Self-diagnosis of malaria by travellers: a cohort study on the use of malaria rapid diagnostic tests provided by a Swiss travel clinic.
The WHO recommends that all suspect malaria cases be tested before receiving treatment. Rapid diagnostic tests (RDT) for malaria can be performed reliably by community health workers with no formal medical background and thus, RDTs could also be provided to travellers for self-diagnosis during visits to endemic regions. RDTs were proposed during pre-travel consultations to pre-defined categories of travellers. A training run on their own blood was performed and, if carried out correctly, the traveller was given a written procedure on how to perform the test and act on its result. The travellers were then proposed to buy a malaria RDT kit and were interviewed upon their return. From February 2012 to February 2017, 744 travellers were proposed RDTs and 692 performed the training run (one could not complete it due to a hand tremor). Among the 691 subjects included, 69% travelled to moderate- or low-risk areas of malaria, 18% to high-risk areas and 13% to mixed-risk areas. The two most frequent categories of travellers to whom RDTs were proposed were long-term travellers (69%) and those travelling to remote areas (57%). 543 travellers (79%) were interviewed upon return. During their trip, 17% (91/543) had a medical problem with fever and 12% (65/543) without fever. Among 91 febrile patients, 57% (52/91) performed an RDT, 22% (20/91) consulted immediately without using the test, and 21% (19/91) did neither. Four RDTs (4/52; 8%) were positive: 2 in low-risk and 2 in high-risk areas (0.7% attack rate of self-documented malaria). Two travellers could not perform the test correctly and attended a facility or took standby emergency treatment. Four travellers with negative results repeated the test after 24 h; all were still negative. Carrying RDTs made travellers feel more secure, especially when travelling with children. 1/6 travellers experienced fever and 4/5 of those reacted appropriately: more than half used RDTs and a quarter consulted immediately. Four travellers (including 2 from low-risk areas) diagnosed themselves with malaria and self-treated successfully. This strategy allows prompt treatment for malaria in high-risk groups and may avoid over-diagnosis (and subsequent inappropriate treatment) of malaria on-site.


Increased rate of cholesterologenesis--a possible cause of hypercholesterolemia in experimental chronic renal failure in rats.
Hypercholesterolemia plays an important role in the lipid abnormalities in chronic renal failure (CRF). It is thought to contribute to both a progression of renal failure and atherosclerosis. Despite intensive research, the etiopathogenesis of hypercholesterolemia in CRF patients is still obscure. The present study was designed to evaluate the possible role of cholesterol overproduction in the development of hypercholesterolemia associated with experimental CRF. We found that plasma total cholesterol and cholesterol distributed in VLDL, LDL and HDL concentrations were significantly enhanced in CRF rats. Simultaneously, the rate of liver cholesterol biosynthesis in vivo (measured by determining the incorporation of tritium from tritiated water intraperitoneally injected into cholesterol ), liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity and liver HMG-CoA reductase mRNA presence were elevated. Significant increases in activity of liver malic enzyme, glucose 6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase, NADPH-producing enzyme (required for cholesterol synthesis) have also been observed in CRF rats. In conclusion, the increased rate of liver cholesterol biosynthesis due to increase of HMG-CoA reductase and NADPH-producing enzyme gene expression could be one of the possible causes of hypercholesterolemia in CRF animals.


AI-Enhanced Diagnosis of Challenging Lesions in Breast MRI: A Methodology and Application Primer.
Computer-aided diagnosis (CAD) systems have become an important tool in the assessment of breast tumors with magnetic resonance imaging (MRI). CAD systems can be used for the detection and diagnosis of breast tumors as a "second opinion" review complementing the radiologist's review. CAD systems have many common parts, such as image preprocessing, tumor feature extraction, and data classification that are mostly based on machine-learning (ML) techniques. In this review article, we describe applications of ML-based CAD systems in MRI covering the detection of diagnostically challenging lesions of the breast such as nonmass enhancing (NME) lesions, and furthermore discuss how multiparametric MRI and radiomics can be applied to the study of NME, including prediction of response to neoadjuvant chemotherapy (NAC). Since ML has been widely used in the medical imaging community, we provide an overview about the state-of-the-art and novel techniques applied as classifiers to CAD systems. The differences in the CAD systems in MRI of the breast for several standard and novel applications for NME are explained in detail to provide important examples, illustrating: 1) CAD for detection and diagnosis, 2) CAD in multiparametric imaging, 3) CAD in NAC, and 4) breast cancer radiomics. We aim to provide a comparison between these CAD applications and to illustrate a global view on intelligent CAD systems based on machine and deep learning in MRI of the breast. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY STAGE: 2.


In vivo thermal conductivity of the human forearm tissues.
The effective thermal conductivities of the skin + subcutaneous (keff skin + fat) and muscle (keff muscle) tissues of the human forearm at thermal steady state during immersion in water at temperatures (Tw) ranging from 15 to 36 degrees C were determined. Tissue temperature (Tt) was continuously monitored by a calibrated multicouple probe during a 3-h immersion of the resting forearm. Tt was measured every 5 mm from the longitudinal axis of the forearm (determined from computed-tomography scanning) to the skin surface. Skin temperature (Tsk), heat loss (Hsk), and blood flow (Q) of the forearm, as well as rectal temperature (Tre) and arterial blood temperature at the brachial artery (Tbla), were measured during the experiments. When the keff values were calculated from the finite-element (FE) solution of the bioheat equation, keff skin + fat ranged from 0.28 +/- 0.03 to 0.73 +/- 0.14 W.degrees C-1.m-1 and keff muscle varied between 0.56 +/- 0.05 and 1.91 +/- 0.19 W.degrees C-1.m-1 from 15 to 36 degrees C. The values of keff skin + fat and keff muscle, calculated from the FE solution for Tw less than or equal to 30 degrees C, were not different from the average in vitro values obtained from the literature. The keff values of the forearm tissues were linearly related (r = 0.80, P less than 0.001) to Q for Tw greater than or equal to 30 degrees C. It was found that the muscle tissue could account for 92 +/- 1% of the total forearm insulation during immersion in water between 15 and 36 degrees C.


Stereochemical features of Lewis acid-promoted glycosidations involving 4'-spiroannulated DNA building blocks.
Tin tetrachloride-catalyzed glycosidation of persilylated nucleobases with acetate donor 6 in CH(2)Cl(2) solution followed by deprotection gave rise very predominantly to alpha-spironucleosides. These stereochemical assignments stem from the determination of NOE interactions and an X-ray crystallographic analysis of the latter product. Computational studies revealed that these results are consistent with the fact that the C5' substituent shields the beta-face of the oxonium ion involved in the coupling reaction while the C3' substituent is projected away from the alpha-underside. Attack from the more open direction is therefore kinetically favored. Entirely comparable calculations suggested that donor 19 should behave comparably. Experimentation involving this donor gave results consistent with this model although more equitable alpha/beta spironucleoside product ratios were seen when acetonitrile was employed as the reaction medium.


Cerebellar Gray Matter Reductions Associate With Decreased Functional Connectivity in Nicotine-Dependent Individuals.
Nicotine dependence (ND) is a chronic, relapsing mental disorder characterized by compulsive cigarette seeking and smoking. Although the cerebellum plays an increasingly implicated role in ND, the exact cerebellar alterations in ND remain unclear. Identifying the localization of these cerebellar abnormalities in ND may help to further understand the role of the cerebellum in ND. Thus, we investigated the structural and functional alterations in the cerebellum in a large sample of smokers using the spatially unbiased infratentorial template (SUIT). High-resolution structural magnetic resonance imaging (MRI) data were acquired from 85 smokers and 41 nonsmokers. We applied voxel-based morphometry (VBM) and the SUIT cerebellar atlas to compare the cerebellar gray matter (GM) volume between smokers and nonsmokers. Using resting-state functional MRI data, we also performed seed-based functional connectivity (FC) analysis to examine the functional correlates of the GM volume changes. Both VBM and lobular analyses revealed smaller GM volume in the bilateral Crus I in smokers. The GM volume of the left Crus I was inversely correlated with the severity of nicotine dependence as assessed by Fagerström Test for Nicotine Dependence (r = -.268, p = .013). We also found reduced FC between the bilateral Crus I and brain regions involved in the default mode network and motor system, as well as the frontal and temporal cortex in smokers. Our results indicate that decreased cerebellar GM volume and corticocerebellar FC are associated with ND, and these may underlie the core ND phenotypes, including automatized smoking behavior, cognitive, and emotional deficits. As smoking remains a worldwide public health problem, identifying the related neural alterations may help to understand the pathophysiology of ND. Based on previous findings in the cerebellum, we investigated the localization of the GM differences and related FC changes in ND subjects. Our findings highlight altered corticocerebellar circuits in ND, suggesting an association between the cerebellum and the phenotypes of ND.


Single Point Insulin Sensitivity Estimator for predicting type 2 diabetes mellitus in obese adolescents.
The prevalence of adolescents with type 2 diabetes mellitus (T2DM) has rapidly increased in Korea over the past few decades with the increase in the number of obese adolescents. The single point insulin sensitivity estimator (SPISE) was recently introduced as a surrogate marker for insulin sensitivity to predict T2DM in adults. We aimed to determine risk factors for T2DM in obese adolescents, including SPISE. This retrospective study included 104 adolescents diagnosed with T2DM at Korea University Hospital between January 2010 and December 2020. We compared clinical and biochemical parameters and the SPISE of normoglycemic overweight and obese individuals with those of prediabetic and diabetic adolescents to determine risk factors for T2DM. Receiver operating characteristic analysis was performed with the Youden index to determine the cutoff point of SPISE. Frequency of fatty liver and family history of T2DM were significantly higher and SPISE level was significantly lower in patients with T2DM than in normoglycemic overweight/obese and prediabetic adolescents (p<0.01). A family history of T2DM, fatty liver, and SPISE value below the cutoff point (4.49) were identified as significant risk factors for T2DM in multiple logistic regression analysis after controlling for age, sex, and body mass index standard deviation score (p<0.01). Family history of T2DM, fatty liver, and low SPISE (<4.49) are risk factors that can independently affect the occurrence of T2DM in obese adolescents. Among these risk factors, SPISE is a promising marker for predicting adolescent T2DM; careful monitoring of these individuals is needed to prevent progression to T2DM.


Big endothelin-converting enzyme activities in subcellular fractions of bovine aortic endothelial cells.
A combination of HPLC elution patterns and peptide sequencing has been used to characterize two distinct activities present in subcellular fractions of bovine aortic endothelial cells (BAECs) capable of converting human big endothelin-1 (big ET-1) to mature (ET-1). A pepstatin-inhibitable activity with an acidic pH optimum present in a lysosome-enriched fraction cleaved big ET-1 at positions 18 and 21 at similar rates. A neutral pH activity present in a postlysosomal organelles subfraction was also able to convert big ET-1, and was inhibited by EDTA, but not by 1-chloro-3-tosylamido-4-phenyl-2-butanone (TPCK), an inhibitor of chymotrypsin-like serine proteases.


Timing of completed suicides among residents of Olmsted County, Minnesota, 1951-1985.
Previous studies of suicide timing may have been biased by incomplete ascertainment of suicides and by delays between the suicidal act and subsequent death. Those potential biases were assessed and minimized in this population-based study by using the unique resources of the Rochester Epidemiology Project in Olmsted County, Minnesota. Using these more accurate data, we confirmed previous reports of no excess suicides on birthdays (+/- 3 days), or during 3 United States national holidays. While most prior reports found excess post-holiday suicides and suicide peaks on Mondays, those findings were not observed in Olmsted County. Because 93% of deaths occurred on the date of the suicidal act, using date of death instead of the actual date of suicide is sufficient for most research purposes.


Regiodivergent Catalysis: A Powerful Tool for Selective Catalysis.
"Regiodivergent catalysis" is discussed as a class of highly selective reactions of chiral substrates in racemic or enantiomerically enriched form using one or both enantiomers of a catalyst. The key point of the reactions is the highly regioselective formation of products that are constitutional isomers. The selectivity is mediated by different interactions of the enantiomerically pure catalysts with both enantiomers of the substrate. Ideally, for racemic substrates, the reactions result in highly efficient parallel resolutions and for enantiomerically pure substrates, in highly regioselective reactions for each enantiomer of the catalyst. "Regiodivergent catalysis" is highly interesting for diversity-oriented synthesis (DOS) because it provides branching points for the generation of functional and structural diversity.


[Cryopreservation of female gametes after the second meiotic division].
During the past few years, experimentation in the field of assisted fertilisation has been focused on the freezing of the female gamete. This technique would allow the ethical problems relating to embryo conservation to be resolved. Unfortunately, in spite of the continuous progress made in embryology, conventional freezing methods have proved lethal to ovocytes owing to the profound morphological and functional changes that take place caused by the low temperature and the toxic action of cryoprotective agents. These alterations include: the thickening of the pellucid zone, thus preventing fertilisation; the confluence of cytoplasmatic organules into vesicles and masses; the depolymerisation of the microtubular apparatus of the meiotic spindle and loss of its orientation towards the egg cell, leading to lack of fertilisation or in the event that fertilisation takes place, a high incidence of chromosomal alterations, such as polyploidy, which are incompatible with subsequent embryonal development. This study aimed to evaluate the possibility of eliminating part of these alterations, in particular those affecting the meiotic spindle, an element of central importance in the formation of the zygote. For this purpose, ovocytes matured in vitro were treated with ionomycin, a substance capable of activating the second meiotic division, and then frozen. The mechanism of action of ionomycin can be attributed to the depolarisation of the plasmatic membrane of the ovocyte, with an increased flow of calcium ions and inhibition of a protein that blocks the second meiotic division. The activation of the second meiotic division has enabled the authors to avoid damage to the meiotic spindle resulting from freezing and to obtain encouraging results in terms of the percentage of fertilisation and embryonal development after freezing, and the subsequent insemination of the ovocyte. Embryonal development ceased during the subsequent phases for reasons that are not yet clear. However, this study showed that severe cellular damage induced by freezing is attributable to alterations to the meiotic spindle that condition the later phases of fertilisation and embryonal development.


Choosing personhood: intentionality and the theory of nursing as caring.
Drawing on a story of a nursing situation for practical context, this article explores the meaning of intentionality within the theoretical context of Nursing as Caring. May's definition of intentionality as the structure that gives meaning to experience is interwoven with the concepts of the theory of Nursing as Caring to explore the topic. Mayeroff's concepts of hope and commitment contribute to an understanding of intentionality in relation to Nursing as Caring. The major thesis of this article, that intentionality is consistently choosing personhood as a way of life and the aim of nursing, is demonstrated in the practice situation.


In vivo protection against strychnine toxicity in mice by the glycine receptor agonist ivermectin.
The inhibitory glycine receptor, a ligand-gated ion channel that mediates fast synaptic inhibition in mammalian spinal cord and brainstem, is potently and selectively inhibited by the alkaloid strychnine. The anthelminthic and anticonvulsant ivermectin is a strychnine-independent agonist of spinal glycine receptors. Here we show that ivermectin is an effective antidote of strychnine toxicity in vivo and determine time course and extent of ivermectin protection. Mice received doses of 1 mg/kg and 5 mg/kg ivermectin orally or intraperitoneally, followed by an intraperitoneal strychnine challenge (2 mg/kg). Ivermectin, through both routes of application, protected mice against strychnine toxicity. Maximum protection was observed 14 hours after ivermectin administration. Combining intraperitoneal and oral dosage of ivermectin further improved protection, resulting in survival rates of up to 80% of animals and a significant delay of strychnine effects in up to 100% of tested animals. Strychnine action developed within minutes, much faster than ivermectin, which acted on a time scale of hours. The data agree with a two-compartment distribution of ivermectin, with fat deposits acting as storage compartment. The data demonstrate that toxic effects of strychnine in mice can be prevented if a basal level of glycinergic signalling is maintained through receptor activation by ivermectin.


Comparison of naturally and synthetically baited spruce beetle trapping systems in the central Rocky Mountains.
We compared naturally baited trapping systems to synthetically baited funnel traps and fallen trap trees for suppressing preoutbreak spruce beetle, Dendroctonus rufipennis Kirby, populations. Lures for the traps were fresh spruce (Picea spp.) bolts or bark sections, augmented by adding female spruce beetles to create secondary attraction. In 2003, we compared a naturally baited system ("bolt trap") with fallen trap trees and with synthetically baited funnel traps. Trap performance was evaluated by comparing total beetle captures and spillover of attacks into nearby host trees. Overall, the trap systems did not significantly differ in spruce beetle captures, although bolt traps caught 6 to 7 times more beetles than funnel traps during the first 4 wk of testing. Funnel traps with synthetic lures had significantly more spillover than either trap trees or bolt traps. The study was repeated in 2004 with modifications including an enhanced blend synthetic lure. Again, trap captures were generally similar among naturally and synthetically baited traps, but naturally baited traps had significantly less spillover. Although relatively labor-intensive, the bolt trap could be used to suppress preoutbreak beetle populations, especially when spillover is undesirable. Our work provides additional avenues for management of spruce beetles and suggests that currently used synthetic lures can be improved.


Pediatric diphtheria and tetanus toxoids-adsorbed vaccine: immune response to the first booster following the diphtheria and tetanus toxoids vaccine primary series.
Diphtheria and tetanus toxoids (DT) vaccine should be given to children at 2, 4 and 6 months of age when there are contraindications to the administration of pertussis vaccine. We have previously reported that such children develop protective antitoxin antibody levels to diphtheria and tetanus antigens. This follow-up study evaluates the decay in antitoxin antibody levels and the booster response elicited to DT antigen when a fourth dose is given at approximately 18 months of age. Twenty-three children receiving DT vaccine were compared to 38 receiving diphtheria and tetanus toxoids-pertussis (DTP) vaccine. The prebooster antibody titer to diphtheria and tetanus at approximately 18 months of age had declined below the recommended protective level in one child who had received DT vaccine and in three children who had received DTP. Following the 18-month booster dose of DT and DTP vaccine, all of the children had protective titers to diphtheria and tetanus toxin. These results suggest that the adjuvant effects of pertussis vaccine are not required to achieve adequate immunization to diphtheria and tetanus when currently available DT vaccine is used in early childhood.


Co-constructing conversations about suicide: the Meeting Space Framework.
This article draws on research conducted for the author's doctoral thesis. It presents the development of the Meeting Space Framework to address what is needed to engage in meaningful conversations about suicide, from the perspective of student nurses. An interpretive methodology of constructivist grounded theory was used, underpinned by the theoretical perspective of symbolic interactionism. The core category of Meeting Spaces resulted; engaging in meaningful conversations about suicide is co-created in illuminating space within the context of a human pivotal encounter (positive) as opposed to an unceremonious pivotal encounter (negative). A certain kind of space is required to support engagement in meaningful conversations about suicide. It requires humanness and an intention and ability to see the whole person beyond the limiting word of 'suicide'.


Acute Feasibility of Neuromuscular Electrical Stimulation in Severely Obese Patients with Obstructive Sleep Apnea Syndrome: A Pilot Study.
Objective. Obesity and obstructive sleep apnea (OSA) are closely interconnected conditions both leading to high cardiovascular risk. Inactivity is frequent and physical activity programs remain difficult in these patients. We investigated the acute feasibility of two neuromuscular electrical stimulation (NMES) modalities in extremely inactive obese patients with OSA. Design. A randomized cross-over study, with two experimental sessions (one per condition: multipath NMES versus conventional NMES). Setting. Outpatient research hospital. Subjects. Twelve patients with obesity, already treated for OSA. Interventions. No intervention. Measures. Feasibility outcomes included NMES current intensity, knee extension force evoked by NMES, and self-reported discomfort. Results. We found higher current intensity, a trend to significantly higher evoked force and lower discomfort during multipath NMES versus conventional NMES, suggesting better tolerance to the former NMES modality. However, patients were rapidly limited in the potential of increasing current intensity of multipath NMES. Conclusion. Both NMES modalities were feasible and relatively well tolerated by obese patients with OSA, even if multipath NMES showed a better muscle response/discomfort ratio than conventional NMES. There is an urgent need for a proof-of-concept study and interventional randomized controlled trials comparing NMES therapy versus current care to justify its utilization in obese and apneic patients with low physical activity levels.


Bone Marrow-Derived Mesenchymal Stem Cells Protect Islet Grafts Against Endoplasmic Reticulum Stress-Induced Apoptosis During the Early Stage After Transplantation.
Early loss of grafted islets is the main obstacle to achieve favorable outcomes of islet transplantation. Mesenchymal stem cells are known to have a protective effect; however, its mechanism remains unclear. We hypothesized that bone marrow-derived mesenchymal stem cells (BMSCs) can protect grafted islets against endoplasmic reticulum stress (ERS)-induced apoptosis. In syngeneic streptozocin-induced diabetic BALB/c mice, islet grafts decreased blood glucose levels; however, the effect was not fully functional from the immediate post-transplant phase. β-Cell apoptosis was proven on days 1 and 3 after transplantation. Ultra-structural evidence of ERS was observed along with increased expressions of marker protein BIP and apoptosis-related protein CHOP. In contrast, BMSC co-transplantation maintained glucose hemostasis, inhibited apoptosis and alleviated ERS. In ex vivo culture, BMSCs improved viability of islets and decreased apoptosis. Increased ERS were observed in cultured islets exposed to hypoxia, but not in the islets cocultured with BMSCs. Furthermore, cocultured BMSCs protected islets against ERS-induced apoptosis as well as improved their insulin secretion, and BMSCs alleviated ERS by improving Myc expression through both stromal cell-derived factor 1 signal and contact effect. In conclusion, BMSCs protected the grafted islets against ERS-induced apoptosis during the early stage after transplantation. This study opens a new arena for ERS-targeted therapy to improve outcomes of islet transplantation. Stem Cells 2018;36:1045-1061.


Plasma, follicular, and uterine levels of prostaglandins in chickens laying soft-shelled and shell-less eggs.
Not all eggs produced by chickens are laid at the expected time of oviposition. Some eggs are laid prematurely, which result in inadequate shells. These uncollectible eggs are referred to as soft-shelled (partial calcification) or shell-less (no calcification) eggs. Of all soft-shelled or shell-less eggs that were laid in the present study, 57% were expelled prematurely. To determine whether prostaglandins were correlated with the expulsion of soft-shelled or shell-less eggs, prostaglandin F2alpha (PGF2alpha), 13,14-dihydro-15 keto prostaglandin F2alpha (PGFM), and 13-14-dihydro-15 keto prostaglandin E2 (PGEM) were measured in the peripheral plasma and follicular and uterine tissues of hens laying soft-shelled eggs and shell-less eggs. Controls were represented by hens laying hard-shelled eggs (normal calcification). Plasma concentrations of PGFM increased (P less than .01) upon the premature oviposition of soft-shelled eggs but not shell-less eggs. The source of the peripheral PGFM may have been the preovulatory follicle, because PGF2alpha levels were higher (P less than .07) in the soft-shelled or shell-less egg layers when compared with the controls. Plasma and tissue levels of PGEM did not differ between hens laying soft-shelled or shell-less eggs versus hard-shelled eggs. These results suggest that PGF2alpha and PGFM are involved in the premature oviposition of some chicken eggs.


Shape Distributions of Nonlinear Dynamical Systems for Video-Based Inference.
This paper presents a shape-theoretic framework for dynamical analysis of nonlinear dynamical systems which appear frequently in several video-based inference tasks. Traditional approaches to dynamical modeling have included linear and nonlinear methods with their respective drawbacks. A novel approach we propose is the use of descriptors of the shape of the dynamical attractor as a feature representation of nature of dynamics. The proposed framework has two main advantages over traditional approaches: a) representation of the dynamical system is derived directly from the observational data, without any inherent assumptions, and b) the proposed features show stability under different time-series lengths where traditional dynamical invariants fail. We illustrate our idea using nonlinear dynamical models such as Lorenz and Rossler systems, where our feature representations (shape distribution) support our hypothesis that the local shape of the reconstructed phase space can be used as a discriminative feature. Our experimental analyses on these models also indicate that the proposed framework show stability for different time-series lengths, which is useful when the available number of samples are small/variable. The specific applications of interest in this paper are: 1) activity recognition using motion capture and RGBD sensors, 2) activity quality assessment for applications in stroke rehabilitation, and 3) dynamical scene classification. We provide experimental validation through action and gesture recognition experiments on motion capture and Kinect datasets. In all these scenarios, we show experimental evidence of the favorable properties of the proposed representation.


Bi-Directional Relationships Between Psychological Symptoms and Environmental Factors in Early Adolescence.
Bi-directional relationships between various environmental factors and psychological symptoms can be seen from childhood to adolescence; however, there has been little prospective cohort study, which investigated the relationships simultaneously. In this study, we first distinguished specific psychological symptoms from general psychopathology using bifactor modeling and then tested the relationships between psychological symptoms and environmental factors from childhood to early adolescence using a structural equation model (SEM). The analyses were based on Tokyo TEEN Cohort (TTC) data collected between October 2012 and March 2016. We obtained self-reported psychological symptoms and environmental factors from both parents and children (at their ages of 10 and 12). Participants were 3,171 children aged 10 [girls = 1,487 (46.9%), mean age, SD = 10.2, 0.28] and subsequently 12 (N = 3,007, follow-up rate 94.8%, mean age, SD = 12.2, 0.31) from three municipalities in Tokyo area. The best-fit symptom models included four unique factors and general psychopathology as the common factor. Combining the good fit bifactor model and the SEM, positive relationships between symptoms and environmental factors at the same waves and some bi-directional relationships were found. Especially, general psychopathology at age 10 was associated with bullying at age 12 and parental depressive symptoms at age 10 with general psychopathology at age 12. However, some negative relationships such as bullying/bullied involvement and later psychological symptoms were also seen. By using the newly introduced methodology, our results were partly consistent with previous literature. Further studies are needed to validate this methodology and accelerate the findings regarding the emergence of psychological symptoms and the impact of environmental factors from childhood to early adolescence.


Henoch-Schönlein purpura: a long-term prospective study in Greek children.
Henoch-Schönlein purpura is a common vasculitis of childhood. The present study, comprising 74 children enrolled during a 9-year period, aimed to delineate the clinical spectrum and the long term follow-up of the disease. Patients were diagnosed strictly on the criteria established by the American College of Rheumatology. The diagnosis was further strengthened by a skin biopsy performed in more than half of cases (42/74), which revealed leukocytoclastic vasculitis in all patients, whereas IgA deposits were found in 37/42 children. There was a predominance of boys (41 males), and the mean age of study population was 5.2 +/- 2.54 years. Palpable purpura was identified in 73/74 children, whereas transient arthritis manifested in 68/74 children. Gastrointestinal blood loss was elicited in 30 children, 11 of whom had also renal involvement. The latter was seen in 19/74 (25.7%) children, and in the long term follow-up (extended to 2004, from 4-12 years, mean duration 7.3 years), 2 children remained with persistent occult hematuria. Relapses occurred in 49 children (66%), and half of them experienced more than 1 recurrence. Arthritis was less common in the relapsed episodes, and this difference was statistically significant (P < 0.001). Relapses tended to be more common in children with renal involvement and colicky abdominal pain without however reaching statistical significance. Despite common relapses, this disease is benign in the long term even if severe renal involvement can occur during its active period. Recurrences often differ to some extent from the initial episode with arthritis being less common with relapses.


Interferential therapy machines as possible vehicles for cross-infection.
Interferential therapy machines are used to apply alternating electric currents to patients for the treatment of various musculo-skeletal complaints. The potential for such machines to transfer skin microflora from one patient to another during treatment was investigated. The efficacy of the current disinfection procedure of the machines was also evaluated. In both the laboratory and clinical situation, interferential treatment, (which involves the direct application of electrodes to the skin surface) resulted in the transfer of micro-organisms from the skin of one subject to another. To decrease the likelihood of transmission of micro-organisms via interferential therapy machines, it is recommended that both the suction cups and sponges are disinfected with 70% isopropyl alcohol after the treatment of each patient. The use of disposable electrodes could also be considered.


Administration of IL-7 to normal mice stimulates B-lymphopoiesis and peripheral lymphadenopathy.
Normal mice were injected with IL-7 (500 ng, twice daily) for various periods of time up to 6 days and the cellularity and phenotypic composition of the thymus, spleen, lymph node, and bone marrow was assessed. After 6 days of treatment, significant increases in the cellularity of the spleen, lymph node, and bone marrow were observed which returned to the normal range within 6 days after cessation of treatment. After 3 days of IL-7 treatment, increased numbers of B220+/surface(s) IgM- bone marrow cells were observed. After 6 days of treatment, these numbers were still further increased and a significant population of B220+/sIgM- cells were observed in the spleen. The numbers of c mu+/sIgM- cells were also increased in the IL-7-treated mice. Analysis of the expression of B220 and BP-1 on the sIgM- bone marrow cells revealed that the B220+/BP-1+ population was dramatically increased after IL-7 treatment and the size of the B220+/BP-1- population did not differ from control mice. The pre-B cell numbers declined rapidly after the cessation of IL-7 treatment. After 6 days of IL-7 treatment, a twofold increase in the number of B cells in the spleen and lymph node was observed. The B cell numbers declined to normal values within 6 days after the cessation of IL-7 administration. In the spleens of the IL-7-treated mice, there was a significant increase in the number of B cells with an immature phenotype (e.g., sIgMhi/sIgDlo, decreased levels of Ia and FcR expression). The numbers of CD8+ and CD4+ T cells were also increased in the lymph node and spleen of the IL-7-treated mice. These numbers declined to normal levels after the cessation of IL-7 treatment.


How you think about an emotion predicts how you regulate: an experience-sampling study.
Emotion evaluations are assumed to play a crucial role in the emotion regulation process. We tested a postulate from our framework of emotion dysregulation (Nowak, U., Wittkamp, M. F., Clamor, A., & Lincoln, T. M. [2021]. Using the Ball-in-Bowl metaphor to outline an integrative framework for understanding dysregulated emotion. Frontiers in Psychiatry, 12, 118), namely that the extent to which individuals evaluate an emotion as harmful and their personal resources to modify and accept/tolerate the emotion as sufficient predict the subsequent use of regulation strategies. Participants (n = 118) from a community sample took part in an experience-sampling assessment over 7 days including 10 daily paired measurements. The first measured momentary affective valence and arousal along with harmfulness evaluations and evaluations of personal resources to modify and accept/tolerate an emotion. The second followed three minutes later and measured emotion regulation strategies. The more harmful individuals evaluated an emotion, the more likely they were to use an emotion regulation strategy. The more harmful individuals evaluated an emotion, and the less sufficient they evaluated their personal resources to accept/tolerate an emotion, the more likely they were to use a maladaptive emotion regulation strategy. We conclude that emotions that people evaluate as harmful or difficult to accept are most likely to be regulated in a maladaptive manner. This implies that modifying beliefs about emotions could represent a promising treatment approach.


[[A treatise on sex ratio in population by marital status: marriage squeeze and widowhood]].
"This study deals with imbalances of sex ratio in population by marital status, particularly focussing on two important demographic problems in Japan...the first relating to an excess of male population in marriageable ages and the second relating to an excess of [single, widowed, or divorced women] in the middle and old ages.... Population ageing [of] unmarried women, whether never married, widowed or divorced, [is examined]....Tables of [the] family life cycle have been constructed for Japanese couples for the periods 1920 to 1985, particularly specifying lengths of widowhood and widowerhood." (SUMMARY IN ENG)


The neuropathology and pathogenesis of systemic lupus erythematosus.
Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease in which neuropsychiatric involvement occurs in about 50% of patients and carries a poor prognosis. Despite extensive research, the precise mechanisms of nervous tissue injury remain the least well understood. This article summarizes the important clinical neuropsychiatric features of SLE and, reviewing classical histopathological and more recent experimental studies, discusses theories concerning their presumed pathogenesis. The distinctive production of diverse autoantibodies seems to be related to defective clearance of apoptotic cells. Antibody-mediated neural cell injury and rheological disturbances represent the two principal suggested mechanisms of tissue injury. An interplay between these processes, underlying genetic factors, their modification by hormones, complicated by a number of secondary factors, may explain the wide spectrum of features encountered in this disease.


Capture and release of alkyne-derivatized glycerophospholipids using cobalt chemistry.
Alkyne-modified phospholipids can be unambiguously identified and differentiated from native species in complex mixtures by formation of dicobalthexacarbonyl complexes. This reaction is specific for alkynes and is unaffected by other glycerophospholipid-related moieties. Enrichment of cells with alkyne-derivatized fatty acids or glycerophospholipids followed by solid-phase sequestration and release is a promising new method for unequivocally monitoring individual glycerophospholipids following incorporation into cells. This technique also facilitates lipidomic analysis of substrates and products.


The effect of gamma-hexachlorocyclohexane (lindane) on blood cells, kidney and liver tissues in rabbits.
The effect of intragastric administration of gamma-hexachlorocyclohexane (lindane) on peripheral blood cells, kidney and liver was studied in rabbits. White blood cells were found to be most affected by lindane, as was shown by the reduced phagocytic activity of neutrophils and the increased number of lymphocytes with inactive nucleoli. The changes in the characteristics of erythrocyte cell membranes depended on the length of time lindane was administered and on its withdrawal. Histological examination of the liver and kidney showed focal degeneration of tissue and cell structure.


Action of Matricaria recutita (chamomile) in the management of radiochemotherapy oral mucositis: A systematic review.
The objective of this study was to evaluate the effect of topical chamomile in the prevention and/or treatment of oral mucositis (OM) in cancer patients. It was a systematic review, which sought articles of the randomized clinical trial according to the PRISMA parameters, registered in the PROSPERO. The databases used were PubMed, Cochrane Library, and Bireme. Descriptors were selected from DeCs/MeSH and the PICO strategy was applied. The search found 148 publications. After all the steps, six articles were selected. The total sample included 492 patients and all studies used the same OM measurement scale. The results showed that the application of topical chamomile was effective in the prevention and/or treatment of OM in four of the six studies, with a dose ranging from 1% to 2.5% and duration that ranged from single to 4 times a day. Some limitations were observed: the minimum age of the patients was not informed, and there was no specification of the sites involved or the chemotherapies used. The application of topical chamomile in the preventive/therapeutic of chemo-induced OM seems to be recommended. In addition, scientific production should be encouraged, as it aims to determine useful protocols for this phytotherapy for the oncology population.


Nucleation, stabilization, and disassembly of branched actin networks.
Arp2/3 complex is an actin filament nucleation and branching machinery conserved in all eukaryotes from yeast to human. Arp2/3 complex branched networks generate pushing forces that drive cellular processes ranging from membrane remodeling to cell and organelle motility. Several molecules regulate these processes by directly inhibiting or activating Arp2/3 complex and by stabilizing or disassembling branched networks. Here, we review recent advances in our understanding of Arp2/3 complex regulation, including high-resolution cryoelectron microscopy (cryo-EM) structures that illuminate the mechanisms of Arp2/3 complex activation and branch formation, and novel cellular pathways of branch formation, stabilization, and debranching. We also identify major gaps in our understanding of Arp2/3 complex inhibition and branch stabilization and disassembly.


Structure of the Tet repressor and Tet repressor-operator complexes in solution from electrooptical measurements and hydrodynamic simulations.
The Tet repressor protein and tet operator DNA fragments and their complexes have been analyzed by electrooptical procedures. The protein shows a positive linear dichroism at 280 nm, a negative linear dichroism at 248 nm, and a strong permanent dipole moment of 3.5 X 10(-27) C m, which is independent of the salt concentration within experimental accuracy. Its rotation time constant of 40 ns indicates an elongated structure, which is consistent with a prolate ellipsoid of 100 A for the long axis and 40 A for the short axis. The time constant can also be fitted by a cylinder of length 78 A and diameter 37 A, which is consistent with nuclease protection data reported on repressor-operator complexes, if the cylinder axis is aligned parallel to the DNA axis. Addition of tetracycline induces changes of the limit dichroism but very little change of the rotation time constant. The rotation time constants observed for the operator DNA fragments show some deviations from the values expected from their contour length; however, these deviations remain relatively small. Formation of repressor-operator complexes leads to some increase of the DNA rotation time constants. Simulations by bead models demonstrate that these time constants can be explained without any major change of the hydrodynamic dimension of the components. The data for the complexes are fitted by bead models with smooth bending of the DNA corresponding to a radius of curvature of 500 A, but at the given accuracy, we cannot rule out that the DNA in the complex remains straight or is bent to a smaller radius of approximately 400 A. Thus, binding of the Tet repressor, which is a helix-turn-helix protein as judged from its sequence, to its operator seems to induce minor bending but does not induce strong bending of the DNA double helix.


Metastasis of Testicular Choriocarcinoma in the Stomach, Complicated by the Development of Choriocarcinoma Syndrome.
Choriocarcinoma (CC) is a very rare and aggressive neoplasm. The characteristic feature of this disease is a rapid hematogenous spread, mainly to the lungs and brain, which largely defines clinical signs of the disease and complicates the diagnosis. Gastrointestinal metastases are rare, and of those, only few cases with gastric location have been reported. There are publications describing choriocarcinoma syndrome (CCS). As a rule, it presents in patients with an advanced disease and is characterized by hemorrhage from metastatic foci, leading to hemoptysis and gastrointestinal bleeding. CCS development is associated with poor prognosis and high mortality. This article describes a case of testicular CC with rare few gastric metastases, complicated by CCS.


Litter addition decreases plant diversity by suppressing seeding in a semiarid grassland, Northern China.
Plant community diversity is conducive to maintain the regional ecosystems stability and ecosystem services. Seed germination is one of the main ways to regulate plant diversity, owing to seedling recruitment as a basis for plant community renewal. However, the exact mechanism of how plant litter affects seedling recruitment, and species richness is not yet fully understood. Therefore, a litter addition and removal experiment was established in a semiarid grassland to study the effects of plant litter on seedling recruitment and species richness from April to August in 2016 and 2017 in Northern China. The positive correlation between species richness and seedling recruitment indicated that a guarantee of seedling recruitment was the main precondition to protect species richness. Adding rather than removing litter significantly reduced species richness. Litter addition inhibited species richness by directly increasing mechanical damage or indirectly reducing photosynthetically active radiation and seedling recruitment. The results of this study are conducive to understand the evolutionary and regulatory mechanisms of community species richness and seedling recruitment in grassland ecosystems after adding or removing plant litter. This article has been awarded Open Data, Open Materials and Preregistered research design Badges. All materials and data are publicly accessible via the Open Science Framework at https://doi.org/10.5061/dryad.5dj3jg5 and http://doi.org/10.5061/dryad.13gj03s.


Prediction of solar cell materials via unsupervised literature learning.
Despite the significant advancement of the data-driven studies for physical science, the textual data that are numerous in the literature are not fully embraced by the physics and materials community. In this manuscript, we successfully employ the natural language processing (NLP) technique to unsupervisedly predict the existence of solar cell types including the dye-sensitized solar cells and the perovskite solar cells based on literatures published prior to their first discovery without human annotation. Enlightened by this, we further identify possible solar cell material candidates via NLP starting with a comprehensive training database of 3.2 million paper abstracts published before 2021. The NLP model effectively predicts the existing solar cell materials, while an uncommon solar cell material namely PtSe2is suggested as an appropriate candidate for the future solar cells. Its optoelectronic properties are comprehensive investigated via first-principles calculations to reveal the decent stability and optoelectronic performance of the NLP-predicted candidate. This study demonstrates the viability of the textual data for the data-driven materials prediction and highlights the NLP method as a powerful tool to reliably predict the solar cell materials.


Performance Evaluation of Focal Plane Array (FPA)-FTIR and Synchrotron Radiation (SR)-FTIR Microspectroscopy to Classify Rice Components.
The development of biochemical analysis techniques to study heterogeneous biological samples is increasing. These techniques include synchrotron radiation Fourier transform infrared (SR-FTIR) microspectroscopy. This method has been applied to analyze biological tissue with multivariate statistical analysis to classify the components revealed by the spectral data. This study aims to compare the efficiencies of SR-FTIR microspectroscopy and focal plane array (FPA)-FTIR microspectroscopy when classifying rice tissue components. Spectral data were acquired for mapping the same sample areas from both techniques. Principal component analysis and cluster imaging were used to investigate the biochemical variations of the tissue types. The classification was based on the functional groups of pectin, protein, and polysaccharide. Four layers from SR-FTIR microspectroscopy including pericarp, aleurone layer, sub-aleurone layer, and endosperm were classified using cluster imaging, while FPA-FTIR microspectroscopy could classify only three layers of pericarp, aleurone layer, and endosperm. Moreover, SR-FTIR microspectroscopy increased the image contrast of the biochemical distribution in rice tissue more efficiently than FPA-FTIR microspectroscopy. We have demonstrated the capability of the high-resolution synchrotron technique and its ability to clarify small structures in rice tissue. The use of this technique might increase in future studies of tissue characterization.


Maximizing Psychotherapy Outcome beyond Evidence-Based Medicine.
Despite evidence that psychotherapy has a positive impact on psychological disorders, 30% of patients fail to respond during clinical trials, and as many as 65% of patients in routine care leave treatment without a measured benefit. In addition, therapists appear to overestimate positive outcomes in their patients relative to measured outcomes and are particularly poor at identifying patients at risk for a negative outcome. These problems suggest the need for measuring and monitoring patient treatment response over the course of treatment while applying standardized methods of identifying at-risk cases. Computer-assisted methods for measuring, monitoring, identifying potential deteriorators, and providing feedback to clinicians are described along with a model that explains why feedback is likely to be beneficial to patients. The results of 12 clinical trials are summarized and suggest that deterioration rates can be substantially reduced in at-risk cases (from baseline rates of 21% down to 13%) and that recovery rates are substantially increased in this subgroup of cases (from a baseline of 20% up to 35%) when therapists are provided this information. When problem-solving methods are added to feedback, deterioration in at-risk cases is further reduced to 6% while recovery/improvement rates rise to about 50%. It is suggested that the feedback methods become a standard of practice. Such a change in patterns of care can be achieved through minimal modification to routine practice but may require discussions with patients about their clinical progress.


Multiplexed detection and applications for separations on parallel microchips.
Much work has been performed since the development of the lab-on-a-chip concept that has brought microfabricated systems to the forefront of bioanalytical research. The success of using these microchips for performing complicated biological assays faster and cheaper than conventional methods has facilitated their emerging popularity among researchers. A recently exploited advantage of microfabricated technology has led to the creation of single wafers with multiple channel manifolds for high-throughput experiments. Efforts toward parallel microchip development have yielded fascinating new devices for chemical separations showing the potential for replacing conventional multiplexing techniques. This review will focus on recent work toward multiplexed separations on microdevices and complementary detection instrumentation.


Synergistic effects of chemical enhancers and therapeutic ultrasound on transdermal drug delivery.
The effects of (i) a series of chemical enhancers and (ii) the combination of these enhancers and therapeutic ultrasound (1 MHz, 1.4 W/cm2, continuous) on transdermal drug transport are investigated. A series of chemical enhancer formulations, including (i) polyethylene glycol 200 dilaurate (PEG), (ii) isopropyl myristate (IM), (iii) glycerol trioleate (GT), (iv) ethanol/pH 7.4 phosphate buffered saline in a 1:1 ratio (50% EtOH), (v) 50% EtOH saturated with linoleic acid (LA/EtOH), and (vi) phosphate buffered saline (PBS), as a control, are evaluated using corticosterone as a model drug. LA/EtOH is the most effective of these enhancers, increasing the corticosterone flux by 900-fold compared to that from PBS. Therapeutic ultrasound (1 MHz, 1.4 W/cm2, continuous) increases the corticosterone permeability from all of the enhancers examined by up to 14-fold (LA/EtOH) and increases the corticosterone flux from the saturated solutions by up to 13,000-fold (LA/EtOH), relative to that from PBS. Similar enhancements are obtained with LA/EtOH with and without ultrasound for four other model drugs, dexamethasone, estradiol, lidocaine, and testosterone. The permeability enhancements for all of these drugs resulting from the addition of linoleic acid to 50% EtOH increase with increasing drug molecular weight. Likewise, the permeability enhancement attained by ultrasound and LA/EtOH relative to passive EtOH exhibits a similar size dependence. A mechanistic explanation of this size dependence is provided. It is suggested that bilayer disordering agents, such as linoleic acid and ultrasound, transform the SC lipid bilayers into a fluid lipid bilayer phase or create a separate bulk oil phase. The difference in diffusivity of a given solute in SC bilayers and in either fluid bilayers or bulk oil is larger for larger solutes, thereby producing greater enhancements for larger solutes.


Morphology of the olivocerebellar projection of the chick: an axonal reconstruction study.
The projection pattern of the olivocerebellar (OC) axons, which terminate mainly as climbing fibers (CFs) in the cerebellar cortex, tightly reflects the compartmental and developmental organization of the cerebellum as revealed by mapping and reconstruction studies in the rat. The avian cerebellum is well lobulated and longitudinally compartmentalized like the mammalian cerebellum. However, the projection pattern of the OC axons has not been studied in detail for most areas of the avian cerebellum. In the present study, we reconstructed labeled chick OC axons resulting from a small focal injection of biotinylated dextran amine into the inferior olive to investigate their morphological characteristics, and to determine their relationship to the general morphology of the chick cerebellum. Labeled CFs were distributed basically in a single longitudinally elongated narrow band-shaped area in lobules I-VIII, but in multiple, transversely widened, band-shaped areas in lobules IX-X. Three of the four reconstructed OC axons terminated in a single longitudinally band-shaped area in lobules IXa-c, whereas the other one terminated in multiple mediolaterally separated areas in lobule IXc, which is part of the flocculus. Single OC axons branched into 14 CFs on average. Two CFs occasionally merged to form a single terminal arbor. Axons also had thin, non-CF collaterals that projected either to a cerebellar nucleus or to the cortex. The results indicate that the morphological characteristics of OC axons, including branching and termination, are basically conserved between the chick and the rat.


[The complexity of repatriating psychiatric patients].
This article describes the method by which the repatriation to the Netherlands of psychiatric patients living abroad is carried out. On the basis of one case, namely that of a psychotic male with low Hb and fear of HIV, it is shown that the repatriation of psychiatric patients can be extremely complex and that a psychiatrist's active involvement in the patient's repatriation can be extremely important.


Clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder.
To examine the clinical and genetic characteristics of Korean male alcoholics with and without attention deficit hyperactivity disorder (ADHD). The present study included 85 male alcoholics who were diagnosed as having DSM-IV alcohol dependence. A total of 28 (32.9%) alcoholics were diagnosed as having DSM-IV ADHD with ongoing symptoms in adulthood. For the evaluation of their psychiatric conditions, the alcohol dependence scale (ADS), Beck depression inventory (BDI), Beck anxiety inventory (BAI), Barratt impulsiveness scale (BIS), brief anger-aggression questionnaire (BAQ), overt aggression scale (OAS), codependence test, and obsessive compulsive drinking scale (OCDS) were administered. The genotype frequencies of the dopamine type 2 receptor gene (DRD2), aldehyde dehydrogenase type 2 gene (ALDH2), functional polymorphism in the regulatory region of the serotonin transporter gene (5-HTTLPR), and catechol-O-methyltransferase gene (COMT) polymorphisms were examined. Compared with alcoholics without ADHD, the mean ages for the onset of pathological drinking and alcohol withdrawal hallucinations were significantly earlier in alcoholics with ADHD. There was also a significant difference in the history of antisocial behaviour between the two groups. Compared with alcoholics without ADHD, the mean scores of the ADS, BDI, BAI, OAS, and OCDS were significantly higher in alcoholics with ADHD. With regard to the codependence test results, the mean scores of the interpersonal problem, low self-esteem and anxiety/fear subscales, and the mean total score of the codependence test were significantly higher in alcoholics with ADHD when compared with those without ADHD. There were no significant differences in the genotype frequencies of the DRD2, ALDH2, 5-HTTLPR, and COMT polymorphisms between alcoholics with and without ADHD. The results of this study suggest that the comorbidity of alcohol dependence and ADHD in this Korean sample forms a distinct clinical phenotype that shows an increased severity of alcohol-related symptoms and behavioural/emotional problems and that ADHD is associated with an increased risk for the early onset of alcohol dependence in Korean male alcoholics.


Evaluation of Renal Oxygenation Level Changes after Water Loading Using Susceptibility-Weighted Imaging and T2* Mapping.
To assess the feasibility of susceptibility-weighted imaging (SWI) while monitoring changes in renal oxygenation level after water loading. Thirty-two volunteers (age, 28.0 ± 2.2 years) were enrolled in this study. SWI and multi-echo gradient echo sequence-based T2(*) mapping were used to cover the kidney before and after water loading. Cortical and medullary parameters were measured using small regions of interest, and their relative changes due to water loading were calculated based on baseline and post-water loading data. An intraclass correlation coefficient analysis was used to assess inter-observer reliability of each parameter. A receiver operating characteristic curve analysis was conducted to compare the performance of the two methods for detecting renal oxygenation changes due to water loading. Both medullary phase and medullary T2(*) values increased after water loading (p < 0.001), although poor correlations were found between the phase changes and the T2(*) changes (p > 0.05). Interobserver reliability was excellent for the T2(*) values, good for SWI cortical phase values, and moderate for the SWI medullary phase values. The area under receiver operating characteristic curve of the SWI medullary phase values was 0.85 and was not different from the medullary T2(*) value (0.84). Susceptibility-weighted imaging enabled monitoring changes in the oxygenation level in the medulla after water loading, and may allow comparable feasibility to detect renal oxygenation level changes due to water loading compared with that of T2(*) mapping.


Malnutrition in School-Going Adolescents in Dessie Town, South Wollo, Ethiopia.
Malnutrition among adolescents is a global public health problem. Nutrient intake is a proxy measure of nutritional status, but studies in developing countries describing the actual nutrient intake condition associated with nutrition in the adolescents are limited. On top of this, there is inconsistent finding on the extent of malnutrition among adolescents. Hence, the aim of this study was to assess malnutrition and the associated factors among adolescents at Dessie high school. A school-based cross-sectional study was conducted among 365 randomly selected high school adolescents. The data were collected using a structured questionnaire adapted from previous literature studies. Nutrient intakes were estimated by ESHA food processor software from a 24-hour recall, and anthropometric indices were calculated from weight, height, age, and sex. The data analysis was managed by SPSS version 23. Binary logistic regression and multinomial logistic regression were used to report the associated factors of malnutrition. Adjusted odds ratio with 95% CI was used to reveal the presence of statistical association. The percentage of being stunted, underweight, and overweight/obese was 15.7%, 6.3%, and 8.2%, respectively. Snack consumption (AOR = 0.38, 95% CI: 0.20, 0.71) was negatively associated with stunting, while MAR <1 (AOR = 3.36, 95% CI: 1.15, 7.82) was positively associated with stunting. Being a male (AOR = 2.76, 95% CI: 1.03, 7.44) and meal consumption <3 times per day (AOR = 4.21, 95% CI: 1.35, 13.11) were factors positively associated with being underweight/thin. Dietary diversity score <5 (AOR = 0.35, 95% CI: 0.13, 0.89) was negatively associated with overweight/obesity, while MAR < 1 (AOR = 3.14, 95% CI: 1.09, 9.09) was positively associated with overweight/obesity. The percent of overweight/obesity among adolescents in the study area was higher compared with the national and regional prevalence, and this was found to be a public health concern. Therefore, increasing snack consumption, sex consideration, increasing meal consumption, and intake of diversified foods should be included in the prevention strategies of malnutrition among adolescents.


[Urinary urease activity in urolithiasis patients].
Urease activity (UA) and the ability of the urine to form crystals (AFC) were assessed in the urine from 149 urolithiasis patients and 11 healthy controls. Patients with primary uroliths had high UA and AFC in 17-18% of the cases, in recurrent urolithiasis this percentage was 29-35%. The speed of phosphate and oxalate crystals formation as well as formation of renal calculus correlated with UA and UA levels. Thus, UA and AFC may be employed as criteria in prognostication of the duration of phosphate and oxalate lithogenesis.


β-catenin mutation is correlated with a favorable prognosis in patients with hepatocellular carcinoma.
The β-catenin gene is frequently mutated in patients with hepatocellular carcinoma (HCC) and has long been thought to be one of the major oncogenes involved in the hepatocarcinogenesis. The prognostic role of β-catenin mutation in HCC remains unclear. To address this issue, a search for relevant studies was performed in the PubMed, Embase and Web of Science databases. The pooled effect was calculated from the available data to evaluate the correlation of β-catenin mutation with overall survival rate and tumor clinicopathological features in patients with HCC. The pooled odds ratio (OR) was calculated using the Mantel-Haenszel model for fixed effects. Three studies met the inclusion criteria. A total of 618 cases were included, and β-catenin mutation was identified in 104 of them. The meta-analysis revealed that the presence of β-catenin mutation (n=104), compared with the control group (n=514), was correlated with a longer overall survival rate [OR, 0.33; 95% confidence interval (CI), 0.21-0.53; P<0.00001] in patients with HCC. No significant heterogeneity was found among the eligible studies (I2=0%; P=0.72). β-catenin mutation was correlated with a relatively lower rate of hepatitis B virus infection (OR, 0.36; 95% CI, 0.21-0.61; P=0.0002), improved tumor differentiation (OR, 0.32; 95% CI, 0.19-0.56; P<0.0001) and a lower tumor-node-metastasis stage (I+II) (OR, 0.23; 95% CI, 0.14-0.38; P<0.00001). These findings suggest that β-catenin mutation may predict a favorable prognosis in patients with HCC.


[High-pressure air-blast injury of the esophagus].
Blast injuries causing pneumatic damage to the oesophagus are very rare. Patients usually present with respiratory distress, subcutaneous and mediastinal emphysema, and may also have pneumothorax. Ruptures need early repair to avoid serious morbidity and potential lethal complications. We report about a successfully treated 47-year-old patient, who has been admitted to our department with compressed air injury of the oesophagus.


Urodynamic and electrophysiologic study of the urinary disturbances caused by cervical myelopathy.
Urinary disturbance is one of the significant symptoms of cervical myelopathy. To make the diagnosis of urinary disturbance, preoperative urodynamic studies and evoked spinal cord potentials (ESCPs) recording were performed on 60 surgical patients with cervical myelopathy. Half (30) of this group complained of urinary disturbance, and 22 (37%) were diagnosed as having neurogenic bladder. The presence of neurogenic bladder was closely correlated with severe limb symptoms and relatively slow ESCP velocity. It was confirmed that neurogenic bladder was caused by severe spinal cord damage. However, for 47% of the patients with urinary complaints, findings of urodynamic examinations were negative; these patients probably had pathologic or psychosomatic factors other than neurogenic bladder due to cervical myelopathy. The prognosis of the neurogenic bladder appears to be influenced by irreversibility of the spinal cord lesions.


Increased cytosol Ca(2+) and type 1 programmed cell death in Bcl-2-positive U937 but not in Bcl-2-negative PC-3 and Panc-1 cells induced by the 5-lipoxygenase inhibitor MK 886.
MK 886, an arachidonic acid-related analog which inhibits the enzyme, 5-lipoxygenase by an indirect mechanism involving the 5-lipoxygenase activating protein, rapidly increased U937 cytosol Ca(2+), much of which localized around the cell nuclei. Five-lipoxygenase activity was not directly involved since the direct redox-dependent 5-LPOx inhibitor, SC-41661A did not increase Ca(2+). U937 cells subsequently undergo classic type 1 programmed cell death. At least initially the ionized calcium originates from internal stores. Coincident with the rise in U937 ionized calcium, MK 886 rapidly increased reactive oxygen species and reduced mitochondrial membrane potential, as judged by several fluorescent probes. The Ca(2+) response of myeloid leukemia-derived HL-60 cells to MK 886 was similar and both cell lines express Bcl-2 protein. Bcl-2-negative Panc-1 and PC-3 cells did not respond to MK 886 with a Ca(2+) signal but did develop oxidative stress and a decline in mitochondrial membrane potential; these events are thought to contribute to the inhibition of cell proliferation and induction of a type 2 PCD. In addition to its marked inhibition of Bcl-2 mRNA synthesis, an interesting hypothesis is that MK 886, serving as a low molecular weight ligand, either by direct or indirect inhibition of U937 Bcl-2 protein function, possibly related to an ion channel activity, alters the distribution of intracellular, possibly nuclear Ca(2+), thereby promoting the development of type 1 programmed cell death.


Regulatory roles for MD-2 and TLR4 in ligand-induced receptor clustering.
LPS, a principal membrane component in Gram-negative bacteria, is recognized by a receptor complex consisting of TLR4 and MD-2. MD-2 is an extracellular molecule that is associated with the extracellular domain of TLR4 and has a critical role in LPS recognition. MD-2 directly interacts with LPS, and the region from Phe(119) to Lys(132) (Arg(132) in mice) has been shown to be important for interaction between LPS and TLR4/MD-2. With mouse MD-2 mutants, we show in this study that Gly(59) was found to be a novel critical amino acid for LPS binding outside the region 119-132. LPS signaling is thought to be triggered by ligand-induced TLR4 clustering, which is also regulated by MD-2. Little is known, however, about a region or an amino acid in the MD-2 molecule that regulates ligand-induced receptor clustering. MD-2 mutants substituting alanine for Phe(126) or Gly(129) impaired LPS-induced TLR4 clustering, but not LPS binding to TLR4/MD-2, demonstrating that ligand-induced receptor clustering is differentially regulated by MD-2 from ligand binding. We further show that dissociation of ligand-induced receptor clustering and of ligand-receptor interaction occurs in a manner dependent on TLR4 signaling and requires endosomal acidification. These results support a principal role for MD-2 in LPS recognition.


Intravitreal ranibizumab (Lucentis) in the treatment of retinal angiomatous proliferation (RAP).
Retinal angiomatous proliferation (RAP) is a distinct variant of neovascular age-related macular degeneration (AMD). The aim of this study is to evaluate the functional and anatomic outcome after intravitreal ranibizumab (Lucentis) treatment in patients with RAP. Prospective study of consecutive patients with newly diagnosed or recurrent RAP treated with intravitreal ranibizumab at the Jules Gonin Eye Hospital between March 2006 and December 2007. Baseline and monthly follow-up visits included best-corrected visual acuity (BCVA), fundus exam and optical coherence tomography. Fluorescein and indocyanine green angiography were performed at baseline and repeated at least every 3 months. Thirty-one eyes of 31 patients were treated with 0.5 mg of intravitreal ranibizumab for RAP between March 2006 and December 2007. The mean age of the patients was 82.6 years (SD:4.9). The mean number of intravitreal injections administered for each patient was 5 (SD: 2.4, range 3 to 12). The mean follow up was 13.4 months (SD: 3, range 10 to 22). The baseline mean logMAR BCVA was 0.72 (SD: 0.45) (decimal equivalent of 0.2). The mean logMAR BCVA was improved significantly (P < 0.0001) at the last follow-up to 0.45, SD: 0.3 (decimal equivalent 0.35). The visual acuity (VA) improved by a mean of 2.7 lines (SD 2.5). Mean baseline central macular thickness (CMT) was 376 microm, and decreased significantly to a mean of 224 microm (P < 0.001) at the last follow-up. Mean reduction of CMT was 152 microm (SD: 58). An average of 81.5% of the total visual improvement and 85% of the total CMT reduction occurred during the first post-operative month after one intravitreal injection of ranibizumab. During follow-up, an RPE tear occurred in one eye (3.2%) of the study group. No injection complications or systemic drug-related side-effects were noted during the follow-up period. Intravitreal ranibizumab injections appeared to be an effective and safe treatment for RAP, resulting in visual gain and reduction in macular thickness. Further long-term studies to evaluate the efficacy of intravitreal ranibizumab in RAP are warranted.


[Chemoprevention of cancers, the point of view of health insurance].
Faced with scientific progress, social security must be concerned by ethics, especially by protection of personal integrity. Financial necessities lead to take into account the efficiency of public health interventions. But in front of potentially toxic drug, are we allowed to compare possible advantages with potentially serious risks for healthy women? For these reasons, social security takes a stand in favour of carefully controlled trials, focused on restricted target populations which are estimated at high risk of cancer. Research of side effects should be included in the follow of the patients and special caution should be taken to avoid premature spreading of this behaviour. About a financial contribution of social security, the National fund for health prevention, education and information (FNPEIS) could perhaps not support such a project, regarding to his experimental nature. CNAMTS-INSERM research contracts could be an alternative.


Stimulation of tear secretion and treatment of dry-eye disease with 3-isobutyl-1-methylxanthine.
We examined the effect of topically applied 3-isobutyl-1-methylxanthine (IBMX), a known secretagogue, on tear secretion and dry-eye disease in a clinical study. We found that IBMX produced a dose-dependent decrease in tear film osmolarity that was significant at 3.0 mmol/L (P less than .0005) in patients with dry-eye disease. This effect was not blocked by prior administration of proparacaine hydrochloride (P less than .05). Throughout a 4-week, open-label, vehicle-controlled study, IBMX decreased tear film osmolarity significantly, whereas vehicle alone did not. After 4 weeks, mean (+/- SEM) osmolarity in IBMX-treated eyes decreased from 325 +/- 3.2 mOsm/L to 312 +/- 1.8 mOsm/L but remained unchanged in vehicle-treated eyes (323 +/- 4.4 mOsm/L vs 320 +/- 4.2 mOsm/L). In our study, IBMX was significantly more effective than vehicle alone in decreasing rose bengal staining (P less than .02). Hence, topical IBMX stimulated tear secretion and decreased ocular surface disease in patients with dry-eye disease.


Existence of a low-threshold and sustained inward current in rabbit atrio-ventricular node cells.
Single myocytes were dissociated from the atrio-ventricular (AV) node of rabbit hearts. Spontaneous action potentials of the N or NH type were recorded from the fusiform AV node cells. Under whole-cell voltage clamp, these cells were characterized by the presence of hyperpolarization-activated cation current (I(f)), delayed rectifier K+ current (IK), and L-type Ca2+ current (ICa,L). After blocking I(f) and IK, depolarizing pulses from -80 mV revealed a sustained inward current, which was suppressed by 1 microM nicardipine. The activation threshold of the sustained inward current was around -60 mV and the maximum amplitude was 25.4 +/- 20.1 pA at -40 mV (n = 15). The current was also blocked by 1 microM verapamil. The sustained inward current was not decreased (125 +/- 32% of control, N = 5) by reducing [Ca2+]o from 1.8 to 0.1 mM, while it was nearly suppressed by depleting [Na+]o, differently from ICa,L. We concluded that the nicardipine-sensitive sustained inward current is largely attributable to Ist described in the rabbit sino-atrial node pacemaker cells. I(f) and Ist were not found in rod-shape AV node cells.


Complete chloroplast genome sequence of a subtropical tree, Actinodaphne cupularis (Lauraceae).
Actinodaphne cupularis is a multi-purpose tree that grows in central or southwest China and is one of the primary source plants for making Hawk tea. In this study, we firstly assembled and characterized the complete chloroplast (cp) genome of A. cupularis using Illumina pair-end sequencing. The results revealed that the total length of the cp genome was 152,748 bp with 39% of the guanine-cytosine content, including a pair of 20,066 bp reverse repeat regions, a large single-copy region with 93,788 bp, and a small single-copy region with 18,828 bp. One hundred twenty-four genes were identified, including eight rRNA genes, 36 tRNA genes, and 80 protein-coding genes. In addition, the maximum likelihood phylogenetic tree was constructed between the cp genome of A. cupularis and its related species. The results suggested that A. cupularis was more closely related to Actinodaphne obovate and then formed a sister clade with the Machilus genus. This study not only analyzed the cp genome characteristic information of A. cupularis but also provided a specific basis and foundation for future research.


Corneomalacia perforans in a patient with rheumatoid arthritis.
Bilateral corneomalacia perforans occurred in a young woman who had had rheumatoid arthritis for 7 years. The perforations appeared to be precipitated by systemic corticosteroid therapy. The only symptom was a sudden loss of vision. Conservative treatment - withdrawal of the steroid therapy and application of soft contact lenses for 3 weeks - resulted in complete healing of the perforations and a marked increase in visual acuity.


Aescin reduces oxidative stress and provides neuroprotection in experimental traumatic spinal cord injury.
Aescin has many physiological functions that are highly relevant to spinal cord injury (SCI), including anti-inflammation, anti-oxidation, anti-oedema, and enhancing vascular tone. The present study investigated the putative therapeutic value of aescin in SCI, with a focus on its neuroprotective, anti-inflammatory, and anti-oxidative properties. Sodium aescinate (1.0mg/kg body weight) or equivalent volume of saline was administered 30min after injury by intravenous injection, with an additional dose daily for seven consecutive days after moderate SCI in rats. After contusion injury of the 8th thoracic (T8) spinal cord, aescin-treated rats developed less severe hind limb weakness than saline controls, as assayed by the Basso-Beattie-Bresnahan scale, the beam walking test, and a footprint analysis. The improved locomotor outcomes in aescin-treated rats corresponded to markedly decreased immune response, oxidative stress, neuronal loss, axon demyelination, spinal cord swelling, and cell apoptosis, measured around T8 after impact. Our data suggest aescin treatment as a novel, early, neuroprotective approach in SCI. Given the known safety of aescin in clinical applications, the results of this study suggest that it is a good candidate for SCI treatment in humans.


Comparative study of the corrosion behavior of MA-956 and conventional metallic biomaterials.
In this work the corrosion behavior of a new biomaterial, the MA-956 superalloy, immersed in Hank's solution is evaluated. A comparison with conventional metallic alloys used as articular implants is established. To determine the corrosion behavior we employed electrochemical methods: evaluation of corrosion potential Ecorr, electrochemical impedance spectroscopy (EIS), and anodic polarization curves. The corrosion resistance of the MA-956 superalloy preoxidized at 1100 degrees C during 100 h is at least two orders of magnitude higher than for the other alloys. This satisfactory behavior is stationary with time. Also the probability of the appearance of the pitting corrosion process is very low. When cracking is generated in the alpha-alumina layer the repassivation process is assured because of the high Cr content in the superalloy. This study is the first step in proposing this new alloy as a biomaterial. The low toxicity of these metallic alloys in the physiological environment suggests that in vivo their biocompatibility could be satisfactory.


Thymus involvement in myasthenia gravis: Epidemiological and clinical impacts of different self-tolerance breakdown mechanisms.
The reasons for the abrogation of self-immunological tolerance in patients with myasthenia gravis (MG) may be different between those with concomitant thymic hyperplasia or thymoma, and those with no evidence of thymic involvement. We conducted a retrospective observational case series study to investigate the epidemiology as well as the clinical, serologic, and electromyographic (EMG) characteristics of individuals diagnosed as having MG. We found that the average age at MG onset of patients with either thymic hyperplasia or thymoma was much younger (by ~20years) than that of MG patients without thymic involvement. Thymic hyperplasia was more common in females than males. There were no differences in the rates of ocular MG vs. generalized MG among those three study groups. There were also no group differences in the rates of neuromuscular junction disfunction, as observed on EMG or by the results of serology tests for acetyl choline receptor antibody. Interestingly, only patients without thymic involvement had other autoimmune diseases, and most of them were females. The patients with other coexisting autoimmune disease had a similar age at MG onset as the other patients with no thymic involvement. These results shed light on the impact of epidemiological and clinical factors that result from different mechanisms of self-immunological tolerance breakdown that occurs in MG.


Rad51 activates polyomavirus JC early transcription.
The human neurotropic polyomavirus JC (JCV) causes the fatal CNS demyelinating disease progressive multifocal leukoencephalopathy (PML). JCV infection is very common and after primary infection, the virus is able to persist in an asymptomatic state. Rarely, and usually only under conditions of immune impairment, JCV re-emerges to actively replicate in the astrocytes and oligodendrocytes of the brain causing PML. The regulatory events involved in the reactivation of active viral replication in PML are not well understood but previous studies have implicated the transcription factor NF-κB acting at a well-characterized site in the JCV noncoding control region (NCCR). NF-κB in turn is regulated in a number of ways including activation by cytokines such as TNF-α, interactions with other transcription factors and epigenetic events involving protein acetylation--all of which can regulate the transcriptional activity of JCV. Active JCV infection is marked by the occurrence of rapid and extensive DNA damage in the host cell and the induction of the expression of cellular proteins involved in DNA repair including Rad51, a major component of the homologous recombination-directed double-strand break DNA repair machinery. Here we show that increased Rad51 expression activates the JCV early promoter. This activation is co-operative with the stimulation caused by NF-κB p65, abrogated by mutation of the NF-κB binding site or siRNA to NFκB p65 and enhanced by the histone deacetylase inhibitor sodium butyrate. These data indicate that the induction of Rad51 resulting from infection with JCV acts through NF-κB via its binding site to stimulate JCV early transcription. We suggest that this provides a novel positive feedback mechanism to enhance viral gene expression during the early stage of JCV infection.


Why is cardiovascular health important in menopausal women?
Since endogenous estrogen shows some preventative benefits against cardiovascular risk factors in premenopausal women, cardiovascular disease (CVD) is often considered a male disease. However, CVD is the biggest cause of death in women, especially after menopause when endogenous estrogen withdrawal has detrimental effects on cardiovascular physiology and whole-body metabolism. Despite this, awareness of the risk of CVD is low in both women and in doctors; this needs rectifying. Women are under-represented in most clinical studies of CVD. Following diagnosis of CVD, the prognosis for women is not systematically similar to that for men. Furthermore, from the few comparisons conducted, gender differences in response to pharmacological interventions are evident, so that results obtained in wholly or largely male-based studies cannot be systematically extrapolated to women. Women with CVD should be afforded equivalent investigations and treatment to men, and it is vital that women be included in clinical trials in sufficient numbers to allow sub-group analyses and subsequent development of appropriate therapies. Since CVD is usually advanced by the time symptoms appear, prevention is the key; health management advice might include smoking cessation, adoption of a healthy diet, and incorporation of physical activity into the lifestyle.


Inhibition of mucopolysaccharide sulfation.
A method of measuring the inhibition of sulfation in mucopolysaccharides employed the coupled enzyme system of Wortman. This procedure utilized the phenol and mucopolysaccharide sulfotransferases of beef cornea extract. Compounds tested against this system included amino acids, salicylates, 2-mercaptoethylamine and a derivative, heterocyclic ethanethiosulfuric acids, arylsulfonamidoethanethiosulfates, and several other compounds. In general, the salicylates and thiosulfates were inhibitory, with sodiumm 2-(4-acetamidobenzenesulfonamido)-ethanethiosulfate being the most inhibitory and 2-mercaptoethylguanidine trithiocarbonic acid the second most inhibitory. Salicylamide and allopurinol, which have been employed in kidney stone therapy, were inhibitors. Kidney stones have a mucopolysaccharide sulfate matrix, which is involved in their growth.


Non-functioning parathyroid gland carcinoma: case report.
Parathyroid gland carcinoma is a rare malignancy. The tumor is mostly functioning, causing severe hyperparathyroidism, with high serum calcium level and severe bone disease. Non-functioning parathyroid carcinomas are extremely rare. We report on a 60-year-old male patient admitted to ENT Department due to a large neck tumor mass compressing the thyroid and trachea. Preoperatively, thyroid hormone, parathyroid hormone (PTH) and calcium serum levels were normal. The following immunohistochemical markers (DAKO, Denmark) were used: bcl-2; CD-10; Chromogranin-A; Cyclin-D1; EMA; Ki-67; Mdm-2; p-53; PGP-9,5; RCC; Synaptophysin; Thyroglobulin; and TTF-1. Immunohistochemical analysis indicated the diagnosis of a primary parathyroid gland carcinoma. Tumor cells showed diffusely positive immunohistochemical staining with chromogranin-A and PGP-9,5, positive staining of variable intensity with synaptophysin, and weakly positive reaction with EMA. Also, the cytoplasm of tumor cells was diffusely positively stained with bcl-2, while the nuclei showed positive reaction with p-53 oncogene and TTF-1. The remaining markers (CD-10, cyclin-D1, Ki-67, Mdm-2, RCC and thyroglobulin) were negative. Four years after the surgery, the patient died from renal carcinoma pulmonary metastases and liver cirrhosis complications. In conclusion, non-functioning parathyroid gland carcinoma is a very rare disease. Detailed immunohistochemical analysis is needed to distinguish it from other thyroid and parathyroid neoplasms and metastatic carcinoma. Surgical treatment is presently the best mode of therapy.


[Effect analysis of treating intracranial wide-neck bifurcation aneurysms through Woven EndoBridge].
Objective: To explore the clinical effect of Woven EndoBridge (WEB) in the treatment of wide-neck bifurcation aneurysms. Methods: The clinical and imaging data of 11 patients with intracranial wide-neck bifurcation aneurysms treated by WEB alone at Department of Neurosurgery of the Northern Theater General Hospital from September 2017 to May 2018, were retrospectively analyzed. The patients were 7 males and 4 females, aged (54±11) years (ranged from 31 to 66 years). The aneurysms of 5 patients were located in the anterior communicating artery, 3 in the top of the basilar artery, and 3 in the bifurcation of the middle cerebral artery. The intraoperative and postoperative conditions of the patients were recorded, and the degree of aneurysm embolization was evaluated by WEB embolization aneurysm occlusion scale (WOS). Results: The intraoperative WEB release of all the 11 patients was good, with 3 cases of WOS grade A, 1 of grade B and 7 of grade C, with no intraoperative acute complications occurring. The imaging follow-up was not carried out in 1 patient due to economic reason, and the clinical follow-up was good until 3 years after the operation; 10 patients were followed up by imaging for 6 months to 3 years, and no postoperative complications occurred in the target treatment area. Among the 2 patients with WOS grade A and 1 patient with grade B during operation, according to the postoperative follow-up, all were WOS grade A; among the 7 patients with WOS grade C during operation, 4 were still of grade C and 3 were of grade D according to the follow-up. Among the 3 patients with WOS grade D, 1 patient received secondary embolization due to poor recurrence morphology, unstable hemodynamics and high possibility of rupture of aneurysm, stent assisted coil embolization was adopted, with good immediate effect; the other 2 cases had recurrent aneurysms, but the aneurysms had good morphology and stable hemodynamics, therefore, clinical follow-up was continued and no secondary surgery was performed. No complications occurred in all these 11 patients. Conclusions: The operation of treating unruptured intracranial wide-neck bifurcation aneurysms with WEB device alone is simple, and there is no need for anticoagulation and antiplatelet treatment before and after the operation, the clinical effect is being good. WEB device provides a new treatment option for intracranial wide-neck bifurcation aneurysms.


Effectiveness of a targeted and tailored pharmacist-led intervention to improve adherence to antihypertensive drugs among patients with type 2 diabetes in Indonesia: A cluster randomised controlled trial.
To assess the effects of a targeted and tailored pharmacist-led intervention among patients with type 2 diabetes (T2DM) who are nonadherent to antihypertensive drugs. A cluster-randomised controlled trial was conducted in 10 community health centres (CHCs) in Indonesia among T2DM patients aged ≥18 years who reported nonadherence to antihypertensive drugs according to the Medication Adherence Report Scale (MARS-5). Patients in CHCs randomised to the intervention group received a tailored intervention based on their adherence barriers (eg, forgetfulness, lack of knowledge, lack of motivation and/or other drug-related problems) using a simple question-based flowchart at baseline and 1-month follow-up. Patients in control CHCs received usual care. Primary outcome was the between-group difference in change in MARS-5 score from baseline to 3-month follow-up. Secondary outcomes included changes in patients' blood pressure and their medication beliefs. Differences in difference in primary and secondary outcomes between groups were assessed using general linear models. In total, 201 patients were screened for eligibility, 113 met the inclusion criteria and participated, and 89 (79%) patients had complete follow-up. Forgetfulness (42%) and lack of knowledge (18%) were the most common adherence barriers identified at baseline. The intervention improved medication adherence by 4.62 points on the MARS-5 scale (95% CI 0.93 to 8.34, P value = 0.008). There were no significant changes in blood pressure levels and beliefs about antihypertensive drugs. A tailored low-cost pharmacist-led intervention aimed at nonadherent T2DM patients resulted in an improvement in medication adherence to antihypertensive drugs. There were no significant changes in secondary outcomes.


Gadd45b deficiency promotes premature senescence and skin aging.
The GADD45 family of proteins functions as stress sensors in response to various physiological and environmental stressors. Here we show that primary mouse embryo fibroblasts (MEFs) from Gadd45b null mice proliferate slowly, accumulate increased levels of DNA damage, and senesce prematurely. The impaired proliferation and increased senescence in Gadd45b null MEFs is partially reversed by culturing at physiological oxygen levels, indicating that Gadd45b deficiency leads to decreased ability to cope with oxidative stress. Interestingly, Gadd45b null MEFs arrest at the G2/M phase of cell cycle, in contrast to other senescent MEFs, which arrest at G1. FACS analysis of phospho-histone H3 staining showed that Gadd45b null MEFs are arrested in G2 phase rather than M phase. H2O2 and UV irradiation, known to increase oxidative stress, also triggered increased senescence in Gadd45b null MEFs compared to wild type MEFs. In vivo evidence for increased senescence in Gadd45b null mice includes the observation that embryos from Gadd45b null mice exhibit increased senescence staining compared to wild type embryos. Furthermore, it is shown that Gadd45b deficiency promotes senescence and aging phenotypes in mouse skin. Together, these results highlight a novel role for Gadd45b in stress-induced senescence and in tissue aging.


Bedside Assessment of the Necessity of Daily Lab Testing for Patients Nearing Discharge.
As part of the Choosing Wisely® campaign, the Society of Hospital Medicine recommends against performing "repetitive complete blood count chemistry testing in the face of clinical and lab stability." With this recommendation as a framework, we targeted 2 hospitalist-run inpatient medicine units that employed bedside, scripted, interdisciplinary rounds. Our multifaceted intervention included prompting the hospitalist to identify clinically stable patients for next-day discharge and to discontinue labs when appropriate. It was coupled with the education of the clinicians and a regular data review for the hospitalists and unit staff. Among 2877 discharges included in a 1-year period, there was a significantly decreasing trend after the intervention in the percentage of patients getting labs in the 24, 48, and 72 hours before discharge (-1.87%, -1.47%, and -0.74% decrease per month, respectively; P < 0.05). Our structured, multifaceted approach effectively reduced daily lab testing in the 24 to 48 hours prior to discharge.


The epidemiology of breast cancer.
Table 5 presents risk factors for breast cancer generally regarded as established, together with their approximate relative risks. With the exception of age, country of birth, and a history of breast cancer in both a mother and a sister, all of the relative risks reported to date are of a relatively modest magnitude. Thus, new risk factors need to be identified and knowledge of existing risk factors refined. Factors for which the evidence of an etiologic role has mounted over the past several years, but which are not yet considered to be established, include the protective effects of parity and lactation in certain age groups and the increased risks associated with alcohol consumption and with DES exposure during pregnancy. In addition, physical activity has emerged as a factor worthy of further study. Some evidence suggests that use of oral contraceptives for several years at an early age modestly increases the risk for breast cancer diagnosed before age 35 and perhaps age 45. Use of estrogen-replacement therapy for 20 years or more has been found by a few studies to increase the risk for breast cancer in the postmenopausal years; further studies of very long-term users are needed. Also, other risks and benefits of these hormones need to be taken into account when women decide whether to use them. Surprisingly elusive has been the etiologic role of endogenous hormones, especially in view of the large number of studies that have been concerned with them. A better understanding of the role of endogenous hormones should help explain the mechanisms of action of known and suspected risk factors. Areas of high priority for further research thus include establishing with more certainty whether the risk for breast cancer is increased in any subgroups of women who use oral contraceptives and estrogen-replacement therapy and determining the etiologic roles of specific endogenous hormones. The possible risks associated with alcohol consumption and lack of physical activity need to be studied more thoroughly, and ideas about new potential risk factors are needed. Although epidemiologic studies will continue to be concerned with diet, enthusiasm for its etiologic role in women has been considerably dampened by the lack of association in many of the studies reported to date. The studies in women exposed to radiation, DES, and oral contraceptives suggest that the timing of some exposures may be critical, since the effects of these agents may mostly be limited to specific time periods of rapid breast development.(ABSTRACT TRUNCATED AT 400 WORDS)


HIV-1 antibodies in prevention of transmission.
To present the data that suggest that antibodies to HIV may prevent HIV-1 infection. Many human monoclonal broadly neutralizing antibodies (bnAbs) have been isolated over the last decade. Numerous experiments of passive immunization in nonhuman primate models have allowed to accumulate strong evidences that bnAbs, opposed to nonneutralizing antibodies, are the best candidates to prevent HIV-1 infection. bnAbs counteract HIV-1 by both blocking the virus at the portal of entry and clearing rapidly viral foci established at distance after dissemination of the virus following infection. Cocktails of bnAbs or modified bi/trispecific antibodies will be necessary to counter the large and evolving antigenic diversity of the HIV-1 species. Two large multicenter phase IIb clinical trials have been initiated. Even if they are not conducted with the most recent and most potent bnAb, the results which are expected in 2022 will inform us on the real potency of bnAbs at preventing HIV-1 acquisition in the real life. If these trials demonstrate the efficacy of bnAbs, they will open the trail toward new strategies for preexposure prophylaxis, eventually postexposure prophylaxis and prevention of mother-to-child transmission.