Effects of comprehensive geriatric assessment-guided interventions on physical performance and quality of life in older patients with advanced cancer: A randomized controlled trial (PROGNOSIS-RCT).
Older patients with frailty starting oncological treatment are at higher risk of experiencing declining physical performance, loss of independence, and quality of life (QoL). This study examines whether comprehensive geriatric assessment (CGA)-guided interventions added to standard oncological care can prevent declining physical performance and QoL in older patients with frailty initiating palliative treatment. Patients aged ≥70 years, with a Geriatric-8 score of ≤14, initiating palliative oncological treatment were enrolled in an open label randomized controlled trial and randomized 1:1 to receive either CGA-guided interventions in addition to oncological standard care or oncological care alone. Baseline characteristics, physical performance measures, and QoL questionnaires were retrieved before group allocation. CGA was performed using a fixed set of domains and validated tests by a geriatrician-led team. The primary endpoint, physical performance, was measured by the 30-s chair stand test (30s-CST) at three months. Additional outcomes included 30s-CST at six months, handgrip strength test, and QoL. Outcomes were analyzed using linear mixed regression models. The trial was registered at clinicaltrials.org (NCT04686851). From November 1, 2020 to May 31, 2022, 181 patients were included; 88 in the interventional arm and 93 in the control arm. Median age was 77 (interquartile range [IQR] 73-81) years, 69% were male, median Geriatric-8 score was 12 (IQR 10-13), 69% had a Performance Status of 0-1, and the median 30s-CST was 9 (IQR 5-11) repetitions. The between-group difference in 30s-CST at three months was 0.67 (95%CI: -0.94 - 2.29) and 1.57 (95%CI: -0.20 - 3.34) at six months, which were not statistically significant. Subgroup analysis including participants with a baseline Geriatric-8 of 12-14 found borderline significant between-group differences in 30s-CST scores at three and six months of 2.04 (95% confidence interval [CI]: -0.07 - 4.2, P = 0.06) and 2.25 (95%CI: 0.01-4.5, P = 0.05), respectively. No within-group or between-group differences in the summary score or the Elderly Functional Index score (measuring QoL) were found. This study did not find significant between-group differences in the 30s-CST in older patients receiving palliative care. However, a tendency towards improved physical performance was seen in the least frail. These patients may represent a target group wherein CGA interventions provide particular benefit.


White-light emitting microtubes of mixed organic charge-transfer complexes.
Self-assembled microtubes of mixed charge-transfer (CT) complexes comprising TCNB and naphthalene can be constructed with pyrene as dopant by an etching-assisted CT-induced interaction. Highly efficient Förster resonance energy transfer (FRET) from the excited naphthalene-TCNB to pyrene-TCNB molecules is obtained in mixed CT complex microtubes. White-light emissive CT complex microtubes can be formed by adjusting the dopant concentration and serve as an active optical waveguide.


Validation of prediction equations for apparent metabolizable energy of corn distillers dried grains with solubles in broiler chicks.
An experiment consisting of 3 nearly identical trials was conducted to determine the AMEn content of distillers dried grains with solubles (DDGS) to validate 4 previously published prediction equations for AMEn of corn DDGS in broilers. In addition, prior research data were used to generate a best-fit equation for AMEn based on proximate analysis. Fifteen samples of DDGS ranging in ether extract (EE) from 4.98 to 14.29% (DM basis) were collected from various dry-grind ethanol plants and were subsequently fed to broiler chicks to determine AMEn content. A corn-soybean meal control diet was formulated to contain 15% dextrose and test diets were created by mixing the control diet with 15% DDGS at the expense of dextrose. In each trial, male Ross × Ross 708 chicks were housed in grower battery cages and received a common starter diet until the experimental period. Each cage was randomly assigned to 1 of the dietary treatments (trial 1 and trial 2: control + 6 test diets, 13 replicates per diet; trial 3: control + 3 test diets, 12 replicates per diet). Experimental diets were fed over a 6-d acclimation period, followed by a 48-h total excreta collection period. On a DM basis, AMEn of the 15 DDGS samples ranged from 1,975 to 3,634 kcal/kg. Analyses were conducted to determine gross energy, CP, EE, DM, starch, total dietary fiber, neutral detergent fiber, crude fiber (CF), acid detergent fiber, and ash content of the DDGS samples. All results were reported on a DM basis. Application of the 4 equations to the validation data resulted in root mean square error (RMSE) values of 335, 381, 488, and 502 kcal/kg, respectively. Least absolute shrinkage and selection operator technique was applied to proximate analysis data for 30 corn coproducts adapted from prior research and resulted in the following best-fit equation: [AMEn (kcal/kg) = 3,673 - (121.35 × CF) + (51.29 × EE) - (121.08 × ash); P < 0.01; R(2) = 0.70; R(2) adj = 0.67; RMSE = 270 kcal/kg]. The RMSE values obtained through validation were not consistent with the expectation of predictive performance based on internal measures of fit for each equation. These results indicated that validation is necessary to quantify the expected error associated with practical application of each individual prediction equation to external data.


Estimating the causal effect of annual PM2.5 exposure on mortality rates in the Northeastern and mid-Atlantic states.
Dozens of cohort studies have associated particulate matter smaller than 2.5 µm in diameter (PM2.5) exposure with early deaths, and the Global Burden of Disease identified PM2.5 as the fifth-ranking mortality risk factor in 2015. However, few studies have used causal modeling techniques. We assessed the effect of annual PM2.5 exposure on all-cause mortality rates among the Medicare population in the Northeastern and mid-Atlantic states, using the difference-in-differences approach for causal modeling. We obtained records of Medicare beneficiaries 65 years of age or more who reside in the Northeastern or mid-Atlantic states from 2000 to 2013 and followed each participant from the year of enrollment to the last year of follow-up. We estimated the causal effect of annual PM2.5 exposure on mortality rates using the difference-in-differences approach in the Poisson survival analysis. We controlled for individual confounders, for spatial differences using dummy variables for each ZIP code and for time trends using a penalized spline of year. We included 112,376,805 person-years from 15,401,064 people, of whom 37.4% died during the study period. The interquartile range (IQR) of the annual PM2.5 concentration was 3 µg/m3, and the mean annual PM2.5 concentration ranged between 6.5 and 14.5 µg/m3 during the study period. An IQR incremental increase in PM2.5 was associated with a 4.04% increase (95% CI = 3.49%, 4.59%) in mortality rates. Assuming no omitted predictors changing differently across ZIP codes over time in correlation with PM2.5, we found a causal effect of PM2.5 on mortality incidence rate.


No evidence of inhibition of horizontal gene transfer by CRISPR-Cas on evolutionary timescales.
The CRISPR (clustered, regularly, interspaced, short, palindromic repeats)-Cas (CRISPR-associated genes) systems of archaea and bacteria provide adaptive immunity against viruses and other selfish elements and are believed to curtail horizontal gene transfer (HGT). Limiting acquisition of new genetic material could be one of the sources of the fitness cost of CRISPR-Cas maintenance and one of the causes of the patchy distribution of CRISPR-Cas among bacteria, and across environments. We sought to test the hypothesis that the activity of CRISPR-Cas in microbes is negatively correlated with the extent of recent HGT. Using three independent measures of HGT, we found no significant dependence between the length of CRISPR arrays, which reflects the activity of the immune system, and the estimated number of recent HGT events. In contrast, we observed a significant negative dependence between the estimated extent of HGT and growth temperature of microbes, which could be explained by the lower genetic diversity in hotter environments. We hypothesize that the relevant events in the evolution of resistance to mobile elements and proclivity for HGT, to which CRISPR-Cas systems seem to substantially contribute, occur on the population scale rather than on the timescale of species evolution.


Sympathoadrenal mechanisms in hemodynamic responses to gastric distension in cats.
There is presently little information on the efferent mechanisms responsible for the reflex cardiovascular activation during passive gastric distension. Therefore, 40 cats anesthetized with alpha-chloralose were studied with passive gastric balloon distention before and during 1) two repeated gastric distensions, 2) beta-adrenergic blockade with propranolol, 3) alpha-adrenergic blockade with phentolamine, or 4) bilateral adrenalectomy. Before and during each distension mean arterial pressure, heart rate, cardiac output, rate of rise of left ventricular pressure (dP/dt) at 40 mmHg developed pressure and calculated systemic vascular resistance were determined. Repeated gastric distension caused similar hemodynamic responses without tachyphylaxis. beta-Blockade significantly reduced the increase in dP/dt from 893 +/- 362 to 150 +/- 63 mmHg/s. alpha-Blockade significantly altered the changes in mean arterial pressure from 33 +/- 5.0 to -2 +/- 4.7 mmHg and systemic vascular resistance from 0.114 +/- 0.019 to 0.004 +/- 0.031 peripheral resistance units. Bilateral adrenalectomy significantly diminished the contractile response from 525 +/- 107 to 50 +/- 85 mmHg/s but did not significantly alter the pressor and vasoconstrictor responses. We conclude that, during passive gastric distension in cats, the increase in myocardial contractility is mediated by beta-adrenergic-receptor stimulation, whereas the arterial vasoconstrictor and pressor responses are mediated by alpha-adrenergic receptor stimulation. Additionally, during gastric distension a substantial portion of the contractile response is dependent on the integrity of the adrenal glands.


Cardiac tamponade induced by dabrafenib and trametinib combination therapy for melanoma: Case report.
BRAF and MEK inhibitors (BRAF/MEKi) are targeted therapy for proto-oncogene BRAF mutated metastatic unresectable melanoma. Compared to monotherapy, an increased cardiovascular toxicity is reported with the combination of Dabrafenib and Trametinib. This case report documents Grade 4 cardiac treatment emergent adverse effect of pericardial effusion and cardiac tamponade induced by this combination therapy. A 52 year old man presented with clinical stage II unresectable melanoma with BRAF mutation, was initiated on treatement with Dabrafenib and Trametinib. He complained of generalised edema and increased his weight by 27 kg. This progressed to shortness of breath and he underwent echocardiogram which revealed cardiac tamponade. Emergent pericardiocentesis was performed. No definited pathology was demonstrated in laboratory analysis of pericardial fluid. Re- initiating treatment resulted in cardiac tamponade and pericardiotomy was performed by video-assisted thoracic surgical (VATS). Pericardial biopsy revealed nonspecific chronic inflammation. Discontinuation of treatment with Dabrafenib and Trametinib and diuretics resolved peripheral edema. Cardiac function normalized after pericardiocentesis and pericardiotomy. Treatment with Dabrafenib and Trametinib caused significant peripheral edema and pericardial effusion resulting in cardiac tamponade. Naranjo score suggests probable association of treatment induced pericardial effusion and cardiac tamponade. This is the first documented report of pericardial effusion and cardiac tamponade induced by Dabrafenib and Trametinib. Cardiac toxicity of BRAF/MEK inhibitors is rare but clinicans must monitor for treatment emergent adverse effects.


How long is the coast of britain? Statistical self-similarity and fractional dimension.
Geographical curves are so involved in their detail that their lengths are often infinite or, rather, undefinable. However, many are statistically "selfsimilar," meaning that each portion can be considered a reduced-scale image of the whole. In that case, the degree of complication can be described by a quantity D that has many properties of a "dimension," though it is fractional; that is, it exceeds the value unity associated with the ordinary, rectifiable, curves.


[Gallstone disease in children with obesity].
Based on the authors own research shown a relationship of metabolic disorders in children with GSD with the metabolic syndrome. Studied the parameters of lipid and carbohydrate metabolism in children with both abdominal and endocrine obesity. Was shown the Significance a high direct correlation in children with cholelithiasis on the background of obesity and metabolic syndrome. Obtained data enable us to assert that in children with cholelithiasis on the background of obesity forms classical clinical picture of metabolic syndrome.


An unusual case of homicide with a crossbow and a hunting knife.
Traumatic lethal injuries caused by crossbows are a rarity in forensic pathology. They occur as accidents, suicide and, more rarely, as murders. We report a case of murder received at the Institute of Legal Medicine in Milan carried out by two weapons - a crossbow and a hunting knife - that resulted in multiple thoraco-abdominal wounds. The case is also rare because of the unique circumstances involving the victim - a local service psychiatrist - and the perpetrator - a former medical specialist in psychiatry, suffering from a delusional psychotic disorder. The crossbow was the decisive instrument in the realization of the murder; it was chosen with premeditation for its high destructive capacity and the fact that it was easily obtainable, and it was used with darts that were specially modified to increase its harmful capacity. The presented case, as well as providing an opportunity to highlight the damaging effects of a rarely used weapon, stresses the problems inherent with access to tools such as the crossbow that are used in sport, and which are potentially dangerous but easily accessible, even to those with serious mental disorders, rendering them legally unfit for using firearms.


Low drug levels and thrombotic complications in high-risk atrial fibrillation patients treated with direct oral anticoagulants.
Essentials Direct oral anticoagulants (DOACs) do not require laboratory monitoring currently. DOAC specific measurements were performed at trough in patients with atrial fibrillation. Patients who developed thromboembolic events showed lower DOAC plasma levels. This study supports the concept of measuring DOAC levels at steady state. Background Direct oral anticoagulants (DOACs) are administered at fixed doses without the need for dose adjustment according to laboratory testing. High interindividual variability in drug blood levels has been shown with all DOACs. To evaluate a possible relationship between DOAC C-trough anticoagulant levels and thromboembolic events, 565 consecutive naive patients with atrial fibrillation (AF) were enrolled in this study performed within the START Laboratory Registry. Methods DOAC-specific measurements (diluted thrombin time or anti-activated factor II calibrated for dabigatran; anti-activated FX calibrated for rivaroxaban or apixaban) at C-trough were performed locally at steady state within 15-25 days after the start of treatment. For each DOAC, the interval of C-trough levels, from the limit of quantification to the highest value, was subdivided into four equal classes, and results were attributed to these classes; the median values of results were also calculated. Thromboembolic complications occurring during 1 year of follow-up were recorded. Results Thromboembolic events (1.8%) occurred in 10 patients who had baseline C-trough levels in the lowest class of drug levels. The incidence of thromboembolic events among patients with DOAC C-trough levels in the lowest level class was 2.4%, and that in the remaining groups was 0%. The patients with thrombotic complications also had a higher mean CHA2 DS2 -VASc score than that of the total patient population: 5.3 (95% confidence interval [CI] 4.3-6.3 versus 3.0 (95% CI 2.9-3.1). Conclusion In this study cohort, thrombotic complications occurred only in DOAC-treated AF patients who had very low C-trough levels, with a relatively high CHA2 DS2 -VASc score. Larger studies are warranted to confirm these preliminary observations.


Reasons for optimism in the search for new vaccines for tuberculosis.
In the development of vaccines for tuberculosis (TB), the combination of the will, funding, scientific rigor, new tools, refined animal models and improved clinical trial designs are all converging at an opportune moment. The lack of optimism that has surrounded the likelihood for finding novel TB vaccines has resulted from a lack of correlates of vaccine-induced protection, a lack of tool candidate vaccines to probe the immunologic space, which may be needed, and the negative result of one recent trial. A vaccine for TB that can be delivered at a reasonable cost to the marketplace will have greater impact on the incidence of new cases of TB than any intervention in world history. Now is the time to increase resources, both financial and human intellectual capacity, for a global tuberculosis vaccine effort.


Hair barrette induced cochlear implant receiver stimulator site infection with extrusion.
Background. Cochlear implant infections and extrusion are uncommon but potentially devastating complications. Recent literature suggests conservative management can be employed. Local measures inclusive of aggressive surgical debridement with vascularized flaps and parenteral antibiotics represent a viable option and often permit device salvage. However, explantation should be considered if there is evidence of systemic, intracranial, or intractable infection. Method. A Case report and literature review. Case Report. This case illustrates a complicated local wound infection associated with cochlear implantation due to transcutaneous adherence of a ferrous hair barrette to a cochlear implant magnet. Reconstruction of computed tomography (CT) data with 3D volume rendering significantly improved the value of the images and facilitated patient counseling as well as operative planning. Conclusion. Cochlear implant infections can be associated with foreign bodies. CT images are beneficial in the evaluation of cochlear implant complications. 3D CT images provide a comprehensive view of the site of interest, displaying the relationship of the hardware to the skull and soft tissues, while minimizing associated artifacts. Cochlear implant patients should consider use of nonmetallic hair devices.


Food Insecurity, Weight Status, and Perceived Nutritional and Exercise Barriers in an Urban Youth Population.
Food insecurity and overweight/obesity coexist among youth; however, evidence for their association has been mixed. Our objectives were to assess the association between (1) level of food security and weight classification and (2) food insecurity and perceived nutritional and exercise barriers in an urban youth population. Patients aged 15 to 25 years completed a US Department of Agriculture Food Security Survey. Chi-square, Kruskal-Wallis tests, and logistic regression models controlling for age and gender assessed the association between food security level, weight classification, and perceived barriers. Among 376 patients, 122 (32%) were food insecure and 221 (59%) were overweight/obese. There were no significant associations between food security level and weight classification. In adjusted analyses, participants with very low food insecurity reported significantly greater odds of 3 nutritional barriers compared to participants with high food security. Food-insecure youth were more likely to report nutritional barriers, which may lead to overweight/obesity over time.


RAD001 inhibits human ovarian cancer cell proliferation, enhances cisplatin-induced apoptosis, and prolongs survival in an ovarian cancer model.
mTOR (mammalian target of rapamycin) plays a central role in regulating cell growth and cell cycle progression and is regarded as a promising therapeutic target. We examined whether mTOR inhibition by RAD001 (everolimus) is therapeutically efficacious in the treatment of ovarian cancer as a single agent and in combination with cisplatin. Using four human ovarian cancer cell lines, we determined the effect of RAD001 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Western blot, and apoptosis assays. We evaluated the association between phospho-AKT/mTOR activity and RAD001 sensitivity. We also determined the effect of RAD001 on tumor growth and malignancy using mice inoculated with human ovarian cancer cells. RAD001 markedly inhibited cell proliferation of human ovarian carcinoma cells with high AKT activity (OVCAR10 and SKOV-3), but the effect was minimal in cells with low AKT activity (OVCAR4 and OVCAR5). Sensitivity to RAD001 was independent of p53 expression. RAD001 inhibited the phosphorylation of downstream 4E-BP1 and p70S6 kinase and attenuated the expression of Myc. RAD001 also attenuated the expression of HIF-1 alpha and vascular endothelial growth factor, important factors in angiogenesis and tumor invasiveness. RAD001 enhanced cisplatin-induced apoptosis in cells with high AKT/mTOR activity, with minimal effect in cells with low AKT-mTOR activity. Mouse xenografts of SKOV-3 cells revealed that RAD001 inhibits tumor growth, angiogenesis, and i.p. dissemination and ascites production and prolongs survival. Moreover, treatment with RAD001 significantly enhanced the therapeutic efficacy of cisplatin in vivo. These results indicate that RAD001 could have therapeutic efficacy in human ovarian cancers with hyperactivated AKT/mTOR signaling.


The effects of copper depletion on structural aspects of cytochrome c oxidase.
The removal of copper from beef heart cytochrome c oxidase by either dialysis against potassium cyanide or by treatment with bathocuproine sulfonate produced changes in the enzyme which are indicative of a spin state transition. In the Soret region of the CD spectrum copper depletion of the enzyme caused a significant decrease in amplitude in combination with a red shift of the peak maximum for oxidized samples, while reduced copper-depleted samples exhibited decreased amplitude and a blue shift of the peak maximum. In the magnetic CD spectra of oxidized copper-depleted samples the peak at 420 nm was shifted to lower wave-length along with a significant increase in amplitude. In reduced samples the peak at 446 nm exhibited a slight red shift concomitant with a substantial decrease in amplitude. The conformational changes indicated by the CD and magnetic CD spectra when copper is removed from the enzyme were supported by the EPR spectra of the NO complex of the reduced copper-depleted enzyme. The removal of copper from cytochrome c oxidase caused the NO complex to exhibit a 3-line splitting pattern of gz in the EPR spectrum instead of the 9 lines seen in the NO complex of the native enzyme. When [15N]NO was used, a 2-line pattern was seen at gz when copper was removed from the enzyme. The changes in the CD and magnetic CD spectra and in the EPR spectra of the NO derivatives of cytochrome c oxidase can be explained by the rearrangement of the axial ligands to iron in cytochrome a3 as a result of copper depletion. These results emphasize the close structural interdependence of the metallic components of this enzyme.


COP1 dynamics integrate conflicting seasonal light and thermal cues in the control of Arabidopsis elongation.
As the summer approaches, plants experience enhanced light inputs and warm temperatures, two environmental cues with an opposite morphogenic impact. Key components of this response are PHYTOCHROME B (phyB), EARLY FLOWERING 3 (ELF3), and CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1). Here, we used single and double mutant/overexpression lines to fit a mathematical model incorporating known interactions of these regulators. The fitted model recapitulates thermal growth of all lines used and correctly predicts thermal behavior of others not used in the fit. While thermal COP1 function is accepted to be independent of diurnal timing, our model shows that it acts at temperature signaling only during daytime. Defective response of cop1-4 mutants is epistatic to phyB-9 and elf3-8, indicating that COP1 activity is essential to transduce phyB and ELF3 thermosensory function. Our thermal model provides a unique toolbox to identify best allelic combinations enhancing climate change resilience of crops adapted to different latitudes.


Comprehensive exosomal microRNA profile and construction of competing endogenous RNA network in autism spectrum disorder: A pilot study.
Exosomes have been demonstrated to exert momentous roles in autism spectrum disorder (ASD). However, few studies have reported a correlation between exosomal microRNAs (miRNAs) and ASD. To date, our understanding of crucial competing endogenous RNA (ceRNA) networks in ASD remains limited. Herein, the exosomal miRNA profile in the peripheral blood of children with ASD and healthy controls was investigated and the level of immune cell infiltration in ASD was evaluated to determine the distribution of immune cell subtypes. Exosomes were isolated from the peripheral blood of 10 children with ASD and 10 healthy controls, and further identified using transmission electron microscopy and western blot analysis. RNA sequencing was conducted to investigate exosomal miRNA profiles in patients with ASD. The mRNA and circular RNA (circRNA) expression profiles were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs), and circRNAs (DEcircRNAs) were identified and ceRNA regulatory networks were constructed. Furthermore, the immune cell infiltration levels in patients with ASD were evaluated. Exosomes were spherical, approximately 100 nm in size, and were confirmed via western blot analysis using exosome-associated markers CD9, CD63, and CD81. Thirty-five DEmRNAs, 63 DEmiRNAs, and 494 DEcircRNAs were identified in patients with ASD. CeRNA regulatory networks, including 6 DEmRNAs, 14 DEmiRNAs, and 86 DEcircRNAs, were established. Correlation analysis indicated that leucine-rich glioma inactivated protein 1 (LGI1) expression was significantly positively correlated with the content of CD8+ T cells. Our findings may be conducive to offering novel insights into this disease and providing further evidence of transcriptomic abnormalities in ASD.


Endothelial TRPV4 channels mediate dilation of cerebral arteries: impairment and recovery in cerebrovascular pathologies related to Alzheimer's disease.
Transient receptor potential vanilloid type 4 (TRPV4) channels are expressed in brain endothelial cells, but their role in regulating cerebrovascular tone under physiological and pathological conditions is still largely unknown. Wild-type (WT) mice and mice that overexpress a mutated form of the human amyloid precursor protein (APP mice, model of increased amyloid β), a constitutively active form of TGF-β1 (TGF mice, model of cerebrovascular fibrosis) or both (APP/TGF mice) were used. Dilations to the selective TRPV4 channel opener GSK1016790A (GSK) or to ACh were measured in posterior cerebral artery segments. Both GSK- and ACh-induced dilations virtually disappeared following endothelium denudation in WT mice. These responses were impaired in vessels from APP, TGF and APP/TGF mice compared with WT. Pre-incubation of WT vessels with the selective TRPV4 channel blocker HC-067047, or with small-conductance (SK channel, apamin) and/or intermediate-conductance (IK channel, charybdotoxin, ChTx) Ca(2+) -sensitive K(+) channel blocker abolished GSK-induced dilations and massively decreased those induced by ACh. These treatments had no or limited effects on ACh-induced dilation in vessels from APP, TGF or APP/TGF mice, and IK and SK channel function was preserved in transgenic mice. Antioxidant superoxide dismutase or catalase normalized GSK- and ACh-mediated dilations only in APP brain arteries. We conclude that endothelial TRPV4 channels mediate ACh-induced dilation in cerebral arteries, that they are impaired in models of cerebrovascular pathology and that they are sensitive, albeit in the reversible manner, to amyloid β-induced oxidative stress.


Quantitative analysis of ultradian luteinizing hormone secretion in normal men.
Basal pulsatile secretion of luteinizing hormone (LH) was studied in 8 healthy adult men and analyzed by mathematical and statistical techniques. LH pulses previously defined by semiquantitative criteria resisted the data-smoothing techniques employed. LH values were shown to have normal distribution in normal men. No correlation was found between mean LH and testosterone levels for the same individual. On the basis of analysis of variance it was shown that the individual variability and not the collection time is important in determining each isolated LH value. The LH levels were located within a particular channel for each individual for each collection time.


Antibiotics as a chemical stressor affecting an aquatic decomposer-detritivore system.
Recent evidence indicates that a variety of antibiotic residues may affect the integrity of streams located downstream from wastewater treatment plants. Aquatic communities comprising bacterial and fungal decomposers and invertebrate detritivores (shredders) play an important role in the decomposition of allochthonous leaf litter, which acts as a primary energy source for small running waters. The aim of the present study was to assess whether an antibiotic mixture consisting of sulfamethoxazole, trimethoprim, erythromycin-H2O, roxithromycin, and clarithromycin has an effect on such a decomposer-detritivore system. Leaf discs were exposed to these antibiotics (total concentration of 2 or 200 microg/L) for approximately 20 d before offering these discs and corresponding control discs to an amphipod shredder, Gammarus fossarum, in a food choice experiment. Gammarus preferred the leaf discs conditioned in the presence of the antibiotic mixture at 200 microg/L over the control discs (pair-wise t test; p = 0.006). A similar tendency, while not significant, was observed for leaves conditioned with antibiotics at a concentration of 2 microg/L. The number of bacteria associated with leaves did not differ between treatments at either antibiotic concentration (t test; p = 0.57). In contrast, fungal biomass (measured as ergosterol) was significantly higher in the 200 microg/L treatment (t test; p = 0.038), suggesting that the preference of Gammarus may be related to a shift in fungal communities. Overall these results indicate that mixtures of antibiotics may disrupt important ecosystem processes such as organic matter flow in stream ecosystems, although effects are likely to be weak at antibiotic concentrations typical of streams receiving wastewater treatment plant effluents.


Soybean Resistance Locus Rhg1 Confers Resistance to Multiple Cyst Nematodes in Diverse Plant Species.
Cyst nematodes consistently threaten agricultural production, causing billions of dollars in losses globally. The Rhg1 (resistance to Heterodera glycines 1) locus of soybean (Glycine max) is the most popular resistance source used against soybean cyst nematodes (H. glycines). Rhg1 is a complex locus that has multiple repeats of an ≈30-kilobase segment carrying three genes that contribute to resistance. We investigated whether soybean Rhg1 could function in different plant families, conferring resistance to their respective cyst nematode parasites. Transgenic Arabidopsis thaliana and potato (Solanum tuberosum) plants expressing the three soybean Rhg1 genes were generated. The recipient Brassicaceae and Solanaceae plant species exhibited elevated resistance to H. schachtii and Globodera rostochiensis and to G. pallida, respectively. However, some negative consequences including reduced root growth and tuber biomass were observed upon Rhg1 expression in heterologous species. One of the genes at Rhg1 encodes a toxic version of an alpha-SNAP protein that has been demonstrated to interfere with vesicle trafficking. Using a transient expression assay for Nicotiana benthamiana, native Arabidopsis and potato alpha-SNAPs (soluble NSF [N-ethylamine sensitive factor] attachment protein) were found to compensate for the toxicity of soybean Rhg1 alpha-SNAP proteins. Hence, future manipulation of the balance between Rhg1 alpha-SNAP and the endogenous wild-type alpha-SNAPs (as well as the recently discovered soybean NSF-RAN07) may mitigate impacts of Rhg1 on plant productivity. The multispecies efficacy of soybean Rhg1 demonstrates that the encoded mechanisms can function across plant and cyst nematode species and offers a possible avenue for engineered resistance in diverse crop species.


[Use of laparoscopic methods in combined surgery].
The authors have made a comparative analysis of the effectiveness of isolated and combined laparoscopic cholecystectomies. The control group consisted of 246 patients subjected to isolated cholecystectomies. The group under study included 22 patients in whom combined cholecystectomies were performed. The comparative analysis included the following clinical data: duration of the operation, number of postoperative days in the hospital, amount of postoperative complications. It was concluded that the little-invasive laparoscopic technique used in one of the steps of the combined operation allowed traumatism of the surgery to be decreased which in its turn allowed wider indications to combined operations.


Ectomycorrhizal Fungal Communities in Urban Parks Are Similar to Those in Natural Forests but Shaped by Vegetation and Park Age.
Ectomycorrhizal (ECM) fungi are important mutualists for the growth and health of most boreal trees. Forest age and its host species composition can impact the composition of ECM fungal communities. Although plentiful empirical data exist for forested environments, the effects of established vegetation and its successional trajectories on ECM fungi in urban greenspaces remain poorly understood. We analyzed ECM fungi in 5 control forests and 41 urban parks of two plant functional groups (conifer and broadleaf trees) and in three age categories (10, ∼50, and >100 years old) in southern Finland. Our results show that although ECM fungal richness was marginally greater in forests than in urban parks, urban parks still hosted rich and diverse ECM fungal communities. ECM fungal community composition differed between the two habitats but was driven by taxon rank order reordering, as key ECM fungal taxa remained largely the same. In parks, the ECM communities differed between conifer and broadleaf trees. The successional trajectories of ECM fungi, as inferred in relation to the time since park construction, differed among the conifers and broadleaf trees: the ECM fungal communities changed over time under the conifers, whereas communities under broadleaf trees provided no evidence for such age-related effects. Our data show that plant-ECM fungus interactions in urban parks, in spite of being constructed environments, are surprisingly similar in richness to those in natural forests. This suggests that the presence of host trees, rather than soil characteristics or even disturbance regime of the system, determine ECM fungal community structure and diversity.IMPORTANCE In urban environments, soil and trees improve environmental quality and provide essential ecosystem services. ECM fungi enhance plant growth and performance, increasing plant nutrient acquisition and protecting plants against toxic compounds. Recent evidence indicates that soil-inhabiting fungal communities, including ECM and saprotrophic fungi, in urban parks are affected by plant functional type and park age. However, ECM fungal diversity and its responses to urban stress, plant functional type, or park age remain unknown. The significance of our study is in identifying, in greater detail, the responses of ECM fungi in the rhizospheres of conifer and broadleaf trees in urban parks. This will greatly enhance our knowledge of ECM fungal communities under urban stresses, and the findings can be utilized by urban planners to improve urban ecosystem services.


Effect of climatic region on the clinical expression of footrot of lesser clinical severity (intermediate footrot) in sheep.
To determine if the clinical classification of intermediate footrot (IFR) is changed to virulent footrot (VFR) by a transfer of the infected flock to a region where climatic conditions are more favourable for the transmission of the disease. Clinical examination of two groups of Merino wethers infected with IFR; one group of 309 in a region considered less favourable for footrot and another group of 343 at a second site considered more favourable. After characterising the form of footrot at the first site, infection was established at the second site by mixing 142 wethers from the first site with 201 unrelated wethers considered to be free of IFR and VFR. Observations of clinical characteristics were made over a 16 month period during which an outbreak of footrot occurred. Clinical assessments were made by inspecting every foot of every sheep at regular intervals and allocating a footscore. Evidence that the same clonal lines of D. nodosus were responsible for the footrot at both sites was provided by serotyping of isolates and using omp gene RFLP as a molecular epidemiological tool. The disease at the first site was classified as IFR because 7% of the sheep developed a maximum footscore (MFS) of 4, the most severe category, despite relatively low rates of transmission. When the outbreak occurred at the second site, which was more suitable for footrot transmission, the maximum proportion of the flock that developed a MFS of 4 was 3.6%, confirming the initial classification of IFR. When a flock infected with IFR was moved to a region where climatic conditions were more favourable for footrot transmission, the clinical classification of the disease remained the same in both the original flock and in sheep exposed to the infection for the first time.


To Evaluate the Efficacy of Combination Antioxidant Therapy on Oxidative Stress Parameters in Seminal Plasma in the Male Infertility.
Infertility is defined as inability to conceive after 1 year of unprotected intercourse and it affects 7% of male population and 8-10% of couples. According to estimates WHO, 13-19 million couples in India are infertile. Oxidative stress is the causative factor in 25% of infertile males. To study the efficacy of antioxidant therapy on oxidative stress parameters in seminal plasma of infertile male. Forty patients of male infertility were enrolled in study after two abnormal semen analyses reports at 2-3 weeks interval, of oligozoospermia and/or asthenozoospermia, as per WHO guide line 1999. First semen sample was collected at a time of enrollment of study and second semen sample was collected three months after combined antioxidant therapy. Semen samples from the infertile male (the second confirmatory sample of oligoasthenozoospermia) were taken and after liquefaction semen sample were utilized for various analyses, 0.5 ml of sample for standard semen analysis, 1.2 ml sample for separation of seminal plasma to evaluate Oxidative stress (OS) parameters like Malondialdehyde (MDA), Protein Carbonyl (PC) and antioxidant capacity by Glutathione (GSH). We followed the patient for three months after completion of the treatment. Semen parameters - Out of 40 patients recruited in the study group 7 patients had only oligospermia (1 to 20 million/ml) and 31 patients had oligoasthenozoospermia (motility range 0-50%) and 2 patients had oligoasthenoteratozoospermia. There was no patient with asthenospermia alone as abnormal semen parameters. After the three months treatment with combined antioxidants the semen parameters like count (mean SD = -1.70±1.44) and motility (mean +SD= -9.56±9.05) were significantly increased (p-value=0.000). Oxidative Stress Assessment - The level of MDA which is a marker of oxidative stress was significantly lower after the three months therapy of antioxidants (p-value=0.002) whereas another marker which is denoted by PC was also lower after the treatment but not statistically significant (p-value=0.584). The level of antioxidants GSH also significantly increased after the treatment (p-value=0.000). After the treatment out of 40, five patients conceived (16.7%). As we have seen through this study antioxidant dramatically reduced the oxidative stress markers and enhancing the antioxidant enzymes. They should be used on routine basis in case of male infertility.


Transition to stress focusing for locally curved sheets.
A rectangular thin elastic sheet is deformed by forcing a contact between two points at the middle of its length. A transition to buckling with stress focusing is reported for the sheets sufficiently narrow with a critical width proportional to the sheet length with an exponent 2/3 in the small thickness limit. Additionally, a spring network model is solved to explore the thick sheet limit and to validate the scaling behavior of the transition in the thin sheet limit. The numerical results reveal that buckling does not exist for the thickest sheets, and a stability criterion is established for the buckling of a curved sheet.


Low numbers of regulatory T cells in common variable immunodeficiency: association with chronic inflammation in vivo.
Common variable immunodeficiency (CVID) is a heterogeneous syndrome characterized by defective immunoglobulin production and high frequency of bacterial infections, autoimmunity and manifestations of chronic inflammation. Abnormalities of CD4+CD25high forkhead box P3 (FoxP3)+ regulatory T cells (Treg) have been associated with autoimmune and inflammatory disorders, and we hypothesized that CVID might be characterized by Treg abnormalities. CD3+ cells from patients and controls were analysed for the expression of FoxP3 mRNA by real time reverse transcription-polymerase chain reaction (RT-PCR). Peripheral blood mononuclear cells from CVID patients and controls were stained for Treg markers, analysed by flow cytometry and compared to clinical characteristics. The main findings were: (i) CVID patients had significantly decreased expression of FoxP3 mRNA and decreased proportions of CD4+CD25highFoxP3+ cells compared to controls; (ii) CVID patients with splenomegaly had even lower proportions of Treg compared to other patients and controls; (iii) serum levels of the inflammatory marker neopterin were correlated negatively with the proportions of Treg within the CVID population, while there was no significant association with bronchiectasis. We have demonstrated decreased proportions of Treg in CVID patients, particularly in those with signs of chronic inflammation. Decreased proportions of TReg are suggested to be pathogenetically important in autoimmunity, and our results suggest that TReg may have a similar role in CVID.


Disturbed vibrotactile sense in finger pulps in patients with Type 1 diabetes--correlations with glycaemic level, clinical examination and electrophysiology.
In a cohort of men and women with Type 1 diabetes, prospectively followed for > 20 years, vibrotactile sense in fingers was investigated and related to neurophysiological tests, glycaemic level and clinical score. Out of 58 patients, diagnosed at the age of 15-25 years and recruited 1984-1985, 32 patients (13 women, median age 52 years, range 44-75 years; 19 men, median age 52 years, range 39-69 years; median duration 33.5 years, range 21-52 years) accepted follow-up in 2006. Vibration thresholds were measured in finger pulps of index and little fingers bilaterally at seven frequencies and related to results of touch (monofilaments), tactile discrimination (two-point discrimination test), electrophysiology (median nerve function), glycaemic level (HbA(1c) levels since 1984-1985) and a clinical score. Vibrotactile sense was reduced in finger pulps, mainly in men, compared with an age- and gender-matched healthy control group with normal HbA(1c) . Vibration thresholds were increased, particularly at 250 and 500 Hz, in both index and little finger pulps. Touch and tactile discrimination correlated with vibration thresholds, but not with each other or with electrophysiology. HbA(1c) levels (at follow-up or mean values from five follow-ups since recruitment) did not correlate with any nerve function variables. Clinical scores correlated with vibrotactile sense, particularly at higher frequencies (> 125 Hz), but not with total Z-scores of electrophysiology. Duration of disease did not correlate with any variables. Examination of vibration thresholds in index and little finger pulps may be valuable to detect neuropathy, where thresholds correlate with symptoms and tests.


Age at menarche is associated with prediabetes and diabetes in women (aged 32-81 years) from the general population: the KORA F4 Study.
The aim of this study was to examine the association between age at menarche and prediabetes as well as diabetes, considering confounding factors and the possible mediating role of adult obesity. This cross-sectional study analysed data on 1,503 women aged 32-81 years from the German population-based KORA (Cooperative Health Research in the Region of Augsburg, South Germany) F4 Study (2006-2008). Data were collected by standardised interviews, physical examinations, and whole blood and serum measurements, including administration of an OGTT in non-diabetic participants. Of the 1,503 women, 226 showed a prediabetic state (impaired fasting glucose and/or impaired glucose tolerance) and 140 persons had diabetes (45 participants with previously undiagnosed diabetes and 95 with known diabetes). In Poisson regression analysis, age at menarche was significantly inversely associated with prediabetes or diabetes after adjustment for year of birth (RR 0.88; 95% CI 0.82, 0.94, p < 0.0001 per additional year of menarche) and after additional adjustment for a number of confounding factors (RR 0.88; 95% CI 0.83, 0.94, p = 0.0001). Further adjustment for current BMI slightly attenuated the association with prediabetes or diabetes (RR 0.89; 95% CI 0.83, 0.95, p = 0.0009), but the association remained clearly significant. Age at menarche seems to be inversely associated with prediabetes and diabetes independent of confounding factors including current BMI. Women at risk for diabetes might be identified by a history of young age at menarche.


Overweight and obesity management strategies in survivors of paediatric acute lymphoblastic leukaemia: a systematic review protocol.
Acute lymphoblastic leukaemia is the most common paediatric cancer. Survivors of childhood acute lymphoblastic leukaemia (SALL) are at risk of obesity and related cardiometabolic diseases including type 2 diabetes, hypertension, stroke and cardiovascular events. Therefore, it is important to address obesity in this population as this may help mitigate future cardiometabolic comorbidities. In this systematic review, we aim to assess current treatment strategies including lifestyle interventions, pharmacotherapy and bariatric surgery to manage overweight and obesity in SALL. We will search the following databases for primary studies: CINAHL, SPORTDiscus, EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. In addition, unpublished primary studies will be searched in ClinicalTrials.gov as well as conference proceedings, presentations, abstracts, editorials and ProQuest Dissertations and Theses A&I. Reviewers will perform title, abstract, and full-text screening as well as data abstraction and risk of bias assessment independently with a third reviewer to be consulted to resolve disagreements. Searches will be run and updated through May 1st, 2018. The overall quality of the evidence will be determined using the Grading of Recommendations, Assessment, Development, and Evaluation criteria for each outcome. A meta-analysis will be performed if two studies deploying similar interventions, populations, and design and outcomes are identified. As individual patient data will not be included, we do not require ethics approval. This review will be published in a peer-reviewed journal. CRD42016051031.


An integrated epigenome and transcriptome analysis identifies PAX2 as a master regulator of drug resistance in high grade pancreatic ductal adenocarcinoma.
Pancreatic ductal adenocarcinoma (PDAC) is notoriously difficult to treat due to its aggressive, ever resilient nature. A major drawback lies in its tumor grade; a phenomenon observed across various carcinomas, where highly differentiated and undifferentiated tumor grades, termed as low and high grade respectively, are found in the same tumor. One eminent problem due to such heterogeneity is drug resistance in PDAC. This has been implicated to ABC transporter family of proteins that are upregulated in PDAC patients. However, the regulation of these transporters with respect to tumor grade in PDAC is not well understood. To combat these issues, a study was designed to identify novel genes that might regulate drug resistance phenotype and be used as targets. By integrating epigenome with transcriptome data, several genes were identified based around high grade PDAC. Further analysis indicated oncogenic PAX2 transcription factor as a novel regulator of drug resistance in high grade PDAC cell lines. It was observed that silencing of PAX2 resulted in increased susceptibility of high grade PDAC cells to various chemotherapeutic drugs. Mechanistically, the study showed that PAX2 protein can bind and alter transcriptionally; expression of many ABC transporter genes in high grade PDAC cell lines. Overall, the study indicated that PAX2 significantly upregulated ABC family of genes resulting in drug resistance and poor survival in PDAC.


Early Detection of Plant Viral Disease Using Hyperspectral Imaging and Deep Learning.
Early detection of grapevine viral diseases is critical for early interventions in order to prevent the disease from spreading to the entire vineyard. Hyperspectral remote sensing can potentially detect and quantify viral diseases in a nondestructive manner. This study utilized hyperspectral imagery at the plant level to identify and classify grapevines inoculated with the newly discovered DNA virus grapevine vein-clearing virus (GVCV) at the early asymptomatic stages. An experiment was set up at a test site at South Farm Research Center, Columbia, MO, USA (38.92 N, -92.28 W), with two grapevine groups, namely healthy and GVCV-infected, while other conditions were controlled. Images of each vine were captured by a SPECIM IQ 400-1000 nm hyperspectral sensor (Oulu, Finland). Hyperspectral images were calibrated and preprocessed to retain only grapevine pixels. A statistical approach was employed to discriminate two reflectance spectra patterns between healthy and GVCV vines. Disease-centric vegetation indices (VIs) were established and explored in terms of their importance to the classification power. Pixel-wise (spectral features) classification was performed in parallel with image-wise (joint spatial-spectral features) classification within a framework involving deep learning architectures and traditional machine learning. The results showed that: (1) the discriminative wavelength regions included the 900-940 nm range in the near-infrared (NIR) region in vines 30 days after sowing (DAS) and the entire visual (VIS) region of 400-700 nm in vines 90 DAS; (2) the normalized pheophytization index (NPQI), fluorescence ratio index 1 (FRI1), plant senescence reflectance index (PSRI), anthocyanin index (AntGitelson), and water stress and canopy temperature (WSCT) measures were the most discriminative indices; (3) the support vector machine (SVM) was effective in VI-wise classification with smaller feature spaces, while the RF classifier performed better in pixel-wise and image-wise classification with larger feature spaces; and (4) the automated 3D convolutional neural network (3D-CNN) feature extractor provided promising results over the 2D convolutional neural network (2D-CNN) in learning features from hyperspectral data cubes with a limited number of samples.


The evaluation of biologically important trace metals in liver, kidney and breast tissue.
The levels of iron (Fe), copper (Cu), zinc (Zn) and potassium (K) have been measured in normal and malignant liver and kidney tissue using X-ray fluorescence. Zn was reduced in liver and kidney tumours by 63% and 26%, respectively. Fe, Cu and K were increased in kidney tumours by 150%, 8% and 90%, and reduced in liver tumours by 76%, 29% and 43%. A synchrotron microprobe was used to map calcium (Ca), Fe, Cu and Zn in breast tissue. The distributions were compared to reference images and higher concentrations of metals correlated with areas of cancer cells. The average increase of Ca, Fe, Cu and Zn concentrations in areas of malignancy were 70%, 43%, 53% and 87%.


Diffuse infiltrating astrocytoma (gliomatosis cerebri) with twenty-two-year history.
The case is described of a man, aged 46 at his time of death, who suffered from focal motor, adversive and generalised seizures for 22 years. He developed a progressive dementia over the last 2 years of his life. Investigation, including angiography and air encephalography early in the course of the illness and repeated CT head scans later, failed to demonstrate any neoplasm. Death occurred abruptly, due to cerebellar tonsillar herniation. At postmortem an extensive diffuse low grade fibrillary astrocytoma infiltrated both cerebral hemispheres, the corpus callosum, central grey matter, midbrain and pons. Thus, there was gliomatosis cerebri. Attention is drawn to the exceptional length of the history in this case, the difficulties which may arise in displaying diffusely infiltrating low grade astrocytomas radiologically and to the rare occurrence of gliomatosis cerebri.


Effectiveness of Violence Prevention Interventions: Umbrella Review of Research in the General Population.
To address the societal harms of violence, many violence prevention interventions have been developed, tested, and implemented in the general population. These have been reported in systematic reviews and meta-analyses, which have typically focused on one type of intervention or outcome. We aimed to provide a comprehensive overview of the current evidence regarding the effectiveness of different psychosocial interventions in reducing all forms of violence toward others. We have conducted an umbrella review of previous meta-analyses using standard approaches and converted findings on effectiveness into odds ratios. We tested for the underlying quality of the meta-analytic evidence by examining heterogeneity, excess statistical significance, prediction intervals, and small study effects. We identified 16 meta-analyses, including nine investigating psychosocial interventions, and five legislative and policy changes. Most meta-analyses reported positive effects of tested interventions. The strongest effects were found for sports-based initiatives, and the weakest for general population programs aimed at early childhood, youth development, and reducing sexual assault perpetration by men. Legislative changes had varying effectiveness. We conclude that simple, scalable, and cost-efficient programs, such as sport-based initiatives, have the clearest empirical support as population-based approaches to violence prevention.


Local rules for protein folding on a triangular lattice and generalized hydrophobicity in the HP model.
We consider the problem of determining the three-dimensional folding of a protein given its one-dimensional amino acid sequence. We use the HP model for protein folding proposed by Dill (1985), which models protein as a chain of amino acid residues that are either hydrophobic or polar, and hydrophobic interactions are the dominant initial driving force for the protein folding. Hart and Istrail (1996a) gave approximation algorithms for folding proteins on the cubic lattice under the HP model. In this paper, we examine the choice of a lattice by considering its algorithmic and geometric implications and argue that the triangular lattice is a more reasonable choice. We present a set of folding rules for a triangular lattice and analyze the approximation ratio they achieve. In addition, we introduce a generalization of the HP model to account for residues having different levels of hydrophobicity. After describing the biological foundation for this generalization, we show that in the new model we are able to achieve similar constant factor approximation guarantees on the triangular lattice as were achieved in the standard HP model. While the structures derived from our folding rules are probably still far from biological reality, we hope that having a set of folding rules with different properties will yield more interesting folds when combined.


[Moritz Kaposi and his sarcoma].
Nowadays, Kaposi sarcoma is a multidisciplinary condition, not only observed by dermatologists. Since the HIV epidemic in the 80s and 90s of the last century, more insight into the aetiology of Kaposi sarcoma has been acquired. However, this sarcoma had already been described in 1872 by a Hungarian dermatologist named Moritz Kaposi (1832-1902). Kaposi described the entity as 'idiopathic multiple pigmented sarcoma of the skin'. This entity was an extraordinary diagnosis at that time, mostly observed in Jewish or Mediterranean men. In 1912, 10 years after the death of Moritz Kaposi, the entity name was changed to Kaposi sarcoma.


Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis.
In previous experiments, replacing the 10-mg/kg of body weight daily dose of rifampin with 7.5 to 10 mg/kg of rifapentine in combinations containing isoniazid and pyrazinamide reduced the duration of treatment needed to cure tuberculosis in BALB/c mice by approximately 50% due to rifapentine's more potent activity and greater drug exposures obtained. In the present study, we performed dose-ranging comparisons of the bactericidal and sterilizing activities of rifampin and rifapentine, alone and in combination with isoniazid and pyrazinamide with or without ethambutol, in BALB/c mice and in C3HeB/FeJ mice, which develop necrotic lung granulomas after infection with Mycobacterium tuberculosis. Each rifamycin demonstrated a significant increase in sterilizing activity with increasing dose. Rifapentine was roughly 4 times more potent in both mouse strains. These results reinforce the rationale for ongoing clinical trials to ascertain the highest well-tolerated doses of rifampin and rifapentine. This study also provides an important benchmark for the efficacy of the first-line regimen in C3HeB/FeJ mice, a strain in which the lung lesions observed after M. tuberculosis infection may better represent the pathology of human tuberculosis.


Echocardiographic features of impaired ventricular function in diabetes mellitus.
In order to study left ventricular diastolic function in diabetes mellitus, simultaneous echo- and phonocardiograms were recorded in 142 diabetics (free from heart disease), 20 normal subjects, and 16 patients with coronary artery disease. The resultant traces were digitised, and left ventricular relaxation and the rate and duration of cavity dimension increase and wall thinning were determined. Diastolic variables of left ventricular function were normal in 12 young diabetics with no complications. Significantly delayed mitral valve opening relative to minimum dimension and aortic valve closure was found in all other groups of diabetics. Forty-four diabetics with severe microvascular complications had significantly reduced peak rate and prolonged duration of wall thinning and dimension increase. The abnormalities were unlike those found in subjects with coronary artery disease. The extent of microvascular complications was significantly correlated to most variables of diastolic function. This relation was maintained in 31 diabetics with significant cavity dimension increase during isovolumic relaxation (incoordinate relaxation). In 42 juvenile onset patients there was good correlation between the duration of diabetes and most variables of diastolic function. These studies show that the primary cardiac abnormality in diabetic micro-angiography is a prolonged duration and reduced rate of posterior wall thinning with impaired left ventricular dimension increase, reflecting abnormal myocardial properties.


Treatment of otitis media with observation and a safety-net antibiotic prescription.
Several studies have demonstrated that acute otitis media (AOM) in children can be managed without antibiotics. Because children with AOM have traditionally been treated with antibiotics in the United States, there are concerns that parents may not be comfortable with their children being treated with pain control alone. Recently, Cates in England showed that antibiotic usage for AOM could be decreased by prescribing a safety-net antibiotic prescription (SNAP) to be filled if symptoms do not resolve with observation after 48 hours. It is not clear whether a SNAP will be acceptable to parents in other settings such as the United States. The objective of our study was to determine whether parents in the United States find a SNAP for AOM acceptable and whether antibiotic usage could be decreased by its use. A pediatric practice-based research network in a midwestern community of 1.8 million was the setting for this study. The Cincinnati Pediatric Research Group (CPRG) includes practices in Ohio, Kentucky, and Indiana. Children who were between 1 and 12 years of age and presented to the offices of the CPRG with uncomplicated AOM were eligible for the study. Children were excluded when they had temperature >101.5 degrees F, had an ear infection in the past 3 months, showed signs of another bacterial infection, or were toxic appearing. Families were given acetaminophen, ibuprofen, or topical otic anesthetic drops for pain control. They were also given a prescription for an antibiotic and instructed not to fill it unless symptoms either increased or did not resolve after 48 hours. The data were entered directly by investigators via an Internet site. A total of 194 children were enrolled in 11 offices over 12 months; 175 (90%) completed the follow-up interview. The average child's age was 5.0 years. Only 55 (31%) of the 175 who were contacted for follow-up had filled their antibiotic prescription. Compared with their previous experience, parents were overwhelmingly willing to treat AOM with pain medication alone (chi(2) = 111). Seventy-eight percent (95% confidence interval: 71%-84%) of parents reported that the pain medication was effective. Sixty-three percent (95% confidence interval: 55%-70%) of parents reported that they would be willing to treat future AOM episodes without antibiotics and with pain medication alone. A subset of parents find a safety-net prescription and pain control acceptable in the treatment of AOM, and antibiotic usage can be lowered with this strategy.


The Long and Short of Next Generation Sequencing for Cryptosporidium Research.
The intestinal parasite Cryptosporidium is a significant cause of severe diarrhoeal disease that can have long term effects. Therapeutic options remain limited despite a significant impact on public health, partly due to various challenges in the field of Cryptosporidium research, including the availability of genomic and transcriptomic data from environmental and clinical isolates. In this review we explore how long read DNA and RNA sequencing technologies have begun to provide novel insights into the biology of the parasite. The increased deployment of these technologies will help researchers address key gaps in the understanding of Cryptosporidium biology, and ultimately drive translational research and better parasite control.


Multiple resolution texture analysis and classification.
Textures are classified based on the change in their properties with changing resolution. The area of the gray level surface is measured at serveral resolutions. This area decreases at coarser resolutions since fine details that contribute to the area disappear. Fractal properties of the picture are computed from the rate of this decrease in area, and are used for texture comparison and classification. The relation of a texture picture to its negative, and directional properties, are also discussed.


Lipopolysaccharide, central in vivo biogenic amine variations, and anhedonia.
Systemic administration of lipopolysaccharide (LPS), a non-specific activator of proinflammatory cytokine release from macrophages, provokes sickness characterized by anorexia, soporific effects, and disturbances of locomotor activity and exploration. In addition, endotoxin treatment may provoke an anhedonic response. Assessment of anhedonia in appetitive paradigms, however, is compromised by the anorexia provoked by the treatment. The present investigation assessed the anhedonic effects of LPS on rewarding lateral hypothalamic brain stimulation. Using a simultaneous discrimination, current titration procedure in the assessment of intracranial self-stimulation (ICSS), it was found that acute systemic administration of LPS (50 microg, 100 microg or 200 microg) reduced ICSS during the ascending sequence of current presentations, but had little effect on responding to a series of descending currents. In a parallel experiment, peripheral administration of LPS (100 microg) increased in vivo dopamine (DA) efflux from the nucleus accumbens, a region thought to be involved in goal-directed responding to positively reinforcing stimuli. It is suggested that LPS alters ICSS in a manner different than that observed following stressor exposure or peripheral IL-2 treatment. Furthermore, LPS may engender an anhedonic effect (possibly secondary to sickness), and the decline of responding reflects the relation between the cost of responding given in the face of sickness and the reward received for responding.


Modeling the system of beliefs that influence driving under the influence of cannabis (DUIC) in Washington State.
Cannabis use is increasing in the U.S. Driving under the influence of cannabis (DUIC) may be increasing as well potentially resulting in fatal and serious injury crashes. The purpose of this article is to explore the belief system associated with driving under the influence of cannabis (DUIC) using structural equation modeling (SEM). A sample (n = 2,084) of surveys collected from adults in the U.S. was analyzed using SEM to reveal the latent structure of the belief system associated with DUIC. The results of this analysis indicated that reported DUIC behavior (frequency and recency) was predicted by willingness that influenced intention. Willingness and intention were directly influenced by control beliefs, attitudes, norms, and attitudes (prototype image) toward people who never DUIC. Intention was also influenced by attitudes toward people who do DUIC. Intention had a stronger influence on DUIC than willingness alone. These components were influenced by underlying behavioral, normative, and control beliefs. Thus, strategies that can change these beliefs may also reduce DUIC.


Selecting Infants With Cryptorchidism and High Risk of Infertility for Optional Adjuvant Hormonal Therapy and Cryopreservation of Germ Cells: Experience From a Pilot Study.
Orchiopexy for congenital cryptorchid testes is recommended between ½ and 1 year of age to preserve testicular germ cell maturation. Early operation is not enough to preserve fertility in 22 and 36% of cases. Aim of this study was to set up a protocol for optional adjuvant hormonal therapy after orchiopexy and thereafter cryopreservation of testicular biopsies from infants with bilateral cryptorchidism and high infertility risk. We included 17 boys with bilateral cryptorchidism, normal FSH, and impaired germ cell number per tubular transverse section (G/T) in testicular biopsies at orchiopexy, 7 months to 3½ years old. Postoperatively, optional adjuvant LHRH (kryptocur®) 0.2 mg/0.1 mL 2× every second day in 16 weeks were offered. Ten boys were applicable for age matching according to parent's choice of treatment regime and G/T. Five of them had kryptocur®, and five were controls. Repeat bilateral testicular biopsy evaluation and cryopreservation were offered to all boys 12 months after primary orchiopexy. For cryopreservation, tissue pieces were incubated with a cryoprotectant with a slow program freezing. Two out of five kryptorcur®-treated boys normalized both the average G/T and the number of adult dark spermatogonia (Ad-S). Another kryptocur®-treated boy with initial low G/T and no Ad-S increased the G/T and achieved normal number of Ad-S at time of cryopreservation. In the control group, two patients reached only normal lower range regarding the G/T and the number of Ad-S. None of boys with less than average 0.2 G/T improved significantly, whether they were kryptocur®-treated or not. Based on literature and the present results, we recommend adjuvant LHRH treatment to boys with cryptorchidism and insufficient genuine gonadotropin stimulation at time of surgery, as these patients have high infertility risk. Cryopreservation should be an option in case of treatment failure of adjuvant LHRH. However, to avoid repeat surgery with biopsy, some parents may choose biopsy for cryopreservation at time of the initial bilateral orchiopexy, well informed that the procedure may only be truly indicated in 22 and 36% of the cases.


Insights Into the Oral Microbiome and Barrett's Esophagus Early Detection: A Narrative Review.
Barrett's esophagus (BE) prevalence has increased steadily over the past several decades and continues to be the only known precursor of esophageal adenocarcinoma. The exact cause of BE is still unknown. Most evidence has linked BE to gastroesophageal reflux disease, which injures squamous esophageal mucosa and can result in the development of columnar epithelium with intestinal metaplasia. However, this relationship is inconsistent-not all patients with severe gastroesophageal reflux disease develop BE. There is increasing evidence that the host microbiome spanning the oral and esophageal environments differs in patients with and without BE. Several studies have documented the oral and esophageal microbiome's composition for BE with inconsistent findings. The scarcity and inconsistency of the literature and the dynamic phenomena of microbiota all warrant further studies to validate the findings and dissect the effects of oral microbiota, which are considered a viable proxy to represent esophageal microbiota by many researchers. This review aims to summarize the variability of the oral and esophageal microbiome in BE by using the example of Streptococcus to discuss the limitations of the current studies and suggest future directions. Further characterization of the sensitivity and specificity of the oral microbiome as a potential risk prediction or prevention marker of BE is critical, which will help develop noninvasive early detection methods for BE, esophageal adenocarcinoma, and other esophageal diseases.


The C-terminal domain of yeast PCNA is required for physical and functional interactions with Cdc9 DNA ligase.
There is compelling evidence that proliferating cell nuclear antigen (PCNA), a DNA sliding clamp, co-ordinates the processing and joining of Okazaki fragments during eukaryotic DNA replication. However, a detailed mechanistic understanding of functional PCNA:ligase I interactions has been incomplete. Here we present the co-crystal structure of yeast PCNA with a peptide encompassing the conserved PCNA interaction motif of Cdc9, yeast DNA ligase I. The Cdc9 peptide contacts both the inter-domain connector loop (IDCL) and residues near the C-terminus of PCNA. Complementary mutational and biochemical results demonstrate that these two interaction interfaces are required for complex formation both in the absence of DNA and when PCNA is topologically linked to DNA. Similar to the functionally homologous human proteins, yeast RFC interacts with and inhibits Cdc9 DNA ligase whereas the addition of PCNA alleviates inhibition by RFC. Here we show that the ability of PCNA to overcome RFC-mediated inhibition of Cdc9 is dependent upon both the IDCL and the C-terminal interaction interfaces of PCNA. Together these results demonstrate the functional significance of the beta-zipper structure formed between the C-terminal domain of PCNA and Cdc9 and reveal differences in the interactions of FEN-1 and Cdc9 with the two PCNA interfaces that may contribute to the co-ordinated, sequential action of these enzymes.


Pediatric SLE--towards a comprehensive management plan.
Systemic lupus erythematosus (SLE) results from complex abnormalities of the innate and acquired immune systems. For reasons that are currently not well understood, the disease course and phenotype associated with SLE, although quite variable, are generally more severe when the diagnosis is made during childhood. Active disease, infections, lupus nephritis, and neuropsychiatric SLE manifestations are associated with higher morbidity and mortality. Unlike in adult-onset SLE, systemic glucocorticoid therapy and immunosuppressive medications are needed for the treatment of the majority of children and adolescents with SLE. The complex nature of childhood-onset SLE demands a comprehensive, multidisciplinary management approach that considers the patients' growth and development, their educational needs, and the unpredictable course of SLE and its complications.


Discoidal Porous Silicon Particles: Fabrication and Biodistribution in Breast Cancer Bearing Mice.
Porous silicon (pSi) is emerging as a promising material in the development of nanovectors for the systemic delivery of therapeutic and imaging agents. The integration of photolithographic patterning, typical of the semiconductor industry, with electrochemical silicon etching provides a highly flexible strategy to fabricate monodisperse and precisely tailored nanovectors. Here, a microfabrication strategy for direct lithographic patterning of discoidal pSi particles is presented that enables precise and independent control over particle size, shape, and porous structure. Discoidal pSi nanovectors with diameters ranging from 500 to 2600 nm, heights from 200 to 700 nm, pore sizes from 5 to 150 nm, and porosities from 40 to 90% are demonstrated. The degradation in serum, interaction with immune and endothelial cells in vitro, and biodistribution in mice bearing breast tumors are assessed for two discoidal nanovectors with sizes of 600 nm × 400 nm and 1000 nm × 400 nm. It is shown that both particle types are degraded after 24 h of continuous gentle agitation in serum, do not stimulate cytokine release from macrophages or affect endothelial cell viability, and accumulate up to about 10% of the injected dose per gram tissue in orthotopic murine models of breast cancer. The accumulation of the discoidal pSi nanovectors into the breast tumor mass is found to be up to five times higher than for spherical silica beads with similar diameters.


[The diagnostic role of chemokines and their receptors in chronic hepatitis C].
The chronic hepatitis C is characterized by the increase of inflammatory disorders and progression of fibrosis of liver The corresponding immunologic mechanisms of hepatic lesions are still undiscovered. The actual review presents the analysis of scientific publications and genuine research data concerning the role of chemokines in pathogenesis of chronic hepatitis C. The chemokines are small cationic proteins enhancing transit and precipitation of migrating cells (leucocytes mainly) in tissues and organs. The significant role of chemokines in tissue homeostasis, in case of inflammation, wound healing and cell proliferation is demonstrated. The particular kinds of chemokines are produced by different types of cells and impact target cells through their specific receptors. According the data of various studies, chemokines and chemokine receptors of CC-families and CXC-families are involved in fibrosing processes and anti-inflammatory activation of hepatic-biliary system under chronic hepatitis C. The diversity of producers and targets of chemokines in liver is very pronounced: hepatocytes, stellar cells, endothelium cells, macrophages (Kupffer cells), dendritic cells, lymphocytes and monocytes. The review considers pathogenesis of chronic hepatitis C from the standpoint of participation of chemokines and chemokine receptors at different stages of cellular transit. The most important cellpopulations involved into pathologic changes under chronic hepatitis C are characterized. The decrease of expression of such gens as CCR1, CCR2, CCR3, and CCR5 in blood leucocytes deserves additional studies to establish their diagnostic values as a marker of disorders of immune system in patients with chronic hepatitis C.


In-hospital outcomes with thrombolytic therapy in patients with renal dysfunction presenting with acute ischaemic stroke.
Thrombolytic therapy is an effective treatment modality for acute ischaemic stroke within 3 hours of symptom onset. Its safety and efficacy have not been studied in patients with chronic kidney disease (CKD), who are known to have abnormalities in coagulation and platelet function. We studied all patients who consecutively received intravenous thrombolytic therapy for acute stroke at our hospital from 2005-2009 (n = 74). Alteplase was administered to patients deemed eligible by National Institute of Health criteria per protocol. We studied associations between admission renal dysfunction [estimated glomerular filtration rate (eGFR) <60ml/min/1.73 m(2)] and in-hospital outcomes: intracranial haemorrhage (ICH), poor functional status (modified Rankin score 3-6) and death. Mean +/- SD age was 66.4 +/- 16.9 years with 39 (52.7%) men and 46 (62.2%) Caucasian. Twenty patients (27.0%) had eGFR <60 and were older, with a higher prevalence of diabetes and coronary artery disease than patients with eGFR > or =60. Presenting stroke severity, blood pressure and time to alteplase were similar in the two groups. Symptomatic ICH occurred in two patients with eGFR > or =60. Asymptomatic and symptomatic ICH considered together showed no difference in these event rates (20% in eGFR <60 vs 11.1% in eGFR > or =60, P = 0.321). There was no difference in poor functional status (70.0% in eGFR <60 vs 57.4% in eGFR > or =60, P = 0.324) or in-hospital death outcomes (10.0% in eGFR <60 vs 7.4% in eGFR > or =60, P = 0.717). Multivariate logistic regression analysis revealed no association between eGFR <60 and in-hospital outcomes, while increasing age was associated with poor functional status [odds ratio 1.03 (1.00-1.06, P = 0.047)]. In our limited sample size study, presence of eGFR <60 in patients receiving thrombolytic therapy for acute stroke was not found to be associated with increased ICH, poor functional outcome or death. These findings suggest that use of thrombolytics in acute stroke is appropriate in patients with renal dysfunction.


Diagnosis and Characterization of Patellofemoral Instability: Review of Available Imaging Modalities.
Patellofemoral instability (PI) is defined as single or multiple episodes of patellar dislocation. Imaging modalities are useful for characterization of patellar malalignment, maltracking, underlying morphologic abnormalities, and stabilizing soft-tissue injuries. Using these findings, orthopedic surgeons can decide when to operate, determine the best operation, and measure degree of correction postoperatively in PI patients. Also, these methods assist with PI diagnosis in some suspicious cases. Magnetic resonance imaging is the preferred method especially in the setting of acute dislocations. Multidetector computed tomography allows a more accurate assessment for malalignment such as patellar tilt and lateral subluxation and secondary osteoarthritis. Dynamic magnetic resonance imaging and 4-dimensional computed tomography have been introduced for better kinematic assessment of the patellofemoral maltracking during extension-flexion motions. In this review article, we will discuss the currently available evidence regarding both the conventional and the novel imaging modalities that can be used for diagnosis and characterization of PI.


Dimethyl sulfoxide (DMSO) inhibits the germination of Candida albicans and the arthrospores of Trichophyton mentagrophytes.
Dimethyl sulfoxide (DMSO) is commonly used as a solvent for antifungal drugs. Earlier the author has reported the inhibitory effect of DMSO on the growth of many strains of dermatophytes' colonies in dermasel agar and proposed that this could cause the variations between results of different studies for the evaluation of the activities of antifungal drugs. In studies regarding the determination of the effect of antifungal drugs on the germination of arthrospores of dermatophytes it was observed that relatively higher concentrations of DMSO were being used as a solvent for the antifungal drugs, the final concentration in the media being 5%. Therefore, the present study was aimed at determining the effect of different concentrations of DMSO (1.25 to 10%) on the growth of germ tubes of arthrospores of Trichophyton mentagrophytes and Candida albicans, in glucose peptone broth. With DMSO 10% there was a negligible growth of germ tubes of both the arthrospores and yeast; between 2.5 and 7.5% there was a rather linear dose-related inhibitory effect; whereas 1.25% had insignificant effect from controls. The present study shows that besides other factors, variations in the results of the susceptibility tests of antifungal drugs might occur due to the effect of DMSO on the growth of fungi and differences in the final concentration of DMSO in the medium.


Transduction of the Geomagnetic Field as Evidenced from alpha-Band Activity in the Human Brain.
Magnetoreception, the perception of the geomagnetic field, is a sensory modality well-established across all major groups of vertebrates and some invertebrates, but its presence in humans has been tested rarely, yielding inconclusive results. We report here a strong, specific human brain response to ecologically-relevant rotations of Earth-strength magnetic fields. Following geomagnetic stimulation, a drop in amplitude of electroencephalography (EEG) alpha-oscillations (8-13 Hz) occurred in a repeatable manner. Termed alpha-event-related desynchronization (alpha-ERD), such a response has been associated previously with sensory and cognitive processing of external stimuli including vision, auditory and somatosensory cues. Alpha-ERD in response to the geomagnetic field was triggered only by horizontal rotations when the static vertical magnetic field was directed downwards, as it is in the Northern Hemisphere; no brain responses were elicited by the same horizontal rotations when the static vertical component was directed upwards. This implicates a biological response tuned to the ecology of the local human population, rather than a generic physical effect. Biophysical tests showed that the neural response was sensitive to static components of the magnetic field. This rules out all forms of electrical induction (including artifacts from the electrodes) which are determined solely on dynamic components of the field. The neural response was also sensitive to the polarity of the magnetic field. This rules out free-radical "quantum compass" mechanisms like the cryptochrome hypothesis, which can detect only axial alignment. Ferromagnetism remains a viable biophysical mechanism for sensory transduction and provides a basis to start the behavioral exploration of human magnetoreception.


[Effect of Different Doses of Herbal Cake-partitioned Moxibustion on Histopathological Changes of Colon Tissue in Ulcerative Colitis Rats].
To observe the effect of different-doses of herbal cake-partitioned moxibustion (Moxi) on histopathological changes of the damaged colon tissue in rats with ulcerative colitis (UC), so as to select an optimal dosage of Moxi in the treatment of UC. Sixty-three male Sprague Dawley (SD) rats were randomized into 7 groups: normal control, model, medication, and 1, 2, 3 and 4 moxa-cone Moxi (n=9 rats per group). The UC model was developed by subcutaneous injection of emulsion (1 mL) containing colon mucosa-prepared protein suspension and complete Freund's adjuvant into the toes, groin and back. On the 38th day, enema of 3% formalin and the aforementioned emulsion was used. Herbal-cake (composed of monkshood, cinnamon, etc.) partitioned Moxi with 1 or 2 moxa-cones (about 5 min/cone) was applied to bilateral "Tianshu" (ST 25) once daily or once every other day. The rat's general conditions (diet, movement, response ability, stool, and body weight) were observed, and histopathological changes (adhesion, ulcer formation and inflammation) of colon tissues were examined after hematoxylin-eosin (HE) staining, and scored (histopathological score). Gross score was given according to the severity of adhesion, ulcer formation and inflammation of colonic tissues under stereo microscope. The average optical density (AOD) values of colonic mucins were detected after periodic acid-schiff (PAS) staining, and those of the sulfated mucus content detected after high iron dia-mine-alcian blue (HID-AB) staining. Compared with the normal group, rats in the model group presented loose stool, or with pus and blood, and slowly increased body weight (P<0.01), obvious congestion of colon with ulcer spots or continuous superficial ulcer regions which had irregular glandular cavities, swelling and serious inflammatory infiltration in lamina propria and submucosa, and increased score of colon tissue damage (P<0.01). PAS and HID-AB staining showed a marked decrease of AOD values of colonic mucins and sulfated mucus in the model group relevant to the normal control group (P<0.01), suggesting a reduction of mucus secretion of intestinal glands. Following the intervention, rats in the Moxi groups presented an increase of the body weight, formed feces, and an improvement of the damaged colon tissues as mucosal healing and inflammatory reduction, and a marked decrease of the damage score relevant to the model rats. No significant differences were found in the gross scores among the medication, 1, 2, 3 and 4 moxa-cone groups (P>0.05). The histopathological scores were significantly lower in the 1 and 4 moxa-cone Moxi groups than in the medication group (P<0.05, P<0.01); and significantly lower in the 1, 3, 4 moxa-cone Moxi groups than in the 2 moxa-cone Moxi group (P<0.05, P<0.01). PAS staining showed a significant increase of the AOD values of colonic mucins in the 1, 2, 3 and 4 moxa-cone and medication groups relevant to the model group (P<0.01); and the AOD values of colonic mucins in the 1, 3, 4 moxa-cone Moxi groups were significantly increased than that in the 2 moxa-cone Moxi group (P<0.05, P<0.01). HID-AB staining showed that the AOD values of sulfated mucus content were significantly higher in the 2 and 4 moxa-cone Moxi groups than in the 3 moxa-cone Moxi group (P<0.01). The two-level two-factor factorial analysis showed an interaction existed between the moxa-cone number and Moxi frequency in reducing the gross score and histopathological score and in facilitating colonic mucin and sulfated mucus secretion. The histopathological score of the 4 moxa-cone Moxi group was significantly lower than that of the 2 moxa-cone Moxi group (P<0.05), and the sulfated mucus content was significantly higher in the 4 moxa-cone group than in the 3 moxa-cone group (P<0.01). The effect of Moxi given on alternate days was superior to that of daily Moxi in improving colonic histological damage. Herbal cake-partitioned moxibustion at ST 25 can promote repair of the damaged colonic tissue and secretion of mucin in UC rats. The number of moxa cones and intervention frequency affect the efficacy of Moxi in improving histopathological changes. The Moxi intervention on alternate days and with 2 moxa-cones every time is recommended.


C3-mediated cytoadherence. Formation of C3 receptor aggregates as prerequisite for cell attachment.
Inhibition of free movement of C3 receptors by either applying low temperature (3 degrees C) or fixing the cell surfce of lymphocytes with glutaraldehyde (2 times 10(-5) to 2 times 10(-1)%) results in loss of firm attachment of EAC142 3b cells to the lympocytes as demonstrated here by loss of rosette formation of Raji lymphoid cells. Under the same conditions soluble C3 can still bind but is unable to induce aggregation of C3 receptors into small patches. It is suggested that the local increase of C3 receptor density by aggregation is a prerequisite for C3-dependent cytoadherence. Microaggregation of corresponding receptor sites may be essential also in other recognition systems.


Electronic and Optical Property Control of Polycation/MXene Layer-by-Layer Assemblies with Chemically Diverse MXenes.
MXenes, 2D nanomaterials derived from ceramic MAX phases, have drawn considerable interest in a wide variety of fields including energy storage, catalysis, and sensing. There are many possible MXene compositions due to the chemical and structural diversity of parent MAX phases, which can bear different possible metal atoms "M", number of layers, and carbon or nitrogen "X" constituents. Despite the potential variety in MXene types, the bulk of MXene research focuses upon the first MXene discovered, Ti3C2T. With the recent discovery of polymer/MXene multilayer assemblies as thin films and coatings, there is a need to broaden the accessible types of multilayers by including MXenes other than Ti3C2Tz; however, it is not clear how altering the MXene type influences the resulting multilayer growth and properties. Here, we report on the first use of MXenes other than Ti3C2Tz, specifically Ti2CTz and Nb2CTz, for the layer-by-layer (LbL) assembly of polycation/MXene multilayers. By comparing these MXenes, we evaluate both how changing M (Ti vs Nb) and "n" (Ti3C2Tzvs Ti2CTz) affect the growth and properties of the resulting multilayer. Specifically, the aqueous LbL assembly of each MXene with poly(diallyldimethylammonium) into films and coatings is examined. Further, we compare the oxidative stability, optoelectronic properties (refractive index, absorption coefficient, optical conductivity, and direct and indirect optical band gaps), and the radio frequency heating response of each multilayer. We observe that MXene multilayers with higher "n" are more electrically conductive and oxidatively stable. We also demonstrate that Nb2CTz containing films have lower optical band gaps and refractive indices at the cost of lower electrical conductivities as compared to their Ti2CTz counterparts. Our work demonstrates that the properties of MXene/polycation multilayers are highly dependent on the choice of constituent MXene and that the MXene type can be altered to suit specific applications.


Impact of individual, household and community characteristics on children's nutritional indicators.
This study analyzed WHO-standardized nutritional indicators of children from selected households within communities that were sampled from all districts of Botswana. Data from the 2007 Botswana Family Health Survey were fitted into multilevel models that seek to account for variability due to the macro- and micro-units that have been hierarchically selected. This allowed for estimation of different levels of intraclass correlations while simultaneously assessing the model-fit by accounting for the influence on the nutritional indicators due to the fixed variables attributable to these macro- and micro-units. The results show that variation in nutritional status of under-five children in Botswana is a function of characteristics of the households and communities within which they live. As much as 17% of variation is due to differences in the communities and households. Economic status of households holds an important key in predicting the nutritional status of children.


Desaturation and elongation of Fatty acids and insulin action.
Insulin resistance is characterized by specific changes of the composition of fatty acids in the serum lipids and in the skeletal muscle membranes. Impaired insulin sensitivity is associated with high proportions of palmitic (16:0) acid and low levels of linoleic (18:2 n-6) acid in serum. In addition, there are apparent changes of the fatty acid desaturase activities, suggesting an increased activity of the Delta9 and Delta6 desaturases and a decreased activity of the Delta5 desaturase. The activity of the fatty acid desaturases is regulated by long-chain polyunsaturated fatty acids and insulin and is probably also dependent on the degree of physical activity. A high ratio between arachidonic (20:4 n-6) and dihomo-gamma linolenic (20:3 n-6) acid, as a measure of Delta5 desaturase activity, in the skeletal muscle phospholipids has been related to good insulin sensitivity. Available knowledge seems to indicate that the degree of saturation of the body lipids, and especially the proportion of palmitic acid in the lipid membranes, may be critical for insulin sensitivity. The strong relationships between the Delta5 desaturase activity, a high content of long-chain polyunsaturated fatty acids in the skeletal muscle, and insulin sensitivity may be due to parallel effects of diet and/or physical activity on the fatty acid composition and on insulin sensitivity.


Air Evacuation of Service Members for COVID-19 in U.S. Central Command and U.S. European Command From 11 March 2020 Through 30 September 2020.
This report documents the numbers of air evacuations for diagnoses of coronavirus disease 2019 (COVID-19) among U.S. active duty service members (ADSMs) from locations in U.S. Central Command (CENTCOM) and U.S. European Command (EUCOM) areas of responsibility. Counted were COVID-19 evacuations both within and out of each of the theaters from 11 March through 30 September 2020. Of the 186 evacuations originating in CENTCOM, 185 resulted in the patients arriving at Landstuhl in EUCOM and 1 was within theater. A total of 169 of the CENTCOM evacuations took place in June through August 2020 and only 1 occurred in September. Of the 39 air evacuations originating in EUCOM, 38 were intra-theater transfers and 1 was to a CONUS facility. Most (n=32) of the EUCOM evacuations occurred in September. Evacuees were most often members of the Army (71%), enlisted personnel (63%), males (91%), and aged 30 years or older (58%). Among a random sample of 56 evacuees, 20% were asymptomatic. Among those with symptoms, the most common were cough, fatigue, congestion, headache, and sore throat.


Improving access to preparatory information for children undergoing general anaesthesia for tooth extraction and their families: study protocol for a Phase III randomized controlled trial.
Children can find anaesthesia induction especially distressing and postoperative psychological and physical morbidity are common. Preparation programmes for general anaesthesia (GA) are highly effective in reducing this distress. A Phase II study has already verified the effectiveness of a prototype preoperative GA-coping computer game to help children cope with induction in a dental GA setting. The biggest patient users of pediatric GA services in the UK are children who need to have teeth removed (estimated to be 100,000 yearly). Tooth decay is the most common disease in children worldwide. This study is a Phase III randomized controlled trial (RCT) and will evaluate the effectiveness of the new internet version of this game. The Phase III RCT will use a double-blind three-armed design. The clinical trial will recruit up to 210 children and will compare the web-based game against standard care and another non-medical game. At least 53 patients in each group will be required for 90% statistical power. Distress will be assessed through an evaluation of the child's behaviour during the visit and later parental reports of physical and psychological morbidity. The satisfaction of parents and children will be measured; the mode of usage of the web-based game will be automatically recorded and the impact on the service (for example, recovery time and throughput) will be reported.The Phase III study primary outcome will measure: (1) patient experience: acceptance of anaesthetic induction, child cooperation and distress, reduction of peri- and postoperative morbidity, child and family satisfaction, and (2) service improvement: anaesthetic time and improvement in throughput. Measures will be administered at baseline, at the time of the GA treatment visit, and at 48 hours and one week postoperatively. This study aims to determine the effectiveness of an online GA-coping game for children and families undergoing tooth extraction under GA. ISRCTN18265148 (registered 24 November 2013).