Influence of scan technology on the accuracy and speed of intraoral scanning systems for the edentulous maxilla: An in vitro study.
To compare the accuracy of three intraoral scanners in terms of trueness and precision relative to the scanner acquisition technology and scan capture mode. Scan speed of each scanner was also evaluated. An edentulous maxillary arch was digitized (reference model) and 3D-printed using an SLA-based 3D-printer (XFAB; DWS, Italy) (n = 10). Each model was scanned using three intraoral scanners, each with different scan technologies: confocal (Trios 3; 3Shape, Copenhagen, Denmark), parallel confocal (iTero; Align Technology), and triangulation (Medit i700). Scan time and scanning accuracy (trueness and precision) were calculated using digital subtraction technique (Geomagic Control X v2020, 3DSystems, USA). One-way analysis of variance (ANOVA) test was used to detect differences in trueness, precision, and scanning time between the tested groups (p < 0.05). ANOVA results showed statistically significant differences in trueness, precision, and scan time among the tested groups. Confocal scanning technique (Trios 3) showed the highest trueness and precision (root mean square estimate [RMSE] 0.094 and 0.096, respectively) followed by iTero displaying parallel confocal technique (RMSE 0.113 and 0.133, respectively); the difference was not significant (p = 0.849, p = 0.488). Further, Trios showed the longest scanning time (100 s) compared to iTero and Medit i700 (p = 0.011 and 0.002, respectively). Medit i700 presenting triangulation scan technology revealed lowest trueness and precision (RMSE 0.268) (p = 0.000, p = 0.001) and fastest scan time (59 s) close to iTero (66 s) (p = 0.802). Scanner technology had an influence on the accuracy and scan speed of the acquired intraoral scans. The Trios 3 scanner featuring the confocal acquisition technology displayed the highest trueness, precision, and longest scan time. Medit i700 IOS with triangulation acquisition concept featured the lowest trueness, precision, and fastest scan speed. There is no ideal scanner with the best combination of accuracy and scan speed.


[The clinical and hemostasiological features of chronic hepatitides of different genesis].
To comparatively characterize clinical, biochemical, and hemostasiological parameters in patients with chronic alcoholic hepatitis (CAH) and chronic mixed hepatitis (CMH), i.e. CAH + chronic hepatitis C. Sixty-three patients (mean age 39.05±4.95 years) with chronic hepatitides of different etiology, who underwent general clinical, biochemical, and hemostasiological studies, were examined. The frequency and duration of major clinical symptoms were maximally pronounced in the patients with CMH. Aspartate aminotransferase concentrations were significantly decreased only in the patients with CAH, remaining at higher levels in CMH. The activity of γ-glutamyl transpeptidase was twice higher in CAH. In the patients of both groups, the total concentration of nitrates and nitrites was recorded within the normal range and the activity of von Willebrand factor was significantly higher than normal. The aggregation of platelets and erythrocytes in the patients of all the groups was significantly lower than that in the healthy individuals, but differed at different disease stages. CMH was ascertained to have a more severe course. The hemostatic system did not significantly depend on the etiology of hepatitis, but was variable in different periods of various hepatitides.


Stent composition and immune response after long-term coronary angioplasty.
There are limited data about the influence of stent composition on immune responses after percutaneous coronary intervention (PCI). The aim was to compare the effects of PCI with conventional cobalt-chromium bare metal stent (BMS) and drug-eluting stent (DES) implantation on the modulation of humoral and cellular immune responses. A randomised, single-centre, open pilot study involving patients with stable coronary artery disease eligible for PCI was performed. Blood samples were collected from the peripheral artery (PA) and the coronary sinus (CS) at baseline and 40 weeks following PCI. IgM and IgG autoantibodies (Abs), anti-oxLDL and anti-ApoB-D, as well as cytokine levels were evaluated by enzyme-linked immunosorbent assay. A total of 30 patients of 60 years mean age were included, 68% of whom were men. At the nine-month follow-up, a modulation in the levels of cytokines and autoantibodies was observed in both stent type groups. However, no difference was observed in the modulation of these markers between stents. The stent type promotes modulations in cellular and humoral immune responses in the long-term, with differences in the magnitude of effects in specific immune responses.


Age factor and implication of human papillomavirus type-specific prevalence in women with normal cervical cytology.
The prevalence and genotype distribution of human papillomavirus (HPV) infection in women with normal cervical cytology varies widely according to the population studied. Two non-overlapping population-based cohort studies of women aged ≥30 years for the periods 2008-2009 (n=5026) and 2004-2005 (n=10 014) were analysed. The prevalence rate of HPV was 11·0% (95% CI 10·5-11·6). HPV infection was significantly associated with age, menopausal status, and inversely associated with hormone replacement therapy. There was an increasing trend of α3/α15, α5/α6, and multiple HPV infections with increasing age. The five most common types were HPV52, 18, 53, 58 and 70, while HPV16, 31, 33 ranked 21st, 25th, and 16th, respectively, in the merged cohort with normal cytology (n=14 724). HPV16, 31, and 33 were significantly associated with abnormal cytology, which could have resulted in their rarity in the total merged cohort (n=15 040).


Vitamin C and vitamin E protect the rat testes from cadmium-induced reactive oxygen species.
Cadmium is an environmental and industrial pollutant that affects the male reproductive system of humans and animals. However, the mechanism of its adverse effect on Leydig cell steroidogenesis remains unknown. The present study points to the possible involvement of oxidative stress in the suppression of steroidogenesis. Cadmium administration caused an increase in reactive oxygen species (ROS) by elevating testicular malondialdehyde (MDA) and decreasing the activities of testicular antioxidant enzymes such as glutathione peroxidase and superoxide dismutase. The mRNA of Steroid Acute Regulatory (StAR) protein was substantially reduced. The activities of testicular delta5-3beta and 17-beta-hydroxysteroid dehydrogenases (HSD) as well as serum testosterone level were also lowered, suggesting that cadmium-induced ROS inhibit testicular steroidogenesis. Supplementation with vitamin C (VC) and or vitamin E (VE) reduced testicular ROS and restored normal testicular function in Cd-exposed rats. We conclude that VC and VE prevent oxidative stress and play vital roles in co-regulating StAR gene expression and steroid production in cadmium-exposed rats.


Human rhinovirus and disease severity in children.
To evaluate retrospectively human rhinovirus (HRV) infections in children up to 5 years old and factors involved in disease severity. Nasopharyngeal aspirates from 434 children presenting a broad range of respiratory infection symptoms and severity degrees were tested for presence of HRV and 8 other respiratory viruses. Presence of host risk factors was also assessed. HRV was detected in 181 (41.7%) samples, in 107 of them as the only agent and in 74 as coinfections, mostly with respiratory syncytial virus (RSV; 43.2%). Moderate to severe symptoms were observed in 28.9% (31/107) single infections and in 51.3% (38/74) coinfections (P = .004). Multivariate analyses showed association of coinfections with lower respiratory tract symptoms and some parameters of disease severity, such as hospitalization. In coinfections, RSV was the most important virus associated with severe disease. Prematurity, cardiomyopathies, and noninfectious respiratory diseases were comorbidities that also were associated with disease severity (P = .007). Our study showed that HRV was a common pathogen of respiratory disease in children and was also involved in severe cases, causing symptoms of the lower respiratory tract. Severe disease in HRV infections were caused mainly by presence of RSV in coinfections, prematurity, congenital heart disease, and noninfectious respiratory disease.


Modified Ti3C2 nanosheets as peroxidase mimetics for use in colorimetric detection and immunoassays.
Since being discovered in 2011, a large class of two-dimensional materials, labeled MXenes, has received increased research enthusiasm both theoretically and experimentally due to the unique physical, optical and electrical properties. Here, we prepared few-layered Ti3C2 nanosheets by a facile two-step liquid exfoliation method and, for the first time, demonstrated their intrinsic peroxidase-like activity in a Ti3C2-TMB-H2O2 system. The as-produced Ti3C2 nanosheets, especially after histidine modification, were characterized with excellent water dispersibility, large specific surface area, and high stability, which contribute to their much higher affinity to both substrates when compared to HRP. We have also established the catalytic mechanism whereby Ti3C2 nanosheets, where Ti switched spontaneously from an oxidized to reduced state, promoted the electron transfer from TMB to H2O2. Given the color reaction of Ti3C2 nanosheets, we have fabricated a colorimetric paper-based sensor integrated with a smartphone to detect glucose and an immunoassay to detect IR-β, enabling Ti3C2 nanosheets to be a powerful tool in the biodetection field.


Oxidative Stress Induces E-Selectin Expression through Repression of Endothelial Transcription Factor ERG.
Oxidative stress induces a prothrombotic state through enhancement of adhesion properties of the endothelium. E-selectin, an endothelial cell adhesion molecule, becomes a therapeutic target for venous thrombosis, whereas the regulatory mechanisms of its expression have not been fully understood. In the present study, we report that H2O2 treatment increases expression of E-selectin but decreases expression of the endothelial transcription factor ETS-related gene (ERG) in HUVECs in a dose- and time-dependent manner. In BALB/c mice treated with hypochlorous acid, E-selectin expression is increased and ERG expression is decreased in endothelial cells of the brain and lung. RNA interference of ERG upregulates E-selectin expression, whereas transfection of ERG-expressing plasmid downregulates E-selectin expression in HUVECs. Knockdown or overexpression of ERG comprises H2O2-induced E-selectin expression in HUVECs. Deletion of the Erg gene in mice results in embryonic lethality at embryonic days 10.5-12.5, and E-selectin expression is increased in the Erg-/- embryos. No chromatin loop was found on the E-selectin gene or its promoter region by capture high-throughput chromosome conformation capture. Chromatin immunoprecipitation and luciferase reporter assay determined that the -127 ERG binding motif mediates ERG-repressed E-selectin promoter activity. In addition, ERG decreases H2O2-induced monocyte adhesion. Together, ERG represses the E-selectin gene transcription and inhibits oxidative stress-induced endothelial cell adhesion.


Prevalence and relationship between major depressive disorder and lung cancer: a cross-sectional study.
The aims of this study were to estimate the prevalence and examine the factors associated with major depressive disorder (MDD) in lung cancer patients. This cross-sectional study was carried out in the oncology clinic of the University Hospital, Chiang Mai University, Thailand. Patients with all stages of lung cancer were included in this study. Demographic data of eligible patients were gathered. The Mini-International Neuropsychiatric Interview, Thai version 5.0.0 was used to identify MDD. The Thai version of the Personal Health Questionnaire Depression Scale was used to assess depression severity. A total of 146 lung cancer patients from the outpatient clinic from July to December 2012 were approached. The 104 patients were included and analyzed in this study. Based on the Mini-International Neuropsychiatric Interview, 14.4% of them were defined as having MDD. Multiple linear regression analysis revealed that Chalder Fatigue Scale, Functional Assessment of Cancer Therapy - Lung, and Pittsburgh Sleep Quality Index scores were significantly correlated with MDD in lung cancer patients. The results suggest that MDD is more prevalent in lung cancer patients. In addition, fatigue, poor quality of life, and sleep disturbance may increase associated MDD. Because of the small sample size, further studies should be conducted to confirm these results.


Specific attitudes which predict psychology students' intentions to seek help for psychological distress.
Although many postgraduate psychology programs address students' mental health, there are compelling indications that earlier, undergraduate, interventions may be optimal. We investigated specific attitudes that predict students' intentions to seek treatment for psychological distress to inform targeted interventions. Psychology students (N = 289; mean age = 19.75 years) were surveyed about attitudes and intentions to seek treatment for stress, anxiety, or depression. Less than one quarter of students reported that they would be likely to seek treatment should they develop psychological distress. Attitudes that predicted help-seeking intentions related to recognition of symptoms and the benefits of professional help, and openness to treatment for emotional problems. The current study identified specific attitudes which predict help-seeking intentions in psychology students. These attitudes could be strengthened in undergraduate educational interventions promoting well-being and appropriate treatment uptake among psychology students.


Long-term follow-up of patients with invasive fungal disease who received adjunctive therapy with recombinant human macrophage colony-stimulating factor.
Mortality of bone marrow transplant (BMT) patients who develop invasive fungal infection is greater than 80%. Long-term follow-up of 46 consecutive BMT patients who received recombinant human macrophage colony-stimulating factor (rhM-CSF) as adjunctive therapy with standard antifungal treatment who were entered into phase I/II trials at The Fred Hutchinson Cancer Research Center is reported. rhM-CSF (100 micrograms/m2 to 2,000 micrograms/m2; Chiron/Cetus Corporation, Emeryville, CA) was administered from day 0 to 28 after determination of progressive fungal disease. Results of long-term follow-up of fungal infection, relapse, and survival were compared with 58 similar historical controls. Multivariable analysis of the patients who received rhM-CSF showed two factors that significantly correlated with poor survival: Karnofsky score < or = 20% and Aspergillus infection. Overall, survival of patients who received rhM-CSF was greater than that of historical patients (27% v 5%) and was entirely because of a 50% survival rate in patients with Candida infection and Karnofsky scores greater than 20%. Prospective, randomized, controlled trials to determine efficiency of rhM-CSF are indicated and should be directed at patients with invasive candidiasis.


Does diet affect breast cancer risk?
The role of specific dietary factors in breast cancer causation is not completely resolved. Results from prospective studies do not support the concept that fat intake in middle life has a major relation to breast cancer risk. However, weight gain in middle life contributes substantially to breast cancer risk. Alcohol is the best established dietary risk factor, probably by increasing endogenous estrogen levels. Hypotheses relating diet during youth to risk decades later will be difficult to test. Nevertheless, available evidence is strong that breast cancer risk can be reduced by avoiding weight gain during adult years, and by limiting alcohol consumption.


All-epiphyseal Anterior Cruciate Ligament Reconstruction Does Not Increase the Risk of Complications Compared With Pediatric Transphyseal Reconstruction.
Complication rates after physeal-sparing anterior cruciate ligament reconstruction (ACLR) are known to be high in the paediatric population compared with the adult population. However, the outcomes of these skeletally immature patients after all-epiphyseal reconstruction have not been compared with those after transphyseal reconstructions in a more similar age group. This study compares clinical outcomes and complications between all-epiphyseal and pediatric transphyseal ACLR. We retrospectively reviewed 1,056 pediatric patients undergoing primary ACLR between 2000 and 2015. Of these, 51 were excluded (5 extra-articular and 46 partial transphyseal reconstructions). Demographic data, intraoperative findings and techniques, postoperative complications (including graft rupture, contralateral anterior cruciate ligament [ACL] tear, and meniscus injuries), clearance for sports, range of motion (ROM), and isokinetic strength testing were recorded. Univariate analysis was followed by stepwise, binary logistic regressions to control for confounding factors. During the study period, 162 patients underwent all-epiphyseal reconstruction (mean age, 12.1 ± 1.8 years) and 843 underwent transphyseal ACLR (mean age, 15.8 ± 1.9 years). At the time of surgery, more meniscus tears were found in the transphyseal group (76% versus 60%; P < 0.01). These patients also had more irreparable meniscus tears requiring partial meniscectomy (35% versus 18%; P < 0.01). Overall, the rates of graft failure, contralateral ACL injury, and new meniscus tears were 10.3%, 6.1%, and 14.2%, respectively. After controlling for confounders in a multivariate model, no difference was found in these postoperative complications between all-epiphyseal and transphyseal ACLR. Furthermore, no clinically significant difference was observed in postoperative ROM or isokinetic strength testing. Skeletally immature patients undergoing all-epiphyseal ACLR had less irreparable meniscus tears than older children undergoing transphyseal reconstruction. After adjusting for age and other confounders, there was no difference in postoperative ROM or strength, nor an increased risk of graft rupture, contralateral ACL injury, or new meniscus tear in these young patients compared with older adolescents undergoing transphyseal ACLR. Level III.


Dynamics of dipoles and vortices in nonlinearly coupled three-dimensional field oscillators.
The dynamics of a pair of harmonic oscillators represented by three-dimensional fields coupled with a repulsive cubic nonlinearity is investigated through direct simulations of the respective field equations and with the help of the finite-mode Galerkin approximation (GA), which represents the two interacting fields by a superposition of 3+3 harmonic-oscillator p-wave eigenfunctions with orbital and magnetic quantum numbers l=1 and m=1, 0, -1. The system can be implemented in binary Bose-Einstein condensates, demonstrating the potential of the atomic condensates to emulate various complex modes predicted by classical field theories. First, the GA very accurately predicts a broadly degenerate set of the system's ground states in the p-wave manifold, in the form of complexes built of a dipole coaxial with another dipole or vortex, as well as complexes built of mutually orthogonal dipoles. Next, pairs of noncoaxial vortices and/or dipoles, including pairs of mutually perpendicular vortices, develop remarkably stable dynamical regimes, which feature periodic exchange of the angular momentum and periodic switching between dipoles and vortices. For a moderately strong nonlinearity, simulations of the coupled-field equations agree very well with results produced by the GA, demonstrating that the dynamics is accurately spanned by the set of six modes limited to l=1.


Beyond proteinuria: VDR activation reduces renal inflammation in experimental diabetic nephropathy.
Local inflammation is thought to contribute to the progression of diabetic nephropathy. The vitamin D receptor (VDR) activator paricalcitol has an antiproteinuric effect in human diabetic nephropathy at high doses. We have explored potential anti-inflammatory effects of VDR activator doses that do not modulate proteinuria in an experimental model of diabetic nephropathy to gain insights into potential benefits of VDR activators in those patients whose proteinuria is not decreased by this therapy. The effect of calcitriol and paricalcitol on renal function, albuminuria, and renal inflammation was explored in a rat experimental model of diabetes induced by streptozotocin. Modulation of the expression of mediators of inflammation by these drugs was explored in cultured podocytes. At the doses used, neither calcitriol nor paricalcitol significantly modified renal function or reduced albuminuria in experimental diabetes. However, both drugs reduced the total kidney mRNA expression of IL-6, monocyte chemoattractant protein (MCP)-1, and IL-18. Immunohistochemistry showed that calcitriol and paricalcitol reduced MCP-1 and IL-6 in podocytes and tubular cells as well as glomerular infiltration by macrophages, glomerular cell NF-κB activation, apoptosis, and extracellular matrix deposition. In cultured podocytes, paricalcitol and calcitriol at concentrations in the physiological and clinically significant range prevented the increase in MCP-1, IL-6, renin, and fibronectin mRNA expression and the secretion of MCP-1 to the culture media induced by high glucose. In conclusion, in experimental diabetic nephropathy VDR activation has local renal anti-inflammatory effects that can be observed even when proteinuria is not decreased. This may be ascribed to decreased inflammatory responses of intrinsic renal cells, including podocytes, to high glucose.


Toll-like receptor 3 activation decreases porcine arterivirus infection.
Porcine reproductive and respiratory syndrome virus (PRRSV) is an RNA virus that initiates infection in pulmonary alveolar macrophages (PAMs), elicits weak immune responses, and establishes a persistent infection. To understand the role of dsRNA intermediates in eliciting host immunity, we sought to determine if toll-like receptor-3 (TLR3), a well-known dsRNA sensor, is involved in the regulation of PRRSV infection. TLR3 gene expression was increased in PAMs of congenitally infected 2-wk-old pigs. Stimulation of PAMs with dsRNA increased gene expression for TLR3 and interferon-beta and suppressed PRRSV infectivity. To investigate activation and signaling parameters, expression constructs of wild-type and functional-domain-truncated porcine TLR3 were used in cell transfection studies. When cells that overexpressed porcine TLR3 were stimulated with dsRNA a rapid and robust calcium influx was induced. Moreover, ligand activation of porcine TLR3 expressed in MARC-145 cells elicited an antiviral response to PRRSV. Conversely, transfection of PAMs with small-interfering RNA targeting porcine TLR3 resulted in up to 80% suppression of TLR3 mRNA expression and an increase in PRRSV infectivity. These data provide fundamental genetic and molecular information for porcine TLR3, and implicate its involvement in PRRSV infection, findings that may suggest new strategies to limit this costly pandemic disease.


Modulation of pulvinar connectivity with cortical areas in the control of selective visual attention.
Selective attention mechanisms operate across large-scale cortical networks by amplifying behaviorally relevant sensory information while suppressing interference from distractors. Although it is known that fronto-parietal regions convey information about attentional priorities, it is unclear how such cortical communication is orchestrated. Based on its unique connectivity pattern with the cortex, we hypothesized that the pulvinar, a nucleus of the thalamus, may play a key role in coordinating and modulating remote cortical activity during selective attention. By using a visual task that orthogonally manipulated top-down selection and bottom-up competition during functional MRI, we investigated the modulations induced by task-relevant (spatial cue) and task-irrelevant but salient (distractor) stimuli on functional interactions between the pulvinar, occipito-temporal cortex, and frontoparietal areas involved in selective attention. Pulvinar activity and connectivity were distinctively modulated during the co-occurrence of the cue and salient distractor stimuli, as opposed to the presence of one of these factors alone. Causal modelling analysis further indicated that the pulvinar acted by weighting excitatory signals to cortical areas, predominantly in the presence of both the cue and the distractor. These results converge to support a pivotal role of the pulvinar in integrating top-down and bottom-up signals among distributed networks when confronted with conflicting visual stimuli, and thus contributing to shape priority maps for the guidance of attention.


Age-related changes in pancreatic elasticity: When should we be concerned about their effect on strain elastography?
Ultrasound strain elastography is one of the useful methods for evaluating pancreatic lesions. During aging, several pancreatic parenchymal changes occur that may interfere with the interpretation of the ultrasound images. We studied age-related changes in pancreatic elasticity using transabdominal ultrasound strain elastography in subjects without known pancreatic disease. This study was conducted at Nagoya University Hospital, which is an academic medical center, and included 102 subjects (66 women and 39 men) aged 20-85years (mean 58.6±17.5) who underwent transabdominal ultrasonography for screening and follow-up for non-pancreatic diseases. Strain elastography of the pancreas was performed, and the results were subjected to quantitative strain histogram analysis. The correlations of age with four elastographic parameters (Mean, Standard deviation, Skewness, and Kurtosis) and other findings, including hyperechoic pancreas, hyperechoic liver, and diabetes, were evaluated. There was a significant correlation between increasing age and elastographic parameters such as the Mean (P=0.004), Skewness (P=0.007), and Kurtosis (P=0.03), and these differences became significant after the age of 40. The prevalence of hyperechoic pancreas increased with age (P<0.001), and the Means were lower in those with hyperechoic pancreas (P=0.004) and a higher body mass index (BMI, P=0.008). No significant correlations with diabetes, hyperechoic liver, or elastographic parameters were demonstrated. Strain elastography demonstrated elastographic changes in the pancreas with aging that included a decreasing Mean and increasing Skewness and Kurtosis after the age of 40. The prevalence of pancreatic hyperechogenicity increased, and the pancreatic hyperechogenicity was significantly negatively correlated with the Mean.


Arabidopsis thaliana alternative dehydrogenases: a potential therapy for mitochondrial complex I deficiency? Perspectives and pitfalls.
Complex I (CI or NADH:ubiquinone oxidoreductase) deficiency is the most frequent cause of mitochondrial respiratory chain defect. Successful attempts to rescue CI function by introducing an exogenous NADH dehydrogenase, such as the NDI1 from Saccharomyces cerevisiae (ScNDI1), have been reported although with drawbacks related to competition with CI. In contrast to ScNDI1, which is permanently active in yeast naturally devoid of CI, plant alternative NADH dehydrogenases (NDH-2) support the oxidation of NADH only when the CI is metabolically inactive and conceivably when the concentration of matrix NADH exceeds a certain threshold. We therefore explored the feasibility of CI rescue by NDH-2 from Arabidopsis thaliana (At) in human CI defective fibroblasts. We showed that, other than ScNDI1, two different NDH-2 (AtNDA2 and AtNDB4) targeted to the mitochondria were able to rescue CI deficiency and decrease oxidative stress as indicated by a normalization of SOD activity in human CI-defective fibroblasts. We further demonstrated that when expressed in human control fibroblasts, AtNDA2 shows an affinity for NADH oxidation similar to that of CI, thus competing with CI for the oxidation of NADH as opposed to our initial hypothesis. This competition reduced the amount of ATP produced per oxygen atom reduced to water by half in control cells. In conclusion, despite their promising potential to rescue CI defects, due to a possible competition with remaining CI activity, plant NDH-2 should be regarded with caution as potential therapeutic tools for human mitochondrial diseases.


Baseline Plasma Zinc and Risk of First Stroke in Hypertensive Patients: A Nested Case-Control Study.
Background and Purpose- We aimed to examine the relation of baseline plasma zinc with the risk of first stroke and investigate any possible effect modifiers in hypertensive patients. Methods- The study population was drawn from the CSPPT (China Stroke Primary Prevention Trial), using a nested case-control design, including 599 first stroke cases and 599 matched controls. Results- Compared with participants with baseline plasma zinc <106.9 μg/dL (median), a significantly lower risk of first hemorrhagic stroke was found in those with plasma zinc ≥106.9 μg/dL (multivariate-adjusted odds ratio, 0.45; 95% CI, 0.21-0.94). Furthermore, the inverse plasma zinc-first hemorrhagic stroke association was significantly stronger in participants with body mass index ≥25.0 kg/m2 or plasma copper <100.1 μg/dL at baseline (Pinteraction <0.05 for both variables). However, there was no significant association between plasma zinc and first ischemic stroke (<103.3 versus ≥103.3 μg/dL [median]; multivariate-adjusted odds ratio, 1.16; 95% CI, 0.83-1.61). Conclusions- In this sample of hypertensive patients, we found a significant, inverse association between plasma zinc and first hemorrhagic stroke. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT00794885.


Effect of Age at Exposure on the Incidence of Lung and Mammary Cancer after Thoracic X-Ray Irradiation in Wistar Rats.
Epidemiology studies have shown that children are at greater overall risk of radiation-induced cancer, but the modifying effect of age at exposure in different tissues is heterogeneous. Early epidemiology findings of increased lung cancer risk with increasing age at the time of exposure have been dismissed, with suggestions that the trend is an artefact from a failure to adequately correct for the effects of tobacco smoking. Yet, differing models used in subsequent analyses have shown that the increased susceptibility with age, counter to the overall solid tumor trend, can either be confirmed or discounted depending on the model parameters used. In this study, we analyzed the induction of tumors in female Wistar rats exposed to increasing thoracic doses of X-ray as neonates, juveniles or young adults, to allow the effect of age at exposure in this early period to be observed in the absence of any interactions with smoking. Histology was used to compare tumor subtypes among groups, and genomic DNA copy number alterations in a number of tumors arising after irradiation at different ages were examined. Induction of lung cancers increased with radiation dose, with the frequency of early occurring lung adenomas greater in rats irradiated at older ages. At the highest dose, the rats irradiated at 5 or 15 weeks of age showed increased age-specific rates of lung adenocarcinomas in later life compared to those irradiated at 1 week of age. However, thoracic mammary gland tumors induced by the highest dose at the later ages significantly decreased the lifespan in these groups, reducing the number of rats at risk of radiation-induced lung adenocarcinoma. There was no induction of mammary tumors outside of the irradiated field. Lung adenocarcinomas showed widespread DNA copy number aberrations at the chromosome level, but the only recurrent lesions were intragenic Fhit deletions and losses on chromosome 4. The results presented here suggest that the risk of radiation-induced lung cancer after irradiation may not monotonically decrease with age, and demonstrate that increasing lung cancer risk with exposure age can be observed independent of corrections for smoking, and that mammary tumors may show a similar relationship with age.


R-ChIP Using Inactive RNase H Reveals Dynamic Coupling of R-loops with Transcriptional Pausing at Gene Promoters.
R-loop, a three-stranded RNA/DNA structure, has been linked to induced genome instability and regulated gene expression. To enable precision analysis of R-loops in vivo, we develop an RNase-H-based approach; this reveals predominant R-loop formation near gene promoters with strong G/C skew and propensity to form G-quadruplex in non-template DNA, corroborating with all biochemically established properties of R-loops. Transcription perturbation experiments further indicate that R-loop induction correlates to transcriptional pausing. Interestingly, we note that most mapped R-loops are each linked to a nearby free RNA end; by using a ribozyme to co-transcriptionally cleave nascent RNA, we demonstrate that such a free RNA end coupled with a G/C-skewed sequence is necessary and sufficient to induce R-loop. These findings provide a topological solution for RNA invasion into duplex DNA and suggest an order for R-loop initiation and elongation in an opposite direction to that previously proposed.


Hybrid Nanocomposite Films Comprising Dispersed VO2 Nanocrystals: A Scalable Aqueous-Phase Route to Thermochromic Fenestration.
Buildings consume an inordinate amount of energy, accounting for 30-40% of worldwide energy consumption. A major portion of solar radiation is transmitted directly to building interiors through windows, skylights, and glazed doors where the resulting solar heat gain necessitates increased use of air conditioning. Current technologies aimed at addressing this problem suffer from major drawbacks, including a reduction in the transmission of visible light, thereby resulting in increased use of artificial lighting. Since currently used coatings are temperature-invariant in terms of their solar heat gain modulation, they are unable to offset cold-weather heating costs that would otherwise have resulted from solar heat gain. There is considerable interest in the development of plastic fenestration elements that can dynamically modulate solar heat gain based on the external climate and are retrofittable onto existing structures. The metal-insulator transition of VO2 is accompanied by a pronounced modulation of near-infrared transmittance as a function of temperature and can potentially be harnessed for this purpose. Here, we demonstrate that a nanocomposite thin film embedded with well dispersed sub-100-nm diameter VO2 nanocrystals exhibits a combination of high visible light transmittance, effective near-infrared suppression, and onset of NIR modulation at wavelengths <800 nm. In our approach, hydrothermally grown VO2 nanocrystals with <100 nm diameters are dispersed within a methacrylic acid/ethyl acrylate copolymer after either (i) grafting of silanes to constitute an amorphous SiO2 shell or (ii) surface functionalization with perfluorinated silanes and the use of a perfluorooctanesulfonate surfactant. Homogeneous and high optical quality thin films are cast from aqueous dispersions of the pH-sensitive nanocomposites onto glass. An entirely aqueous-phase process for preparation of nanocrystals and their effective dispersion within polymeric nanocomposites allows for realization of scalable and viable plastic fenestration elements.


Growing pains: when healthcare facilities merge.
The article discusses how the loss prevention services department at a large Midwestern healthcare system was able to meet the security needs of a wide range of disparate affiliates--including a dozen hospitals, clinics, long-term care facilities, pharmacies, a home healthcare service and social service agency, and an array of support facilities.


New perspectives in cancer immunotherapy: targeting IL-6 cytokine family.
Chronic inflammation has been recognized as a canonical cancer hallmark. It is orchestrated by cytokines, which are master regulators of the tumor microenvironment (TME) as they represent the main communication bridge between cancer cells, the tumor stroma, and the immune system. Interleukin (IL)-6 represents a keystone cytokine in the link between inflammation and cancer. Many cytokines from the IL-6 family, which includes IL-6, oncostatin M, leukemia inhibitory factor, IL-11, IL-27, IL-31, ciliary neurotrophic factor, cardiotrophin 1, and cardiotrophin-like cytokine factor 1, have been shown to elicit tumor-promoting roles by modulating the TME, making them attractive therapeutic targets for cancer treatment.The development of immune checkpoint blockade (ICB) immunotherapies has radically changed the outcome of some cancers including melanoma, lung, and renal, although not without hurdles. However, ICB shows limited efficacy in other solid tumors. Recent reports support that chronic inflammation and IL-6 cytokine signaling are involved in resistance to immunotherapy. This review summarizes the available preclinical and clinical data regarding the implication of IL-6-related cytokines in regulating the immune TME and the response to ICB. Moreover, the potential clinical benefit of combining ICB with therapies targeting IL-6 cytokine members for cancer treatment is discussed.


Isoflavones as Ah Receptor Agonists in Colon-Derived Cell Lines: Structure-Activity Relationships.
Many of the protective responses observed for flavonoids in the gastrointestinal track resemble aryl hydrocarbon receptor (AhR)-mediated effects. Therefore, we examined the structure-activity relationships of isoflavones and isomeric flavone and flavanones as AhR ligands on the basis of their induction of CYP1A1, CYP1B1, and UGT1A1 gene expression in colon cancer Caco2 cells and young adult mouse colonocyte (YAMC) cells. Caco2 cells were significantly more Ah-responsive than YAMC cells, and this was due, in part, to flavonoid-induced cytotoxicity in the latter cell lines. The structure-activity relationships for the flavonoids were complex and both response and cell context specific; however, there was significant variability in the AhR activities of the isomeric substituted isoflavones and flavones. For example, 4',5,7-trihydroxyisoflavone (genistein) was AhR-inactive whereas 4',5,7-trihydroxyflavone (apigenin) induced CYP1A1, CYP1B1, and UGT1A1 in Caco2 cells. In contrast, both 5,7-dihydroxy-4-methoxy substituted isoflavone (biochanin A) and flavone (acacetin) induced all three AhR-responsive genes; 4',5,7-trimethoxyisoflavone was a potent AhR agonist, and the isomeric flavone was AhR-inactive. These results coupled with simulation studies modeling flavonoid interaction within the AhR binding pocket demonstrate that the orientation of the substituted phenyl ring at C-2 (flavones) or C-3 (isoflavones) on the common 4-H-chromen-4-one ring strongly influences the activities of isoflavones and flavones as AhR agonists.


Sterilization matters: consequences of different sterilization techniques on gold nanoparticles.
Nanoparticles (NPs) can offer many advantages over traditional drug design and delivery, as well as toward medical diagnostics. As with any medical device or pharmaceutical drug intended to be used for in vivo biomedical applications, NPs must be sterile. However, very little is known regarding the effect of sterilization methods on the intrinsic properties and stability of NPs. Herein a detailed analysis of physicochemical properties of two types of AuNPs upon sterilization by means of five different techniques is reported. In addition, cell viability and production of reactive oxygen species are studied. The results indicate that sterilization by ethylene oxide seems to be the most appropriate technique for both types of NPs. It is concluded that it is crucial to test several methods in order to establish the specific type of sterilization to be performed for each particular NP.


A prospective cohort study of disability pension due to mental diagnoses: the importance of health factors and behaviors.
Previous studies have found associations between various health factors and behaviors and mental disorders. However, knowledge of such associations with disability pension (DP) due to mental diagnoses is scarce. Moreover, the influence of familial factors (genetics and family background) on the associations are mainly unknown. The aim of the study was to investigate associations between health factors and behaviors and future DP due to mental diagnoses in a twin cohort, accounting for familial confounding. A prospective cohort study of Swedish twins (N=28 613), including survey data and national register data on DP and other background factors was conducted. Cox proportional hazards regression models were used to calculate hazard ratios (HR) with 95% confidence intervals (CI) for the whole twin cohort, and for discordant twin pairs. During follow-up 1998-2008 (median 10 years), 2.2% of the cohort was granted a DP with a mental diagnosis. In the fully adjusted analyses of the whole cohort, the associations of poor or moderate self-rated health (SRH), under- or overweight, former or current tobacco use, or being an abstainer from alcohol were significantly associated with risk of DP due to mental diagnoses. Analyses of discordant twin pairs confirmed all these associations, except for current tobacco use, being independent from familial confounding. Exclusion of individuals with current or previous depression or anxiety at baseline did not influence the associations found. Poor or moderate SRH, under- or overweight, former tobacco use or being an abstainer from alcohol seem to be strong direct predictors of DP due to mental diagnoses, independently of several confounders of this study, including familial factors.


Placental production of progestins is fully effective in villous cytotrophoblasts and increases with the syncytiotrophoblast formation.
Placental syncytiotrophoblast (ST) is considered as the main placental endocrine tissue secreting progesterone, a steroid essential for maintenance of pregnancy. However, each step of progestins production has been poorly investigated in villous cytotrophoblast (VCT) regarding ST formation. We aimed to characterize progestins production during human differentiation of VCT into ST. VCTs were isolated from term placenta and cultivated, with or without forskolin (FSK), to stimulate trophoblast differentiation. Secreted progestins concentrations were determined by immuno-assay and Gas Chromatography-tandem mass spectrometry. Intracellular expression of cholesterol transporter and enzymes involved in steroidogenesis were studied by immunofluorescence, western-blot, and RT-qPCR. Progesterone and pregnenolone are produced by VCT and their secretion increases with VCT differentiation while 17-hydroxyprogesterone concentration remains undetectable. HSD3B1 enzyme expression increases whereas MLN64, the cholesterol placental mitochondrial transporter and P450SCC expressions do not. FSK induces progestins production. Progestins placental synthesis is effective since VCT and increases with ST formation thanks to mitochondria.


Maternal diabetes and neonatal macrosomia. Dynamic skinfold thickness measurements.
Skinfold thickness measurements were obtained in 206 neonates of nondiabetic mothers and 98 neonates of diabetic mothers within 28 hours of birth. Birthweights ranged from 680 to 5530 gm and gestational ages ranged from 25 to 46 weeks. Skinfold thickness measured 60 seconds after application of a Harpenden caliper correlated linearly with birthweight both for infants of nondiabetics mothers (r = 0.86 at the midtricipital site and 0.81 at the subscapular site) and for infants of diabetic mothers (r = 0.58 and 0.63). The slopes of the regression line for infants of diabetic and nondiabetic mothers were identical, but the y-intercept was higher for infants of diabetic mothers. Thus, at any given birthweight, infants of diabetic mothers appeared to have more subcutaneous fat. Dynamic skinfold thickness measurements were obtained in 75 neonates of nondiabetic mothers and 29 neonates of diabetic mothers with a Harpenden caliper connected to a chart recorder. The mean magnitude and rate of decline of skinfold thickness measurement during the 60 seconds after application of the caliper were affected neither by the presence of maternal diabetes nor by the degree of intrauterine growth of the neonates. These data suggest that neonatal macrosomia and maternal diabetes do not affect the amount of subcutaneous interstitial water.


Profiling gene expression ratios of paired cancerous and normal tissue predicts relapse of esophageal squamous cell carcinoma.
Esophageal squamous cell carcinoma has heterogeneous clinical outcomes that cannot be predicted well using any existing clinical or molecular prognostic factors. Gene expression profiling may enable more precise prediction of the clinical outcome of these patients. We developed a new approach using gene expression ratios of paired cancerous and normal tissue specimens from the same patient to reduce the effects of variation among individuals. Using oligonucleotide microarrays, we analyzed total RNA expression levels corresponding to 12,600 transcript sequences in 24 paired cancerous and normal tissue operative specimens from 12 patients with esophageal squamous cell carcinoma. Hierarchical clustering analysis using gene expression ratios (cancer:normal) divided the 12 patients into two groups; all 7 patients in the first cluster survived without relapse (median follow-up, 483 days), whereas all 5 patients in the second cluster relapsed (median relapse-free survival time, 280 days; log-rank test, P = 0.006). In contrast, clustering either with cancerous tissue alone or with normal tissue alone did not show significant differences in the outcomes. The expressions of a variety of genes related with cell cycle, gene-repair, apoptosis and chemoradiotherpay resistance were up-regulated in the poor prognostic cluster. These results suggest that ratios of paired gene expression profiles may more efficiently predict relapse-free survival of esophageal squamous cell carcinoma than existing prognostic factors or than gene expression profiling with cancerous tissue alone.


Four-year follow-up of the community intervention '10,000 steps Ghent'.
The purpose of this study was to examine the 4-year follow-up effects of the '10,000 steps Ghent' project, which had shown increases in pedometer steps after the first year of implementation (2005-06). All adults who had participated in 2005-06 (n = 866) were recontacted in 2009 and invited to complete the International Physical Activity Questionnaire and a 7-day pedometer log. Long-term effects were analysed using repeated measures analysis of variance tests (time × community, n = 420). In subgroup analyses, age, gender, educational level, employment status, health and risk profile were also included. Results showed that daily step counts increased slightly from 2005 to 2009 in the intervention community (Ghent) and decreased in the comparison community (Aalst) (time × community: P = 0.008). Subgroup analyses showed a positive interaction effect for higher educated (P = 0.026) and healthy (P = 0.005) participants and a negative interaction for those with a poor to moderate health (P = 0.026). For self-reported physical activity, a positive interaction effect was found in those who had already reached 10,000 steps in 2005 (P = 0.037). To conclude, the positive effects seen after 1 year were not maintained after 4 years. However, a decrease from baseline to follow-up, which was seen in the comparison community, was prevented in all Ghent participants, except those with a poor to moderate health.


[Jan Ewangelista Purkynie in medicine, science and the Polish culture].
The author refers to the place of Jan Ewangelista Purkynie (1787-1868) in the world science and the Czech national culture. Numerous discoveries of Purkynie have still bear his name, e.g. fibers of the hearth conduction system. In the years 1823-1850 he worked as professor of the Department of Physiology in Wrocław and he distinguished himself as a scientist of wide horizons and modern ideas, as well as a teacher and protector of his students. The periodical Opera Omnia that has been published in Prague from 1938 (until now 13 volumes have been published) in volume number six, known as the Wroclaw volume, offers to us works of Purkynie's fourteen doctoral students. One of the them was Bogusław Palicki (1813-1868), author of the doctoral thesis entitled De musculari cordic structura. In 1839 the "Rocznik Wydziału Lekarskiego w Uniwersytecie Jagiellońiskim" /Yearbook of the Jagiellonian University Faculty of Medicine/ published a work describing the fibers of the conductions system of the heart which anticipated a similar work in German. Purkynie had numerous contacts with the liberal Krakow, he visited the health resort in Cieplice where he met Wincenty Pol and Kornel Ujejski. His contacts with Poznański had both scientific and literary character. He was also in touch with Warsaw and the Congress Kingdom. There are also traces of his contacts with the Polish emigration in Paris, which had an interdisciplinary character. The scientific ideas of Purkynie have still been a source of inspiration for Czech and Polish scientists which is confirmed by numerous symposiums and congresses dedicated to him.


Murine cytomegalovirus stimulates natural killer cell function but kills genetically resistant mice treated with radioactive strontium.
Treatment of C3H/St mice with 100 microCi of 89Sr weakened their genetic resistance to murine cytomegalovirus (MCMV) infection. The criteria utilized to detect increased susceptibility were: (i) survival of mice; (ii) numbers of MCMV-infected cells in the spleens and liver; and (iii) serum glutamic pyruvic transaminase levels. The natural killer (NK) cell activity of spleen cells from mice treated with 89Sr is very low. However, the NK activities of spleen cells of both normal and 89Sr-treated mice were greatly augmented 3 days after infection with MCMV. These NK cells lysed a variety of tumor cells and shared several features with conventional NK cells, but were not lysed by anti-Nk-1.2 serum (specific for NK cells) plus complement. Splenic adherent cells did not lyse tumor cells themselves but were necessary for the stimulation of NK cells by MCMV. The paradox of high NK cell function and poor survival in 89Sr-treated mice infected with MCMV was a surprise. We conclude that these augmented NK cells, of themselves, cannot account for the genetic resistance of C3H/St mice to infection with MCMV.


Redox artifacts in electrophysiological recordings.
Electrophysiological techniques make use of Ag/AgCl electrodes that are in direct contact with cells or bath. In the bath, electrodes are exposed to numerous experimental conditions and chemical reagents that can modify electrode voltage. We examined voltage offsets created in Ag/AgCl electrodes by exposure to redox reagents used in electrophysiological studies. Voltage offsets were measured in reference to an electrode separated from the solution by an agar bridge. The reducing reagents Tris-2-carboxyethly-phosphine, dithiothreitol (DTT), and glutathione, as well as the oxidizing agent H(2)O(2) used at experimentally relevant concentrations reacted with Ag in the electrodes to produce voltage offsets. Chloride ions and strong acids and bases produced offsets at millimolar concentrations. Electrolytic depletion of the AgCl layer, to replicate voltage clamp and sustained use, resulted in increased sensitivity to flow and DTT. Offsets were sensitive to electrode silver purity and to the amount and method of chloride deposition. For example, exposure to 10 μM DTT produced a voltage offset between 10 and 284 mV depending on the chloride deposition method. Currents generated by these offsets are significant and dependent on membrane conductance and by extension the expression of ion channels and may therefore appear to be biological in origin. These data demonstrate a new source of artifacts in electrophysiological recordings that can affect measurements obtained from a variety of experimental techniques from patch clamp to two-electrode voltage clamp.


Association between interleukin-8 gene alleles and human susceptibility to tuberculosis disease.
Interleukin (IL)-8 is involved in the pathogenesis of human tuberculosis (TB). However, the contribution of polymorphisms of the IL-8 gene and its receptor genes CXCR-1 and CXCR-2 to human TB susceptibility remains untested. In a case-control study, white subjects with TB disease were more likely to be homozygous for the IL-8 -251A allele, compared with control subjects (odds ratio [OR], 3.41; 95% confidence interval [CI], 1.52-7.64). African Americans with TB also showed an increased odds of being homozygous for this allele (OR, 3.46; 95% CI, 1.48-8.08). To exclude population artifacts in the case-control study, a separate analysis that used a transmission-disequilibrium test with 76 informative families confirmed that the IL-8 -251A allele was preferentially transmitted to TB-infected children (P=.02). CXCR-1 and CXCR-2 did not demonstrate significant associations with TB susceptibility. These data suggest that IL-8 is important in the genetic control of human TB susceptibility.


Assignment of genes encoding dihydrofolate reductase and hexosaminidase B to Mus musculus chromosome 13.
The murine gene encoding dihydrofolate reductase (DHFR) has been localized to a particular mouse chromosome by complementation mapping. Microcells prepared from diploid mouse fibroblasts were fused with mutant hamster cells lacking the dihydrofolate reductase gene (Dhfr), and DHFR+ microcell hybrids were selected in medium lacking purines and pyrimidines. The complemented hybrids expressed wild-type levels of DHFR enzyme activity, and selectively retained a single mouse chromosome--chromosome 13. Genomic Southern blots of DNAs prepared from these hybrids and from an independently derived collection of clones isolated without selection on the DHFR phenotype confirmed the assignment of murine Dhfr gene sequences to chromosome 13. This assignment provides further evidence for the existence of genetic homology between regions of mouse chromosome 13 and human chromosome 5. In support of this view, we show that the gene encoding hexosamindase B, a chromosome 5 marker in man, also maps to mouse chromosome 13.


Give spontaneity and self-discovery a chance in ASD: spontaneous peripheral limb variability as a proxy to evoke centrally driven intentional acts.
Autism can be conceived as an adaptive biological response to an early unexpected developmental change. Under such conceptualization one could think of emerging biological compensatory mechanisms with unique manifestations in each individual. Within a large group of affected people this would result in a highly heterogeneous spectral disorder where it would be difficult to tap into the hidden potentials of any given individual. A pressing question is how to treat the disorder while harnessing the capabilities and predispositions that the individual has already developed. It would indeed be ideal to use such strengths to accelerate the learning of self-sufficiency and independence, important as the person transitions into adulthood. In this report, we introduce a new concept for therapeutic interventions and basic research in autism. We use visuo-spatial and auditory stimuli to help augment the physical reality of the child and sensory-substitute corrupted kinesthetic information quantified in his/her movement patterns to help the person develop volitional control over the hand motions. We develop a co-adaptive child-computer interface that closes the sensory-motor feedback loops by alerting the child of a cause-effect relationship between the statistics of his/her real-time hand movement patterns and those of external media states. By co-adapting the statistics of the media states and those of the child's real-time hand movements, we found that without any food/token reward the children naturally remained engaged in the task. Even in the absence of practice, the learning gains were retained, transferred and improved 2-4 weeks later. This new concept demonstrates that individuals with autism do have spontaneous sensory-motor adaptive capabilities. When led to their self-discovery, these patterns of spontaneous behavioral variability (SBV) morph into more predictive and reliable intentional actions. These can unlock and enhance exploratory behavior and autonomy in the individual with autism spectrum disorders (ASD).


Gabapentin in the Management of Pain following Tonsillectomy: A Randomized Double-Blind Placebo-Controlled Trial.
Objective To determine if a single dose of oral gabapentin given prior to tonsillectomy decreases postoperative morbidity. Study Design Prospective randomized double-blind placebo-controlled trial. Setting Southern District Health Board University Hospitals, New Zealand, over a 10-month period. Subjects and Methods Seventy-three adults undergoing tonsillectomy were randomized to receive either a single preoperative dose of oral gabapentin (600 mg) or placebo. A standard analgesic protocol was prescribed for 14 postoperative days. The primary outcome was a patient-assigned visual analog scale pain score during rest and swallow; secondary outcomes were analgesic consumption, nausea, vomiting, and return to normal diet and activities. Complications and adverse effects were also recorded. Results Thirty-seven participants were allocated to the placebo group and 36 to the gabapentin group. After withdrawals, data were analyzed from 31 in the placebo group and 27 in the gabapentin group. Pain scores between groups were not significantly different within the first 6 hours. The gabapentin group recorded significantly higher pain scores between days 5 and 10 (maximal difference, day 8: 17.6 mm; effect size, -8.87; P = .03; 95% CI, -16.883 to -0.865). There was no significant difference in swallow pain scores or early postoperative fentanyl consumption. Consumption of paracetamol ( P = .01 at day 13 and P = .004 at day 14) and codeine ( P < .05 at days 3-5, 7, 8, 10, 14) was higher in the gabapentin group. No significant difference between groups was found for the other outcomes. Conclusions Preemptive gabapentin (600 mg) was associated with greater postoperative pain scores and analgesic consumption following adult tonsillectomy when compared with placebo.


Intracellular Photoactivation of Caspase-3 by Molecular Glues for Spatiotemporal Apoptosis Induction.
Caspase-3 (Casp-3) is an enzyme that efficiently induces apoptosis, a form of programmed cell death. We report a dendritic molecular glue PCGlue that enables intracellular delivery of Casp-3 and its photoactivation. PCGlue carrying multiple guanidinium (Gu+) ion pendants via photocleavable linkages can tightly adhere to Casp-3 and deliver it into the cytoplasm mainly by direct penetration through the plasma membrane. Casp-3, whose surface is covered by PCGlue, is unable to interact with its cellular substrates and can therefore not induce apoptosis. However, upon exposure to UV or two-photon near-infrared (NIR) light, PCGlue is cleaved off to liberate Casp-3, triggering the apoptotic signaling cascade. This intracellular photoactivation of Casp-3 allows spatiotemporal induction of apoptosis in irradiated cells.


Insights into protein structure using cryogenic light microscopy.
Fluorescence microscopy has witnessed many clever innovations in the last two decades, leading to new methods such as structured illumination and super-resolution microscopies. The attainable resolution in biological samples is, however, ultimately limited by residual motion within the sample or in the microscope setup. Thus, such experiments are typically performed on chemically fixed samples. Cryogenic light microscopy (Cryo-LM) has been investigated as an alternative, drawing on various preservation techniques developed for cryogenic electron microscopy (Cryo-EM). Moreover, this approach offers a powerful platform for correlative microscopy. Another key advantage of Cryo-LM is the strong reduction in photobleaching at low temperatures, facilitating the collection of orders of magnitude more photons from a single fluorophore. This results in much higher localization precision, leading to Angstrom resolution. In this review, we discuss the general development and progress of Cryo-LM with an emphasis on its application in harnessing structural information on proteins and protein complexes.


Plasmonics nanoprobes: detection of single-nucleotide polymorphisms in the breast cancer BRCA1 gene.
This paper describes the application of plasmonics-based nanoprobes that combine the modulation of the plasmonics effect to change the surface-enhanced Raman scattering (SERS) of a Raman label and the specificity of a DNA hairpin loop sequence to recognize and discriminate a variety of molecular target sequences. Hybridization with target DNA opens the hairpin and physically separates the Raman label from the metal nanoparticle thus reducing the plasmonics effect and quenching the SERS signal of the label. We have successfully demonstrated the specificity and selectivity of the nanoprobes in the detection of a single-nucleotide polymorphism (SNP) in the breast cancer BRCA1 gene in a homogenous solution at room temperature. In addition, the potential application of plasmonics nanoprobes for quantitative DNA diagnostic testing is discussed.


A comparison between radiographic and sonographic assessment of hand and wrist bones for the estimation of skeletal age in the child patient.
The purpose of this study was to examine, with a sonographic investigation, the hand and wrist bones of a group of young patients and to compare the results with those obtained with a classical radiographic assessment. Some 25 subjects, 9-18 years of age, who presented problems concerning their short stature or precocious puberty, were evaluated. Each subject was examined by a standard radiographic assessment and by a sonographic investigation with real-time imaging. Sonographic examination was performed on the metacarpus-phalanx articulation of the first finger in order to locate the sesamoid bone. Sonographic examination was also performed on the second and third phalanxes of the third finger and on the distal portion of the radius to evaluate the characteristics of growth cartilage in the area. In all the cases where a sesamoid bone was present, this was correctly identified by the sonogram, even up to the initial appearance of its ossification nucleus. Sensitivity, specificity, and diagnostic accuracy were all 100%. The capping phenomenon seen in radiographs was not detected by sonographic investigation in any of the cases. Sonographic evaluation of the fertile cartilage of the third finger distal phalanx demonstrated a sensitivity of 89%, a specificity of 100% and a diagnostic accuracy of 92%. Sonographic evaluation of the radius cartilage showed a sensitivity of 95%, a specificity of 100% and a diagnostic accuracy of 96%. Sonographic evaluation of hand and wrist bones cannot accurately reproduce the results of the classical radiographic evaluation. However, the sonographic investigation may be useful, when integrated in a radiographic investigation.


Yersinia enterocolitica in milk and dairy products.
Yersinia enterocolitica was first recognized during the 1960's as an important human enteropathogen. The species as later redefined includes both pathogenic and nonpathogenic forms. Pathogenic strains that retain the virulence plasmid can be identified in several animal models and four indirect tests (calcium dependency, autoagglutination, Congo red uptake, serological detection of outer membrane antigen) and by tissue culture assay, serotype, and biotype. Y. enterocolitica and related bacteria have frequently been isolated from raw milk, but none of the isolates, with the possible exception of serotype 05,27, are recognizable as pathogens. Under normal circumstances Y. enterocolitica does not survive pasteurization. If introduced into pasteurized milk, it can grow well at refrigeration temperatures. Two outbreaks of yersiniosis have occurred that involved pasteurized milk. Pigs, which frequently carry pathogenic Y. enterocolitica in their throat, were the probable source in one of these outbreaks. The most rapid enrichment procedure available for isolation of Y. enterocolitica requires 6 d. No isolation method is available for selective isolation of pathogenic Y. enterocolitica in the presence of related bacteria common in milk and other foods.


[The importance of modern research methods with the use photo- and video-documentation used in phoniatric cabinets based at cultural institutions].
The modern equipment extensively used at present in phoniatric cabinets based at cultural institutions makes it possible visualize the laryngoscopic and laryngostroboscopic features of singers in a variety of situations with the help of videorecording and photographic methods. The objective changes in the larynx revealed by these methods are not necessarily accompanied by complaints of the patients. However, they provide materials for a deeper insight into different forms of phoniatric pathology, create a basis for the revision of the popular views and the development of alternative approaches to the correction of the emerging disturbances. Archivation of these data are of great importance for resolving debatable problems, supporting expert opinions, and addressing issues arising in the course of scientific research. The demonstration of the changes recorded by photo- and video-techniques to the examined singers may be helpful in the work with musicians designed to improve their compliance with the recommendations concerning voice hygiene and treatment of diseases of the vocal apparatus.


Multivariate analysis of factors affecting the immunogenicity of trivalent inactivated influenza vaccine in school-age children.
We examined factors affecting the immunogenicity of trivalent inactivated influenza vaccination (TIV) in children using the antibody titres of children participating in a Hong Kong community-based study. Antibody titres of strains included in the 2009-2010 northern hemisphere TIV [seasonal A(H1N1), seasonal A(H3N2) and B (Victoria lineage)] and those not included in the TIV [2009 pandemic A(H1N1) and B (Yamagata lineage)] were measured by haemagglutination inhibition immediately before and 1 month after vaccination. Multivariate regression models were fitted in a Bayesian framework to characterize the distribution of changes in antibody titres following vaccination. Statistically significant rises in geometric mean antibody titres were observed against all strains, with a wide variety of standard deviations and correlations in rises observed, with the influenza type B antibodies showing more variability than the type A antibodies. The dynamics of antibody titres after vaccination can be used in more complex models of antibody dynamics in populations.


[Taste aversions in the ontogeny of the rat].
The characteristics of acquisition and extinction of conditioned taste aversion (CTA) were studied in rats of both sexes and various ages by pairing of saccharin solution consumption with discomfort (LiCl intoxication, rotation). Pairing of saccharin consumption with LiCl in adult rats led to acquisition of CTA, more profound in male rats than in female ones. In rats of both sexes 30 days old, a profound CTA, comparable in intensity with CTA of adult male rats was acquired. In 2 months after acquisition of CTA in adult rats its magnitude did not change, while in rats of the junior group which by that time had reached puberty, CTA was reduced in females and did not change in males. Pairing of saccharin intake and rotation led to acquisition of CTA only in rats 30 days old. The role of external factors in duration of retention of CTA acquired by pairing of saccharin solution consumption with LiCl injection was studied in male and female rats 1 and 3.5 months old. In all cases CTA was extinguished much sooner in home cages than in experimental chambers, and in the elder group sex dimorphism was found: in both situations CTA disappeared sooner in female rats. The obtained data allow to suggest modulating influences of hormonal background and of contextual stimuli on CTA acquisition and retention.


Atrial flutter after coronary artery bypass grafting: proposed mechanism as illuminated by independent predictors.
The aim of this study was to evaluate the cause and treatment of atrial flutter after coronary artery bypass grafting (CABG). Between July 1999 and July 2000, 96 CABGs were performed at the Cardiovascular Center of Aichi Prefectural Owari Hospital. We compared two groups of patients: those with atrial flutter after CABG (group A) and those without atrial flutter (group B). We treated the atrial flutter group with medication, electrical defibrillation, and overdrive pacing. Six of these cases later required radiofrequency catheter ablation (RFCA). These were all with common-type atrial flutter, treated by RFCA for the posterior isthmus, without difficulty. The frequency of direct cannulation to the coronary sinus for retrograde cardioplegia was significantly higher in group A. Incidence of atrial flutter after CABG was influenced by surgical damage arising from direct cannulation to the coronary sinus for retrograde cardioplegia. Preoperative viability of the myocardium (in addition to good myocardial protection during surgery) also seems to be associated with an increased likelihood of postoperative atrial flutter.


Diagnosis and treatment of Sagliker syndrome: a case series from Iran.
Sagliker syndrome was introduced in 2004 in patients with end-stage renal disease and severe secondary hyperparathyroidism. This syndrome describes maxillary and mandibular deformities, dental abnormalities, benign soft tissue tumors in mouth, and various kinds of skeletal changes including short stature and fingertip abnormalities. There are a few reports from different regions of the world. The aim of this study is to report 5 cases of the Sagliker syndrome from Iran.


Spatio-temporal and -spectral coupling of shaped laser pulses in a focusing geometry.
The spatio-temporal coupling of shaped laser pulses is measured using scanning SEA TADPOLE as a function of propagation distance through the focal region of a plano-convex lens. A double pulse sequence is measured to have a gradually changing spectral phase across the beam front as a function of propagation distance. When a sinusoidal spectral phase is applied to the shaper a saw-tooth spectral amplitude is measured across the beam front before and after the focal plane of the lens. The measured spatio-spectral phase and amplitude for these two common pulse shapes are consistent with the predictions of a theoretical model.


The glutathione peroxidases.
There are several proteins in mammalian cells that can metabolize hydrogen peroxide and lipid hydroperoxides. These proteins include four selenium-containing glutathione peroxidases that are found in different cell fractions and tissues of the body. This review considers the structure and distribution of the selenoperoxidases and how this relates to their biological function. The functions of the selenoperoxidases were originally studied in systems where their activity was manipulated by changing dietary selenium levels. More recently, molecular techniques have allowed overexpression of selenoperoxidases in cell lines and animals. Additionally, cellular glutathione peroxidase knockout mice have been used to investigate the functions of this protein. From this work it is clear that the selenoperoxidases are involved in cell antioxidant systems. However, they also have more subtle functions in ensuring the regulation and formation of arachadonic acid metabolites that are derived from hydroperoxide intermediates. The range of biological processes, which are potentially dependent on optimal selenoperoxidase activity in mammals, emphasises the importance of achieving adequate selenium intake in the diet.


Archaeological mitogenomes illuminate the historical ecology of sea otters (Enhydra lutris) and the viability of reintroduction.
Genetic analyses are an important contribution to wildlife reintroductions, particularly in the modern context of extirpations and ecological destruction. To address the complex historical ecology of the sea otter (Enhydra lutris) and its failed 1970s reintroduction to coastal Oregon, we compared mitochondrial genomes of pre-extirpation Oregon sea otters to extant and historical populations across the range. We sequenced, to our knowledge, the first complete ancient mitogenomes from archaeological Oregon sea otter dentine and historical sea otter dental calculus. Archaeological Oregon sea otters (n = 20) represent 10 haplotypes, which cluster with haplotypes from Alaska, Washington and British Columbia, and exhibit a clear division from California haplotypes. Our results suggest that extant northern populations are appropriate for future reintroduction efforts. This project demonstrates the feasibility of mitogenome capture and sequencing from non-human dental calculus and the diverse applications of ancient DNA analyses to pressing ecological and conservation topics and the management of at-risk/extirpated species.


Toxicity of amorphigenin from the seeds of Amorpha fruticosa against the larvae of Culex pipiens pallens (Diptera: Culicidae).
The larvicidal activity of the crude petroleum ether, ethyl acetate, acetone, chloroform and ethanol extracts of Amorpha fruticosa seeds was individually assayed for toxicity against the early fourth-instar larva of the mosquito, Culex pipiens pallens after 24 h exposure. Of the tested extracts, the ethanol one exhibited the highest larvicidal activity (LC50 = 22.69 mg/L). Amorphigenin (8'-hydroxyrotenone), a rotenoid compound which exhibits a strong larvicidal activity with LC50 and LC90 values of 4.29 and 11.27 mg/L, respectively, was isolated from the ethanol extract by column chromatograpy. Its structure was elucidated by 1H-NMR, UV and IR spectral data. Furthermore, investigation of amorphigenin's effects on mitochondrial complex I activity and protein synthesis in C. pipiens pallens larvae reveals that amorphigenin decreases mitochondrial complex I activities to 65.73% at 10.45 μmol/L, compared to the control, when NADH were used as the substrate. Meanwhile, amorphigenin at 10.45 μmol/L also caused a 1.98-fold decrease in protein content, compared to the control larvae treated with acetone only.


Temporal dynamics of gene expression in the lung in a baboon model of E. coli sepsis.
Bacterial invasion during sepsis induces disregulated systemic responses that could lead to fatal lung failure. The purpose of this study was to relate the temporal dynamics of gene expression to the pathophysiological changes in the lung during the first and second stages of E. coli sepsis in baboons. Using human oligonucleotide microarrays, we have explored the temporal changes of gene expression in the lung of baboons challenged with sublethal doses of E. coli. Temporal expression pattern and biological significance of the differentially expressed genes were explored using clustering and pathway analysis software. Expression of selected genes was validated by real-time PCR. Cytokine levels in tissue and plasma were assayed by multiplex ELISA. Changes in lung ultrastructure were visualized by electron microscopy. We found that genes involved in primary inflammation, innate immune response, and apoptosis peaked at 2 hrs. Inflammatory and immune response genes that function in the stimulation of monocytes, natural killer and T-cells, and in the modulation of cell adhesion peaked at 8 hrs, while genes involved in wound healing and functional recovery were upregulated at 24 hrs. The analysis of gene expression modulation in response to sepsis provides the baseline information that is crucial for the understanding of the pathophysiology of systemic inflammation and may facilitate the development of future approaches for sepsis therapy.


The identification of contributory mechanisms for the development and progression of congestive heart failure in animal models.
Congestive heart failure is a clinical syndrome which results from left ventricular pump dysfunction. Animal models of congestive heart failure have been developed to better understand the complex mechanisms which contribute to the clinical syndrome of heart failure. The species and lesions used to create chronic left ventricular dysfunction in animals are as varied as the etiologic factors which cause congestive heart failure in human beings. However, a central issue to the animal models of congestive heart failure is how closely they mimic the human syndrome of congestive heart failure. The findings derived from the study of an animal model of left ventricular dysfunction should be carefully interpreted, keeping in mind the complexity of the human disease process. With careful interpretation of the results, important insights into the pathogenesis of congestive heart failure in patients can be realized. For example, the rat coronary artery ligation model provided fundamental information on the role of the angiotensin-converting enzyme system on left ventricular function and survival. Chronic pressure and volume overload, as well as rate overdrive (rapid pacing), models have provided temporal and mechanistic information on left ventricular remodeling and the transition to left ventricular dysfunction and, subsequently, congestive heart failure. Preclinical studies using animal models of heart failure are needed to investigate the effects of pharmacologic interventions in the progression of congestive heart failure. Animal models which have been produced with specific gene product deletions or over-expression will increase our ability to identify potential contributory mechanisms for the progression of left ventricular dysfunction. Animal models of congestive heart failure are clearly helpful to define the mechanisms responsible for this syndrome and to develop effective strategies to slow or better reverse its progress.


Unilateral absence of the vas deferens. A useful clinical sign.
The vas deferens is infrequently palpated at the time of routine physical examination or even during examination of the scrotum. Its absence, especially unilaterally, has been associated both clinically and at the time of autopsy with ipsilateral renal anomalies, especially agenesis. Twenty-six patients with unilateral agenesis of the vas deferens were examined for the presence of an ipsilateral renal unit; 25 patients were examined by intravenous pyelography and one by bone scan. Twenty-two patients were missing the ipsilateral renal unit. Contralateral abnormalities occurred in seven (33%) of these 22 patients also. The absence of the vas deferens is a significant anomaly, and examination for the presence of the ipsilateral renal unit is mandatory.


Combination of antisense oligonucleotide and low-dose chemotherapy in hematological malignancies.
Current conventional chemotherapy for the treatment of hematological malignancies, although quite effective, has associated toxicities to normal tissue and organs, which is still a major dose limiting factor. In addition, high dose chemotherapy followed by autologous stem cell transplantation is limited by tumor cell contamination in the stem cell harvest. The use of conventional chemotherapy alone to purge these tumor cell contaminants is known to damage normal hematopoietic progenitor cells, resulting in delayed engraftment. The combination of antisense oligodeoxynucleotides (ODN) and low doses of chemotherapy offer a potential regiment which may lower the doses of conventional therapeutics required to effectively combat disease, thus lowering cytotoxicity experienced by normal cells. Transient downregulation of genes by ODN treatment, which are involved in the transformation or perpetuation of the cancerous disease state, can remove the growth and survival advantages exploited by tumor cells. Many groups are currently investigating this combination and have produced intriguing results. This review article discusses the current research investigating the combination of antisense ODN therapy with conventional chemotherapy in the treatment of hematological malignancies. Although further improvements in this strategy are required, the results thus far support a future for this strategy in clinical management of hematological malignancy.


A right to health care.
What does it mean to say that there is a right to health care? Health care is part of a cooperative project that organizes finite resources. How are these resources to be distributed? This essay discusses three rival theories. The first two, a utilitarian theory and an interst theory, are both instrumental, in that they collapse rights to good states of affairs. A third theory, offered by Thomas Pogge, locates the question within an institutional legal context and distinguishes between a right to health care that results in claimable duties and other dimensions of health policy that do not. Pogge's argument relies on a list of "basic needs," which itself, however, relies on some kind of instrumental reasoning. The essay offers a reconstruction of Pogge's argument to bring it in line with a political conception of a right to health care. Health is a matter of equal liberty and equal citizenship, given our common human vulnerability. If we are to live as equal members in a political community, then our institutions need to create processes by which we are protected from the kinds of suffering that would make it impossible for us to live as equal members.


Surface-emitting distributed feedback terahertz quantum-cascade lasers in metal-metal waveguides.
Single-mode surface-emitting distributed feedback terahertz quantum-cascade lasers operating around 2.9 THz are developed in metal-metal waveguides. A combination of techniques including precise control of phase of reflection at the facets, and use of metal on the sidewalls to eliminate higher-order lateral modes allow robust single-mode operation over a range of approximately 0.35 THz. Single-lobed far-field radiation pattern is obtained using a pi phase-shift in center of the second-order Bragg grating. A grating device operating at 2.93 THz lased up to 149 K in pulsed mode and a temperature tuning of 19.7 GHz was observed from 5 K to 147 K. The same device lased up to 78 K in continuous-wave (cw) mode emitting more than 6 mW of cw power at 5 K. In general, maximum temperature of pulsed operation for grating devices was within a few Kelvin of that of multi-mode Fabry-Perot ridge lasers.


Postnatal persistence of epidermoid rests in the human middle ear.
It is widely believed that congenital cholesteatoma originates from epidermoid cell rests in the temporal bone. Congenital cholesteatomas of the anterior-superior middle ear may arise from such a rest, known as the epidermoid formation (EF), which has been described by Michaels and others. The EF is thought to disappear by 33 weeks' gestation in most cases; however, if it persists beyond fetal life, it may provide a nidus for cholesteatoma formation. The authors studied human temporal bones from individuals ranging from 20 weeks' gestation to 5 years of age to investigate pre- and postnatal occurrence of the EF. A total of 106 temporal bones were surveyed; 76 of these were fetal specimens and 30 were postnatal. EFs were present in 14 (18.4%) of the fetal specimens; they were identified in four (13.3%) of the postnatal temporal bones, with the oldest being 2 years, 7 months of age. Multiple EFs within a single temporal bone were also present in some cases. Although the EFs were composed of cells morphologically identical to those of the external ear canal epidermis, none of the specimens showed keratinization. These findings support the contention that EFs do occasionally persist into postnatal life and may be a source of cholesteatoma. However, a clear transition from epidermoid formation to unequivocal cholesteatoma has not yet been demonstrated.


Separation and measurement of Pa, Th, and U isotopes in marine sediments by microwave-assisted digestion and multiple collector inductively coupled plasma mass spectrometry.
This manuscript describes a new protocol for determination of Pa/Th/U in marine sediments. It is based on microwave-assisted digestion and represents an important reduction of working time over conventional hot-plate digestion methods, and the use of HClO(4) is avoided. Although Th and U are completely dissolved with a first microwave step, around 40% of (231)Pa remains undissolved, and a short hot-plate step with reverse aqua regia is required to achieve total digestion and spike equilibration. Next, the method involves a separation of these elements and a further purification of the Pa fraction using Dowex AG1-X8 resin. Separation with Bio-Rad and Sigma-Aldrich resins was compared; although both perform similarly for Th and U, Pa yields are higher with Bio-Rad. Finally, samples are measured using a Nu instruments multiple collector inductively coupled plasma mass spectrometer (MC-ICPMS). Overall chemical yields range around 50% for Pa, 60% for Th, and 70% for U.


Electrospun membranes: control of the structure and structure related applications in tissue regeneration and drug delivery.
This article presents an overview focusing on the structural control of electrospun membranes on a multilevel scale ranging from the morphology of single nanofibers to the packing and alignment of nanofibers and the patterns and shapes of fibrous scaffolds. The typical structures of electrospun membranes and the specific electrospinning strategies used to produce these structures are reviewed. In addition, potential applications of these controlled structures in tissue engineering and drug delivery are highlighted. Finally, this review concludes with a perspective on the challenges and future directions for the design and fabrication of electrospun scaffolds using controlled structures along with an investigation of the relationship between the structures of electrospun membranes and the cell and drug delivery behaviors.


Prosthetic management of soft palate cleft--a case report.
The treatment of cleft in the soft palate can be achieved essentially by surgical reconstruction or prosthetic obturation. The goals of prosthetic intervention are to prevent food and liquid leakage into the nose and to improve speech intelligibility by ensuring functional velopharyngeal port closure. In this report, the prosthetic management of a 5-year-old child with soft palatal cleft is presented. The impression of the cleft was taken with tissue conditioner, Visco -gel, TM (De Trey, Amalgamated Dental London) and the pharyngeal obturator (speech bulb) was made in clear acrylic resin. Patient tolerated the appliance well and was referred to speech therapist for speech articulation.


Electron-beam computed tomography in the assessment of coronary artery disease after heart transplantation.
Our aim was to compare the electron-beam CT (EBCT) features of coronary arteries in heart transplant recipients with those of biplane coronary angiography and intracoronary ultrasound (ICUS). We examined 112 heart transplant recipients (25 female; age, 17 to 69 years; median, 52 years) 1 to 153 months (median, 46 months) after surgery by EBCT to detect coronary artery calcifications. Calcifications were quantified by the Agatston scoring system. EBCT scores were compared with coronary angiography in all patients and ICUS of the left anterior descending coronary artery (LAD) in 100 patients. Coronary artery calcifications were found in 84 patients (75%). Angiographically, 16 patients displayed >50% coronary artery stenoses, all of whom had some degree of coronary artery calcification and only 1 of whom had a score of <55 (P<0.0001). With this threshold, EBCT had a sensitivity of 94%, a specificity of 79%, a positive predictive value of 43%, and a negative predictive value of 99% for detecting stenosis. ICUS confirmed the presence of calcified plaques in all patients with an LAD score >9. EBCT total calcium score was associated with the degree of intimal proliferation in that patients without ICUS features of allograft vasculopathy had a median score of 0 (25th percentile, 0; 75th percentile, 0), whereas patients with Stanford class IV vasculopathy had a median score of 41 (9 to 98, P<0.0001). EBCT is a promising noninvasive test for the detection of coronary heart disease in cardiac transplant recipients.


Energy metabolism in relation to skeletal muscle fibre properties during treadmill exercise.
The skeletal muscle metabolism of horses with a wide range of cardiocirculatory capacities was studied during a standardised near-maximal exercise test in relation to muscle fibre composition. Although the same amount of work was performed by all horses the amount of triglycerides and glycogen utilised and lactate accumulated differed widely. Both blood and muscle lactate accumulation were positively related to the amount of glycogen utilised. These factors were in turn positively associated with the percentage of Type IIB fibres and consequently negatively associated with the percentage of Type IIA fibres. The percentage of Type IIB fibres was negatively correlated to the activities of the oxidative enzymes citrate synthase and 3-hydroxyacyl-CoA-dehydrogenase and positively associated with the lactate dehydrogenase activity. The results indicate that the horses with a high proportion of Type IIB fibres had a lower muscle oxidative capacity and were, therefore, for energy production, more dependent upon glycolysis with subsequent lactate accumulation than horses which had a high proportion of Type IIA fibres. The different metabolic properties of the muscle fibre types indicate that the pattern of muscle fibre recruitment could have a significant effect on intramuscular substrate utilisation.


Risk of metabolic syndrome among children living in metropolitan Kuala Lumpur: a case control study.
With the increasing prevalence of childhood obesity, the metabolic syndrome has been studied among children in many countries but not in Malaysia. Hence, this study aimed to compare metabolic risk factors between overweight/obese and normal weight children and to determine the influence of gender and ethnicity on the metabolic syndrome among school children aged 9-12 years in Kuala Lumpur and its metropolitan suburbs. A case control study was conducted among 402 children, comprising 193 normal-weight and 209 overweight/obese. Weight, height, waist circumference (WC) and body composition were measured, and WHO (2007) growth reference was used to categorise children into the two weight groups. Blood pressure (BP) was taken, and blood was drawn after an overnight fast to determine fasting blood glucose (FBG) and full lipid profile, including triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC). International Diabetes Federation (2007) criteria for children were used to identify metabolic syndrome. Participants comprised 60.9% (n = 245) Malay, 30.9% (n = 124) Chinese and 8.2% (n = 33) Indian. Overweight/obese children showed significantly poorer biochemical profile, higher body fat percentage and anthropometric characteristics compared to the normal-weight group. Among the metabolic risk factors, WC ≥90th percentile was found to have the highest odds (OR = 189.0; 95%CI 70.8, 504.8), followed by HDL-C≤1.03 mmol/L (OR = 5.0; 95%CI 2.4, 11.1) and high BP (OR = 4.2; 95%CI 1.3, 18.7). Metabolic syndrome was found in 5.3% of the overweight/obese children but none of the normal-weight children (p < 0.01). Overweight/obese children had higher odds (OR = 16.3; 95%CI 2.2, 461.1) of developing the metabolic syndrome compared to normal-weight children. Binary logistic regression showed no significant association between age, gender and family history of communicable diseases with the metabolic syndrome. However, for ethnicity, Indians were found to have higher odds (OR = 5.5; 95%CI 1.5, 20.5) compared to Malays, with Chinese children (OR = 0.3; 95%CI 0.0, 2.7) having the lowest odds. We conclude that being overweight or obese poses a greater risk of developing the metabolic syndrome among children. Indian ethnicity is at higher risk compared to their counterparts of the same age. Hence, primary intervention strategies are required to prevent this problem from escalating.


Oxidative Stress Status in COVID-19 Patients Hospitalized in Intensive Care Unit for Severe Pneumonia. A Pilot Study.
A key role of oxidative stress has been highlighted in the pathogenesis of COVID-19. However, little has been said about oxidative stress status (OSS) of COVID-19 patients hospitalized in intensive care unit (ICU). Biomarkers of the systemic OSS included antioxidants (9 assays), trace elements (3 assays), inflammation markers (4 assays) and oxidative damage to lipids (3 assays). Blood samples were drawn after 9 (7-11) and 41 (39-43) days of ICU stay, respectively in 3 and 6 patients. Vitamin C, thiol proteins, reduced glutathione, γ-tocopherol, β-carotene and PAOT® score were significantly decreased compared to laboratory reference values. Selenium concentration was at the limit of the lower reference value. By contrast, the copper/zinc ratio (as a source of oxidative stress) was higher than reference values in 55% of patients while copper was significantly correlated with lipid peroxides (r = 0.95, p < 0.001). Inflammatory biomarkers (C-reactive protein and myeloperoxidase) were significantly increased when compared to normals. The systemic OSS was strongly altered in critically ill COVID-19 patients as evidenced by increased lipid peroxidation but also by deficits in some antioxidants (vitamin C, glutathione, thiol proteins) and trace elements (selenium).


Impact of COVID-19 Pandemic on Pathology Residency Program: An Experience from India.
To study the impact of the COVID-19 pandemic on pathology residents through a questionnaire-based survey. We designed a Google survey questionnaire with 20-questions and distributed it to the pathology residents across India via e-mail and WhatsApp. All the responses collected were analysed using appropriate statistical methods. We received a total of 81 responses. The majority (n=55, 68.8%) of the residents were aged 26-30 years with a male-female ratio of 1:2.2. Residents reported a significant decrease in classes as compared to pre-covid times. However, most institutions (90%) shifted to the virtual method for various teaching sessions. About 94.7% of the residents felt a fall in the quality of training due to Covid. A significant number of junior residents (76.92%) reported an inability to complete the target thesis enrolment. The residents saw a substantial decrease in the number of peripheral smears, bone marrow, cytology, and histopathology cases compared to pre-Covid times (p value < 0.001 for all). An overwhelming 83.8% of the pathology residents were posted for COVID-19 duties. About 48.8% turned Covid positive. About 77.5% (n=62) of residents felt that the necessary training period would be extended. The COVID-19 pandemic has immensely affected the training and teaching of pathology residents in India. Similarly, this pandemic must have affected pathology residents all across the globe. Therefore, institutions can consider offering an extended period of up to one year, depending upon residents' requests.


Markers of atherosclerosis and inflammation for prediction of coronary heart disease in older adults.
Although both inflammatory and atherosclerosis markers have been associated with coronary heart disease (CHD) risk, data directly comparing their predictive value are limited. The authors compared the value of 2 atherosclerosis markers (ankle-arm index (AAI) and aortic pulse wave velocity (aPWV)) and 3 inflammatory markers (C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha)) in predicting CHD events. Among 2,191 adults aged 70-79 years at baseline (1997-1998) from the Health, Aging, and Body Composition Study cohort, the authors examined adjudicated incident myocardial infarction or CHD death ("hard" events) and "hard" events plus hospitalization for angina or coronary revascularization (total CHD events). During 8 years of follow-up between 1997-1998 and June 2007, 351 participants developed total CHD events (197 "hard" events). IL-6 (highest quartile vs. lowest: hazard ratio = 1.82, 95% confidence interval: 1.33, 2.49; P-trend < 0.001) and AAI (AAI < or = 0.9 vs. AAI 1.01-1.30: hazard ratio = 1.57, 95% confidence interval: 1.14, 2.18) predicted CHD events above traditional risk factors and modestly improved global measures of predictive accuracy. CRP, TNF-alpha, and aPWV had weaker associations. IL-6 and AAI accurately reclassified 6.6% and 3.3% of participants, respectively (P's < or = 0.05). Results were similar for "hard" CHD, with higher reclassification rates for AAI. IL-6 and AAI are associated with future CHD events beyond traditional risk factors and modestly improve risk prediction in older adults.