G allele of the -930A>G polymorphism of the CYBA gene is associated with insulin resistance in obese subjects.
It has been shown that NADPH oxidase plays a role in oxidative stress which has been involved in the development of metabolic syndrome. The -930A/G polymorphism of the CYBA gene (that codes p22phox, a major component of the NADPH oxidase) has been associated with human hypertension and with a reduction in NADPH oxidase activity. In this work, we have examined the influence of the -930A/G polymorphism on obesity risk and insulin resistance in a case-control study of Spanish subjects (n=313). In the obese group (n=159), there was a statistically significant association between the GG genotype of the -930A/G polymorphism of the CYBA gene and fasting insulin levels and HOMA index. This outcome agrees with previous findings concerning functional analyses of this polymorphism and reinforces the hypothesis that insulin resistance is associated with oxidative stress. In conclusion, a protective effect in carriers of the -930A/G polymorphism of the p22phox gene against insulin resistance in a population of Spanish obese adults has been found.


Lipopolysaccharide-Activated Leukocytes Enhance Thymic Stromal Lymphopoietin Production in a Mouse Air-Pouch-Type Inflammation Model.
Thymic stromal lymphopoietin (TSLP) is a key cytokine that exacerbates allergic and fibrotic reactions. Several microbes and virus components have been shown to induce TSLP production, mainly in epithelial cells. TLR4 activators, such as lipopolysaccharide (LPS), induce TSLP production in vivo, although the underlying mechanisms remain unclear. In this study, we investigated the contribution of LPS-activated leukocytes to the production of TSLP in a mouse air-pouch-type inflammation model. LPS induced the production of TSLP in this model but not in the mouse keratinocyte cell line PAM212. Transfer of the infiltrated leukocytes collected from an LPS-injected air pouch to the air pouch of another mouse enhanced TSLP production. Further, the LPS-activated leukocytes produced tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β); a deficiency in these cytokines attenuated the LPS-induced production of TSLP. TSLP production was induced by TNF-α and enhanced by IL-1β and LPS in the PAM212 cells. These results demonstrated that TNF-α and IL-1β, which are partly produced by LPS-activated leukocytes, contribute to TSLP production via TLR4 activation in vivo.


Re-oxygenation of hypoxic simian virus 40 (SV40)-infected CV1 cells causes distinct changes of SV40 minichromosome-associated replication proteins.
Hypoxia interrupts the initiation of simian virus 40 (SV40) replication in vivo at a stage situated before unwinding of the origin region. After re-oxygenation, unwinding followed by a synchronous round of viral replication takes place. To further characterize the hypoxia-induced inhibition of unwinding, we analysed the binding of several replication proteins to the viral minichromosome before and after re-oxygenation. T antigen, the 34-kDa subunit of replication protein A (RPA), topoisomerase I, the 48-kDa subunit of primase, the 125-kDa subunit of polymerase delta, and the 37-kDa subunit of replication factor C (RFC) were present at the viral chromatin already under hypoxia. The 70-kDa subunit of RPA, the 180-kDa subunit of polymerase alpha, and proliferating cell nuclear antigen (PCNA) were barely detectable at the SV40 chromatin under hypoxia and significantly increased after re-oxygenation. Immunoprecipitation of minichromosomes with T antigen-specific antibody and subsequent digestion with micrococcus nuclease revealed that most of the minichromosome-bound T antigen was associated with the viral origin in hypoxic and in re-oxygenated cells. T antigen-catalysed unwinding of the SV40 origin occurred, however, only after re-oxygenation as indicated by (a) increased sensitivity of re-oxygenated minichromosomes against digestion with single-stranded DNA-specific nuclease P1; (b) stabilization of RPA-34 binding at the SV40 minichromosome; and (c) additional phosphorylations of RPA-34 after re-oxygenation, probably catalysed by DNA-dependent protein kinase. The results presented suggest that the subunits of the proteins necessary for unwinding, primer synthesis and primer elongation first assemble at the SV40 origin in form of stable, active complexes directly before they start to work.


Old warp, new weft: weaving a new life fabric after anoxia.
A young New Zealander reweaves a new life after a severe anoxic brain injury. His mother, a teacher, works from an educational perspective to construct an individualized lifestyle plan (ILP), implemented in the community by a team of support workers. This approach to learning is holistic and encompasses the physical, cognitive, emotional and spiritual dimensions of human healing. This article, part of the requirements for a Master's degree in Special Education, recounts part of the new journey, which is described in the language of capacity, achievement and love, rather than that of dysfunction, disability and disappointment.


Cation-cation contact pairing in water: guanidinium.
The formation of like-charge guanidinium-guanidinium contact ion pairs in water is evidenced and characterized by X-ray absorption spectroscopy and first-principles spectral simulations based on molecular dynamics sampling. Observed concentration-induced nitrogen K-edge resonance shifts result from π* state mixing and the release of water molecules from each first solvation sphere as two solvated guanidinium ions associate into a stacked pair configuration. Possible biological implications of this counterintuitive cation-cation pairing are discussed.


Preconceptional Nutrition Interventions for Adolescent Girls and Adult Women: Global Guidelines and Gaps in Evidence and Policy with Emphasis on Micronutrients.
Much of the global nutrition efforts in recent years have been focused on improving the nutritional status of children during the window of the first 1000 d of life, from conception to 2 y of age. However, as the world transitions from the Millennium Development Goals to the Sustainable Development Goals, women's and adolescent girls' overall health and well-being are being placed at the center of the global agenda. It is also increasingly recognized that a woman's nutritional status before pregnancy affects maternal and child outcomes and thus needs to be improved to ensure optimal outcomes. This article reviews the global picture of preconception nutrition in women and girls, including some of the key factors that influence women's outcomes, as well as their children's outcomes, if they do become pregnant. This article describes the current global guidelines on preconceptional nutrition interventions for girls and women; highlights related gaps in evidence, guidelines, and policy; and discusses research to forward the agenda of improving women's and girls' preconceptional nutrition.


Inducing malignant transformation of endometriosis in rats by long-term sustaining hyperestrogenemia and type II diabetes.
This study aimed to induce malignant transformation of endometriosis in Sprague-Dawley rats by hyperestrogenemia and type II diabetes and evaluate its similarity with human disease in biological features. Rats with surgically induced endometriosis were randomized into two groups: those treated with estradiol (5 mg/kg three times/week after surgery), streptozotocin (25 mg/kg, 1 month after surgery), and high carbohydrate-and-fat feed (Es group); and those treated with placebo saline and standard feed (control group). All rats were randomly killed 2, 4, or 8 months after surgery. The endometriosis lesions and the corresponding eutopic endometria were subjected to morphological evaluation, TUNEL, and immunohistochemical analysis for the expressions of proliferating cell nuclear antigen, phosphatase and tensin homolog, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin proteins. In the Es group, three cases (6.0%) of endometriosis showed atypical hyperplasia accompanied by simple hyperplastic eutopic endometria, and two cases (4.0%) of endometriosis showed endometrioid carcinoma accompanied by atypical hyperplastic eutopic endometria. In the Es group, the activity of organelles and the expressions of proliferating cell nuclear antigen, phosphorylated protein kinase B, and phosphorylated mammalian target of rapamycin increased, and the level of phosphatase and tensin homolog and TUNEL positivity decreased progressively in the order of endometriosis, atypical endometriosis, and malignant endometriosis. The same tendency was found in the corresponding eutopic endometria. The induced malignant endometriosis showed similarities with human disease in the pathological process and histomorphological and molecular biological features. The method is feasible. The malignant transformations of endometriosis and eutopic endometria may have correlations and similarities, but the former may suffer a higher risk of canceration.


A recurrent 11q aberration pattern characterizes a subset of MYC-negative high-grade B-cell lymphomas resembling Burkitt lymphoma.
The genetic hallmark of Burkitt lymphoma (BL) is the t(8;14)(q24;q32) and its variants leading to activation of the MYC oncogene. It is a matter of debate whether true BL without MYC translocation exists. Here, we identified 59 lymphomas concordantly called BL by 2 gene expression classifiers among 753 B-cell lymphomas. Only 2 (3%) of these 59 molecular BL lacked a MYC translocation, which both shared a peculiar pattern of chromosome 11q aberration characterized by interstitial gains including 11q23.2-q23.3 and telomeric losses of 11q24.1-qter. We extended our analysis to 17 MYC-negative high-grade B-cell lymphomas with a similar 11q aberration and showed this aberration to be recurrently associated with morphologic and clinical features of BL. The minimal region of gain was defined by high-level amplifications in 11q23.3 and associated with overexpression of genes including PAFAH1B2 on a transcriptional and protein level. The recurrent region of loss contained a focal homozygous deletion in 11q24.2-q24.3 including the ETS1 gene, which was shown to be mutated in 4 of 16 investigated cases. These findings indicate the existence of a molecularly distinct subset of B-cell lymphomas reminiscent of BL, which is characterized by deregulation of genes in 11q.


Avian torpor or alternative thermoregulatory strategies for overwintering?
It is unclear whether torpor really is uncommon amongst passerine birds. We therefore examined body temperature and thermoregulatory strategies of an Austral passerine, the white-browed babbler (Pomatostomus superciliosus), which has characteristics related to a high probability of torpor use; it is a sedentary, insectivorous, cooperative breeding species, which we studied during winter in a temperate habitat. Wild, free-living babblers maintained normothermy overnight, even at sub-zero ambient temperatures, with a mean minimum body temperature of 38.5±0.04°C that was independent of minimum black bulb temperature. Physiological variables measured in the laboratory revealed that babblers had a low basal metabolic rate and evaporative water loss, but their body temperature and thermal conductance were typical of those of other birds and they had a typical endothermic response to low ambient temperature. Huddling yielded significant energy savings at low temperatures and a roost nest created a microclimate that buffered against low temperatures. Low basal energy requirements, communal roosting and the insulation of a roost nest confer sufficient energetic benefits, allowing babblers to meet energy requirements without resorting to heterothermia, even in their depauperate, low-productivity landscape, suggesting that passerine birds use alternatives to torpor to balance their energy budgets when possible.


Distribution of polyamines may be altered in different scalp regions of patients with hair loss.
Hair loss, from the vertex or front of the head, generally occurs due to increased androgenic steroid levels. Androgenic steroids, particularly testosterone and dihydrotestosterone, are distributed differently across the vertex and occipital regions and are involved in inducing ornithine decarboxylase expression. Therefore, we hypothesized that the distribution of polyamines may be altered in different scalp regions. For the overall metabolic profiling of polyamines in patients with hair loss, a liquid chromatography-mass spectrometry was used. We investigated the differential polyamine levels in different regions of the hair of patients with male pattern baldness and those with female pattern hair loss. The levels of most polyamines were higher in the vertex region than in the occipital region, and N-acetyl polyamine levels differed significantly. We proposed to test our hypothesis by profiling polyamines in human hair fibre to evaluate the distribution of metabolites in various regions of the scalp.


Sarkosyl defines three intermediate steps in transcription initiation by RNA polymerase III: application to stimulation of transcription by E1A.
We used Sarkosyl to analyze steps along the pathway of transcription initiation by RNA polymerase III. Sarkosyl (0.015%) inhibited transcription when present prior to incubation of RNA polymerase III, TFIIIB, and TFIIIC with the VAI gene, whereas it had no detectable effect on initiation or reinitiation of transcription when added subsequently. The formation of the corresponding 0.015% Sarkosyl-resistant complex required the presence of TFIIIC, TFIIIB, and RNA polymerase III but not nucleoside triphosphates. The addition of 0.05% Sarkosyl after this early step selectively inhibited a later step in the preinitiation pathway, allowing a single round of transcription after nucleoside triphosphate addition but blocking subsequent rounds of initiation. This step occurred prior to initiation because nucleoside triphosphates were not required for the formation of the corresponding 0.05% Sarkosyl-resistant complex. These observations provided a means to distinguish effects of regulatory factors on different steps in promoter activation and function. Using 0.05% Sarkosyl to limit reinitiation, we determined that the E1A-mediated stimulation of transcription by RNA polymerase III resulted from an increase in the number of active transcription complexes.


A configurational temperature Nosé-Hoover thermostat.
We propose two new thermostats which can be employed in computer simulations to ensure that two different variants of the configurational temperature fluctuate around their equilibrium values. These new thermostats differ from one previously introduced by Delhommelle and Evans [Mol. Phys. 99, 1825 (2001)] in several important ways. First, our thermostats are derived in the same spirit as the Nosé-Hoover thermostat and therefore generate the canonical phase-space distribution. Second, our thermostats involve simpler equations of motion, which do not involve spatial gradients of the configurational temperature. They do not suffer from problems stemming from stiff equations of motion and furthermore, in large temperature perturbation simulations, the measured temperature follows the set-point temperature without any overshoot, and with good damping of oscillations. We show that both of our configurational thermostats are special cases of a more general set of Nosé-Hoover equations proposed by Kusnezov et al. [Ann. Phys. 204, 155 (1990)]. The new thermostats are expected to be highly useful in nonequilibrium simulations, particularly those characterized by spatial inhomogeneities. They should also find applicability in simulations involving large changes in temperature over small time scales, such as temperature quench molecular dynamics and radiation damage modeling.


Indinavir-Loaded Nanostructured Lipid Carriers to Brain Drug Delivery: Optimization, Characterization and Neuropharmacokinetic Evaluation.
As an anti-retroviral Protease Inhibitor (PI), Indinavir (IDV) is part of the regimen known as Highly Active Anti-Retroviral Therapy (HAART) widely used for Human Immunodeficiency Virus (HIV) infection. The drug efficiency in treatment of the brain manifestations of HIV is, however, limited which is mainly due to the efflux by P-glycoprotein (P-gp) expressed at the Blood-Brain Barrier (BBB). To overcome the BBB obstacle, NLCs were used in this study as carriers for IDV, which were optimized through two steps: a "one-factor-at-a-time" screening followed by a systematic multiobjective optimization. Spherical smooth-surfaced Nanoparticles (NPs), average particle size of 161.02±4.8 nm, Poly-Dispersity Index (PDI) of 0.293±0.07, zeta potential of -40.62±2.21 mV, entrapment efficiency of 93±1.58%, and loading capacity of 9.15±0.15% were obtained after optimization which were, collectively, appropriate in terms of the objective of this study. The surface of the optimized NPs was, then, modified with human Transferrin (TR) to improve the drug delivery. The particle size, zeta potential, and PDI of the TR-modified NLCs were 185.29±6.7nm, -28.68±3.37 mV, and 0.247±0.06, respectively. The in vitro release of IDV molecules from the NPs was best fitted to the Weibull model indicating hybrid diffusion/erosion behavior. As the major in vivo findings, compared to the free drug, the NLCs and TR-NLCs displayed significantly higher and augmented concentrations in the brain. In this case, NLC and TR-NLC were 6.5- and 32.75-fold in their values of the brain uptake clearance compared to free drug.


In Hospitals With More Nurses Who Have Baccalaureate Degrees, Better Outcomes For Patients After Cardiac Arrest.
In 2010, prompted by compelling evidence that demonstrated better patient outcomes in hospitals with higher percentages of nurses with a bachelor of science in nursing (BSN), the Institute of Medicine recommended that 80 percent of the nurse workforce be qualified at that level or higher by 2020. Using data from the American Heart Association's Get With the Guidelines-Resuscitation registry (for 2013-18), RN4CAST-US hospital nurse surveys (2015-16), and the American Hospital Association (2015), we found that each 10-percentage-point increase in the hospital share of nurses with a BSN was associated with 24 percent greater odds of surviving to discharge with good cerebral performance among patients who experienced in-hospital cardiac arrest. Lower patient-to-nurse ratios on general medical and surgical units were also associated with significantly greater odds of surviving with good cerebral performance. These findings contribute to the growing body of evidence that supports policies to increase access to baccalaureate-level education and improve hospital nurse staffing.


Lagrangian coherent structures and internal wave attractors.
For a nonuniformly stratified layer of fluid, internal gravity waves propagate at varying angles depending on the local buoyancy and Coriolis (in geophysical applications) frequencies. Relatively confined geometries, such as multiple submarine ridges, can support internal wave attractors, which can be viewed as Lagrangian coherent structures for the energy density flux. Since traditional approaches for locating these structures prove cumbersome, here we develop an approach that efficiently extracts the locations of internal wave attractors, as well as quantifying the rate of attraction. Using realistic geometry and stratification from ocean observations, we find that a significant northern portion of the Luzon ridge can support internal wave attractors.


Male preference and family size.
The influence on family size of the sex of the first children was studied in a sample of 1851 families of students in Sevilla University. Significantly more families limited family size to two or three children when the two or three children were of the same sex than in the opposite case. Significantly more families limited family size to three children when not all the three first children were females. The frequency of families having more than three children is not increased to a larger extent when the three first children are males than in the other cases.


EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity.
EHDs [EH (Eps15 homology)-domain-containing proteins] participate in different stages of endocytosis. EHD2 is a plasma-membrane-associated EHD which regulates trafficking from the plasma membrane and recycling. EHD2 has a role in nucleotide-dependent membrane remodelling and its ATP-binding domain is involved in dimerization, which creates a membrane-binding region. Nucleotide binding is important for association of EHD2 with the plasma membrane, since a nucleotide-free mutant (EHD2 T72A) failed to associate. To elucidate the possible function of EHD2 during endocytic trafficking, we attempted to unravel proteins that interact with EHD2, using the yeast two-hybrid system. A novel interaction was found between EHD2 and Nek3 [NIMA (never in mitosis in Aspergillus nidulans)-related kinase 3], a serine/threonine kinase. EHD2 was also found in association with Vav1, a Nek3-regulated GEF (guanine-nucleotide-exchange factor) for Rho GTPases. Since Vav1 regulates Rac1 activity and promotes actin polymerization, the impact of overexpression of EHD2 on Rac1 activity was tested. The results indicated that wt (wild-type) EHD2, but not its P-loop mutants, reduced Rac1 activity. The inhibitory effect of EHD2 overexpression was partially rescued by co-expression of Rac1 as measured using a cholera toxin trafficking assay. The results of the present study strongly indicate that EHD2 regulates trafficking from the plasma membrane by controlling Rac1 activity.


Effect of amiodarone on retrograde conduction and refractoriness of the His-Purkinje system in man.
The effects of long term treatment with oral amiodarone on retrograde conduction ( S2H2 interval) and refractoriness of the His-Purkinje system were studied in 11 patients using His bundle electrograms and the ventricular extrastimulus method. Ten patients had ventricular tachycardia and one supraventricular tachycardia. Electrophysiological studies were carried out before and after the patients had been taking their maintenance dose for a mean duration of 84 days. After amiodarone treatment the HV interval was prolonged in seven patients and unchanged in four. At comparable S1S2 intervals, the S2H2 intervals were longer after treatment with amiodarone in all patients than before. Similarly, the longest S2H2 intervals achieved after amiodarone were longer than the control values. Amiodarone significantly increased the relative, effective, and functional refractory periods of the His-Purkinje system. Thus amiodarone exerts important effects on the His-Purkinje system.


Aspects of the mechanisms of action of biguanides on trophozoites and cysts of Acanthamoeba castellanii.
A non-radioactive method was used to investigate the uptake by Acanthamoeba castellanii of chlorhexidine diacetate (CHA) and polyhexamethylene biguanide (PHMD). Based on the Giles et al. (1974) hypothesis, the uptake of CHA by trophozoites appeared to be of the L3 pattern whereas that of cysts was C2. Unlike CHA, trophozoites took up PHMB with an L2 pattern at low concentrations followed by a C-type pattern at higher concentrations, the uptake by cysts was found to be of the C2 pattern with a plateau effect at high concentrations. A diphasic leakage effect was found in trophozoites whereas a relatively low peak of maximal leakage occurred from cysts treated with high biocide concentrations. The amount of pentose release depended on the formulation ingredients. No correlation between pentose leakage and trophozoicidal or cysticidal activity was found.


A case management of hypertension in the elderly in sub-Sahara Africa: lessons from Granny.
Management of chronic disease conditions in the elderly is challenging. They usually have many co-morbidities requiring multiple drug regimens, and memory or cognitive problems that can interfere with management. Also, they sometimes have a degree of social problems as they might often live alone, and thereby cater for their daily activities with minimal assistance. Multiple drug use combined with their fragile health predispose them to adverse drug reactions, drug-drug interactions, and direct drug toxicity from overdosing. We report and discuss the lessons learnt from the case of an elderly woman in an urban setting in sub-Saharan Africa who presented with problems of drug dosing, adverse drug effect, and drug-drug interaction that might prove useful in the future management of hypertension with angiotensin converting enzyme inhibitors.


Aetiological, clinical and metabolic profile of hypokalaemic periodic paralysis in adults: a single-centre experience.
Hypokalaemic periodic paralysis constitutes a heterogeneous group of disorders that present with acute muscular weakness. In this analysis, we discuss the aetiological factors that appear to be more common in the Indian population. From 1995 to 2001, 31 patients presented with periodic paralysis (mean age 34.5 years, range 11-68 years). Of the 31 patients, 19 were men. The clinical and laboratory data of these patients were analysed. Patients were investigated for possible secondary causes of hypokalaemla. There were 13 patients (42%) with renal tubular acidosis, 13 with primary hyperaldosteronism (42%), 2 each with thyrotoxic periodic paralysis and sporadic periodic paralysis, and I with Gitelman syndrome. Of the 13 patients with renal tubular acidosis, 10 had proximal and 3 distal renal tubular acidosis. Three of these patients with renal tubular acidosis had Sjogren syndrome. The patients diagnosed to have renal tubular acidosis had significantly lower serum bicarbonate (18.7 [14.6] v. 29.6 [5.0] mEq/L; p < 0.05) and higher levels of chloride (107.5 [6.0] v. 99.5 [3.4] mEq/L; p < 0.05) compared with those who had primary hyperaldosteronism, although the potassium values were similar (2.4 [0.65] v. 2.26 [0.48] mEq/L; p = 0.43). All patients with primary hyperaldosteronism had hypertension at presentation and were proven to have adrenal adenomas. A significant number of patients in this study had secondary and potentially reversible causes of hypokalaemic periodic paralysis. The common causes were renal tubular acidosis and primary hyperaldosteronism. A detailed work-up for secondary causes should be undertaken in Indian patients with hypokalaemic periodic paralysis.


Hybrid Deep Eutectic Solvents with Flexible Hydrogen-Bonded Supramolecular Networks for Highly Efficient Uptake of NH3.
Serious environmental concerns have led to a great demand for efficient uptake of NH3 by solvents. However, traditional aqueous absorbents have many shortcomings and efforts to use ionic liquids have met with limited success. A hybrid deep eutectic solvents (DESs) designed with a flexible hydrogen-bonded supramolecular network exhibits both exceptional NH3 uptake capacity and superior desorption-regeneration performance, along with superb NH3 /CO2 selectivity and environmental merit. Elucidated by molecular dynamic simulations and spectroscopic analysis, the abundant hydrogen-bonding sites in the hybrid DESs bind every atom of the NH3 molecule and enable strong physical reversible solvation, whereas the multiple interactions among the hybrid components create a flexible hydrogen-bonded supramolecular network and allow for solvent-unbreaking absorption to ensure the full participation of the solvent and process stability. A mass solubility of NH3 up to 0.13 g g-1 was achieved at 313 K and 101 kPa by the hybrid DES choline chloride/resorcinol/glycerol (1:3:5), which is higher than all reported ionic liquids and ordinary DESs. Moreover, the performance remained the same after ten absorption-desorption cycles and the DESs could be easily regenerated.


HLA class I phenotype and gene frequencies in parts of southern Nigeria.
HLA-A, B and C antigens were determined in 101 healthy subjects from two major and several minor ethnic groups in some parts of Southern Nigeria. Compared to earlier data based on a panel of expatriate Nigerians, significant differences were observed in antigen phenotype and gene frequencies particularly at the HLA-A locus. At least three antigenic specificities not previously observed in the expatriate Nigerians were detected in the present study. These included HLA-B8. B14 and CW1. These antigens however occurred at low frequencies. The antigens A23 and B7 were in positive linkage disequilibrium along with others which involved CW4 with B53 or B35. It is concluded from our findings that HLA polymorphisms in Nigerians may not be completely reflected in major population group studies alone. It is possible that more specificities may be detected by continued testing of the minor ethnic groups. The importance of this could be immense in disease association studies involving HLA genes as well as in anthropology.


A meta-analysis of studies of dietary fat and breast cancer risk.
There is strong evidence that breast cancer risk is influenced by environmental factors, and animal experiments and human ecological data suggest that increased dietary fat intake increases the incidence of the disease. Epidemiological evidence on the relationship of dietary fat to breast cancer from cohort and case control studies has however been inconsistent. To examine the available evidence we have carried out a meta-analysis to summarise quantitatively the large published literature on dietary fat in the aetiology of breast cancer. After assembling all of the published case control and cohort studies, we extracted the relative risk in each study that compared the highest to the lowest level of intake. We then calculated a summary relative risk for all studies. The summary relative risk for the 23 studies that examined fat as a nutrient was 1.12 (95% CI 1.04-1.21). Cohort studies had a summary relative risk of 1.01 (95% CI 0.90-1.13) and case control studies a relative risk of 1.21 (95% CI 1.10-1.34). Summary estimates of risk for specific types of fat excluded unity for only saturated fat. For the 19 studies that examined food intake, the summary relative risks were 1.18 (95% CI 1.06-1.32) for meat, 1.17 (95% CI 1.04-1.31) for milk, and 1.17 (95% CI 1.02-1.36) for cheese. Summary relative risks for total fat intake were examined for several potential modifying factors. Regression analysis showed that European studies were more likely than studies done in other countries to show an increased relative risk associated with dietary fat and breast cancer, after taking into account potential modifying factors that included study design and quality.


Cosmography Using Strongly Lensed Gravitational Waves from Binary Black Holes.
Third generation gravitational wave (GW) detectors are expected to detect millions of binary black hole (BBH) mergers during their operation period. A small fraction of them (∼1%) will be strongly lensed by intervening galaxies and clusters, producing multiple observable copies of the GW signals. The expected number of lensed events and the distribution of the time delay between lensed images depend on the cosmology. We develop a Bayesian analysis method for estimating cosmological parameters from the detected number of lensed events and their time delay distribution. The expected constraints are comparable to that obtained from other cosmological measurements, but probing a different redshift regime (z∼10) that is not explored by other probes.


Root abnormalities, talon cusps, dentes invaginati with reduced alveolar bone levels: case report.
This is a case report of a Caucasian female who presented with an unusual combination of dental anomalies: short roots on the maxillary central incisors and premolars, talon cusps, dentes invaginati, low alveolar bone heights, tubercles of Carabelli on the maxillary first and second permanent molars, with pyramidal root morphology in three of the second permanent molars. None of the anomalies alone are particularly uncommon but they have not previously been reported together. The occurrence of the anomalies is probably incidental as the conditions are aetiologically unrelated.


Effect of tachycardia on mRNA andf protein expression of the principal components of the lipolytic system in the rat's heart ventricles.
There is a convincing piece of evidence showing that most of free fatty acids (FFA) entering cardiomyocytes are first esterified into triacylglycerols (TG) before being oxidized or used for synthesis of complex lipids. The enzyme adipose triglyceride lipase (ATGL) initiates lipolysis of TG by hydrolyzing the first ester bond of the compound. As a result, free fatty acid and diacylglycerol (DG) are released in that process. Finally, DG may be further hydrolyzed by the enzyme hormone sensitive lipase (HSL). The aim of the present study was to examine effect of tachycardia on mRNA and protein expression of ATGL, CGI-58 (an activator of ATGL), G0S2 (an inhibitor of ATGL) and HSL in the left and right ventricle of the rat. The experiments were carried out on male Wistar rats, 240 - 260 grams of body weight. After anesthesia, two electrodes were inserted in the right jugular vein and connected to SC-04 stimulator. The rats were randomly allocated into one of the three groups, namely: control, 30 min and 60 min of the heart stimulation at the rate of 600 times/min. The expressions of ATGL, CGI-58, G0S2 and HSL were evaluated at both gene and protein levels using real-time PCR and Western Blot analysis, respectively. Both 30 and 60 min stimulation reduced ATGL, HSL, CGI-58 and G0S2 mRNA content in the left ventricle. The stimulation had only insignificant impact on ATGL, HSL and CGI-58 transcript levels in the right ventricle. Interestingly, Western Blot analysis showed that the stimulation, regardless of the time, reduced the ATGL and G0S2 protein expression, but did not change the CGI-58 and HSL expression in the left ventricle. Furthermore, in the right ventricle, the protein expressions of ATGL, HSL and G0S2 decreased after stimulation. In conclusion, the obtained results clearly show that tachycardia affects both mRNA and protein expression of particular compounds of the TG lipolytic system in the heart ventricles. Additionally, there are marked differences in the expressions of the examined compounds between the ventricles.


Experiments on Vapor Pressure of KCl at Different Molar Fractions in Mixtures of KCl + K2SO4.
The objective of this paper is to measure the vapor pressure of potassium chloride (KCl) in its mixture with potassium sulfate (K2SO4). Evaporation behavior of pure salts of KCl, K2SO4, and their mixtures at different molar fractions were examined using a simultaneous thermogravimetric analyzer (STA) at different temperatures with a pair of crucibles (outer: platinum; inner: alumina). The dependence of the vapor pressure of KCl on its molar fraction in mixtures of KCl + K2SO4 was obtained on the basis of relative pressure. Results show that vapor pressure of KCl is increased to 1.2 times when a small amount of K2SO4 (molar fraction from 0.05 to 0.20) is added. Evaporation of KCl will be inhibited by K2SO4 when the molar fraction of K2SO4 is higher than 0.27, which is its fraction in the eutectic system of KCl + K2SO4. Vapor pressure of KCl decreases significantly with increasing molar fractions of K2SO4 at its inhibition scope.


Perceived partner support in pregnancy predicts lower maternal and infant distress.
Maternal postpartum emotional distress is quite common and can pose significant risk to mothers and infants. The current study investigated mothers' relationships with their partners during pregnancy and tested the hypotheses that perception of prenatal partner support is a significant predictor of changes in maternal emotional distress from midpregnancy to postpartum, and contributes to maternal ratings of infant distress to novelty. Using a prospective longitudinal design, 272 adult pregnant women were interviewed regarding their partner support, relationship satisfaction, and interpersonal security (attachment style and willingness to seek out support), and they completed standardized measures of prenatal symptoms of depression and anxiety (distress). At 6 to 8 weeks' postpartum, mothers reported these symptoms again and completed measures of their infants' temperament. Structural equation modeling (SEM) was used to test direct and indirect contributions of partner support, relationship satisfaction, and interpersonal security to maternal and infant postpartum distress. Mothers who perceived stronger social support from their partners midpregnancy had lower emotional distress postpartum after controlling for their distress in early pregnancy, and their infants were reported to be less distressed in response to novelty. Partner support mediated the effects of mothers' interpersonal security and relationship satisfaction on maternal and infant outcomes. A high-quality, supportive partner relationship during pregnancy may contribute to improved maternal and infant well-being postpartum, indicating a potential role for partner relationships in mental health interventions, with possible benefits for infants as well.


Lymphatic Complications Following Sentinel Node Biopsy or Pelvic Lymphadenectomy for Endometrial Cancer.
Sentinel node biopsy (SNB) is performed worldwide in patients with endometrial cancer (EC). The aim of this study was to evaluate and compare the occurrence rate of lymphatic complications between SNB and pelvic lymphadenectomy (LND) for EC. The medical records of women who underwent SNB or pelvic LND for EC between September 2012 and April 2022 were assessed. A total of 388 patients were enrolled in the current study. Among them, 201 patients underwent SNB and 187 patients underwent pelvic LND. The occurrence rates of lower-extremity lymphedema (LEL) and pelvic lymphocele (PL) were compared between the patients who underwent SNB and those who underwent pelvic LND. The SNB group had a significantly lower occurrence rate of lower-extremity LEL than the pelvic LND group (2.0% vs. 21.3%, p < 0.01). There were no patients who had PL in the SNB group; however, 4 (2.1%) patients in the pelvic LND group had PL. The occurrence rates of lower-extremity LEL and PL were significantly lower in patients who underwent SNB than those who underwent pelvic LND. SNB for EC has a lower risk of lymphatic complications compared to systemic LND.


A new species of the genus Aporcelinus Andrássy, 2009 (Nematoda, Dorylaimida, Aporcelaimidae) from Costa Rica.
A new species of the genus Aporcelinus, A. elongicaudatus sp. n., collected from natural habitats of Costa Rica, is described and illustrated. The new species is characterized by its 0.92-1.05 mm long body, lip region offset by weak constriction and 15 µm broad, odontostyle 15-18 µm or 1.0-1.2 times the lip region diameter, neck 270-300 µm long, pharyngeal expansion 130-150 µm long or 45-55% of total neck length, uterus 33-41 µm long or 0.70-0.85 times the corresponding body diameter (but certainly longer), vulva transverse (V = 49-51), and tail conical elongated (45-71 µm, c = 14-22, c' = 2.0-3.2) and dorsad bent.


The role of the family in managing therapy in minority children with type 2 diabetes mellitus.
The difficulties of managing therapy in minority children with type 2 diabetes mellitus (DM) are discussed, and the importance of family support for patients in adhering to their therapy schedules and requirements is emphasized. The results of a study comparing the efficacy of family involvement in managing treatment for children with type 2 DM are discussed. The study compared two groups of African-American children: group 1 (7 children), direct family supervision, with the caregiver actively participating in diabetes management; and group 2 (5 children), without direct supervision by a family caregiver, who randomly and inconsistently participated in management. Glycosylated hemoglobin (HbA1c) was measured at baseline and 1 year later by high performance liquid chromatography. Results of the study indicate that direct supervision of children with DM has a positive effect on glycemic control, resulting in a statistically significant decrease of HbA1c as compared to the group of unsupervised children. Despite some adolescents' demands for greater autonomy, or cultural pressures to assume greater personal responsibilities during teenage years, continuing family involvement in the management of adolescent patients with DM is strongly advised for optimum therapeutic results.


Practices and attitudes toward complementary and alternative medicine in inflammatory bowel disease: a survey of gastroenterologists.
Use of complementary and alternative medicine (CAM) is increasingly prevalent among patients with inflammatory bowel disease (IBD). We sought to characterize the practices and attitudes of IBD physician providers toward CAM. A web-based survey was sent to non-trainee physician members of the American Gastroenterological Association with an interest in IBD. The survey included multiple-choice and Likert scale questions which queried physician perceptions of CAM and their willingness to discuss CAM with patients. The vast majority of respondents (80%) considered themselves IBD subspecialists with 75% holding academic appointments. Nearly a third reported initiating conversations on CAM in the majority of their patient interactions, while 90% perceived that a majority of their patients were reluctant to bring up the topic of CAM. Nearly three quarters (72%) of respondents felt comfortable discussing CAM, while those that did not most frequently cited lack of knowledge as the reason. More than half (55%) stated they had no systematic approach to discussing CAM. Most gastroenterologists (65%) reported no formal training in CAM. Most gastroenterologists had recommended use of probiotics, and nearly half had recommended acupuncture. A vast majority believed that there was adjunctive role for CAM in treatment of IBD. Academic IBD specialists were receptive to the use of CAM, and most felt that it had a role in the treatment of IBD, without necessarily compromising conventional therapy. Formal educational initiatives and societal recommendations on the use of CAM may facilitate a more systematic approach to its use in daily practice.


[Crosstalk between cholesterol homeostasis and drug metabolism].
Nowadays cardiovascular diseases are among the major causes of mortality in the developed world. High cholesterol level in blood and atherosclerosis play the main role in progression of cardiovascular diseases. Reducing serum cholesterol level has been shown to avoid deleterious effects, whereas in serious diseases it improves the outcome. A widely used, statin-based therapy induces a decrease in de novo cholesterol biosynthesis in the liver. Another possibility for lowering serum cholesterol level is to block the uptake of dietary cholesterol from intestine (e.g. ezetimibe). Coadministration of statins and cholesterol uptake inhibitors provides an efficient therapeutical strategy. Several therapeutic agents, reducing serum cholesterol level, are able to regulate the expression of not only cholesterogenic enzymes, but of the major drug metabolizing enzymes, cytochromes P450. The crosstalk between cholesterol homeostasis and drug metabolism is mediated by nuclear receptors, activating target genes in response of endogenous and exogenous ligands. Better understanding of the crosstalk between cholesterol homeostasis and drug metabolism is essential for developing an adequate strategy in therapy and in novel drug development.


Impact of A Smoking Prevention Interactive Experience (ASPIRE), an interactive, multimedia smoking prevention and cessation curriculum for culturally diverse high-school students.
Few studies have examined the long-term efficacy of computer-based smoking prevention and cessation programs. We analyzed the long-term impact of A Smoking Prevention Interactive Experience (ASPIRE), a theoretically sound computer-based smoking prevention and cessation curriculum for high school students. Sixteen predominantly minority, inner-city high schools were randomly assigned to receive the ASPIRE curriculum or standard care (receipt of the National Cancer Institute's Clearing the Air self-help booklet). A total of 1160 students, 1098 of whom were nonsmokers and 62 smokers at baseline, were included. At 18-month follow-up, among baseline nonsmokers, smoking initiation rates were significantly lower in the ASPIRE condition (1.9% vs. 5.8%, p < .05). Students receiving ASPIRE also demonstrated significantly higher decisional balance against smoking and decreased temptations to smoke. Differences between groups in self-efficacy and resistance skills were not significant. There was a nonsignificant trend toward improved smoking cessation with ASPIRE, but low recruitment of smokers precluded conclusions with respect to cessation. ASPIRE demonstrated the potential for an interactive multimedia program to promote smoking prevention. Further studies are required to determine ASPIRE's effects on cessation.


Effect of estrogen replacement on insulin sensitivity, serum lipid and bone resorption marker in hypogonadal males.
Recent reports of osteoporosis in congenital estrogen deficiency in humans from estrogen resistance or aromatase deficiency have called attention to the importance of estrogen in males. It is the purpose of the present study to evaluate the effects of low- dose estrogen on glucose, lipid and bone metabolism in males with hypogonadism. Nine Thai males with primary or secondary hypogonadism were included in the study. Testosterone was discontinued at least 8 weeks before the study. The subjects received 0.3 mg of conjugated equine estrogen (CEE) daily for 4 weeks. Serum C-terminal telopeptide of type 1 collagen (CTX), total cholesterol (TC), LDL cholesterol (LDL-C), HDL cholesterol (HDL-C), triglyceride (TG) and parameters related to insulin sensitivity were measured at baseline and 4 weeks after treatment. Insulin sensitivity was assessed by frequent intravenous glucose tolerance test. The mean age of subjects was 35.77 years (22-70 years). Insulin sensitivity index (SI) did not change significantly after the administration of CEE (P=0.09). Likewise, no change in acute insulin response (AIR(glucose)) was detected. However, glucose effectiveness (SG) significantly decreased after CEE (P<0.05). No significant change in serum TC, LDL-C, HDL-C or TG was detected. In regard to bone turnover, serum CTX significantly decreased after CEE administration (P<0.05). We concluded that low-dose estrogen administration in hypogonadal males for 4 weeks causes a decrease in bone turnover and an increase in glucose effectiveness. No effect on serum lipid concentrations or insulin sensitivity and secretion was detected.


Shear breakage of nylon membrane microcapsules in a turbine reactor.
The breakage of nylon membrane microcapsules is proposed as a new method to study and quantify shear effects in biological systems. A critique of this method shows that a narrower particle size distribution may be an important improvement in the breakage study as well as breakage control in many bioreactor and biotechnological applications. In a turbine reactor, it was shown that the primary process which determines the microcapsule breakage is the shear effect. The breakage kinetics are first order with regard to the microcapsule concentration. The breakage kinetic constant was ob served to be dependent on the temperature and the particle size, and proportional to the average shear rate and the third power of the turbine angular velocity. Decrease of the breakage kinetic constant with temperature can be explained by a decrease of fluid viscosity and a change in nylon membrane properties. An increase in the breakage kinetic constant with the microcapsule diameter can be due to a lowering of internal pressure and a reduction of the membrane resistance with size. Proportionality between the breakage kinetic constant and the shear rate shows that shear is the main process which leads to microcapsule breakage. The additional intervention in the shear rate expression of the turbine angular speed in the form of the turbine and particle velocities, results in the dependence of the breakage kinetic constant on the third power of the angular velocity.


Fluoroquinolones and resistance in the treatment of uncomplicated urinary tract infection.
Acute uncomplicated cystitis is one of the most common problems for which young women seek medical attention. Most of these infections are caused by Escherichia coli which are susceptible to many oral antimicrobials, although resistance is increasing to some of the commonly used agents, especially trimethoprim/sulphamethoxazole (TMP/SMX). In women with risk factors for infection with resistant bacteria, or in the setting of a high prevalence of TMP/SMX resistance, a fluoroquinolone or nitrofurantoin should be considered for empirical treatment. Use of nitrofurantoin does not share cross-resistance with more commonly prescribed antimicrobials and its more widespread use is justified from a public health perspective as a fluoroquinolone-sparing agent. beta-lactams and fosfomycin should be considered second-line agents for empirical treatment of cystitis. For acute uncomplicated pyelonephritis, fluoroquinolones are superior to TMP/SMX for empirical therapy due to the relatively high prevalence of TMP/SMX resistance among uropathogens causing pyelonephritis. TMP/SMX, effective for patients with mild to moderate disease, is an appropriate drug if the uropathogen is known to be susceptible. It is reasonable to use a 7-10 day oral fluoroquinolone regimen for outpatient management of mild to moderate pyelonephritis in the setting of a susceptible causative pathogen and rapid clinical response to therapy. Most women with acute uncomplicated pyelonephritis are now managed safely and effectively as outpatients.


Phylogenetic analysis of the outer-membrane-protein genes of Chlamydiae, and its implication for vaccine development.
Examination of 18 complete and 6 partial sequences of the major outer-membrane protein from 24 chlamydiae isolates was used to reconstruct their evolutionary relationships. From this analysis, assuming that the clades with 100% bootstrap support are correct, come the following conclusions: (1) The tree of these sequences is not congruent with the phylogeny of the hosts, and thus host switching would seem to have occurred, thereby limiting the extent to which there has been coevolution of parasite and host. (2) The tree is also noncongruent with clustering by type of cell infected, thereby limiting the extent to which there has been coevolution of parasite and the cell type that it infects. (3) The tree is also noncongruent with clustering by the organ infected (eyes or genitalia), thereby limiting the extent to which there has been coevolution of parasite and the organ that it infects. (4) The tree is also noncongruent with genital strains arising from lymphogranuloma venereum strains. (5) The tree is also noncongruent with the geographic site at which the isolates were obtained, thereby limiting the extent of divergence explained by geographic separation. (6) There are estimated to be 185 amino acid positions that are invariable (as opposed to unvaried) in the major outer-membrane protein. There are 10 unvaried positions in the variable domains, of which 9 appear to be invariable, giving some reason to hope that development of a vaccine might be possible. (7) The rate of change of this protein is too small to see increased divergence over the time span of isolation of these genes, giving hope to any vaccine having longevity. Bootstrapping supports those portions of the tree on which the first five conclusions above depend. The picture that these results provide is more one of pathogen versatility than one of coevolutionary constraints. In addition, we examined 10 60-KDa, outer-membrane protein-2 genes, all but one of which were from these same strains. The tree was not, among the trachomatis strains, congruent with the major-outer-membrane protein tree, suggesting that gene exchange could be occurring among strains. Moreover, there is an apparent slowdown in divergence in this gene, among the trachomatis strains.


Germ cell apoptosis induced by experimental cryptorchidism is mediated by multiple molecular pathways in Cynomolgus Macaque.
Experimental cryptorchidism is a common model for examining the expression and function of heat-sensitive spermatogenesis-related genes in testis. Previous studies have shown that germ cells in cryptorchid testis die mainly in an apoptotic way. The molecular mechanism, however, is still unclear. We have established unilateral cryptorchid monkey model (Cynomolgus Macaque) to identify possible molecules involved in the germ cell apoptosis. The degree of germ cell apoptosis, the morphology of the cryptorchid testis, and the changes in the serum concentration of FSH, LH and testosterone after cryptorchid surgery were analyzed. Sertoli cell marker molecule vimentin, the orphan receptor LRH-1, as well as the mitochondria-related protein HSP60 and Bcl-2 were examined. Our results showed that the weight of the cryptorchid testis decreased in a time-dependent manner started from day 7 after the surgery, while the weight of the scrotal testis had no obvious change. HE staining showed that from day 5, some germ cells were detached from the epithelium. A massive degeneration of the seminiferous epithelium characteristic of epithelial structural disorganization and the formation of multinucleated giant cells as well as vacuoles was observed on day 10 and 15. The cryptorchidism induced a marked germ cell apoptosis on day 3 after the operation, reaching a peak level on day 7.


Timing and sequence of eruption of permanent teeth in a longitudinal sample of children from Oregon.
A longitudinal sample of children was examined for timing and sequence of eruption of permanent teeth. Separate consideration was given to 124 boys and 163 girls from the Child Study Clinic longitudinal growth study. Girls show more variability in age at eruption than boys, and eruption is generally earlier in girls. The degree of variation in sequences of eruption of the first seven permanent teeth is distinct. The most common sequence in girls' maxillas occurred in only 11.4% of subjects; in boys, the most common sequence appeared in 13.4% of subjects. Predictability efficiency of eruption of the first three permanent teeth is not higher than 0.74.


Regulation of Epithelial-Mesenchymal Transition by Transmission of Mechanical Stress through Epithelial Tissues.
Epithelial-mesenchymal transition (EMT) is a phenotypic shift wherein epithelial cells lose or loosen attachments to their neighbors and assume a mesenchymal-like morphology. EMT drives a variety of developmental processes, but may also be adopted by tumor cells during neoplastic progression. EMT is regulated by both biochemical and physical signals from the microenvironment, including mechanical stress, which is increasingly recognized to play a major role in development and disease progression. Biological systems generate, transmit and concentrate mechanical stress into spatial patterns; these gradients in mechanical stress may serve to spatially pattern developmental and pathologic EMTs. Here we review how epithelial tissues generate and respond to mechanical stress gradients, and highlight the mechanisms by which mechanical stress regulates and patterns EMT.


Characterization of immunoreactive motilin from the rat small intestine.
Immunocytochemistry, radioimmunoassay, chromatography, and biological assay using a rabbit isolated duodenal muscle strip preparation were used in attempting to characterize motilin from the rat small intestine. Several different antisera and monoclonal antibodies directed against natural porcine motilin were used. A variety of fixation techniques using Bouin's, paraformaldehyde, and benzoquinone with different staining methods including, fluorescein-conjugated second antibody, peroxidase-antiperoxidase or peroxidase-conjugated second antibody techniques were used. All methods failed to detect immunoreactive motilin cells in the rat small intestine. The same antisera were used in radioimmunoassays for motilin to evaluate extracts of rat intestinal tissue. Two of these detected immunoreactive motilin in gut extracts, and these antisera showed a different distribution for the peptide. Samples containing immunoreactive motilin obtained from cation exchange chromatography on SP-Sephadex-G25 were concentrated and assayed for biological activity in a rabbit duodenal muscle strip preparation. Desensitization of duodenal tissue to porcine motilin could be demonstrated by pretreatment with this peptide. The biological activity of partially purified rat intestinal immunoreactive motilin was not prevented by pretreatment of the tissue with motilin. Further purification of this preparation on Bio-Gel P-10 yielded an immunoreactive motilin peak that co-eluted with natural porcine motilin. Rat intestinal immunoreactive motilin did not co-elute with natural porcine motilin following high pressure liquid chromatography on a Waters microBondapak C18 reversed-phase column using a linear gradient of water-acetonitrile (10-45%) over 30 min. Although of similar molecular size, rat motilin is probably structurally dissimilar to other mammalian motilins.


Histopathology of culture-associated skin erosions and papillary hyperplasia of Atlantic halibut, Hippoglossus hippoglossus (L.).
Atlantic halibut, Hippoglossus hippoglossus (L.), that were cultured in tanks with a smooth bottom (gel-coated fibreglass) substrate developed papillary hyperplasia and skin erosions on the blind (ventral) side. No viruses, bacteria or parasites were observed in any sections of affected skin. Comparison of microscopic pathology with that of skin from normal, wild-caught halibut showed severe epidermal proliferation with foci of severe mucous cell hyperplasia. Both epidermal thickness and mucous cell density were significantly greater in fish held on a smooth substrate compared to skin of healthy fish. Spongiosis was present, especially at the base of the papillary, hyperplastic epidermis, and there was a chronic inflammatory infiltrate in the scale pockets composed of lymphocytes, histiocytes and erythrocytes. Skin erosions had various degrees of epidermal loss, in some cases to the basement membrane. A predisposing factor for the epidermal sloughing may have been related to the spongiosis, and the vacuolated, degenerated basal cells. When affected halibut were cultured for an additional 28, 62 or 97 days on a sand substrate, which is conducive to skin lesion healing, there was no apparent change in epidermal thickness over time. However, mucous cell density significantly increased from day 0 to 97 during the healing process.


Deep Learning-Based Electrocardiograph in Evaluating Radiofrequency Ablation for Rapid Arrhythmia.
This study is aimed at analyzing the important role of deep learning-based electrocardiograph (ECG) in the efficacy evaluation of radiofrequency ablation in the treatment of tachyarrhythmia. In this study, 158 patients with rapid arrhythmia treated by radiofrequency ablation were divided into effective treatment group (142 cases) and ineffective treatment group (16 cases). ECG examination was performed on all patients, and the indicators of ECG examination were quantified by the deep learning-based convolutional neural network model. The indicators of ECG examination of the effective treatment group and the ineffective treatment group were compared. The results showed that compared with the ineffective treatment group, the end-systolic volume (ESV), end-diastolic volume (EDV), end-systolic volume index (ESVI), and end-diastolic volume index (EDVI) of the effective treatment group were significantly decreased, and the left ventricular ejection fraction (LVEF) was significantly increased (P < 0.05). After radiofrequency ablation, the ventricular rate of patients in the effective treatment group was significantly lower than that of the ineffective treatment group at 12 h and 24 h after treatment (P < 0.05). In addition, compared with patients in the ineffective treatment group, the QT dispersion of the ECG in the effective treatment group was significantly higher (P < 0.05). The accuracy, specificity, and sensitivity of ECG in evaluating the therapeutic effect of patients with tachyarrhythmia were 86.81%, 84.29%, and 77.27%, respectively. The area under the curve was determined as 0.798 according to the receiver operating characteristic (ROC) curve of the subjects. In summary, indicators of ECG examination based on deep learning can provide auxiliary reference information for the efficacy evaluation of radiofrequency ablation in the treatment of tachyarrhythmia.


Surface crafting and entrapment of CsPbBr3 perovskite QDs in ZIF-8 for ammonia recognition.
The substantial optical features of perovskite quantum dots (PQD) lead to rapid growth in the investigation of their surface and lattice doping for optoelectronic and biochemical sensor advancements. Herein, we have used the surface ligand crafting model of PQD by ammonia and its optimum response to recognise ammonia in the sensing cellulose paper. The PQD with acetyl amine and octanoic acid capped were synthesized and entrapped in zeolites imidazole framework to delay the instant quenching and envisaged response to ammonia with high sensitivity. The hybrid perovskite quantum dots and Zeolite imidazolate framework-8 (PQD@ZIF-8) materials were further immersed in cellulose paper for solid-state sensor fabrication for the detection of ammonia by naked-eye and a Xiaomi Note-5 mobile camera. The ammonia was measured with high sensitivity at ambient conditions, with a detection limit of 16 ppm and a linear detection range of 1 to 500 ppm. This research provides a new platform for designing sensor selectivity and sensitivity, which could be used to further develop fluorescent nanomaterials-based sensors for small molecule detection.


A case of primary mesenteric embryonal carcinoma.
We describe a case of primary mesenteric embryonal carcinoma. The patient was a 73-year-old man who presented with a huge mass palpable at the right upper side of the abdomen. Laboratory evaluations showed very high alpha-fetoprotein and PIVKA-II levels, and an abdominal computed tomographic scan demonstrated a mass contiguous with the liver. These findings suggested hepatic cell carcinoma extending beyond the liver. However, angiography showed the mass to be supplied mainly by the middle colic artery and greater omentum artery, suggesting a mesenteric tumor. Gastroscopy demonstrated a IIc lesion in the anterior wall of the antrum. This lesion was histologically diagnosed to be moderately differentiated adenocarcinoma. The large tumor adjacent to the liver was diagnosed to be a primary mesenteric tumor or a metastatic mesenteric tumor from arising gastric cancer. At laparotomy, a huge tumor was found in the gastrocolic ligament. The tumor adhered to the distal part of stomach, the transverse colon, and the gallbladder. En-bloc resection of the tumor was performed, including the distal part of stomach, Part of the transverse colon, and the gall-bladder. The tumor mass measured 26.0 x 21.0 x 9.0 cm, weighted 2750 g, and showed central necrosis and hemorrhage. The histopathological diagnosis was a primary embryonal carcinoma originating in the mesentery. Primary mesenteric embryonal carcinoma is extremely rare. To our knowledge, no other cases have been reported. We describe this case and briefly discuss the related literature.


Measurement of the absolute energy level and hyperfine structure of the 87Rb 4D5/2 state.
We have measured the absolute frequency of the excited state transition 5P(3/2)-4D(5/2) in a (87)Rb atom with a femtosecond frequency comb, utilizing the recently developed spectroscopic technique of the double resonance optical pumping method. The absolute energy level of the 4D(5/2) state is determined by measuring the absolute frequency of the 5S(1/2)-5P(3/2) transition simultaneously. The hyperfine structure constants of the 4D(5/2) state are obtained by using the measured frequency. The magnetic dipole constant, A, is determined to be (-16.747+/-0.010) MHz with an uncertainty reduced 60-fold compared with a previous result. The electric quadrupole constant, B, is determined, for what is to our knowledge the first time, to be (4.149+/-0.059) MHz.


Immunity and beta-endorphin concentrations in hypothalamus and plasma in rats with steroid-induced polycystic ovaries: effect of low-frequency electroacupuncture.
The human endocrinological disorder polycystic ovary syndrome (PCOS) is a common cause of reproductive failure. Even though the cause of PCOS is unknown, hormone and immune disturbances as well as hyperactivity in the sympathetic nervous system are likely to be involved in the pathogenesis of the disease. The present study was undertaken to elucidate if rats with estradiol valerate (EV)-induced polycystic ovaries (PCO) have altered beta-endorphin concentrations in the hypothalamus and in plasma and if they have alterations in circulating immune cell populations and the activity. Repeated low-frequency (2 Hz) electroacupuncture (EA) treatments are known to modulate the release of beta-endorphin, immune responses, and the activity in the autonomic nervous system. We therefore also investigated the effect of EA treatments on the beta-endorphin and the immune systems. Low-frequency EA was given 12 times, 25 min each, over 30 days starting 2-3 days after i.m. injection of EV. The beta-endorphin concentrations in the hypothalamus and in plasma as well as the frequencies of CD4+ T cells and CD8+ T cells were significantly lower in EV-injected control rats as compared to oil-injected control rats. Repeated EA treatments in EV-injected rats significantly increased beta-endorphin concentrations in the hypothalamus. In conclusion, these findings show that both the beta-endorphinergic and the immune system are significantly impaired in rats with steroid-induced PCO and that repeated EA treatments can restore some of these disturbances.


Quality assurance and radiotherapy.
As mentioned in several chapters of this report, administering the radioactive dosage requires a high level of precision. Demands on precision dosimetry have increased with modern curative radiotherapy. A few percent increase or decrease in the dose level may, in some cases, represent the difference between successful and unsuccessful therapy (Chapter 10). High precision is therefore required of basic dosimetry for different types and qualities of radiation, and in applied dosimetry for, eg, dose planning and in vivo dosimetry. External audits should be used to avoid systemic error. Comparative dose measurements are important, both to establish variations within a department and between departments. Simulators and/or therapeutic equipment should be checked regularly to assure that the direction of the radioactive beam and the field size complies with the plan. Margins that are too narrow can miss part of the target volume and increase the risk for relapse. If, on the other hand, the margins are too wide, the reaction to radiation in nearby organs at risk may be unacceptable. Accessible field control images should therefore be integrated in regular routines, at least when the margins between tumors and risk organs are small.


Proteomic analysis of antioxidant strategies of Staphylococcus aureus: diverse responses to different oxidants.
The high resolution 2-D protein gel electrophoresis technique combined with MALDI-TOF MS and a recently developed fluorescence-based thiol modification assay were used to investigate the cellular response of Staphylococcus aureus to oxidative stress. Addition of hydrogen peroxide, diamide, and the superoxide generating agent paraquat to exponentially growing cells revealed complex changes in the protein expression pattern. In particular, proteins involved in detoxification, repair systems, and intermediary metabolism were found to be up-regulated. Interestingly, there is only a small overlap of proteins induced by all these stressors. Exposure to hydrogen peroxide mediated a significant increase of DNA repair enzymes, whereas treatment with diamide affected proteins involved in protein repair and degradation. The activity of proteins under oxidative stress conditions can be modulated by oxidation of thiol groups. In growing cells, protein thiols were found to be mainly present in the reduced state. Diamide mediated a strong increase of reversibly oxidized thiols in a variety of metabolic enzymes. By contrast, hydrogen peroxide resulted in the reversible oxidation especially of proteins with active site cysteines. Moreover, high levels of hydrogen peroxide influenced the pI of three proteins containing cysteines within their active sites (GapA1, AhpC, and HchA) indicating the generation of sulfinic or sulfonic acid by irreversible oxidation of thiols.


Vertebral bone attenuation on low-dose chest CT: quantitative volumetric analysis for bone fragility assessment.
This study evaluated the use of low-dose chest computed tomography (LDCT) for detecting bone fragility. LDCT-measured vertebral bone attenuation by volumetric methods showed good correlation with bone mineral density (BMD) measured by dual-energy x-ray absorptiometry (DXA, and good diagnostic performance for identifying osteoporosis and compression fractures. The results of this study suggest the feasibility of obtaining comprehensive information on bone health in subjects undergoing LDCT. Osteoporosis is a prevalent but underdiagnosed disease that increases fracture risk. This study evaluated the utility of vertebral attenuation derived from low-dose chest computed tomography (LDCT) compared to dual-energy x-ray absorptiometry (DXA) for detecting bone fragility. A total of 232 subjects (78 men and 154 women) aged above 50 years who underwent both LDCT and DXA within 30 days were evaluated. LDCT-measured bone attenuation in Hounsfield units (HU) of four vertebrae (T4, T7, T10, and L1) was evaluated using volumetric methods for correlation with DXA-measured bone mineral density (BMD) and for the diagnosis of compression fractures, osteoporosis, and low BMD (osteoporosis or osteopenia) in men and women, with DXA measurements as the reference standard. The average attenuation of the four vertebrae showed strong correlation with DXA-measured BMD of the lumbar spine (r = 0.726, p < 0.05). In receiver-operating characteristic (ROC) analyses, the area under the curve (AUC) across LDCT-measured thresholds of the average attenuation to distinguish compression fractures was 0.827, and a threshold of 129.5 HU yielded 90.9 % sensitivity and 64.4 % specificity. Similarly, average attenuation showed high AUCs and good diagnostic performance for detecting osteoporosis and low BMD in both men and women. Among 44 subjects with compression fractures, the average bone attenuation showed strong negative correlation with both the worst fracture grade (r = -0.525, p < 0.05) and cumulative fracture grade score (r = -0.633, p < 0.05). LDCT-measured bone attenuation by volumetric methods showed good correlation with BMD measured by DXA and good diagnostic performance for identifying bone fragility.


Right ventricular failure and pathobiology in patients with congenital heart disease - implications for long-term follow-up.
Right ventricular dysfunction represents a common problem in patients with congenital heart defects, such as Tetralogy of Fallot or pulmonary arterial hypertension. Patients with congenital heart defects may present with a pressure or volume overloaded right ventricle (RV) in a bi-ventricular heart or in a single ventricular circulation in which the RV serves as systemic ventricle. Both subsets of patients are at risk of developing right ventricular failure. Obtaining functional and morphological imaging data of the right heart is technically more difficult than imaging of the left ventricle. In contrast to findings on mechanisms of left ventricular dysfunction, very little is known about the pathophysiologic alterations of the right heart. The two main causes of right ventricular dysfunction are pressure and/or volume overload of the RV. Until now, there are no appropriate models available analyzing the effects of pressure and/or volume overload on the RV. This review intends to summarize clinical aspects mainly focusing on the current research in this field. In future, there will be increasing attention to individual care of patients with right heart diseases. Hence, further investigations are essential for understanding the right ventricular pathobiology.


Averaging principle for a type of Caputo fractional stochastic differential equations.
The averaging principle for Caputo fractional stochastic differential equations has recently attracted much attention. In this paper, we investigate the averaging principle for a type of Caputo fractional stochastic differential equation. Comparing with the existing literature, we shall use different estimate methods to investigate the averaging principle, which will enrich the development of theory for Caputo fractional stochastic differential equations.


Vestibular and somatosensory afferents modulate masseter muscle activity.
The aim of the research was to investigate whether somatosensory impulses starting from the forelimbs could modulate masseter muscle activity in anesthetized guinea pigs. The effect of interactions between radial nerve and vestibular stimulations on the masseter motor unit responses was also studied. Results show that electrical stimulation of both radial nerves induces responses in the masseter motor units most frequently characterized by excitation at latency ranging from 14 to 29 ms. The radial nerve responses were strongly reduced by conditioning electrical stimulation of the vestibular ampullar receptors. Similarly, the vestibular responses were reduced by conditioning radial nerve stimulation. The natural activation of the vestibular macular receptors can either decrease or increase the masseter motor unit responses evoked by electrical stimulation of the radial nerve. These complex inhibitory-excitatory interactions between the two sensory inputs could control the masseter postural tone in relation to the head and limb positions in space.


Angiotensin II, Aldosterone, and Anti-Inflammatory Lymphocytes: Interplay and Therapeutic Opportunities.
Inflammation is recognized as an important factor in the pathophysiology of hypertension, with the renin-angiotensin-aldosterone system (RAAS) playing a key role in the disease. Initially described because of its contribution to extracellular fluid and electrolyte homeostasis, the RAAS has been implicated in endothelial dysfunction, vascular remodeling, oxidative stress, proinflammatory cytokine production, and adhesion molecule synthesis by the vascular wall. Both angiotensin II and aldosterone are involved in these systemic effects, activating innate and adaptive immune responses. This paper highlights some aspects connecting RAAS to the hypertensive phenotype, based on experimental and clinical studies, with emphasis on new findings regarding the contribution of an increasingly studied population of T lymphocytes: the T-regulatory lymphocytes. These cells can suppress inflammation and may exert beneficial vascular effects in animal models of hypertension.


N-acetylcysteine prevents preterm birth by attenuating the LPS-induced expression of contractile associated proteins in an animal model.
Intrauterine infection is associated with maternal immune activation (MIA) leading to preterm birth through upregulation of contractile associated proteins (CAPs). We hypothesized that N-acetylcysteine would decrease NF-κB activation and CAP expression in a MIA model for preterm birth. Pregnant CD-1 mice were given intrauterine LPS or saline on day 15/20. They received NAC or saline prior to injection and were monitored until delivery. The rate of preterm birth in the control, LPS, and LPS + NAC animals was determined. In another group, animals were sacrificed 6 h after treatment and myometrium was collected. COX-2, connexin 43, and oxytocin receptor expression was determined. LPS administration resulted in preterm birth and this effect was attenuated by NAC. LPS increased COX-2, connexin 43, and oxytocin receptor expression. NAC significantly decreased COX-2 expression. LPS increased NF-κB activation; this was attenuated by NAC. NAC may be beneficial in prevention of MIA-related preterm birth through attenuation of NF-κB activation and COX-2 upregulation.


Multimodal thrombectomy device for treatment of acute deep venous thrombosis.
Deep vein thrombosis (DVT) is a potentially deadly medical condition that is costly to treat and impacts thousands of Americans every year. DVT is characterized by the formation of blood clots within the deep venous system of the body. If a DVT dislodges it can lead to venous thromboembolism (VTE) and pulmonary embolism (PE), both of which can lead to significant morbidity or death. Current treatment options for DVT are limited in both effectiveness and safety, in part because the treatment of the DVT cannot be confined to a defined sequestered treatment zone. We therefore developed and tested a novel thrombectomy device that enables the sequesteration of a DVT to a defined treatment zone during fragmentation and evacuation. We observed that, compared to a predicate thrombectomy device, the sequestered approach reduced distal DVT embolization during ex vivo thrombectomy. The sequestered approach also facilitated isovolumetric infusion and suction that enabled clearance of the sequestered treatment zone without significantly impacting vein wall diameter. Results suggest that our novel device using sequestered therapy holds promise for the treatment of high risk large-volume DVTs.


An organization-wide approach for an effective communication system, Part 2.
This is the second article in a two-part series that describes an organization's approach to designing, implementing, and evaluating a communication system. Part 1 of this series, published in the March 1998 issue, focused on the design and implementation of this system. This article addresses the evaluation of outcomes related to identified goals to improve communication flow and decision making on multiple levels and to promote accountability for clinical and operational performance. Implementation strategies involving change management, emergence of issues with related implications, and planned evolution of this system also are discussed for ongoing organizational performance improvement.


Prasugrel, Māori, and personalised medicine in New Zealand.
The response to thienopyridine antiplatelet therapy is heterogeneous and is in part explained by clinical and genetic factors. A recent meta-analysis has demonstrated the clinical significance of a genetic polymorphism in the cytochrome P450 2C19 gene. Carriers of this polymorphism have a higher incidence of stent thrombosis and cardiovascular death, whilst on the thienopyridine clopidogrel. The polymorphism and rarer variants display higher carrier frequencies in ethnic groups with disproportionate cardiovascular mortality, such as Māori. Knowledge of an individual's genetic status may assist in optimising antiplatelet therapy, thereby reducing the cost of adverse events, expenditure on new medicines, and the ethnic disparities seen in healthcare outcomes. A demonstration of the cost-effectiveness of genetic testing, on a population basis, and a proven alternative, personalised strategy is required before the adoption of this technology can be advocated.


Dynamics of Disordered Proteins under Confinement: Memory Effects and Internal Friction.
Many proteins are disordered under physiological conditions. How efficiently they can search for their cellular targets and how fast they can fold upon target binding is determined by their intrinsic dynamics, which have thus attracted much recent attention. Experiments and molecular simulations show that the inherent reconfiguration timescale for unfolded proteins has a solvent friction component and an internal friction component, and the microscopic origin of the latter, along with its proper mathematical description, has been a topic of considerable debate. Internal friction varies across different proteins of comparable length and increases with decreasing denaturant concentration, showing that it depends on how compact the protein is. Here we report on a systematic atomistic simulation study of how confinement, which induces a more compact unfolded state, affects dynamics and friction in disordered peptides. We find that the average reconfiguration timescales increase exponentially as the peptide's spatial dimensions are reduced; at the same time, confinement broadens the spectrum of relaxation timescales exhibited by the peptide. There are two important implications of this broadening: First, it limits applicability of the common Rouse and Zimm models with internal friction, as those models attempt to capture internal friction effects by introducing a single internal friction timescale. Second, the long-tailed distribution of relaxation times leads to anomalous diffusion effects in the dynamics of intramolecular distances. Analysis and interpretation of experimental signals from various measurements that probe intramolecular protein dynamics (such as single-molecule fluorescence correlation spectroscopy and single-molecule force spectroscopy) rely on the assumption of diffusive dynamics along the distances being probed; hence, our results suggest the need for more general models allowing for anomalous diffusion effects.


Heat treatments at varying ambient temperatures and durations differentially affect plant defense to Blumeria hordei in a resistant and a susceptible Hordeum vulgare line.
Our previous research showed that a powdery mildew resistant barley line (MvHV07-17) maintains its resistance to Blumeria hordei (Bh) even if plants are exposed to long-term high temperature of 35 ⁰C for 120 h before Bh inoculation, while such high temperature pre-treatment further increases susceptibility to infection in the susceptible barley line MvHV118-17. In the present study, we extend this approach using short-term high-temperature water treatment (49 ⁰C 30 s) in order to determine how it affects powdery mildew resistance in these barley lines. We found that this short-term heat shock (HS) impaired plant defense responses, as reflected by development of Bh colonies and visible necrotic spots on leaves of MvHV07-17, which does not develop visible symptoms upon Bh inoculation under optimal growth conditions. In contrast, both HS and long-term heat stress enhanced susceptibility to Bh in MvHV118-17 plants. These results were supported by the measurement of Bh biomass using a qPCR method. Furthermore, microscopic examinations showed that HS elevated the rate of successful Bh penetration events, the spread of cell death in the surrounding mesophyll area and allowed colony formation and sporulation in resistant barley while early and effective plant defense responses, such as papilla formation and single-cell epidermal hypersensitive response were significantly reduced. Furthermore, we found that the accumulation of hydrogen peroxide in both resistant and susceptible barley was correlated with susceptibility induced by HS and long-term heat-stress. This study may contribute to a better understanding of plant defense responses to Bh in barley exposed to heat.


Estimating dose-response effects in psychological treatment trials: the role of instrumental variables.
We present a relatively non-technical and practically orientated review of statistical methods that can be used to estimate dose-response relationships in randomised controlled psychotherapy trials in which participants fail to attend all of the planned sessions of therapy. Here we are investigating the effects on treatment outcome of the number of sessions attended when the latter is possibly subject to hidden selection effects (hidden confounding). The aim is to estimate the parameters of a structural mean model (SMM) using randomisation, and possibly randomisation by covariate interactions, as instrumental variables. We describe, compare and illustrate the equivalence of the use of a simple G-estimation algorithm and two two-stage least squares procedures that are traditionally used in economics.


Comparison of Linear Poly Ethylene Imine (LPEI) and Poly L-Lysine (PLL) in Fabrication of CHOK1 Cell-Loaded Multilayer Alginate Microcapsules.
Purpose: Poly l-lysine (PLL) has been introduced as a strengthening covering layer for alginate microcapsules which are the most convenient way for cell encapsulation. Some disadvantages of PLL such as high price and low biocompatibility have prompted scientists to find better alternatives. Linear poly ethylene imine (LPEI), thanks to its highly similar structure to PLL, could be considered as a proper cost-effective alternative. In this study LPEI and PLL were compared as covering layers of cell-loaded alginate-LPEI-alginate (cALA) and alginate-PLL-alginate (cAPA) microcapsules. Methods: In addition to the physico-mechanical properties, the encapsulation efficiency, cell survival post encapsulation, cell viability, and cellular metabolic activity within the microcapsules were evaluated using trypan blue, live/dead cell staining, and MTT test, respectively. Results: Physico-mechanical evaluation of the microcapsules revealed that the cell microencapsulation process did not affect their shape, size, and mechanical stability. Although the encapsulation efficiency for cALA and cAPA was not different (P >0.05), cell survival post encapsulation was higher in cALA than in cAPA (P<0.05) which could be the reason for the higher cell viability and also cellular metabolic activity within these microcapsules in comparison to cAPA. Conclusion: Here, based on these results, ALA could be introduced as a preferable alternative to APA for cell encapsulation.


Conceptual and practical challenges in the assessment of physician competencies.
Abstract The shift to using outcomes-based competency frameworks in medical education in many countries around the world requires educators to find ways to assess multiple competencies. Contemporary medical educators recognize that a competent trainee not only needs sound biomedical knowledge and technical skills, they also need to be able to communicate, collaborate and behave in a professional manner. This paper discusses methodological challenges of assessment with a particular focus on the CanMEDS Roles. The paper argues that the psychometric measures that have been the mainstay of assessment practices for the past half-century, while still valuable and necessary, are not sufficient for a competency-oriented assessment environment. New assessment approaches, particularly ones from the social sciences, are required to be able to assess non-Medical Expert (Intrinsic) roles that are situated and context-bound. Realist and ethnographic methods in particular afford ways to address the challenges of this new assessment. The paper considers the theoretical and practical bases for tools that can more effectively assess non-Medical Expert (Intrinsic) roles.


Asymmetric C1 Extension of Aldehydes through Biocatalytic Cascades for Stereodivergent Synthesis of Mandelic Acids.
The development of mild, efficient, and enantioselective methods for preparing chiral building blocks from simple, renewable carbon units has been a long-term goal of the sustainable chemical industry. Mandelate derivatives are valuable pharmaceutical intermediates and chiral resolving agents, but their manufacture relies heavily on highly toxic cyanide. Herein, we report (S)-4-hydroxymandelate synthase (HmaS)-centered biocatalytic cascades for the synthesis of mandelates from benzaldehydes and glycine. We show that HmaS can be engineered to perform R-selective hydroxylation by single-point mutation, empowering the stereodivergent synthesis of both (S)- and (R)-mandelate derivatives. These biocatalytic cascades enabled the production of various mandelate derivatives with high atom economy as well as excellent yields (up to 98 %) and ee values (up to >99 %). This methodology offers an effective cyanide-free technology for greener and sustainable production of mandelate derivatives.


Smooth information flow in temperature climate network reflects mass transport.
A directed climate network is constructed by Granger causality analysis of air temperature time series from a regular grid covering the whole Earth. Using winner-takes-all network thresholding approach, a structure of a smooth information flow is revealed, hidden to previous studies. The relevance of this observation is confirmed by comparison with the air mass transfer defined by the wind field. Their close relation illustrates that although the information transferred due to the causal influence is not a physical quantity, the information transfer is tied to the transfer of mass and energy.


Patient-derived podocyte spheroids reveal new insights into the etiopathogenesis of Alport syndrome.
Alport syndrome (AS) is a rare disease characterized by defective glomerular basement membranes, caused by mutations in COL4A3, COL4A4, and COL4A5, which synthesize collagen type IV. Patients present with progressive proteinuria, hematuria and podocyte loss. There is currently no cure for Alport syndrome, and this is mainly due to its complex and variable pathogenesis, as well as the lack of models that can faithfully mimic the human phenotype. Here we have developed a novel human culture model of Alport syndrome and used it to study the effects of different mutations on podocyte development and biology. First, we established a differentiation protocol that allowed us to generate podocyte spheroids from patient-derived human induced pluripotent stem cells (hiPSCs). We have then carried out discovery proteomics and demonstrated that a total of 178 proteins were differentially expressed between Alport (AS1 and AS3) and control (LT) podocytes. GO analysis indicated alterations in several metabolic pathways, such as oxidative phosphorylation, RNA maturation, chromatin condensation, and proliferation. Although functional assays showed no changes in lactate production and mitochondrial potential compared to healthy controls, immunofluorescence and electron microscopy analysis showed key morphological changes related to the phenotypical maturation of Alport podocytes. Moreover, the studied mutations led to persistent proliferation, increased reactive oxygen species (ROS) production and the concomitant expression of peroxisome proliferator-activated receptors α and γ (PPARα and PPARγ) in podocytes. These data on patient-derived podocytes provide evidence that collagen mutations, in addition to playing a central role in the defective development of the glomerular filtration barrier, cause significant alterations in podocyte development and metabolism very early in development, even before the formation of the filtering apparatus. In conclusion, our study provides a new methodological platform for the differentiation of podocytes and to study human podocytopathies in a personalized manner, and reveals new insights into the etiopathogenesis and pathobiology of Alport syndrome.


Parametric geometry exploration of the human carotid artery bifurcation.
A parametric computational model of the human carotid artery bifurcation is employed to demonstrate that it is only necessary to simulate approximately one-half of a single heart pulse when performing a global exploration of the relationships between shear stress and changes in geometry. Using design of experiments and surface fitting techniques, a landscape is generated that graphically depicts these multi-dimensional relationships. Consequently, whilst finely resolved, grid and pulse independent results are traditionally demanded by the computational fluid dynamics (CFD) community, this strategy demonstrates that it is possible to efficiently detect the relative impact of different geometry parameters, and to identify good and bad regions of the landscape by only simulating a fraction of a single pulse. Also, whereas in the past comparisons have been made between the distributions of appropriate shear stress metrics, such as average wall shear stress and oscillatory shear index, this strategy requires a figure of merit to compare different geometries. Here, an area-weighted integral of negative time-averaged shear stress, tau , is used as the principal objective function, although the discussion reveals that the extent as well as the intensity of reverse flow may be important. Five geometry parameters are considered: the sinus bulb width, the angles and the outflow diameters of the internal carotid artery (ICA) and external carotid artery (ECA). A survey of the landscape confirms that bulb shape has the dominant effect on tau with maximum tau occurring for large bulb widths. Also, it is shown that different sets of geometric parameters can produce low values of tau by either relatively small intense areas, or by larger areas of less intense reverse flow.


[Surgical standards in rectal cancer].
At present, a differentiated surgical treatment approach allows a curative resection (R0) for carcinoma of the rectum to be obtained in up to 80% of cases. Through the introduction of organ-preserving therapeutic procedures (polypectomy and transanal full-thickness excision), as well as the consequent extension of sphincter-preserving procedures (deep anterior rectum resection with stapler anastomosis and abdomino-peranal rectum resection with colo-anal anastomosis), the rate of sphincter-preserving operations has been increased to 80-85%. A detailed knowledge of the mode of spread of carcinoma of the rectum forms the basis for all differential diagnostic considerations as well as the operative technique. Observance of an adequate margin of clearance as dependent on tumour stage as well as the performance of an anatomically--and oncologically--correct pelvic dissection are requisites for a radical treatment of carcinoma of the rectum. Only a strict compliance of the indications criteria which have been worked out permit the use of limited therapeutic procedures.


Co(2+)@Mesoporous Silica Monoliths: Tailor-Made Nanoreactors for Confined Soft Chemistry.
Mesoporous silica monoliths with various ordered nanostructures containing transition metal M(2+) cations in variable amounts were elaborated and studied. A phase diagram depicting the different phases as a function of the M(2+) salt/tetramethyl orthosilicate (TMOS) and surfactant P123/TMOS ratios was established. Thermal treatment resulted in mesoporous monoliths containing isolated, accessible M(2+) species or condensed metal oxides, hydroxides, and salts, depending on the strength of the interactions between the metal species and the ethylene oxide units of P123. The ordered mesoporosity of the monoliths containing accessible M(2+) ions was used as a nanoreactor for the elaboration of various transition metal compounds (Prussian blue analogues, Hofmann compounds, metal-organic frameworks), and this opens the way to the elaboration of a large range of nanoparticles of multifunctional materials.


A simple technique to straighten the curved tip of a "J" guidewire.
We describe a simple technique to straighten the curved tip of a "J" guidewire when the plastic introducer is not readily available. This technique may expedite angiographic procedures.


Detection of Latin American strains of Histoplasma in a murine model by use of a commercially available antigen test.
During a Histoplasma outbreak in a colony of fruit bats at a southern United States zoo, it was observed that although Histoplasma was recovered in culture from multiple sites at necropsy, none of the samples collected from those bats tested positive for Histoplasma antigen (HAg). Five of the Histoplasma isolates from the bats were subsequently identified as Latin American (LA) clade A, restriction fragment length polymorphism (RFLP) class 6. These observations raised concern as to whether the commercially available HAg test could detect Histoplasma antigen not of the North American clade upon which the HAg test had been developed. To evaluate this concern, a murine model of disseminated histoplasmosis was established, and mice were infected with multiple LA Histoplasma isolates, including clinical isolates recovered from Brazilian AIDS patients (RFLP class 5 and class 6) and isolates recovered from the bats during the outbreak (RFLP class 6). Histoplasma antigen was detected in all infected mice in our experiments, even when Histoplasma was not recovered in culture. Because the currently available HAg test is able to detect Histoplasma antigen in mice infected with Latin American isolates, this suggests that bat host factors rather than differences among Histoplasma RFLP classes were responsible for the inability to detect HAg in infected bats.


Observations on "orthogonality" in comprehensive two-dimensional separations.
The concept and definition of orthogonality in the context of comprehensive two-dimensional (2D) separations are interesting topics of active discussion. Over the years, several approaches have been taken to quantify the degree of orthogonality, primarily to serve as a metric to optimize (and compare) comprehensive 2D separations. Recently, a mathematical function was reported that is qualitatively instructive for the purpose of providing such a metric. However, the mathematical function has some quantitative shortcomings. Herein, we both explore and partially correct this function. The orthogonality metric, referred to previously and herein as the orthogonality, O, was mathematically related to the fraction of the 2D separation space occupied by compounds (i.e., fractional coverage) and the peak capacity, P, for one dimension of the 2D separation. The fractional coverage, f, is simply related to the percentage coverage, which is equal to 100%(f). Our main finding was that the values for O as a function of P for a given percentage coverage achieve a constant value at large P but deviate severely to lower O values at small P. For comprehensive 2D separations operated such that the second dimension is at small P, the findings we report have consequences for those who consider applying the O metric. Finally, it is discussed that the percentage coverage may be a better metric to gauge the extent to which the compounds in a given sample mixture have been disseminated in the 2D separation space.