Assessment of microplastics derived from mariculture in Xiangshan Bay, China.
Mariculture activities including enclosure, raft and cage cultures employ a variety of plastic gear such as fishing nets, buoyant material and net cages. The plastic gear poses a potential source of microplastics to the coastal environment, but relevant data on the impacts of mariculture are still limited. To this end, a semi-enclosed narrow bay (i.e., Xiangshan Bay, China) with a long-term mariculture history was investigated to assess how mariculture activities affect microplastics in seawater and sediment. The results indicated that mariculture-derived microplastics accounted for approximately 55.7% and 36.8% of the microplastics in seawater and sediment, respectively. The average microplastic abundances of seawater and sediment were 8.9 ± 4.7 (mean ± SD, n = 18) items/m3 seawater and 1739 ± 2153 (n = 18) items/kg sediment, respectively. The types of mariculture-derived microplastics included polyethylene (PE) foam, PE nets, PE film, polypropylene (PP) rope, polystyrene (PS) foam and rubber. PE foam had the highest proportion (38.6%) in the seawater samples. High usage rates and the porous structure of PE foam led to the high abundance. The average microplastic sizes of seawater and sediment are 1.54 ± 1.53 mm and 1.33 ± 1.69 mm, respectively. The spatial variations in the abundance and size of microplastics implied that the mariculture-derived microplastics in Xiangshan Bay were transported along the Bay to the open sea. The results of this study indicate that mariculture activity can be a significant source of microplastics. Further research is required to investigate how the high microplastic abundance in mariculture zone affects marine organisms, especially cultured seafood.


Naringin time-dependently lowers hepatic cholesterol biosynthesis and plasma cholesterol in rats fed high-fat and high-cholesterol diet.
The flavonoid naringin was investigated for its differential effects on hepatic cholesterol regulation when supplemented for 3 weeks and 6 weeks. Sprague-Dawley rats were fed a high-fat and high-cholesterol diet with or without 0.02% naringin supplement for 3 or 6 weeks. Supplementation with naringin resulted in a significant decrease in the plasma cholesterol and triglyceride concentrations in the 6-week trial. Although high-density lipoprotein (HDL)-cholesterol was not altered in either trial, the HDL-cholesterol/total cholesterol ratio (in percent) was significantly higher, and the atherogenic index was significantly lower in the naringin-supplemented groups in the 6-week trial. The hepatic cholesterol content was also lowered by naringin supplementation only in the 6-week trial. The hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase activity was lower in the rats supplemented with naringin for 6 weeks, while the hepatic acyl-coenzyme A:cholesterol acyltransferase activity was lower in both the 3-week and 6-week trials. Results indicate that supplementation with naringin for 3 weeks did not exhibit a hypolipidemic effect when given with a HFHC diet. Naringin can, however, be beneficial for lowering hepatic cholesterol biosynthesis and levels of plasma lipids when supplemented for 6 weeks in this animal model.


Results of a multicenter study investigating the potential impact of the overall treatment time on outcomes of radiation therapy alone with 5×4 Gy for metastatic epidural spinal cord compression.
A 5×4 Gy program is commonly used for metastatic epidural spinal cord compression (MESCC). It is unclear whether an overall treatment time (OTT) of 5 days (5 consecutive fractions) results in better outcomes than an OTT of 7 days (ie, no irradiation during the weekend). A total of 111 patients who received 5×4 Gy over 5 consecutive days were retrospectively compared with 277 patients treated with 5×4 Gy over 7 days (no irradiation during the weekend) for effect on motor function, local control of MESCC, and overall survival (OS). Ten further characteristics were evaluated: age, gender, interval tumor diagnosis to MESCC, visceral metastases, other bone metastases, primary tumor type, time developing motor deficits, walking ability, vertebrae involved, and performance status. On multivariate analysis regarding post-radiation therapy motor function, primary tumor type (P = .011) and time developing motor weakness (P < .001) were significant, whereas the OTT did not even achieve significance on univariate analysis (P = .99). On multivariate analysis of local control, visceral metastases (P = .006) were significant. Again, the OTT was not even significant on univariate analysis (P = .81). On multivariate analysis of OS, interval tumor diagnosis to MESCC (P = .015), visceral metastases (P .001), tumor type (P = .003), walking ability (P < .001), and Eastern Cooperative Oncology Group performance score (P < .001) achieved significance. Even on univariate analysis, OTT did not have an effect on OS (P = .79). Longer OTT did not impair outcomes of irradiation with 5×4 Gy for MESCC; thus, no compensation (for example an additional radiation fraction) is necessary if the radiation treatment is not continued during the weekend.


Hepatitis A Outbreaks in European Homosexual Men.
Hepatitis A virus (HAV) is a small RNA, non-enveloped agent predominantly transmitted via the fecal/oral route through person-to-person contact or contaminated food and water. The mean incubation period is 28 days (range: 15-50). Acute hepatitis A is always self-limited and very rarely fatal. Moreover, it never progresses to chronicity. Acutely infected persons are most likely to transmit HAV before the onset of jaundice, when viral particle concentration in stool is highest.


[Effect of pseudophacic mini-monovision as an option for independence of spectacles in everyday life].
Modern day patients who undergo bilateral cataract surgery expect to be spectacles-independent after surgery. The options that are available to attain this goal are pseudophakic monovision, implanting multifocal IOLs or alternatively accommodative IOLs. The aim of this study is to establish the suitability in daily life when attaining minor monovision, named hereafter mini-monovision. In this clinical retrospective study 30 patients were examined. These subjects where bilaterally pseudophake and received either AcrySof®-IOL or Acreos® Adapt-IOL with a slight anisometropia of between 0.5 and 1.75 D and with a maximal astigmatism up to 1.5 D. Visual acuity (VA) for distance (ETDRS), intermediate (Jaeger 80 cm) and near (Jaeger 40 cm) as well as defocus curves were assessed. Furthermore were examined: the reading speed using the font size of the Radner reading chart, anisoconia (FA Oculus according to Esser), stereopsis (Titmus), subjective patient satisfaction (adapted VF-14-questionnaire) and the subjective dependence on having to wear spectacles. The median anisometropia was at 0.75 D; the age was between 61 and 80 (median being at 73 years). 12 patients were male and 18 female. When examined with binocular vision 100 % could attain distance VA of at least decimal 1.0 (LogMAR 0) and an intermediate VA of at least decimal 0.8 (LogMAR 0.1), up to 86.57 % a near VA of at least Jaeger 5, (LogMAR 0.4); up to 63.33 % even managed at least Jaeger 3 (LogMAR 0.3). The median average reading speed for binocular uncorrected reading under photopic conditions was 145 words/minute and under mesopic conditions 117 words/minute. The critical font size was LogRAD 0.60 (Jaeger 5-6), the anisoconia at 2 % and stereopsis at 80 arc seconds. The general dependence on glasses was reduced from 100 % preoperatively to 13 %, postoperatively. Simultaneously a high patient satisfaction score of 93.18 in the VF-14 questionnaire was attained. The result is comparable to those quoted in the literature on full monovision and mulitifocal IOLs. To attain spectacles independency, pseudophake mini-monovision is a cost efficient alternative to multifocal lenses for well selected patients. A relative reduction in near VA must be taken into account. To establish the refractive target further examinations are required. Establishing the accurate depth of vision will be helpful in attaining this.


Transcriptomic dissection reveals wide spread differential expression in chickpea during early time points of Fusarium oxysporum f. sp. ciceri Race 1 attack.
Plants' reaction to underground microorganisms is complex as sessile nature of plants compels them to prioritize their responses to diverse microorganisms both pathogenic and symbiotic. Roots of important crops are directly exposed to diverse microorganisms, but investigations involving root pathogens are significantly less. Thus, more studies involving root pathogens and their target crops are necessitated to enrich the understanding of underground interactions. Present study reported the molecular complexities in chickpea during Fusarium oxysporum f. sp. ciceri Race 1 (Foc1) infection. Transcriptomic dissections using RNA-seq showed significantly differential expression of molecular transcripts between infected and control plants of both susceptible and resistant genotypes. Radar plot analyses showed maximum expressional undulations after infection in both susceptible and resistant plants. Gene ontology and functional clustering showed large number of transcripts controlling basic metabolism of plants. Network analyses demonstrated defense components like peptidyl cis/trans isomerase, MAP kinase, beta 1,3 glucanase, serine threonine kinase, patatin like protein, lactolylglutathione lyase, coproporphyrinogen III oxidase, sulfotransferases; reactive oxygen species regulating components like respiratory burst oxidase, superoxide dismutases, cytochrome b5 reductase, glutathione reductase, thioredoxin reductase, ATPase; metabolism regulating components, myo inositol phosphate, carboxylate synthase; transport related gamma tonoplast intrinsic protein, and structural component, ubiquitins to serve as important nodals of defense signaling network. These nodal molecules probably served as hub controllers of defense signaling. Functional characterization of these hub molecules would not only help in developing better understanding of chickpea-Foc1 interaction but also place them as promising candidates for resistance management programs against vascular wilt of legumes.


Contribution of Perceived Cognitive Functioning to Quality of Life in Service Members and Veterans With Posttraumatic Stress Disorder.
Perceived cognitive impairment is a core clinical feature of posttraumatic stress disorder (PTSD) and may be an important determinant of quality of life (QOL) in those who suffer from this disorder. Using a clinical data repository, we evaluated this hypothesis in a cross-sectional sample of U.S. military service members and veterans who served after September 11, 2001, and were seeking mental health treatment at a tertiary outpatient clinic. A consecutive series of 117 patients with a clinical diagnosis of PTSD completed a battery of questionnaires at intake, including the PTSD Checklist (Weathers, Litz, Herman, Huska, & Keane, 1993), a 4-item Cognitive Symptom subscale of the Neurobehavioral Symptom Inventory (Cicerone & Kalmar, 1995), the Depression Anxiety Stress Scale-21 (Lovibond & Lovibond, 1995), and the Quality of Life Enjoyment and Satisfaction Questionnaire (Endicott, Nee, Harrison, & Blumenthal, 1993). Cognitive symptom reporting was very high, even in the subgroup without a history of traumatic brain injury. In a regression analysis, cognitive symptom severity was independently associated with QOL (β = -.204). This relationship was not explained by comorbid traumatic brain injury, but was restricted to patients with comorbid depression (β = -.278 in the subgroup with an elevated Depression Anxiety Stress Scale-21 Depression subscale; n = 91). In conclusion, perceived cognitive impairment was common in this PTSD sample and helped to explain impairments in QOL, especially in patients with comorbid depression.


Dielectric Engineering of Electronic Correlations in a van der Waals Heterostructure.
Heterostructures of van der Waals bonded layered materials offer unique means to tailor dielectric screening with atomic-layer precision, opening a fertile field of fundamental research. The optical analyses used so far have relied on interband spectroscopy. Here we demonstrate how a capping layer of hexagonal boron nitride (hBN) renormalizes the internal structure of excitons in a WSe2 monolayer using intraband transitions. Ultrabroadband terahertz probes sensitively map out the full complex-valued mid-infrared conductivity of the heterostructure after optical injection of 1s A excitons. This approach allows us to trace the energies and line widths of the atom-like 1s-2p transition of optically bright and dark excitons as well as the densities of these quasiparticles. The excitonic resonance red shifts and narrows in the WSe2/hBN heterostructure compared to the bare monolayer. Furthermore, the ultrafast temporal evolution of the mid-infrared response function evidences the formation of optically dark excitons from an initial bright population. Our results provide key insight into the effect of nonlocal screening on electron-hole correlations and open new possibilities of dielectric engineering of van der Waals heterostructures.


Inhibitory activity and molecular mechanism of protegrin-1 against porcine reproductive and respiratory syndrome virus in vitro.
Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe diseases affecting the swine industry worldwide. Currently, no vaccination regimen has proven sustained success in preventing PRRSV infection. Therefore, there is an urgent need for new antiviral strategies to control PRRSV. In this study, the inhibitory effects and molecular mechanism of antimicrobial peptide protegrin-1 (PG-1) isolated from porcine leukocytes against PRRSV were evaluated in vitro. Marc-145 cells or porcine alveolar macrophages (PAMs) were infected with PRRSV in the presence or absence of PG-1 for 36 h. The inhibitory effects of PG-1 were assessed by measuring the transcript and protein level of PRRSV ORF7 in cells and virus titres in the supernatants. Virus attachment and entry assays were performed to explore the molecular mechanism of PG-1 action. We demonstrated that PG-1 strongly inhibited PRRSV infection and replication by suppressing virus RNA and protein synthesis, virus progeny production and viral particles release. Furthermore, in the PRRSV life cycle, PG-1 mainly blocked viral attachment in Marc-145 cells. However, in PAMs, PG-1 could neither inhibit PRRSV replication nor elevate antiviral cytokine expression. Our findings for the first time show that PG-1 is an antiviral peptide with effective inhibitory effects on PRRSV infection and replication in Marc-145 cells.


Left ventricular systolic function in subjects conceived through assisted reproductive technologies.
Over the past decades, assisted reproductive technologies (ART) have gained remarkable influence in the treatment of infertility and account for more than 2 % of births in European countries nowadays. Accumulating evidence suggests ART to cause cardiovascular alterations, including left ventricular (LV) dysfunctions, within its offspring. The aim of this study was to assess LV systolic function in subjects conceived through ART in comparison to spontaneously conceived peers. For the assessment of LV morphology and LV function, M-Mode echocardiography, pulsed wave Doppler and two-dimensional speckle tracking echocardiography (2DSTE) were applied. LV ejection fraction (EF) and fractional shortening (FS) were assessed in M-Mode and calculated by Teichholz formula. EF was additionally assessed semiautomatically through 2DSTE. In total, 64 ART subjects and 83 spontaneously conceived controls with no significant differences in age (12.52 ± 5.64 years vs. 13.20 ± 5.95 years, p = 0.486) and sex were included in the analysis. In the ART cohort, significantly lower values were observed for M-Mode assessed EF (63.63 ± 5.17 % vs. 65.35 ± 5.10 %, p = 0.046) and FS (34.26 ± 3.87 % vs. 35.60 ± 3.84 %, p = 0.038). However, after the adjustment for birth weight percentile and gestational age, M-Mode assessed EF and FS displayed no significant differences between both groups. LV morphology and remaining systolic function parameters, such as mitral annular plane systolic excursion, aortic velocity time integral, global peak longitudinal strain and 2DSTE measured EF, were comparable between both groups. This study suggests a lower LV systolic function in ART subjects, visualized by significantly lower values for M-Mode assessed EF and FS, compared to spontaneously conceived peers. The clinical relevance of these findings has to be investigated as the above-mentioned parameters were in normal reference range. In addition, LV systolic function parameters evaluated by other echocardiographic imaging modalities were comparable between both groups. Therefore, further studies will be required to evaluate the influence of ART on LV systolic function and cardiovascular morbidity in the future.


Guidelines for assessment and intervention with persons with disabilities: An executive summary.
This article provides an executive summary of the American Psychological Association's (APA's) revised Guidelines for Assessment and Intervention With Persons With Disabilities. The revision was requested by the Committee on Disability Issues in Psychology and was approved by the APA Council of Representatives in February 2022. The task force updated and expanded the guidelines' empirical bases; squarely situated the guidelines in a changing sociocultural landscape (reflected in discussions of disability models, biases and barriers, language use, intersectionality, and respectful and fair assessment and intervention); and added many concrete suggestions for conceptualizing disability and working with disabled clients and their support systems. In this executive summary, we include key points from each of the 23 guidelines. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Conversion of school nurse policy and procedure manual to electronic format.
Policy and procedure manuals are essential to establishing standards of practice and ensuring quality of care to students and families. The Olathe District Schools (Kansas) Technology Department created the Virtual File Cabinet to provide online access to employee policies, school board policies, forms, and other documents. A task force of school nurses was formed to convert the nursing department's policies, procedures, protocols, and forms from hard copy to electronic format and make them available on the district's Virtual File Cabinet. Having the policy and procedure manuals in electronic format allows for quick access and ease in updating information, thereby guaranteeing the school nurses have access to the most current information. Cost savings were realized by reducing the amount of paper and staff time needed to copy, collate, and assemble materials.


Automatic Measurement of Spine Curvature on 3-D Ultrasound Volume Projection Image With Phase Features.
This paper presents an automated measurement of spine curvature by using prior knowledge on vertebral anatomical structures in ultrasound volume projection imaging (VPI). This method can be used in scoliosis assessment with free-hand 3-D ultrasound imaging. It is based on the extraction of bony features from VPI images using a newly proposed two-fold thresholding strategy, with information of the symmetric and asymmetric measures obtained from phase congruency. The spinous column profile is detected from the segmented bony regions, and it is further used to extract a curve representing spine profile. The spine curvature is then automatically calculated according to the inflection points along the curve. The algorithm was evaluated on volunteers with the different severity of scoliosis. The results obtained using the newly developed method had a good linear correlation with those by the manual method (r ≥ 0.90, p <; 0.001) and X-ray Cobb's method (r = 0.83, p <; 0.001). The bigger variations observed in the manual measurement also implied that the automatic method is more reliable. The proposed method can be a promising approach for facilitating the applications of 3-D ultrasound imaging in the diagnosis, treatment, and screening of scoliosis.


Atopic dermatitis, attachment and partnership: a psychodermatological case-control study of adult patients.
Adult patients with atopic dermatitis were examined from a psychodermatological perspective with respect to attachment attitudes and satisfaction with partnerships. In addition, the correlation between these variables and skin symptoms, as well as the skin-specific quality of life, was also studied. A total of 62 adult patients with atopic dermatitis were compared with a parallel control group with healthy skin (n = 62). There were significant correlations between the patients' attachment characteristics on the one hand and the detriment to skin-specific quality of life on the other. In contrast, partnership satisfaction was not as severely impaired as expected; however, it showed significant correlations with attachment attitudes.


Hyperactivation of ATM upon DNA-PKcs inhibition modulates p53 dynamics and cell fate in response to DNA damage.
A functional DNA damage response is essential for maintaining genome integrity in the presence of DNA double-strand breaks. It is mainly coordinated by the kinases ATM, ATR, and DNA-PKcs, which control the repair of broken DNA strands and relay the damage signal to the tumor suppressor p53 to induce cell cycle arrest, apoptosis, or senescence. Although many functions of the individual kinases have been identified, it remains unclear how they act in concert to ensure faithful processing of the damage signal. Using specific inhibitors and quantitative analysis at the single-cell level, we systematically characterize the contribution of each kinase for regulating p53 activity. Our results reveal a new regulatory interplay in which loss of DNA-PKcs function leads to hyperactivation of ATM and amplification of the p53 response, sensitizing cells for damage-induced senescence. This interplay determines the outcome of treatment regimens combining irradiation with DNA-PKcs inhibitors in a p53-dependent manner.


Digital preconception interventions targeting weight, diet and physical activity: A systematic review.
Optimising preconception health increases the likelihood of conception, positively influences short- and long-term pregnancy outcomes and reduces intergenerational chronic disease risk. Our aim was to synthesise study characteristics and maternal outcomes of digital or blended (combining face to face and digital modalities) interventions in the preconception period. We searched six databases (PubMed, Cochrane, Embase, Web of Science, CINHAL and PsycINFO) from 1990 to November 2022 according to the PRISMA guidelines for randomised control trials, quasi-experimental trials, observation studies with historical control group. Studies were included if they targeted women of childbearing age, older than 18 years, who were not currently pregnant and were between pregnancies or/and actively trying to conceive. Interventions had to be delivered digitally or via digital health in combination with face-to-face delivery and aimed to improve modifiable behaviours, including dietary intake, physical activity, weight and supplementation. Studies that included women diagnosed with type 1 or 2 diabetes were excluded. Risk of bias was assessed using the Academy of Nutrition and Dietetics quality criteria checklist. Study characteristics, intervention characteristics and outcome data were extracted. Ten studies (total participants n=4,461) were included, consisting of nine randomised control trials and one pre-post cohort study. Seven studies received a low risk of bias and two received a neutral risk of bias. Four were digitally delivered and six were delivered using blended modalities. A wide range of digital delivery modalities were employed, with the most common being email and text messaging. Other digital delivery methods included web-based educational materials, social media, phone applications, online forums and online conversational agents. Studies with longer engagement that utilised blended delivery showed greater weight loss. More effective interventions appear to combine both traditional and digital delivery methods. More research is needed to adequately test effective delivery modalities across a diverse range of digital delivery methods, as high heterogeneity was observed across the small number of included studies.


[Prepuce plastic surgery, known as the Lille operation, in distal hypospadias. Apropos of 138 cases].
Distal hypospadias with meatus situated on the glans, in the balano-penile furrow, even on the distal part of the shaft, are the most frequent hypospadias. Without chordee, it's only a cosmetic handicap. The aim of surgery is to produce the esthetic appearance of a normal penis. In France, circumcision is not usual and most people prefer a child with prepuce. The best technique in this case is to keep the meatus in its hypospadial situation and get the prepuce circular with a ventral suture. It's an easy technique. The hospital stay is short, 2 or 3 days, without any diversion of the urine. This operation is made when the child is about 3 years. Saint-Aubert described this procedure in 1967. The authors present their technique and results. Since 1971, 138 boys underwent this operation with few complications: 2% of fistulas and 2% of phimosis on the last hundred of cases.


The Double-Faced Role of Nitric Oxide and Reactive Oxygen Species in Solid Tumors.
Disturbed redox homeostasis represents a hallmark of cancer phenotypes, affecting cellular metabolism and redox signaling. Since reactive oxygen and nitrogen species (ROS/RNS) are involved in regulation of proliferation and apoptosis, they may play a double-faced role in cancer, entailing protumorigenic and tumor-suppressing effects in early and later stages, respectively. In addition, ROS and RNS impact the activity and communication of all tumor constituents, mediating their reprogramming from anti- to protumorigenic phenotypes, and vice versa. An important role in this dichotomic action is played by the variable amounts of O2 in the tumor microenvironment, which dictates the ultimate outcome of the influence of ROS/RNS on carcinogenesis. Moreover, ROS/RNS levels remarkably influence the cancer response to therapy. The relevance of ROS/RNS signaling in solid tumors is witnessed by the emergence of novel targeted treatments of solid tumors with compounds that target ROS/RNS action and production, such as tyrosine kinase inhibitors and monoclonal antibodies, which might contribute to the complexity of redox regulation in cancer. Prospectively, the dual role of ROS/RNS in the different stages of tumorigenesis through different impact on oxidation and nitrosylation may also allow development of tailored diagnostic and therapeutic approaches.


lncRNA Gene Signatures for Prediction of Breast Cancer Intrinsic Subtypes and Prognosis.
Background: Breast cancer is intrinsically heterogeneous and is commonly classified into four main subtypes associated with distinct biological features and clinical outcomes. However, currently available data resources and methods are limited in identifying molecular subtyping on protein-coding genes, and little is known about the roles of long non-coding RNAs (lncRNAs), which occupies 98% of the whole genome. lncRNAs may also play important roles in subgrouping cancer patients and are associated with clinical phenotypes. Methods: The purpose of this project was to identify lncRNA gene signatures that are associated with breast cancer subtypes and clinical outcomes. We identified lncRNA gene signatures from The Cancer Genome Atlas (TCGA )RNAseq data that are associated with breast cancer subtypes by an optimized 1-Norm SVM feature selection algorithm. We evaluated the prognostic performance of these gene signatures with a semi-supervised principal component (superPC) method. Results: Although lncRNAs can independently predict breast cancer subtypes with satisfactory accuracy, a combined gene signature including both coding and non-coding genes will give the best clinically relevant prediction performance. We highlighted eight potential biomarkers (three from coding genes and five from non-coding genes) that are significantly associated with survival outcomes. Conclusion: Our proposed methods are a novel means of identifying subtype-specific coding and non-coding potential biomarkers that are both clinically relevant and biologically significant.


Porous Uranyl Borophosphates with Unique Three-Dimensional Open-Framework Structures.
Two novel alkali-metal uranyl borophosphates have been prepared and characterized for the first time, namely, K5(UO2)2[B2P3O12(OH)]2(OH)(H2O)2 and K2(UO2)12[B(H2PO4)4](PO4)8(OH)(H2O)6 denoted as KUPB1 and KUPB2, respectively. KUPB1 was obtained hydrothermally at 220 °C and crystallizes in a monoclinic structure in the chiral space group P21. The unit cell parameters of KUPB1 are a = 6.7623(2) Å, b = 19.5584(7) Å, c = 11.0110(4) Å, α = γ = 90°, β = 95.579(3)°, and V = 1449.42(8) Å3. It features a unique three-dimensional (3D) open-framework structure, composed of two corner-sharing linked one-dimensional (1D) anionic borophosphates (BP), [B2P3O13]5-, along the a axis and uranyl phosphate (UP), [(UO2)(PO4)3]7-, chains along the c axis, further bridged by PO4 tetrahedra. Multi-intersectional channels can be observed within the structure, in which the largest 11-ring (11-R) tunnel size is ∼7.0 Å × 8.8 Å. Its simplified framework can be described as a new 4-nodal net topological type with a point symbol of {4.84.10}{42.6}2{220.127.116.11}{82.10}. By modification of the synthetic conditions of KUPB1 through an increase in the amount of H3BO3 as flux 4-fold and a reduction of water as the reaction medium, the novel compound KUPB2 is generated. The unit cell parameters of KUPB2 are a = b = 21.8747(3) Å, c = 7.0652(2) Å, α = β = γ = 90°, and V = 3380.72(12) Å3. KUPB2 crystallizes in a tetragonal structure in the polar space group I4̅2m, and its structure is based on a highly complex 3D framework, {(UO2)12[B(PO4)4](PO4)8}9-, in which 1D 8-R UP [(UO2)(PO4)]- tubes can be observed along the c axis. The [(UO2)(PO4)]- tubes consist of three uranyl chains along the c axis, which are linked alternately by [PO4]3- tetrahedra. Those isolated 1D [(UO2)(PO4)]- tubes are further bridged through [(UO2)4B(PO4)4]- clusters, forming an exceptional 3D open-framework structure. Its simplified cation network is a new 5-nodal net topological type such as {126.96.36.199.7.8}8{220.127.116.11}8{4.62.83}4{42.6}4{44.62}. Their facile hydrothermal synthetic routes, porous structure topology, thermal stability, and Raman spectroscopy properties are reported and discussed.


Spatial distribution, risk assessment, and source identification of pollutants around gold tailings ponds: a case study in Pinggu District, Beijing, China.
This work investigated heavy metal and cyanide pollution in surface soils and edible plants around Yanzhuang gold tailings ponds in the region of Yanzhuang Village in Pinggu District, Beijing. Surface soil samples were collected from 33 sites around gold tailings ponds, and concentrations of seven heavy metals (i.e., Sb, As, Cd, Cu, Pb, Zn, and Hg) and cyanide were analyzed to determine their spatial distributions, pollution degrees, and sources. The potential ecological risks of As, Cd, Cu, Pb, Zn, and Hg were preliminarily assessed. The results showed that the mean cyanide, Sb, As, Cd, Cu, and Pb concentrations were higher than the standard values. The pollutant concentrations around the tailings ponds were high and decreased with increasing distance from the ponds. The single pollution index indicated that cyanide, As, and Cd were the main pollutants. The Nemerow pollution index revealed a large region and serious degree of heavy metal pollution in soils. The potential ecological risk level of the study area was moderate, with Cd and As posing the main risks. Multivariate statistical analysis suggested that the heavy metal and cyanide pollution present mainly derived from gold tailings, with agricultural pollution also had a certain effect. However, the 12 edible plants sampled were basically not polluted.


Efficacy, safety, and tolerability of extended-release once-daily tolterodine treatment for overactive bladder in older versus younger patients.
To evaluate the efficacy, safety, and tolerability of a new, once-daily extended-release (ER) formulation of tolterodine in treating overactive bladder in older (> or =65) and younger (<65) patients. A 12-week double-blind, placebo-controlled clinical trial. An international study conducted at 167 medical centers. One thousand fifteen patients (43.1% aged > or =65) with urge incontinence and urinary frequency. Patients were randomized to treatment with tolterodine ER 4 mg once daily (qd) (n = 507) or placebo (n = 508) for 12 weeks. Efficacy, measured with micturition charts (incontinence episodes, micturitions, volume voided per micturition) and subjective patient assessments, safety, and tolerability endpoints were evaluated, relative to placebo, according to two age cohorts: younger than 65 and 65 and older. Mean age in the older and younger patient cohorts was 74 (range 65-93) and 51 (range 20-64), respectively. Compared with placebo, significant improvements in micturition chart variables with tolterodine ER showed no age-related differences. Irrespective of age, significantly more tolterodine ER recipients than placebo recipients reported an improvement in urgency symptoms. After 12 weeks of treatment with tolterodine ER, a fivefold increase in the percentage of patients able to finish tasks before voiding in response to urgency was noted in both age groups (<65: from 6.5-32.8%, > or =65: from 5.1-26.2%). Tolterodine ER recipients, irrespective of age, also had significant improvements in their bladder condition than did placebo recipients. Overall, a greater percentage of patients, irrespective of age, perceived any benefit with tolterodine ER than with placebo (P <.001). Dry mouth (of any severity) was the most common adverse event in both the tolterodine ER and placebo treatment arms, irrespective of age (<65: ER 22.7%, placebo 8.1%; > or =65: ER 24.3%, placebo 7.2%). Few patients (<2%) experienced severe dry mouth. No central nervous system, visual, cardiac (per electrocardiogram), or laboratory safety concerns were noted. Withdrawal rates due to adverse events on tolterodine ER 4 mg qd were comparable in the two age cohorts (<65: 5.5%; > or =65: 5.1%; P =.87). The new, once-daily ER formulation of tolterodine is efficacious, safe, and well tolerated in the treatment of patients with symptoms of overactive bladder, irrespective of age.


Pharmacologic treatment of eating disorders.
Eating disorders are a serious group of conditions that affect 3% of women in industrialized nations over their lifetimes. Recent years have seen considerable progress in the treatment of these disorders. This article reviews the current body of evidence for the pharmacologic treatment of eating disorders. We undertook a literature review. For patients with anorexia nervosa (AN), drug trials have been disappointing. In contrast, numerous studies have demonstrated a clear role for antidepressants in the treatment of bulimia nervosa (BN). Pharmacologic investigations of binge eating disorder (BED), a more recently defined entity, have identified several promising drugs. There is also support for the utility of combined medication and psychotherapy. Continued research efforts are necessary, particularly regarding the long-term effects of therapy and the development of new pharmacologic strategies.


Low-dose perinatal supplementation with Enterococcus faecalis increases concentrations of short-chain fatty acids in the offspring but does not protect against allergic asthma.
Childhood allergic asthma is associated with a dysbiotic gut microbiome in early life, and maternal perinatal treatment with probiotics is a potential way alter the infant microbiome, which may improve asthma outcomes. This study used a mouse model to examine the effect of maternal supplementation with the probiotic Enterococcus faecalis on faecal short-chain fatty acid (SCFA) concentrations and asthma risk in the offspring. Pregnant/lactating mice were treated daily, from gestation day 6 to postnatal day 21, with an oral suspension of 106, 107 or 108 colony-forming units of a live preparation of the probiotic E. faecalis (Symbioflor®1). At weaning, offspring were subjected to an ovalbumin-induced experimental asthma protocol. Faeces were collected from the mothers and offspring at several different time points to determine SCFA concentrations. It was found that maternal supplementation with E. faecalis did not alter litter size, sex ratio or offspring weight, and was associated with an increase in SCFAs in offspring faeces at weaning and after allergy induction. However, allergic offspring from E. faecalis supplemented mothers showed no difference in asthma severity when compared with allergic offspring from control mothers. In conclusion, although maternal perinatal supplementation with low-dose E. faecalis was associated with increased faecal SCFAs in the offspring, it did not protect against offspring asthma. This is may be because SCFA concentrations were not increased to an immunoprotective level. We recommend that future studies concentrate on probiotic supplementation in high-risk cases, for instance, to repair gut dysbiosis resulting from antibiotic use in pregnant mothers or their infants.


Morphometric comparison of human nerve cells: pyramidal motor system.
We compared morphological and morphometric data on various motor neurons in the human pyramidal system using the modified Klüver-Barrera staining method with extremely minimized shrinkage ratio and an image-analyzer. We classified motor neurons in the human pyramidal system into three groups according to the measurement data. This report may be of interest to better understand the process of nerve conduction in the human pyramidal system.


Transcriptional upregulation of MT2-MMP in response to hypoxia is promoted by HIF-1α in cancer cells.
Hypoxia is a critical event in solid tumor development, invasion, and metastasis. Cellular adaptation to hypoxic microenvironment is essential for tumor progression and is largely mediated by hypoxia-inducible factor-1α (HIF-1α) through coordinated regulation of hypoxia-responsive genes. In this study, we found that membrane type-2 matrix metalloproteinase (MT2-MMP), one of the matrix metalloproteinase (MMP) family members, was a novel hypoxia-responsive gene and was upregulated by HIF-1α under hypoxia. When cancer cells were subjected to hypoxia (1% O(2) ) treatment, the mRNA and protein levels of MT2-MMP were significantly increased in a time-dependent manner in all three tested cancer cell lines including pancreatic cancer cells (PANC-1), nonsmall cell lung cancer cells (A-549), and cervix cancer cells (HeLa). Further analyses indicated that there were two hypoxia-responsive elements (HREs) in the MT2-MMP promoter, and HRE1 but not HRE2 was essential for MT2-MMP transcriptional activation under hypoxia. HIF-1α specifically and directly bound to MT2-MMP promoter was analyzed by HIF-1α binding/competition and chromatin immunoprecipitation (ChIP) assays. Furthermore, we found that upregulation of MT2-MMP under hypoxia could confer resistance to hypoxia-induced apoptosis and increase invasiveness of cancer cells. These findings provided a new insight into how cancer cells overcome hypoxic stress and trend to survive and invade, demonstrated a new regulatory mechanism of MT2-MMP expression in caner cells, and also revealed that MT2-MMP was a novel hypoxia-responsive gene and was upregulated by HIF-1α under hypoxia. © 2011 Wiley-Liss, Inc.


Organizational Facilitators and Barriers to Medication for Opioid Use Disorder Capacity Expansion and Use.
Medication for opioid use disorder (MOUD) is a key strategy for addressing the opioid use disorder crisis, yet gaps in MOUD provision impede this strategy's benefits. The research reported here sought to understand what distinguishes low- and high-performing organizations in building and using capacity to provide MOUD. As part of a mixed methods MOUD implementation trial, semi-structured telephone interviews were conducted with personnel from low- and high-performing MOUD-providing organizations. Seventeen individuals from 17 organizations were interviewed. Findings demonstrate the importance of individual, organization, and community-level factors in supporting the building and use of MOUD capacity. Low- and high-performing organizations showed different patterns of facilitators and barriers during the implementation process. The key difference between low- and high-performing organizations was the level of organizational functioning. A better understanding of an organization's assets and deficits at the individual, organizational, and community levels would allow decision-makers to tailor their approaches to MOUD implementation.


Tofacitinib versus etanercept or placebo in patients with moderate to severe chronic plaque psoriasis: patient-reported outcomes from a Phase 3 study.
Tofacitinib is an oral Janus kinase inhibitor that is being investigated for psoriasis. Psoriasis impacts on physical and psychological well-being; improvements in health-related quality of life (HRQoL) with etanercept in psoriasis are well documented. To evaluate HRQoL with tofacitinib, vs. placebo or etanercept, in the Phase 3, randomized, placebo-controlled, non-inferiority, Oral-treatment Psoriasis Trial (OPT) Compare Study (NCT01241591). Adults with moderate to severe chronic plaque psoriasis were randomized 3:3:3:1 to tofacitinib 10 or 5 mg twice daily (BID), etanercept 50 mg twice weekly or placebo, for 12 weeks. Patient-reported outcomes (PROs) included Dermatology Life Quality Index (DLQI), Itch Severity Item and Patient Global Assessment of psoriasis. At baseline, 83.4% (911/1092) of patients had a DLQI score ranging between 6 and 30, indicating a substantial burden of disease. By Week 12, 47.3%, 43.6% and 30.9% of patients in the tofacitinib 10 mg BID, etanercept and tofacitinib 5 mg BID groups, respectively, had a DLQI score of 0 or 1 (no effect of psoriasis on QoL) vs. 7.8% for placebo (all P < 0.0001). Tofacitinib significantly reduced itch vs. placebo (P < 0.05 both doses) and etanercept (P < 0.0001 both doses) within 1 day of starting treatment. Furthermore, reductions in itch were greater with tofacitinib 10 mg BID, vs. etanercept, at Weeks 2-12 (all time points P < 0.05). At Week 2, an Itch Severity Item score of 'little or no itch' was more frequent with tofacitinib 10 mg (68.6%) vs. etanercept (57.4%) and placebo (12.2%), and the PtGA response rate was significantly greater with tofacitinib 10 mg vs. placebo (P < 0.05). Oral tofacitinib provided significant improvements across multiple PROs by Week 12. Improvements with tofacitinib 10 mg BID were comparable to etanercept, and improvements in itch were greater and more rapid with tofacitinib 10 mg BID.


The prognostication problem.
With increased focus on end-of-life care; prognosis may be finally receiving the attention it deserves. Hopefully, this will result in further research, the development of effective tools, and adequate education and training related to prognostication.


Hydrogen-deuterium exchange experiments to probe the decomposition reaction of sodium alanate.
NaAlH(4) is the archetypical complex hydride for hydrogen storage. The extraordinary effect of dopants on the sorption kinetics triggered the investigation of this empirical finding. In this paper, a short review of the state of the art is given. To gain further understanding of the mechanisms involved we label the interacting species during the sorption process. This was experimentally realized by hydrogen-deuterium exchange measurements during the decomposition of NaAlH(4) followed by thermogravimetry, Raman spectroscopy and mass spectrometry. By these experiments we are able to obtain specific information on the diffusing species and formation of intermediates. The activation energy of tracer diffusion in NaAlH(4) is found to be 0.28 eV. The results are evidence for a vacancy-mediated desorption process of NaAlH(4).


A Rough-to-Fine Evolutionary Multiobjective Optimization Algorithm.
This article presents a rough-to-fine evolutionary multiobjective optimization algorithm based on the decomposition for solving problems in which the solutions are initially far from the Pareto-optimal set. Subsequently, a tree is constructed by a modified k -means algorithm on N uniform weight vectors, and each node of the tree contains a weight vector. Each node is associated with a subproblem with the help of its weight vector. Consequently, a subproblem tree can be established. It is easy to find that the descendant subproblems are refinements of their ancestor subproblems. The proposed algorithm approaches the Pareto front (PF) by solving a few subproblems in the first few levels to obtain a rough PF and gradually refining the PF by involving the subproblems level-by-level. This strategy is highly favorable for solving problems in which the solutions are initially far from the Pareto set. Moreover, the proposed algorithm has lower time complexity. Theoretical analysis shows the complexity of dealing with a new candidate solution is O(M logN) , where M is the number of objectives. Empirical studies demonstrate the efficacy of the proposed algorithm.


Dispersing nanotubes with surfactants: a microscopic statistical mechanical analysis.
A first theoretical study of surfactant-stabilized carbon nanotube dispersions is presented. Density functional theory is used to compute potential of mean force between nanotubes in an aqueous solution of cationic surfactant n-decyltrimethylammonium chloride. In agreement with experimental results, it is found that stable dispersions can be prepared for surfactant bulk concentrations below the critical micelle concentration. Computed density profiles of head and tail segments indicate that surfactants adsorb on nanotube surfaces in a random fashion rather than form cylindrical micelles, which is also in agreement with recent small-angle neutron scattering measurements.


Interferon production by human and murine lymphocytes in response to alloantigens.
The production of interferon (IF) by human and mouse lymphocytes sensitized to alloantigens in mixed lymphocyte cultures (MLC) was analyzed. During primary MLC, IF appeared in the culture fluid on day 2 and was maximal on day 5. Based on several biologic criteria, the IF produced is of the "immune" type. When lymphocytes sensitized to alloantigens were reestimulated in vitro, IF was produced within a few hours of culture. In all stimulated cultures, cell proliferation was observed in spite of the high concentrations of IF. The IF-producing cells in human MLC were identified as T lymphocytes lacking the receptor for the Fc fragment of IgG molecules (Fc gamma R(-)). Human MLC supernatants containing immune type IF mediate the enhancement of natural killer (NK) cell activity and protect NK target cells from lysis.


Blood pressure measurement modalities and indexed left ventricular mass in men with low-risk hypertension confirmed by ambulatory monitoring.
Blood pressure (BP) measurement modalities such as ambulatory monitoring (ABPM) and noninvasive central aortic systolic pressure (CASP), have been reported to improve prediction of hypertension-mediated organ damage (HMOD) compared with conventional clinic BP. However, clinic BP is often confounded by poor measurement technique and 'white-coat hypertension' (WCH). We compared prediction of cardiac MRI (cMRI)-derived left ventricular mass index (LVMI) by differing BP measurement modalities in young men with elevated BP, confirmed by ABPM. One hundred and forty-three treatment-naive men (<55 years) with hypertension confirmed by ABPM and no clinical evidence of HMOD or cardiovascular disease (37% with masked hypertension) were enrolled. Relationships between BP modalities and cMRI-LVMI were evaluated. Men with higher LVMI (upper quintile) had higher clinic, central and ambulatory SBP compared with men with lower LVMI. Regression coefficients for SBP with LVMI did not differ across BP modalities ( r = 0.32; 0.3; 0.31, for clinic SBP, CASP and 24-h ABPM, respectively, P < 0.01 all). Prediction for high LVMI using receiver-operated curve analyses was similar between measurement modalities. No relationship between DBP and LVMI was seen across measurement modalities. In younger men with hypertension confirmed by ABPM and low cardiovascular risk, clinic SBP and CASP, measured under research conditions, that is, with strict adherence to guideline recommendations, performs as well as ABPM in predicting LVMI. Prior reports of inferiority for clinic BP in predicting HMOD and potentially, clinical outcomes, may be due to poor measurement technique and/or failure to exclude WCH.


Normal osteoid tissue.
The results of a histological study of normal osteoid tissue in man, the monkey, the dog, and the rat, using thin microtome sections of plastic-embedded undecalcified bone, are described. Osteoid tissue covers the entire bone surface, except for areas of active resorption, although the thickness of the layer of osteoid tissue varies at different sites and in different species of animals. The histological features of osteoid tissue, apart from its amount, are the same in the different species studied. Distinct bands or zones are recognizable in some layers of osteoid tissue, particularly those of greatest thickness, and their significance is discussed. Some of the histological features of the calcification front are described.


Mesostructured TiO2 Gated Periodic Mesoporous Organosilica-Based Nanotablets for Multistimuli-responsive Drug Release.
A multistimuli-responsive drug carrier is designed and successfully synthesized by self-assembly of thiol-modified periodic mesoporous organosilica (PMO) nanoparticles, coated gold nanoparticles (AuNPs), and mesostructured titanium dioxide (TiO2). Dye-loaded PMO-Au@TiO2 nanotablets are shown to respond to environmental changes (pH, temperature, and light) to achieve controlled release.


Evaluation of the dose-effect relationship of a new ace inhibitor (perindopril) by an automatic blood pressure recorder.
Repeated blood pressure recordings by non-invasive devices are of better predictive value than single measurements in the evaluation of antihypertensive treatment. Such a method has been used to establish the dose-effect relationship of perindopril. After a two-week placebo run-in period, 40 patients with essential hypertension (age 56.6 +/- 1.5 years, 31 males, nine females) were treated with placebo or 2, 4 or 8 mg of perindopril once daily for one month following a randomized double-blind design. They were included if at least 75% of diastolic blood pressure recordings, made over an 8 h diurnal period using an automatic blood pressure recorder, were greater than 95 mmHg on placebo. Values (mean +/- SEM) before and after treatment were assessed using analysis of variance. These data showed a significantly greater reduction of blood pressure with 4 mg and 8 mg daily doses compared to placebo and the 2 mg daily dose. Such results were not obtained with blood pressure levels recorded by a mercury sphygmomanometer, confirming the value of an automatic blood pressure recorder as a tool in therapeutic trials.


Leiomyoma originating from axilla: A rare case report and differential diagnosis.
Leiomyoma is a form of benign tumor originated in hypertrophy of the smooth muscles, which is most prevalent in the uterus and gastrointestinal tract. However, Leiomyoma originating from smooth muscle at the vessels lying on deep soft tissue is very rare. Our case was a rare case of leiomyoma originating from the axillary region, which was initially diagnosed as a fibroadenoma on radiological examination. The mass was separated from surrounding tissues and totally resected. Pathologically, hematoxylin-eosin-stained biopsy tissue showed the typical findings of leiomyoma. Postoperative follow-up observation was done for 1 year, without any complications or recurrence. Notably, a leiomyoma in the axillary region is difficult to differentiate from other benign or malignant tumors on preoperative radiological examinations such as ultrasonography or computed tomgraphy. Therefore, when an indefinite asymptomatic mass that is not lymphadenopathy or common benign tumor is identified in the axillary region, leiomyoma can be considered as one of the differential diagnoses.


Abundance and composition of near surface microplastics and plastic debris in the Stockholm Archipelago, Baltic Sea.
We collected plastic debris in the Stockholm Archipelago using a manta trawl, and additionally along a transect in the Baltic Sea from the island of Gotland to Stockholm in a citizen science study. The samples were concentrated by filtration and organic material was digested using hydrogen peroxide. Suspected plastic material was isolated by visual sorting and 59 of these were selected to be characterized with Fourier transform infrared spectroscopy. Polypropylene and polyethylene were the most abundant plastics identified among the samples (53% and 24% respectively). We found nearly ten times higher abundance of plastics near central Stockholm than in offshore areas (4.2×105plastics km-2 compared to 4.7×104plastics km-2). The abundance of plastic debris near Stockholm was similar to urban areas in California, USA, and the overall abundance in the Stockholm Archipelago was similar to plastic abundance reported in the northwestern Mediterranean Sea.


Permanent muscle weakness in hypokalemic periodic paralysis.
To map the phenotypic spectrum in 55 individuals with mutations in CACNA1S known to cause hypokalemic periodic paralysis (HypoPP) using medical history, muscle strength testing, and muscle MRI. Adults with a mutation in CACNA1S known to cause HypoPP were included. Medical history was obtained. Muscle strength and MRI assessments were performed. Fifty-five persons were included. Three patients presented with permanent muscle weakness and never attacks of paralysis. Seventeen patients presented with a mixed phenotype of periodic paralysis and permanent weakness. Thirty-one patients presented with the classical phenotype of periodic attacks of paralysis and no permanent weakness. Four participants were asymptomatic. Different phenotypes were present in 9 of 18 families. All patients with permanent weakness had abnormal replacement of muscle by fat on MRI. In addition, 20 of 35 participants with no permanent weakness had abnormal fat replacement of muscle on MRI. The most severely affected muscles were the paraspinal muscles, psoas, iliacus, the posterior muscles of the thigh and gastrocnemius, and soleus of the calf. Age was associated with permanent weakness and correlated with severity of weakness and fat replacement of muscle on MRI. Our results show that phenotype in individuals with HypoPP-causing mutations in CACNA1S varies from asymptomatic to periodic paralysis with or without permanent muscle weakness or permanent weakness as sole presenting picture. Variable phenotypes are found within families. Muscle MRI reveals fat replacement in patients with no permanent muscle weakness, suggesting a convergence of phenotype towards a fixed myopathy with aging.


Lodgement of haemopoietic cells in the course of haemopoiesis on cellulose ester membrane: an experimental model for haemopoietic cell trapping.
Intraperitoneally implanted cellulose ester membrane in mice was used as a model to study the lodgement of haemopoietic cells into haemopoietic organs. A heterogeneous cellular coat developed on the membrane. Its upper layer ( epilayer ) thinned out and formed a veil over the cellular coat. Numerous microvilli developed on its free surface. They were randomly oriented. A week after implantation, mice were given total body irradiation (400 cGy) and were infused intraperitoneally with 10(5) marrow cells. Two days after infusion round cells were penetrating the epilayer . Extensive interaction was noted between the surface of the penetrating cells and the microvilli of the epilayer . Penetration was through a single cell in the epilayer and not at the junction of two cells. These observations suggest specific interaction between haemopoietic cells and the supporting tissue leading to lodgement of haemopoietic cells. Intraperitoneally implanted cellulose ester membrane may provide an experimental model for haemopoietic cell trapping.


The Kinocilia of Cochlear Hair Cells: Structures, Functions, and Diseases.
Primary cilia are evolutionarily conserved and highly specialized organelles that protrude from cell membranes. Mutations in genes encoding ciliary proteins can cause structural and functional ciliary defects and consequently multiple diseases, collectively termed ciliopathies. The mammalian auditory system is responsible for perceiving external sound stimuli that are ultimately processed in the brain through a series of physical and biochemical reactions. Here we review the structure and function of the specialized primary cilia of hair cells, termed kinocilia, found in the mammalian auditory system. We also discuss areas that might prove amenable for therapeutic management of auditory ciliopathies.


A new approach for high-yield metal-molecule-metal junctions by direct metal transfer method.
The realization of high-yield, stable molecular junctions has been a long-standing challenge in the field of molecular electronics research, and it is an essential prerequisite for characterizing and understanding the charge transport properties of molecular junctions prior to their device applications. Here, we introduce a new approach for obtaining high-yield, vertically structured metal-molecule-metal junctions in which the top metal electrodes are formed on alkanethiolate self-assembled monolayers by a direct metal transfer method without the use of any additional protecting interlayers in the junctions. The fabricated alkanethiolate molecular devices exhibited considerably improved device yields (∼70%) in comparison to the typical low device yields (less than a few %) of molecular junctions in which the top metal electrodes are fabricated using the conventional evaporation method. We compared our method with other molecular device fabrication methods in terms of charge transport parameters. This study suggests a potential new device platform for realizing robust, high-yield molecular junctions and investigating the electronic properties of devices.


Tuberculosis Presenting With Acute Myocarditis and Systolic Heart Failure.
Tuberculosis presenting with myocarditis and severe systolic dysfunction is rarely reported. So far, only a few cases were reported from India. Our aim is to report this rare presentation of a common disease that we encountered at Narayana Multispecialty Hospital, Jaipur. A 34-year-old lady having disseminated tuberculosis involving lung, lymph node, and myocardium with severe left ventricular systolic dysfunction received medical treatment in our hospital. She had elevated cardiac biomarkers, severe left ventricular regional wall hypokinesis with an ejection fraction of 25-30%, bilateral upper and middle lobe ground-glass opacities, as well as mediastinal and hilar lymphadenopathies on chest computed tomography scan and normal coronary angiogram. The patient was started with anti-tuberculosis therapy, a beta-blocker, an angiotensin-converting enzyme inhibitor, and a corticosteroid and discharged after one week in a stable condition. The third month of follow up showed recovery and improvement in cardiac function.


Origin of Fueguian-Patagonians: an approach to population history and structure using R matrix and matrix permutation methods.
A complicated history of isolation between Fueguian and Patagonian groups (originated by the appearance of the Straits of Magellan) as much as differences in population structure and life strategies constitute important factors in the clustering pattern of those groups. The aim of this work was to test several hypotheses about population structure and history of Fueguian-Patagonians to propose a model that incorporates predictions for future studies. R matrix methods and matrix permutation analyses were performed upon a data matrix of craniofacial measurements of 441 skulls divided into nine samples pertaining to six Patagonian and three Fueguian populations. Association of biological distances with three matrices representing several settlement patterns was tested using matrix permutation tests. Results of R matrix study show that the minimum genetic distance obtained confirms separation between Fueguians and Patagonians. Moreover, an analysis of residual variances from the expected regression line confirms admixture between Andean and Pampean populations and Araucanian groups, consistent with ethnohistorical observations. A model representing a long history of isolation between Fueguian and Patagonians, rather than a model emphasizing differences in life-strategies, presented the best correlation with the biological distance matrix. Because similar results were already obtained in archaeological, molecular, and morphological studies, a model for the settlement of Tierra del Fuego is proposed. It is summarized by four main hypotheses that can be tested independently by different disciplines in the future.


Prevalence of feline coronavirus antibodies in Japanese domestic cats during the past decade.
From 2001 to 2010, 17,392 Japanese cats were examined for feline coronavirus (FCoV) antibodies. The seroprevalence of purebreds (66.7%) was higher than that of random breds (31.2%). Seroprevalence increased greatly in purebreds by three months of age, while it did not fluctuate greatly in random breds with aging, indicating that cattery environments can contribute to FCoV epidemics. Purebreds from northern regions of Japan were likely to be seropositive (76.6% in Hokkaido, 80.0% in Tohoku), indicating cattery cats in cold climates might be more closely confined. Among purebreds, the American shorthair, Himalayan, Oriental, Persian, and Siamese showed low seroprevalence, while the American curl, Maine coon, Norwegian forest cat, ragdoll and Scottish fold showed high seroprevalence. There would also be breed-related differences in Japan similar to the previous studies in Australia.


Is there a question of safety with continuous wear?
The availability of silicone-containing hydrogel contact lenses (SCHCLs) has refocused attention on the risks associated with continuous wear (CW). The major barrier to optometrists prescribing CW in Western societies is a perceived danger of microbial keratitis (MK). This perception has been shaped largely by educators who have developed their opinions from case reports in the ophthalmic literature, sensationalist lay press reports and later epidemiological studies and from prominent physicians in tertiary referral centres, following an increased incidence of MK with extended wear (EW) of traditional hydrogel materials. The basis for the perceived lack of safety is the higher risk of MK with EW compared to daily wear and incidence figures that suggest an unacceptable level of MK in a population at risk, albeit a small risk on an individual basis. In this paper, I re-evaluate the validity of the previous data and challenge the conclusions regarding the nature of the risk with traditional hydrogel lens materials. Areas under scrutiny include diagnostic criteria, morbidity caused by different micro-organisms, potential bias in studies and reports, analysis of visual outcomes and cost to the community, and improvements over time in the understanding and handling of contact lens-related complications. Significant loss of vision with EW appears to be less frequent than is the common perception. When the risks are placed in the perspective of other data such as that for refractive surgery, the arguments against EW do not seem so compelling. The high oxygen transmissibility of SCHCLs may enable safe CW but a large-scale epidemiological study is needed to allay remaining doubts. Any such future studies should note the points outlined in this document.


Stereoselective total synthesis of arachnid harvestmen natural product: (4S,5S)‑4-hydroxy-γ-decalactone.
Herein, we described the novel synthetic strategy for the total synthesis of harvestmen natural product (4S,5S)‑4-hydroxy-γ-decalactone (minor) from an inexpensive precursor ((R)-2,2-dimethyl-1,3-dioxolane-4-carbaldehyde) with 31% overall yield. Hydroxy-γ-lactones represent a special class of harvestmen exocrine defense compounds. The present convergent synthesis utilizes classical reactions like the Barbier reaction, the Grignard reaction, and the employment of an olefin as a masked carboxylic acid functionality followed by lactone formation as key steps.


A combined reed bed/freezing bed technology for septage treatment and reuse in cold climate regions.
A combined reed bed-freezing bed (RB-FB) technology was effective at treating septage under Canadian climatic conditions over a 5-year period with average loading rates of 82-104 kg TS/m2/y. Varying hydraulic and solid loading rates as well as the increasing sludge cake with time had little to no effect on treatment efficiency, with almost complete removal of organic matter, solids, heavy metals and nutrients. Filtrate concentrations varied significantly between the freeze-thaw and growing seasons for many parameters, although the differences were not important from a treatment or reuse perspective with filtrate quality similar to a low to medium strength domestic wastewater. The potential to reuse the filtrate as a source of irrigation water will depend upon local regulations. The dewatered sludge cake consistently met biosolids land application standards in terms of pathogen and metals content, with Escherichia coli numbers declining with time as sludge cake depth increased. A combined RB-FB technology can provide a cost-effective solution for septage management in northern rural communities with potential for beneficial reuse of both the filtrate and dewatered sludge cake.


Factor analysis of the Pediatric Symptom Checklist with a chronically ill pediatric population.
The psychometric properties and factor structure of a widely used screening measure for behavioral and emotional dysfunction, the Pediatric Symptom Checklist (PSC), was extended to a population of chronically ill children. Parents of 404 children ranging from 6 to 17 years of age and diagnosed with either insulin-dependent diabetes mellitus (IDDM) or sickle cell disease (SCD) completed the PSC while waiting for a routine medical appointment. The measure's internal consistency was found to be high, Cronbach's alpha = .89, and test-retest reliability across 4 months was observed to be acceptable, r = .77. A principal components analysis with an oblique (promax) rotation yielded a four-factor solution with factors that included items representative of internalizing, externalizing, attention, and chronic illness-related problems, respectively. Cronbach alpha estimates ranged from .78 to .83 for the first three factors but was lower for the chronic illness-related problems factor (Cronbach's alpha = .60). A three-factor solution and reliability estimates were recomputed without the chronic illness items that yielded the same reliability estimates for each of the three factors and for the full scale. The three-factor solution was also found to be similar to a published factor structure obtained with a primary care sample, r(c) = .90-.91. The findings lend support to extending the PSC's clinical utility to tertiary care pediatric settings. Further research is recommended with a broader range of chronic illness groups to increase generalizability.


Degree of roasting of carob flour affecting the properties of gluten-free cakes and cookies.
Carob flour is a product rich in fibre obtained from by-products of the locust bean gum extraction processing. The flour is commercialised with different degrees of roasting in order to improve its organoleptic characteristics. In this study, carob flour with three different roasting degrees was used to replace rice flour (15%) in gluten-free cakes and cookies. The influence of this replacement was studied on the psychochemical characteristics and acceptability of the final products. The incorporation of carob flour increased the viscosity of cake batters and increased the solid elastic-like behaviour of the cookie doughs, indicating a stronger interaction among the formula ingredients. The inclusion of carob flour, with a low time of roasting, did not lead to any significant differences in the specific volume and hardness of the cakes, but reduced cake staling and the thickness and width of the cookies. Darker colours were obtained when carob flour was incorporated into the product. The acceptability of cakes was only reduced with the addition of highly roasted carob flour, while in the case of cookies there was a decline in the acceptability of all carob flour cookies, which was mostly perceived with the highest roasting degree, something mainly attributed to the bitter taste of the products.


Shallow-water seismoacoustic noise generated by tropical storms Ernesto and Florence.
Land-based seismic observations of double frequency (DF) microseisms generated during tropical storms Ernesto and Florence are dominated by signals in the 0.15-0.5 Hz band. In contrast, data from sea floor hydrophones in shallow water (70 m depth, 130 km off the New Jersey coast) show dominant signals in the ocean gravity-wave frequency band, 0.02-0.18 Hz, and low amplitudes from 0.18 to 0.3 Hz, suggesting significant opposing wave components necessary for DF microseism generation were negligible at the site. Florence produced large waves over deep water while Ernesto only generated waves in coastal regions, yet both storms produced similar spectra. This suggests near-coastal shallow water as the dominant region for observed microseism generation.


MORPHOLOGICAL DIFFERENTIATION AND GENETIC COHESIVENESS OVER A MICROENVIRONMENTAL GRADIENT IN THE MARINE SNAIL LITTORINA SAXATILIS.
The marine gastropod Littorina saxatilis has different ecotypes in shores only a few meters apart. This has both taxonomic and evolutionary implications. Here we report on an extreme type of within-shore dimorphism in shell characters. In the wave-exposed rocky shores in northwestern Spain, we found one form of L. saxatilis in the upper-level barnacle zone. It had a white, ridged shell, with black bands in the grooves. Another form confined to the lower-shore mussel belt had a smooth shell that was either white and tessellated or darkly colored. These two forms cooccured in a narrow midshore zone together with individuals that had combined characters, but were present in low frequencies (11%-29%). We used principal-component analysis of metric shell characters to study variation in shell size and shape. We found that the upper-shore form was larger than the lower-shore form. We also found small but significant differences in shell shape. Experiments in a common laboratory environment suggested the differences in shell ornamentation and color are inherited, but the individuals did not develop the morph-specific characters until a shell height of about 3 mm. The occurrence of mainly two distinct forms may suggest the presence of two species that hybridize. An analysis of five polymorphic enzyme loci in populations of snails from three geographically separated sites indicated, however, that there was no positive correlation between morphological distances and genetic distances among populations on a geographic scale (tens of kilometers). Thus, we rejected the hypothesis of two species. However, on a microgeographic scale (meters), genetic differentiation between groups with the same form was less than differentiation between forms. This indicated a partial barrier to gene flow between the two forms, and preliminary mate choice data suggested this was caused by nonrandom mating in the midshore zone of overlap.


Novel paradigms for the gut-brain axis during alcohol withdrawal, withdrawal-associated depression, and craving in patients with alcohol use disorder.
Patients with alcohol use disorder (AUD) exhibit symptoms such as alcohol withdrawal, depression, and cravings. The gut-immune response may play a significant role in manifesting these specific symptoms associated with AUD. This study examined the role of gut dysfunction, proinflammatory cytokines, and hormones in characterizing AUD symptoms. Forty-eight AUD patients [men (n = 34) and women (n = 14)] aged 23-63 years were grouped using the Clinical Institute Withdrawal Assessment of Alcohol Scale (CIWA) as clinically significant (CS-CIWA [score > 10] [n = 22]) and a clinically not-significant group (NCS-CIWA [score ≤ 10] [n = 26]). Clinical data (CIWA, 90-day timeline followback [TLFB90], and lifetime drinking history [LTDH]) and blood samples (for testing proinflammatory cytokines, hormones, and markers of intestinal permeability) were analyzed. A subset of 16 AUD patients was assessed upon admission for their craving tendencies related to drug-seeking behavior using the Penn-Alcohol Craving Score (PACS). CS-CIWA group patients exhibited unique and significantly higher levels of adiponectin and interleukin (IL)-6 compared to NCS-CIWA. In the CS group, there were significant and high effects of association for the withdrawal score with gut-immune markers (lipopolysaccharide [LPS], adiponectin, IL-6, and IL-8) and for withdrawal-associated depression with gut-immune markers (scored using MADRS with LPS, soluble cells of differentiation type 14 [sCD14], IL-6, and IL-8). Craving (assessed by PACS, the Penn-Alcohol Craving Scale) was significantly characterized by what could be described as gut dysregulation (LBP [lipopolysaccharide binding protein] and leptin) and candidate proinflammatory (IL-1β and TNF-α) markers. Such a pathway model describes the heavy drinking phenotype, HDD90 (heavy drinking days past 90 days), with even higher effects (R2 = 0.955, p = 0.006) in the AUD patients, who had higher ratings for cravings (PACS > 5). The interaction of gut dysfunction cytokines involved in both inflammation and mediating activity constitutes a novel pathophysiological gut-brain axis for withdrawal symptoms and withdrawal-associated depression and craving symptoms in AUD. AUD patients with reported cravings show a significant characterization of the gut-brain axis response to heavy drinking. ClinicalTrials.gov, identifier: NCT# 00106106.


Sudden unexpected death caused by infantile acute lymphoblastic leukaemia.
A 7-week-old girl with a normal birth history suddenly developed respiratory distress while feeding. Cardiopulmonary resuscitation was initiated at home after she had a cardiac arrest and was continued in the emergency room but all efforts at resuscitation proved unsuccessful and she died 2 h after presentation. Investigations performed in the emergency room revealed that she had a significantly high white blood cell count and severe anaemia. The cause of death was identified as KMT2A-rearranged infantile acute lymphoblastic leukaemia based on cytogenetic tests. She had no abnormalities at the 4-week check-up; however, she developed a skin nodule on her abdomen thereafter, and the family did not consult a doctor for fear of contracting COVID-19. Early detection and diagnosis could have changed the prognosis of the patient. The present case highlights the negative impact of the reduction of outpatient consultations during the COVID-19 pandemic.


Dilemma of renal disease in elderly.
The aging process results in profound anatomic and functional changes in a number of human body systems. Changes in kidney function with normal aging are the most dramatic of any human organ or organ system. These include anatomical, physiological, hemodynamic and immunological changes. Increased propensities of systemic diseases and exposure to poly-pharmacy of the aged group have an additive deleterious effect. The aforementioned changes have its implications on clinical presentations, management and prognosis of all renal diseases in elderly. Atypical presentation, more frequent and longer course are the characteristics of acute renal failure in this age group. Also, presentation of glomerular diseases, clinical course, prognosis, decision of performing a renal biopsy and use of immunosuppressive drugs in elderly specially those subgroup above 80 years of age are still a big challenges that needs a consensus and standardization.


A Systematic Review and Meta-analysis of Optimized CMV Preemptive Therapy and Antiviral Prophylaxis for CMV Disease Prevention in CMV High-Risk (D+R-) Kidney Transplant Recipients.
The optimal strategy for cytomegalovirus (CMV) disease prevention in CMV donor/recipient kidney transplant recipients remains uncertain. Conclusions of prior meta-analyses that CMV disease rates with preemptive therapy (PET) and universal prophylaxis (UP) were comparable may have been affected by inclusion of studies lacking key determinants of efficacy of the respective strategies. We conducted a systematic review and meta-analysis of PET with weekly CMV polymerase chain reaction monitoring for ≥3 mo and UP with 6 mo of valganciclovir. PubMed and Embase databases were reviewed from January 1, 2010, to April 1, 2022. Risk of bias was assessed with 3 instruments (Cochrane RoB, Cochrane RoBINS-I, and an instrument for assessing risk in observational studies). The primary outcome was CMV disease incidence by 1-y posttransplant. Secondary outcomes by 1-y were graft loss, acute allograft rejection, and mortality. Results were synthesized using generalized linear mixed model meta-analysis. PET studies were stratified into low-threshold (LT) and high-threshold (HT) PET based on the viral load threshold for initiation of antiviral therapy. Twenty-five studies met inclusion criteria (6 PET, 19 UP). CMV disease incidence was significantly higher in HT (0.30 [95% confidence interval (CI), 0.22-0.39]) versus LT PET (0.06 [95% CI, 0.03-0.12]). LT PET was associated with a significantly lower CMV disease incidence (0.06 [95% CI, 0.03-0.12]) versus UP (0.21 [95% CI, 0.17-0.27]). Incidence of graft loss, acute allograft rejection, or mortality was not significantly different between LT PET and UP (P > 0.05 for all comparisons). Receipt of lymphocyte-depleting antibodies was not associated with a significant difference in CMV disease incidence (odds ratio = 1.34 [95% CI, 0.80-2.25]). LT PET is associated with a significantly lower incidence of CMV disease compared to UP with similar rates of other clinical outcomes. These findings provide rationale and preliminary data for a randomized superiority trial of optimized LT-PET versus UP in donor seropositive recipient seronegative kidney transplant recipients.


A small sequence in the third intracellular loop of the VPAC(1) receptor is responsible for its efficient coupling to the calcium effector.
The stimulatory effect of VIP on intracellular calcium concentration ([Ca(2+)](i)) has been investigated in Chinese hamster ovary cells stably transfected with the reporter gene aequorin, and expressing human VPAC(1), VPAC(2), chimeric VPAC(1)/VPAC(2), or mutated receptors. The VIP-induced [Ca(2+)](i) increase was linearly correlated with receptor density and was higher in cells expressing VPAC(1) receptors than in cells expressing a similar VPAC(2) receptor density. The study was performed to establish the receptor sequence responsible for that difference. VPAC(1)/VPAC(2) chimeric receptors were first used for a broad positioning: those having the third intracellular loop (IC(3)) of the VPAC(1) or of the VPAC(2) receptor behaved, in that respect, phenotypically like VPAC(1) and VPAC(2) receptor, respectively. Replacement in the VPAC(2) receptor of the sequence 315-318 (VGGN) within the IC(3) by its VPAC(1) receptor counterpart 328-331 (IRKS) and the introduction of VGGN in state of IRKS in VPAC(1) was sufficient to mimic the VPAC(1) and VPAC(2) receptor characteristics, respectively. Thus, a small sequence in the IC(3) of the VPAC(1) receptor, probably through interaction with G(alphai) and G(alphaq) proteins, is responsible for the efficient agonist-stimulated [Ca(2+)](i) increase.


Pressure-Sensitive Supramolecular Adhesives Based on Lipoic Acid and Biofriendly Dynamic Cyclodextrin and Polyrotaxane Cross-Linkers.
Slide-ring materials are polymer networks with mobile cross-links that exhibit impressive stress dissipation and fracture resistance owing to the pulley effect. On account of their remarkable ability to dissipate the energy of deformation, these materials have found their way into advanced materials such as abrasion-resistant coatings and elastic battery electrode binders. In this work, we explore the role of mobile cross-links on the properties of a biofriendly pressure-sensitive adhesive made using composites of cyclodextrin-based macromolecules and poly(lipoic acid). We modify cyclodextrin-based hosts and polyrotaxanes with pendant groups of lipoic acid (a commonly ingested antioxidant) to incorporate them as cross-links in poly(lipoic acid) networks obtained by simple heating in open air. By systematically varying the adhesive formulations while probing their mechanical and adhesive properties, we uncover trends in structure-property relationships that enable one to tune network properties and access biofriendly, high-tack adhesives.


RNA11 protein is associated with the yeast spliceosome and is localized in the periphery of the cell nucleus.
The yeast rna mutations (rna2 through rna10/11) are a set of temperature-sensitive mutations that result in the accumulation of pre-mRNAs at the nonpermissive temperature. Most of the yeast RNA gene products are involved in and essential for mRNA splicing in vitro, suggesting that they code for components of the splicing machinery. We tested this proposal by using an in vitro-synthesized RNA11 protein to complement the temperature-sensitive defect of the rna11 extract. During the in vitro complementation, the input RNA11 protein was associated with the 40S spliceosome and a 30S complex, suggesting that the RNA11 protein is indeed a component of the spliceosome. The formation of the RNA11-associated 30S complex did not require any exogenous RNA substrate, suggesting that this 30S particle is likely to be a preassembled complex involved in splicing. The RNA11-specific antibody inhibited the mRNA splicing in vitro, confirming the essential role of the RNA11 protein in mRNA splicing. Finally, using the anti-RNA11 antibody, we localized the RNA11 protein to the periphery of the yeast nucleus.


Excitability is mediated by the T1 domain of the voltage-gated potassium channel.
The T1 domain of voltage-gated K+ (Kv) channel is the N-terminal cytoplasmic part of the channel preceding the transmembrane pore domain of the channel. Several crystal structures of the T1 domain show that the four T1 subunits are arranged in a rotationally symmetric tetramer. The subunit interface of the T1 domain encodes the assembly specificity of intact functional Kv channels. Along the fourfold symmetry axis of the T1 tetramer, a water-filled cavity exists. K+ ions, however, do not pass through this T1 cavity. Instead, they are believed to enter the transmembrane pore through four identical inter-subunit spaces created between the membrane-facing C-terminal side of the T1 tetramer and the inner leaflet of the membrane. Several point mutations have been introduced into the putative membrane-facing region of the T1 tetramer. These mutations led to a systematic change of the channel's voltage sensitivity. Such functional change was accompanied by a distinct structural change in the C-terminal membrane-facing side of the T1 tetramer. Interestingly, a similar structural alteration that renders the channel more excitable is also induced by the binding of a cytoplasmic protein Kv beta subunit. Within this conformationally flexible part of the T1 tetramer, non-Shaker type Kv channel subunits invariably contain one Zn2+ per subunit. With the Kv4.2 T1, we demonstrated that the tetramer can be reversibly converted to monomers by chelating zinc away from the protein. The rate of removal of Zn2+ is pH-dependent. The structural ability of the T1 tetramer to alter conformation could be an essential property to mediate and process protein protein interaction events in the cytoplasm to control excitability of intact full-length Kv channels.


A family 13 thioesterase isolated from an activated sludge metagenome: Insights into aromatic compounds metabolism.
Activated sludge is produced during the treatment of sewage and industrial wastewaters. Its diverse chemical composition allows growth of a large collection of microbial phylotypes with very different physiologic and metabolic profiles. Thus, activated sludge is considered as an excellent environment to discover novel enzymes through functional metagenomics, especially activities related with degradation of environmental pollutants. Metagenomic DNA was isolated and purified from an activated sludge sample. Metagenomic libraries were subsequently constructed in Escherichia coli. Using tributyrin hydrolysis, a screening by functional analysis was conducted and a clone that showed esterase activity was isolated. Blastx analysis of the sequence of the cloned DNA revealed, among others, an ORF that encodes a putative thioesterase with 47-64% identity to GenBank CDS reported genes, similar to those in the hotdog fold thioesterase superfamily. On the basis of its amino acid similarity and its homology-modelled structure we deduced that this gene encodes an enzyme (ThYest_ar) that belongs to family TE13, with a preference for aryl-CoA substrates and a novel catalytic residue constellation. Plasmid retransformation in E. coli confirmed the clone's phenotype, and functional complementation of a paaI E. coli mutant showed preference for phenylacetate over chlorobenzene as a carbon source. This work suggests a role for TE13 family thioesterases in swimming and degradation approaches for phenyl acetic acid. Proteins 2017; 85:1222-1237. © 2017 Wiley Periodicals, Inc.


A phosphorylation hotspot within the occludin C-terminal domain.
Tight junctions (TJs) form paracellular barriers defining the permeability characteristics of epithelial and endothelial cell layers in our body. Tetraspanin integral membrane proteins, including occludin, tricellulin, MarvelD3, and a set of claudins, form a network of anastomosing strands bringing the membranes of neighboring cells into close contact. Occludin is assumed to play an important role in the regulation of TJ formation, structure, and function, and is tightly regulated by phosphorylation. We here summarize the role of occludin phosphorylation on assembly/disassembly and function of TJs and specifically focus on a cluster of 11 amino acids in the C-terminal cytoplasmic domain of occludin (Tyr398-Ser408), including highly conserved phosphorylation sites for c-Src, PKCs, and CK2. Phosphorylation by these kinases affects occludin localization, dynamics, and interaction with other TJ proteins. Interestingly, this phosphorylation hotspot is localized in an unstructured region close to the ZO-1 binding site, and a cysteine residue which is involved in intermolecular disulfide-bond formation thus contributing to occludin dimerization. We discuss potential consequences and open questions in respect to the functional role of this phosphorylation hotspot.


The Use of Pain Severity and Its Impact as a Predictor for MRI Findings: A Cross-Sectional Study in Ta'if, Saudi Arabia.
Background Low back pain (LBP) is common and considerably impacts daily lives across all age groups. MRI is not frequently used as a first-line investigation for patients presenting with LBP, except in the presence of red-flag symptoms. This study aimed to use pain severity and its impact as a predictor for MRI findings to help physicians decide whether a patient needs an MRI. Methods This cross-sectional study was conducted at the outpatient clinic of the neurosurgery department. The questionnaire included demographic data of the patients, red-flag symptoms, and the Dallas Pain Questionnaire (DPQ). The primary physician then determines whether the patient should have an MRI appointment. Results The study included 100 patients with LBP, of which 71 had chronic LBP (CLBP). Out of these 71, an MRI was requested for 62, but only 26 had findings related to LBP. Regarding the impact of CLBP on daily activities as measured by the DPQ, there was a significant association between those whose CLBP affected their daily activities and the decision to request an MRI. However, no significant statistical association was found between the three other parameters of the DPQ and the primary physician's decision to request an MRI. Conclusion Concerning the use of the DPQ questionnaire to predict MRI findings in patients with CLBP, the study indicates that significant pain impact on the DPQ does not necessarily correlate with MRI findings related to LBP. This suggests that the DPQ evaluation tool has no advantage over a physician's clinical judgment.


Ab initio based force field and molecular dynamics simulations of crystalline TATB.
An all-atom force field for 1,3,5-triamino-2,4,6-trinitrobenzene (TATB) is presented. The classical intermolecular interaction potential for TATB is based on single-point energies determined from high-level ab initio calculations of TATB dimers. The newly developed potential function is used to examine bulk crystalline TATB via molecular dynamics simulations. The isobaric thermal expansion and isothermal compression under hydrostatic pressures obtained from the molecular dynamics simulations are in good agreement with experiment. The calculated volume-temperature expansion is almost one dimensional along the c crystallographic axis, whereas under compression, all three unit cell axes participate, albeit unequally.


A prospective, randomised controlled trial of femoral ring allograft versus a titanium cage in circumferential lumbar spinal fusion with minimum 2-year clinical results.
The literature reports on the safety and efficacy of titanium cages (TCs) with additional posterior fixation for anterior lumbar interbody fusion. However, these papers are limited to prospective cohort studies. The introduction of TCs for spinal fusion has resulted in increased costs, without evidence of superiority over the established practice. There are currently no prospective controlled trials comparing TCs to femoral ring allografts (FRAs) for circumferential fusion in the literature. In this prospective, randomised controlled trial, our objective was to compare the clinical outcome following the use of FRA (current practice) to the use of TC in circumferential lumbar spinal fusion. Full ethical committee approval and institutional research and development departmental approval were obtained. Power calculations estimated a total of 80 patients (40 in each arm) would be required to detect clinically relevant differences in functional outcome. Eighty-three patients were recruited for the study fulfilling strict entry requirements (>6 months chronic discogenic low back pain, failure of conservative treatment, one- or two-level discographically proven discogenic low back pain). The patients completed the Oswestry Disability Index (ODI), Visual Analogue Score (VAS) for back and leg pain and the Short-Form 36 (SF-36) preoperatively and also postoperatively at 6, 12 and 24 months, respectively. The results were available for all the 83 patients with a mean follow-up of 28 months (range 24-75 months). Five patients were excluded on the basis of technical infringements (unable to insert TC in four patients and FRA in one patient due to the narrowing of the disc space). From the remaining 78 patients randomised, 37 received the FRA and 41 received the TC. Posterior stabilisation was achieved with translaminar or pedicle screws. Baseline demographic data (age, sex, smoking history, number of operated levels and preoperative outcome measures) showed no statistical difference between groups (p<0.05) other than for the vitality domain of the SF-36. For patients who received the FRA, mean VAS (back pain) improved by 2.0 points (p<0.01), mean ODI improved by 15 points (p=<0.01) and mean SF-36 scores improved by >11 points in all domains (p<0.03) except that of general health and emotional role. For patients who received the TC, mean VAS improved by 1.1 points (p=0.004), mean ODI improved by 6 points (p=0.01) and SF-36 improved significantly in only two of the eight domains (bodily pain and physical function). Revision procedures and complications were similar in both groups. In conclusion, this prospective, randomised controlled clinical trial shows the use of FRA in circumferential lumbar fusion to be associated with superior clinical outcomes when compared to those observed following the use of TCs. The use of TCs for circumferential lumbar spinal fusion is not justified on the basis of inferior clinical outcome and the tenfold increase in cost.


[Did Alzheimer research fail entirely? : Failure of amyloid-based clinical studies].
Numerous amyloid-based clinical studies have recently failed. Does this mean that the mechanisms of Alzheimer's disease have to be reinvestigated and that amyloid is not the trigger of the disease? Strong genetic evidence from familial Alzheimer's disease contradicts this fatalistic opinion. Mutations in all genes associated with familial Alzheimer's disease affect amyloid metabolism and aggregation. Moreover, a protective mutation reduces amyloid production by 20-30% throughout the lifetime. Clinical studies rather failed because secretase inhibitors block cleavage of numerous other physiologically important substrates of secretases. Moreover, the disease is initiated decades before symptoms occur. Successful treatment attempts with anti-amyloid medication based on other prototype amyloidoses are described. Finally, new therapeutic target molecules expressed in microglia cells are discussed.


Resveratrol protects against oxidative damage of retinal pigment epithelium cells by modulating SOD/MDA activity and activating Bcl-2 expression.
Age-related macular degeneration (AMD) is mainly characterized by dysfunction of retinal pigment epithelium (RPE) cells. This study aimed to investigate the protective effects of resveratrol on oxidative damaged RPE cells. Human D407 cells were divided into normal control (NC), H2O2 treated (H2O2, treating with H2O2 at a final concentration of 200 mol/l) and resveratrol treatment groups (treating with resveratrol at a concentration of 12.5, 25, 50 and 100 mg/l). Malondialdehyde (MDA) and superoxide dismutase (SOD) activities were examined using enzyme-linked immunosorbent assay (ELISA). 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and cell count kit-8 (CCK-8) were used to examine cell viability. Cell cycle phase distribution and apoptosis of D407 cells were evaluated using flow cytometry assay. B-cell lymphoma-2 (Bcl-2) and cleaved caspase 3 expression were detected using quantitative real-time PCR (qRT-PCR) and Western blot assay, respectively. Resveratrol significantly decreased inhibitive ratios of D407 cell growth compared to that of H2O2 group (p<0.05). Resveratrol significantly increased SOD activity compared to that of H2O2 group (p<0.05). Resveratrol significantly reduced MDA activity compared to that of H2O2 group (p<0.05). Resveratrol affected cell cycle phase distribution of D407 cells compared to that of H2O2 group (p<0.05). Resveratrol significantly decreased the early stage and late stage apoptosis rates compared to that of H2O2 group (p<0.05). Resveratrol significantly enhanced Bcl-2 levels and decreased cleaved caspase 3 levels compared to that of H2O2 group (p<0.05). Resveratrol protected against the oxidative damage of RPE cells by modulating SOD/MDA activity and activating Bcl-2 expression.


Role of BMP-4 in the inducing ability of the head organizer in Xenopus laevis.
BMP-4 has been implicated in the patterning of the Dorsal-Ventral axis of mesoderm and ectoderm. In this study, we describe the posteriorizing effect of BMP-4 on the neural inducing ability of dorsal mesoderm (dorsal lip region) in Xenopus gastrulae. Dorsal lip explants dissected from stage 10.25 embryos retained anterior inducing ability when precultured for 6 hrs until sibling embryos reach stage 12. When the dorsal lips from stage 10.25 embryos were treated with a range of BMP-4 concentrations, posterior tissues were induced in adjacent ectoderm in a dose-dependent manner. Thus activin-treated explants able to act as head inducers can also induce posterior structures in the presence of BMP-4. To investigate whether BMP-4 directly affects the inducing ability of dorsal mesoderm, we blocked the BMP-4 signaling pathway by injection of mRNA encoding a truncated form of the BMP-4 receptor (tBR) mRNA. Under these conditions, activin-treated explants induced anterior tissues following BMP-4 treatment. Taken together, these results indicate that BMP-4 may affect the head inducing ability of dorsal mesoderm and confer trunk-tail inducing ability during Xenopus gastrulation.


Protein synthesis inhibitors cycloheximide and anisomycin induce interleukin-6 gene expression and activate transcription factor NF-kappaB.
In two human cell lines, MDA-MB-231 and HeLa, the inducible expression of the interleukin-6 (IL-6) gene by two protein synthesis inhibitors, cycloheximide and anisomycin, was compared with the induction by the most potent physiological inducer of IL-6 described to date, interleukin-1beta (IL-1beta). In cycloheximide or anisomycin treated cells, the accumulation of the IL-6 message and the activation of transcription factors required for IL-6 gene expression occurs at an extent similar to that obtained with IL-1beta. Furthermore, IL-6 mRNA accumulation stimulated by cycloheximide or anisomycin is almost completely inhibited in the presence of actinomycin D, indicating that this effect occurs mainly through the activation of the transcriptional machinery. These data indicate that transcriptional induction of the IL-6 gene by inhibitors of protein synthesis is triggered by the same nuclear signals as other inducers.