Assessing the impact of intrafraction motion correction on PTV margins and target and OAR dosimetry for single-fraction free-breathing lung stereotactic body radiation therapy.
The objective of this research is to investigate intrafraction motion correction on planning target volume (PTV) margin requirements and target and organ-at-risk (OAR) dosimetry in single-fraction lung stereotactic body radiation therapy (SBRT). Sixteen patients (15 with upper lobe lesions, 1 with a middle lobe lesion) were treated with single-fraction lung SBRT. Cone-beam computed tomography (CBCT) images were acquired before the treatment, between the arcs, and after the delivery of the treatment fraction. Shifts from the reference images were recorded in anterior-posterior (AP), superior-inferior (SI), and lateral (LAT) dimensions. The deviations from the reference image were calculated for 3 clinical scenarios: not applying intratreatment couch shifts and not correcting for pretreatment deviations < 3 mm ( scenario 1), not applying intratreatment couch shifts and correcting for pretreatment deviations < 3 mm ( scenario 2), and applying all pre- and intratreatment couch shifts (scenario 3). PTV margins were determined using the van Herk formalism for each scenario and maximum and average deviations were assessed. The clinical scenarios were modelled in the treatment planning system based on each patient dataset to assess target and OAR dosimetry. Calculated lower-bound PTV margins in the AP, SI, and LAT dimensions were [4.6, 3.5, 2.3] mm in scenario 1, [4.6, 2.4, 2.2] mm in scenario 2, and [1.7, 1.2, 1.0] mm in scenario 3. The margins are lower bounds because they do not include contributions from nonmotion related errors. Average and maximum intrafraction deviations were larger in the AP dimension compared to the SI and LAT dimensions for all scenarios. A unidimensional movement (several mm) in the negative AP dimension was observed in clinical scenarios 1 and 2 but not scenario 3. Average intrafraction deviation vectors were 1.2, 1.1, and 0.3 mm for scenarios 1, 2, and 3, respectively. Modelled clinical scenarios revealed that using scenario 3 yields significantly fewer treatment plan objective failures compared to scenarios 1 and 2 using a Wilcoxon signed-rank test. Intratreatment motion correction between each arc may enable reductions PTV margin requirements. It may also compensate for unidimensional negative AP movement, and improve target and OAR dosimetry.


Cardiac involvement in patients recovering from Delta Variant of COVID-19: a prospective multi-parametric MRI study.
The cardiac injury and sequelae of Delta Variant of coronavirus disease 2019 (COVID-19) remain unknown. This study aimed to evaluate the presence of cardiac involvement in patients recovering from Delta Variant of COVID-19 based on multi-parametric cardiac magnetic resonance imaging (MRI). We prospectively assessed patients recovering from Delta Variant of COVID-19 using multi-parametric cardiac magnetic resonance imaging (MRI) between June 2021 and July 2021. Comparison was made with 25 healthy controls. Forty-four patients (median age 51 years, 28 women) recovering from Delta Variant were recruited and had a median time of 35 days between diagnosis and cardiac MRI. There were no patients with chest pain (0/44, 0%) and high sensitivity cardiac troponin T troponin elevation (median levels 2.20 pg/mL, IQR levels 0.85-4.40 pg/mL). Regarding the cardiac imaging findings, a total of 14 (32%) patients presented cardiac tissue feature abnormalities, and a total of 9 (20%) patients had a myocarditis-like injury based on cardiac MRI 2018 Lake Louise criteria. When we further assessed the T1 and T2 mapping values for of patients' individual, abnormal raised global native T1, T2, and extracellular volume were seen in 6 (14%), 6 (14%), and 4 (9%) patients, respectively. Comparing with controls, the patients had lower LV global longitudinal strain and (-22.2 ± 2.8% vs. -24.6 ± 2.0%, P < 0.001) and global circumferential strain (-20.7 ± 6.8% vs. -24.3 ± 2.9%, P = 0.014), but higher global native T1 (1318.8 ± 55.5 ms vs. 1282.9 ± 38.1 ms, P = 0.006). Four (9%) patients presented myocardial late gadolinium enhancement with subepicardial pattern mostly common seen, and two (5%) patients presented pericardial enhancement. The cardiac MRI could detect subclinical functional and myocardial tissue characteristic abnormalities in individuals who were recovering from Delta Variant without cardiac-related clinical findings. The native T1 mapping and strain imaging may be a sensitive tool for the noninvasive detection of a subset of patients who are at risk for cardiac sequelae and more prone to myocardial damage in survivors with Delta Variant.


Overview of Microarray Technology.
Microarray technology, with its high-throughput advantage, has been applied to analyze various biomaterials, such as nucleic acids, proteins, glycans, peptides, and cells.


Correction to: Clinical Outcomes With Extended Versus Intermittent Infusion of Anti-Pseudomonal Beta-Lactams in Patients With Gram-Negative Bacteremia.
[This corrects the article DOI: 10.1093/ofid/ofad170.].


Semantic mapping reveals distinct patterns in descriptions of social relations in adults with autism spectrum disorder.
Adults with autism spectrum disorder (ASD) may describe other individuals differently compared with typical adults. In this study, we first asked participants to describe closely related individuals such as parents and close friends with 10 positive and 10 negative characteristics. We then used standard natural language processing methods to digitize and visualize these descriptions. The complex patterns of these descriptive sentences exhibited a difference in semantic space between individuals with ASD and control participants. Machine learning algorithms were able to automatically detect and discriminate between these two groups. Furthermore, we showed that these descriptive sentences from adults with ASD exhibited fewer connections as defined by word-word co-occurrences in descriptions, and these connections in words formed a less "small-world" like network. Autism Res 2016, 9: 846-853. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.


Helicobacter Pylori and Celiac Disease Antibody Positivity Have a Higher Prevalence in Patients With Distal Gastrectomy: A Cross-Sectional Retrospective Study.
Aims and objectives Distal gastrectomy was a widely used therapeutic option for peptic ulcer and gastroesophageal reflux disease until quite recently. The consequences of anatomical and physiological changes following surgery in the gastric mucosa have been the object of interest for the scientist. In this study, we aimed to determine whether Helicobacter pylori (HP) infection and celiac disease were more common in patients with a history of distal gastrectomy. Materials and methods This is an observational retrospective study conducted at Giresun University Faculty of Medicine. The medical files of 35 patients with dyspepsia who had a history of distal gastrectomy for benign etiologies (antrectomy group) and 50 patients with dyspepsia (control group) were retrospectively analyzed. Results There were more males and older patients in the antrectomy group. Concerning the lab parameters, platelets, lymphocyte, and albumin levels were significantly lower, and urea, creatinine, anti-Endomisium Ig A (anti-EMA), and anti-tissue transglutaminase IgA (anti-tTGA) antibody positivity were significantly higher in the antrectomy group. Gastric biopsy results revealed a higher positivity of HP, atrophy, neutrophil, and lymphocytes in the antrectomy group. Correlation analysis revealed an inverse correlation between albumin and anti-EMA/atrophy positivity whereas a positive correlation between anti-EMA and HP/atrophy positivity. Conclusions HP infection and coeliac disease (CD) could be the problems that distal gastrectomy patients with dyspepsia can face during their follow-up. Concerning the pre-malignant potential of HP, its screening and eradication should be performed to prevent the malignant transformation of the remnant gastric tissue.


Optimization of culture conditions for osteogenically-induced mesenchymal stem cells in β-tricalcium phosphate ceramics with large interconnected channels.
The aim of this study was to optimize culture conditions for human mesenchymal stem cells (hMSCs) in β-tricalcium phosphate ceramics with large interconnected channels. Fully interconnected macrochannels comprising pore diameters of 750 µm and 1400 µm were inserted into microporous β-tricalcium phosphate (β-TCP) scaffolds by milling. Human bone marrow-derived MSCs were seeded into the scaffolds and cultivated for up to 3 weeks in both static and perfusion culture in the presence of osteogenic supplements (dexamethasone, β-glycerophosphate, ascorbate). It was confirmed by scanning electron microscopic investigations and histological staining that the perfusion culture resulted in uniform distribution of cells inside the whole channel network, whereas the statically cultivated cells were primarily found at the surface of the ceramic samples. It was also determined that perfusion with standard medium containing 10% fetal calf serum (FCS) led to a strong increase (seven-fold) of cell numbers compared with static cultivation observed after 3 weeks. Perfusion with low-serum medium (2% FCS) resulted in moderate proliferation rates which were comparable to those achieved in static culture, although the specific alkaline phosphatase (ALP) activity increased by a factor of more than 3 compared to static cultivation. Gene expression analysis of the ALP gene also revealed higher levels of ALP mRNA in low-serum perfused samples compared to statically cultivated constructs. In contrast, gene expression of the late osteogenic marker bone sialoprotein II (BSPII) was decreased for perfused samples compared to statically cultivated samples.


The costs of leaving home: ants disperse myrmecochorous seeds to low nutrient sites.
Leucospermum conocarpodendron (L.) Buek (Proteaceae) seedlings were excavated several months after a fire in Cape fynbos. Seedlings under burnt parental skeletons had short hypocotyls (mean 25 mm) indicating passive dispersal whereas seedlings in the open were more deeply buried (mean 48 mm) by ants. Soil nutrient concentrations at the site of germination were negatively related to depth of burial and distance from parent. Ant dispersal resulted in seedlings emerging in soils with lower nutrient concentrations than passively dispersed seeds. Tissue analysis supported the soil results with lower P content in seedlings from open (ant dispersed) sites. Seedling survival in the first year of establishment was also lower in open sites, but not significantly so. However seedlings were slightly taller in the open. The results of this study, the first on naturally occurring intraspecific variation in myrmecochory, strongly contradict current explanations for the high incidence of myrmecochory in nutrient poor environments.


Extracellular HSP90: conquering the cell surface.
Heat shock protein 90 (HSP90) is a highly conserved molecular chaperone, assisting intracellularly in the folding and conformational regulation of a multitude of client proteins that play a crucial role in growth, cell survival and developmental processes. Moreover HSP90 interacts with a great number of molecules that are involved in the development and/or survival of cancer cells, allowing mutant proteins to retain or gain function while permitting cancer cells to tolerate the imbalanced signaling that such oncoproteins create. Prime examples include the HER-2 receptor, c-Raf-1, Akt/PKB, CDK4 and mutant p53. Highly specific inhibitors of HSP90 have been identified and are currently under clinical evaluation. These include geldanamycin and its derivatives 17-allylamino-17-demethoxygeldanamycin and 17-dimethylaminoethylamino-17-demethoxygeldanamycin, which inhibit cancer cell proliferation in vitro and tumor growth in vivo. Recently, a pool of HSP90 has been identified at the cell surface, where it was shown to be involved in cancer cell invasion. Here, we propose a model concerning the molecular mechanism underlying the role of HSP90 in cancer cell invasion. We suggest that surface HSP90 interacts specifically with the extracellular domain of HER-2 and that this interaction is necessary for the receptor's activation and heterodimerization with ErbB-3, which in turn will mediate signal transduction pathways via MAPK and PI3K-Akt, leading to actin re-arrangement and cell motility. Furthermore we propose that the selective inhibition of cell surface HSP90 with a cell-impermeable function blocking monoclonal antibody, mAb 4C5, may have clinical benefits in limiting cancer invasion and metastasis.


Shared and unique phosphoproteomics responses in skeletal muscle from exercise models and in hyperammonemic myotubes.
Skeletal muscle generation of ammonia, an endogenous cytotoxin, is increased during exercise. Perturbations in ammonia metabolism consistently occur in chronic diseases, and may blunt beneficial skeletal muscle molecular responses and protein homeostasis with exercise. Phosphorylation of skeletal muscle proteins mediates cellular signaling responses to hyperammonemia and exercise. Comparative bioinformatics and machine learning-based analyses of published and experimentally derived phosphoproteomics data identified differentially expressed phosphoproteins that were unique and shared between hyperammonemic murine myotubes and skeletal muscle from exercise models. Enriched processes identified in both hyperammonemic myotubes and muscle from exercise models with selected experimental validation included protein kinase A (PKA), calcium signaling, mitogen-activated protein kinase (MAPK) signaling, and protein homeostasis. Our approach of feature extraction from comparative untargeted "omics" data allows for selection of preclinical models that recapitulate specific human exercise responses and potentially optimize functional capacity and skeletal muscle protein homeostasis with exercise in chronic diseases.


Partial resection of the posterior wall for hip dislocation in severe acetabular protrusio: a useful surgical option.
In elderly patients with osteoarthritis and protrusio who require arthroplasty, dislocation of the hip is difficult due to migration of the femoral head. Traditionally, neck osteotomy is performed in situ, so this is not always achieved. Therefore, the purpose of this study is to describe a partial resection of the posterior wall in severe protrusio. This is a descriptive observational study, which describes the surgical technique of the partial resection of the posterior wall during hip arthroplasty in patients with severe acetabular protrusio operated on between January 2007 and February 2017. In all, 49 hip arthroplasties were performed. The average age of patients was 60 years, and idiopathic was the most frequent aetiology of protrusio. All patients were treated with femoral head autograft and no intra- or postoperative complications were reported. No patients required revision surgery. Partial resection of the posterior wall demonstrated to be a safe surgical technique with 100% survival in a follow-up to ten years in total hip arthroplasty due to severe acetabular protrusio.Cite this article: Bone Joint Open 2020;1-7:431-437.


Quantitative autoradiographic studies of 5-HT-accumulating neurones in the nodose ganglia of the cat after perikaryal or terminal uptake.
The distributions of ganglionar cell bodies, specifically labeled with 3H-5-HT, were studied in light microscope autoradiographs of the cat nodose ganglion. The size, number and localization of labeled cells were examined under different experimental conditions: after in vitro incubation of the ganglion with 3H-5-HT and after retrograde transport of 3H-5-HT injected into the nucleus of the solitary tract (NST) which receives primary visceral sensory projections from nodose ganglia cells of the vagal nerve. Following incubation of the nodose ganglia with a low concentration of 3H-5-HT (10(-6) M), some ganglionar cell bodies took up and retained the tracer. In both the right and left ganglia, they were significantly smaller in size than the unreactive neurones. The mean diameter of their perikaryon was 36.97 +/- 0.52 microns, compared with 45.76 +/- 0.87 microns in unreactive neurones. About 600 labeled cell bodies were counted in each ganglion, corresponding to 2-3% of the total nodose ganglion cell population. These reactive neurones were not localized in one particular area of the ganglia, but scattered throughout both of them. Following bilateral or unilateral microinjections of 3H-5-HT in the NST, retrogradely labeled cell bodies were observed, 24 h later, in the nodose ganglia. Their mean diameter was estimated to be 36.14 +/- 0.69 microns and they represented approximately 2% of the total ganglion cell population. As in in vitro experiments, the labeled cells were not grouped in any particular region of the ganglion. These experiments show that the distribution of both populations of labeled cells, observed under these conditions, are comparable. On an anatomical and quantitative basis one may reasonably suppose that the perikaryal or terminal uptakes concern the same neuronal population.


Chemical-Induced Vitiligo.
Chemical-induced depigmentation of the skin has been recognized for more than 75 years, first as an occupational hazard but then extending to those using household commercial products as common as hair dyes. Since their discovery, these chemicals have been used therapeutically in patients with severe vitiligo to depigment their remaining skin and improve their appearance. Because chemical-induced depigmentation is clinically and histologically indistinguishable from nonchemically induced vitiligo, and because these chemicals appear to induce melanocyte autoimmunity, this phenomenon should be known as "chemical-induced vitiligo," rather than less accurate terms that have been previously used.


Somatomedin-C (SM-C). Study in diabetic patients with and without retinopathy.
In the present study we evaluated somatomedin-C (Sm-C) plasma levels in diabetic patients, with and without retinopathy. One hundred and thirty four diabetic patients (65 type I and 69 type II) and 90 controls, strictly matched for age and sex, were enrolled in the study. Ophthalmoscopy and fluorescein angiography allowed to distinguish: 49 patients without retinopathy, 45 patients with background retinopathy, and 40 with proliferative retinopathy. Growth hormone (GH) and Sm-C plasma levels were measured using a pool of 20-24 blood samples over 24h. Sm-C levels in type I (0.62 +/- 0.11 U/ml) and type II (0.56 +/- 0.09 U/ml) patients were significantly decreased (p less than 0.01) when compared to controls (0.89 +/- 0.30 U/ml). The mean daily secretion of GH was significantly (p less than 0.01) greater in diabetic patients (7.8 +/- 2.6 ng/ml) than in controls (4.1 +/- 1.5 ng/ml), but no correlation was found between Sm-C and GH (r = 0.15; p = n.s.). Our findings did not show any correlation between Sm-C plasma levels and either the existence of retinopathy, regardless of the degree of microvascular damage, or duration of the disease, or degree of metabolic control, as evaluated by HbA1c.


Pirprofen-associated hepatic injury.
Four cases of hepatic injury attributed to the use of pirprofen (Rengasil) were reported to the Monitoring Centres for Adverse Reactions of Belgium, The Netherlands and the German Medical Association. One man and three women developed severe hepatic injury between 3 1/2 and 6 1/2 months after starting treatment with 400-1200 mg pirprofen daily. Histology showed acute hepatocellular damage, often with bridging necrosis. Two patients died. The other two patients made an incomplete recovery. It is possible that this severe type of hepatic injury is due to a metabolic idiosyncrasy to pirprofen, as this reaction seems to be rare and unpredictable but is not associated with immunoallergic signs.


A unified model for high resolution mapping of global lake (>1 ha) clarity using Landsat imagery data.
Lake clarity, usually measured by Secchi disc depth (SDD), is a reliable proxy of lakes trophic status due to its close link with total suspended matter, chlorophyll-a, and nutrients. Trained with in-situ measured SDD and match-up Landsat images, we established various regression models to estimate SDD for global lakes. We selected a unified model which demonstrated good spatiotemporal transferability, and has potential to map SDD in different years with good quality of Landsat top-of-atmosphere (TOA) images embedded in Google Earth Engine (GEE). The unified model was successfully calibrated (n = 3586 data points, R2 = 0.84, MAPE = 29.8%) against SDD measured in 2235 lakes across the world, and the validation (n = 1779, R2 = 0.76, MAPE = 38.8%) also exhibited stable performance. The unified model was tuned to historical SDD measurements coincident with different Landsat sensors (L5-TM, L7-ETM+, L8-OLI) launched over the past four decades (1984-2020), thus confirming its temporal stability. Global SDD was mapped using GEE with OLI TOA products mainly acquired in 2019 to examine the spatial variation of lake water clarity (lake surface area ≥ 1 ha) all over the world. Worldwide, lake water clarity averaged 3.13 ± 1.71 m in 2019, but exhibited remarkable spatial variability due to catchment hydrological and landscape settings, lake morphology, elevation and anthropogenic impact. Inland waters in Europe (4.18 ± 1.82 m) and North America (3.84 ± 1.77 m) had the highest clarity due to greater water depth combined with less human disturbance in the high latitude regions. Lakes in South America (2.50 ± 2.33 m), Asia (2.44 ± 1.63 m) and Africa (2.36 ± 0.72 m) displayed intermediate clarity. Lakes in Oceania (1.97 ± 1.48 m) exhibited the lowest clarity for all continents except Antarctica. Further, we used the mapped SDD to evaluate water trophic status using the Carlson trophic state index. Our results indicate that, in 2019, about 63.6% of the lake areas and 47.8% of total lake numbers (2,219,627/4,646,056) were oligotrophic for global lakes, while about 23.6% areal percent and 37.1% of lake numbers are eutrophic mostly as a result of their being located in agricultural and urban-dominated drainage basins. This study, for the first time, provides water clarity information for lakes with area ≥ 1 ha all over the world with 30-m resolution and facilitates the understanding of the water clarity relevant to TSM (r = 0.95), Chl-a (r = 0.73), total phosphorus (r = 0.75), total nitrogen (r = 0.60), which could further provide water clarity data and technical support for trophic level evaluations as well. This unified model could serve as a powerful research tool for long-term monitoring of aquatic ecosystems and assessing their resilience to anthropogenic disturbance and climate change-related stressors.


Late breast recurrence after lumpectomy and irradiation.
For 276 patients with early breast cancer followed from 10-21 years after lumpectomy and radiotherapy, the recurrence rate in the treated breast was 15.6%, and 7.2% developed contralateral breast cancer. Only 63% of breast recurrences occurred within 5 years, and the remainder were "late failures," with 5 of the 43 recurrences observed after 10 years. The proportion of failures occurring late was greater for T1 than for T2 tumors (53% vs 25%). Twenty-six percent of early recurrences were inoperable, and an adverse impact of early recurrence on 10-year survival was clearly demonstrable. Late recurrences were all operable and did not appear to be associated with decreased survival. Only 16 of the 36 patients (44%) with operable breast recurrence ever developed metastatic disease, and 5 year survival following salvage therapy was 62%. Although the treated breast remains at continuous cancer risk even beyond 5 year, the prognosis of late recurrence appears quite similar to that of contralateral breast cancer. We do not consider the phenomenon of late recurrence to lend support to a policy of primary mastectomy, just as the existence of contralateral breast cancer does not justify routine "prophylactic" contralateral mastectomy.


Interactions of erythrosin B (U.S. F, D & C Red 3) with rat cortical membranes.
Erythrosin B inhibits Na,K-ATPase in rat brain tissue as demonstrated by studying glycoside binding, ATPase activity and ion fluxes. The potency of the noncompetitive inhibition of [3H]-ouabain binding by erythrosin B is influenced by glycoside concentration, monovalent cation concentration, and incubation time. [14C]-Erythrosin B binds to synaptic membranes prepared from rat cortex. Erythrosin B and some of its structural analogs inhibit both [3H]-ouabain and [14C]-erythrosin B binding, but ouabain and other glycosides do not inhibit the binding of [14C]-erythrosin B. Subcellular distributions of [3H]-ouabain and [14C]-erythrosin B binding in fractionated cortical tissue preparations are equivalent and parallel ATPase activity. The dissimilar response of [3H]-ouabain binding and [14C]-erythrosin B binding to changes in tissue preparation, incubation temperature, and partial solubilization of binding sites by deoxycholate (DOC) suggests two separate binding sites for erythrosin and ouabain to rat cortical membranes.


Smart synthetic maghemite nanoparticles with unique surface properties encode binding specificity toward AsIII.
Pristine ɣ-Fe2O3 nanoparticles, called surface active maghemite nanoparticles (SAMNs) display unprecedented colloidal stability and specific binding properties. Herein, the interactions of SAMNs with AsV and AsIII as surface molecular probes were comparatively studied. Thermodynamic and kinetic characterizations, along with chemical and structural analysis of SAMN@As complexes, evidenced two distinct binding modalities. Arsenite, emerged as an elective and specific ligand for SAMNs, whereas arsenate adsorption was more labile, pH dependent and ruled by different binding possibilities. In particular, AsIII oxyacid exclusively interacts through inner-sphere coordination occupying available surface crystal positions resembling a key-lock fitting, while AsV leads to both outer-sphere and inner-sphere complexes. Noteworthy, discrimination between AsV and AsIII was never reported for nanostructured maghemite evidencing the importance of synthetic route on surface properties of the nanomaterial. The present report, besides enriching the chemistry of nanosized iron oxides, suggests SAMNs application for the remediation of water contaminated by AsIII, the most threatening As species in water.


CHOICES-TEEN: Reducing Substance-Exposed Pregnancy and HIV among Juvenile Justice Adolescent Females.
The feasibility and acceptability of CHOICES-TEEN - a 3-session intervention to reduce overlapping risks of alcohol-exposed pregnancy (AEP), tobacco-exposed pregnancy (TEP) and HIV - was assessed among females in the juvenile justice system. Females 14-17 on community probation in Houston, Texas were eligible if presenting with aforementioned health risks. Outcome measures - obtained at one- and three-months post baseline - included the Timeline Followback, Client Satisfaction Questionnaire-8, session completion/checklists, Working Alliance Inventory-Short, and open-ended questions. Twenty-two participants enrolled (82% Hispanic/Latina; mean age=16). The results suggest strong acceptability and feasibility with high client satisfaction and client/therapist ratings, 91% session completion, and positive open-ended responses. All youth were at risk at baseline, with the following proportions at reduced risk at follow-up: AEP (90% 1-month; 71.4% at 3-months; TEP (77% of smokers (n=17) at reduced risk at 1-month; 50% at 3-months); and HIV (52.4% 1-month; 28.6% at 3-months).


Prediction of the outlet flow temperature in a flat plate solar collector using artificial neural network.
In the current research, the efficiency of a solar flat plate collector (SFPC) was examined experimentally, while the system was modeled with an artificial neural network (ANN) under semi-arid weather conditions of Rafsanjan, Iran. Based on the backpropagation algorithm, a feedforward neural network was established to estimate and forecast the outlet flow temperature of SFPC. To identify the most appropriate model, the ANN topology hidden layer, the number of hidden neurons, iteration, and statistical indicators were analyzed. In the first ANN modeling (CASE I), five parameters, including solar radiation, inlet flow temperature, flow rate, ambient temperature, and wind speed, were applied in the input layer of the network, while the output flow temperature (subsequently efficiency) was in the output layer. In the second artificial neural network modeling (CASE II), the wind speed was omitted from the input of the ANN model. Results showed that the ANN with four inputs yields more accurate results for both estimation and prediction of outlet flow temperature.


Old is bad? The effect of age on peripheral stem cell mobilization and transplantation outcomes.
Allogeneic stem cell transplantation (Allo-SCT) is a well-established treatment option for hematological malignancies. With the introduction of reduced-intensity conditioning regimens (RIC) and better supportive measures the elderly are able to receive Allo-SCT. A considerable number of patients are elderly, and often their HLA matched sibling donor is elderly, moreover. Here, we aim to explore the effect of donors' age on stem cell harvesting, engraftment duration after Allo-SCT, and product quality. Sixty-one healthy allogeneic stem cell donors aged 50 years and older who underwent stem cell mobilization at our center between 2009-2019 were enrolled for the study. All donors received 4-5 days of G-CSF, mostly filgrastim or lenograstim and their biosimilar equivalents were given subcutaneously as a total dose of 10 mcg/kg/day. Groups were separated into three groups as aged 50-54 group A, 55-59 group B, aged 60 and older group C. Pre-apheresis peripheral blood CD34+ count was similar all groups (p = 0.2). One day apheresis was sufficient for 72.7 % of group A, 27.3 % for group B and 47.1 % for group C (p = 0.02). Total harvested CD34+ cells were comparable among groups (p = 0.5). Adequate stem cell harvest in older donors is feasible. Older donors may require more than one apheresis procedure and generally procedure was well tolerated. When assessing donors, age should represent less significance.


A dynamic interpretation of κFLC index for the diagnosis of multiple sclerosis: a change of perspective.
Previous studies attempted to define the best threshold for κ free light chains (κFLC) index, confirming higher sensitivity (Se) but less specificity (Sp) compared with IgG oligoclonal bands (OCB) for the diagnosis of MS. To evaluate the diagnostic accuracy of different κFLC index intervals in a miscellaneous cohort of neurological patients, proposing a procedural flowchart for MS diagnosis. We analyzed data from 607 patients diagnosed with MS (179), CIS (116), other inflammatory (94) or non-inflammatory neurological diseases (218). Measures of diagnostic accuracy were reported for different potential thresholds of κFLC index, and for IgG OCB and IgG index. Binary logistic regression was to used to calculate the odds of being diagnosed with MS based on each increase of κFLC index. CSF IgG OCB showed 72.2% Se (CI 95% 68.4-75.7) and 95.2% Sp (CI 95% 93.1-96.7) in discriminating between MS/CIS and controls, with an AUC of 0.84 (CI 95% 0.80-0.87). The highest diagnostic accuracy was reported for κFLC index cut-off of 5.0 (Se = 85.4%, Sp = 90.4%, AUC = 0.88), while a threshold of 11.0 exhibited higher Sp (95.5%, 95% CI 93.1-97.1) than IgG OCB. AUCs for all thresholds between 4.25 and 6.6 were not significantly different from each other, but were significantly higher than the AUC of IgG OCB (p < 0.05). The odds of being diagnosed with MS/CIS increased by 17.1% for each unit increase of κFLC index (OR = 1.17; 95% CI 1.12-1.23; p < 0.001). κFLC index performed better than CSF IgG OCB in supporting the diagnosis of MS/CIS, with the advantage of being a cost-effective and quantitative analysis.


Sequential versus optimized pulmonary vein isolation for paroxysmal atrial fibrillation: a pilot study.
We aimed to investigate whether the sequence of wide circumferential pulmonary vein isolation (PVI) ablation had an effect on the acute reconnection or long-term effectiveness in patients with paroxysmal atrial fibrillation (AF). One hundred consecutive paroxysmal AF patients, who were scheduled to accept PVI, were enrolled and randomized into two groups: (1) optimized group. Lesions were first applied to the anterior/posterior carina and the ridge between the left atrial (LA) appendage and the left pulmonary vein (PV). Then both circles were closed with continuous lesions. (2) Sequential group-continuous circular lesions were created counter-clockwise and started from the site of 6 o'clock. The primary endpoint was the freedom from non-blanking period recurrence of any atrial tachyarrhythmias lasting for 30 s or longer during the 1-year follow-up period after a single procedure. The secondary endpoint included safety endpoints, LA dwelling time, and fluoroscopy time/dose. Forty-nine patients in the optimized group and 48 patients in the sequential group were available for analysis. There was no difference between the AF-free rate of the optimized group and the sequential group (75.5% vs. 72.9%, p = 0.7715). Cox regression analysis found that acute reconnection had the potential to predict long-term recurrence at 1 year (Risk ratio 2.175, p = 0.0818). Both groups had similar safety endpoints, LA dwelling time, and fluoroscopy time/dose. Adjusting the ablation sequence of PVI by ablating the anterior/posterior carina and the ridge between the left PV and the LA appendage first did not improve 1-year AF-free rate for paroxysmal AF.


Effects of phospholemman expression on swelling-activated ion currents and volume regulation in embryonic kidney cells.
Phospholemman (PLM) is a 72-amino-acid phosphoprotein that is a major substrate for cAMP-dependent protein kinase, protein kinase C, and NIMA kinase. In lipid bilayers, PLM forms ion channels selective for Cl-, K+, and taurine. Effluxes of these abundant intracellular osmolytes play an important role in the control of dynamic cell volume changes in many cell types. We measured swelling-activated ion currents and regulatory volume decrease (RVD) in human embryonic kidney cells stably overexpressing canine cardiac PLM. In response to swelling, two clonal cell lines overexpressing PLM had increased swelling-activated ion current densities and faster and more extensive RVD. A third clonal cell line overexpressing mutant PLM showed reduced ion current densities and a diminished RVD response. These results suggest a role for PLM in the regulation of cell volume, perhaps as a modulator of an endogenous swelling-activated signal transduction pathway or possibly by participating directly in swelling-induced osmolyte efflux.


Two pathogenic species of Pythium: P. aphanidermatum and P. diclinum from a wheat field.
During a survey of pathogenic and non-pathogenic Pythium spp. in different localities in Egypt, several isolates of Pythia were obtained and maintained on corn meal agar. Among these isolates, Pythium aphanidermatum and Pythium diclinum were obtained from rhizosphere of wheat plants grown in Dear Attia village, Minia, Egypt. Identification was made using morphological and molecular analyses. P. aphanidermatum and P. diclinum were able to cause reductions in emergence and adulating in wheat in laboratory scale. P. aphanidermatum appeared to be the most aggressive parasite under agar and pot experimental conditions.


Na doping into Li-rich layered single crystal nanoparticles for high-performance lithium-ion batteries cathodes.
Lithium-rich layered manganese-based cathodes (LRLMOs) with first-class energy density (∼1000 W h kg-1) have attracted wide attention. Nevertheless, the weak cycle stability and bad rate capability obstruct their large-scale commercial application. Here, single crystal Li1.2-xNaxNi0.2Mn0.6O2(x = 0, 0.05, 0.1, 0.15) nanoparticles are designed and successfully synthesized due to the single crystal structure with smaller internal stress and larger ionic radius of Na. The synergistic advantages of single crystal structure and Na doping are authenticated as cathodes for Li ion batteries (LIBs), which can consolidate the crystallographic structure and be benefit for migration of lithium ion. Among all the Na doping single crystals, Li1.1Na0.1Ni0.2Mn0.6O2cathode possesses supreme cycling life and discharge capacity at large current density. To be more specific, it exhibits a discharge capacity of 264.2 mAh g-1after 50 charge and discharge cycles, higher than that of undoped material (214.9 mAh g-1). The discharge capacity of Li1.1Na0.1Ni0.2Mn0.6O2cathode at 10 C (1 C = 200 mA g-1) is enhanced to 160.4 mAh g-1(106.7 mAh g-1forx = 0 sample). The creative strategy of Na doping single crystal LRLMOs might furnish an idea to create cathode materials with high energy and power density for next generation LIBs.


The interaction of SiO2 nanoparticles with the neuronal cell membrane: activation of ionic channels and calcium influx.
To clarify the mechanisms of interaction between SiO2 nanoparticles (NPs) and the plasma membrane of GT1-7 neuroendocrine cells, with focus on the activation of calcium-permeable channels, responsible for the long lasting calcium influx and modulation of the electrical activity in these cells. Nontoxic doses of SiO2 NPs were administered to the cells. Calcium imaging and patch clamp techniques were combined with a pharmacological approach. TRPV4, Cx and Panx-like channels are the major components of the NP-induced inward currents. Preincubation with the antioxidant N-acetyl-L-cysteine strongly reduced the [Ca2+]i increase. These findings suggest that SiO2 NPs directly activate a complex set of calcium-permeable channels, possibly by catalyzing free radical production.


Responses of Aquatic Organisms to Cyanobacteria and Elodea in Microcosms.
The aim of the present study is investigation of the impact of mass development of cyanobacteria and Elodea on population characteristics (abundance, biomass, fecundity) and "health" parameters (the state of embryos, heart rate, and thermal resistance) of aquatic invertebrates in experiments with controlled conditions. In July-August 2018, in four variants of microcosms, the conditions were modeled characteristic of the coastal zone of the Rybinsk Reservoir in the period of mass development of cyanobacteria. Mass species were placed in microcosms of planktonic (with domination (80%) Daphnia longispina) and bottom animals (Unio pictorum, Gmelinoides fasciatus, Asellus aquaticus), as well as Elodea canadensis. In the variants with cyanobacteria, the toxic microcystins LR were revealed (24-53% of the sum of toxins, or from 6.6-66.5 μg/L). The presence of cyanobacteria (Aphanizomenon flos-aquae, Microcystis aeruginosa, and Gloeoitrichia spp.) influenced structural parameters of plankton: the quantity to green algae decreased, small-sized crustaceans increased. Influence of cyanobacteria caused reliable changes in parameters of aquatic animal from those of the control: thermal resitance of mollusks and amphipods decreased, time of restoration of heart rate after loads (salinity test) in mollusks increased; in amphipods, individual fecundity decreased, frequency of abnormalities and of mortality of embryos increased. The presence of Elodea intensified these effects. Thus, mass development of cyanobacteria and Elodea influences ecological-physiological parameters of aquatic animals, decreasing their adaptivity to natural stresses and deteriorating the quality of the progeny.


tCONCOORD-GUI: visually supported conformational sampling of bioactive molecules.
Conformational flexibility of bioactive molecules poses a major challenge to computational biology. tCONCOORD generates structure ensembles based on geometrical considerations and has been successfully applied to predict protein conformational flexibility and essential degrees of freedom. We have now developed a graphical user interface (GUI) for tCONCOORD, which substantially facilitates the simulation setup and provides valuable insights into the structure analysis and constraint definition process in tCONCOORD. Moreover, users can influence the constraint definition process by interactively turning interactions on and off, defining completely rigid or flexible regions, or by applying artifical constraints that cause a biased sampling of the conformational space. This interface offers a versatile environment not only for the setup and analysis of tCONCOORD simulations, but also for molecular modeling and structure analysis in general. Both tCONCOORD* and the tCONCOORD-GUI(dagger) are distributed freely.


AAV5-miHTT Lowers Huntingtin mRNA and Protein without Off-Target Effects in Patient-Derived Neuronal Cultures and Astrocytes.
Huntington disease (HD) is a fatal neurodegenerative genetic disorder, thought to reflect a toxic gain of function in huntingtin (Htt) protein. Adeno-associated viral vector serotype 5 (AAV5)- microRNA targeting huntingtin (miHTT) is a HD gene-therapy candidate that efficiently lowers HTT using RNAi. This study analyzed the efficacy and potential for off-target effects with AAV5-miHTT in neuronal and astrocyte cell cultures differentiated from induced pluripotent stem cells (iPSCs) from two individuals with HD (HD71 and HD180). One-time AAV5-miHTT treatment significantly reduced human HTT mRNA by 57% and Htt protein by 68% in neurons. Small RNA sequencing showed that mature miHTT was processed correctly without off-target passenger strand. No cellular microRNAs were dysregulated, indicating that endogenous RNAi machinery was unaffected by miHTT overexpression. qPCR validation of in silico-predicted off-target transcripts, next-generation sequencing, and pathway analysis confirmed absence of dysregulated genes due to sequence homology or seed-sequence activity of miHTT. Minor effects on gene expression were observed in both AAV5-miHTT and AAV5-GFP-treated samples, suggesting that they were due to viral transduction rather than miHTT. This study confirms the efficacy of AAV5-miHTT in HD patient iPSC-derived neuronal cultures and lack of off-target effects in gene expression and regulation in neuronal cells and astrocytes.


p-Type MoS2 and n-Type ZnO Diode and Its Performance Enhancement by the Piezophototronic Effect.
A plasma-induced p-type MoS2 flake and n-type ZnO film diode, which exhibits an excellent rectification ratio, is demonstrated. Under 365 nm optical irradiation, this p-n diode shows a strong photoresponse with an external quantum efficiency of 52.7% and a response time of 66 ms. By increasing the pressure on the junction to 23 MPa, the photocurrent can be enhanced by a factor of four through the piezophototronic effect.


Direct comparison of urinary free cortisol excretion in patients with depression and panic disorder.
Urinary free cortisol (UFC) excretion in 31 patients with major depression is directly compared to UFC levels in 65 patients with panic disorder and 36 controls. Patients with depression demonstrated significantly higher UFC excretion [43 +/- 37 micrograms/g creatinine (cr)] than patients with panic disorder (29 +/- 13 micrograms/g-cr) or controls (22 +/- 10 micrograms/g-cr) (F = 8.5, df = 129, p less than 0.001). Panic patients with a secondary depression (35 +/- 17 micrograms/g-cr) or those with agoraphobia (34 +/- 14 micrograms/g-cr) had UFC levels that were in-between patients with primary major depression and panic patients without these complications (25 +/- 11 micrograms/g-cr). These findings support the hypothesis that patients with major depression, whether primary or secondary, and those with agoraphobia excrete more UFC than patients with uncomplicated panic disorder. This occurs despite the fact that panic disorder might also be expected to raise the stress-responsive hormone cortisol.


Genetic polymorphism of apolipoprotein A-IV in five different regions of Europe. Relations to plasma lipoproteins and to history of myocardial infarction: the EARS study. European Atherosclerosis Research Study.
As a part of the EARS study we assessed the role of the common apo A-IV polymorphism in determining the hereditary predisposition to cardiovascular disease. The study population consisted of 1261 controls and 629 cases (students whose father had MI before 55 years) from five different European regions. The apo A-IV 1-1 phenotype accounted for 85% of the individuals. One per cent of subjects were homozygous for the apo A-IV2 allele. There was significant regional variation in the apo A-IV allele frequencies from North to South in Europe, with the lowest A-IV2 frequency in Finland. The distribution of the apo A-IV phenotypes was similar in cases and controls, as was the regional variation. The apo A-IV polymorphism did not affect HDL cholesterol. There was no correlation between apo A-IV alleles and the plasma concentration of apo A-IV. The plasma concentration of apo A-IV was lower in females than in males; furthermore, there was a significant difference in apo A-IV concentrations between oral contraceptive users and nonusers: users had the lowest values. As no strongly significant genetic difference could be demonstrated between plasma lipid concentration in cases and controls, and as the apo A-IV polymorphism did not significantly influence plasma lipid concentration, we conclude that the apo A-IV gene is not a major determinant of the risk for MI and/or CHD.


Sliding mode controllers for a tempered glass furnace.
This paper investigates the design of two sliding mode controllers (SMCs) applied to a tempered glass furnace system. The main objective of the proposed controllers is to regulate the glass plate temperature, the upper-wall temperature and the lower-wall temperature in the furnace to a common desired temperature. The first controller is a conventional sliding mode controller. The key step in the design of this controller is the introduction of a nonlinear transformation that maps the dynamic model of the tempered glass furnace into the generalized controller canonical form; this step facilitates the design of the sliding mode controller. The second controller is based on a state-dependent coefficient (SDC) factorization of the tempered glass furnace dynamic model. Using an SDC factorization, a simplified sliding mode controller is designed. The simulation results indicate that the two proposed control schemes work very well. Moreover, the robustness of the control schemes to changes in the system's parameters as well as to disturbances is investigated. In addition, a comparison of the proposed control schemes with a fuzzy PID controller is performed; the results show that the proposed SDC-based sliding mode controller gave better results.


Determination of optimal 68 Ga-PSMA PET/CT imaging time in prostate cancers by total-body dynamic PET/CT.
68 Ga-PSMA PET/CT has been widely used in patients with prostate cancer. Due to the limited axial field of view of conventional PET scanners, whole-body dynamic 68 Ga-PSMA PET/CT has not been performed. We investigated the time-activity curves (TACs) of prostate cancer pathological lesions and physiologic bladder activity to determine the optimal 68 Ga-PSMA PET/CT imaging time by total-body (TB) PET/CT. Dynamic TB-PET performed on 11 patients with prostate cancer was analyzed. TACs were obtained by drawing regions of interest in normal organs and pathological lesions (primary prostate lesions and lymph nodes and bone metastases). We evaluated the 68 Ga-PSMA uptake pattern of normal organs, urinary bladder, and pathological lesions. The urinary bladder TAC increased slowly between 180 and 330 s post-injection and then rapidly between 5.5 and 60.0 min post-injection. The pathological lesion uptake increased rapidly during the first 5 min post-injection and then slowly through the remaining 55 min. Six minutes post-injection was the optimal time with the highest pathological lesion SUVmean values still higher than the urinary bladder activity value. However, these prostate lesion, lymph node metastasis, and bone metastasis SUVmean values were one-third, one-half, and one-half the corresponding values 60 min post-injection, suggesting that early imaging might miss low PSMA uptake lesions. A minimum of 35 min post-injection was required for the pathological lesions to have SUVmean values similar to the corresponding values at 60 min post-injection (all P > 0.05), even though the pathological lesion SUVmean values showed a continuous upward trend through the 60 min. Combining early dynamic 68 Ga-PSMA PET (75-360 s) and conventional static imaging 60 min post-injection could avoid the urinary bladder activity interference to better detect pathological lesions and lesions with relatively low PSMA uptake. The pathological lesion SUVmean values at 35-59 min and 60 min post-injection were similar, so 68 Ga-PSMA PET imaging could also be made at 35-59 min post-injection.


Gully evolution and geomorphic adjustments of badlands to reforestation.
Badlands and gullied areas are among those geomorphic environments with the highest erosion rates worldwide. Nevertheless, records of their evolution and their relations with anthropogenic land transformation are scarcer. Here we combine historical data with aerial photographs and tree-ring records to reconstruct the evolution of a badland in a Mediterranean environment of Central Spain. Historical sources suggest an anthropogenic origin of this badland landscape, caused by intense quarrying activities during the 18th century. Aerial photographs allowed detection of dramatic geomorphic changes and the evolution of an emerging vegetation cover since the 1960s, due to widespread reforestation. Finally, tree-ring analyses of exposed roots allowed quantification of recent channel incision of the main gully, and sheet erosion processes. Our results suggest that reforestation practices have influenced the initiation of an episode of incision in the main channel in the 1980s, through the hypothesized creation of disequilibrium in water-sediment balance following decoupling of hillslopes from channel processes. These findings imply an asymmetry in the geomorphic response of badlands to erosion such that in the early evolution stages, vegetation removal results in gullying, but that reforestation alone does not necessarily stabilize the landforms and may even promote renewed incision.


Specific activity and activity ratios of radionuclides in soil collected about 20 km from the Fukushima Daiichi Nuclear Power Plant: Radionuclide release to the south and southwest.
Soil samples at different depths (0-2, 5-7 and 10-12cm) were collected from J Village, about 20km south of Fukushima Daiichi Nuclear Power Plant (FNPP) to determine their radionuclide specific activities and activity ratios. The concentrations and activity ratios of (131)I, (134, 136, 137)Cs and (129m)Te were obtained, but only trace amounts of (95)Nb, (110m)Ag and (140)La were detected which were too low to provide accurate concentrations. Radionuclides such as (95)Zr, (103, 106)Ru and (140)Ba that were found in Chernobyl fallout, were not found in these soil samples. This suggests that noble gasses and volatile radionuclides predominated in the releases from FNPP to the terrestrial environment. The average activity ratios of (131)I/(137)Cs, (134)Cs/(137)Cs, (136)Cs/(137)Cs and (129m)Te/(137)Cs were 55, 0.90, 0.22 and 4.0 (corrected to March 11, 2011) in the 0-2cm soil samples of April 20 and 28, 2011.


Digital clubbing: a unique case and a new hypothesis.
A study of a unique case of unilateral digital clubbing secondary to a true posttmaumatic aneurysm of the ulnar artery in the palm is presented. The clubbing of the digits resolved following resection of the aneurysm. Detailed evaluation of the patient included Doppler flow studies, differential pulse pressure recordings, measurement of reactive hyperemia, angiography, and differential capillary blood gas determinations. The contralateral hand of this otherwise healthy young patient was employed as a control. Findings of increased blood flow, decreased peripheral resistance, and increased oxygenation then were evaluated in light of the findings of other investigators. This study and the information gathered from an extensive review of the literature strongly suggest that a neurocirculatory reflex is the common denominator of the various conditions associated with clubbing. The afferent and efferent limbs of this reflex are proposed.


Structure and topology of Slc11a1(164-191) with G169D mutation in membrane-mimetic environments.
Solute carrier family 11 member 1 (Slc11a1) is a proton-mediated divalent metal cation transporter with 12 putative transmembrane domains. Variation in it reveals alterations in host resistance against intracellular pathogens. A naturally occurring glycine to aspartic acid mutation at position 169 (G169D) in the putative transmembrane domain 4 (TM4) makes mice susceptible to Salmonella typhimurim, Leishmania donovani, and Mycobacterium bovis. In this work, a 28-residue peptide corresponding to Slc11a1(164-191), including TM4 of Slc11a1, with G169D mutation is characterized using CD and NMR methods in 2,2,2-trifluoroethanol solvent and SDS micelles and the results of present study on the G169D peptide are compared with those of previous study on the wild-type peptide. Similarly to the wild-type peptide, the G169D peptide forms a predominantly alpha-helical structure and is totally embedded in SDS micelles as a homologous assembly. However, the G169D mutation changes the local conformation near the mutation site, the cooperative manner in proton binding of the residue Asp located in the center of SDS micelles and the interaction strength of this residue with Mn2+ ions.


Material Hardship in Families With Low Income: Positive Effects of Coparenting on Fathers' and Mothers' Parenting and Children's Prosocial Behaviors.
Families with low income experience high levels of economic insecurity, but less is known about how mothers and fathers in such families successfully navigate coparenting and parenting in the context of material hardship. The current study utilized a risk and resilience framework to investigate the underlying family processes linking material hardship and children's prosocial behaviors in a sample of socioeconomically disadvantaged mother-father families with preschoolers from the Building Strong Families project (N = 452). Coparenting alliance and mothers' and fathers' responsive parenting were examined as mediators. Results of structural equation modeling showed that coparenting alliance was associated with higher levels of both mothers' and fathers' responsive parenting. Subsequently, both parents' responsive parenting were associated with higher levels of children's prosocial behaviors. Material hardship was not associated with coparenting alliance and either parent's responsive parenting. Tests of indirect effects confirmed that the effects of coparenting alliance on children's prosocial behaviors were mediated through both mothers' and fathers' responsive parenting. Overall, these results suggest that when mothers and fathers have a strong coparenting alliance, they are likely to withstand the negative effects of material hardship and thus engage in positive parenting behaviors that benefit their children's prosocial development. Family strengthening interventions, including responsible fatherhood programs, would do well to integrate a strong focus on enhancing a positive coparenting alliance between mothers and fathers.


Localization of aromatase in the brain of the male African catfish, Clarias gariepinus (Burchell), by microdissection and biochemical identification.
Aromatase activity was determined in small discrete areas of the brain of the African catfish, Clarias gariepinus, by a radiometric assay. The fore- and midbrain were divided into eighteen 500-microns transverse sections. From these sections several punches (0.3 mg of tissue) were taken and incubated with [19-3H]-androstenedione. The aromatase activity, calculated from the release of tritium label during aromatization, is expressed in pmol mg-1 tissue hour-1. The highest activity (3.7 pmol) was detected in the preoptic region. The more caudally located area tuberalis, including the nucleus lateralis tuberis and the nucleus recessus lateralis, also showed a relatively high activity (2.5 pmol). A similar activity was found in the most rostral part of the telencephalon and the dorsal parts of the mesencephalon, i.e., the tectum opticum and torus semicircularis (2.3 pmol). A moderate aromatase activity was observed in remaining parts of the brain, except the cerebellum and hindbrain, in which aromatase activity was hardly detectable (0.1-0.3 pmol). It is concluded that a high aromatase activity is present in regions known to be involved in the regulation of reproduction. Since both the torus semicircularis and the tectum opticum display a high aromatase activity, it is suggested that also these structures are involved in reproductive processes.


Ultrasound-guided thrombin injection of iatrogenic pseudoaneurysm at a community hospital.
The purpose of this study was to report the success rate of treating pseudoaneurysm using ultrasound-guided thrombin injection at a community hospital. Over 16-month period, 42 patients with femoral artery pseudoaneurysms were treated using ultrasound-guided thrombin injection. Our results showed that ultrasound-guided thrombin injection has a high success rate, and can be safely performed at a community hospital.


Population-scale detection of non-reference sequence variants using colored de Bruijn graphs.
With the increasing throughput of sequencing technologies, structural variant (SV) detection has become possible across tens of thousands of genomes. Non-reference sequence (NRS) variants have drawn less attention compared with other types of SVs due to the computational complexity of detecting them. When using short-read data, the detection of NRS variants inevitably involves a de novo assembly which requires high-quality sequence data at high coverage. Previous studies have demonstrated how sequence data of multiple genomes can be combined for the reliable detection of NRS variants. However, the algorithms proposed in these studies have limited scalability to larger sets of genomes. We introduce PopIns2, a tool to discover and characterize NRS variants in many genomes, which scales to considerably larger numbers of genomes than its predecessor PopIns. In this article, we briefly outline the PopIns2 workflow and highlight our novel algorithmic contributions. We developed an entirely new approach for merging contig assemblies of unaligned reads from many genomes into a single set of NRS using a colored de Bruijn graph. Our tests on simulated data indicate that the new merging algorithm ranks among the best approaches in terms of quality and reliability and that PopIns2 shows the best precision for a growing number of genomes processed. Results on the Polaris Diversity Cohort and a set of 1000 Icelandic human genomes demonstrate unmatched scalability for the application on population-scale datasets. The source code of PopIns2 is available from https://github.com/kehrlab/PopIns2. Supplementary data are available at Bioinformatics online.


Abdominal involvement in neurofibromatosis 1: sonographic findings.
Neurofibromatosis 1 (NF1) has been studied from many viewpoints, but its abdominal involvement has rarely been reported. Sonography (US) is now the initial diagnostic tool for abdominal exploration, which prompted us to determine the clinical manifestations and US findings of abdominal involvement in NF1. We analyzed the US findings and clinical data of eight NF1 cases with abdominal involvement. Abdominal involvement included neurofibromatous tumor growth in the liver, mesentery, and retroperitoneum, in addition to mesenteric leiomyomatosis and gastric carcinoma. Color Doppler US was useful not only in detecting blood flows in the lesions but also in preventing hazardous vascular injury during tumor biopsy. A better understanding of the clinical manifestations and US findings of abdominal involvement in NF1 translates into improved NF1 patient care.


Incubation of conditional suppression is an associatively-based phenomenon.
Ten rats were deprived of water and trained to lick a tube for saccharin reinforcement. In each of the two sessions that followed, the rats received six contiguous pairings of a 30-second illumination of the houselight and a 0.75 second, 0.10 mA electric shock while licking. No sign of conditioning was observed during the first experimental session, but profound conditioning was observed on the first and subsequent trials of the second conditioning session. No comparable change in the rate of licking was observed in groups of rats that received only presentations of the visual stimulus, only presentations of the electric shock, or random presentation of the visual stimulus and electric shock during the first conditioning session. These data establish that the incubation of conditional suppression is an associative phenomenon.


Severe Mycoplasma hominis infections in two renal transplant patients.
Systemic infections due to Mycoplasma hominis are rare and occur mainly in immunocompromised patients. Reported here are the cases of two renal transplant patients with peritonitis who did not respond to empirical antimicrobial treatment. Effective treatment with doxycycline was administered only after definitive identification of Mycoplasma hominis was achieved. For this identification, the new genetic amplification-sequencing method was invaluable.


Synthesis of amino acyl adenylates using the tert-butoxycarbonyl protecting group.
Alayl, [ 14c]-alanyl, phenylalanyl, and methionyl adenylates have been synthesized in high yields and relatively good purities. Elemental analysis 1H nmr and ir spectra have been utilized for the characterization of these extremely labile compounds. The present synthesis, which uses readily available N-tert-butoxycarbonyl amino acids, is compared with previous methods.


Early-Life Multiple Sevoflurane Exposures Alleviate Long-term Anxiety-Like Behaviors in Mice via the proBDNF/ERK Pathway.
Early-life multiple anesthetics exposure causes neurotoxicity and hence cognitive dysfunction on developing brain. However, the effects of early-life multiple sevoflurane exposures on emotional changes, especially upon stress, are far beyond understood. In young male C57BL6/J mice, the present study showed that 3% sevoflurane inhalation for 2 h in three consecutive days did not influence anxiety-like behaviors as measured by open field test, light dark transition, and elevated plus maze test. In addition, foot shocks stress induced both the short- and long-term anxiety-like behaviors. However, triple sevoflurane exposures ameliorated the long-term anxiety-like behaviors induced by the foot shocks. In parallel, foot shocks stress upregulated the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and brain-derived neurotrophic factor precursor (proBDNF) in the anterior cingulate cortex (ACC), which were significantly inhibited by triple sevoflurane exposures. Immunofluorescence further indicated that the increased p-ERK was mainly expressed in the proBDNF-positive staining cells. Intra-ACC injection of recombinant proBDNF protein upregulated the p-ERK expression and blocked the anxiolytic effect of sevoflurane exposure on long-term anxiety-like behaviors. Therefore, our study demonstrated that multiple sevoflurane exposures alleviate long-term anxiety-like behaviors upon acute stress in young mice by inhibiting proBDNF-ERK signaling in the ACC.


A versatile tRNA aminoacylation catalyst based on RNA.
Aminoacyl-tRNA synthetase (ARS) ribozymes have potential to develop a novel genetic coding system. Although we have previously isolated such a ribozyme that recognizes aromatic amino acids, it could not be used as a versatile catalyst due to its limited ability of aminoacylation to a particular tRNA used for the selection. To overcome this limitation, we used a combination of evolutionary and engineering approaches to generate an optimized ribozyme. The ribozyme, consisting of 45 nucleotides, displays a broad spectrum of activity toward various tRNAs. Most significantly, this ribozyme is able to exhibit multiple turnover activity and charge parasubstituted Phe analogs onto an engineered suppressor tRNA (tRNA(Asn)(CCCG)). Thus, it provides a useful and flexible tool for the custom synthesis of mischarged tRNAs with natural and nonnatural amino acids.


Forearm compartment syndrome in the newborn: report of 24 cases.
Isolated cases of ischemia, compartment syndrome, or Volkmann's ischemic contracture in the forearm of the newborn infant have been reported in the past. The purpose of this study is to review a large series of patients with neonatal forearm compartment syndrome and to report the important clinical features. A search of medical records from 1980 to 2000 identified 24 children with evidence of ischemia of the forearm at the time of birth. Records and images were reviewed for prenatal and birth history, maternal factors, medical conditions, pattern of involvement, treatment, and outcomes. Patients were grouped according to the extent of initial soft-tissue involvement. All patients presented with a sentinel forearm skin lesion. Patterns of involvement ranged from mild skin and subcutaneous lesions to dorsal and volar compartment syndrome with or without distal tissue loss. Early treatment intervention was limited to a single case in which the diagnosis of compartment syndrome was made and an emergency fasciotomy was performed with a good outcome. In other cases tissue loss, compressive neuropathy, muscle loss, and late skeletal changes were responsible for impaired function. Distal bone growth abnormality was common. Forearm compartment syndrome in the newborn is not as uncommon as previously thought. The skin lesion was the common, salient, initial diagnostic finding. Early diagnosis and appropriate referral led to the salvage of a functional limb in 1 of the patients in this series. The severity of the initial insult correlated with the degree of impairment in growth and function. The delayed diagnosis and treatment of an evolving compartment syndrome may compromise further final function.


Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1.
We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg. These results provide proof of concept that CCR5 antagonism is a viable antiretroviral therapeutic approach.


Circ_0007841 knockdown confers cisplatin sensitivity to ovarian cancer cells by down-regulation of NFIB expression in a miR-532-5p-dependent manner.
Cisplatin (DDP) is first-line management for ovarian cancer (OC). Previous data have suggested that circular RNA_0007841 (circ_0007841) regulates OC progression; however, there is no data on its role in the sensitivity of OC cells to DDP. RNA expression of circ_0007841, microRNA-532-5p (miR-532-5p) and nuclear factor I B (NFIB) was detected by quantitative real-time polymerase chain reaction in OC patient samples and OC cell lines. Protein expression was checked by Western blotting analysis. Cell viability, proliferation, cell apoptotic rate, migration and invasion were investigated by 3-(4,5)-dimethylthiahiazo (-z-y1)-3,5-diphenytetrazoliumromide, 5-Ethynyl-29-deoxyuridine, flow cytometry analysis, scratch test and transwell assays, respectively. The interactions among circ_0007841, miR-532-5p and NFIB were identified by a dual-luciferase reporter assay. Xenograft mouse model assay was performed to determine the effect of circ_0007841 on DDP sensitivity in vivo. Circ_0007841 and NFIB expression were upregulated, whereas miR-532-5p was downregulated in DDP-resistant OC tissues and cells compared with controls. Circ_0007841 silencing improved DDP sensitivity, inhibited cell proliferation, invasion and migration, but induced cell apoptosis in DDP-resistant OC cells. Circ_0007841 acted as a miR-532-5p sponge and regulated DDP resistance and OC cell malignancy through miR-532-5p in DDP-resistant OC cells. Besides, the overexpression of NFIB, a target of miR-532-5p, remitted miR-532-5p-mediated effects in DDP-resistant OC cells. Circ_0007841 depletion conferred DDP sensitivity to DDP-resistant OC cells in vivo. Further, circ_0007841 was secreted from DDP-resistant OC cells through being packaged into exosomes. Circ_0007841 conferred DDP resistance to DDP-resistant OC cells through the miR-532-5p/NFIB axis, suggesting the potential of circ_0007841 as a therapeutic target for OC.


Construction workers' reasons for not reporting work-related injuries: an exploratory study.
Although under-reporting of work-related injuries by workers is recognized as a significant problem in construction and other industries, little is known about the specific reasons for such occurrences. Qualitative and quantitative methods were used in this study to (a) identify reasons why construction workers may choose not to report work-related injuries, and (b) to investigate the frequency of the identified reasons. Twenty-seven percent of a sample of construction workers (N = 135) indicated that they had failed to report a work-related injury. The most frequent reasons given were related to perceptions of injuries as "small" and "part of the job" as well as fear of negative consequences, which may follow injury reporting. These findings are discussed in terms of practical implications. Strategies to overcome these reasons are suggested to decrease the under-reporting of injuries in the construction industry.


Differentiation and stromal-induced growth promotion of murine prostatic tumors.
We have derived a panel of p53-null prostatic "basal" and "luminal" epithelial cell lines and their ras transformed counterparts to study stromal/epithelial interactions and the properties of tumors arising from "basal" and "luminal" cells. Previously derived normal murine prostatic "basal" epithelial (PE-B-1) and "luminal" epithelial (PE-L-1) cell lines were transformed with N-Ras. These lines and a spontaneously transformed "luminal" cell line were inoculated subcutaneously or orthotopically into athymic mice, alone or in combination with normal prostatic smooth muscle cells (SMC). All transformed lines formed subcutaneous tumors. SMC significantly enhanced the growth rate of the tumors arising from the "basal" and one of the "luminal" cell lines. The transformed "basal" line gave rise to tumors expressing both "basal" and "luminal" cytokeratins. Prostatic SMC promote the growth of transformed epithelial cells, suggesting that prostatic stroma may promote tumor development. Furthermore, transformed "basal" cells give rise to tumors containing "luminal" cells, suggesting that although most human tumors have a "luminal" phenotype, they may originate from transformed "basal" cells.


Lewis Acid Enabled Copper-Catalyzed Asymmetric Synthesis of Chiral β-Substituted Amides.
Here we report that readily available silyl- and boron-based Lewis acids in combination with chiral copper catalysts are able to overcome the reactivity issues of unactivated enamides, known as the least reactive carboxylic acid derivatives, toward alkylation with organomagnesium reagents. Allowing unequaled chemo-reactivity and stereocontrol in catalytic asymmetric conjugate addition to enamides, the method is distinguished by its unprecedented reaction scope, allowing even the most challenging and synthetically important methylations to be accomplished with good yields and excellent enantioselectivities. This catalytic protocol tolerates a broad temperature range (-78 °C to ambient) and scale up (10 g), while the chiral catalyst can be reused without affecting overall efficiency. Mechanistic studies revealed the fate of the Lewis acid in each elementary step of the copper-catalyzed conjugate addition of Grignard reagents to enamides, allowing us to identify the most likely catalytic cycle of the reaction.


Lack of significant associations between single nucleotide polymorphisms in LPAL2-LPA genetic region and all cancer incidence and mortality in Japanese population: The Japan public health center-based prospective study.
High lipoprotein (a) level is an established cardiovascular risk, but its association with non-cardiovascular diseases, especially cancer, is controversial. Serum lipoprotein (a) levels vary widely by genetic backgrounds and are largely determined by the genetic variations of apolipoprotein (a) gene, LPA. In this study, we investigate the association between SNPs in LPA region and cancer incidence and mortality in Japanese. A genetic cohort study was conducted utilizing the data from 9923 participants in the Japan Public Health Center-based Prospective Study (JPHC Study). Twenty-five SNPs in the LPAL2-LPA region were selected from the genome-wide genotyped data. Cox regression analysis adjusted for the covariates and competing risks of death from other causes, were used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of overall and site-specific cancer incidence and mortality, for each SNP. No significant association was found between SNPs in the LPAL2-LPA region and cancer incidence or mortality (overall/site-specific cancer). In men, however, HRs for stomach cancer incidence of 18SNPs were estimated higher than 1.5 (e.g., 2.15 for rs13202636, model free, 95%CI: 1.28-3.62) and those for stomach cancer mortality of 2SNPs (rs9365171, rs1367211) were estimated 2.13 (recessive, 95%CI:1.04-4.37) and 1.61 (additive, 95%CI: 1.00-2.59). Additionally, the minor allele for SNP rs3798220 showed increased death risk from colorectal cancer (CRC) in men (HR: 3.29, 95% CI:1.59 - 6.81) and decreased CRC incidence risk in women (HR: 0.46, 95%CI: 0.22-0.94). Minor allele carrier of any of 4SNPs could have risk of prostate cancer incidence (e.g., rs9365171 dominant, HR: 1.71, 95%CI: 1.06-2.77). None of the 25 SNPs in the LPAL2-LPA region was found to be significantly associated with cancer incidence or mortality. Considering the possible association between SNPs in LPAL2-LPA region and colorectal, prostate and stomach cancer incidence or mortality, further analysis using different cohorts is warranted.


The role of the metabolite cargo of extracellular vesicles in tumor progression.
Metabolomic reprogramming in tumor and stroma cells is a hallmark of cancer but understanding its effects on the metabolite composition and function of tumor-derived extracellular vesicles (EVs) is still in its infancy. EVs are membrane-bound sacs with a complex molecular composition secreted by all living cells. They are key mediators of intercellular communication both in normal and pathological conditions and play a crucial role in tumor development. Although lipids are major components of EVs, most of the EV cargo studies have targeted proteins and nucleic acids. The potential of the EV metabolome as a source for biomarker discovery has gained recognition recently, but knowledge on the biological activity of tumor EV metabolites still remains limited. Therefore, we aimed (i) to compile the list of metabolites identified in tumor EVs isolated from either clinical specimens or in vitro samples and (ii) describe their role in tumor progression through literature search and pathway analysis.


Advantages of growth and competitive ability of the invasive plant Solanum rostratum over two co-occurring natives and the effects of nitrogen levels and forms.
Atmospheric nitrogen (N) deposition has often been considered as a driver of exotic plant invasions. However, most related studies focused on the effects of soil N levels, and few on those of N forms, and few related studies were conducted in the fields. In this study, we grew Solanum rostratum, a notorious invader in arid/semi-arid and barren habitats, and two coexisting native plants Leymus chinensis and Agropyron cristatum in mono- and mixed cultures in the fields in Baicheng, northeast China, and investigated the effects of N levels and forms on the invasiveness of S. rostratum. Compared with the two native plants, S. rostratum had higher aboveground and total biomass in both mono- and mixed monocultures under all N treatments, and higher competitive ability under almost all N treatments. N addition enhanced the growth and competitive advantage of the invader under most conditions, and facilitated invasion success of S. rostratum. The growth and competitive ability of the invader were higher under low nitrate relative to low ammonium treatment. The advantages of the invader were associated with its higher total leaf area and lower root to shoot ratio compared with the two native plants. The invader also had a higher light-saturated photosynthetic rate than the two native plants in mixed culture (not significant under high nitrate condition), but not in monoculture. Our results indicated that N (especially nitrate) deposition may also promote invasion of exotic plants in arid/semi-arid and barren habitats, and the effects of N forms and interspecific competition need to be taken into consideration when studying the effects of N deposition on invasion of exotic plants.


Diet with Low Molecular Weight Chitosan exerts neuromodulation in Rotenone induced Drosophila model of Parkinson's disease.
Rotenone (ROT) is well known pesticide been used in agriculture due to its low cost and rapid action. This has also been widely used to establish Parkinson's disease (PD) models in rodents. Here we have evaluated the role of well established potent molecule 'Low Molecular Weight Chitosan (LMWC)' against ROT induced neurotoxicity in Drosophila melanogaster. Male adult flies (8-10 days) were induced for neurotoxicity using ROT (500 μM) and treated with LMWC (5 & 10 mg/mL basal media) during 7 days experiment. Subsequently, neurodegenerative and behavioural parameters were assessed. As a result, flies exposed to ROT alone showed decreased locomotor behaviour in negative geotaxis and open-field studies and had a higher incidence of mortality compared to control group. These effects were accompanied by decrease in dopamine level, ETC complexes and increase in reactive oxygen species (ROS) production and cholinergic activities in head and body of the flies, suggesting ROT was able to induce oxidative stress. Co-exposure of LMWC reversed the ROT induced locomotor impairment, exploratory deficits and changes the biochemical parameters to normal level and increased the survival rate to 16 days. Thus, we suggested LMWC may be considered as better supplement in the prevention and management of Parkinson's disease.


Pharmacokinetics and pharmacodynamics of Abelacimab (MAA868), a novel dual inhibitor of Factor XI and Factor XIa.
Factor XI (FXI) inhibition offers the promise of hemostasis-sparing anticoagulation for the prevention and treatment of thromboembolic events. Abelacimab (MAA868) is a novel fully human monoclonal antibody that targets the catalytic domain and has dual activity against the inactive zymogen Factor XI and the activated FXI. To investigate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of single dose intravenous and multiple dose subcutaneous administration of abelacimab in healthy volunteers and patients with atrial fibrillation, respectively. In study ANT-003, healthy volunteers were administered single intravenous doses of abelacimab (30-150 mg) or placebo. The ANT-003 study also included a cohort of obese but otherwise healthy subjects. In study ANT-004, patients with atrial fibrillation were administered monthly subcutaneous doses of abelacimab (120 mg and 180 mg), or placebo, for 3 months. Key PK and PD parameters, including activated partial thromboplastin time (aPTT) and free FXI levels, as well as anti-drug antibodies (ADA) were assessed. Following intravenous administration of abelacimab, the terminal elimination half-life ranged from 25 to 30 days. One hour after the start of the intravenous infusion greater than 99% reductions in free FXI levels were observed. Following once monthly subcutaneous administration, marked reductions from baseline in free FXI levels were sustained. Parenteral administration of abelacimab demonstrated a favorable safety profile with no clinically relevant bleeding events. Intravenous and multiple subcutaneous dose administration of abelacimab were safe and well tolerated. The safety, PK, and PD data from these studies support the clinical development of abelacimab.


Relationship between whole blood base excess and CO2 content in vivo.
Empirical relationships are demonstrated for whole blood base excess (BE) and CO2 content (CCO2), both calculated from in vivo measurements of PCO2, pH, hemoglobin concentration and O2 saturation. Comparisons are provided by measurements from three separate studies: (1) supine exercise (arterial and mixed venous samples); (2) chronic obstructive disease patients (arterial samples) breathing air and 100% O2; and (3) maximal seated exercise on a bicycle ergometer with and without added inspired CO2 (arterial samples before, during and after). Two standardized values of CCO2 (vol.%) are derived which closely relate to BE (mmol/l). The CCO2 at a PCO2 of 40 mmHG [CCO2(40)] for all samples (n = 220) demonstrated a curvilinear relationship: CCO2 (40) = 45.37 + 1.48(BE) + 0.0156(BE)2, r = + 0.996, SEE = 0.88 vol.%. The CCO2 at a pH of 7.4 [CCO2(7.4)] gave a linear relationship: CCO2(7.4) = 45.09 + 2.58(BE), r = + 0.998, SEE = 1.19 vol.%. Empirical computations for the Haldane factor from studies 1 and 2 gave values of 0.285 in terms of CCO2 (vol.%/vol.%) and 0.266 for BE (mmol/l/mmol reduced Hb). The BE values can serve as useful estimates of lactate concentrations during exercise and the excellent relationships between standardized CCO2 and BE demonstrate their equivalency and either can be utilized, depending on whether quantification of the CO2 dissociation curve or acid-base status is desired.


Intussusception: an uncommon cause of postoperative small bowel obstruction after gastric bypass.
Intussusception of the jejuno-jejunal anastomosis is a rare complication of the Roux-en-Y gastric bypass (RYGBP). There are only 3 previous cases reported in the surgical literature. We describe 2 adults who developed jejuno-jejunal intussusception requiring emergent laparotomy several months after RYGBP. Both patients underwent exploratory laparotomy after the diagnosis was made with abdominal CT scan. Each patient had an uneventful postoperative course after bowel resection and revision of the enteroenterostomy. Small bowel obstruction due to intussusception may occur many months after RYGBP and may present with non-specific symptoms such as crampy abdominal pain, nausea, and vomiting. The diagnosis of this rare entity is typically made via abdominal CT scan. Treatment mandates urgent abdominal exploration with reduction.


The cotton rat (Sigmodon hispidus) as an animal model for respiratory tract infections with human pathogens.
Respiratory viral infection is a great human health concern, resulting in disease, death and economic losses. Cotton rats (Sigmodon hispidus) have been particularly useful in the study of the pathogenesis of human respiratory virus infections, including the development and testing of antiviral compounds and vaccines. In this article, the authors outline the advantages of the cotton rat compared with the mouse as a model for infection with measles virus, respiratory syncytial virus, influenza virus, human parainfluenza virus and human metapneumovirus. From the literature and their own experience, the authors summarize guidelines for handling, maintaining and breeding cotton rats. In addition, they offer technical tips for carrying out infection experiments and provide information about the large array of immunological assays and reagents available for the study of immune responses (macrophages, dendritic cells, T cells, B cells, antibodies, chemokines and cytokines) in cotton rats.


High-efficiency transformation by biolistics of soybean, common bean and cotton transgenic plants.
This protocol describes a method for high-frequency recovery of transgenic soybean, bean and cotton plants, by combining resistance to the herbicide imazapyr as a selectable marker, multiple shoot induction from embryonic axes of mature seeds and biolistics techniques. This protocol involves the following stages: plasmid design, preparation of soybean, common bean and cotton apical meristems for bombardment, microparticle-coated DNA bombardment of apical meristems and in vitro culture and selection of transgenic plants. The average frequencies (the total number of fertile transgenic plants divided by the total number of bombarded embryonic axes) of producing germline transgenic soybean and bean and cotton plants using this protocol are 9, 2.7 and 0.55%, respectively. This protocol is suitable for studies of gene function as well as the production of transgenic cultivars carrying different traits for breeding programs. This protocol can be completed in 7-10 months.


"If I feel disgusted, I must be getting ill": emotional reasoning in the context of contamination fear.
Patients suffering from anxiety disorders have been shown to infer danger on the basis of their anxiety responses "if I feel anxious, there must be danger." This tendency logically hampers the identification of false alarms and may thus act in a way to confirm the a priori threat value of the feared stimuli/situations. Since disgust is assumed to play a critical role in the persistence of contamination fears in OCD, the question rises whether individuals suffering from fear of contamination perhaps similarly infer danger on the basis of their disgust response: "If I feel disgusted, it must be contagious." Therefore, this study tested whether indeed disgust-based reasoning might be involved in fear of contamination. On the basis of the contamination fear subscale of the Padua Inventory (PI), we selected a group of participants scoring higher than the established clinical range (n=31, PI>13) and a group of participants low (n=27, PI<5) in contamination fear. Each participant was presented with a series of 2 times 4 types of scripts that systematically varied in the absence/presence of objective threat of contamination and the absence/presence of the actor's disgust response. Following each script, participants rated their perceived threat of contamination/illness. In line with the hypothesis that disgust-based reasoning might be involved in fear of contamination, specifically high contamination fearful individuals inferred risk of becoming ill on the basis of experienced disgust (in addition to objective threat), as was evidenced by a significant Group (high vs. low)×Threat (yes vs. no)×Disgust response (yes vs. no) interaction. This finding might not only help to explain the persistence of contamination fears, but also provides some fresh clues to improve currently available treatment options.


Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?
To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P < .001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P = .021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P = .025). While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.


Effect of dietary carbamyl phosphate on dentine apposition in rat molars.
In rats, sucrose increases dental caries and impairs odontoblastic function by reducing dentine apposition during primary dentinogenesis. A high-sucrose diet also affects negatively a pulp or dentine function that appears to regulate solute or fluid movement within rat dentinal tissue. In earlier work it was found that carbamyl phosphate could significantly reverse sucrose-induced cariogenesis and also stimulate sucrose-depressed movement of dentinal fluid through a mechanism involving parotid function(s). In the current study, the possibility that carbamyl phosphate could overcome the sucrose-induced reduction in dentine apposition was examined. Weanling rats were fed a high-sucrose diet supplemented or not with carbamyl phosphate for 5 weeks. Dentine apposition was measured planimetrically in sagittal sections of the molars. The effect of carbamyl phosphate was similarly tested in parotidectomized animals. Carbamyl phosphate significantly reduced the deleterious effect of sucrose on dentine apposition by 58% in the first molars. However, the reduction in dentine apposition that followed parotidectomy was not altered by carbamyl phosphate supplementation. The possibility that the beneficial effect of carbamyl phosphate on dentinogenesis involves a parotid function is entertained.


Development of Curcumin loaded chitosan polymer based nanoemulsion gel: In vitro, ex vivo evaluation and in vivo wound healing studies.
In the present study, various nanoemulsions were prepared using Labrafac PG+Triacetin as oil, Tween 80 as a surfactant and polyethylene glycol (PEG 400) as a co-surfactant. The developed nanoemulsions (NE1-NE5) were evaluated for physicochemical characterizations and ex-vivo for skin permeation and deposition studies. The highest skin deposition was observed for NE2 with 46.07% deposition amongst all developed nanoemulsions (NE1-NE5). Optimized nanoemulsion (NE2) had vesicle size of 84.032±0.023nm, viscosity 78.23±22.2 cps, refractive index 1.404. Nanoemulsion gel were developed by incorporation of optimized nanoemulsion (NE2) into 1-3% chitosan and characterized by physical evaluation and rheological studies. Chitosan gel (2%) was found to be suitable for gelation of nanoemulsion based on its consistency, feel and ease of spreadability. The flux of nanoemulsion gel was found 68.88μg/cm2/h as compared to NE2 (76.05μg/cm2/h) is significantly lower suggesting limited skin permeation of curcumin form gel. However, the retained amount of curcumin on skin by gel formulation (980.75±88μg) is significantly higher than NE2 (771.25±67μg). Enhanced skin permeation of NE2 (46.07%) was observed when compared to nanoemulsion gel (31.25%) and plain gel (11.47%). The outcome of this study evidently points out the potential of curcumin entrapped nanoemulsion gel in wound healing.


The Process of Deciding Mother's Role for Preparing Children as Part of an Online Sexual Crime-Free Digital Society: A Grounded Theory.
In this technological era, there is a serious global threat to child development, the phenomenon of child sexual abuse via the internet (Internet Child Sexual Abuse/ICSA), and mothers must adapt to the era's needs. The purpose of this study is to explore the decision-making process regarding the role of mothers in protecting their children from sexual harassment in the digital age. A grounded theory approach was used in Bengkulu, Indonesia, in 2021. Data were obtained through focus group discussions on 12 mothers, 4 girls, and 4 female activists (who were selected by theoretical sampling), which were analyzed using thematic analysis. Memos were generated after categorical analysis was sorted after saturation occurred. Five theoretical categories formed the core category. The five categories of the theory were "mother's views on sexual education in children," "strategies for sexual communication with children," "the negative impact of online media," "limits in carrying out supervision," and "preparation needed by children." The memo was drawn theoretically, "new challenges in parenting," which was then made into a core category. The core category was "preparing children to be part of a sex crime-free digital society." Parents teach their kids self-control, awareness, and the importance of using virtual media wisely and selectively. The parenting and technology recommendations assist mothers in protecting their children from internet-based sexual crimes. Maternity nurses should promote reproductive health through the creation of relevant media.


DEPTOR Prevents Osteoarthritis Development Via Interplay With TRC8 to Reduce Endoplasmic Reticulum Stress in Chondrocytes.
Endoplasmic reticulum (ER) stress has been shown to promote chondrocyte apoptosis and osteoarthritis (OA) progression, but the precise mechanisms via which ER stress is modulated in OA remain unclear. Here we report that DEP domain-containing mTOR-interacting protein (DEPTOR) negatively regulated ER stress and OA development independent of mTOR signaling. DEPTOR is ubiquitinated in articular chondrocytes and its expression is markedly reduced along with OA progression. Deletion of DEPTOR in chondrocytes significantly promoted destabilized medial meniscus (DMM) surgery-induced OA development, whereas intra-articular injection of lentivirus-expressing DEPTOR delayed OA progression in mice. Proteomics analysis revealed that DEPTOR interplayed with TRC8, which promoted TRC8 auto-ubiquitination and degraded by the ubiquitin-proteasome system (UPS) in chondrocytes. Loss of DEPTOR led to TRC8 accumulation and excessive ER stress, with subsequent chondrocyte apoptosis and OA progression. Importantly, an inhibitor of ER stress eliminated chondrocyte DEPTOR deletion-exacerbated OA in mice. Together, these findings establish a novel mechanism essential for OA pathogenesis, where decreasing DEPTOR in chondrocytes during OA progression relieves the auto-ubiquitination of TRC8, resulting in TRC8 accumulation, excessive ER stress, and OA progression. Targeting this pathway has promising therapeutic potential for OA treatment. © 2020 American Society for Bone and Mineral Research (ASBMR).


The relationship between accessibility of healthcare facilities and medical care utilization among the middle-aged and elderly population in Taiwan.
The purpose of this study was to explore the relationship between accessibility of healthcare facilities and medical care utilization among the middle-aged and elderly population in Taiwan. Cross-sectional study from 2007 Taiwan Longitudinal Study on Ageing (TLSA) survey. Community-based study. A total of 4249 middle-aged and elderly subjects were recruited. None. Outpatient visits within 1 month, and hospitalization, emergency visits as well as to shop in pharmacy stores within 1 year, respectively. Adjusting for important confounding variables, the middle-aged and elderly with National Health Insurance (NHI) and commercial insurance compared with those with NHI alone tended to have outpatient visits. The middle-aged and elderly with longer time to access healthcare facilities were less likely to shop in pharmacy stores compared with those with <30 min. The middle-aged and elderly who perceived inconvenient to access health care tended to shop in pharmacy stores compared with those with perceived convenience. Our study of Taiwan's experience could provide a valuable lesson for countries that are planning to launch universal health insurance system, locate budgets in health care and transportation. The middle-aged and elderly who were facing more challenges in accessing health care, no matter in perceived accessibility or real time to access health care, had less outpatient visits and more drug stores shopping. Strategic policies are needed to improve accessibility in increasing patients' perception on access and escalating convenience of transportation system for improving accessibility.