Factors associated with home delivery in rural Sindh, Pakistan: results from the global network birth registry.
According to global estimates for 2017, nearly 295,000 maternal deaths occurred worldwide. Thus, approximately 810 women die every day due to pregnancy-related complications. This burden of maternal deaths in LMICs is primarily due to poor healthcare service utilization, as indicated by relatively low rates of institutional deliveries and skilled-birth attendance (SBA). We conducted this study with an aim to assess the factors associated with home delivery and its subsequent effect on the pregnancy outcome in rural Sindh, Pakistan. Data for this study were taken from The Global Network's Maternal Newborn Health Registry (MNHR), which is a prospective, population-based observational cohort study. Registry data for 2018-2019 for District Thatta, Pakistan was retrieved for the analysis. Multivariable logistic regression models were used to determine the effect of each independent variable on the place of delivery by including all predictors and covariates. Results of the regression analyses are presented with crude odds ratios (OR) and adjusted odds ratios (aOR) with 95% confidence intervals (CIs). A total of 4649 women were included in the study, of these, 1286 (27.7%) women had delivered at home. Of those who delivered at home, a larger proportion was illiterate (90%), had a BMI of less than 18.5 kg/m2 (26.0%), had parity of 3 or more (48.1%), and had a history of pregnancy loss as compared to women who had institutional delivery. In addition, two-thirds of women (63.4%) who had delivered at home had less than 4 ANC visits, whereas 15.6% did not receive any ANC. On multivariable logistic regression we found that home delivery was significantly associated with being illiterate (aOR = 1.60; [95% CI: 1.34, 2.04]), having high parity (aOR = 1.91; [95% CI: 1.58, 2.32]), and no ANC visit (aOR = 14.8; [95% CI: 10.2, 21.5]). More than a quarter of our study sample women delivered at home. These women were illiterate, multiparous, and did not receive antenatal care during pregnancy. It is essential to conduct extensive educational interventions for the women and their family members regarding the potential benefits of delivering in a safe and skilled environment. Moreover, the provision of comprehensive and quality antenatal care should be ensured as it improves the mothers' health-seeking behavior and helps them make informed decisions about their health and well-being.


Unwrapping a full temporal cycle in time domain thermoreflectance for enhanced measurement sensitivity in thermally insulating materials.
Time delayed pump-probe measurement techniques, such as Time Domain Thermoreflectance (TDTR), have opened up a wealth of opportunities for metrology at ultra-fast timescales and nanometer length scales. For nanoscale thermal transport measurements, typical thermal lifetimes used to measure thermal conductivity and thermal boundary conductance span from sub-picosecond to ∼6 nanoseconds. In this work, we demonstrate a simple rearrangement and validation of a configuration that allows access to the entire 12.5 ns time delay available in the standard pulse train. By reconfiguring a traditional TDTR system so that the pump and probe arrive concurrently when the delay stage reaches its midpoint, followed by unwrapping the temporal scan, we obtain a dataset that is bounded only by the oscillator repetition rate. Sensitivity analysis along with conducted measurements shows that great increases in measurement sensitivity are available with this approach, particularly for thin films with low thermal conductivities.


Study of the Mechanical Behavior of Organic Matters Contained in Source Rocks: New Insights into the Role of Bitumen.
Assessment of mechanical properties of organic matters contained in unconventional formations is needed to understand the geomechanics of source rocks. The organic matters are part of the source rock matrix, and they are made of kerogen and bitumen. Although the literature has some studies addressing the properties of kerogen and bitumen, no apparent attempts were made to address the mechanical behavior of organic matters as a combination of both. Isolation of organic matters from the rocks for experimental assessments has some risks of altering the original properties because of their delicate nature and their existence as micro- and nanoconstituents. Some computational approaches such as molecular simulation can serve as an alternative platform for the purpose of delineating organic matter properties including the mechanical ones. This work implements available 3D molecular modeling of kerogen and bitumen with different ratios to mimic organic matters that can be investigated for the mechanical properties. Upon the recreation of different configurations of organic matters molecularly, mechanical parameters such Young's, bulk, and shear constants, as well as the stress-strain relationship for the elastic and plastic deformations were extracted. The mechanical behavior was closely monitored before and after saturation with a number of gases that are commonly found in subsurface formations such as methane, carbon dioxide, and nitrogen. The results revealed that the organic matters had a mechanical behavior envelope similar to what were reported for organic-based materials such as polymers. Moreover, the structures containing bitumen exhibited larger values of Poisson's ratio, indicating less likelihood of them to degrade upon applied stresses. The presented data substantiate the importance of accounting for both bitumen and kerogen in modeling the petrophysics and the mechanical behavior of the organic matters.


Operating modes of a charge-transfer-plate liquid-crystal phase modulator.
New results for an electron-beam-addressed liquid-crystal phase modulator are presented. Local, as well as global, control of liquid-crystal molecular reorientation is demonstrated, and the results of five different operating modes are discussed. Linear phase modulation with depths up to 30pi are demonstrated with this device, as are two-dimensional arrays of computer-generated spherical lenses with actively variable focal lengths. The spherical lenses were written without the use of specialized transfer functions to compensate for device nonlinearities. Applications are discussed in the context of adaptive optics in spaceborne systems.


Systemic Amyloidosis Caused by Monoclonal Immunoglobulins: Soft Tissue and Vascular Involvement.
Clinical features of soft tissue amyloid light-chain (AL) amyloidosis include macroglossia, arthropathy, muscle pseudohypertrophy, skin plaques, and carpal tunnel syndrome. Vascular manifestations of AL amyloid include periorbital ecchymosis, jaw or limb claudication, and even myocardial infarction caused by occlusion of small vessel coronary arteries. Some of these features, such as macroglossia, periorbital ecchymosis, and the so-called shoulder-pad sign, are pathognomonic for AL amyloidosis. These findings may be the initial presenting features of the disease, and the recognition of these red flag symptoms is very important for the diagnosis and early intervention on the underlying plasma cell disease.


Analysis of Eating Habits and Body Composition of Young Adult Poles.
Obesity and overweight affect a large proportion of the world's population. Increasingly, this problem can be observed among young adults. The aim of the study was to identify the motivations and barriers to healthy eating habits among young Poles, the relationship between physical activity and healthy eating and the impact of healthy eating on the body composition of the young. The method used in the research was a diagnostic survey using direct personal interviews. The research was conducted in the years 2016-2019 on a group of 399 young Poles aged 18-26. Their body composition was analyzed by determining resistance and reactance using the biological impedance method, with a TANITA SC-330ST Body Composition Analyzer. The main reasons for healthy eating among young Poles are the intent to follow a doctor's recommendations, to lose weight and to live a healthy lifestyle and to follow a trend. On the other hand, the largest barriers to proper nutrition are: lack of time to prepare healthy meals and of financial resources, inability to prepare meals and limited knowledge of the principles of healthy eating. The eating behavior varied significantly in relation to the physical activity of the respondents. Active people's eating habits were the best, and those of sedentary people the worst. Healthy eaters also had normal body composition indicators (adipose tissue level, BMI, body type). Young adults should be educated on the principles of healthy eating and have access to healthy food in canteens and vending machines, both at work and at university.


Identification of novel genes and pathways regulating SREBP transcriptional activity.
Lipid metabolism in mammals is orchestrated by a family of transcription factors called sterol regulatory element-binding proteins (SREBPs) that control the expression of genes required for the uptake and synthesis of cholesterol, fatty acids, and triglycerides. SREBPs are thus essential for insulin-induced lipogenesis and for cellular membrane homeostasis and biogenesis. Although multiple players have been identified that control the expression and activation of SREBPs, gaps remain in our understanding of how SREBPs are coordinated with other physiological pathways. To identify novel regulators of SREBPs, we performed a genome-wide cDNA over-expression screen to identify proteins that might modulate the transcription of a luciferase gene driven from an SREBP-specific promoter. The results were verified through secondary biological assays and expression data were analyzed by a novel application of the Gene Set Enrichment Analysis (GSEA) method. We screened 10,000 different cDNAs and identified a number of genes and pathways that have previously not been implicated in SREBP control and cellular cholesterol homeostasis. These findings further our understanding of lipid biology and should lead to new insights into lipid associated disorders.


Benefits of social media for nurses and service users.
People with mental health problems are increasingly using social media channels as part of their recovery and to improve their lives. This article discusses social media and how it can be used to complement healthcare, offers useful tips on using social media, and explores case studies for nurses to use in clinical practice.


Assessment of Transport Mechanisms Underlying the Bicoid Morphogen Gradient.
Morphogen gradients dictate the spatial patterning of multicellular organisms and are established via transport mechanisms. One of the best-characterized morphogens, Bicoid, acts as a polarity determinant in the Drosophila embryo through spatial-temporal control of gap gene expression. The prevailing model for establishment of the gradient has been localized anterior translation, subsequent diffusion, and spatially uniform degradation, consistent with the observed exponential anterior-posterior decay. However, a recent direct measurement of the Bicoid diffusion coefficient via fluorescence recovery after photobleaching (FRAP) resulted in a surprisingly low estimate, which challenged the prevailing model and led to more complicated active transport models. Here, we reassessed this conclusion using a detailed computational model of the FRAP experiment and analysis. In our model, we found disagreement between the input diffusion coefficient and the resulting estimated diffusion coefficient, as measured by previous methods. By using the model to reproduce the original data, we estimate that Bicoid's mitotic diffusion coefficient is 3-fold larger than the originally reported value. Thus, the long-standing diffusive transport model still holds.


Medicare program; monthly actuarial rates, supplementary medical insurance premium rate, and catastrophic coverage premium beginning January 1, 1990--HCFA. Notice.
This notice announces the monthly actuarial rates for aged (age 65 or over) and disabled (under age 65) enrollees in the Medicare supplementary medical insurance (SMI) program for calendar year 1990, and the monthly SMI premium rate based on these actuarial rates to be paid by all enrollees during calendar year 1990. The 1990 monthly SMI premium will be increased from $27.90 to $29.00. This notice also announces the catastrophic coverage monthly premium for 1990 imposed by the Medicare Catastrophic Coverage Act of 1988 (Pub. L. 100-360).


The prevalence of antimicrobial resistance in human faecal flora in South Africa.
Between January and March 1992, 361 faecal specimens were collected from the healthy black population in the Transvaal Province of South Africa. Each specimen was examined for the prevalence of antimicrobial resistance in commensal bacteria. Volunteers, from both rural and urban dwellings, were divided into four age groups. The overall carriage rate of resistance varied from 88.6% for ampicillin, 74.2% for trimethoprim, 52.6% for chloramphenicol, 10.2% for nalidixic acid to 7.5% for gentamicin. The carriage of resistance found to each individual antimicrobial agent was slightly higher in the rural population rather than the urban population but there was no correlation between the prevalence of antimicrobial resistance and the age group.


Long-term outcomes of early surgery for asymptomatic severe chronic mitral regurgitation.
The long-term outcomes of early surgery in patients with asymptomatic severe chronic mitral regurgitation (MR) and the impact of preoperative left ventricular dysfunction, atrial fibrillation (AF) and/or pulmonary hypertension (PH) on outcomes in this patient group, were evaluated. Between 1992 and 2007, a total of 212 patients (mean age 50 +/- 15 years) with asymptomatic severe chronic degenerative MR underwent early mitral valve surgery within 12 months after echocardiographic diagnosis at the authors' institution. Mitral valve repair was attempted in all cases. The mean follow up period was 82 +/- 36 months. The patients were allocated to two groups; 111 with preoperative left ventricular dysfunction, AF and/or PH (group A), and 101 patients without those findings (group B). The outcomes were compared using univariate and multivariate analyses. Mitral valve repair was performed successfully in 211 patients (99.5%). The operative mortality was 0.5% (1/212). The 10-year actuarial survivals were 97.3% in all patients, 95.1% in group A, and 100% in group B. The 10-year cardiac adverse event-free rates (cardiac death, mitral valve reoperation or readmission with congestive heart failure) were 94.7% in all patients, 92.7% in group A, and 96.2% in group B. The seven-year freedom rates from recurrent MR were 93.1% in all patients, 90.0% in group A, and 97.0% in group B. In comparative analyses, group A had poorer late outcomes than group B, although the differences were not statistically significant. The multivariate analysis failed to show that preoperative left ventricular dysfunction, AF and/or PH were significantly associated with late cardiac adverse event (HR: 2.1, 95% CI: 0.4 to 10.8; p = 0.392). Early surgery for asymptomatic chronic MR demonstrated excellent early and late outcomes. The study results failed to confirm that preoperative left ventricular dysfunction, AF and/or PH were significantly associated with adverse outcomes of early mitral valve surgery in this patient group.


Neuronal and axonal degeneration in experimental spinal cord injury: in vivo proton magnetic resonance spectroscopy and histology.
Longitudinal in vivo proton magnetic resonance spectroscopy (1H-MRS) and immunohistochemistry were performed to investigate the tissue degeneration in traumatically injured rat spinal cord rostral and caudal to the lesion epicenter. On 1H-MRS significant decreases in N-acetyl aspartate (NAA) and total creatine (Cr) levels in the rostral, epicenter, and caudal segments were observed by 14 days, and levels remained depressed up to 56 days post-injury (PI). In contrast, the total choline (Cho) levels increased significantly in all three segments by 14 days PI, but recovered in the epicenter and caudal, but not the rostral region, at 56 days PI. Immunohistochemistry demonstrated neuronal cell death in the gray matter, and reactive astrocytes and axonal degeneration in the dorsal, lateral, and ventral white-matter columns. These results suggest delayed tissue degeneration in regions both rostrally and caudally from the epicenter in the injured spinal cord tissue. A rostral-caudal asymmetry in tissue recovery was seen both on MRI-observed hyperintense lesion volume and the Cho, but not NAA and Cr, levels at 56 days PI. These studies suggest that dynamic metabolic changes take place in regions away from the epicenter in injured spinal cord.


Prevalence of HIV infection among patients with leprosy in African countries and Yemen.
Screening for human immunodeficiency viruses types 1 and 2 (HIV-1 and HIV-2) antibodies was carried out in the serum of 1,245 leprous patients and 5,731 controls selected in nine different centers from the Congo, Ivory Coast, Senegal, and Yemen Arab Republic. In Yemen, all sera were negative. In the Congo, the seropositivity among patients and controls was, respectively, 3.8 and 5.2%; in Senegal, it was 1.3 and 0.6%; and in the Ivory Coast 4.8 and 3.9%. Differences were not statistically significant, even considering lepromatous or tuberculoid forms (3.6% and 3.7%, respectively). HIV-2 antibodies were only detected in subjects from the Ivory Coast and Senegal. Using appropriate criteria for seropositivity (confirmation by Western blot, reactivity to HIV envelope glycoproteins) and a large selection of patients (several countries with several centers), it appears that leprosy (and specially the lepromatous form) is not a factor for HIV infection.


Rhodopsin kinase: expression in baculovirus-infected insect cells, and characterization of post-translational modifications.
Structure-function studies of rhodopsin kinase (RK; EC 184.108.40.206) require a variety of mutants. Therefore, there is need for a suitable system for the expression of RK mutant genes. Here we report on a study of expression of the RK gene in baculovirus-infected Sf21 cells and characterization of the enzyme produced as purified to near homogeneity. Particular attention has been paid to the post-translational modifications, autophosphorylation and isoprenylation, found in the native bovine RK. The protein produced has been purified using, successively, heparin-Sepharose, Mono Q, and Mono S FPLC (fast protein liquid chromatography) and was obtained in amounts of about 2 mg from 1 liter of cell culture. The enzyme from the last step of purification was obtained in two main fractions that differ in the level of phosphorylation. The protein peak eluted first carries two phosphate groups per protein, whereas the second protein peak is monophosphorylated. Further, while both peaks are isoprenylated, the isoprenyl groups consist of mixtures of C5, C10, C15, and C20 isoprenyl moieties. From these results, we conclude that the above expression system is suitable for some but not all aspects of structure-function studies.


Second hand smoke exposure in public venues and mental disorder: a representative nationwide study of China.
Many studies have clearly linked exposure to Second Hand Smoke (SHS) to various somatic diseases, however, few studies have examined the relationship between SHS and mental disorders and those that have were only conducted with specific groups. The purpose of this study was to examine the association between SHS exposure and mental disorders among Chinese residents in both worksites and public places. A cross-sectional multistage sampling design was used to interview subjects from 21 selected cities in China. Using a standardized questionnaire including demographic characteristics, SHS exposure, and mental health information was collected. Multiple logistic regression analysis was used to assess the association between SHS exposure and mental disorders. Sixteen-thousand-eight-hundred-sixty-six valid questionnaires were collected and utilized in this study. Of 11,206 non-smokers, SHS exposure prevalence in workplaces and public places were respectively 78.4 % (95 % C.I.:74.3-82.5 %) and 80.7 % (95 % C.I.:74.6-86.5 %). Multiple logistic regressions showed SHS exposures in these venues were positively related to mental disorder. These findings further support the health hazards of SHS exposure. Findings underscore the importance of controlling SHS exposure, and can be used to inform future SHS control policies and reinforce the need for public education in China.


Association between WWOX/MAF variants and dementia-related neuropathologic endophenotypes.
The genetic locus containing the WWOX and MAF genes was implicated as a clinical Alzheimer's disease (AD) risk locus in two recent large meta-analytic genome wide association studies (GWAS). In a prior GWAS, we identified a variant in WWOX as a suggestive risk allele for hippocampal sclerosis. We hypothesized that the WWOX/MAF locus may be preferentially associated with non-plaque- and non-tau-related neuropathological changes (NC). Data from research participants with GWAS and autopsy measures from the National Alzheimer's Coordinating Center and the Religious Orders Study and the Rush Memory and Aging Project were meta-analyzed. Notably, no variants in the locus were significantly associated with ADNC. However, several WWOX/MAF variants had significant adjusted associations with limbic-predominant age-related TDP-43 encephalopathy NC (LATE-NC), HS, and brain arteriolosclerosis. These associations remained largely unchanged after adjustment for ADNC (operationalized with standard semiquantitative staging), suggesting that these associations are independent of ADNC. Thus, WWOX genetic variants were associated pathologically with LATE-NC, not ADNC.


New troglomorphic species of Tomocerus with well-developed postantennal organs (Collembola: Tomoceridae).
Three new troglobitic species of Tomocerus are described from the southwestern karsts of China. All of them have well developed postantennal organs. Tomocerus dong sp. nov. is similar to Tomocerus postantennalis Yu, Zhang & Deharveng and Tomocerus deharvengi sp. nov., but is different from them mainly in the number of prelabral chaetae and the dorsal body chaetotaxy. T. deharvengi sp. nov. is very similar to T. postantennalis but differs from the latter in the cephalic chaetotaxy, the number of manubrial pseudopores and the number of dental spines. T. cthulhu sp. nov. is peculiar for the multi-furcated vesicles of ventral tube, and is different from the three aforementioned species mainly in the dorsal body chaetotaxy. The position of the new species and the relationships between them are discussed.


Home use of two doses of misoprostol after mifepristone for medical abortion: a pilot study in Sweden and France.
To test the feasibility, safety, and efficacy of home use of two doses of misoprostol for medical abortion (MA) in European settings. One hundred thirty women (100 in Sweden, 30 in France) presenting for first-trimester MA were administered oral mifepristone in the clinic and sent home with two 400 microg doses of misoprostol, along with instructions to take the misoprostol at 24 h intervals. Women were also asked to complete a daily symptom diary. Outcomes of interest included effectiveness, side-effects, and adherence to and acceptability of the home-use regimen. Three women (all in France) were lost to follow-up. Of the remaining 127 women, 124 (98%) had a successful MA. All women adhered successfully to the home-use regimen, and satisfaction with home use was high (98%). Most women experienced noticeable, if transitory, side effects after both the first and second doses of misoprostol (97% and 94%, respectively). Misoprostol may successfully and satisfactorily be used at home as part of a MA regimen in European settings as it has been for years in the US. Further research to determine if two doses of misoprostol are more effective than a single dose would be useful.


Variation in the use of red blood cell transfusions. A study of four common medical and surgical conditions.
This study assessed variation in red cell transfusion practice among adult patients hospitalized with ulcer disease (ULCER), and those undergoing coronary artery bypass grafting (CABG), hip surgery (HIP), or total knee replacement (KNEE). The study design was a retrospective analysis of the 1989 MedisGroups Hospital Comparative Database, and the participants were adult patients presenting for their first admission with ULCER (N = 4,664), CABG (N = 6,812), HIP (N = 4,131) or KNEE (N = 3,042) in the MedisGroups Hospital Comparative Database. Outcome measures were whether a patient was transfused, and the number of units transfused. Logistic regression was used to analyze the decision to transfuse, and linear regression to analyze the number of units transfused. In these analyses, patient characteristics, hospital characteristics, and unique hospital identity were used as independent variables. The percentage of patients transfused was ULCER 50%, CABG 81%, HIP 69%, and KNEE 51%. The range among hospitals in the percentage of patients transfused was ULCER 11% to 76%, CABG 51% to 100%, HIP 36% to 95%, and KNEE 9% to 97%. When only patient characteristics were entered in the linear regression analyses, the R2 values were ULCER 0.33, CABG 0.11, HIP 0.11, and KNEE 0.07. When hospital was added, the R2 increased to ULCER 0.38, CABG 0.29, HIP 0.19, and KNEE 0.20 (P < 0.0001 for the change for all analyses). The results of the logistic regression analyses of the probability of transfusion were similar. There is substantial interhospital variation in the proportion of patients transfused and number of units transfused in the four conditions studied. Patient demographic and clinical characteristics explain a substantial proportion of the variation in transfusion practices for ulcer patients, but little of the variation in the three surgical conditions.


Cholecystokinin excites interneurons in rat basolateral amygdala.
The amygdala formation is implicated in generation of emotional states such as anxiety and fear. Many substances that modulate neuronal activity in the amygdala alter anxiety. Cholecystokinin (CCK) is an endogenous neuropeptide that induces anxiety states in behavioral studies in both animals and humans. Using a brain slice preparation, we found that application of CCK increases inhibitory synaptic transmission measured in projection neurons of the basolateral amygdala. To determine the source of the increased inhibition we examined the direct effect of CCK on local interneurons in this region. CCK most strongly depolarized fast-spiking interneurons. Burst-firing and regular-firing interneurons were also depolarized, although to a lesser degree. However, another distinct group of interneurons was unaffected by CCK. These effects were mediated by the CCKB receptor subtype. The excitatory effect of CCK appeared to be mediated by both a nonselective cation and a K+ current.


Application of a biologically-based RFD estimation method to tetrachlorodibenzo-p-dioxin (TCDD) mediated immune suppression and enzyme induction.
The current methods for a reference dose (RfD) determination can be enhanced through the use of biologically-based dose response analysis. Methods developed here utilizes information from tetrachlorodibenzo-p-dioxin (TCDD) to focus on noncancer endpoints, specifically TCDD mediated immune system alterations and enzyme induction. Dose-response analysis, using the Sigmoid-Emax (EMAX) function, is applied to multiple studies to determine consistency of response. Through the use of multiple studies and statistical comparison of parameter estimates, it was demonstrated that the slope estimates across studies were very consistent. This adds confidence to the subsequent effect dose estimates. This study also compares traditional methods of risk assessment such as the NOAEL/safety factor to a modified benchmark dose approach which is introduced here. Confidence in the estimation of an effect dose (ED10) was improved through the use of multiple datasets. This is key to adding confidence to the benchmark dose estimates. In addition, the Sigmoid-Emax function when applied to dose-response data using nonlinear regression analysis provides a significantly improved fit to data increasing confidence in parameter estimates which subsequently improve effect dose estimates.


Telomere erosion-induced mitotic catastrophe in continuously grown chinese hamster don cells.
We have previously reported that telomere erosion is the earliest chromatin modification in cells entering the apoptotic pathway. The purpose of this investigation was to determine whether loss of telomeric DNA was involved in inducing mitotic catastrophe and death in Chinese hamster Don cells. Don, a male Chinese hamster-derived cell line which requires daily subculturing to remain diploid, was grown without subculturing for 1-4 days at 37 degrees C and analyzed cytologically. Our results indicated that (1) the frequency of metaphase chromosomes with structural anomalies was significantly higher in 3-day continuously grown cells than in 1-day control cells (8.2% vs 5.7%; P < 0.01), (2) the mitotic index was considerably lower in 3-day continuously grown cells (0.13%) than in control cells (3.64%), (3) cells grown for 3 days continuously showed a higher incidence (7.6%) of endoreduplicated metaphase chromosomes than did control cells (4.9%), (4) 4-day continuously grown Don cells showed significantly smaller amounts of telomeric DNA in interphase nuclei than did control cells, and (5) apoptotic cells were more frequent in 4-day cell cultures (40.6%) than in control cells (4.3%). These results support our earlier observations and contribute additional support for our hypothesis that telomere reduction is the cause of mitotic catastrophe and that cell death in continuously grown Don cells occurs because of the loss of telomeric DNA.


Preparation and characterization of electrospun PLGA/gelatin nanofibers as a drug delivery system by emulsion electrospinning.
Novel biocompatible poly(lactide-co-glycolide) (PLGA) nanofiber mats with favorable biocompatibility and good mechanical strength were prepared, which could serve as an innovative type of tissue engineering scaffold or an ideal controllable drug delivery system. Both hydrophobic and hydrophilic drugs, Cefradine and 5-fluorouracil were successfully loaded into PLGA nanofiber mats by emulsion electrospinning. The natural bioactive protein gelatin (GE) was incorporated into the nanofiber mats to improve the surface properties of the materials for cell adhesion. Nanofibrous scaffolds were characterized by scanning electron microscopy, X-ray diffraction, differential scanning calorimetry, contact angle and tensile measurements. Emulsion electrospun fibers with GE had perfect hydrophilic and good mechanical property. The in vitro release test showed thedrugs released from emulsion electrospun fibers, which achieved lower burst release. The cells cytotoxicity experiment indicated that emulsion electrospun fibers were less toxic and tended to promote fibroblasts cells attachment and proliferation, which implied that the electrospun fibers had promising potential application in tissue engineering or drug delivery.


Distinction in genetic determinants for injury-induced neointimal hyperplasia and diet-induced atherosclerosis in inbred mice.
Five inbred strains of mice differing in susceptibility to diet-induced atherosclerosis were compared for neointimal hyperplasia after endothelial denudation with an epoxy resin-modified catheter probe. Results showed that all animals responded similarly to the arterial injury, with increased medial area and thickness after 14 days. In contrast, a significant strain-specific difference in neointimal formation after injury was observed. The atherosclerosis-susceptible C57L/J mice were also susceptible to injury-induced neointimal hyperplasia, and the C3H mice were resistant to both forms of vascular diseases. The 129/Sv mice, which displayed an intermediate level of diet-induced atherosclerosis, also displayed an intermediate level of injury-induced neointimal hyperplasia. Interestingly, the atherosclerosis-susceptible C57BL/6 mice were resistant to neointimal hyperplasia after endothelial denudation, whereas the atherosclerosis-resistant FVB/N mice were susceptible, displaying massive neointimal hyperplasia after arterial injury. All (C57L/JxC57BL/6)F1 hybrid mice were resistant to injury-induced neointimal hyperplasia. Moreover, N2 mice generated from backcrossing the F1 hybrid mice to the susceptible C57L/J mice displayed a range of arterial response to injury, spanning the most severe to the most resistant phenotype. These results indicate that injury-induced neointimal hyperplasia and diet-induced atherosclerosis are controlled by distinct sets of genes; the former appeared to be determined by recessive genes at > or =2 loci.


Heterosis Derived From Nonadditive Effects of the BnFLC Homologs Coordinates Early Flowering and High Yield in Rapeseed (Brassica napus L.).
Early flowering facilitates crops to adapt multiple cropping systems or growing regions with a short frost-free season; however, it usually brings an obvious yield loss. In this study, we identified that the three genes, namely, BnFLC.A2, BnFLC.C2, and BnFLC.A3b, are the major determinants for the flowering time (FT) variation of two elite rapeseed (Brassica napus L.) accessions, i.e., 616A and R11. The early-flowering alleles (i.e., Bnflc.a2 and Bnflc.c2) and late-flowering allele (i.e., BnFLC.A3b) from R11 were introgressed into the recipient parent 616A through a breeding strategy of marker-assisted backcross, giving rise to eight homozygous near-isogenic lines (NILs) associated with these three loci and 19 NIL hybrids produced by the mutual crossing of these NILs. Phenotypic investigations showed that NILs displayed significant variations in both FT and plant yield (PY). Notably, genetic analysis indicated that BnFLC.A2, BnFLC.C2, and BnFLC.A3b have additive effects of 1.446, 1.365, and 1.361 g on PY, respectively, while their dominant effects reached 3.504, 2.991, and 3.284 g, respectively, indicating that the yield loss caused by early flowering can be successfully compensated by exploring the heterosis of FT genes in the hybrid NILs. Moreover, we further validated that the heterosis of FT genes in PY was also effective in non-NIL hybrids. The results demonstrate that the exploration of the potential heterosis underlying the FT genes can coordinate early flowering (maturation) and high yield in rapeseed (B. napus L.), providing an effective strategy for early flowering breeding in crops.


Upscaling between an agent-based model (smoothed particle approach) and a continuum-based model for skin contractions.
Skin contraction is an important biophysical process that takes place during and after recovery of deep tissue injury. This process is mainly caused by fibroblasts (skin cells) and myofibroblasts (differentiated fibroblasts which exert larger pulling forces and produce larger amounts of collagen) that both exert pulling forces on the surrounding extracellular matrix (ECM). Modelling is done in multiple scales: agent-based modelling on the microscale and continuum-based modelling on the macroscale. In this manuscript we present some results from our study of the connection between these scales. For the one-dimensional case, we managed to rigorously establish the link between the two modelling approaches for both closed-form solutions and finite-element approximations. For the multi-dimensional case, we computationally evidence the connection between the agent-based and continuum-based modelling approaches.


Microbiota of periapical lesions refractory to endodontic therapy.
The periapical microbiota of 36 teeth with refractory apical periodontitis was investigated. None of the teeth had responded to conventional endodontic or long-term (> 6 months), calcium-hydroxide treatment. Eight patients had received antibiotics systemically. After anaerobic culture, a total of 148 microbial strains were detected among 67 microbial species. One of the 36 lesions was culture-negative. Approximately half (51.0%) of the bacterial strains were anaerobic. Gram-positive species constituted 79.5% of the flora. Facultative organisms, such as Staphylococcus, Enterococcus, Enterobacter, Pseudomonas, Stenotrophomonas, Sphingomonas, Bacillus, or Candida species were recovered from 27 of the lesions (75%). Sulfur granules were found in 9 lesions (25%). In these granules Actinomyces israelii, A. viscosus, A. naeslundii, and A. meyeri were identified. Other bacterial species, both gram-positive and gram-negative, were detected in the granules as well. Two sulfur granules did not contain Actinomyces. Scanning electron microscopy demonstrated rod- and spirochete-like cells in the granules, and transmission electron microscopy revealed organisms with copious amounts of extracellular material. Outer membrane vesicles were also seen. Some of the granules were calcified. This study demonstrated a wide variety of microorganisms, particularly gram-positive ones, in the periapical lesions of teeth with refractory apical periodontitis.


Conversion of Alcohols to Phosphorothiolates Using a Thioiminium Salt as Coupling Agent.
We report a method for the direct and rapid conversion of primary and secondary alcohols to the corresponding phosphorothiolates in yields ranging from 64% to 97%, using as a coupling agent the iminium salt prepared from N,N-dimethylthioformamide and Meerwein's salt. Selective reaction of primary alcohols in the presence of secondary alcohols is possible. The reaction of secondary alcohols proceeds stereospecifically with inversion of configuration.


Nonhomologous recombination in the human genome: deletions in the human factor VIII gene.
Four deletions in the human factor VIII gene have been characterized at the sequence level in patients with hemophilia A. Deletion JH 1 extends 57 kb from IVS 10 to IVS 18. Intron 13 and exon 14 are partially deleted in patients JH 7 and JH 37, with a loss of 3.2 and 2.4 kb of DNA, respectively. The 3' deletion breakpoint of the JH 21 event resides in intron 3 and extends 5' into intron 1, resulting in the loss of exons 2 and 3. Seven of the eight breakpoints sequenced (5' and 3' for each of the four deletions) occur in nonrepetitive sequence, while the 3' breakpoint of the JH 1 resides in an Alu repetitive element. All of the deletions are the result of nonhomologous recombination. The 5' and 3' breakpoints of JH 1, JH 7, and JH 37 share 2- to 3-bp homologies at the deletion junctions. In contrast, two nucleotides have been inserted at the JH 21 deletion junction. Short sequence homologies may facilitate end-joining reactions in nonhomologous recombination events.


Exercise training alters the balance between vasoactive compounds in skeletal muscle of individuals with essential hypertension.
The effects of physical training on the formation of vasodilating and vasoconstricting compounds, as well as on related proteins important for vascular function, were examined in skeletal muscle of individuals with essential hypertension (n=10). Muscle microdialysis samples were obtained from subjects with hypertension before and after 16 weeks of physical training. Muscle dialysates were analyzed for thromboxane A(2), prostacyclin, nucleotides, and nitrite/nitrate. Protein levels of thromboxane synthase, prostacyclin synthase, cyclooxygenase 1 and 2, endothelial nitric oxide synthase (eNOS), cystathionine-γ-lyase, cytochrome P450 4A and 2C9, and the purinergic receptors P2X1 and P2Y2 were determined in skeletal muscle. The protein levels were compared with those of normotensive control subjects (n=12). Resting muscle dialysate thromboxane A(2) and prostacyclin concentrations were lower (P<0.05) after training compared with before training. Before training, dialysate thromboxane A(2) decreased with acute exercise, whereas after training, no changes were found. Before training, dialysate prostacyclin levels did not increase with acute exercise, whereas after training there was an 82% (P<0.05) increase from rest to exercise. The exercise-induced increase in ATP and ADP was markedly reduced after training (P<0.05). The amount of eNOS protein in the hypertensive subjects was 40% lower (P<0.05) than in the normotensive control subjects, whereas cystathionine-γ-lyase levels were 25% higher (P<0.05), potentially compensating for the lower eNOS level. We conclude that exercise training alters the balance between vasodilating and vasoconstricting compounds as evidenced by a decrease in the level of thromboxane, reduction in the exercise-induced increase in ATP and a greater exercise-induced increase in prostacyclin.


Combining Protein and Metabolic Engineering Strategies for High-Level Production of O-Acetylhomoserine in Escherichia coli.
O-acetylhomoserine (OAH) is a promising platform chemical for the production of l-methionine and other valuable compounds. However, the relative low titer and yield of OAH greatly limit its industrial production and cost-effective application. In this study, we successfully constructed an efficient OAH-producing strain with high titer and yield by combining protein and metabolic engineering strategies in E. coli. Initially, an OAH-producing strain was created by reconstruction of biosynthetic pathway and deletion of degradation and competitive pathways, which accumulated 1.68 g/L of OAH. Subsequently, several metabolic engineering strategies were implemented to improve the production of OAH. The pathway flux of OAH was enhanced by eliminating byproduct accumulation, increasing oxaloacetate supply and promoting the biosynthesis of precursor homoserine, resulting in a 1.79-fold increase in OAH production. Moreover, protein engineering was applied to improve the properties of the rate-limiting enzyme homoserine acetyltransferase (MetXlm) based on evolutionary conservation analysis and structure-guided engineering. The resulting triple F147L-M182I-M240A mutant of MetXlm exhibited a 12.15-fold increase in specific activity, and the optimized expression of the MetXlm mutant led to a 57.14% improvement in OAH production. Furthermore, the precursor acetyl-CoA supply and NADPH generation were also enhanced to facilitate the biosynthesis of OAH by promoting CoA biosynthesis, overexpressing heterogeneous acetyl-CoA synthetase (ACS), and introducing NADP-dependent pyruvate dehydrogenase (PDH). Finally, the engineered strain OAH-7 produced 62.7 g/L of OAH with yield and productivity values of 0.45 g/g glucose and 1.08 g/L/h, respectively, in a 7.5 L fed-batch fermenter, which was the highest OAH production ever reported.


Early abdominal complications following heart and heart-lung transplantation.
In the first 11 years of the heart and heart-lung transplantation programme at Papworth Hospital, Cambridge, 356 patients underwent heart transplantation, and 73 patients received both heart and lungs. Out of 429 patients 41 (9.5 per cent) developed abdominal complications within the first 30 days, and 20 of the 41 required surgery. The complications included pancreatitis (10), peptic ulceration (8), and pseudo-obstruction (8), in addition to colonic perforation and small bowel obstruction. When laparotomy was performed it was well tolerated. This paper supports the view that successful management of abdominal complications following transplantation requires prompt diagnosis and treatment. Where doubt exists in the presence of an acute abdomen, laparotomy is the appropriate way to establish a definitive diagnosis.


CASE-REPORT Case study of a patient presenting both type II bipolar affective disorder and Klinefelter syndrome.
Klinefelter syndrome (KS) is the most common sex chromosomal disorder with an estimated prevalence of 1 in 500-1000. Increased incidences of anxiety, depression, substance abuse, psychotic and behavioral disorders, and sexual disorders have been reported in patients with KS. The aim of this case study was to report a case of a man with untreated KS who was also diagnosed with type II bipolar disorder. This case report raises awareness regarding psychiatric diagnoses that may be associated with such a highly prevalent condition. A 46-year-old man who had previously been diagnosed with an untreated KS was examined in our Psychiatric Department with an acute hypomanic episode. Clinical improvement was observed within 4 days and psychiatric symptoms were resolved in 7 days without use of medication. A psychiatric history of a depressive episode and at least two hypomanic episodes, as well as a family history of two relatives diagnosed with bipolar disorder, strongly suggest that our patient has type II bipolar disorder. Bipolar disorder may be a comorbid disorder in patients with KS. Routine screening for mood disorders and appropriate referral and evaluation should be performed. Future genetic research is warranted to explore why some chromosomal abnormalities (e.g., duplications), especially those located on the X chromosome, such as Klinefelter syndrome, may be associated with a bipolar or psychotic disorder in some individuals but not in others.


Neochrysosporazines: Precursor-Directed Biosynthesis Defines a Marine-Derived Fungal Natural Product P-Glycoprotein Inhibitory Pharmacophore.
Upregulation of ATP binding cassette (ABC) transporter efflux pumps (i.e. P-glycoprotein, P-gp) can impart multidrug resistance, rendering many chemotherapeutics ineffective and seriously limiting treatment regimes. While ABC transporters remain an attractive target for therapeutic intervention, the development of clinically useful small-molecule inhibitors has proved challenging. In this report, we describe the structure-activity relationship (SAR) analysis of a newly discovered P-gp inhibitory pharmacophore, phenylpropanoid piperazine chrysosporazines, produced by co-isolated marine-derived fungi. In the absence of any total syntheses, we apply an innovative precursor-directed biosynthesis strategy that successfully repurposed fungal biosynthetic output, allowing us to isolate, characterize, and identify the structurally diverse neochrysosporazines A-Q. SAR analysis utilizing all known (and new) neochrysosporazines, chrysosporazines, and azachrysosporazines, plus semi-synthetic analogues, established the key structure requirements for the P-gp inhibitory pharmacophore, and, in addition, identified non-essential sites that allow for the design of affinity and other conjugated probes.


Suppressive effect of cyclosporin A on the development of Leishmania tropica-induced lesions in genetically susceptible BALB/c mice.
The effect of cyclosporin A (CyA) application on the development of cutaneous lesions was analyzed in genetically susceptible BALB/c mice infected s.c. with Leishmania tropica promastigotes. Daily i.p. injections of CyA, beginning 2 days before or at the day of the infection, dose dependently inhibited the development of parasite-induced lesions; no effect on the lesions was observed, however, if CyA application was started 14 days after the infection. Cessation of CyA administration after having successfully suppressed the cutaneous lesions for a period of 42 days, resulted in the development of lesions within 3 days. CyA had no inhibitory effect on lesions developing in L. tropica infected hypothymic BALB/c nu/nu mice. CyA or CyA-containing mouse serum did not directly affect the viability and the growth rate of L. tropica promastigotes, suggesting that the effect of the agent was imposed on the cells participating in the formation of the cutaneous lesions. Quantitative analysis of the cell distribution in the spleens of infected mice revealed that CyA markedly suppressed the infection-associated numerical increase of splenocytes. Within the Thy-1+ lymphocyte compartment, CyA had its most pronounced effect on the Lyt-1+ T lymphocyte subset. Early in the disease, the frequency of splenic cells proliferating in response to L. tropica antigen in vitro was clearly inhibited by CyA; in the later stages of the infection, however, this effect could not be observed, indicating the presence of L. tropica-inducible T cells being relatively resistant to CyA. Taken together, our findings indicate that CyA reversibly inhibits or delays the parasite-induced expansion of Lyt-1+ splenic T lymphocytes, and thus suppresses the biological function of those T cells that are instrumental for the formation of cutaneous lesions in L. tropica-infected BALB/c mice.


[Health impact of working conditions at the Ruashi mine in the Democratic Republic of Congo].
The purpose of this study was to evaluate the health impact of working conditions at the Ruashi mine in the Katanga Province in the Democratic Republic of Congo. A cross-sectional etiological study was conducted in two cohorts including 100 miners and 109 students. Data necessary to allow comparison disease symptoms in the two cohorts were collected using a questionnaire. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated. A secondary analysis was performed to compare different mine workstations, i.e., diggers (n=61) versus non-diggers (n=39). Two logistical regression models were used to estimate adjusted OR and 95% CI for the association between occupation/workstation and disease symptoms. In comparison with students, miners exhibited higher frequencies for all symptoms even after adjustment. The highest ORs were observed for musculoskeletal disorders, i.e., low back pain (OR=36.5) and upper (OR = 20.7) or lower (OR = 18.3)] extremity pain. They were followed by respiratory disorders (OR = 5.91) and headache (OR = 5.34). The high exposure frequencies and OR's observed in this study underline the negative health impact of mine working conditions. Further occupational study will be needed to obtain and compare more data.


Demonstration of a keratan sulfate-containing proteoglycan in atherosclerotic aorta.
Proteoglycans were isolated from either grossly normal or atherosclerotic pigeon aortas after extraction with 4 M guanidine hydrochloride and purification by ion-exchange and size-exclusion chromatography. The small-size proteoglycans (Kav 0.4, on Sepharose CL-4B) from both normal and atherosclerotic tissue contained primarily a dermatan sulfate proteoglycan with an intact molecular size of 220-330 kd and a 45-kd core protein. In addition to the dermatan sulfate proteoglycan, the preparation contained a proteoglycan recognized by monoclonal antibody (MAb) 5-D-4, indicating the presence of sulfated poly-N-acetyllactosamine sequences common to corneal and cartilage keratan sulfate. Electrophoresis on sodium dodecyl sulfate-polyacrylamide gel revealed a polydisperse proteoglycan of 60-150 kd that was recognized by MAb 5-D-4. Significantly greater immunoreactivity with MAb 5-D-4 was observed for atherosclerotic compared with normal artery. After endo-beta-D-galactosidase treatment of the proteoglycan from atherosclerotic aorta, diminished MAb 5-D-4 reactivity observed by both Western blot analysis and enzyme-linked immunosorbent assay demonstrated that the material was keratan sulfate. Endo-beta-D-galactosidase treatment of the intact proteoglycan generated core proteins of 28 and 38 kd. These studies suggest the presence of one or more keratan sulfate proteoglycans in grossly normal and atherosclerotic arteries. Immunochemical data suggest that sulfation of the keratan sulfate proteoglycan may be greater in atherosclerotic aorta.


Increased cardiovascular risk and reduced quality of life are highly prevalent among individuals with hepatitis C.
Hepatitis C virus (HCV) infection is common. Although treatment is effective, with oral antivirals curing >95% of patients, most individuals have comorbidities that persist long term. Therefore, our aim was to determine the prevalence of potentially modifiable health problems in patients with HCV and develop an HCV care bundle to identify and target comorbidities. Cross-sectional, observational single-centre study that recruited consecutive patients with HCV from our viral hepatitis clinics. Data were collected on cardiovascular (CV) risk factors, lifestyle behaviours, anthropometry and health-related quality of life (HRQoL). QRISK 3 was used to predict 10-year CV event risk. 100 patients were recruited (67% male, 93% white, median age 52 years (range 24-80); 71% were treated for HCV; 34% had cirrhosis; 14% had diabetes; 61% had hypertension; 31% had metabolic syndrome; and 54% were smokers). The median 10-year CV event risk was 8.3% (range 0.3%-63%). 45% had a predicted 10-year CV event risk of >10%. Only 10% of individuals were treated with statins and 27% with antihypertensives. 92% had a predicted 'heart age' greater than their chronological age (median difference +7 (-4 to +26) years). HRQoL was reduced in all SF36v2 domains in the cohort. Factors independently associated with HRQoL included cirrhosis, metabolic syndrome, history of mental health disorder, sedentary behaviour and HCV viraemia. A large proportion of patients with HCV presented with increased risk of CV events, and rates of smoking and sedentary behaviour were high, while prescribing of primary prophylaxis was infrequent. HRQoL was also reduced in the cohort. A 'care bundle' was developed to provide a structured approach to treating potentially modifiable health problems.


Split-field drift tube/mass spectrometry and isotopic labeling techniques for determination of single amino acid polymorphisms.
A combination of split-field drift tube/mass spectrometry and isotopic labeling techniques is evaluated as a means of identifying single amino acid polymorphisms (SAAPs) in proteins. The method is demonstrated using cytochromec (equine and bovine) and hemoglobin (bovine and sheep). For these studies, proteins from different species are digested with trypsin, and the peptides are labeled at primary amine groups [using either a light (H(3))- or heavy (D(3))-isotopic reagent]. SAAP analysis is carried out by mixing the light-labeled peptides of one species with the heavy-labeled peptides of the other and electrospraying the resulting mixture into a split-field drift tube/mass spectrometer. Peptides having the same sequence in both species appear as doublets in the mass spectrum [shifted in mass-to-charge (m/z) according to the number of incorporated labels]; additionally, these species have identical mobility distributions. Peptides having sequences that differ by one amino acid appear as peaks in the mass spectrum that are shifted in m/z according to the mass difference associated with the SAAP and the number of incorporated labels. The ion mobility distributions for these peptides (differing by only a single amino acid) can often be rationalized by their expected similarities or differences providing additional evidence that they are related. In all, 12 and 26 peptide variants (between species) corresponding to 5 and 11 amino acid polymorphisms have been identified for the cytochrome c and hemoglobin protein samples, respectively.


Bufalin inhibits the malignant development of non-small cell lung cancer by mediating the circ_0046264/miR-522-3p axis.
Bufalin is an active component of the traditional Chinese medicine "Chan Su" and is reported to play anti-tumor roles in cancer development, but its functional mechanism is largely unclear. This study intends to explore a potential action mode of bufalin in NSCLC. The malignant properties of NSCLC, including cell viability, proliferation, adhesion capacity, migration and invasion, were monitored by cell counting kit-8 (CCK-8), adhesion assay and transwell assay, respectively. The expression of circ_0046264 and miR-522-3p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The expression of proliferation- and migration-related markers was examined by western blot. The putative relationship between circ_0046264 and miR-522-3p was verified by dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Animal experiments in nude mice were performed to investigate the role of bufalin in vivo. Bufalin treatment inhibited cell viability, colony formation, cell adhesion capacity, migration and invasion in NSCLC cells. Bufalin facilitated the expression of circ_0046264, and circ_0046264 overexpression also inhibited NSCLC cell viability, colony formation, cell adhesion capacity, migration and invasion. Besides, circ_0046264 knockdown partially counteracted the effects of bufalin. Further, miR-522-3p was identified as a target of circ_0046264, and its deficiency reversed the effects of circ_0046264 knockdown to suppress malignant activities of NSCLC cells. In addition, bufalin restrained the tumor growth and development in vivo via enhancing the expression of circ_0046264. Bufalin played an anti-tumor role in NSCLC by modulating the circ_0046264/miR-522-3p pathway, which might be a potential functional mechanism of bufalin in NSCLC.


Keratin expression in the normal breast and in breast carcinoma.
The immunohistochemical reactivities of 69 cases of breast carcinoma were examined on methacarn-fixed, paraffin-embedded sections using eight different monoclonal antibodies which recognize one or a few keratin polypeptides. In the normal breast, the monoclonal antibodies RPN1162, RPN1165 and AE1 stained almost all the luminal cells but not the basal (myoepithelial) cells. The monoclonal antibodies 35BH11, M20, CK5 and CK8.12 stained only a subset of the luminal cells. In contrast, 312C8-1 stained basal cells but not luminal cells. All the tumour specimens reacted with AE1, while over 80% of them also reacted with 35BH11 (57/69), CK5 (57/69) and RPN1165 (55/69); 30% reacted with CK8.12 (21/69) and 16% with RPN1162 (11/69). Basal cell-specific keratin, as defined by 312C8-1, was detected in only 1% of cases (1/69). Monoclonal antibodies to different keratin polypeptides may be of use in the characterization and subdivision of breast cancer.


Awareness, treatment, and control of LDL cholesterol are lower among U.S. adults with undiagnosed diabetes versus diagnosed diabetes.
Diabetes is often undiagnosed, resulting in incorrect risk stratification for lipid-lowering therapy. We conducted a cross-sectional analysis of the National Health and Nutrition Examination Survey (NHANES) 2005-2010 to determine the prevalence, awareness, treatment, and control of elevated LDL cholesterol (LDL-C) among U.S. adults with undiagnosed diabetes. Fasting NHANES participants 20 years of age or older who had 10-year Framingham coronary heart disease (CHD) risk scores <20% and were free of CHD or other CHD risk equivalents (n = 5,528) were categorized as having normal glucose, impaired fasting glucose, undiagnosed diabetes, or diagnosed diabetes. High LDL-C was defined by the 2004 Adult Treatment Panel (ATP) III guidelines. The prevalence of diagnosed and of undiagnosed diabetes was 8 and 4%, respectively. Mean LDL-C was 102 ± 2 mg/dL among those with diagnosed diabetes and 117 ± 3 mg/dL for those with undiagnosed diabetes (P < 0.001). The prevalence of high LDL-C was similar among individuals with undiagnosed (81%) and diagnosed (77%) diabetes. Among individuals with undiagnosed diabetes and high LDL-C, 38% were aware, 27% were treated, and 16% met the ATP III LDL-C goal for diabetes. In contrast, among individuals with diagnosed diabetes and high LDL-C, 70% were aware, 61% were treated, and 36% met the ATP III goal. Subjects with undiagnosed diabetes remained less likely to have controlled LDL-C after multivariable adjustment (prevalence ratio, 0.42; 95% CI, 0.23-0.80). Improved screening for diabetes and reducing the prevalence of undiagnosed diabetes may identify individuals requiring more intensive LDL-C reduction.


Human Cardiomyocyte Progenitor Cells in Co-culture with Rat Cardiomyocytes Form a Pro-arrhythmic Substrate: Evidence for Two Different Arrhythmogenic Mechanisms.
Background: Cardiomyocyte progenitor cells (CMPCs) are a promising cell source for regenerative cell therapy to improve cardiac function after myocardial infarction. However, it is unknown whether undifferentiated CMPCs have arrhythmogenic risks. We investigate whether undifferentiated, regionally applied, human fetal CMPCs form a pro-arrhythmic substrate in co-culture with neonatal rat ventricular myocytes (NRVMs). Method: Unipolar extracellular electrograms, derived from micro-electrode arrays (8 × 8 electrodes) containing monolayers of NRVMs (control), or co-cultures of NRVMs and locally seeded CMPCs were used to determine conduction velocity and the incidence of tachy-arrhythmias. Micro-electrodes were used to record action potentials. Conditioned medium (Cme) of CMPCs was used to distinguish between coupling or paracrine effects. Results: Co-cultures demonstrated conduction slowing (5.6 ± 0.3 cm/s, n = 50) compared to control monolayers (13.4 ± 0.4 cm/s, n = 26) and monolayers subjected to Cme (13.7 ± 0.6 cm/s, n = 11, all p < 0.001). Furthermore, co-cultures had a more depolarized resting membrane than control monolayers (-47.3 ± 17.4 vs. -64.8 ± 7.7 mV, p < 0.001) and monolayers subjected to Cme (-64.4 ± 8.1 mV, p < 0.001). Upstroke velocity was significantly decreased in co-cultures and action potential duration was prolonged. The CMPC region was characterized by local ST-elevation in the recorded electrograms. The spontaneous rhythm was faster and tachy-arrhythmias occurred more often in co-cultured monolayers than in control monolayers (42.0 vs. 5.4%, p < 0.001). Conclusion: CMPCs form a pro-arrhythmic substrate when co-cultured with neonatal cardiomyocytes. Electrical coupling between both cell types leads to current flow between a, slowly conducting, depolarized and the normal region leading to local ST-elevations and the occurrence of tachy-arrhythmias originating from the non-depolarized zone.


Evaluation of a rapid enzyme immunoassay for detection of influenza A virus.
The Directigen FLU-A enzyme immunoassay for the detection of influenza A virus was compared with direct smear and culture in 211 clinical specimens. The FLU-A enzyme immunoassay proved to be a reliable, rapid screen for influenza A from symptomatic patients and was less dependent on technical expertise for interpretation than were direct smears.


Identification and analysis of ongoing registered clinical intervention trials on COVID-19.
The World Health Organization declared the disease caused by the novel coronavirus (SARS-CoV-2), a pandemic on March 11, 2020. Several studies have been proposed and started since then, mainly covering prevention, diagnosis, management, and treatment. To identify and categorize all intervention studies up to the end of May related to SARS-CoV-2 infection, according to population and geo-graphical location (emphasis in Latin America) and to verify if there is any correlation according to purpose, phase, and recruitment status. One thousand six hundred seventy-two trials were selected from 1705 until May 24 on the World Health Organization clinical trials platform related to COVID-19. Jupyter and Python tools were used for data processing and cleaning. One thousand six hundred seventy-two intervention studies related to SARS-CoV-2 infection were found. China, The United States, Iran, France, and Spain are the countries participating in the largest number of studies, while only 4,1% are from Latin America (mostly Brazilian). 28 studies are focusing only on older adults, and ten studies are based exclusively on populations under 19 years of age. The worldwide interest in this new disease is reflected in the increasing number of intervention studies that are being carried out to date. How-ever, the studies analyzed do not cover the most vulnerable age groups proportionally and do not have equitable participation of all the coun-tries. In Latin America, this problem is exacerbated by the region's social, economic, and political limitations. Because it is an emerging disease, there is still not enough information to establish strong correlations between the analyzed variables, and the standardization of protocols is not yet definite because most of the studies are in progress.


Microstructural Effects on the Interfacial Adhesion of Nanometer-Thick Cu Films on Glass Substrates: Implications for Microelectronic Devices.
Improving the interface stability for nanosized thin films on brittle substrates is crucial for technological applications such as microelectronics because the so-called brittle-ductile interfaces limit their overall reliability. By tuning the thin film properties, interface adhesion can be improved because of extrinsic toughening mechanisms during delamination. In this work, the influence of the film microstructure on interface adhesion was studied on a model brittle-ductile interface consisting of nanosized Cu films on brittle glass substrates. Therefore, 110 nm thin Cu films were deposited on glass substrates using magnetron sputtering. While film thickness, residual stresses, and texture of the Cu films were maintained comparable in the sputtering processes, the film microstructure was varied during deposition and via isothermal annealing, resulting in four different Cu films with bimodal grain size distributions. The interface adhesion of each Cu film was then determined using stressed Mo overlayers, which triggered Cu film delaminations in the shape of straight, spontaneous buckles. The mixed-mode adhesion energy for each film ranged from 2.35 J/m2 for the films with larger grains to 4.90 J/m2 for the films with the highest amount of nanosized grains. This surprising result could be clarified using an additional study of the buckles using focused ion beam cutting and quantification via confocal laser scanning microscopy to decouple and quantify the amount of elastic and plastic deformation stored in the buckled thin film. It could be shown that the films with smaller grains exhibit the possibility of absorbing a higher amount of energy during delamination, which explains their higher adhesion energy.


Assessing Operative Skill in the Competency-based Education Era: Lessons From the UK and Ireland.
Decisions regarding the operative competence of surgical residents in the United Kingdom and Ireland are informed by operative workplace-based assessments (WBAs) and operative number targets for index procedures. This review seeks to outline the validity evidence of these assessment methods. A review of the MEDLINE (Pubmed), EMBASE and Cochrane Library databases was undertaken in accordance with the Joanna Briggs Institute Protocol for Scoping Reviews (2020). Articles were included if they provided evidence of the validity of procedure-based assessments, direct observation of procedural skills, or indicative operative number targets. The educational impact of each article was evaluated using a modified Kirkpatrick model. Twenty-eight articles outlining validity evidence of WBAs and operative number targets were synthesised by narrative review. Five studies documented users' views on current assessment methods (Kirkpatrick level 1). Two articles recorded changes in attitudes towards current operative assessments (level 2a). Ten studies documented the ability of current assessments to record improvements in operative competence (level 2b). Ten studies measured a change in behaviour as a result of the introduction of these assessments (level 3). One article studied the ability of operative assessments to predict clinical outcomes (level 4b). Operative WBAs are reliable. Scores achieved correlate with both time spent in training and recorded operative experience. Trainers and residents have concerns regarding the subjectivity of these assessments and the opportunistic nature in which they are used. Operative number targets are not criterion-referenced, lack validity evidence, and may be set too low to ensure operative competence.


Comprehensive detection of viruses in pediatric patients with acute liver failure using next-generation sequencing.
Pediatric acute liver failure (PALF) is a rare and severe syndrome that frequently requires liver transplantation. Viruses are one of the most frequent causes of this disease, however, pathogenic viruses are not determined in many patients. Recently next-generation sequencing (NGS) has been applied to comprehensively detect pathogens of infectious diseases of unknown etiology. To evaluate an NGS-based approach for detecting pathogenic viruses in patients with PALF or acute hepatitis of unknown etiology. To detect virus-derived DNA and RNA sequences existing in sera/plasma from patients, both DNA and RNA sequencing were performed. First, we validated the ability of NGS to detect viral pathogens in clinical serum/plasma samples, and compared different commercial RNA library preparation methods Then, serum/plasma of fourteen patients with PALF or acute hepatitis of unknown etiology were evaluated using NGS. Among three RNA library preparation methods, Ovation RNA-Seq System V2 had the highest sensitivity to detect RNA viral sequences. Among fourteen patients, sequence reads of torque teno virus, adeno-associated virus, and stealth virus were found in the sera of one patient each, however, the pathophysiological role of these three viruses was not clarified. Significant virus reads were not detected in the remaining 11 patients. This finding might be due to low virus titer in blood at the time of referral or a non-infectious cause might be more frequent. These results suggest an NGS-based approach has potential to detect viral pathogens in clinical samples and would contribute to clarification of the etiology of PALF.


Tangible words are recognized faster: the grounding of meaning in sensory and perceptual systems.
Sensory experience rating (SER), a new variable motivated by the grounded cognition framework of conceptual processing (e.g., Barsalou, 2008 ), indexes the degree to which a word evokes sensory/perceptual experiences. In the present study, SERs were collected for over 2,850 words. While SER is correlated with imageability, age of acquisition, and word frequency, the latter variables (along with seven others) account for less than 30% of the variance in SER. Reanalyses of two large-scale studies demonstrate that SER significantly predicts lexical decision times when other established predictor variables are statistically controlled. These results suggest that conceptual processing is grounded in sensory systems. Additionally, a major benefit of this variable is that it allows psycholinguistic researchers to examine semantic-perceptual links for all word classes with a single rating.


Citalopram may reduce sympathoadrenal hyperactivity in elderly depressed patients: an open multicenter study in Belgium and Luxembourg.
Through effects of catecholamines upon the heart, blood vessels and platelets, sympathoadrenal hyperactivity contributes to the development of cardiovascular diseases in elderly depressed patients. To assess the cardiovascular effect of Citalopram in elderly depressed patients, data from an open multicenter study in Belgium and Luxembourg, in which a total of 811 patients were evaluated, was retrospectively analysed. Although the aim of the study was to assess the efficacy and safety of Citalopram, blood pressure and heart rate were also monitored. Patients included in the study were referred either by psychiatrists, geriatricians or general practitioners. Clinical assessment included ratings on the Hamilton Rating Depression Scale, the Clinical Global Impression Scale, the UKU Side effect rating scale and the assessment of side effects spontaneously reported. With few side effects, Citalopram significantly improves the clinical condition of elderly patients suffering from depressive symptoms. A series of repeated multivariate analyses of covariance were performed on heart rate and blood pressure controlling for the effect of age. Interestingly, a sustained decrease of these parameters was shown during the whole study period reaching significance for systolic blood pressure (p<0.05). These effects were observed both in responding as well as non-responding patients, and were somewhat more marked in responders for heart rate (p=0.058). The slight but significant decrease in systolic blood pressure and heart rate suggests that citalopram may reduce sympathoadrenal hyperactivity and the related increased cardiovascular morbidity and mortality associated with depression.


Heavy metals and potential risks in edible seaweed on the market in Italy.
The seaweed food has always been important in Asia, but recently increased in the Western diet. Superfood known for health benefits and rich in essential elements, can also accumulate high contents of heavy metals and iodine from the environment, becoming a health hazard. In particular for iodine, an appropriate labelling of seaweed is needed to warn the consumer of the potential risks. The aim of the study was to analyze the content of 20 heavy metals in seaweeds, distributed in Italy, by ICP-MS, also determining iodine and arsenic (total and inorganic fraction). A total of 72 samples of European and Asian seaweed of 8 genera were analyzed and the results correlated the content of heavy metals to genus, geographical origin and type of sample; 8.33% of the products lacked in the label of the indications of allergens, while 9.72% had irregularities in the label language. The highest concentration of elements was found in the Rhodophyta. The Aluminum level was the highest in the mixed seaweed (165.39 mg/kg) and for the Cadmium in the Asian seaweed (1.16 mg/kg). The amounts of Iron, Zinc and Magnesium, was highest in the Asian seaweed. The values of Arsenic (total and inorganic contents) were compared with the limits: 2.78% exceeds France and USA limits for inorganic, while higher content of total was found in Phaeophyta, which also showed the highest Iodine content (6770.80 mg/kg) that can be dangerous if not reported correctly in the label.


CRC-derived exosomes containing the RNA binding protein HuR promote lung cell proliferation by stabilizing c-Myc mRNA.
HuR overexpression is related to poor survival in patients with colon cancer. HuR overexpression leads to stabilization of tumor-promoting mRNAs by binding to 3'UTR-resident AREs. Exosomes, nanosized lipid bilayer vesicles, mediate many steps in cancer progression. The potential role of exosomal HuR in colon cancer lung metastasis is unclear. HuR expression was assessed immunohistochemically in tumor tissue samples from 20 patients with metastatic or nonmetastatic colon cancer and colon cancer lung metastasis and benign lung disease samples from ten patients. Exosomes were isolated from HCT116 WT and HuR KO colon cancer cells, and uptake of PKH67- and PKH26-labeled exosomes by BEAS-2B cells was evaluated using fluorescence and confocal microscopy. C-Myc and p21protein and mRNA levels were measured by western blotting and RT-qPCR, respectively. In clinical patients, HuR overexpression was significantly enhanced in colon tissues of patients with lung metastasis. HuR expression was higher in lung tissue with metastasis of colonic origin than with benign lung disease. The effect of HuR-containing CRC exosomes compared to HuR-deficient exosomes on wound closure was observed as enhanced proliferation. BEAS-2B cell migration and invasion were enhanced after HuR-containing exosomes treatment. BEAS-2B cells showed similar uptake of PKH67 (HCT116 WT)- and PKH26 (HCT116 HuR KO)-labeled exosomes. Exosomal HuR stabilized c-Myc mRNA and downregulated p21 expression, leading to G1/S transition, in human bronchial epithelial cells. HuR overexpression is associated with lung metastasis in colon cancer patients. Exosomal HuR derived from colon cancer cells alter the biological effect on normal lung epithelial cells.


Motion-generated optical information allows event perception despite blurry vision in AMD and amblyopic patients.
Events consist of objects in motion. When objects move, their opaque surfaces reflect light and produce both static image structure and dynamic optic flow. The static and dynamic optical information co-specify events. Patients with age-related macular degeneration (AMD) and amblyopia cannot identify static objects because of weakened image structure. However, optic flow is detectable despite blurry vision because visual motion measurement uses low spatial frequencies. When motion ceases, image structure persists and might preserve properties specified by optic flow. We tested whether optic flow and image structure interact to allow event perception with poor static vision. AMD (Experiment 1), amblyopic (Experiments 2 and 3), and normally sighted observers identified common events from either blurry (Experiments 1 and 2) or clear images (Experiment 3), when either single image frames were presented, a sequence of frames was presented with motion masks, or a sequence of frames was presented with detectable motion. Results showed that with static images, but no motion, events were not perceived well by participants other than controls in Experiment 3. However, with detectable motion, events were perceived. Immediately following this and again after five days, participants were able to identify events from the original static images. So, when image structure information is weak, optic flow compensates for it and enables event perception. Furthermore, weakened static image structure information nevertheless preserves information that was once available in optic flow. The combination is powerful and allows events to be perceived accurately and stably despite blurry vision.


Optical generation of gigahertz-frequency shear acoustic waves in liquid glycerol.
Picosecond laser ultrasonic techniques for acoustic wave generation and detection have been employed to probe shear acoustic waves in liquid glycerol at gigahertz frequencies. The experimental approach uses a unique laser pulse shaping technique and a crystallographically canted metal layer to generate frequency-tunable transverse acoustic waves, and uses time-domain coherent Brillouin scattering to detect the waves after they propagate through a liquid layer and into a solid substrate. A linear frequency dependence is found for both the shear speed and attenuation rate in glycerol.


Diacerein: Recent insight into pharmacological activities and molecular pathways.
Diacerein is a symptomatic slow-acting drug in osteoarthritis (SYSADOA) and the active metabolite is rhein. It is a non-steroidal anti-inflammatory drug with unique pharmacological properties as anti-oxidant and anti-apoptosis. Diacerein has recently shown to have a potential role by mediating anti-inflammatory as well as anti-oxidant and anti-apoptosis in kidney injury, diabetes mullites, and a beneficial effect on pain relief. It may have a therapeutic role in cancer, ulcerative colitis, testicular injury and cervical hyperkeratosis. Furthermore, diacerein has a valuable addition in combination therapy as a synergetic agent. This review, the first of its kind, highlights the proposed roles of diacerein in osteoarthritis and discusses recent results supporting its emerging roles with a particular focus on how these new insights may facilitate the rational development of diacerein for targeted therapies in the future.


Therapeutic results of resection, transcatheter arterial embolization and percutaneous transhepatic ethanol injection in 3225 patients with hepatocellular carcinoma: a retrospective multicenter study.
The outcome in 3225 patients with hepatocellular carcinoma (HCC) was studied in groups with equivalent prognosis treated with resection, transcatheter arterial embolization (TAE), and percutaneous transhepatic ethanol injection (PEI). Significant factors for better clinical background included a tumor diameter of < or = 30 mm, tumor number < or = 3 and (clinical) Stage I. In patients with Stage I disease having tumors of < or = 30 mm and < or = 3 in number, survival afer resection and PEI did not differ, while survival after TAE was significantly worse. In those patients with Stage II disease, survival after PEI was significantly better than after resection or TAE. In patients with Stage I or II disease having tumors > or = 31 in size and < or = 3 number, survival after resection was significantly better than after TAE. In patients with Stage I disease having tumors of > or = 31 mm and > or = 4 in number, survival after resection was significantly better than after TAE. Our conclusions are as follows. Firstly, resection or PEI is recommended for patients with Stage I disease having < or = 3 tumors all < or = 30 mm in size. Secondly, PEI is recommended for patients with Stage II disease having < or = 3 tumors all < or = 30 mm in size. Thirdly, for patients with Stage I disease having tumors 31 mm or larger in size, whatever the number of tumors, resection should be selected rather than TAE.


Predictive factors for pure steatosis in alcoholic patients.
Bearing in mind the mechanisms involved in nonalcoholic fatty liver disease, this study aims to verify whether metabolic syndrome or its various individual components are independent predictive factors for steatosis > or =10% in alcoholic patients. This study included 281 consecutive alcoholic patients with abnormal liver tests and either normal liver histology or steatosis <10% (n = 119) or steatosis > or =10% (n = 162). Logistic regression analysis was used to study the relationship between metabolic syndrome components and various risk factors and the presence of steatosis > or =10%. We assessed apolipoprotein A1 (ApoA-1) levels, a major protein component of plasma high-density lipoprotein (HDL), rather than HDL-cholesterol levels. Plasma ApoA-1 levels (p < 0.01), body mass index (BMI) (p < 0.01), and waist circumference (p < 0.05) were significantly higher in patients with steatosis > or =10% than in patients with normal liver histology or steatosis <10%. A higher percentage of patients with steatosis > or =10% had high blood pressure (p = 0.003) than patients with normal liver histology or steatosis <10%. In the logistic regression, ApoA-1 [odds ratio (OR) = 1.57 (1.10-2.22)], BMI [OR = 1.10 (1.01-1.23)], and high blood pressure [OR = 1.84 (1.10-3.06)] were positively and independently correlated with the presence of steatosis > or =10%. In the multivariate regression high blood pressure was independently and positively correlated with steatosis score (r = 0.55 +/- 0.26; p < 0.05). On the other hand, when the presence of high blood pressure was the dependent variable, the presence of steatosis > or =10% positively and independently correlated with it [OR = 1.82 (1.05-3.15)]. In alcoholic patients without fibrosis, ApoA-1, BMI, and high blood pressure on the next morning after the admission were predictive of steatosis > or =10%. High blood pressure was the only metabolic syndrome component associated with the presence of alcoholic steatosis >/=10% and was not correlated with other metabolic syndrome components. These findings suggest that steatosis mechanisms are different in alcoholic and nonalcoholic fatty liver.


Sensitization during visual habituation sequences: procedural effects and individual differences.
Although individual differences in visual habituation have long been interpreted in terms of processes derived from comparator theory, research over the last decade has suggested that arousal or arousability as manifest in sensitization may contribute to infants' attentional profiles, and thus, to individual differences in those profiles. We explored this possibility by habituating 4-month-old infants to 4 x 4, 10 x 10, or 20 x 20 checkerboards in a fixed-trial paradigm. The first specific aim was to examine the attentional characteristics of infants with habituation patterns showing sensitization versus those that did not. The second specific aim was to determine whether patterns of attention suggestive of sensitization effects reported in past research might be attributable to the use of illuminated interstimulus intervals (ISIs). Trends were observed for sensitization to occur more frequently with more complex than with less complex checkerboards. Infants who showed looking patterns characteristic of sensitization looked longer and did not habituate as readily as infants who did not show sensitization. Finally, different ISIs did not engender different levels of sensitization, but dark ISIs significantly increased infants' looking times to stimuli during trials.


The impact of prophylactic dexamethasone on nausea and vomiting after thyroidectomy: a systematic review and meta-analysis.
We carried out a systematic review and meta-analysis to evaluate the impact of prophylactic dexamethasone on post-operative nausea and vomiting (PONV), post-operative pain, and complications in patients undergoing thyroidectomy. We searched Pubmed, Embase, and Cochrane Library databases for randomized controlled trials (RCTs) that evaluated the prophylactic effect of dexamethasone versus placebo with or without other antiemetics for PONV in patients undergoing thyroidectomy. Meta-analyses were performed using RevMan 5.0 software. Thirteen RCTs that considered high quality evidence including 2,180 patients were analyzed. The meta-analysis demonstrated a significant decrease in the incidence of PONV (RR 0.52, 95% CI 0.43 to 0.63, P < 0.00001), the need for rescue anti-emetics (RR 0.42, 95% CI 0.30 to 0.57, P<0.00001), post-operative pain scores (WMD -1.17, 95% CI -1.91 to -0.44, P = 0.002), and the need for rescue analgesics (RR 0.65, 95% CI 0.50-0.83, P = 0.0008) in patients receiving dexamethasone compared to placebo, with or without concomitant antiemetics. Dexamethasone 8-10mg had a significantly greater effect for reducing the incidence of PONV than dexamethasone 1.25-5mg. Dexamethasone was as effective as other anti-emetics for reducing PONV (RR 1.25, 95% CI 0.86-1.81, P = 0.24). A significantly higher level of blood glucose during the immediate post-operative period in patients receiving dexamethasone compared to controls was the only adverse event. Prophylactic dexamethasone 8-10mg administered intravenously before induction of anesthesia should be recommended as a safe and effective strategy for reducing the incidence of PONV, the need for rescue anti-emetics, post-operative pain, and the need for rescue analgesia in thyroidectomy patients, except those that are pregnant, have diabetes mellitus, hyperglycemia, or contraindications for dexamethasone. More high quality trials are warranted to define the benefits and risks of prophylactic dexamethasone in potential patients with a high risk for PONV.


Sympathetic response to intracranial NGF infusion in the absence of afferent input: axonal sprouting without neurotransmitter production.
The anatomical relationships between postganglionic sympathetic neurons, their targets, and their afferent inputs provide an opportunity to experimentally distinguish between the anterograde and the retrograde influences on neuronal responsivity to growth factors. In the present study, the effect of decentralization of the superior cervical ganglion (SCG) on the NGF-induced sympathetic sprouting response by mature cerebrovascular axons was assessed in young adult rats. Growth by the perivascular axons associated with the intradural segment of the internal carotid artery was quantified using electron microscopy and changes in norepinephrine (NE) levels were monitored using high-performance liquid chromatography coupled with electrochemical detection. The mean number of perivascular axons observed in the treatment group receiving decentralization of the SCG prior to NGF infusion was not significantly different from that in NGF-infused cases, suggesting that central input was not required for axonal growth of intact sympathetic neurons. However, decentralization prevented the typical NGF-induced increase in perivascular NE associated with the ICA, indicating that afferent input was necessary for the neurotransmitter increase to occur. Thus, afferent input appears to play a role in the regulation of neurotransmitter expression of the sprouted axons but is not required for trophic factor-induced axonal growth.


Restoring KLF5 in esophageal squamous cell cancer cells activates the JNK pathway leading to apoptosis and reduced cell survival.
Esophageal cancer is the eighth most common cancer in the world and has an extremely dismal prognosis, with a 5-year survival of less than 20%. Current treatment options are limited, and thus identifying new molecular targets and pathways is critical to derive novel therapies. Worldwide, more than 90% of esophageal cancers are esophageal squamous cell cancer (ESCC). Previously, we identified that Krüppel-like factor 5 (KLF5), a key transcriptional regulator normally expressed in esophageal squamous epithelial cells, is lost in human ESCC. To examine the effects of restoring KLF5 in ESCC, we transduced the human ESCC cell lines TE7 and TE15, both of which lack KLF5 expression, with retrovirus to express KLF5 upon doxycycline induction. When KLF5 was induced, ESCC cells demonstrated increased apoptosis and decreased viability, with up-regulation of the proapoptotic factor BAX. Interestingly, c-Jun N-terminal kinase (JNK) signaling, an important upstream mediator of proapoptotic pathways including BAX, was also activated following KLF5 induction. KLF5 activation of JNK signaling was mediated by KLF5 transactivation of two key upstream regulators of the JNK pathway, ASK1 and MKK4, and inhibition of JNK blocked apoptosis and normalized cell survival following KLF5 induction. Thus, restoring KLF5 in ESCC cells promotes apoptosis and decreases cell survival in a JNK-dependent manner, providing a potential therapeutic target for human ESCC.


Simultaneous detection of Aeromonas salmonicida, Flavobacterium psychrophilum, and Yersinia ruckeri, three major fish pathogens, by multiplex PCR.
A multiplex PCR assay based on the 16S rRNA genes was developed for the simultaneous detection of three major fish pathogens, Aeromonas salmonicida, Flavobacterium psychrophilum, and Yersinia ruckeri. The assay proved to be specific and as sensitive as each single PCR assay, with detection limits in the range of 6, 0.6, and 27 CFU for A. salmonicida, F. psychrophilum, and Y. ruckeri, respectively. The assay was useful for the detection of the bacteria in artificially infected fish as well as in fish farm outbreaks. Results revealed that this multiplex PCR system permits a specific, sensitive, reproducible, and rapid method for the routine laboratory diagnosis of infections produced by these three bacteria.


Thermal Destruction of Staphylococcus aureus in Human Milk.
Rates of thermal destruction of Staphylococcus aureus were determined in mature human milk using a continuous flow high-temperature short-time pasteurization system. D and z values for inactiviation of S. aureus were determined from data on survivors capable of forming colonies in an appropriate selective medium. The effects of thermal injury on D and z values were assessed by survivor colony forming units (CFU) on Staphylococcus medium 110 (SMI 10), nutrient agar (NA), Trypticase Soy Agar (TSA), Trypticase Soy Agar with 7.5% NaCi (TSAS) and Baird-Parker medium (BP) (Difco Laboratories, Detroit, MI). D values for inactivation of S. aureus at 52, 58 and 60 and 62°C were used to predict D at 60°C of 15.3 s and 24.3 s when based on survivor CFU in SM 110 and nutrient agar, respectively. The z value was 4.9°C in either medium. D-values for inactivation of S. aureus at 60, 62, 64 and 67°C were used to predict D at 60°C of 41.2 s, 41.0 s and 34.7 s when based on survivor CFU in BP, TSA and TSAS, respectively. The z values were 6.5, 6.5 and 6.4°C, respectively.


Complete Genome Sequence of Bacillus sp. Strain NC3, Isolated from Trichonephila Spider Ground Extract.
Bacillus sp. strain NC3, an aerobic Gram-positive bacterium, was isolated from a suspension of ground Trichonephila clavata specimens in saline in Japan. Here, we report the complete genome sequence of this bacterium, which has a 3.72-Mbp genome, containing 3,717 protein-coding sequences, 24 rRNA-coding sequences, and 81 tRNA-coding sequences.


1,25-Dihydroxyvitamin D3 differentially regulates the production of insulin-like growth factor I (IGF-I) and IGF-binding protein-4 in mouse osteoblasts.
1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces differentiation and inhibits proliferation in many cell types including bone cells. These effects may be mediated by the modulation of the insulin-like growth factor (IGF) regulatory system. Therefore we investigated the effects of 1,25-(OH)2D3 on transcript and protein levels of both IGF-I and IGF binding proteins (IGFBPs) in clonal mouse osteoblasts. Subconfluent cultures were treated in serum-free medium with 1,25-(OH)2D3. Secreted IGF-I was measured using a RIA under conditions eliminating the interference of IGFBPs. 1,25-(OH)2D3 (10(-11)-10(-8) M) inhibited IGF-I release in a dose dependent manner at 24 h (maximally to 30 +/- 5% of control, mean +/- SEM of seven independent experiments). In a time course study IGF-I increased in the media of control cultures over a 48-h period, while IGF-I secretion was completely prevented from 6 h onward in 1,25-(OH)2D3 treated cultures. Northern blot analysis revealed four IGF-I transcripts of 0.9, 1.8, 4.4, and 7.5 kilobases (kb). 1,25-(OH)2D3 decreased levels of the 7.5 kb IGF-I transcript from 4-48 h, with maximal inhibition occurring at 24 h (25% of control). Western ligand blots of the culture medium demonstrated secretion of a 25-kilodalton IGFBP, which comprised greater than or equal to 90% of the secreted IGFBPs. The 25-kilodalton IGFBP had previously been shown to have sequence similarity with IGFBP-4, a binding protein which inhibits the action of IGFs on bone cells. 1,25-(OH)2D3 treatment increased secretion of IGFBP-4 up to 14-fold over 24 h. 1,25-(OH)2D3 also increased IGFBP-4 (2.2 kb) transcript levels within 30 min, with the maximal stimulation of 8-fold occurring after 8 h. [3H]Thymidine incorporation into cells was inhibited by 1,25-(OH)2D3 both under basal and serum-stimulated conditions. Our results are consistent with the hypothesis that the effects of 1,25-(OH)2D3 on osteoblast proliferation may be mediated in part by decreased levels of IGF-I and increased concentrations of inhibitory IGFBP-4. It is proposed that this alteration in the IGF system may be an important functional autocrine or paracrine switch in the transition of osteoblasts from states of proliferation to differentiation.


Reductive and Emergent Views on Motor Learning in Rehabilitation Practice.
To allow different views on motor learning to inform rehabilitation research, the authors aimed to explicate a frequently missed yet fundamental difference in starting point of such views. By considering how rehabilitation in practice answers the question of what parts an activity consists of, reductive and emergent approaches to motor learning are identified and traced throughout rehabilitation practice. The authors show that when a task is cut up along reductive dimensions while also apparently relying on emergent components, this unequally favors the reductive approach and acts to limit the views on motor learning available. By showing the approaches in practice, the authors hope to inspire an awareness that brings both approaches the opportunity to independently inform research so that new theories and practices can proliferate.


Network analyses structure genetic diversity in independent genetic worlds.
DNA flows between chromosomes and mobile elements, following rules that are poorly understood. This limited knowledge is partly explained by the limits of current approaches to study the structure and evolution of genetic diversity. Network analyses of 119,381 homologous DNA families, sampled from 111 cellular genomes and from 165,529 phage, plasmid, and environmental virome sequences, offer challenging insights. Our results support a disconnected yet highly structured network of genetic diversity, revealing the existence of multiple "genetic worlds." These divides define multiple isolated groups of DNA vehicles drawing on distinct gene pools. Mathematical studies of the centralities of these worlds' subnetworks demonstrate that plasmids, not viruses, were key vectors of genetic exchange between bacterial chromosomes, both recently and in the past. Furthermore, network methodology introduces new ways of quantifying current sampling of genetic diversity.


Initial outcomes of laparoscopic paraesophageal hiatal hernia repair with mesh.
The use of mesh in laparoscopic paraesophageal hiatal hernia repair (LHR) may reduce the risk of late hernia recurrence. The aim of this study was to evaluate initial outcomes and recurrence rate of 92 patients who underwent LHR reinforced with a synthetic bioabsorbable mesh. Surgical approaches included LHR and Nissen fundoplication (n = 64), LHR without fundoplication (n = 10), reoperative LHR (n = 9), LHR with a bariatric operation (n = 6), and emergent LHR (n = 3). The mean length of hospital stay was 2 ± 3 days (range, 1 to 30 days). There were no conversions to open laparotomy and no intraoperative complications. One of 92 patients (1.1%) required intensive care unit stay. The 90-day mortality was zero. Minor complications occurred in 3.3 per cent, major complications in 2.2 per cent, and late complications in 5.5 per cent of patients. There were no perforations or early hernia recurrence. The 30-day reoperation rate was 1.1 per cent. For patients with available 1-year follow-up, the overall recurrence rate was 18.5 per cent with a mean follow-up of 30 months (range, 12 to 51 months). LHR repair with mesh is associated with low perioperative morbidity and no mortality. The use of bioabsorbable mesh appears to be safe with no early hiatal hernia recurrence or late mesh erosion. Longer follow-up is needed to determine the long-term rate of hernia recurrence associated with LHR with mesh.