Abnormal chromatin remodeling caused by ARID1A deletion leads to malformation of the dentate gyrus.
ARID1A, an SWI/SNF chromatin-remodeling gene, is commonly mutated in cancer and hypothesized to be a tumor suppressor. Recently, loss-of-function of ARID1A gene has been shown to cause intellectual disability. Here we generate Arid1a conditional knockout mice and investigate Arid1a function in the hippocampus. Disruption of Arid1a in mouse forebrain significantly decreases neural stem/progenitor cells (NSPCs) proliferation and differentiation to neurons within the dentate gyrus (DG), increasing perinatal and postnatal apoptosis, leading to reduced hippocampus size. Moreover, we perform single-cell RNA sequencing (scRNA-seq) to investigate cellular heterogeneity and reveal that Arid1a is necessary for the maintenance of the DG progenitor pool and survival of post-mitotic neurons. Transcriptome and ChIP-seq analysis data demonstrate that ARID1A specifically regulates Prox1 by altering the levels of histone modifications. Overexpression of downstream target Prox1 can rescue proliferation and differentiation defects of NSPCs caused by Arid1a deletion. Overall, our results demonstrate a critical role for Arid1a in the development of the hippocampus and may also provide insight into the genetic basis of intellectual disabilities such as Coffin-Siris syndrome, which is caused by germ-line mutations or microduplication of Arid1a.


Functional testing of hepatocytes following their recovery from cryopreservation.
Various tests of function have been suggested for assessing hepatocytes recovered from cryopreservation. In this study we have investigated hepatocyte attachment during tissue culture and cellular density in order to assess function and compared them with two classical dye exposure tests. The ability of hepatocytes to exclude trypan blue dye (TB) and metabolize fluorescein diacetate (FDA) was demonstrated. In populations of freshly prepared hepatocytes 88.07% were able to exclude TB and 87.31% were able to metabolize FDA. However in populations of hepatocytes recovered after cryopreservation using 1.5 M dimethyl sulfoxide as cryoprotectant only 33.44% were able to exclude TB and 31.59% able to metabolize FDA. Both of these tests gave the same estimate of functional ability. Density gradient centrifugation of hepatocytes on Percoll 400 (Pharmacia, Uppsala, Sweden) separated two populations of hepatocytes; one (density ca.1.07 g/ml Percoll) in which most of the cells were able to exclude TB and the second (density ca. 1.02 g/ml Percoll) in which they were stained blue. The dense population was highly enriched in dye-excluding hepatocytes: freshly prepared hepatocytes, 92.4%, and cryopreserved hepatocytes, 88.66%. When samples of these cells (2 x 10(6) dye-excluding cells per dish) were tested for their ability to attach to tissue culture dishes only 17.28% of the cryopreserved hepatocytes were able to attach compared to 55.28% of the freshly prepared cells. We conclude that cryopreservation of hepatocytes produces a population of cells which are not metabolically identical to a population of freshly prepared hepatocytes even though they appear to have the same buoyant density and dye-excluding capabilities.(ABSTRACT TRUNCATED AT 250 WORDS)


Optimal control strategies for dengue transmission in pakistan.
This paper presents a deterministic model for dengue virus transmission. The model is parameterized using data from the 2017 dengue outbreak in Pakistan. We estimated the basic reproduction number (R0) without any interventions for the 2017 dengue outbreak in Peshawar district of Pakistan as R0≈2.64, the distribution of the reproduction number lies in the range R0∈[1.21,5.24] (with a mean R0≈2.64). Optimal control theory is then applied to investigate the optimal strategy for curtailing the spread of the disease using two time-dependent control variables determined from sensitivity analysis. These control variables are insecticide use and vaccination. The results show that the two controls avert the same number of infections in the district regardless of the weights on the costs this is due to the reciprocal relationship between the cost of insecticide use and vaccination. A strong reciprocal relationship exists between the use of insecticide and vaccination; as the cost of insecticide increases the use of vaccination increases. The use of insecticide on the other hand slightly increases when vaccination level decreases due to increase in cost.


Biological and Genetic Characterization of Physostegia Chlorotic Mottle Virus in Europe Based on Host Range, Location, and Time.
Application of high throughput sequencing (HTS) technologies enabled the first identification of Physostegia chlorotic mottle virus (PhCMoV) in 2018 in Austria. Subsequently, PhCMoV was detected in Germany and Serbia on tomatoes showing severe fruit mottling and ripening anomalies. We report here how prepublication data-sharing resulted in an international collaboration across eight laboratories in five countries, enabling an in-depth characterization of PhCMoV. The independent studies converged toward its recent identification in eight additional European countries and confirmed its presence in samples collected 20 years ago (2002). The natural plant host range was expanded from two to nine species across seven families, and we confirmed the association of PhCMoV presence with severe fruit symptoms on economically important crops such as tomato, eggplant, and cucumber. Mechanical inoculations of selected isolates in the greenhouse established the causality of the symptoms on a new indexing host range. In addition, phylogenetic analysis showed a low genomic variation across the 29 near-complete genome sequences available. Furthermore, a strong selection pressure within a specific ecosystem was suggested by nearly identical sequences recovered from different host plants through time. Overall, this study describes the European distribution of PhCMoV on multiple plant hosts, including economically important crops on which the virus can cause severe fruit symptoms. This work demonstrates how to efficiently improve knowledge on an emergent pathogen by sharing HTS data and provides a solid knowledge foundation for further studies on plant rhabdoviruses.[Formula: see text] Copyright © 2022 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.


Patient Access to Online Visit Notes: Perceptions of Doctors and Patients at an Urban HIV/AIDS Clinic.
Patients living with HIV/AIDS face large societal and medical challenges. Inviting patients to read their doctors' visit notes via secure electronic portals may empower patients and improve health. We investigated whether utilization and perceptions about access to doctors' notes differed among doctors and patients in an HIV/AIDS clinic versus primary care setting. We analyzed pre- and 1-year postintervention data from 99 doctors and 3819 patients. HIV clinic patients did not report differences in perceived risks and benefits compared to primary care clinic patients, however, they were more likely to share notes with friends (33% versus 9%, P=.002), other health professionals (24% versus 8%, P=.03), or another doctor (38% versus 9%, P<.0001). HIV clinic doctors were less likely than primary care doctors to change the level of candor in visit notes (P<.04). Our findings suggest that HIV clinic patients and doctors are ready to share visit notes online.


Modular real-time PCR screening assay for common European animal families.
A screening assay based on real-time PCR and melt curve analysis was developed to detect DNA from nine common European animal families/species and human. The assay consists of a 10-cycle universal pre-amplification followed by specific nested PCR and was designed to exploit the different melting temperatures (T m) of family/species-specific 12S ribosomal ribonucleic acid and cytochrome b fragments, which are amplified in duplex reactions. Case-related modular application is possible. Beyond determination of the animal family and discrimination from human DNA, evaluation of the melt curve in some cases additionally allows for species determination (e.g. cat vs. lynx). The method presents a quick, flexible and sample-saving approach to assess non-human DNA at low expenses, and it is especially useful in resolution of DNA mixtures.


Association of hyperleptinemia with peripheral arterial disease in hypertensive patients.
Hypertension is a risk factor for peripheral artery disease (PAD). Serum leptin plays an important role in promoting endothelial dysfunction. The aim of this study is to investigate whether the leptin level is associated with PAD in hypertensive patients. Ninety-eight hypertensive patients were enrolled in this study. Ankle-brachial index (ABI) values were measured using an automated oscillometric device. Patients with an ABI value <0.9 were considered the low ABI group. C-reactive protein (CRP) was measured using standard enzymatic automated methods. Serum levels of human leptin were determined using a commercially available enzyme immunoassay. Eighteen (18.4%) hypertensive patients were included in the low ABI group. Hypertensive patients in the low ABI group had higher serum creatinine (P < 0.001), CRP (P = 0.003), and leptin (P < 0.001) levels, higher prevalence of diabetes (P = 0.036), and current smoking (P = 0.034) than patients in the normal ABI group. Univariate linear regression analyses revealed that body weight (P = 0.014), waist circumference (P = 0.010), body mass index (P = 0.002), and logarithmically transformed CRP (log-CRP, P = 0.001) were positively correlated with serum log-leptin levels in hypertensive patients. Multivariate stepwise linear regression analysis showed that log-leptin (β = 0.439, adjusted R2 change = 0.224, P < 0.001) was also an associated factor of PAD in hypertensive patients. A higher log-leptin value is an independent predictor of PAD in hypertensive patients.


Interactions of phosphate solubilising microorganisms with natural rare-earth phosphate minerals: a study utilizing Western Australian monazite.
Many microbial species are capable of solubilising insoluble forms of phosphate and are used in agriculture to improve plant growth. In this study, we apply the use of known phosphate solubilising microbes (PSM) to the release of rare-earth elements (REE) from the rare-earth phosphate mineral, monazite. Two sources of monazite were used, a weathered monazite and mineral sand monazite, both from Western Australia. When incubated with PSM, the REE were preferentially released into the leachate. Penicillum sp. released a total concentration of 12.32 mg L-1 rare-earth elements (Ce, La, Nd, and Pr) from the weathered monazite after 192 h with little release of thorium and iron into solution. However, cultivation on the mineral sands monazite resulted in the preferential release of Fe and Th. Analysis of the leachate detected the production of numerous low-molecular weight organic acids. Gluconic acid was produced by all microorganisms; however, other organic acids produced differed between microbes and the monazite source provided. Abiotic leaching with equivalent combinations of organic acids resulted in the lower release of REE implying that other microbial processes are playing a role in solubilisation of the monazite ore. This study demonstrates that microbial solubilisation of monazite is promising; however, the extent of the reaction is highly dependent on the monazite matrix structure and elemental composition.


Oxidative stress-induced apoptosis and autophagy: Balancing the contrary forces in spermatogenesis.
Spermatogenesis is a complex process in the testis and is a cornerstone of male infertility. The abundance of unsaturated fatty acid and high cell division rate make male germs cells prone to DNA deterioration. ROS-mediated oxidative stress triggers DNA damage, autophagy, and apoptosis in male germ cells, which are critical causative factors that lead to male infertility. The complex connection and molecular crosstalk between apoptosis and autophagy is seen at multifaceted levels that interconnect the signaling pathways of these two processes. Multilevel interaction between apoptosis and autophagy is a seamless state of survival and death in response to various stressors. Interaction between multiple genes and proteins such as the mTor signaling pathway, Atg12 proteins, and the death adapter proteins, such as Beclin 1, p53, and Bcl-2 family proteins, validates such a link between these two phenomena. Testicular cells being epigenetically different from somatic cells, undergo numerous significant epigenetic transitions, and ROS modulates the epigenetic framework of mature sperm. Epigenetic deregulation of apoptosis and autophagy under oxidative stress conditions can cause sperm cell damage. The current review recapitulates the current role of prevailing stressors that generate oxidative stress leading to the induction of apoptosis and autophagy in the male reproductive system. Considering the pathophysiological consequences of ROS-mediated apoptosis and autophagy, a combinatorial approach, including apoptosis inhibition and autophagy activation, should be implemented as a therapeutic strategy to treat male idiopathic infertility. Understanding the crosslink between apoptosis and autophagy under stress conditions in male germ cells may play an essential role in developing therapeutic strategies to treat infertility.


Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans.
Parallels between T cell kinetics in mice and men have fueled the idea that a young mouse is a good model system for a young human, and an old mouse, for an elderly human. By combining in vivo kinetic labeling using deuterated water, thymectomy experiments, analysis of T cell receptor excision circles and CD31 expression, and mathematical modeling, we have quantified the contribution of thymus output and peripheral naive T cell division to the maintenance of T cells in mice and men. Aging affected naive T cell maintenance fundamentally differently in mice and men. Whereas the naive T cell pool in mice was almost exclusively sustained by thymus output throughout their lifetime, the maintenance of the adult human naive T cell pool occurred almost exclusively through peripheral T cell division. These findings put constraints on the extrapolation of insights into T cell dynamics from mouse to man and vice versa.


Synthesis of L-methionine-loaded chitosan nanoparticles for controlled release and their in vitro and in vivo evaluation.
Therapeutically popular controlled release-enabling technology has forayed into the nutrition sector. Polymer coated forms of L-methionine used in soy protein diets, and its intermediate metabolite, S-adenosyl-L-methionine, used in myriad of medical conditions have proved more efficacious over (highly catabolized) free forms. In this premier study, L-methionine-loaded chitosan nanoparticles (M-NPs) were synthesized using ionic gelation method and their efficacy was evaluated. Biophysical characterization of the NPs was done using a Nanopartica SZ 100 analyser, transmission electron microscopy, and Fourier transform infrared spectroscopy. The M-NPs were spherical and smooth and 218.9 ± 7.4 nm in size and in vitro testing confirmed the controlled release of methionine. A 60-days feeding trial in L. rohita fish fingerlings was conducted. A basal diet suboptimal (0.85%) in methionine was provided with one of the supplements as under: none (control), 0.8% chitosan NPs (0.8% NPs), 1.2% L-methionine (1.2% M) (crystalline free form), 0.6% M-NPs and 1.2% M-NPs. While the addition of 0.6% M-NPs to the basal diet complemented towards meeting the established dietary requirement and resulted in significantly highest (P < 0.05) growth and protein efficiency and sero-immunological test scores (serum total protein, serum globulin, serum albumin: globulin ratio, phagocytic respiratory burst/NBT reduction and lysozyme activity), 1.2% supplementation in either form (free or nano), for being 0.85% excess, was counterproductive. Liver transaminases and dehydrogenases corroborated enhanced growth. It was inferred that part of the methionine requirement in nano form (M-NPs) can confer intended performance and health benefits in animals relying on plant proteins-based diets limiting in this essential amino acid. The study also paves the way for exploring chitosan NPs-based sustained delivery of amino acids in human medical conditions.


Fine structure of the cerebellum of "staggerer-reeler", a double mutant of mice affected by staggerer and reeler conditions. I. The premature disappearance of the external granular layer and ensuing cerebellar disorganization.
It was reasoned that cerebella of mice carrying both staggerer and reeler conditions, called double mutant, might accentuate some of the anomalies observed in single mutants, thus revealing further details otherwise undetectable. As expected, the cerebellar hypoplasia, the paucity of fissures, granule cells and interneurons of the molecular layer, and the external granular layer hypoplasia, common in both staggerer and reeler, were much more pronounced in double mutant. However, the most striking feature of the double mutant cerebellum was the premature disappearance of the external granular layer. The external granular layer is smaller both in staggerer and reeler as compared to the normal but it persists beyond the normal time (around day 15). In double mutant, however, the external granular layer disappeared by day 7 or 8, reducing the density of granule cells even further. This observation was interpreted as indicating that both the staggerer and reeler genes effect the premature disappearance of the external granular layer. Most of the gross cerebellar anomalies in double mutant such as cerebellar hypoplasia, paucity of fissures and Purkinje and Golgi epithelial cell disalignment could be explained as the result of this premature disappearance of the external granular layer. On the other hand, anomalies of Purkinje cells and Bergmann fibers, which are also present both in staggerer and reeler, did not follow the same additive change.


Seven years of experience with high-intensity focused ultrasound for prostate cancer: advantages and limitations.
The aim of this study was to evaluate oncologic outcomes and adverse events for patients with prostate cancer after treatment by high-intensity focused ultrasound (HIFU). Between February 2004 and August 2010, patients with prostate cancer who underwent HIFU treatment were reviewed about oncologic outcomes and complications. Biochemical recurrence (BCR) was defined as prostate-specific antigen (PSA) nadir plus 1.2 ng/ml. Kaplan-Meier analysis was performed to evaluate BCR- and disease progression-free survival according to risk stratification. Predictors for BCR and disease progression were identified using the Cox-proportional hazard method. The overall BCR rate was 59.5%, and median time to BCR was 13.8 months. The 5-year BCR-free survival rates of the low-, intermediate-, and high-risk groups were 66.3, 40.2, and 21.0% (P = 0.001), respectively, and the 5-year disease progression-free survival rates were 73.5, 46.0, and 29.2%, respectively (P = 0.008). Multivariate analysis showed that risk stratification, PSA nadir, and time to PSA nadir were significant predictors of BCR and disease progression. In the first 3 months post-op, 11 patients (8.7%) had complications. There were no patients who required blood transfusions or who had wound problems, stroke, deep vein thrombosis, or bowel dysfunction. HIFU treatment does not provide effective oncologic outcomes even in low risk patients with prostate cancer as well as in the intermediate or high risk groups. Therefore, patients selected to undergo HIFU treatment for prostate cancer must be very carefully chosen. On the other hand, HIFU treatment for prostate cancer had a very low rate of complications.


The mechanism of end product inhibition of serine biosynthesis. V. Mechanism of serim inhibition of phosphoglycerate dehydrogenases.
The reduction of enzyme-bound DPN constitutes a half-reaction of phosphoglycerate dehydrogenase and has been investigated fluorometrically. Serine was found to inhibit the half-reaction to the same extent and with the same degree of cooperation as the steady state reaction. This finding identifies the ternary complex conversion as the point in the reaction sequence at which serine inhibition occurs. Delta H determinations for the half-reaction showed no difference whether serine was or was not present and led to the conclusion that the inhibitory effect of serine could only manifest itself through the delta S term in the expression for the formation of the activated transition state complex. DL-3-P[2-2H]glyceric acid showed no primary isotope effect in the half-reaction. This result excludes hydrogen transfer as the rate-limiting step in the half-reaction and confirms that an isomerization step, affected by serine, exists in the ternary complex conversion scheme. The deuterated 3-P-glyceric acid shows an isotope effect of 2 in the steady state reaction.


Effect of thyroid state on H2O2 production by rat liver mitochondria.
It has been suggested that activation of mitochondrial respiration by thyroid hormone results in oxidative tissue injury secondary to increased reactive oxygen species production. In order to throw light on this subject, the effects of thyroid state on O2 consumption and H2O2 release by rat liver mitochondria were investigated. Hypothyroidism decreased the rates of O2 consumption and H2O2 release by succinate or pyruvate/malate-supplemented mitochondria during both State 4 and State 3 respiration, whereas hyperthyroidism increased such rates. Conversely, with both substrates and during either respiration phase, the percentage of O2 released as H2O2 was not significantly affected by thyroid state. On the other hand, the capacity of mitochondria to remove H2O2 increased by about 17% in hyperthyroid rats and decreased by about 35% in hypothyroid ones. This result indicates that the ratio between H2O2 production and release and so the percentage of O2 turned into H2O2 instead of being reduced to water increase in the transition from hypothyroid to hyperthyroid state. In light of previous observations that mitochondrial content of cytochromes and ubiquinone also increases in such a transition, the modifications of H2O2 production appear to be due to a modulation by thyroid hormone of the mitochondrial content of the autoxidisable electron carriers. This view is supported by measurements of H2O2 release in the presence of respiratory inhibitors, which show that the thyroid state-linked changes in H2O2 production occur at H2O2 generator sites of both Complex I and Complex III.


[Production of HMGN2 polyclonal antibody by immunization with recombinant GST-HMGN2 fusion protein and its application to analysis of HMGN2 distribution in human monocytes].
To prepare high mobility group chromosomal protein N2 (HMGN2) polyclonal antibodies and determine the subcellular localization of HMGN2 in human monocytes. The recombinant prokaryotic expression vector pGEX-1lambdaT-HMGN2 was constructed and E. coli-based product of GST-HMGN2 fusion protein was prepared and used to immunize rabbit for producing the anti-serum against HMGN2. The polyclonal antibodies were partially purified by caprylic acid and ammonium sulfate precipitation. The titter of specific polyclonal antibodies against HMGN2 was detected by ELISA. The immunocytochemical staining was performed to determine the distribution of HMGN2 in THP-1 cells. Gel electrophoresis of the enzyme-digested recombinant plasmid and the DNA sequencing confirmed that the recombinant prokaryotic expression vector pGEX-1lambdaT-HMGN2 was correctly constructed. After IPTG induction, the recombinant-transformed E. coli produced a bulk of GST-HMGN2 fusion protein. The polyclonal antibodies to HMGN2 was obtained from the serum of rabbit immunized with GST-HMGN2 fusion protein and its ELISA titer was 1:2000. The immunocytochemistry staining indicated that when stimulated with LPS, HMGN2 was present not only in THP-1 nucleus but also in the cytoplasm. The presence of HMGN2 was also detected in the culture supernatant. This result suggests that recombinant peptide fusion protein could be used to produce peptide antibody. HMGN2 could be present in the cytoplasm of monocytes and release to the extracellular environment when stimulated with lipopolysaccharide (LPS).


Palliative gastroenterostomy for pancreatic cancer.
The records of 125 consecutive patients with unresectable pancreatic cancer treated between 1958 and 1979 were evaluated to determine the benefit or morbidity of gastroenterostomy performed on a routine basis. One hundred three patients had no evidence of gastric outlet obstruction from tumor extension as determined at the time of initial operation. Fifty-seven of these patients underwent biliary diversion as their only operative procedure. The morbidity and mortality in this group was 31 and 14 percent, respectively. Six of these 57 patients required decompressing gastroenterostomy at a later date to relieve gastric outlet obstruction. Forty-six patients underwent both biliary and prophylactic gastric outlet diversion with a 15 percent mortality rate and a 46 percent incidence of morbidity. The most common complication in this group was delayed gastric emptying (14 percent). These findings, and the high incidence of delayed gastric emptying after gastroenterostomy and the relatively infrequent occurrence of gastric outlet obstruction (11 percent) after initial biliary diversion, suggest that gastroenterostomy should be performed on a selective basis only.


Synthesis and biological evaluation of novel steroid-modified ether phospholipids.
Platelet activating factor is one of the most potent inflammatory ether phospholipid mediators known and structurally modified analogues are of considerable interest as potential therapeutic preparations. Inspired by the proposed structure for a novel endogenous hydroxy-PAF analogue isolated recently from gingival crevicular fluid, we designed and prepared two novel steroid-modified ether phospholipids. These two novel compounds exhibit marked chemical and biological similarities to their endogenous prototype and they antagonize it being less active in inducing washed platelet aggregation through PAF receptors.


Public cost and access to primary care for hyperglycemic emergencies, Clark County, Nevada.
Diabetes mellitus accounts for 5.8% of the total health care costs of citizens of the United States. Hospitalization expenses produce 40.5% of these costs. We sought to determine the public expenditure and major precipitators of admissions for uninsured diabetic hyperglycemic emergencies at a large public hospital. Of 247 diabetic emergency admissions over a 30 month period 49% (n = 121) of these patients had no medical insurance. The uninsured patients were younger and had relatively mild disease in comparison to the insured patients. These patients identified a primary physician in only 6% of the cases and had a higher incidence of admissions associated with lack of medications. We conclude that public funds to provide access to primary care and enhancement of employer-sponsored health insurance programs may decrease the numbers and costs of hospitalizations due to hyperglycemic emergencies in uninsured patients with diabetes mellitus.


The Use of Anatomical Information for Molecular Image Reconstruction Algorithms: Attenuation/Scatter Correction, Motion Compensation, and Noise Reduction.
PET and SPECT are important tools for providing valuable molecular information about patients to clinicians. Advances in nuclear medicine hardware technologies and statistical image reconstruction algorithms enabled significantly improved image quality. Sequentially or simultaneously acquired anatomical images such as CT and MRI from hybrid scanners are also important ingredients for improving the image quality of PET or SPECT further. High-quality anatomical information has been used and investigated for attenuation and scatter corrections, motion compensation, and noise reduction via post-reconstruction filtering and regularization in inverse problems. In this article, we will review works using anatomical information for molecular image reconstruction algorithms for better image quality by describing mathematical models, discussing sources of anatomical information for different cases, and showing some examples.


Trends in Obesity Prevalence Among Children and Adolescents in the United States, 1988-1994 Through 2013-2014.
Previous analyses of obesity trends among children and adolescents showed an increase between 1988-1994 and 1999-2000, but no change between 2003-2004 and 2011-2012, except for a significant decline among children aged 2 to 5 years. To provide estimates of obesity and extreme obesity prevalence for children and adolescents for 2011-2014 and investigate trends by age between 1988-1994 and 2013-2014. Children and adolescents aged 2 to 19 years with measured weight and height in the 1988-1994 through 2013-2014 National Health and Nutrition Examination Surveys. Survey period. Obesity was defined as a body mass index (BMI) at or above the sex-specific 95th percentile on the US Centers for Disease Control and Prevention (CDC) BMI-for-age growth charts. Extreme obesity was defined as a BMI at or above 120% of the sex-specific 95th percentile on the CDC BMI-for-age growth charts. Detailed estimates are presented for 2011-2014. The analyses of linear and quadratic trends in prevalence were conducted using 9 survey periods. Trend analyses between 2005-2006 and 2013-2014 also were conducted. Measurements from 40,780 children and adolescents (mean age, 11.0 years; 48.8% female) between 1988-1994 and 2013-2014 were analyzed. Among children and adolescents aged 2 to 19 years, the prevalence of obesity in 2011-2014 was 17.0% (95% CI, 15.5%-18.6%) and extreme obesity was 5.8% (95% CI, 4.9%-6.8%). Among children aged 2 to 5 years, obesity increased from 7.2% (95% CI, 5.8%-8.8%) in 1988-1994 to 13.9% (95% CI, 10.7%-17.7%) (P < .001) in 2003-2004 and then decreased to 9.4% (95% CI, 6.8%-12.6%) (P = .03) in 2013-2014. Among children aged 6 to 11 years, obesity increased from 11.3% (95% CI, 9.4%-13.4%) in 1988-1994 to 19.6% (95% CI, 17.1%-22.4%) (P < .001) in 2007-2008, and then did not change (2013-2014: 17.4% [95% CI, 13.8%-21.4%]; P = .44). Obesity increased among adolescents aged 12 to 19 years between 1988-1994 (10.5% [95% CI, 8.8%-12.5%]) and 2013-2014 (20.6% [95% CI, 16.2%-25.6%]; P < .001) as did extreme obesity among children aged 6 to 11 years (3.6% [95% CI, 2.5%-5.0%] in 1988-1994 to 4.3% [95% CI, 3.0%-6.1%] in 2013-2014; P = .02) and adolescents aged 12 to 19 years (2.6% [95% CI, 1.7%-3.9%] in 1988-1994 to 9.1% [95% CI, 7.0%-11.5%] in 2013-2014; P < .001). No significant trends were observed between 2005-2006 and 2013-2014 (P value range, .09-.87). In this nationally representative study of US children and adolescents aged 2 to 19 years, the prevalence of obesity in 2011-2014 was 17.0% and extreme obesity was 5.8%. Between 1988-1994 and 2013-2014, the prevalence of obesity increased until 2003-2004 and then decreased in children aged 2 to 5 years, increased until 2007-2008 and then leveled off in children aged 6 to 11 years, and increased among adolescents aged 12 to 19 years.


The potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.
Herpes simplex virus type 1 (HSV-1) is a common human pathogen causing cold sores and even more serious diseases. It can establish a latent stage in sensory ganglia after primary epithelial infections, and reactivate in response to stress or sunlight. Previous studies have demonstrated that viral immediate-early protein ICP0 plays a key role in regulating the balance between lytic and latent infection. Recently, It has been determined that promyelocytic leukemia (PML) nuclear bodies (NBs), small nuclear sub-structures, contribute to the repression of HSV-1 infection in the absence of functional ICP0. In this review, we discuss the fundamentals of the interaction between ICP0 and PML NBs, suggesting a potential link between PML NBs and ICP0 in regulating lytic and latent infection of HSV-1.


Preatherosclerotic aortic lesions in cystic fibrosis.
Patients with cystic fibrosis have fat malabsorption, providing an experimental model for evaluation of the hypothesis that a low-fat intake may prevent atherosclerosis. We studied the frequency and extent of aortic precursor lesions (fatty streaks, early fibromusculoelastic lesions, late fibromusculoelastic lesions) found at autopsy in this disease as well as in other patients with debilitating disorders but with no apparent impairment of fat absorption. Fatty streaks were less common in the cystic fibrosis group, as were the late fibromusculoelastic lesions. There was no significant difference in the frequency, length, or thickness of the early fibromusculoelastic lesions. The findings suggest that fat may be responsible for progression but not initiation of the fibromusculoelastic precursor lesions, and support the concept that early restriction of dietary fat may prevent, delay, or otherwise modify atherosclerosis in the adult.


The combined supplementation of melatonin and salicylic acid effectively detoxifies arsenic toxicity by modulating phytochelatins and nitrogen metabolism in pepper plants.
The main objective of the study was to assess if joint application of melatonin (MT, 0.1 mM) and salicylic acid (SA 0.5 mM) could improve tolerance of pepper plants to arsenic (As) as sodium hydrogen arsenate heptahydrate (0.05 mM). The imposition of arsenic stress led to accumulation of As in roots and leaves, and increased contents of leaf proline, phytochelatins, malondialdehyde (MDA) and H2O2, but it reduced plant biomass, chlorophylls (Chl), PSII maximum efficiency (Fv/Fm) and leaf water potential. Melatonin and SA applied jointly or alone enhanced nitrogen metabolism by triggering the activities of glutamate synthase, glutamine synthetase, and nitrite reductases and nitrate. In comparison with a single treatment of MT or SA, the joint treatment of MT and SA had better impact on enhancing growth and key biological events and decreasing tissue As content. This clearly shows a cooperative function of both agents in enhancing tolerance to As-toxicity in pepper plants.


Initial Experience with the Nit-Occlud ASD-R: Short-Term Results.
We aim to assess the safety, feasibility and efficacy of the new Nit-Occlud ASD-R (NOASD-R) device. From 2014 to 2015, transcatheter closure of atrial septal defect (ASD) using the NOASD-R was performed in 30 consecutive patients. The standard deployment technique as the left upper pulmonary vein approach was used in 25 patients. Right upper pulmonary vein approach was required in five. The median age was 6 years (range 3.5-60 years), and median weight was 21.5 kg (14-79 kg). Implantation was successful in all patients. The median size of devices was 16 mm (12.0-26.0 mm). The mean device size/2D defect diameter ratio was 1.26 ± 0.09 (1.12-1.40). The mean device size/color flow diameter ratio was 1.07 ± 0.06 (range 1.0-1.22). Releasing problem was encountered in three patients. A device-related erosion on the day after the closure was observed in one patient. No further device-related complication (erosion, embolization or dislodgement of the device) was encountered in a median follow-up period of 10 months (range 2-14 months). Complete occlusion has occurred in all at follow-up. NOASD-R is a feasible and effective device for use in the transcatheter occlusion of moderate to large secundum ASDs in selected patients. The occurrence of the erosion on the right atrial roof may be due to the high localization of the device and the larger size of the right disk.


Regional differences in bioavailability of an opioid tetrapeptide in vivo in rats after administration to the respiratory tract.
TArPP (Tyr-D-Arg-Phe-Phe-NH(2)), 1-10 micromol/kg, was administered to anesthetized rats by nasal microinfusion, intratracheal microinfusion, intratracheal nebulization, aerosol inhalation, and i.v. bolus and infusion. Plasma concentrations of TArPP and its deamidated metabolite were determined by LC-MS-MS. Regional differences in bioavailability (F), first-pass metabolism, and absorption rate were found for TArPP after delivery to the respiratory tract. Absorption was rapid after both pulmonary and nasal administration (t(max) approximately 10-20 min). After nasal microinfusion, F was 52 +/- 9%. For all the pulmonary groups, F was higher (72-114%). First-pass metabolism of TArPP was lower in the lung than in the nasal cavity. It is evident that the pulmonary route is attractive for successful systemic delivery of small, hydrophilic and enzymatic susceptible peptides.


Calorie restriction delays cardiac senescence and improves cardiac function in obese diabetic rats.
The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac senescence in an animal model of diabetes and examine the signal transduction mechanisms for changes in cell survival as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into 2 groups: a group fed ad libitum (AL), and a group fed with CR (30% energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were divided into 3 groups: a high fat diet (HFD) group with a 22% increase in caloric intake, a CR group, and a group fed AL. At 40 weeks of age, the telomere length was significantly shorter in the heart tissue of HFD rats but was not altered by CR in experimental rats with or without CR, however, telomerase activity in both strains of CR rats was significantly elevated. Protein expression of IGF-1, Sirt 1 and phospho-FoxO1 was increased in both CR groups. Echocardiography showed that CR preserved LV diastolic function with a significantly shorter E-wave deceleration time and a greater E/A ratio compared with the AL groups. These findings suggest that CR protocol increased telomerase activity without changing of telomere length, enhanced autophagy and improved LV diastolic function in animal model of diabetes rats. It is finally suggested that those impacts may be important for the maintenance of normal cardiac function and for delayed cardiac aging.


Prognostic impact of systolic hypertension on asymptomatic patients with chronic severe aortic regurgitation and initially normal left ventricular performance at rest.
The influence of systolic hypertension (SH) on the natural history of chronic aortic regurgitation (AR) and the clinical effect of antihypertensive medication on patients who have hypertension and AR are incompletely defined. Therefore, we reviewed the clinical course of 80 unoperated patients who were entered prospectively into an assessment of natural history of AR and its predictors and were asymptomatic with normal left ventricular ejection fraction (LVEF) at rest at study entry; 30 of 80 patients had SH (systolic blood pressure >140 mm Hg); 20 of 80 patients (16 had SH) used antihypertensive drugs for the long term (not mandated by protocol). During an average 7.2-year event-free follow-up, 24 patients developed symptoms alone (n = 14), subnormal LVEF with or without symptoms (n = 8), or died suddenly (n = 2). SH tripled the average annual risk of cardiac events (8.47% vs 2.85%, p = 0.004). The effect of systolic blood pressure was independent of age, gender, diastolic blood pressure, LV diastolic dimension, fractional shortening, and LVEF at rest (p = 0.004 to <0.008). However, positive prognostic interactions existed between systolic blood pressure and pulse pressure (p <0.001), LVEF during exercise (p <0.001), change in LVEF from rest to exercise (p <0.001), and the contractility index (p <0.02). Among patients who had SH, antihypertensive therapy predicted increased event risk (average annual risk 15.46% vs 3.98%, p <0.02) and remained predictive when analysis was adjusted for potentially confounding subgroup variations at study entry (p <0.03, all models). In conclusion, SH portends poor clinical outcome in chronic severe AR. As a group, antihypertensive drugs do not mitigate outcome, although the effect of individual drugs is uncertain and at least some may be deleterious. The theoretically based practice of giving antihypertensive drugs to patients who have AR requires reexamination.


Reproductive responses of male Brandt's voles (Lasiopodomys brandtii) to 6-methoxybenzoxazolinone (6-MBOA) under short photoperiod.
The plant secondary metabolite 6-methoxybenzoxazolinone (6-MBOA) can stimulate and enhance animal reproduction. This compound has been successfully detected in Leymus chinensis, which is the main diet of Brandt's voles. The aim of this study was to investigate the effect of different 6-MBOA doses on the reproductive physiology of male Brandt's voles under a short photoperiod. The results showed that 6-MBOA administration increased relative testis weight, regardless of the dose, but it had little effect on the body mass. Low and middle doses of 6-MBOA increased the concentrations of luteinizing hormone and testosterone in the serum and the mRNA levels of StAR and CYP11a1 in the testes. However, 6-MBOA did not cause any significant increase in the mRNA levels of KiSS-1, GPR54, and GnRH compared to those in the control group. The mRNA level of KiSS-1 in the arcuate nucleus (ARC) was higher than that in the anteroventral periventricular nucleus (AVPV). Collectively, our results demonstrated that the number of KiSS-1-expressing neurons located in the ARC was the highest, and that 6-MBOA, which might modulate the reproductive activity along the hypothalamic-pituitary-gonadal axis, had a dose-dependent stimulatory effect on the reproductive activity of Brandt's voles under a short photoperiod. Our study provided insights into the mechanism of 6-MBOA action and the factors influencing the onset of reproduction in Brandt's voles.


Light-Sheet Fluorescence Microscopy: Chemical Clearing and Labeling Protocols for Ultramicroscopy.
Light-sheet microscopy is an effective technique in neuroscience, developmental biology, and cancer research for visualizing and analyzing cellular networks and whole organs in three dimensions. Because this technique requires specimens to be translucent they commonly have to be cleared before microscopy inspection. Here, we provide 3DISCO based protocols for preparing cleared samples of immuno-stained neural networks, lectin-labeled vascular networks, and Methoxy-X04 labeled beta-amyloid plaques in mice. 3DISCO utilizes the lipophilic solvents tetrahydrofuran (THF) and dibenzylether (DBE) for dehydration and successive clearing. Crucial steps for obtaining transparent tissues and preserving the fragile endogenous GFP are the transcardial perfusion, as well as the proper implementation of the 3DISCO clearing process using peroxide free chemicals. We further provide a protocol for resin embedding of 3DISCO cleared specimens that allows long term archiving of samples for years with virtually no loss in signal quality.


Population Based Paternity Rate and Partner Birth Outcomes Among Utah Men With Inflammatory Bowel Disease.
Crohn's disease (CD) and ulcerative colitis (UC) impact an estimated 350,000 reproductive age men in the United States. The reproductive consequences are largely unknown. The objective of this study was to evaluate the effects of CD and UC on reproductive outcomes. From the Utah Population Database, we identified a cohort of male patients with CD (1,245) and UC (1,368). Male-sibling controls were identified, and birth outcome data from offspring were obtained. Analyses for CD and UC were completed separately. Among UC patients (473) with at least one male sibling (1,020), 66% had offspring, which was not different compared with siblings (61%, P=0.16). Birth outcomes were not different between UC patients and male siblings: congenital malformations (UC 6% vs. 6%, P=0.99), perinatal complications (UC 35% vs. 31%, P=0.23), mean birth weight (UC 3,347 vs. 3,357 g, P=0.53), mean length of gestation (UC 39.0 vs. 39.1 weeks, P=0.54). Among CD patients (421) with at least one male sibling (833), 58% had offspring, which did not differ compared with siblings (57%, P=0.77). Similarly, there were no differences in partner birth outcomes: congenital malformations (CD 7% vs. 6%, P=0.27), perinatal complications (CD 35% vs. 32%, P=0.12), mean birth weight (CD 3,276 vs. 3,324 g, P=0.13), or mean length of gestation (38.8 vs. 39 weeks, P=0.24). We found no differences in paternity rate or female partner birth outcomes in Utah men with UC or CD compared with male-sibling controls. UC and CD do not appear to affect the reproductive outcomes of men in Utah.


The prevalence of computed tomography-defined leaflet thrombosis in intra- versus supra-annular transcatheter aortic valve prostheses.
Leaflet thrombosis (LT) defined by computed tomography (CT) following transcatheter aortic valve replacement (TAVR) has been shown to increase cerebrovascular events. The neo-sinus plays an important role in the development of LT. Intra-annular valves (IAV) have a larger neo-sinus when compared to supra-annular valves (SAV), and has been associated with larger thrombus burden. The prevalence of LT with IAV and SAV in a larger, diverse cohort is unknown. We performed a systematic review to assess the prevalence of LT in IAV versus SAV TAVR prostheses. Inclusion criteria were (1) reported CT-defined LT following TAVR, (2) comparison between LT and non-LT cohort, (3) separate registry/database, and (4) fully published status. A total of 2,013 citations were reviewed and 7 studies were included. Overall, 1,644 patients were included from 7 observational studies and the prevalence of LT following TAVR was 12.8%. The Portico valve system (IAV) had the highest prevalence of LT with 35.2%, followed by Symetis Acurate Neo (SAV) at 15.4% and the Lotus valve system (IAV) at 14.5%. LT occurred more frequently in IAV than SAV (13.5% vs. 7%, P = 0.02). Subanalysis of IAV versus SAV with the exclusion of the Portico valve was performed to ensure results were not influenced by this valve system and revealed IAV still had higher rates of LT (12.1% vs. 7%, P = 0.05). In summary, IAV prostheses appear to be associated with higher rates of LT when compared with SAV.


Synthesis and in vitro biological evaluation of new pyrimidines as glucagon-like peptide-1 receptor agonists.
The therapeutic success of peptide glucagon-like peptide-1 (GLP-1) receptor agonists for the treatment of type 2 diabetes mellitus has inspired discovery efforts aimed at developing orally available small-molecule GLP-1 receptor agonists. In this study, two series of new pyrimidine derivatives were designed and synthesized using an efficient route, and were evaluated in terms of GLP-1 receptor agonist activity. In the first series, novel pyrimidines substituted at positions 2 and 4 with groups varying in size and electronic properties were synthesized in a good yield (78-90%). In the second series, the designed pyrimidine templates included both urea and Schiff base linkers, and these compounds were successfully produced with yields of 77-84%. In vitro experiments with cultured cells showed that compounds 3a and 10a (10-15-10-9M) significantly increased insulin secretion compared to that of the control cells in both the absence and presence of 2.8mM glucose; compound 8b only demonstrated significance in the absence of glucose. These findings represent a valuable starting point for the design and discovery of small-molecule GLP-1 receptor agonists that can be administered orally.


Monitoring respiratory rates with a wearable system using a stretchable strain sensor during moderate exercise.
Respiratory rate, a sensitive indicator of respiratory status, is rarely measured during the field walking test. Our objective was to develop and validate a non-invasive, wearable monitoring system using stretchable strain sensors and an accompanying algorithm capable of providing real-time measurements of respiration during exercise. Twenty-four healthy volunteers wore stretchable sensors during a walking test protocol that included standing, sitting, walking, and walking with a stick. Sensors were placed on the ribcage and abdomen. The Bland-Altman method was used to assess the accuracy and precision of breath counts; total respiration time and inspiration time ratio were determined by custom algorithms and compared with measurements obtained with the standard flow sensor. The output signal from the stretchable sensor was highly synchronized with flow signals. The limits of agreement were within 3 breaths/min throughout the test protocol. Differences between sensors for total respiration time and inspiration time ratio were less than 14% and 26%, respectively. The agreement was maintained regardless of respiratory rate or volume. The wearable respiratory monitoring system yielded accurate and precise breath counts and total duration of respiratory cycle during moderate exercise in healthy young individuals, suggesting that it might be useful in clinical practice. Graphical abstract.


Regulation of cyclic nucleotide phosphodiesterase forms by serum and insulin in cultured fibroblasts.
A rapid reduction of cyclic nucleotide phosphodiesterase activity occurs after the replating of confluent cultures of BHK 21 c/13 fibroblasts into fresh medium. This reduction in activity depends on the density to which the cultures are reseeded and the concentration of serum in the medium. Enzyme activity in BHK cells is restored after 24 to 48 hours if cells are diluted into medium containing 10% fetal calf serum or 0.5% fetal calf serum supplemented with insulin (10(-6)M), but not into 0.5% serum alone. The restoration in enzyme activity is blocked by cycloheximide or Actinomycin D. When BHK cells become quiescent by maintanance in 0.5% serum conditions for 48 hours, a rapid (15--60 minutes) increase in cyclic AMP phosphodiesterase activity occurs when 10% serum is added to the cultures. Enzyme activity is increased even further after 24 to 48 hours in the 10% serum. Cycloheximide or Actinomycin D do not affect the rapid increase in enzyme activity in response to serum, but completely inhibit the long term increase. In contrast to serum, insulin (10(-8) to 10(-6)M) has no short term effect, but does increase enzyme activity after 24 to 48 hours to levels comparable to those seen with addition of 10% serum. As is the case with serum, this long term effect of insulin on enzyme activity is prevented by inhibitors of protein and RNA synthesis. Kinetic analyses of cyclic AMP phosphodiesterase activity in homogenates of quiescent BHK cells indicate the presence of only high Km (congruent to 20 muM) enzyme activity. Addition of serum or insulin to quiescent cells results in the appearance of apparent low Km enzyme activity in homogenates. Sucrose gradient analysis of BHK cells displays two forms of cyclic AMP phosphodiesterase enzyme activity: a 3--4 S form and 5--6 S form. In quiescent cells, the 5--6 S form greatly predominates relative to the 3--4 S form. Addition of serum to quiescent cells results in a rapid appearance of increased 3--4 S form enzyme activity. Insulin also increases the activity of this higher affinity 3--4 S enzyme form after 24 to 48 hours in culture. The functional significance of short and long term regulation of cyclic nucleotide phosphodiesterase(s) in cells is discussed.


Crack detection and classification of repaired concrete beams by acoustic emission monitoring.
In this study, acoustic emission (AE) monitoring was used to investigate the cracking behavior of normal concrete beams repaired with fiber-reinforced cementitious composites (FRCC). The investigated beams were strengthened at two locations: tension side and compression side of the beam. Two different fibers were used in FRCC strengthening material: steel fibers and polyvinyl alcohol fibers. One normal concrete beam and two fully cast FRCC beams were also tested for comparison. All beams were tested under four-point loading until failure. The investigation considered the variations in several AE parameters such as number of hits, cumulative signal strength, signal amplitude, peak frequency, absolute energy, and b-value analysis. In addition, rise time/amplitude analysis was successfully utilized in this study to classify the failure modes (flexural or shear/debonding failure between the repair layer and existing beam) for all beams. The impact of the fiber type, strengthening location, and sensor location on the aforementioned parameters was clearly highlighted. Varying the fiber type of the FRCC or changing the repair location of the beam seemed to have a significant impact on the resulting AE parameters. A good correlation was found in repaired and unrepaired beams between AE parameters and the progression of cracks beyond the first crack until failure. The results also indicated that the AE analysis carried out in this study led to the identification of the first crack in repaired and unrepaired beams.


Three-dimensional analysis of the vestibulo-ocular reflex and the ability to distinguish the direction of centripetal acceleration in humans during eccentric rotation with the right ear facing downwards.
This study was conducted to evaluate the linear vestibulo-ocular reflex (lVOR) mediated by the saccule, and to investigate the relationship between the lVOR and the ability to distinguish the direction of centripetal acceleration during centric and eccentric rotation. Participants sat on a chair in darkness, with the right ear facing downwards, either directly above the center of rotation, or with their nose out, nose in, right shoulder out, or left shoulder out against the center of rotation (eccentric rotation). Participants were given no information about the chair position, and were rotated sinusoidally at 0.1-0.7 Hz. Three-dimensional eye movements during rotation were analyzed. Participants were asked to describe the position of the chair after rotation. Correctly reporting the five possible chair positions requires recognition of the direction of centripetal acceleration. We analyzed the rate of correct answers to assess participants' ability to identify the direction of centripetal acceleration. lVOR mediated by the saccule was observed only at high rotational frequencies. The rate of correct answers was higher at high rotational frequencies than that at low rotational frequencies. These results indicate that high rotational frequency is important for both lVOR mediated by the saccule and distinguishing the direction of centripetal acceleration.


Hyaluronan oligosaccharides perturb lymphocyte slow rolling on brain vascular endothelial cells: implications for inflammatory demyelinating disease.
Inflammatory demyelinating diseases like multiple sclerosis are characterized by mononuclear cell infiltration into the central nervous system. The glycosaminoglycan hyaluronan and its receptor, CD44, are implicated in the initiation and progression of a mouse model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE). Digestion of hyaluronan tethered to brain vascular endothelial cells by a hyaluronidase blocks the slow rolling of lymphocytes along activated brain vascular endothelial cells and delays the onset of EAE. These effects could be due to the elimination of hyaluronan or the generation of hyaluronan digestion products that influence lymphocytes or endothelial cells. Here, we found that hyaluronan dodecasaccharides impaired activated lymphocyte slow rolling on brain vascular endothelial cells when applied to lymphocytes but not to the endothelial cells. The effects of hyaluronan dodecasaccharides on lymphocyte rolling were independent of CD44 and a receptor for degraded hyaluronan, Toll-like receptor-4. Subcutaneous injection of hyaluronan dodecasaccharides or tetrasaccharides delayed the onset of EAE in a manner similar to subcutaneous injection of hyaluronidase. Hyaluronan oligosaccharides can therefore act directly on lymphocytes to modulate the onset of inflammatory demyelinating disease.


Physiological changes in male and female pikeperch Sander lucioperca (Linnaeus, 1758) subjected to different photoperiods and handling stress during the reproductive season.
Pikeperch broodstocks were exposed to different photoperiods: constant light (24L:0D), constant darkness (0L:24D), and 12 h light, 12 h darkness (12L:12D), for 40 days. Half of the broodstocks of each photoperiod were exposed to handling stress at a specific time of the day. Results showed that cortisol and lactate did not reveal any significant difference. However, glucose levels in females increased in the stress-free darkness period in comparison with stressful darkness photoperiods (0L:24D-s). Red blood cells in males and white blood cells in females showed a significant difference under different photoperiod regimes. Both sexes showed no significant difference in the differential count of leukocytes under different photoperiods and handling stress. Constant photoperiods and handling stress affected the hematological parameters, particularly, the number of lymphocytes and neutrophils in females. Our findings revealed that due to a long-term exposure to stressors, pikeperch brooders become adapted to stressful conditions.


Small-scale structure of the geodynamo inferred from Oersted and Magsat satellite data.
The 'geodynamo' in the Earth's liquid outer core produces a magnetic field that dominates the large and medium length scales of the magnetic field observed at the Earth's surface. Here we use data from the currently operating Danish Oersted satellite, and from the US Magsat satellite that operated in 1979/80, to identify and interpret variations in the magnetic field over the past 20 years, down to length scales previously inaccessible. Projected down to the surface of the Earth's core, we found these variations to be small below the Pacific Ocean, and large at polar latitudes and in a region centred below southern Africa. The flow pattern at the surface of the core that we calculate to account for these changes is characterized by a westward flow concentrated in retrograde polar vortices and an asymmetric ring where prograde vortices are correlated with highs (and retrograde vortices with lows) in the historical (400-year average) magnetic field. This pattern is analogous to those seen in a large class of numerical dynamo simulations, except for its longitudinal asymmetry. If this asymmetric state was reached often in the past, it might account for several persistent patterns observed in the palaeomagnetic field. We postulate that it might also be a state in which the geodynamo operates before reversing.


Relevance of adverb distribution for the analysis of sentence representation in agrammatic patients.
In this study, it is shown that functional categories are present in agrammatic grammar. Specifically, the verb-adverb order is investigated in three agrammatic patients by means of a constituent ordering task. It is shown that when the verb is in a nonfinite form, it either precedes or follows the specifier-like adverb (both positions are correct), but when the verb is finite, the adverb always follows it (which is the only possible order). The conclusions are that (i) a functional category (namely Inflection), which is responsible for the relative order verb-adverb (of the relevant class), must exist in agrammatic grammar, and (ii) agrammatic aphasia cannot be described as a syntactic impairment involving basic sentence structure.


Intra-Session Reliability of Sprint Performance on a Non-Motorised Treadmill for Healthy Active Males and Females.
This study examined the intra-session reliability of sprint performance on a non-motorized treadmill amongst healthy, active male and female adults. One hundred and twenty participants (males n = 77; females n = 45) completed two familiarization sessions, followed by a third session that consisted of three trials (T1, T2, T3) of maximal sprints (4-s), interspersed by three minutes of recovery. Combining males and females exhibited moderate-to-excellent test-retest reliability (intra-class correlation coefficient, ICC), minimal measurement error (coefficient of variation, CV) and trivial differences between trials (effect size, ES) for speed, power, total work and acceleration (ICC = 0.82-0.98, CV = 1.31-8.45%, ES = 0.01-0.22). The measurement error was improved between comparisons of T1 vs. T2 (CV = 1.62-8.45%, ES = 0.12-0.22) to T2 vs. T3 (CV = 1.31-6.56%, ES = 0.01-0.07) and better for females (CV = 1.26-7.94%, ES = 0.001-0.26) than males (CV = 1.33-8.53%, ES = 0.06-0.31). The current study demonstrated moderate-to-excellent reliability and good-moderate measurement error during a 4-s sprint on a non-motorized treadmill. However, sex had a substantial impact with females exhibiting better values. Practitioners should employ at least two separate trials within a session, in addition to multiple familiarization sessions, to achieve reliable non-motorized treadmill sprint performances.


Randomized, prospective trial of leuprolide acetate and conventional superovulation in first cycles of in vitro fertilization and gamete intrafallopian transfer.
Ovarian stimulation after pituitary suppression with gonadotropin-releasing hormone agonists (GnRH-a) has been effective in women who have exhibited a poor response to conventional superovulation strategies. Their effectiveness in unselected women undergoing their first cycle of in vitro fertilization or gamete intrafallopian transfer, however, remains to be established. To address this question, we randomized 114 women to one of two treatment protocols. Protocol 1 consisted of 100 mg of clomiphene citrate on days 5 to 9, followed by 150 IU human menopausal gonadotropin (hMG) beginning on day 9. Protocol 2 consisted of daily GnRH-a beginning in the midluteal phase. Stimulation with 150 IU hMG commenced after pituitary down regulation and ovarian suppression were achieved. Human menopausal gonadotropin was continued in both protocols until adequate follicular development and serum estradiol concentrations were obtained. Protocol 2 patients reached egg retrieval significantly more often (87%) than Protocol 1 patients (61%), but the mean number of mature eggs retrieved and the pregnancy rate per retrieval were not significantly different between the two groups.


Congenital dyserythropoietic anaemia, types I and II: aberrant pattern of erythrocyte membrane proteins in CDA II, as revealed by two-dimensional polyacrylamide gel electrophoresis.
The protein composition of the erythrocyte membrane of two patients with CDA I and four patients with CDA II has been investigated by two-dimensional polyacrylamide gel electrophoresis. The two-dimensional patterns of erythrocyte membrane proteins of the patients with CDA were compared with the well-established pattern of normal individuals. No alterations could be detected in the patients with CDA I, but a striking deviation from normal was observed in all patients with CDA II. The major aberrations of the erythrocyte membrane proteins in CDA II are the lack of protein B1.1, the drastically increased concentration of protein B1.4 and the presence of a new component, C2'. These results are discussed in relation to the known morphological and immunological abnormalities of the erythrocyte membrane in CDA II.


Effects of substance P-(1-9) nonapeptide amide on inactivation of substance P in vitro.
The effects of substance P nonapeptide amide on inactivation of substance P by the guinea-pig ileum and urinary bladder preparations and of substance P hexapeptide amide, bradykinin and acetylcholine by the guinea-pig urinary bladder, have been investigated. Significant inhibition of inactivation of Substance P was found only in the urinary bladder. None of the other agents were significantly affected. These results suggest that the previously reported agonist effects of substance P nonapeptide may be due to inhibition of inactivation of SP in vivo and this effect is possibly specific.


Selective 5-HT1B agonists identify the 5-HT autoreceptor in lumbar spinal cord of rat.
The purpose of the present study was to characterize the 5-HT autoreceptor in the lumbar spinal cord of the rat. The effect of selective 5-HT1A and 5-HT1B agonists on K+-evoked release of [3H]5-HT and the binding of [3H]5-HT were examined. The 5-HT1B compounds, mCPP and quipazine were more potent than exogenous 5-HT at decreasing K+-evoked release of [3H]5-HT in slices of spinal cord. The pEC40 values of 5-HT agonists tested, determined from release assays, significantly correlated with the relative affinities (pKD's) of these compounds for the binding of [3H]5-HT to the 5-HT1B receptor subtype in the presence of 2 microM 8-OHDPAT, as determined from radioligand binding studies (r = 0.98, P = 0.003). Conversely, the potencies of the 5-HT1A agonists 5-MeODMT and 8-OHDPAT, at the 5-HT autoreceptor, were negatively correlated (r = -0.77, P less than 0.10) with their potencies at displacing [3H]5-HT from the 5-HT1A subsite (binding of [3H]5-HT in the presence of 1 microM mCPP). Thus, the 5-HT autoreceptor in spinal cord appears to bear a significant pharmacological similarity to the 5-HT1B binding site. Further testing of the present results requires the development of new 5-HT1 agonists which are selective (1000-fold difference) for the 5-HT1A and 5-HT1B subsites.


Nitric Oxide Resistance, Induced in the Myocardium by Diabetes, Is Circumvented by the Nitric Oxide Redox Sibling, Nitroxyl.
Aim: Impairment of tissue responsiveness to exogenous and endogenous nitric oxide (NO•), known as NO• resistance, occurs in many cardiovascular disease states, prominently in diabetes and especially in the presence of marked hyperglycemia. In this study, we sought to determine in moderate and severe diabetes (i) whether NO• resistance also occurs in the myocardium, and (ii) whether the NO• redox sibling nitroxyl (HNO) circumvents this. Results: The spectrum of acute NO• effects (induced by diethylamine-NONOate), including vasodilation, and enhanced myocardial contraction and relaxation were impaired by moderately diabetic rats ([blood glucose] ∼20 mM). In contrast, acute HNO effects (induced by isopropylamine-NONOate) were preserved even in more severe diabetes ([blood glucose] >28 mM). Intriguingly, the positive inotropic effects of HNO were significantly enhanced in diabetic rat hearts. Further, progressive attenuation of soluble guanylyl cyclase (sGC) contribution to myocardial NO• responses occurred with increasing severity of diabetes. Nevertheless, activation of sGC by HNO remained intact in the myocardium. Innovation: Diabetes is associated with marked attenuation of vascular and myocardial effects of NO and NO donors, and this NO• resistance is circumvented by HNO, suggesting potential therapeutic utility for HNO donors in cardiovascular emergencies in diabetics. Conclusion: These results provide the first evidence that NO• resistance occurs in diabetic hearts, and that HNO largely circumvents this problem. Further, the positive inotropic and lusitropic effects of HNO are enhanced in a severely diabetic myocardium, a finding that warrants further mechanistic interrogation. The results support a potential role for therapeutic HNO administration in acute treatment of ischemia and/or heart failure in diabetics.


A novel approach for 3D reconstruction of mice full-grown oocytes by time-of-flight secondary ion mass spectrometry.
Currently two techniques exist for 3D reconstruction of biological samples by time-of-flight secondary ion mass spectrometry (ToF-SIMS). The first, based on microtomy and combining of successive section images, is successfully applied for tissues, while the second, based on sputter depth profiling, is widely used for cells. In the present work, we report the first successful adaptation of sectioning technique for ToF-SIMS 3D imaging of a single cell-fully grown mouse germinal vesicle (GV) oocyte. In addition, microtomy was combined with sputter depth profiling of individual flat sections for three-dimensional reconstruction of intracellular organelles. GV oocyte sectioning allowed us to obtain molecule-specific 3D maps free from artifacts associated with surface topography and uneven etching depth. Sputter depth profiling of individual flat slices revealed fine structure of specific organelles inside the oocyte. Different oocyte organelles (cytoplasm, germinal vesicle, membranes, cumulus cells) were presented on the ion images. Atypical nucleoli referred to as "nucleolus-like body" (NLB) was detected inside the germinal vesicle in PO3- and CN- ions generated by nucleic acids and proteins respectively. Significant difference in PO3- intensity in the NLB central area and NLB border was found. This difference appears as a bright halo around the center area. The NLB size calculated for PO3- and CN- ion images is 12.9 ± 0.2 μm and 11.9 ± 0.2 μm respectively, which suggests that bright halo of PO3- ions is a chromatin compaction on the NLB surface. Areas of approximately 1.0-2.5 μm size inside nucleoplasm with increased PO3- and CN- signal were registered in germinal vesicle. Observed compartments have different sizes and shapes, and they are likely attributed to chromocenters or chromosomes.


Predicting the retention of first-time donors using an extended Theory of Planned Behavior.
Donor retention is vital to blood collection agencies. Past research has highlighted the importance of early career behavior for long-term donor retention, yet research investigating the determinants of early donor behavior is scarce. Using an extended Theory of Planned Behavior (TPB), this study sought to identify the predictors of first-time blood donors' early career retention. First-time donors (n=256) completed three surveys on blood donation. The standard TPB predictors and self-identity as a donor were assessed 3 weeks (Time 1) and at 4 months (Time 2) after an initial donation. Path analyses examined the utility of the extended TPB to predict redonation at 4 and 8 months after initial donation. The extended TPB provided a good fit to the data. Post-Time 1 and 2 behavior was consistently predicted by intention to redonate. Further, intention was predicted by attitudes, perceived control, and self-identity (Times 1 and 2). Donors' intentions to redonate at Time 1 were the strongest predictor of intention to donate at Time 2, while donors' behavior at Time 1 strengthened self-identity as a blood donor at Time 2. An extended TPB framework proved efficacious in revealing the determinants of first-time donor retention in an initial 8-month period. The results suggest that collection agencies should intervene to bolster donors' attitudes, perceived control, and identity as a donor during this crucial post-first donation period.


Cervical cancer screening uptake and determinant factors among women in Ambo town, Western Oromia, Ethiopia: Community-based cross-sectional study.
Cervical cancer is the second most common cancer and the leading cause of cancer-related death in Ethiopian women. About 77.6% of women died of 6294 new cases reported in 2019. Early screening for cervical cancer has substantially reduced morbidity and mortality attributed to it. In Ethiopia, most of the women visit the health facilities at the late stage of the disease in which the offered intervention is not promising. Therefore, we aimed to assess the level of cervical cancer screening uptake and its determinant among women of Ambo town, Ethiopia. Community-based cross-sectional study was conducted among 422 women aged 20-65 years. An interviewer-administered questionnaire was used to collect the data. Data were analyzed using SPSS version 25. Estimates were presented using an odds ratio (OR) with 95% CI. Statistical significance was declared at a p value of <0.05. In the present study, 392 women were participated giving a response rate of 93%. Only 8.7% (34) of the study participants were received cervical cancer screening in their lifetime. Being in the age group of 30-39 years (AOR = 3.2, 95% CI: 1.22, 8.36), having cervical cancer-related discussions with a healthcare provider (AOR = 3.5; 95% CI: 1.17, 10.7), and knowing the availability of cervical cancer screening service (AOR = 2.8; 95% CI: 1.03, 7.87) were significantly associated with uptake of cervical cancer screening. In this study, cervical cancer screening uptake is very low. Our study identifies clues for determinants of cervical cancer screening uptake. Thus, further studies using a better study design might be helpful to explore determinants of low utilization of CC screening services and suggest an appropriate intervention that increases CC screening uptake in the study area.


[How have Japanese primary care physicians carried out vaccinations against COVID-19? : Attempts at making the non-scalable 'scalable'].
Vaccine rollouts have been underway to combat the COVID-19 pandemic globally. Based on ongoing interviews with ten primary care physicians 'in the field', this paper elucidates how in practice the vaccinations were carried out in Japan in 2021 from a cultural anthropological perspective. We examine what the primary care physicians did to prepare for the rollouts, what problems they faced, and how they responded to these problems. Large-scale vaccination projects are supposed to proceed smoothly and quickly, or to have what Anna Tsing calls 'scalability'. In practice, however, they required a variety of tasks for coordination, information sharing, and promotion. Despite feeling stressed by the lack of information and exhausted by the work overload, the primary care physicians carried out the vaccinations as an important service to their patients and communities. The findings of this paper will provide valuable materials for improving future vaccine rollouts.


Intercontinental collaborative experience with abdominal, retroperitoneal and pelvic schwannomas.
Schwannomas are rare tumours that pose a significant management challenge in the abdomen, retroperitoneum and pelvis. No data are available to inform management strategy. A collaborative international cohort study, across specialist sarcoma units, was conducted to include adults presenting between 2000 and 2017 with histopathologically confirmed schwannomas within the abdomen, retroperitoneum or pelvis. Of 485 patients across 12 centres, 38 (7·8 per cent) were discharged without follow-up, 199 (41·0 per cent) underwent early resection and 248 (51·1 per cent) had radiological monitoring. Of these 248 patients, 96 (38·7 per cent) eventually had surgery, giving an overall resection rate of 60·8 per cent (295 of 485). At baseline, median tumour volume was 90·1 (i.q.r. 26·5-262·0) cm3 . The estimated growth rate was 10·5 (95 per cent c.i. 9·4 to 11·6) per cent per year, and was consistent in the short term (within 2 years of diagnosis) and long term (beyond 2 years) (ρ = 0·405, P = 0·021). A decision to operate was more common in symptomatic patients (P < 0·001) and for rapidly growing tumours (growth rate more than 20 per cent per year) (P = 0·025). R0/R1 resection was achieved in 91·6 per cent of patients (263 of 287). Kaplan-Meier long-term recurrence rates after R0/R1 resection were 2·3 and 6·7 per cent at 3 and 5 years respectively. Specific recommendations include: indications for early surgery, prediction of growth from radiological monitoring, promotion of selective submacroscopic resection and cessation of postoperative imaging surveillance.


Stimulation of spermatogenesis with recombinant human follicle-stimulating hormone (follitropin alfa; GONAL-f): long-term treatment in azoospermic men with hypogonadotropic hypogonadism.
To demonstrate the efficacy and safety of follitropin alfa administered with hCG on spermatogenesis in adult male hypogonadotropic hypogonadism (HH) patients. Phase III, multicenter, open-label, noncomparative. Seven US medical centers. A total of 36 adult males with severe HH. A total of 1,000 U hCG on alternate days for 3 to 6 months, with dose adjustments after 2 months, if necessary, to normalize T levels, followed by follitropin alfa 150 U and hCG on the same alternate days for 18 months, with dose adjustments as necessary. Proportion of patients with sperm density > or =1.5 x 10(6)/mL. Pubertal advancement and long-term safety and tolerability were also evaluated. In total, 22 of 29 patients (75.9%) who received > or =1 dose of follitropin alfa and 20 of 25 patients (80%) who completed 18 months of hCG + follitropin alfa treatments achieved a sperm concentration > or =1.5 x 10(6)/mL. A sperm concentration >20 x 10(6)/mL was achieved by 8 of 29 men (27.5%). Median sperm concentration at 18 months was 5.2 x 10(6)/mL. Pubertal development continued during the study, and testis volumes increased. Five clinical pregnancies were achieved. Acne (52% of patients) was the most common side effect, and gynecomastia was reported in 10% of patients. Long-term treatment of azoospermic HH men using follitropin alfa and hCG is effective for stimulating spermatogenesis and is well-tolerated.


Lean Strategies in the Operating Room.
Lean strategies can be readily applied to health care in general and operating rooms specifically. The emphasis is on the patient as the customer, respect and engagement of all providers, and leadership from management. The strategy of lean is to use continuous improvement to eliminate waste from the care process, leaving only value-added activities. This iterative process progressively adds the steps of identifying the 7 common forms of waste (transportation, inventory, motion, waiting, overproduction, overprocessing, and defects), 5S (sort, simplify, sweep, standardize, sustain), visual controls, just-in-time processing, level-loaded work, and built-in quality to achieve the highest quality of patient care.


Induction of SCE by DNA cross-links in human fibroblasts exposed to 8-MOP and UVA irradiation.
To study the SCE-inducing effect of psoralen cross-links in the DNA of normal, human fibroblasts, cell cultures were exposed to PUVA (0.2-1 micrograms of 8-MOP per ml, followed by UVA irradiation at 0.04 J/cm2) and carefully washed to remove non-covalently bound psoralen. Some cell cultures were then given a second dose of UVA (1.1 J/cm2), either immediately after PUVA or 1-3 days later. By this type of treatment, cells with different proportions of DNA cross-links are obtained. The initial PUVA treatment will mainly give rise to psoralen monoadducts and only few cross-links in the DNA, and the second UVA irradiation will convert a number of the psoralen monoadducts into cross-links. SCE analysis was carried out on cells grown for 2 cell cycles in the presence of BrdUrd (10 mumoles/1). PUVA treatment alone did not induce an increase in the SCE frequency, whereas a clear increase of SCE was observed in cells treated with PUVA immediately followed by the second UVA dose. This PUVA + UVA-induced increase of SCE was also observed after incubation of the cells for 3 days at confluency, as well as when a period of 3 days at confluency was introduced between the PUVA exposure and the second irradiation with UVA. In contrast, the SCE frequency gradually returned to the normal level when PUVA + UVA-treated cells were allowed to proliferate for 1-2 days, or when a proliferation period of 2-4 days was introduced between the PUVA exposure and the second irradiation. Because the SCE frequency was not changed by the initial PUVA treatment but markedly increased by PUVA + UVA, it is concluded that psoralen cross-links are considerably more effective at inducing SCE than monoadducts. The results also indicate that SCE-inducing PUVA damage is removed very slowly if at all from the DNA of confluent cells. In contrast, repair functions that eliminate cross-links as well as monoadducts seem to become activated during cell proliferation.


Stevia rebaudiana leaves fermented by Lactobacillus plantarum exhibit resistance to microorganisms and cancer cell lines in vitro: A potential sausage preservative.
Natural preservatives are causing a rethinking of current preservation means. As a sweetener resource, exploitation of Stevia rebaudiana leaves (SRLs) is still restricted due to human conventional cognition. Herein, Lactobacillus plantarum fermented SRLs containing diverse free secondary metabolites derived from microbial deglycosylation and bioenzymatic decomposition were investigated. The apparent resistance to typical foodborne bacteria (Escherichia coli, Staphylococcus aureus, Bacillus subtilis, Pseudomoas aeruginosa, Bacillus amyloliquefaciens) by fermented SRLs and their extracts were validated. The metabolite diversity and in-depth organic solvent extraction gave the possibilities for better antimicrobial actions, anti-HepG2/SGC-7901 cells in vitro in contrast with aqueous extract of unfermented SRLs. Crucially, compound identification and attribution revealed that fermentation products may be maximally contributing to antimicrobial and antitumor mechanisms rather than intrinsic plant and/or microbial components. Additionally, pork sausage models with 15 g/kg ethyl acetate extract as a preservative candidate presented preferred storage characteristics (21 days and 37 °C) compared to those without ethyl acetate extract, e.g. the minimal total plate count (3.86 ± 0.27 log CFU/g), peroxsignide value (8.02 ± 0.92 meq/kg), and acid value (2.01 ± 0.04 (KOH)/(mg/g)).


Scar extent evaluated by late gadolinium enhancement CMR: a powerful predictor of long term appropriate ICD therapy in patients with coronary artery disease.
Coronary artery disease (CAD) patients are at risk for life-threatening ventricular arrhythmias (VA) related to scar tissue. Late gadolinium enhancement cardiovascular magnetic resonance (LGE-CMR) can accurately identify myocardial scar extent. It has been shown that scar extent, particularly scar transmurality, percent scar and scar mass, are associated with the occurrence of appropriate implantable cardioverter-defibrillator (ICD) therapy. However, quantification of transmurality extent has never been studied. The purpose of our study was to evaluate whether different methods quantifying scar transmurality, percent scar and scar mass (assessed with LGE-CMR) can predict appropriate ICD therapy in CAD patients with a long term follow-up period. We enrolled retrospectively 66 patients with chronic CAD referred for primary or secondary preventive ICD implantation and LGE-CMR before ICD implantation. Using LGE-CMR, scar extent was assessed by measuring scar mass, percent scar and transmural scar extent using four different methods. The median follow-up duration was 41.5 months (interquartile range 22-52). The endpoint was the occurrence of appropriate device therapy and occurred in 14 patients. Pre-ICD revascularization and transmural scar extent were significantly associated with the study endpoint but the latter was especially highly dependent on the method used. Patients with appropriate device therapy had also larger scar mass (29.6 ± 14.5 g vs 17.1 ± 8.8 g, p = 0.004), and larger percent scar (15.1 ± 8.2% vs 9.9 ± 5.6%, p = 0.03) than patients without appropriate device therapy. In multivariate analysis, scar extent variables remained significantly associated with the study end-point. In this study of CAD patients implanted for primary or secondary preventive ICD, pre-ICD revascularization and scar extent studied by LGE-CMR were significantly associated with appropriate device therapy and can identify a subgroup of CAD patients with an increased risk of life-threatening VA. Depending of the method used, transmural scar extent may vary significantly and needs further studies to obtain a validated and consensual study method.


[Occipital encephalocele and associated anomalies including bilateral eyelid coloboma, bilateral cleft lip/cleft palate, amniotic bands on the right leg with absence of toes on right and left feet at the University Clinics of Graben Butembo 2021: a case report].
Encephalocele is a malformation due to a defect in the closure of the neural tube causing herniation of brain tissue and/or meninges through this congenital skull defect. The size of encephalocele varies from a few centimeters to a huge mass called "giant encephalocele". Content usually consists of degenerative neural tissue, meninges and a cystic part. We here report the case of a 4-month-old infant, born of non-consanguineous parents, who was referred with congenital occipital mass. Upon arrival at our clinic, clinical examination revealed a weight of 3500g, a head circumference of 33 cm, with a non-bulging anterior fontanelle. She presented with a huge renitent occipital mass measuring 43X25cm, with a height of 15cm was found. absence of both eyelids, bilateral lip and palate fissures; a constriction ring on the right leg, absence of toes on the right and left feet. A diagnosis of an amniotic band syndrome was made, with as components: occipital encephalocele associated with a bilateral palpebral coloboma, a bilateral cleft lip and palate, and amniotic bands on the right leg, and amputation of the toes of the right and left feet.


Off-pump long onlay bypass grafting using left internal mammary artery for diffusely diseased coronary artery.
Surgical treatment of a diffusely diseased coronary artery has been considered a relative contraindication for off-pump coronary artery bypass grafting. To our knowledge, long onlay-patch grafting with off-pump coronary artery bypass grafting has not been described. Two sets of Octopus 3 tissue stabilizers were placed longitudinally along the target coronary artery. This allowed us to perform surgical angioplasty and bypass grafting without cardiopulmonary bypass support (double Octopus technique). We report our early experience with off-pump long onlay bypass grafting in patients with a diffusely diseased coronary artery using double Octopus tissue stabilizers. Diffusely diseased coronary artery; off-pump coronary artery bypass grafting; coronary artery reconstruction; coronary artery bypass grafting; onlay patch anastomosis


Four V-Y islanded flap reconstruction of full thickness defect of chin and labial sulcus.
Few techniques are described specifically for reconstruction of full thickness defects involving the chin. We present a new method of reconstruction of a large full thickness defect over the chin and lower labial sulcus with four V-Y island flaps. Two of these were mental neurovascular island flaps. The other two were islanded musculomucosal flap. The mental flaps, previously described for reconstruction of the lower lip, were cosmetically more suitable for reconstruction of tissue defects of the chin. The principle of covering the tissue defect of chin with local tissue to provide good matching and function is achieved.


Plant-based diet indices and lipoprotein particle subclass profiles: A cross-sectional analysis of middle- to older-aged adults.
Plant-based diets (PBDs) are associated with favourable lipid profiles and cardiometabolic outcomes. However, limited data regarding PBD indices (PDIs) and lipoprotein subclasses exist. We examined overall PDI, healthful PDI (hPDI) and unhealthful PDI (uPDI) associations with lipid and lipoprotein profiles. This cross-sectional analysis includes 1,986 middle- to older-aged adults from the Mitchelstown Cohort. The PDI, hPDI and uPDI scores were calculated from validated food frequency questionnaires. Higher PDI, hPDI and uPDI scores indicate a more PBD, healthful PBD and unhealthful PBD, respectively. Lipoprotein particle size and subclass concentrations were measured using nuclear magnetic resonance spectroscopy. Relationships between PDIs and lipid and lipoprotein profiles were examined via correlation and regression analyses adjusted for covariates. In fully adjusted regression analyses, higher PDI scores were associated with lower high-density lipoprotein (HDL) cholesterol concentrations and more triglyceride-rich lipoprotein and small very low-density lipoprotein (VLDL) particles. Higher hPDI scores were negatively associated with non-HDL cholesterol concentrations, large VLDL and small HDL particles, the Lipoprotein Insulin Resistance Index (LP-IR) score and VLDL particle size. Higher uPDI scores were associated with lower HDL cholesterol and greater triglyceride concentrations and more medium and large VLDL, total LDL, small LDL and total non-HDL particles, less large LDL and large HDL particles, a greater LP-IR score, greater VLDL particle size and smaller LDL and HDL particle size. This study provides novel evidence regarding associations between PBD quality and lipoprotein subclasses. A more unhealthful PBD was robustly associated with a more pro-atherogenic lipoprotein profile.


The interplay between gastrocnemius medialis force-length and force-velocity potentials, cumulative EMG activity and energy cost at speeds above and below the walk to run transition speed.
What is the central question of the study? Are the changes in force potentials (at the muscle level) related with metabolic changes at speeds above and below the walk-to-run transition? What is the main finding and its importance? The force-length and force-velocity potentials of gastrocnemius medialis during human walking decrease as a function of speed; this decrease is associated with an increase in cumulative EMG activity and in the energy cost of locomotion. Switching from fast walking to running is associated to an increase in the force potentials, supporting the idea that the 'metabolic trigger' that determines the transition from walking to running is ultimately driven by a reduction of the muscle's contractile capacity. The aim of this study was to investigate the interplay between the force-length (F-L) and force-velocity (F-V) potentials of gastrocnemius medialis (GM) muscle fascicles, the cumulative muscle activity per distance travelled (CMAPD) of the lower limb muscles (GM, vastus lateralis, biceps femori, tibialis anterior) and net energy cost (Cnet ) during walking and running at speeds above and below the walk-to-run transition speed (walking: 2-8 km h-1 ; running: 6-10 km h-1 ). A strong association was observed between Cnet and CMAPD: both changed significantly with walking speed but were unaffected by speed in running. The F-L and F-V potentials decreased with speed in both gaits and, at 6-8 km h-1 , were significantly larger in running. At low to moderate walking speeds (2-6 km h-1 ), the changes in GM force potentials were not associated with substantial changes in CMAPD (and Cnet ), whereas at walking speeds of 7-8 km h-1 , even small changes in force potentials were associated with steep increases in CMAPD (and Cnet ). These data suggest that: (i) the walk to run transition could be explained by an abrupt increase in Cnet driven by an upregulation of the EMG activity (e.g., in CMAPD) at sustained walking speeds (>7 km h-1 ) and (ii) the reduction in the muscle's ability to produce force (e.g., in the F-L and F-V potentials) contributes to the increase in CMAPD (and Cnet ). Switching to running allows regaining of high force potentials, thus limiting the increase in CMAPD (and Cnet ) that would otherwise occur to sustain the increase in locomotion speed.


Vagus nerve-dependent effects of fluoxetine on anxiety- and depression-like behaviors in mice.
The vagus nerve is a major pathway in the body that is responsible for regulating the activity of the parasympathetic nervous system, which plays an important role in mood disorders including anxiety and depression. Fluoxetine, also known as Prozac, is widely used to treat depression. Nevertheless, there are few studies on the vagus nerve-mediated action of fluoxetine. In this study, we aimed to investigate the vagus nerve-dependent actions of fluoxetine in mice with restraint stress-induced or antibiotics-induced anxiety- and depression-like behaviors. Compared to sham operation, vagotomy alone did not exhibit significant effects on behavioral changes and serotonin-related biomarkers in mice not exposed to stress, antibiotics, or fluoxetine. Oral administration of fluoxetine significantly alleviated anxiety- and depression-like behaviors. However, celiac vagotomy significantly attenuated the anti-depressive effects of fluoxetine. The vagotomy also inhibited the effect of fluoxetine to attenuate restraint stress- or cefaclor-induced reduction in serotonin levels and Htr1a mRNA expression in the hippocampus. These findings suggest that the vagus nerve may regulate the efficacy of fluoxetine for depression.


Human urinary bladder carcinomas express adenovirus attachment and internalization receptors.
The use of adenoviral vectors as potent gene delivery systems requires expression of the Coxsackievirus/adenovirus receptor (CVADR) on the target cell surface. This receptor is important for virus attachment to the cell surface. For effective internalization of the vector into the target cell the integrins alpha(v)beta(3) and/or alpha(v)beta(5) are needed. Since there have been reports of loss of CVADR in bladder cancer cell lines, we wanted to investigate the expression of this receptor in bladder carcinoma biopsies. Surgical biopsies, as well as five human bladder cancer cell lines, were analyzed for expression of CVADR, the integrins alpha(v)beta(3) and alpha(v)beta(5) and MHC class I. Further, we studied the ability to transduce these cell lines using adenoviral vectors. Immunohistochemistry revealed that all biopsies (27/27) were positive for CVADR. Some variation in expression was evident, and superficially growing tumors stained more strongly than invasive ones. Most human tumors expressed the integrin alpha(v)beta(5) (14/24), whereas integrin alpha(v)beta(3) was less frequently seen (3/20). The established cell lines were efficiently transduced with adenoviral vectors, and transduction could be reduced with anti-CVADR antibodies. The abundance of appropriate viral receptors on tumor biopsy cells is a further argument for using adenoviral vectors in gene therapy of bladder cancer.


Clinical profiles and outcomes in patients with ulcerative colitis receiving standard and higher-than-standard doses of vedolizumab: findings from a real-world study in Europe.
Vedolizumab is an antibody targeting α4β7 integrin used in the treatment of ulcerative colitis (UC). Patients are commonly prescribed higher-than-standard doses if treatment response is inadequate, but little is known about the drivers and impact of increased dosing. Our objective was to use real-world data to describe vedolizumab dosages in current clinical practice, patient characteristics, physicians' reasons for prescribing vedolizumab, and physician treatment satisfaction. Data were derived from the Adelphi Real World UC vedolizumab Chart Review, a cross-sectional survey of gastroenterologists and their UC patients, conducted in France, Germany, Italy, Spain, and the United Kingdom between December 2022 and March 2023. Gastroenterologists provided data on patient demographics, clinical characteristics, treatment and vedolizumab dosage history, reasons for dose choice, and treatment satisfaction. Data were returned on 448 patients by 112 gastroenterologists. Overall, 83.5% of patients were on a standard vedolizumab dose and 10.3% were on a higher-than-standard dose. The worsening of symptoms was the most cited reason for higher doses. Most reported symptoms at survey were fatigue, abdominal distention or pain, diarrhea, and bowel urgency, with the latter particularly in higher-than-standard dose patients. Patients on higher-than-standard dose had high rates of mild (37.0%) or moderate (26.1%) disease, and low rates of remission (33.8%). Physicians were dissatisfied with treatment control for 2.7% of standard and 26.1% of higher-than-standard dose patients. Over 10% of patients were receiving a higher-than-standard dose of vedolizumab, but despite this were found to have suboptimal clinical outcomes and low physician satisfaction.


Paired exchange kidney transplantation experience of Turkey.
Paired-exchange kidney transplantation (PKD) has gained in importance because of the difficulty to obtain suitable organs. The aim of this study was to compare the biochemical and clinical parameters of PKT with those of living-related kidney transplantation (LD). We compared 272 PKD performed in 3 transplant centers with 1885 LD. The 2 groups were compared for graft and patient survivals, rejection episodes, serum creatinine levels, and other biochemical parameters. The median human leukocyte antigen, mismatch was similar: PKD, 4 (95% confidence interval [CI], 3-4) and LD; 3 (95% CI, 3-4; P = .1292). The mean creatinine level among the PKT group of 1.07 ± .37 was lower then the LD group 1.17 ± .56 (P = .0043), but after the second year it was lower in the LD group (1.39 ± 0.61 and 1.16 ± 0.43; P < .0001). The rates of patient death (PKT, 3.31% vs LD 3.58; P = .9603), graft loss (2.74% vs 2.71%; P = .8647) and acute rejection episodes (19.48% vs 19.36%; P = 0.9719), were similar between the 2 groups. Paired donation expands the living donor pool and decreases the number of waiting list patients. It is cost effective according to ABO incompetible transplantation.


An assay for the detection of superoxide dismutase in individual Escherichia coli colonies.
A method for detecting superoxide dismutase activity in individual colonies of Escherichia coli was developed. The assay involves the lysis of individual cells in colonies on filter papers by a series of lysozyme, chloroform, and freeze-thaw treatments. Filters are placed on agar plates to allow diffusion of cellular enzymes into a solid matrix. A nitroblue tetrazolium overlay is applied to detect superoxide dismutase activity. Colonies possessing activity produce achromatic zones against a dark Formazan background. The assay can detect the presence of superoxide dismutase and the relative amount of enzyme as well. This assay provides a method for screening a population of cells for mutants deficient in or overproducing superoxide dismutase.