Nicotine effects on thermoregulatory responses of men and women during acute cold exposure.
Due to the impact of nicotine (NIC) on the physiological processes involved in temperature regulation during cold exposure, it is conceivable that NIC may affect the body's thermoregulatory abilities during a cold stress. Thus, the purpose of this study was to examine the effects of NIC on thermoregulatory responses during acute cold exposure. There were six men and six women between the ages of 18 and 25 yr who participated in this study. All subjects were active, apparently healthy smokers. Each subject performed two cold air trials consisting of a 30-min baseline period (BASE) and a 120-min exposure to 10 degrees C air. One cold air trial was performed following a NIC dosing using a 21-mg transdermal patch while the other trial was performed after a placebo (PL) treatment. During the cold air trials, there were no differences in rectal temperature (Tre) or mean skin temperature (Tsk) between the PL and NIC treatments in either sex (p > 0.05). However, in men, heat production (M) was 12% lower (p < or = 0.05) and tissue insulation was 17% higher (p < or = 0.05) during the NIC treatment compared with the PL treatment, while these responses in women were unaffected. In both men and women, finger skin vascular conductance (SVCfin), expressed as a percentage of the BASE value, was higher during the NIC treatment compared with the PL treatment during the cold air trials (p < or = 0.05). Lastly, throughout the cold air trials, there was no difference in thermal sensation between the PL and NIC treatments (p > 0.05). In conclusion, although NIC administration resulted in sex-specific alterations in M and tissue insulation during cold exposure, the response in Tre was unaffected.


Effects of prostaglandin E2, F2alpha, and latanoprost acid on isolated ocular blood vessels in vitro.
The vascular effects of PGE2, PGF2alpha and latanoprost acid on isolated bovine long posterior ciliary arteries and episcleral veins have been investigated using a small vessel myograph. PGE2 caused vasorelaxation both in the ciliary artery and episcleral vein (EC50: 7.9x10(-9) M and 2.1x10(-8) M respectively). Blockade of thromboxane receptors with GR 32191B, a TP receptor antagonist, shifted the concentration-response curves to the left in both preparations, probably indicating a slight co-stimulation of TP receptors in these vessels. Blockade of tachykinin NK-1 receptors had no effect on the PGE2 concentration-response curve. PGF2alpha caused a concentration dependent contraction in half of the ciliary arteries examined and relaxation in the other half. In the presence of the thromboxane receptor antagonist (GR 3211B) PGF2alpha always induced relaxation of the ciliary artery (EC50:1.3x10[-5] M). At higher concentrations PGF2alpha tended to slightly constrict the episcleral veins, but in the presence of the TP receptor antagonist (GR 32191B) only relaxation was observed. Latanoprost acid contracted the ciliary artery at concentrations above 10(-6) M. This effect was completely abolished by the TP receptor antagonist (GR 32191B). In the episcleral vein latanoprost acid induced a slight relaxation but in the presence of the TP receptor antagonist (GR 32191B) no effect was observed. These results indicate that PGE2 invariably induces vasorelaxation of bovine ciliary arteries and episcleral veins, whereas both PGF2alpha and latanoprost acid at high concentrations can cause vasoconstriction probably by stimulating TP receptors. PGF2alpha causes marked relaxation of both ciliary arteries and episcleral veins in the presence of the TP blocker which seems unlikely to be mediated by FP receptors.


[Propofol ameliorates rat liver ischemia-reperfusion injury possibly by inhibiting nuclear factor-kappaB expression].
To explore the role of nuclear factor-kappaB (NF-kappaB) in the protective effects of propofol against liver ischemia-reperfusion (IR) injury. Forty male rats were randomized into 4 equal groups, namely the sham operation (N) group, IR group with hepatic IR injury (induced by ischemia of the left, right and median hepatic lobes for 1 h followed by reperfusion for 2 h), propofol (P) group with sham operation and propofol perfusion at 10 mg kg(-1) h(-1), and propofol treatment (PIR) group with IR injury and propofol perfusion. RT-PCR was used to detect the transcription level of NF-kappaB, and Western blotting was used for assaying NF-kappaB protein expression in the liver. Compared with either the N or the P group, the IR group showed obvious swelling, fatty degeneration and scatter focal necrosis of the hepatocytes as well as mild congestion in the hepatic sinusoid, with significantly increased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels and NF-kappaB expressions at both mRNA and protein levels (P<0.05). In the PIR group, the histopathological changes of the liver was lessened as compared with the IR group, and ALT and AST elevation was significantly inhibited (P<0.05) as was the protein expression of NF-kappaB (P<0.05), but NF-kappaB transcription level was further enhanced (P<0.05). Propofol can protect the liver from IR injury possibly by inhibiting NF-kappaB expression.


A young couple's grave found in the Rakhigarhi cemetery of the Harappan Civilization.
The Harappan Civilization, one of the earliest complex societies in the world, flourished on the Indian subcontinent. Although many additional Harappan settlements and cemeteries have been discovered and investigated, no coupled burials at Harappan cemeteries have been reported to date. In 2013-2016, we excavated the cemetery of the Rakhigarhi site (Haryana), the largest city of the Harappan Civilization. At the site, we found a grave that turned out to be a coupled (joint) burial of the primary type. This report is the first anthropologically confirmed case of coupled burial from a Harappan cemetery.


Classical scrapie transmission in ARR/ARR genotype sheep.
The ARR allele is considered to provide a very strong resistance against classical scrapie infection in sheep. In this study, we report the occurrence of clinical transmissible spongiform encephalopathy in ARR/ARR sheep, following their inoculation by the intracerebral route with a classical scrapie isolate. On first passage, the disease displayed an incomplete attack rate transmission, with incubation periods exceeding 6 years. On second passage, the obtained prion did not display better abilities to propagate than the original isolate. These transmission results contrasted with the 100 % attack rate and the short incubation periods observed in ARQ/ARQ sheep challenged with the same isolate. These data confirm that ARR/ARR sheep cannot be considered to be fully resistant to classical scrapie. However, they also support the contention that classical scrapie has a very limited capacity to transmit and adapt to ARR/ARR sheep.


Neonatal Hypoxic-Ischemic Encephalopathy Yields Permanent Deficits in Learning Acquisition: A Preclinical Touchscreen Assessment.
Neonatal hypoxic-ischemic encephalopathy (HIE) remains a common problem world-wide for infants born at term. The impact of HIE on long-term outcomes, especially into adulthood, is not well-described. To facilitate identification of biobehavioral biomarkers utilizing a translational platform, we sought to investigate the impact of HIE on executive function and cognitive outcomes into adulthood utilizing a murine model of HIE. HIE mice (unilateral common carotid artery occlusion to induce ischemia, followed by hypoxia with a FiO2 of 0.08 for 45 min) and control mice were tested on discrimination and reversal touchscreen tasks (using their noses) shown to be sensitive to loss of basal ganglia or cortical function, respectively. We hypothesized that the HIE injury would result in deficits in reversal learning, revealing complex cognitive and executive functioning impairments. Following HIE, mice had a mild discrimination impairment as measured by incorrect responses but were able to learn the paradigm to similar levels as controls. During reversal, HIE mice required significantly more total trials, errors and correction trials across the paradigm. Analysis of specific stages showed that reversal impairments in HIE were driven by significant increases in all measured parameters during the late learning, striatal-mediated portion of the task. Together, these results support the concept that HIE occurring during the neonatal period results in abnormal neurodevelopment that persists into adulthood, which can impact efficient associated learning. Further, these data show that utilization of an established model of HIE coupled with touchscreen learning provides valuable information for screening therapeutic interventions that could mitigate these deficits to improve the long-term outcomes of this vulnerable population.


Predictive Model of Severity in SARS CoV-2 Patients at Hospital Admission Using Blood-Related Parameters.
Blood test alterations are crucial in SARS CoV-2 (COVID-19) patients. Blood parameters, such as lymphocytes, C reactive protein (CRP), creatinine, lactate dehydrogenase, or D-dimer, are associated with severity and prognosis of SARS CoV-2 patients. This study aims to identify blood-related predictors of severe hospitalization in patients diagnosed with SARS CoV-2. Observational retrospective study of all rt-PCR and blood-test positive (at 48 hours of hospitalization) SARS CoV-2 diagnosed inpatients between March-May 2020. Deceased and/or ICU inpatients were considered as severe cases, whereas those patients after hospital discharge were considered as non-severe. Multivariate logistic regression was used to identify predictors of severity, based on bivariate contrast between severe and mild inpatients. The overall sample comprised 540 patients, with 374 mild cases (69.26%), and 166 severe cases (30.75%). The multivariate logistic regression model for predicting SARS CoV-2 severity included lymphocytes, C reactive protein (CRP), creatinine, total protein levels, glucose and aspartate aminotransferase as predictors, showing an area under the curve (AUC) of 0.895 at a threshold of 0.29, with 81.5% of sensitivity and 81% of specificity. Our results suggest that our predictive model allows identifying and stratifying SARS CoV-2 patients in risk of developing severe medical complications based on blood-test parameters easily measured at hospital admission, improving health-care resources management and distribution.


Deformation of attractor landscape via cholinergic presynaptic modulations: a computational study using a phase neuron model.
Corticopetal acetylcholine (ACh) is released transiently from the nucleus basalis of Meynert (NBM) into the cortical layers and is associated with top-down attention. Recent experimental data suggest that this release of ACh disinhibits layer 2/3 pyramidal neurons (PYRs) via muscarinic presynaptic effects on inhibitory synapses. Together with other possible presynaptic cholinergic effects on excitatory synapses, this may result in dynamic and temporal modifications of synapses associated with top-down attention. However, the system-level consequences and cognitive relevance of such disinhibitions are poorly understood. Herein, we propose a theoretical possibility that such transient modifications of connectivity associated with ACh release, in addition to top-down glutamatergic input, may provide a neural mechanism for the temporal reactivation of attractors as neural correlates of memories. With baseline levels of ACh, the brain returns to quasi-attractor states, exhibiting transitive dynamics between several intrinsic internal states. This suggests that top-down attention may cause the attention-induced deformations between two types of attractor landscapes: the quasi-attractor landscape (Q-landscape, present under low-ACh, non-attentional conditions) and the attractor landscape (A-landscape, present under high-ACh, top-down attentional conditions). We present a conceptual computational model based on experimental knowledge of the structure of PYRs and interneurons (INs) in cortical layers 1 and 2/3 and discuss the possible physiological implications of our results.


Development of aminoglycoside and β-lactamase resistance among intestinal microbiota of swine treated with lincomycin, chlortetracycline, and amoxicillin.
Lincomycin, chlortetracycline, and amoxicillin are commonly used antimicrobials for growth promotion and infectious disease prophylaxis in swine production. In this study, we investigated the shifts and resistance development among intestinal microbiota in pregnant sows before and after lincomycin, chlortetracycline, and amoxicillin treatment by using phylogenetic analysis, bacterial enumeration, and PCR. After the antimicrobial treatment, shifts in microbial community, an increased proportion of resistant bacteria, and genes related to antimicrobial resistance as compared to the day before antimicrobial administration (day 0) were observed. Importantly, a positive correlation between antimicrobial resistance gene expression in different categories, especially those encoding aminoglycoside and β-lactamase and antimicrobial resistance, was observed. These findings demonstrate an important role of antimicrobial usage in animals in the development of antimicrobial resistance, and support the notion that prudent use of antimicrobials in swine is needed to reduce the risk of the emergence of multi-drug resistant zoonotic pathogens.


The effect of 17beta-estradiol at doses of 0.5, 1 and 2 mg compared with placebo on early postmenopausal bone loss in hysterectomized women.
In a randomized double-masked placebo-controlled parallel-group trial 166 hysterectomized (+/- oophorectomy) perimenopausal and postmenopausal women aged 45-55 years with a follicle stimulating hormone level above 20 IU/l were treated with one daily dose of either 0.5 mg 17beta-estradiol (E2), 1 mg E2, 2 mg E2 or placebo for 2 years. Bone mineral density (BMD) and biochemical bone markers were determined. All three doses of E2 were significantly better than placebo with respect to change in BMD at the lumbar spine (L1-L4) (p<0.0001 for all pairwise comparisons) and hip (femoral neck, trochanter, Ward's triangle). The mean percentage change from baseline at the lumbar spine was -0.2%, 0.8% and 1.8% in the 0.5, 1 and 2 mg E2 groups respectively compared with -3.5% in the placebo group. Both 1 and 2 mg E2 were significantly better than placebo in increasing the BMD at the femoral neck (p<0.001), trochanter (p<0.01) and Ward's triangle (p<0.0001), while 0.5 mg E2 was significantly better than placebo at the femoral neck (p<0.001) and Ward's triangle (p<0.0001). The overall difference in mean percentage change in BMD at the femoral neck versus placebo (-0.2%) was 3.8% for 0.5 mg, 4.0% for 1 mg and 3.9% for 2 mg E2; the corresponding numbers for trochanter were 1.3%, 3.3% and 3.2%, respectively, and -2.2%,, 2.9, 2.9% and 4.0%, respectively, for Ward's triangle. More than half the women who received placebo presented with a decrease in BMD at the hip. The percentage of women in the 0.5 mg E2 group who maintained or increased BMD at the femoral neck, trochanter and Ward's triangle was 69%, 56% and 44%, respectively. For 1 mg E2 the numbers were 69%, 78% and 61% respectively, and for 2 mg E2 were 59%, 68% and 59% respectively. Osteocalcin, serum pyridinium crosslinks, urinary pyridinium cross-links and urinary hydroxyproline/creatinine decreased significantly (p<0.0001, p<0.05) in the 0.5, 1 and 2 mg E2 groups compared with the placebo group after 6 and 24 months of treatment.


Eco-evolutionary maintenance of diversity in fluctuating environments.
Growing evidence suggests that temporally fluctuating environments are important in maintaining variation both within and between species. To date, however, studies of genetic variation within a population have been largely conducted by evolutionary biologists (particularly population geneticists), while population and community ecologists have concentrated more on diversity at the species level. Despite considerable conceptual overlap, the commonalities and differences of these two alternative paradigms have yet to come under close scrutiny. Here, we review theoretical and empirical studies in population genetics and community ecology focusing on the 'temporal storage effect' and synthesise theories of diversity maintenance across different levels of biological organisation. Drawing on Chesson's coexistence theory, we explain how temporally fluctuating environments promote the maintenance of genetic variation and species diversity. We propose a further synthesis of the two disciplines by comparing models employing traditional frequency-dependent dynamics and those adopting density-dependent dynamics. We then address how temporal fluctuations promote genetic and species diversity simultaneously via rapid evolution and eco-evolutionary dynamics. Comparing and synthesising ecological and evolutionary approaches will accelerate our understanding of diversity maintenance in nature.


The development and concurrent validity of a real-time algorithm for temporal gait analysis using inertial measurement units.
The use of inertial measurement units (IMUs) for gait analysis has emerged as a tool for clinical applications. Shank gyroscope signals have been utilized to identify heel-strike and toe-off, which serve as the foundation for calculating temporal parameters of gait such as single and double limb support time. Recent publications have shown that toe-off occurs later than predicted by the dual minima method (DMM), which has been adopted as an IMU-based gait event detection algorithm.In this study, a real-time algorithm, Noise-Zero Crossing (NZC), was developed to accurately compute temporal gait parameters. Our objective was to determine the concurrent validity of temporal gait parameters derived from the NZC algorithm against parameters measured by an instrumented walkway. The accuracy and precision of temporal gait parameters derived using NZC were compared to those derived using the DMM. The results from Bland-Altman Analysis showed that the NZC algorithm had excellent agreement with the instrumented walkway for identifying the temporal gait parameters of Gait Cycle Time (GCT), Single Limb Support (SLS) time, and Double Limb Support (DLS) time. By utilizing the moment of zero shank angular velocity to identify toe-off, the NZC algorithm performed better than the DMM algorithm in measuring SLS and DLS times. Utilizing the NZC algorithm's gait event detection preserves DLS time, which has significant clinical implications for pathologic gait assessment.


Identification with the retail organization and customer-perceived employee similarity: effects on customer spending.
Two constructs important to academicians and managers are the degree to which employees and customers identify with an organization, employee organizational identification (employee OI) and customer-company identification (customer identification), respectively. This research examines the effects of these identification constructs and the related construct of customer perceived similarity to employees on customer spending. Via a 1-year multilevel study of 12,047 customers and 1,464 store employees (sales associates) covering 212 stores of a specialty apparel retailer, our study contributes to the literature in 2 critical ways. First, we expand the theoretical network of employee OI and customer identification by examining the related construct of a customer's perceived similarity to store employees. We examine the incremental (not fully mediated) main and interaction effects of customer-perceived similarity to employees and employee OI on customer spending. Second, we examine the effect of customer identification on customer spending relative to the effect of customer satisfaction on customer spending. Thus, our study also contributes by demonstrating a potential complementary route to achieve customer spending (customer identification), a route that may be more readily affected by management than the efforts required for a sustained increase in customer satisfaction. Implications for academics and managers are offered.


Quick chip assay using locked nucleic acid modified epithelial cell adhesion molecule and nucleolin aptamers for the capture of circulating tumor cells.
The role of circulating tumor cells (CTCs) in disease diagnosis, prognosis, monitoring of the therapeutic efficacy, and clinical decision making is immense and has attracted tremendous focus in the last decade. We designed and fabricated simple, flat channel microfluidic devices polydimethylsiloxane (PDMS based) functionalized with locked nucleic acid (LNA) modified aptamers (targeting epithelial cell adhesion molecule (EpCAM) and nucleolin expression) for quick and efficient capture of CTCs and cancer cells. With optimized flow rates (10 μl/min), it was revealed that the aptamer modified devices offered reusability for up to six times while retaining optimal capture efficiency (>90%) and specificity. High capture sensitivity (92%) and specificity (100%) was observed in whole blood samples spiked with Caco-2 cells (10-100 cells/ml). Analysis of blood samples obtained from 25 head and neck cancer patients on the EpCAM LNA aptamer functionalized chip revealed that an average count of 5 ± 3 CTCs/ml of blood were captured from 22/25 samples (88%). EpCAM intracellular domain (EpICD) immunohistochemistry on 9 oral squamous cell carcinomas showed the EpICD positivity in the tumor cells, confirming the EpCAM expression in CTCs from head and neck cancers. These microfluidic devices also maintained viability for in vitro culture and characterization. Use of LNA modified aptamers provided added benefits in terms of cost effectiveness due to increased reusability and sustainability of the devices. Our results present a robust, quick, and efficient CTC capture platform with the use of simple PDMS based devices that are easy to fabricate at low cost and have an immense potential in cancer diagnosis, prognosis, and therapeutic planning.


Physical therapy and exercise interventions in Huntington's disease: a mixed methods systematic review protocol.
The review seeks to evaluate the effectiveness of physical therapy and exercise interventions in Huntington's disease (HD). The review question is: What is the effectiveness of physiotherapy and therapeutic exercise interventions in people with HD, and what are patients', families' and caregivers' perceptions of these interventions?The specific objectives are:This mixed methods review seeks to develop an aggregated synthesis of quantitative, qualitative and narrative systematic reviews on physiotherapy and exercise interventions in HD, in an attempt to derive conclusions and recommendations useful for clinical practice and policy decision-making.


Within-day variation and effect of acute stress on plasma and milk cortisol in lactating goats.
An experiment was carried out to study the effect of acute stress on cortisol concentration in goat milk (milk cortisol; MC) and its suitability for stress assessment. Additional variables studied were plasma cortisol (PC), blood glucose (BG), and somatic cell count (SCC). Ten goats free of mastitis at 2 mo of lactation were divided into 2 groups. One group of animals was exposed to acute stress (visual and auditory, but not physical, contact with a barking dog for 3 min) immediately before the 1000 h sampling (STR), and the other group was considered as the control group, not exposed to acute stress (CON). The animals were gradually accustomed to the sampling schedule for 1 wk before the stress treatment (pre-experimental period). The variables PC, MC, BG, SCC, and milk composition (fat, lactose, whey protein, true protein, and casein) were recorded at 0600, 1000, 1130, 1400, 1800, 2200, and 0200 h. Milk variables were recorded in both glands separately. The right gland (n=10) was completely milked and the left gland (n=10) was milked to 30 mL at every sampling except at 1000 h, when complete milking was carried out on both glands. Variables were analyzed by using a linear mixed model. Both PC and MC concentrations varied throughout the day, with values being highest in the morning. Higher PC levels were recorded in the STR group immediately after treatment compared with CON (36.9 vs 16.3 ng/mL). For MC, differences between treatments were noted 1.5h after STR treatment (1.27 vs 0.25 ng/mL). Blood glucose increased immediately after treatment in STR animals, being different from CON until 1.5h after treatment sampling (101 vs. 58 mg/dL). The SCC was not increased by STR treatment, showing higher values in the morning and afternoon compared with evening and night (5.6±0.13 to 5.87±0.13 log10 SCC). The STR treatment had no significant effect on milk composition, and overall milk yield of a complete day after stress stimulus of both groups was similar (STR: 2,067±280 g/d; CON: 2,134±427 g/d). We conclude that plasma and milk cortisol concentrations in control dairy goats varied throughout the day; MC showed significant differences in the STR group if samples were taken 1.5h after the stressing stimulus, whereas PC showed significant differences in samples taken immediately after the stressing stimulus. Additionally, MC sampling has the advantage of being noninvasive compared with blood sampling.


Eupatorin and Salvigenin Potentiate Doxorubicin-Induced Apoptosis and Cell Cycle Arrest in HT-29 and SW948 Human Colon Cancer Cells
Background: Cancer persists as one of the world's most pressing maladies. Notable points about chemotherapy are drug side effects which are almost universally encountered. Emerging knowledge focusing on mechanisms of toxicity due to chemotherapy has led to characterization of novel methods, including the exploitation of natural compounds, in combination therapies. Flavonoids are natural polyphenolic compounds that play protective roles against tumor cell development. The focus of this study was apoptotic effects of two flavonoids, eupatorin and salvigenin, in combination with doxorubicin on a cellular model of colon cancer. Method: Upon establishing a non-effective dose of doxorubicin, and effective doses of eupatorin (100μM) and salvigenin (150μM) via MTT, morphological features of apoptosis were distinguished using DAPI staining and cell cycle blockage in the sub-G1 phase. Apoptosis was determined by annexin/ PI and western blotting. ROS levels and MMP were measured to show any role of mitochondria in apoptosis. Results: Co-administration of flavonoids with doxorubicin induced apoptosis via the mitochondrial pathway as mitochondrial membrane potential and ROS production were changed. Annexin/PI analysis demonstrated that apoptosis frequency was increased with the combination treatments in colon cancer cells. Finally, the combination of these flavonoids with doxorubicin increased the Bax/Bcl-2 ratio, caspase-3 expression and PARP cleavage. Conclusion: Combination of flavonoids with doxorubicin induces apoptosis and enhances effect on cancer cells which might allow amelioration of side effects by dose lowering.


Escherichia coli plasmid production in fermenter.
Escherichia coli harboring a recombinant plasmid was grown in a fermenter to study the effects of selected process parameters on the growth of the microbe and on plasmid amplification with chloramphenicol treatment. Eighteen fermentations were carried out according to a statistical experimental design in which the fermentation temperature, pH, and turbidity of culture at the onset of plasmid amplification were the selected independent process variables. Static regression models describing the process were derived from the experimental results. It turned out that recombinant plasmid copy numbers could be influenced by controlling fermentation temperature and pH. The maximal copy number during bacterial growth phase and the optimal plasmid production were found to require fermentation conditions different from those needed for optimal bacterial growth and cell division. The conditions also differed significantly from those routinely used in research laboratories for plasmid preparation. The chloramphenicol treatment increased the plasmid copy number compared with chromosome numbers up to fivefold. Some of the data suggest that under certain conditions the number of chromosome molecules in E. coli cells may rise during the plasmid amplification stage. Statistical experimental design, a nucleic acid sandwich hybridization technique for plasmid quantification, and regression models proved to be useful in this study.


Comparative efficacy of five most common traditional Chinese medicine monomers for promoting recovery of motor function in rats with blunt spinal cord injury: a network meta-analysis.
This research employed a network meta-analysis (NMA) to examine the effectiveness of five traditional Chinese medicine (TCM) monomers for promoting motor function recovery in rats with blunt spinal cord injury (SCI). Wangfang, China National Knowledge Infrastructure, Web of Science, Embase, Chinese Scientific Journal Database, PubMed, and the Chinese Biomedical Literature Databases were searched for retrieving relevant articles published from their inception to December 2022. Two reviewers performed screening of search results, data extraction, and literature quality assessment independently. For this meta-analysis, 59 publications were included. Based on the recovery of motor function at weeks 1, 2, 3, and 4 in NMA, almost all TCM groups had significantly increased positive effects than the negative control animals. In terms of cumulative probability, the tanshinone IIA (TIIA) group ranked first in restoring motor function in the first week after blunt SCI, and the resveratrol (RSV) group ranked first during the last 3 weeks. The NMA revealed that TCM monomers could effectively restore motor function in the rat model of blunt SCI. In rats with blunt SCI, TIIA may be the most effective TCM monomer during the first week, whereas RSV may be the most effective TCM monomer during the last 3 weeks in promoting motor function recovery. For better evidence reliability in preclinical investigations and safer extrapolation of those findings into clinical settings, further research standardizing the implementation and reporting of animal experiments is required. https://inplasy.com/, identifier INPLASY202310070.


Axial differences in the musculature of uropeltid snakes: the freight-train approach to burrowing.
The shield-tailed snakes (family Uropeltidae) extend and widen the tunnels in which they live by alternately curving and straightening the anterior portion of their vertebral columns within the skin, a burrowing method that proves to be most effective for tunneling amid roots and rocks, as well as for producing tunnels wider than the trunk through unpredictably heterogeneous substrates. The muscles of the anterior portion of the uropeltid trunk are larger and thicker than those of the posterior and are further modified by the inclusion of large amounts of myoglobin, numerous mitochondria, and diverse other ultrastructural and enzymatic specializations, which presumably represent adaptations for sustained work loads. The very much thinner, serially homologous, but unmodified musculature of the posterior trunk occupies only a much smaller fraction of the cross-sectional area. This regional modification increases the effectiveness of the posterior body for storing viscera and developing embryos.


PECAM-1 is a critical mediator of atherosclerosis.
Atherosclerosis is a chronic inflammatory disease of large arteries in which lesion development preferentially occurs at vessel sites exposed to rapid changes in flow. We have previously shown that platelet endothelial cell adhesion molecule (PECAM-1), a surface receptor of the immunoglobulin superfamily, is involved in mechanosensing of rapid changes in flow. We wondered whether apolipoprotein E deficient (ApoE(-/-)) mice, predisposed to development of atheromas, would be protected from atherosclerosis by deficiency in PECAM-1. Using double knockout (DKO) mice for both PECAM-1 and ApoE (ApoE(-/-)/PECAM-1(-/-)) we found a significant reduction of sudanophilic lesions in their aortae compared to single knockout (SKO) (ApoE(-/-)/PECAM-1(+/+)) mice maintained on a high-fat Western diet. Immunostaining of aortic sinus cross sections demonstrated significantly lower ICAM-1 expression in DKO lesions compared with SKO lesions, and en face preparations of vessel regions subjected to disturbed and laminar flow showed less disruption of junctional connexin 43 in DKO than in SKO mice. Thus, PECAM-1 deficiency reduced the extent of lesions at the aortic arch and the aortic sinus, and lowered atherogenic indices. These results suggest that PECAM-1 is an important factor in the atherogenic changes seen in the ApoE-deficient mouse model and thus should be considered as a potential target for protection against atherosclerosis.


Differential Diagnosis of Parotid Lipoma in a Breast Ca Patient.
Lipomas are common benign tumors usually detected on the torso, neck, upper thighs, and upper arms. However, they are rarely found in the parotid gland region. Because of their rarity at this site, they are not often considered in the differential diagnosis of parotid tumors. This report describes a rare case of a lipoma in the superficial lobe of parotid gland. A 71-year-old female patient admitted to our department complaining about swelling and pain in the posterior area of the left mandibular region since one month. Her medical history included mastectomy after breast CA fifteen years ago. Clinical examination revealed a smooth-surfaced, soft, and painful mass, with well-defined margins in the left mandibular region. Differential diagnosis of metastasis, inflammatory neck swellings, and benign salivary gland tumors were considered for the patient. Advanced imaging methods such as ultrasonography and contrast tomography revealed that the lesion was a lipoma of parotid gland. A surgical intervention under general anesthesia was planned for the removal of the mass; however patient refused the surgical treatment. Patient was placed on six-month periodic recall. This article reviews the radiographic appearance and differential diagnoses of lipoma in this rare location.


Intensifying screens in soft tissue radiography.
Certain screen-film combinations were tested in the low voltage range (26 to 40 kV, tungsten target) and compared with an optimal non-screen industrial film. The dose reduction was of no consequence as compared with the loss in image quality. Some physical properties of the screens giving rise to the failure are discussed.


Comparative assessment of local tolerance of alcohols commonly used in alcohol-based hand rubs for hand hygiene.
Hand hygiene plays a key role in nosocomial infection prevention. To achieve users' adherence, products' dermal tolerance is essential. We aimed at making a comparative assessment of skin irritation and phototoxicity of the 3 alcohols commonly used in alcohol-based hand rubs (Ethanol, Propan-2-ol, Propan-1-ol) at 60, 70, 80 or 85% w/w in water or with co-formulates (hydrating, emollient and skin protective agents). In vitro validated OECD methods 439 and 432 were used. For irritation, EpiSkin™ Small Model was the chosen Reconstructed Human Epidermis (RhE). For phototoxicity, co-formulates alone or in mixture with and without alcohol were tested using BALB/c 3T3 cell cultures. Whilst Ethanol and Propan-2-ol could not be differentiated and displayed good skin tolerance profiles, Propan-1-ol based products lead to significant viability impairments of RhE at 60, 70 or 80% and at 60% in the presence of co-formulates. However, these results could not be reproduced in another RhE model. Taking also into account bibliographic data on Propan-1-ol, this suggests that our results are probably related to a lack of specificity of the used RhE. Therefore, it can be relevant in case of significant results to use two different RhE models before performing any classification and/or performing any complementary tests.


Surgical versus endovascular treatment of traumatic thoracic aortic rupture.
Blunt traumatic thoracic aortic rupture is a life-threatening surgical emergency associated with high mortality and morbidity. The recent development of endovascular stent-graft prostheses offers a potentially less invasive alternative to open chest surgery, especially in patients with associated injuries. We sought to compare the results of conventional surgical repair and endovascular treatment of traumatic aortic rupture in a single center. From July 1998 to January 2004, 20 patients with acute blunt traumatic aortic rupture underwent treatment at our institution. All patients had a lesion limited to the isthmus, and associated injuries. Initial management included fluid resuscitation, treatment of other severe associated lesions, and strict monitoring of blood pressure. Eleven patients (9 men, 2 women; mean age, 32 years) underwent surgical repair, including direct suturing in 6 patients and graft interposition in 5 patients. Ten patients were operated on with cardiopulmonary support (left bypass with centrifugal pump, n = 2; extracorporeal circulation, n = 8). The delay between trauma and surgery was 2.6 days (range, 0-21 days). Nine patients (8 men, 1 woman; mean age, 32 years) underwent endovascular treatment with commercially available devices (Excluder, n = 2; Talent, n = 7). In all patients 1 stent graft was deployed. In 2 patients the left subclavian artery was intentionally covered with the device. The delay between trauma and endovascular treatment was 17.8 days (range, 1-68 days). One patient in the surgical group (9.1%) died during the intervention. Three surgical complications occurred in 3 patients (27%), including left phrenic nerve palsy (n = 1), left-sided recurrent nerve palsy (n = 1), and hemopericardium 16 days after surgery that required a repeat intervention (n = 1). No patient in this group had paraplegia. In the endovascular group successful stent-graft deployment was achieved in all patients, with no conversion to open repair. No patient died, and no procedure-related complications, including paraplegia, occurred in this group. Control computed tomography scans obtained within 7 days after endovascular treatment showed exclusion of pseudoaneurysm in all cases. Length of follow-up for endovascular treatment ranged from 3 to 41 months (mean, 15.1 months). Computed tomography scans obtained 3 months after endovascular treatment showed complete disappearance of pseudoaneurysm in all patients. In the treatment of blunt traumatic thoracic aortic rupture, the immediate outcome in patients who receive endovascular stent grafts appears to be at least as good as observed after conventional surgical repair. Long-term follow-up is necessary to assess long-term effectiveness of such management.


Adjuvant intraoperative photodynamic therapy in head and neck cancer.
There is an immediate need to develop local intraoperative adjuvant treatment strategies to improve outcomes in patients with cancer who undergo head and neck surgery. To determine the safety of photodynamic therapy with 2-(1-hexyloxyethyl)-2-devinyl pyropheophorbide-a (HPPH) in combination with surgery in patients with head and neck squamous cell carcinoma. Nonrandomized, single-arm, single-site, phase 1 study at a comprehensive cancer center among 16 adult patients (median age, 65 years) with biopsy-proved primary or recurrent resectable head and neck squamous cell carcinoma. Intravenous injection of HPPH (4.0 mg/m2), followed by activation with 665-nm laser light in the surgical bed immediately after tumor resection. Adverse events and highest laser light dose. Fifteen patients received the full course of treatment, and 1 patient received HPPH without intraoperative laser light because of an unrelated myocardial infarction. Disease sites included larynx (7 patients), oral cavity (6 patients), skin (1 patient), ear canal (1 patient), and oropharynx (1 patient, who received HPPH only). The most frequent adverse events related to photodynamic therapy were mild to moderate edema (9 patients) and pain (3 patients). One patient developed a grade 3 fistula after salvage laryngectomy, and another patient developed a grade 3 wound infection and mandibular fracture. Phototoxicity reactions included 1 moderate photophobia and 2 mild to moderate skin burns (2 due to operating room spotlights and 1 due to the pulse oximeter). The highest laser light dose was 75 J/cm2. The adjuvant use of HPPH-photodynamic therapy and surgery for head and neck squamous cell carcinoma seems safe and deserves further study. clinicaltrials.gov Identifier: NCT00470496.


Increasing CD8+ T lymphocytes predict subsequent development of intraoral lesions among individuals in the early stages of infection by the human immunodeficiency virus.
Determining the progression of human immunodeficiency virus (HIV) type 1 infection based on cellular and clinical markers has become increasingly important. Although a number of studies have shown a relationship between the presence of certain oral lesions and progression to AIDS, few data exist regarding the association with T lymphocyte counts. In this study, the question of whether intraoral lesions preceded or were the consequences of changes in T lymphocyte counts was examined. A total of 116 HIV-infected patients participating in two randomized double-blind placebo-controlled trials of zidovudine at the University of Minnesota AIDS Clinical Trials Unit (ACTU) were enrolled in a prospective dental study. Patients were examined for the presence of hairy leukoplakia, candidiasis, herpes simplex, herpes zoster, aphthae, atypical gingivitis, HIV-associated periodontitis, and necrotizing ulcerative gingivitis, as well as other oral lesions, every 3 months for a maximum of four examinations over a 1-year period. T lymphocyte counts before and after each patient's oral examination were obtained. No significant differences were found at examination 1 for differences in gender, race, age, education, tobacco smoking status, ethanol consumption habits, duration in ACTU drug protocol, duration in dental study protocol, or mean T lymphocyte counts between individuals with or without oral lesions at any time in the dental study.(ABSTRACT TRUNCATED AT 250 WORDS)


Chemokine gene expression and secretion by cytokine-activated human microvascular endothelial cells. Differential regulation of monocyte chemoattractant protein-1 and interleukin-8 in response to interferon-gamma.
The elicitation of leukocytes from the circulation to inflamed tissue depends on the activation of both the leukocyte and endothelial cell. In this study we determined the gene expression and secretion patterns for the chemokines interleukin-8 (IL-8) and monocyte chemoattractant protein-1 (MCP-1) in cytokine- and lipopolysaccharide (LPS)-treated cultured human lung microvascular endothelial cells (HLE). HLE constitutively expressed low levels of MCP-1 and IL-8. Treatment of HLE with a variety of cytokines and LPS up-regulated both IL-8 mRNA expression and release of immunoreactive IL-8 with an order of potency tumor necrosis factor-alpha (TNF-alpha) >> IL-1 alpha > LPS, whereas interferon-gamma (IFN-gamma) had no effect on IL-8 mRNA or antigenic levels. However, IFN-gamma, in combination with high doses of IL-1 alpha, resulted in a synergistic increase in IL-8 generation. MCP-1 gene expression and secretion was induced in a dose-dependent manner after IL-1 alpha, TNF-alpha, IFN-gamma, and LPS activation of HLE. IL-1 alpha was the most potent inducer of MCP-1 generation and LPS was relatively ineffective. IFN-gamma, in combination with low doses of IL-1 alpha, resulted in a synergistic increase in MCP-1 generation by HLE. These results demonstrate that although IL-8 and MCP-1 generation by HLE occurs on cytokine treatment, the relative ability of a given cytokine to elicit IL-8 generation is not directly parallel to effects on MCP-1 generation. These data suggest that the regulation of IL-8 and MCP-1 expression exhibit significant differences in their mechanisms. Such differences in the expression of specific chemokines may explain the specific appearance of various leukocytes at sites of inflammation and injury. These data also directly demonstrate that the lung microvascular endothelium contribute to the cytokine network of the lung, with the ability to respond to locally generated cytokines and to produce potent mediators of the local inflammatory response.


In vivo functional characterization of the SARS-Coronavirus 3a protein in Drosophila.
The Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV) 3a locus encodes a 274 a.a. novel protein, and its expression has been confirmed in SARS patients. To study functional roles of 3a, we established a transgenic fly model for the SARS-CoV 3a gene. Misexpression of 3a in Drosophila caused a dominant rough eye phenotype. Using a specific monoclonal antibody, we demonstrated that the 3a protein displayed a punctate cytoplasmic localization in Drosophila as in SARS-CoV-infected cells. We provide genetic evidence to support that 3a is functionally related to clathrin-mediated endocytosis. We further found that 3a misexpression induces apoptosis, which could be modulated by cellular cytochrome c levels and caspase activity. From a forward genetic screen, 78 dominant 3a modifying loci were recovered and the identity of these modifiers revealed that the severity of the 3a-induced rough eye phenotype depends on multiple cellular processes including gene transcriptional regulation.


St. George's Respiratory Questionnaire has longitudinal construct validity in lymphangioleiomyomatosis.
Lymphangioleiomyomatosis (LAM) is an uncommon, progressive, cystic lung disease that causes shortness of breath, hypoxemia, and impaired health-related quality of life (HRQL). Whether St. George's Respiratory Questionnaire (SGRQ), a respiratory-specific HRQL instrument, captures longitudinal changes in HRQL in patients with LAM is unknown. Using data from the Multicenter International Lymphangioleiomyomatosis Efficacy and Safety of Sirolimus trial, we performed analyses to examine associations between SGRQ scores and values for four external measures (anchors). Anchors included (1) FEV₁, (2) diffusing capacity of the lung for carbon monoxide, (3) distance walked during the 6-min walk test, and (4) serum vascular endothelial growth factor-D. SGRQ scores correlated with the majority of anchor values at baseline, 6 months, and 12 months. Results from longitudinal analyses demonstrated that SGRQ change scores tracked changes over time in values for each of the four anchors. At 12 months, subjects with the greatest improvement from baseline in FEV₁ experienced the greatest improvement in SGRQ scores (Symptoms domain, -13.4 ± 14.6 points; Activity domain, -6.46 ± 8.20 points; Impacts domain, -6.25 ± 12.8 points; SGRQ total, -7.53 ± 10.0 points). Plots of cumulative distribution functions further supported the longitudinal validity of the SGRQ in LAM. In LAM, SGRQ scores are associated with variables used to assess LAM severity. The SGRQ is sensitive to change in LAM severity, particularly when change is defined by FEV₁, perhaps the most clinically relevant and prognostically important variable in LAM. The constellation of results here supports the validity of the SGRQ as capable of assessing longitudinal change in HRQL in LAM.


Ion-driven photoluminescence modulation of quasi-two-dimensional MoS2 nanoflakes for applications in biological systems.
Quasi-two-dimensional (quasi-2D) molybdenum disulfide (MoS2) is a photoluminescence (PL) material with unique properties. The recent demonstration of its PL, controlled by the intercalation of positive ions, can lead to many opportunities for employing this quasi-2D material in ion-related biological applications. Here, we present two representative models of biological systems that incorporate the ion-controlled PL of quasi-2D MoS2 nanoflakes. The ion exchange behaviors of these two models are investigated to reveal enzymatic activities and cell viabilities. While the ion intercalation of MoS2 in enzymatic activities is enabled via an external applied voltage, the intercalation of ions in cell viability investigations occurs in the presence of the intrinsic cell membrane potential.


Bringing the age-related macular degeneration high-risk allele age-related maculopathy susceptibility 2 into focus with stem cell technology.
Age-related macular degeneration (AMD) is a major cause of blindness in older adults in developed countries. It is a multifactorial disease triggered by both environmental and genetic factors. High-temperature requirement A serine peptidase 1 (HTRA1) and age-related maculopathy susceptibility 2 (ARMS2) are two genes that are strongly associated with AMD. Because ARMS2 is an evolutionarily recent primate-specific gene and because the ARMS2/HTRA1 genes are positioned at a locus on chromosome 10q26 in a region with strong linkage disequilibrium, it is difficult to distinguish the functions of the individual genes. Therefore, it is necessary to bring these genes into focus. Patient-specific induced pluripotent stem cell (iPSC)-derived retinal pigment epithelium (RPE) provides direct access to a patient's genetics and allows for the possibility of identifying the initiating events of RPE-associated degenerative diseases. In this paper, a review of recent epidemiological studies of AMD is offered. An argument for a definite correlation between the ARMS2 gene and AMD is presented. A summary of the use of ARMS2 genotyping for medical treatment is provided. Several ARMS2-related genetic models based on such stem cells as iPSCs are introduced. The possibility of applying gene-editing techniques and stem-cell techniques to better explore the mechanisms of the ARMS2 high-risk allele, which will lead to important guidance for treatment, is also discussed.


Biogeography of Aspergillus species in soil and litter.
Based on counts of Aspergillus species reported in over 250 studies of microfungi from soils and litter, chi-square analyses were conducted on species occurrence in five biomes and five latitude ranges to determine variations from expected distributions. There was no overall trend in distribution of the members of the entire genus by biome, however, individual sections of the genus appeared to have distinct distribution patterns. Most members of sections Aspergillus, Nidulantes, Flavipedes and Circumdati occurred at greater than expected frequencies in desert soils. There was no distinct pattern of species occurrence for forest, wetland, or cultivated soils, although members of section Nidulantes were quite rare in cultivated soils. Most species occurred at or below expected frequencies in grassland soils. Members of the genus tended to occur at greater than expected frequencies at latitudes in the subtropical/warm temperate zone between 26 and 35 degrees. Most species occurred at expected frequencies in the lower latitudes, and below expected frequencies in latitudes greater than 35 degrees.


Monoamine neurotransmitters and mood swings: a dynamical systems approach.
Serotonin, dopamine and norepinephrine are monoamine neurotransmitters that modulate our mood state. Hence, imbalances in the levels of these neurotransmitters have been linked to the incidence of several psychiatric disorders. Here, a mathematical model written in terms of ordinary differential equations is proposed to represent the interaction of these three neurotransmitters. It is analytically and numerically shown that this model can experience a Hopf bifurcation. Thus, by varying a parameter value, the neurotransmitter levels can change from a steady state to an oscillatory behavior, which may be at least a partial explanation of the mood swings observed in depressed people.


High-Performance and Rapid-Response Electrical Heaters Based on Ultraflexible, Heat-Resistant, and Mechanically Strong Aramid Nanofiber/Ag Nanowire Nanocomposite Papers.
High-performance and rapid response electrical heaters with ultraflexibility, superior heat resistance, and mechanical properties are highly desirable for the development of wearable devices, artificial intelligence, and high-performance heating systems in areas such as aerospace and the military. Herein, a facile and efficient two-step vacuum-assisted filtration followed by hot-pressing approach is presented to fabricate versatile electrical heaters based on the high-performance aramid nanofibers (ANFs) and highly conductive Ag nanowires (AgNWs). The resultant ANF/AgNW nanocomposite papers present ultraflexibility, extremely low sheet resistance (minimum Rs of 0.12 Ω/sq), and outstanding heat resistance (thermal degradation temperature above 500 °C) and mechanical properties (tensile strength of 285.7 MPa, tensile modulus of 6.51 GPa with a AgNW area fraction of 0.4 g/m2), benefiting from the partial embedding of AgNWs into the ANF substrate and the extensive hydrogen-bonding interactions. Moreover, the ANF/AgNW nanocomposite paper-based electrical heaters exhibit satisfyingly high heating temperatures (up to ∼200 °C) with rapid response time (10-30 s) at low AgNW area fractions and supplied voltages (0.5-5 V) and possess sufficient heating reliability, stability, and repeatability during the long-term and repeated heating and cooling cycles. Fully functional applications of the ANF/AgNW nanocomposite paper-based electrical heaters are demonstrated, indicating their excellent potential for emerging electronic applications such as wearable devices, artificial intelligence, and high-performance heating systems.


The relation of exposure to asbestos and smoking habit with pulmonary function tests and chest radiograph.
Environmental cum medical study was conducted in asbestos cement factory. The environment was evaluated for asbestos fiber by the methods recommended by BIS. Total 355 exposed and 312 suitably matched control workers were investigated by spirometer, Wright's peak flow meter and full sized postero-anterior chest radiograph. The levels of asbestos fiber were 2 to 3 times higher than TLV i.e. 2 f/ml in pipe cutting dept., crude fiber grinding inlet count was more than the ACGIH recommended limit i.e. 5 mpccf of air in pipe cutting dept. and silica mill. In the rest of the department, fiber level as well as dust particle count were below prescribed limit. The comparison of mean values of PFT parameters of workers with 16-20 years exposure history with control one was showing statistically significant decline in mean values of FVC only suggesting restrictive type of PFT impairment in this group of workers. But in workers with more than 20 years exposure, the mean values of all the parameters studied were reduced as compared to control one suggesting combined type of PFT impairment. When the mean values of PFT parameters of exposed smokers were compared with exposed non-smokers there was statistically no significant difference. This can be due to marginal contribution of smoking habit in impairment of PFT parameters of exposed smokers. The percentages of workers with parenchymal and pleural changes due to asbestos exposure were nearly two times more in more than 20 years exposure groups as compared to 11-20 years exposure groups. The parenchymal and pleural changes due to asbestos exposure were more common in exposed smokers as compared exposed non-smokers. However the detailed analysis revealed that if smoking contributes to the development of interstitial fibrosis, the contribution is a marginal one in comparison to the effect of asbestos dust exposure.


Development of adjunctive therapies for bacterial meningitis and lessons from knockout mice.
Bacterial meningitis is a medical emergency and is optimally managed in an intensive care environment. Despite the use of antibiotics, the prognosis of this disease is poor because of central nervous system complications such as brain edema formation, cerebrovascular alterations, intracranial hemorrhage, and hydrocephalus. Effective adjunctive therapies are still missing. Experimental studies with animal models have provided new insights into the pathophysiology during the acute phase of bacterial meningitis. In recent years, knockout mice have become a powerful tool to investigate the role of particular genes and have also been applied in bacterial meningitis research. The use of these mice offered new insights into the role of different cytokines, proteases, and oxidants involved in the inflammatory cascade. Translating this knowledge into new therapies will provide new treatment strategies for this serious disease in the future.


Oral misoprostol for premature rupture of membranes at term.
The study was undertaken to compare the efficacy, safety, and maternal satisfaction of oral misoprostol and intravenous oxytocin for labor induction in women with premature rupture of membranes at term. One hundred five women were stratified by parity and randomly assigned to oral misoprostol 75 microg every 4 hours as needed to establish labor or to intravenous oxytocin. The induction to vaginal delivery time with oral misoprostol was 737 (+/-426) minutes compared with 573 (+/-318) minutes with oxytocin (P=.04). The incidence of hyperstimulation was lower in the misoprostol group (6.0% vs 27.1%, P=.005). Women were more likely to be very satisfied with their care in the misoprostol group (86.0% vs 63.4%, P=.02). In women at term with premature rupture of membranes, oral misoprostol resulted in a longer induction to vaginal delivery interval but increased maternal satisfaction and less hyperstimulation compared with intravenous oxytocin. Further research is needed to assess uncommon neonatal and maternal outcomes.


Convergent adaptation to dangerous prey proceeds through the same first-step mutation in the garter snake Thamnophis sirtalis.
Convergent phenotypes often result from similar underlying genetics, but recent work suggests convergence may also occur in the historical order of substitutions en route to an adaptive outcome. We characterized convergence in the mutational steps to two independent outcomes of tetrodotoxin (TTX) resistance in separate geographic lineages of the common garter snake (Thamnophis sirtalis) that coevolved with toxic newts. Resistance is largely conferred by amino acid changes in the skeletal muscle sodium channel (NaV 1.4) that interfere with TTX-binding. We sampled variation in NaV 1.4 throughout western North America and found clear evidence that TTX-resistant changes in both lineages began with the same isoleucine-valine mutation (I1561V) within the outer pore of NaV 1.4. Other point mutations in the pore, shown to confer much greater resistance, accumulate later in the evolutionary progression and always occur together with the initial I1561V change. A gene tree of NaV 1.4 suggests the I1561V mutations in each lineage are not identical-by-decent, but rather they arose independently. Convergence in the evolution of channel resistance is likely the result of shared biases in the two lineages of T. sirtalis-only a few mutational routes can confer TTX resistance while maintaining the conserved function of voltage-gated sodium channels.


Meprin Metalloproteases Generate Biologically Active Soluble Interleukin-6 Receptor to Induce Trans-Signaling.
Soluble Interleukin-6 receptor (sIL-6R) mediated trans-signaling is an important pro-inflammatory stimulus associated with pathological conditions, such as arthritis, neurodegeneration and inflammatory bowel disease. The sIL-6R is generated proteolytically from its membrane bound form and A Disintegrin And Metalloprotease (ADAM) 10 and 17 were shown to perform ectodomain shedding of the receptor in vitro and in vivo. However, under certain conditions not all sIL-6R could be assigned to ADAM10/17 activity. Here, we demonstrate that the IL-6R is a shedding substrate of soluble meprin α and membrane bound meprin β, resulting in bioactive sIL-6R that is capable of inducing IL-6 trans-signaling. We determined cleavage within the N-terminal part of the IL-6R stalk region, distinct from the cleavage site reported for ADAM10/17. Interestingly, meprin β can be shed from the cell surface by ADAM10/17 and the observation that soluble meprin β is not capable of shedding the IL-6R suggests a regulatory mechanism towards trans-signaling. Additionally, we observed a significant negative correlation of meprin β expression and IL-6R levels on human granulocytes, providing evidence for in vivo function of this proteolytic interaction.


[Prevention of tuberculosis in care settings].
The hospital is a favourable setting for the transmission of tubercle bacilli. The presence of susceptible subjects, often immunocompromised, increases the dangers. This risk extends to the patients' visitors and to the staff. It is therefore the responsibility of the hospital to establish preventative measures capable of reducing the risk of transmission or to reduce the effects by appropriate management of exposed subjects. The modes and vectors of transmission are well established. The standardised prevention of transmission is achieved by isolation, the indications and duration of which are based on incomplete information. The surveillance of the carers by the doctor in charge, is based on precise recommendations depending on the risk of exposure. The objectives are a reduction diagnostic delay, a better determination of infectivity and its duration during treatment, and a more complete census of cases of hospital acquired tuberculosis. The management of tuberculosis in hospital requires co-ordination of all involved including those outside the institution and a deliberate policy in the institution itself.


Selected Risk Factors for Cancer among Koreans Residing in California.
Preliminary analysis of data (N=2,441) drawn from an ongoing population-based study of people of Korean descent who reside in California revealed the presence of selected cancer risk factors, especially tobacco use and lack of vigorous exercise. Men and women differed in cancer risks, with men being more likely than women to be smokers, less likely to exercise, more likely to be obese, and more likely to consume alcohol. Although relationships between demographic characteristics and cancer risks differed in strength by gender, patterns of correlation were similar among men and women. Future studies should explore the relationship between lifestyle and health risk interactions by gender in greater detail.


Calcium Intake and Bone Mineral Acquisition during the Pubertal Growth Spurt: Three-Year Follow-Up of the Kitakata Kids Health Study in Japan.
Calcium intake during a growth spurt may influence bone mineral acquisition. However, no population-based cohort studies have examined the relationship between calcium intake and whole-body bone mineral acquisition in Japanese children. The present study investigated the relationship between calcium intake and whole-body bone mineral acquisition in community-dwelling children in a northeast region of Japan using dual-energy X-ray absorptiometry. The source population for the baseline survey comprised all school children in 4th through 6th grades (275 children; age range, 10-12 y) in the Shiokawa area of Kitakata City, Fukushima. We obtained complete information from 220 children (100 girls and 120 boys), and analyzed total body less head (TBLH) bone mineral content (BMC), TBLH areal bone mineral density (aBMD), and bone mineral apparent density (BMAD) as an estimate of volumetric bone density. The Food Frequency Questionnaire for the Prevention and Management of Osteoporosis was validated in a previous study and used to estimate dietary nutrient intake. At baseline, mean calcium intake was 641 mg/d in girls and 660 mg/d in boys. Calcium intake in boys showed a significant (p<0.05) relationship with TBLH BMC and TBLH aBMD at follow-up, and with changes in TBLH BMC, TBLH aBMD, and TB BMAD from baseline to follow-up. After adjusting for potential confounding factors including body weight, we found no significant relationships between calcium intake and bone mineral parameters. Further studies are needed to clarify whether calcium intake affects bone mineral acquisition during pubertal growth spurts in the Japanese population.


Allyl Isothiocianate Induces Ca2+ Signals and Nitric Oxide Release by Inducing Reactive Oxygen Species Production in the Human Cerebrovascular Endothelial Cell Line hCMEC/D3.
Nitric oxide (NO) represents a crucial mediator to regulate cerebral blood flow (CBF) in the human brain both under basal conditions and in response to somatosensory stimulation. An increase in intracellular Ca2+ concentrations ([Ca2+]i) stimulates the endothelial NO synthase to produce NO in human cerebrovascular endothelial cells. Therefore, targeting the endothelial ion channel machinery could represent a promising strategy to rescue endothelial NO signalling in traumatic brain injury and neurodegenerative disorders. Allyl isothiocyanate (AITC), a major active constituent of cruciferous vegetables, was found to increase CBF in non-human preclinical models, but it is still unknown whether it stimulates NO release in human brain capillary endothelial cells. In the present investigation, we showed that AITC evoked a Ca2+-dependent NO release in the human cerebrovascular endothelial cell line, hCMEC/D3. The Ca2+ response to AITC was shaped by both intra- and extracellular Ca2+ sources, although it was insensitive to the pharmacological blockade of transient receptor potential ankyrin 1, which is regarded to be among the main molecular targets of AITC. In accord, AITC failed to induce transmembrane currents or to elicit membrane hyperpolarization, although NS309, a selective opener of the small- and intermediate-conductance Ca2+-activated K+ channels, induced a significant membrane hyperpolarization. The AITC-evoked Ca2+ signal was triggered by the production of cytosolic, but not mitochondrial, reactive oxygen species (ROS), and was supported by store-operated Ca2+ entry (SOCE). Conversely, the Ca2+ response to AITC did not require Ca2+ mobilization from the endoplasmic reticulum, lysosomes or mitochondria. However, pharmacological manipulation revealed that AITC-dependent ROS generation inhibited plasma membrane Ca2+-ATPase (PMCA) activity, thereby attenuating Ca2+ removal across the plasma membrane and resulting in a sustained increase in [Ca2+]i. In accord, the AITC-evoked NO release was driven by ROS generation and required ROS-dependent inhibition of PMCA activity. These data suggest that AITC could be exploited to restore NO signalling and restore CBF in brain disorders that feature neurovascular dysfunction.


Efficient production of nanoparticle-loaded orodispersible films by process integration in a stirred media mill.
Orodispersible films possess a great potential as a versatile platform for nanoparticle-loaded oral dosage forms. In this case, poorly water-soluble organic materials were ground in a stirred media mill and embedded into a polymer matrix. The aim of this study was the shortening of this manufacturing process by the integration of several process steps into a stirred media mill without facing disadvantages regarding the film quality. Furthermore, this process integration is time conserving due to the high stress intensities provided in the mill and applicable for high solids contents and high suspension viscosities. Two organic materials, the model compound Anthraquinone and the active pharmaceutical ingredient Naproxen were investigated in this study. Besides the impact of the film processing on the crystallinity of the particles in the orodispersible film, a particle load of up to 50% was investigated with the new developed processing route. Additionally, a disintegration test was developed, combining an appropriate amount of saliva substitute and a clear endpoint determination. In summary, high nanoparticle loads in orodispersible films with good particle size preservation after film redispersion in water as well as a manufacturing of the film casting mass within a few minutes in a stirred media mill was achieved.


FEASibility testing a randomized controlled trial of an exercise program to improve cognition for T2DM patients (the FEAST trial): A study protocol.
While cognitive dysfunction is an important concern in persons with type 2 diabetes mellitus (T2DM), it has received little attention in the T2DM literature. Although it often remains unrecognized, cognitive dysfunction associated with T2DM can lead to severe consequences. Prior research studies have consistently shown that aerobic exercise enhances cognitive function among healthy subjects. However, very few studies have examined the effects of aerobic exercise on cognitive function in persons with T2DM. In addition, one important single-nucleotide polymorphism that influences cognition in humans is the brain-derived neurotrophic factor (BDNF) Val66Met variant. Despite strong evidence suggesting aerobic exercise has a beneficial effect on cognitive function, there is significant variability in individual response to exercise programs on cognitive outcomes among Val/Val versus Met carriers. However, the evidence on how the BDNF Val66Met variant influences cognitive outcomes following an aerobic exercise intervention among individuals with T2DM is currently lacking. Therefore, the purpose of this randomized controlled trial is to pilot-test a 3-month supervised exercise program to improve plasma BDNF levels and cognition, overall and according to genotypes of the BDNF Val66Met variant. A total of 81 patients with T2DM will be randomly assigned to either aerobic exercise group (n = 54) or attention control group (n = 27) for 3 months. Outcomes of interest include postintervention changes in plasma BDNF levels, fasting blood glucose, hemoglobin A1c, body mass index, executive function, memory, and processing speed. This study will provide further evidence on use of exercise as a non-pharmaceutical, low-cost intervention to improve cognition in this population.


The impact of heat waves on mortality in Northwest India.
Heat waves are anticipated to worsen with climate change. India, an understudied area with >15% of the world's population, commonly experiences temperature extremes and already resembles potential future climates of more temperate regions. Registry data from local municipal corporations and government offices were collected and translated, yielding daily all-cause mortality for 4 communities in Northwest India for all or part of the period 2000-2012. Heat waves were defined as ≥2 days with local temperature ≥97th percentile for that community. An alternate definition matching that used by the Indian Meteorological Department was also developed, to enhance policy relevance. Community-specific average daily maximum temperature over the entire record ranged from 32.5 to 34.2 °C (90.5-93.6 °F). Across communities, total mortality increased 18.1% during heat wave days compared with non-heat-wave days [95% confidence interval (CI): -5.3%, 47.3%], with the highest risk in Jaipur (29.9% [95% CI: 24.6%, 34.9%]). Evidence of effect modification by heat wave characteristics (intensity, duration, and timing in season) was limited. Findings indicate health risks associated with heat waves in communities with high baseline temperatures. Results can inform heat wave-health assessments in temperate regions in future, and improve our understanding of temperature-health associations under climate change. Further investigation of potential effect modification by heat wave characteristics is needed.


The construction, identification and characterisation of plasmids containing human alpha-lactalbumin cDNA sequences.
We describe the cloning of double-stranded cDNA synthesized from lactating human mammary gland total poly(A)-containing RNA, into the EcoRI site of the plasmid pAT153. Nine recombinants were shown to contain alpha-lactalbumin cDNA sequences as determined by positive hybridisation translation of complementary RNA. Restriction enzyme maps were determined for six of these. Alignment of the restriction map with the known amino acid sequence of human alpha-lactalbumin provided evidence that two plasmids, designated phO-53 and phB-35, contained the complete coding sequence of the primary translation product (pre-alpha-lactalbumin). Hybridisation studies using purified human, monkey and guinea-pig alpha-lactalbumin cDNA demonstrated that greater nucleotide sequence divergence has occurred within the rodents than the primates, and that rodent alpha-lactalbumin mRNAs retain regions of homology with primate alpha-lactalbumin mRNAs.


Clinical interest of the combined use of serum CD26 and alpha-L-fucosidase in the early diagnosis of colorectal cancer.
The purpose of this study was to assess if the combination of CD26 and alpha-L-fucosidase has a role in the diagnosis of colorectal cancer, paying particular attention to the stages in which the tumour is not yet disseminated. CD26 concentration and alpha-L-fucosidase activity were determined in sera from 110 colorectal cancer patients and 46 donors. The combination of CD26 and alpha-L-fucosidase showed a specificity of 100% with a sensitivity of 64% in the diagnosis of colorectal cancer. Interestingly, the combination of both markers had a sensitivity of 75% in the stage I at the highest specificity (100%), providing also high sensitivity levels for the other non-disseminated stages (66% for stages II and III). In conclusion, the combined use of CD26 and alpha-L-fucosidase offers high sensitivity with high specificity in the diagnosis of colorectal cancer, especially at the earliest stage (TNM I).


The effect of surface roughness on the Weibull distribution of porcelain strength.
The purpose of the present study was to test the hypothesis that glazing will affect the Weibull modulus or the mean flexural strength of dental porcelain. Four groups (n = 30) of specimens were prepared from feldspathic body porcelain (Vita VMK 68). The specimens were tested in groups: original glazed condition (control), and after grinding separately with 1,000-grit, 600-grit, and 100-grit silicon carbide abrasive. A three-point flexure test was undertaken for each specimen. The flexural strength of porcelain and the Weibull modulus were then obtained using a computer program and load-to-failure data. Flexural strength decreased as surface roughness increased, and the differences were significant (p < 0.05), as determined by Tukey's multiple range test, except between the 600-grit group and the 100-grit group. The Weibull modulus of the glazed group was the largest (16.3), and the surface roughness was found to influence the Weibull modulus.


Olfactory dysfunction.
Otolaryngologists, neurologists and other medical practitioners are often not well equipped for assessing olfactory (dys)function. They either use no or inadequate olfactory tests. This problem of inadequate olfactory testing was systematically attacked by American psychologists in the early 80's and led to the construction of odour identification tests which are easy to administer. Combining the advantages of two of these American tests we developed a Dutch odour identification test (GITU), consisting of two subsets of 18 natural odourants and applicable in two ways: one for use in the ENT clinic, the other for industrial purposes. The first results of this test indicate that the incidence of serious olfactory disorder among adults in the Netherlands may be conservatively estimated at about 1%. The GITU readily discriminates between patients and controls and is sensitive to variables known to affect olfaction (gender, age). The recognition of olfactory dysfunction as a major problem has led in the U.S.A. to the establishment of clinical research centers for the study of human chemoreception. Evaluation results of four of those clinics together with data of three more case series--with a total number of patients of 4000--show that two thirds of all patients fall into three etiological categories: 1. Nasal disease and/or paranasal sinus disease. 2. Viral infection of the upper respiratory pathway. 3. Head trauma. For each of the three categories the literature is reviewed in order to arrive at a clearer picture of the olfactory patient with respect to age, gender, degree of olfactory deficit, spontaneous recovery, effectiveness of therapy and localization of the defect along the olfactory pathway. Finally an appeal is made to clinicians with interest in the subject to exchange more information with research scientists in olfaction. Such exchange is considered essential to making progress in this field.


Retinal blood flow measurements and neuroretinal rim damage in glaucoma.
To assess retinal blood flow characteristics in subjects with normal tension glaucoma (NTG), primary open angle glaucoma (POAG), and a group of controls using the Heidelberg retina flowmeter (HRF). The vascular parameters were correlated against structural damage of the optic nerve head, assessed using the Heidelberg retina tomograph (HRT). HRF images were obtained in 76 subjects with NTG, 58 with POAG, and 38 controls. Optic nerve head images, acquired using the HRT, were analysed with Moorfields Regression Analysis software. The HRF variables, measured adjacent to a rim segment identified as "abnormal," were compared with the vascular parameters of the "normal" rim segments. The HRF parameters of the segments identified as normal in glaucoma subjects were compared with matched control segments. The glaucoma subjects had significantly lower retinal haemodynamics than the control subjects. There were no significant differences in the HRF parameters between the NTG and POAG subjects. The discs that had been identified as having abnormal segments had lower HRF values than those with a corresponding normal segment. The glaucoma subjects with normal rim segments had statistically significant lower velocity, flow, and volume measurements than the controls for each location sampled. This study shows a relation between structural damage of the optic nerve head and the level of retinal blood flow. The changes in the circulation could indicate that it may be an early marker of the pathological process.


A Novel Model for Studying Voltage-Gated Ion Channel Gene Expression during Reversible Ischemic Stroke.
The dysfunction of voltage-gated ion channels contributes to the pathology of ischemic stroke. In this study, we developed rat models of transient ischemic attack (TIA) and reversible ischemic neurological deficit (RIND) that was induced via the injection of artificial embolic particles during full consciousness, that allow us to monitor the neurologic deficit and positron emission tomography (PET) scans in real-time. We then evaluated the infarction volume of brain tissue was confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, and gene expressions were evaluated by quantitative real-time PCR (qPCR). We found that rats with TIA or RIND exhibited neurological deficits as determined by negative TTC and PET findings. However, the expression of voltage-gated sodium channels in the hippocampus was significantly up-regulated in the qPCR array study. Furthermore, an altered expression of sodium channel β-subunits and potassium channels, were observed in RIND compared to TIA groups. In conclusion, to our knowledge, this is the first report of the successful evaluation of voltage-gated ion channel gene expression in TIA and RIND animal models. This model will aid future studies in investigating pathophysiological mechanisms, and in developing new therapeutic compounds for the treatment of TIA and RIND.


Alpha-internexin expression in medulloblastomas and atypical teratoid-rhabdoid tumors.
To determine whether medulloblastomas and atypical teratoid/rhabdoid tumors express alpha-internexin, an intermediate filament protein that is expressed in normal neurons undergoing maturation and differentiation. 28 medulloblastomas and 5 atypical teratoid/rhabdoid tumors were examined for the immunohistochemical expression of alpha-internexin, as well as the neuronal markers peripherin and synaptophysin, and glial fibrillary acidic protein. Overall, 21 of 28 medulloblastomas (75%) expressed alpha-internexin. More specifically, alpha-internexin expression was observed in 6 of 10 (60%) classic medulloblastomas, 12 of 14 (86%) desmoplastic medulloblastomas, 2 of 3 (67%) nodular medulloblastomas, and in one medullomyoblastoma. Similarly, 4 of 5 (80%) atypical teratoid/rhabdoid tumors expressed alpha-internexin. The extent of staining for alpha-internexin tended to be less than that of synaptophysin for both medulloblastomas (75% vs 93%) and atypical teratoid/rhabdoid tumors (80% vs 100%). In contrast to alpha-internexin, peripherin was expressed in only 4 medulloblastomas and one atypical teratoid/rhabdoid tumor. Alpha-internexin is expressed in the majority of medulloblastomas and atypical teratoid/rhabdoid tumors, indicating that these primitive tumors usually exhibit neuronal differentiation.


Effects of berberine on the growth performance, antioxidative capacity and immune response to lipopolysaccharide challenge in broilers.
This study evaluated the effects of berberine on growth performance, immunity, haematological parameters, antioxidant capacity, and the expression of immune response-related genes in lipopolysaccharide (LPS)-challenged broilers. We assigned 120 one-day-old male broilers (Ross 308) to two treatment groups; each group included two subgroups, each of which included six replicates of five birds per replicate. The experiment used a 2 × 2 factorial arrangement with berberine treatment (0 or 60 mg/kg dietary) and challenge status [injection of saline (9 g/L w/v) or LPS (1.5 mg/kg body weight)] as the main factors. On days 14, 16, 18 and 20, broilers were intraperitoneally injected with LPS or physiological saline. Blood and liver samples were collected on day 21. Dietary berberine supplementation significantly alleviated the compromised average daily gain and average daily feed intake (p < 0.05) caused by LPS. The LPS challenge led to increased lymphocyte and white blood cell (WBC) counts, malondialdehyde (serum and liver) content, and immunoglobulin G and M, tumour necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) expression (p < 0.05) and significantly reduced serum total superoxide dismutase (T-SOD) activity (p < 0.05). Dietary berberine significantly mitigated the LPS-induced decreases in the mRNA expression of nuclear factor-kappa B (NF-κB), TNF-α, IL-1β, inducible nitrite synthase and cyclooxygenase-2 (p < 0.05) in the liver. In conclusion, berberine supplementation has a positive effect on LPS challenge, which may be related to the increase in antioxidant enzyme activity and inhibition of both NF-κB signalling and the expression of inflammatory mediators.


Spontaneous obliteration of spontaneous vertebral arteriovenous fistula associated with fibromuscular dysplasia after partial surgery: A case report.
We describe a patient with spontaneous obliteration of spontaneous vertebral arteriovenous fistula (VAVF) associated with fibromuscular dysplasia (FMD) after partial surgery. A 52-year-old hypertensive female woke up one morning with left shoulder pain and weakness of the left upper extremity. A few days later, she developed left-sided audible bruit. She was treated for left frozen shoulder and supportive treatment for audible bruit for four years. She was referred from her general physician to a neurosurgeon because of left arm weakness. Physical examination showed signs of cervical radiculomyelopathy. Magnetic resonance imaging (MRI) showed an extradural mass on the left side of the cervical spinal canal from level C2 to C6. Provisional diagnosis was epidural vascular tumour. Laminectomy and partial removal of the mass was performed at level C5 to C6. Pathological report revealed suspected vascular malformation. Postoperative MRI showed thrombosed epidural vascular structure. Angiography showed dysplastic changes of both vertebral arteries representing FMD with VAVF of the left vertebral artery at level C1-C2. Two years after surgery, follow-up MRI demonstrated complete spontaneous resolution of the large thrombosed epidural vein. Disappearance of her audible bruit immediately after surgery and gradual improvement of her cervical radiculomyelopathy were observed after two years of clinical follow-up. From the literature, we found another 11 patients with 12 VAVFs who had spontaneous obliteration or cure of their fistulas. In the present case, spontaneous obliteration of the fistula seems to correlate with surgery inducing closure of the epidural venous exit leading to thrombosis of the enlarged epidural draining vein.


Magnetic switching of ferroelectric domains at room temperature in multiferroic PZTFT.
Single-phase magnetoelectric multiferroics are ferroelectric materials that display some form of magnetism. In addition, magnetic and ferroelectric order parameters are not independent of one another. Thus, the application of either an electric or magnetic field simultaneously alters both the electrical dipole configuration and the magnetic state of the material. The technological possibilities that could arise from magnetoelectric multiferroics are considerable and a range of functional devices has already been envisioned. Realising these devices, however, requires coupling effects to be significant and to occur at room temperature. Although such characteristics can be created in piezoelectric-magnetostrictive composites, to date they have only been weakly evident in single-phase multiferroics. Here in a newly discovered room temperature multiferroic, we demonstrate significant room temperature coupling by monitoring changes in ferroelectric domain patterns induced by magnetic fields. An order of magnitude estimate of the effective coupling coefficient suggests a value of ~1 × 10(-7) sm(-1).


Composition of the Gut Microbiota in Attention Deficit Hyperactivity Disorder: A Systematic Review and Meta-Analysis.
The latest research accumulates information to explore the correlation between gut microbiota and neurodevelopmental disorders, which may lead to new approaches to treat diseases such as attention deficit/hyperactivity disorder (ADHD). However, the conclusions of previous studies are not completely consistent. The objective of the systematic review and meta-analysis was to identify evidence on the dysbiosis of gut microbiota in ADHD and find potential distinctive traits compared to healthy controls. Electronic databases, including PubMed, Embase, Web of Science, Cochrane Library, and PsycINFO, were searched up to August 24, 2021, using predetermined terms. Meta-analysis was performed to estimate the comparison of microbiota profiles (alpha and beta diversity) and the relative abundance of gut microbiota in ADHD patients and healthy controls. A total of eight studies were included in the meta-analysis, containing 316 ADHD patients and 359 healthy controls. There was a higher Shannon index in ADHD patients than in healthy controls (SMD = 0.97; 95% CI, 0.13 to 1.82; P = 0.02; I2 = 96%), but the significance vanished after sensitivity analysis because of high heterogeneity. No significant differences in other alpha diversity indexes were found. Regarding the relative abundance of gut microbiota, the genus Blautia was significantly elevated in ADHD patients compared with controls (SMD = 0.34; 95% CI, 0.06 to 0.63; P = 0.02; I2 = 0%). Patients with ADHD had gut microbiome alterations compared to healthy controls. Though more studies with strict methodology are warranted due to the high heterogeneity, further studies to translate the findings of gut microbiota dysbiosis to clinical application in ADHD patients are needed and may guide targeted therapies. [https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=273993], identifier PROSPERO (CRD42021273993).


Evaluation of a CAT Database and Expert Appraisal of CATs Developed by Students.
Five steps have been recommended to provide evidence-based patient care: formulating a clinical question, searching for literature, evaluating the validity and applicability of results, implementing results into practice, and assessing if the new evidence has led to improved health care. Students can be trained in these steps by the development of knowledge summaries such as critically appraised topics (CATs). The aim of the present project was the development, use, and evaluation of a German-language CAT database and an appraisal of the quality of CATs developed by students. A total of 153 fifth-year veterinary medical students (in 21 groups) were enrolled in the project. Each group developed a CAT and most students participated in a survey. To learn more about the quality of the CATs, we asked experts to appraise the texts written by the students. The CATs were indexed with key words and assigned to specific fields corresponding to the European Colleges of Veterinary Specialisation. Currently, 57 CATs have been developed. The majority of students stated that writing CATs is a good exercise and that "it is important to teach the assessment of scientific information." In total, 13 experts completed the questionnaires, out of which 9 graded the CAT they appraised as good. In addition to English-language CAT databases, German tools should also be available for students and practitioners.


Use of thiols as protecting ligands in reflective surface films of silver nanoparticles.
We report the preparation of metal liquid-like films (MELLFs) of silver nanoparticles stabilized by thiolate surface ligands. These surface films, composed of particles with diameters of about 100 nm, are highly reflective and can be employed in the fabrication of liquid mirrors. A number of different thiols are considered as stabilizing ligands, including alkanethiols, aromatic thiols and dithiols. Under identical preparation conditions, some lead to the spontaneous formation of reflective surface films, whereas others do not. Shorter chain alkanethiols (C2 to C8), thiophene and thiophenol are found to be effective whereas longer chain alkanethiols (C10 and C12) and short dithiols (C2 and C3) do not produce reflective films. Ethanethiol and propanethiol protected particles form surface films with reflectivities in the near-IR that surpass those of a previous generation of MELLFs prepared with 1,10-dimethylphenanthroline as the ligand. This enhanced reflectivity is attributed to a more closely packed nanoparticle film with a higher metal volume fraction. The closer proximity of the particles, however, leads to enhanced coupling of their surface plasmon resonance and increased absorption in the visible region of the spectrum. Short chain dithiols do not produce MELLFs but rather provoke particle aggregation. In the case of 1,2-ethanedithiol, the particles are found to precipitate in a continuous organic matrix, presumably caused by oxidative polymerization of the dithiol to a polydisulfide. Finally, preliminary investigations indicate that a large variety of organic solvants can be employed in the preparation of thiol protected MELLFs.


Comparative Study of the Prophylactic Effects of Intravenous Injection of Dexmedetomidine, Ondansetron, and Pethidine on Postoperative Shivering of Abdominal Surgery under General Anesthesia: A Randomized Clinical Trial.
postoperative shivering is a common complication of various surgical, so far no acceptable theory has been presented on the prevention of it. The aim of this study was to compare the effect of intravenous injection of dexmedetomidine, ondansetron, and pethidine on postoperative shivering among patients under abdominal surgery. In a double-blind clinical trial study, 128 patients undergoing abdominal surgery were selected and randomly divided into four groups of 32. In the 4 groups, 0.5 μg/kg dexmedetomidine, 0.5 mg/kg pethidine, 0.1 mg/kg ondansetron, and the same volume of normal saline were injected intravenously when anesthetics were discontinued and the incidence and severity of postoperative shivering were determined and compared in four groups. The incidence of postoperative shivering was 12.5% in the dexmedetomidine group, 31.3% in the ondansetron group, 31.3% in the pethidine group, and 50% in the control group (P = 0.015). The mean of shivering severity in the four groups was 1.33 ± 0.5, 0.17 ± 0.8, 1.09 ± 0.4, and 1.13 ± 0.39, and the difference between the four groups was significant (P = 0.005). The use of all three drugs of dexmedetomidine, ondansetron, and pethidine is effective in decreasing the incidence of postoperative shivering, but the use of dexmedetomidine is associated with less postoperative shivering, better hemodynamic stability, and fewer other postoperative complications.


Algorithm to Identify Systemic Cancer Therapy Treatment Using Structured Electronic Data.
With the shift in the majority of oncology clinical care in the United States from paper records to electronic health records, researchers need efficient and validated processes to obtain accurate data about the entire treatment history of patients diagnosed with cancer. The objective of this study was to develop and validate an algorithm that is agnostic to the source of data but that can identify specific regimens in the entire course of systemic therapy treatment for patients diagnosed with breast, colorectal, or lung cancer. A cohort of patients with incident breast, colorectal, and lung cancer were randomly distributed into six groups. The algorithm was iteratively modified, and the performance was assessed until no additional modifications could be identified in the first three groups. The performance of the algorithm was confirmed in the three groups that remained. The final model produced ranges of sensitivity between 97.2% and 100% for first-course systemic therapy across all cancers, with a false-positive rate of 0%. The algorithm matched the exact number of courses and the exact regimens of systemic therapy agents as captured by infusion, pharmacy, and procedure electronic medical record data for all courses of therapy 88% to 100% of the time. Use of our validated algorithm that characterizes entire courses of systemic therapy treatment in patients diagnosed with breast, colorectal, and lung cancer will allow researchers in a variety of settings to conduct comparative effectiveness studies related to the uptake, safety, outcomes, and costs associated with the use of both novel and standard regimens.


BMI and risk of serious upper body injury following motor vehicle crashes: concordance of real-world and computer-simulated observations.
Men tend to have more upper body mass and fat than women, a physical characteristic that may predispose them to severe motor vehicle crash (MVC) injuries, particularly in certain body regions. This study examined MVC-related regional body injury and its association with the presence of driver obesity using both real-world data and computer crash simulation. Real-world data were from the 2001 to 2005 National Automotive Sampling System Crashworthiness Data System. A total of 10,941 drivers who were aged 18 years or older involved in frontal collision crashes were eligible for the study. Sex-specific logistic regression models were developed to analyze the associations between MVC injury and the presence of driver obesity. In order to confirm the findings from real-world data, computer models of obese subjects were constructed and crash simulations were performed. According to real-world data, obese men had a substantially higher risk of injury, especially serious injury, to the upper body regions including head, face, thorax, and spine than normal weight men (all p<0.05). A U-shaped relation was found between body mass index (BMI) and serious injury in the abdominal region for both men and women (p<0.05 for both BMI and BMI(2)). In the high-BMI range, men were more likely to be seriously injured than were women for all body regions except the extremities and abdominal region (all p<0.05 for interaction between BMI and sex). The findings from the computer simulation were generally consistent with the real-world results in the present study. Obese men endured a much higher risk of injury to upper body regions during MVCs. This higher risk may be attributed to differences in body shape, fat distribution, and center of gravity between obese and normal-weight subjects, and between men and women. Please see later in the article for the Editors' Summary.


[Radiation pneumonitis. Morphology and pathogenesis].
Radiation-induced pulmonary damage is an inflammatory process which progresses in stages. The quantity rather than quality of pulmonary reactions depends on the given radiation dose. Damage to endothelial cells of capillaries and of respiratory epithelium is the initial event in the development of radiation pneumonitis. Release or activation of cytogenic and serum-derived mediators, increased permeability of the capillary wall, and damage to pneumocytes II are the most important factors in pathogenesis. There is no morphological latent stage. The latency between exposure to irradiation and manifestation of clinical symptoms of pneumonitis may be explained by the morphologic findings. Several non-radiation-induced lung diseases are predisposing factors. There is a tendency to bacterial, viral or mycological superinfections in patients with radiation pneumonitis. Radiotherapy leaves behind a latent pulmonary lesion with continuously changing reactions to most various irritations.


Ultra-narrow linewidth vertical-cavity surface-emitting laser based on external-cavity weak distributed feedback.
We demonstrate an ultra-narrow linewidth vertical-cavity surface-emitting laser (VCSEL) based on external-cavity weak distributed feedback from Rayleigh backscattering (RBS). A single longitudinal mode VCSEL with the linewidth as narrow as 435 Hz and a contrast of 55 dB are experimentally achieved by RBS fiber with a feedback level of RBS signal of -27.6 dB. By adjusting the thermal resistance of the VCSEL from 4.5 kΩ to 7.0 kΩ, the laser wavelength can be tuned from 1543.324 nm to 1542.06 nm with a linear tuning slope of -0.506 nm/kΩ. In the tuning process, the linewidth fluctuates in the range of 553-419 Hz.