational materials (mean = 65%; SD = 19%) and audit and feedback (mean = 65%; SD = 20%). Clinical leads reflected positively about the interventions, with time constraints being the greatest barrier to their use. Our targeted, theory-informed interventions were delivered with moderate fidelity, and were well received by clinical leads. Despite clinical leads experiencing challenges of time constraints, the level of fidelity had a positive effect on successfully de-implementing non-evidence-based care in infants with bronchiolitis. These findings will inform widespread rollout of our bronchiolitis interventions, and guide future practice change in acute care settings. Australian and New Zealand Clinical Trials Registry: ACTRN12616001567415 .


A Single Metabolite which Modulates Lipid Metabolism Alters Hematopoietic Stem/Progenitor Cell Behavior and Promotes Lymphoid Reconstitution.
Fatty acid β-oxidation (FAO), the breakdown of lipids, is a metabolic pathway used by various stem cells. FAO levels are generally high during quiescence and downregulated with proliferation. The endogenous metabolite malonyl-CoA modulates lipid metabolism as a reversible FAO inhibitor and as a substrate for de novo lipogenesis. Here we assessed whether malonyl-CoA can be exploited to steer the behavior of hematopoietic stem/progenitor cells (HSPCs), quiescent stem cells of clinical relevance. Treatment of mouse HSPCs in vitro with malonyl-CoA increases HSPC numbers compared with nontreated controls and ameliorates blood reconstitution capacity when transplanted in vivo, mainly through enhanced lymphoid reconstitution. Similarly, human HSPC numbers also increase upon malonyl-CoA treatment in vitro. These data corroborate that lipid metabolism can be targeted to direct cell fate and stem cell proliferation. Physiological modulation of metabolic pathways, rather than genetic or pharmacological inhibition, provides unique perspectives for stem cell manipulations in health and disease.


Hierarchical beat perception develops throughout childhood and adolescence and is enhanced in those with musical training.
Most music is temporally organized within a metrical hierarchy, having nested periodic patterns that give rise to the experience of stronger (downbeat) and weaker (upbeat) events. Musical meter presumably makes it possible to dance, sing, and play instruments in synchrony with others. It is nevertheless unclear whether or not listeners perceive multiple levels of periodicity simultaneously, and if they do, when and how they learn to do this. We tested children, adolescents, and musically trained and untrained adults with a new meter perception task. We presented excerpts of human-performed music paired with metronomes that matched or mismatched the metrical structure of the music at 2 hierarchical levels (beat and measure), and asked listeners to provide a rating of fit of metronome and music. Fit ratings suggested that adults with and without musical training were sensitive to both levels of meter simultaneously, but ratings were more strongly influenced by beat-level than by measure-level synchrony. Sensitivity to two simultaneous levels of meter was not evident in children or adolescents. Sensitivity to the beat alone was apparent in the youngest children and increased with age, whereas sensitivity to the measure alone was not present in younger children (5- to 8-year-olds). These findings suggest a prolonged period of development and refinement of hierarchical beat perception and surprisingly weak overall ability to attend to 2 beat levels at the same time across all ages. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Jung and the Nazis: some implications for psychoanalysis.
The involvement of Jung with German psychotherapy in the 1930s revealed a strong tendency to collaborate with the Nazis, even though his behaviour was more contradictory than has often been acknowledged. In part this was due to anti-Semitic sentiments; some of it was fueled by the apparent opportunity to make Jungian psychology dominant over its "Jewish" Freudian rival; and in part Jung's admiration for the energy of the Nazi movement seems to have been genuine. This paper traces some of the elements in Jung's activities of that period in order to highlight the mixture of pragmatic and ideological investments that also applied to many other psychotherapists, and to some German psychoanalysts at the time.


Morphological and chemical characterizations of the interface of a hydroxyapatite-coated implant.
The present study aimed at morphological and chemical characterization of the coating-substrate interface of a commercially available dental implant coated with plasma-sprayed hydroxyapatite (HA). For this purpose, elements in the chemically and mechanically exposed substrate surfaces were analyzed by EPMA and XPS. A thin titanium oxide film containing Ca and P was found at the interface. When the implant was subjected to mechanical stress, a mixed mode of cohesive and interfacial fractures occurred. The cohesive fracture was due to separation of the oxide film from the substrate, while the interfacial fracture was due to exfoliation of the coating from the oxide film bonded to the substrate. Analysis showed diffusion of Ca into the metal substrate, hence indicating the presence of chemical bond at the interface. However, mechanical interlocking seemed to play the major role in the interfacial bond.


Health status of newly arrived refugees in Toronto, Ont: Part 1: infectious diseases.
To determine the prevalence of selected infectious diseases among newly arrived refugee patients and whether there is variation by key demographic factors. Retrospective chart review. Primary care clinic for refugee patients in Toronto, Ont. A total of 1063 refugee patients rostered at the clinic from December 2011 to June 2014. Demographic information (age, sex, and region of birth); prevalence of HIV, hepatitis B, hepatitis C, Strongyloides, Schistosoma, intestinal parasites, gonorrhea, chlamydia, and syphilis infections; and varicella immune status. The median age of patients was 29 years and 56% were female. Refugees were born in 87 different countries. Approximately 33% of patients were from Africa, 28% were from Europe, 14% were from the Eastern Mediterranean Region, 14% were from Asia, and 8% were from the Americas (excluding 4% born in Canada or the United States). The overall rate of HIV infection was 2%. The prevalence of hepatitis B infection was 4%, with a higher rate among refugees from Asia (12%, P < .001). Hepatitis B immunity was 39%, with higher rates among Asian refugees (64%, P < .001) and children younger than 5 years (68%, P < .001). The rate of hepatitis C infection was less than 1%. Strongyloides infection was found in 3% of tested patients, with higher rates among refugees from Africa (6%, P = .003). Schistosoma infection was identified in 15% of patients from Africa. Intestinal parasites were identified in 16% of patients who submitted stool samples. Approximately 8% of patients were varicella nonimmune, with higher rates in patients from the Americas (21%, P < .001). This study highlights the importance of screening for infectious diseases among refugee patients to provide timely preventive and curative care. Our data also point to possible policy and clinical implications, such as targeted screening approaches and improved access to vaccinations and therapeutics.


Mucosal chemokines in Helicobacter pylori infection.
Chemokines are a family of low-molecular-weight proinflammatory cytokines that have leukocyte chemotactic and activating properties. Chemokine protein and mRNA are increased in the gastric mucosa of Helicobacter pylori infection and they are considered to regulate migration of leukocyte populations. The increase of C-X-C chemokines (e.g. IL-8, GRO-alpha) which effect primarily neutrophils is significantly associated with gastric polymorphonuclear cell activity suggesting that these chemokines play a primary role in active gastritis induced by H. pylori infection. In vitro enhanced epithelial chemokine responses are induced by cagA positive strains which have been clinically associated with more severe clinical outcome. Infection with cagA-positive H. pylori strains associates in vivo specifically with a C-X-C profile and enhanced polymorphonuclear infiltration in the gastric mucosa. Whilst infection with H. pylori, especially cag positive strains, is associated with more severe disease, genetic variability in host chemokine responses may also contribute to disease outcome.


Comparison of characteristics, management practices, and outcomes of patients between the global registry and the gulf registry of acute coronary events.
The Arab Middle East is a unique region of the developing world where little is known about the outcomes of patients hospitalized with an acute coronary syndrome (ACS), despite playing an important role in the global burden of cardiovascular disease. The primary objectives of this observational study were to compare patients with ACS hospitalized in the Arab Middle East to patients enrolled in a multinational non-Arabian ACS registry. The study cohort consisted of patients hospitalized in 2007 with an ACS including 4,445 from the Global Registry of Acute Coronary Events (GRACE) and 6,706 from the Gulf Registry of Acute Coronary Events (Gulf RACE). Average age of patients in Gulf RACE was nearly a decade younger than that in GRACE (56 vs 66 years). Patients in Gulf RACE were more likely to be men, diabetic, and smoke and less likely to be hypertensive compared to patients in GRACE. Patients in Gulf RACE had higher odds of receiving aspirin and a lower likelihood of receiving angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, β blockers, and clopidogrel during their index hospitalization. Although most eligible patients with ST-elevation myocardial infarction in Gulf RACE received thrombolytics, most of their counterparts in GRACE underwent a primary percutaneous coronary intervention. Multivariable adjusted in-hospital case-fatality rates were not significantly different between patients in Gulf RACE and those in GRACE. In conclusion, despite differences in patient characteristics and treatment practices, short-term mortality rates were comparable in patients with ACS enrolled in these 2 registries. Future studies should explore the effects of these differences on long-term prognosis and other pertinent patient outcomes.


[Research on Acupuncture Anesthesia-analgesia].
In the present paper, the author retrospects the historical developmental stages of acupuncture anesthesia-analgesia from 1) preliminary exploration:the creative application of acupuncture therapy to surgery with lower dosage or without anesthetics began in Shanghai and Xi'an in 1958; 2) clinical popularization:the acupuncture anesthesia-analgesia became popularized from 1965, peaked in 1970s' and declined from 1980s'; 3) mechanism study:from 1970 to 2000, a large quantity of research papers were published to confirm the validity of acupuncture analgesia (AA), and in 1997, NIH Consensus Conference for acupuncture was held, promoting the related research in the world; 4) focused research:from 2007 to now, the acupuncture anesthesia-analgesia was listed as one of the key research program in China; 5) theoretical summary:in view of the uncertainty of the scientific basis of the meridian system of traditional Chinese medicine, the nerve fibers distributed under the acupoint are now considered to be the indispensable components for AA, and the knowledge of modern neuroscience is competent to explain the underlying mechanism of AA; 6) returning to reality:AA has been accepted by the international scientific community, and the "acupuncture-assisted anesthesia", or "compound acupuncture and anesthetics anesthesia" has been used as the first choice for some types of surgical operation. The research on acupuncture anesthesia-analgesia greatly facilitates clinical application of acupuncture therapy in the world, and also promotes the development of acupuncture therapy itself and neuroscience. However, the transformation between theory and practice and their mutual interaction are endless endeavor. Thus, a careful review of the half-century-long practice of acupuncture anesthesia-analgesia is painstakingly necessary in order to clarifying the mechanisms, to raise the efficacy of clinical practice and to correct the possible errors referred to this concept.


Sudden arrhythmic death without overt heart disease.
Nine patients (eight males) are reported with one or more episodes of circulatory collapse in the absence of overt heart disease or other known causes of arrhythmias; sudden arrhythmic death occurred in one of these patients. Age at first episode ranged from 16 to 41 (mean, 28) years. In seven patients, ventricular fibrillation was documented at the time of resuscitation. One patient had ventricular flutter. In the remaining patient, documentation of the arrhythmia during the collapse was not available. Four patients had frequent early ventricular premature beats, and in three of these patients, they were accompanied by episodes of rapid nonsustained polymorphic ventricular tachycardia. Failure to suppress this ectopic activity by drug therapy seems to be of prognostic significance. Of the three patients showing persistence of frequent early ventricular premature beats, one died suddenly, and two had recurrences of symptomatic arrhythmic episodes. The value of noninvasive and invasive tests in the management of these patients is not clear, with the exception of exercise testing in patients with exercise-related arrhythmias and long-term electrocardiographic monitoring in patients with frequent spontaneous ventricular ectopic activity. Follow-up varied from 21 to 192 (mean, 84) months. One patient died suddenly 21 months after his first collapse. Selection of antiarrhythmic drug therapy was largely empirical. In view of the relative rarity of sudden arrhythmic death in the absence of heart disease and the many uncertainties about its mechanism(s) and management, a worldwide registry of these patients is suggested.