Prevalence and Correlates of Psychological Distress and Psychiatric Disorders in Asylum Seekers and Refugees Resettled in an Italian Catchment Area.
In recent years there has been a progressive rise in the number of asylum seekers and refugees displaced from their country of origin, with significant social, economic, humanitarian and public health implications. The aim of this study is to describe the frequency and correlates of psychological distress and psychiatric disorders in asylum seekers and refugees resettled in an Italian catchment area. In the catchment area of Verona, all male asylum seekers and refugees aged 18 or above included in the Italian protection system for asylum seekers and refugees during a period of 1 year were screened for psychological distress and psychiatric disorders using validated questionnaires. During the study period, 109 asylum seekers or refugees were recruited. The frequency of traumatic events experienced was very high. More than one-third of the participants (36%) showed clinically relevant psychological distress, and one-fourth (25%), met the criteria for a psychiatric diagnosis, mainly PTSD and depressive disorders. In multivariate analyses, time after departure, length of stay in the host country and number of traumatic events were independent factors associated with psychological distress and psychiatric disorders. In an unselected sample of male asylum seekers and refugees, after around 1 year of resettlement in an Italian catchment area, the frequency of psychological distress and psychiatric disorders was substantial and clinically relevant. Health care systems should include a mental health component to recognise and effectively treat mental health conditions.


Activation of EGFR-PI3K-AKT signaling is required for Mycoplasma hyorhinis-promoted gastric cancer cell migration.
Persistent infection of Mycoplasma hyorhinis (M. hyorhinis) was associated with gastric cancer cell migration and invasion, but the mechanisms were not well understood. Herein, we found that M. hyorhinis activated phosphoinositide 3-kinase (PI3K)-AKT signaling axis in gastric cancer cell lines. Epidermal growth factor receptor (EGFR) was upstream of PI3K-AKT signaling in the context of M. hyorhinis infection, because phosphorylation of AKT Serine 473 was almost completely attenuated by the EGFR inhibitor AG1478 or by EGFR knockdown. Phosphorylation of AKT S473 induced by M. hyorhinis infection was also abolished by PI3K inhibitor wortmannin. Furthermore, we found that p37, a membrane protein of M. hyorhinis, could also promote M. hyorhinis-induced PI3K-AKT signaling activation and cell migration. In addition, pre-treatment with AG1478 or wortmannin significantly inhibited cell migration induced by M. hyorhinis infection or p37 treatment. In conclusion, EGFR-PI3K-AKT signaling plays an important role in M. hyorhinis-promoted cell migration in gastric cancer cells, thus providing a clue to the pathogenesis of M. hyorhinis in gastric cancer.


Persistent short stature in children with intrauterine growth retardation: use of growth hormone treatment.
Since the early 1970s, it has been demonstrated that growth hormone (GH) treatment improves the short-term growth rate of children with short stature due to intrauterine growth retardation (IUGR). However, it is only in recent years that studies have been conducted in which children with IUGR have been followed to final height. It is appreciated that pharmacological doses of GH are required for the treatment of short children with IUGR, and that the initial effect of rapid advancement of epiphyseal maturation is probably due more to the natural history of growth in children with IUGR than to the GH treatment. Initial studies are promising, showing that the rapid improvement in growth rate is eventually translated into an improvement in final height. However, studies involving a larger number of children with IUGR are necessary in order to quantify this improvement in final height.


Genome-wide analysis reveals the unique stem cell identity of human amniocytes.
Human amniotic fluid contains cells that potentially have important stem cell characteristics, yet the programs controlling their developmental potency are unclear. Here, we provide evidence that amniocytes derived from multiple patients are marked by heterogeneity and variability in expression levels of pluripotency markers. Clonal analysis from multiple patients indicates that amniocytes have large pools of self-renewing cells that have an inherent property to give rise to a distinct amniocyte phenotype with a heterogeneity of pluripotent markers. Significant to their therapeutic potential, genome-wide profiles are distinct at different gestational ages and times in culture, but do not differ between genders. Based on hierarchical clustering and differential expression analyses of the entire transcriptome, amniocytes express canonical regulators associated with pluripotency and stem cell repression. Their profiles are distinct from human embryonic stem cells (ESCs), induced-pluripotent stem cells (iPSCs), and newborn foreskin fibroblasts. Amniocytes have a complex molecular signature, coexpressing trophoblastic, ectodermal, mesodermal, and endodermal cell-type-specific regulators. In contrast to the current view of the ground state of stem cells, ESCs and iPSCs also express high levels of a wide range of cell-type-specific regulators. The coexpression of multilineage differentiation markers combined with the strong expression of a subset of ES cell repressors in amniocytes suggests that these cells have a distinct phenotype that is unlike any other known cell-type or lineage.


Personal narratives of adolescent mothers-to-be: contraception, decision making, and future expectations.
Results not discussed in a previously published qualitative study (Spear, 2001) are presented in this article. Analysis of the personal narratives of eight pregnant adolescents who attended an alternative school for pregnant teens yielded the following categories: decision making, contraceptive behavior and sexual attitudes, and future expectations. The findings revealed that decisions regarding pregnancy were made with little deliberation and some participants implied that pregnancy was planned. Although knowledgeable about how to prevent pregnancy, participants did not consistently practice contraception and their sexual experiences were marked by indifference and lacked intimacy. Future expectations consistently included support from the fathers of their unborn children. Implications for nursing practice and further research are discussed.


Predicting non-melanoma skin cancer via a multi-parameterized artificial neural network.
Ultraviolet radiation (UVR) exposure and family history are major associated risk factors for the development of non-melanoma skin cancer (NMSC). The objective of this study was to develop and validate a multi-parameterized artificial neural network based on available personal health information for early detection of NMSC with high sensitivity and specificity, even in the absence of known UVR exposure and family history. The 1997-2015 NHIS adult survey data used to train and validate our neural network (NN) comprised of 2,056 NMSC and 460,574 non-cancer cases. We extracted 13 parameters for our NN: gender, age, BMI, diabetic status, smoking status, emphysema, asthma, race, Hispanic ethnicity, hypertension, heart diseases, vigorous exercise habits, and history of stroke. This study yielded an area under the ROC curve of 0.81 and 0.81 for training and validation, respectively. Our results (training sensitivity 88.5% and specificity 62.2%, validation sensitivity 86.2% and specificity 62.7%) were comparable to a previous study of basal and squamous cell carcinoma prediction that also included UVR exposure and family history information. These results indicate that our NN is robust enough to make predictions, suggesting that we have identified novel associations and potential predictive parameters of NMSC.


Radiofrequency ablation and immunostimulant OK-432: combination therapy enhances systemic antitumor immunity for treatment of VX2 lung tumors in rabbits.
To evaluate whether antitumor immunity is enhanced systemically by combining radiofrequency ablation (RFA) and local injection of an immunostimulant, OK-432. Experiments were approved by the institutional animal care committee. Experimental Japanese rabbits inoculated with VX2 tumors in the lung and the auricle were randomized into four groups of eight: control (supportive care), RFA (RFA of lung tumor), OK-432 (direct injection of OK-432 into lung tumor), and combination therapy (lung RFA and direct OK-432 injection into lung tumor). All procedures were performed 1 week after implantation of VX2 tumors (week 1). In addition, a VX2 tumor rechallenge test was performed in the RFA and combination therapy groups. Survival time was evaluated by means of the Kaplan-Meier method and by using the log-rank test for intergroup comparison. Mean auricle tumor volumes were calculated every week. Specific growth rates (SGRs) were calculated and compared by using the Mann-Whitney test. The median survival times of the control, RFA, OK-432, and combination therapy groups were 23, 36.5, 46.5, and 105 days, respectively. Survival was significantly prolonged in the combination therapy group when compared with the other three groups (P <.05). The mean auricle tumor volume decreased only in the combination therapy group. The mean auricle tumor volumes of the combination therapy group from week 1 to week 7 were 205, 339, 264, 227, 143, 127, and 115 mm(3). SGR in the combination therapy group became significantly smaller than those in the other three groups (P < .05). In the rechallenge test, the volume of all reimplanted tumors decreased. Combining RFA with local injection of immunostimulant OK-432 may lead to indirectly activation of systemic antitumor immunity.


Evaluation of Root Dentin Damage during Retreatment Procedure using Various Engine-Driven Retreatment File Systems-A Micro-CT Study.
The aim of this research was to assess the damage to root dentin that arises from retreatment with different engine-driven NiTi retreatment files employing micro-computed tomography. Sixty mandibular premolar teeth having a single root and root canal that were recently extracted were gathered and stored. The specimens were de-coronated at the cementoenamel junction under water irrigation to achieve a homogeneous root length of 16 millimeters. Gutta-percha cones were coated with sealants and placed within the radicular canal till the WL. All sixty premolars were randomly assigned to one of the following three groups, with every group comprising 20 sample teeth each. Group 1: MTwo Retreatment files, Group 2: ProTaper Universal Retreatment files, Group 3: Edge File XR Retreatment rotary files. The quantity of root dentinal injury was estimated by deducting the dentin volume (mm3) in the pre- and post-therapy micro-CT scans at apical, middle, and cervical 3rd points. An intra-group comparative scrutiny showed that lower radicular dentinal injury was noted at apical 3rd (0.31 ± 0.16, 0.62 ± 0.02) in Edge File XR Retreatment file system and MTwo Retreatment file system in that order. The statistically significant disparity was seen amid the MTwo Retreatment file, Edge File XR Retreatment file system and ProTaper Universal Retreatment file, Edge File XR Retreatment file system with P value of 0.001on intergroup assessment. In spite of the limitations that this research had, it was inferred that each assessed file system proficiently eradicated the obturated material through the retreatment procedure performed. In addition, it was seen that the Edge File XR group showed lesser root dentin damage in contrast to MTwo and ProTaper Universal file systems.


Isolation and analysis of free fatty aldehydes from rat, dog, and bovine heart muscle.
Procedures are described for the isolation of free fatty aldehydes from total lipid extracts of rat, dog, and bovine heart muscle. These aldehydes did not arise from hydrolysis of the naturally occurring alkenyl ethers in either the extraction or isolation procedures. The free fatty aldehydes were present in heart muscle in amounts between 0.27 and 0.56 micromole per 100 mg of lipid. Hexadecanal and octadecanal are the principal free fatty aldehydes present, except in dog heart muscle where an unidentified, unusual aldehyde constitutes 20% of the mixture.


Severe Cushing's syndrome from an ectopic adrenocorticotropic hormone-secreting neuroendocrine tumour treated by osilodrostat.
Severe Cushing's syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare but often demands rapid diagnostics and treatment of hypercortisolism with its comorbidities. Pharmacotherapy of hypercortisolism by ketoconazole, metyrapone and osilodrostat is currently available. If unsuccessful or insufficient a bilateral adrenalectomy is an option. We present a 28-year-old female with severe Cushing's syndrome caused by a bronchial metastatic neuroendocrine tumour (NET). Hypercortisolism was efficiently treated by osilodrostat with block-replace and then titration regimen. A once-daily dose was finally used with normalised cortisol levels. Androgen levels measured by liquid chromatography-mass spectrometry were slightly elevated during the treatment but without any symptoms. A simple once-daily use of osilodrostat with titration regimen led to normalised cortisol levels in a severe Cushing's syndrome patient with an uncurable bronchial NET. Transient hypocortisolism during treatment appeared but was easily treated by hydrocortisone. Cushing's syndrome from an ectopic adrenocorticotropic hormone-producing tumour is rare. Cortisol upregulation is often severe and rapid, though clinical signs are not always fully pronounced. Rapid treatment is a key for preventing and reducing complications such as fractures, thromboembolism, bleeding, hyperglycaemia, and arterial hypertension. The novel potent steroidogenesis inhibitor osilodrostat can be used as first-line treatment for reducing hypercortisolism.


Use of a robust dehydrogenase from an archael hyperthermophile in asymmetric catalysis-dynamic reductive kinetic resolution entry into (S)-profens.
Described is an efficient heterologous expression system for Sulfolobus solfataricus ADH-10 (Alcohol Dehydrogenase isozyme 10) and its use in the dynamic reductive kinetic resolution (DYRKR) of 2-arylpropanal (Profen-type) substrates. Importantly, among the 12 aldehydes tested, a general preference for the (S)-antipode was observed, with high ee's for substrates corresponding to the NSAIDs (nonsteroidal anti-inflammatory drugs) naproxen, ibuprofen, flurbiprofen, ketoprofen, and fenoprofen. To our knowledge, this is the first application of a dehydrogenase from this Sulfolobus hyperthermophile to asymmetric synthesis and the first example of a DYRKR with such an enzyme. The requisite aldehydes are generated by Buchwald-Hartwig-type Pd(0)-mediated alpha-arylation of tert-butyl propionate. This is followed by reduction to the aldehyde in one [lithium diisobutyl tert-butoxyaluminum hydride (LDBBA)] or two steps [LAH/Dess-Martin periodinane]. Treatment of the profenal substrates with SsADH in 5% EtOH/phosphate buffer, pH 9, with catalytic NADH at 80 degrees C leads to efficient DYRKR, with ee's exceeding 90% for 9 aryl side chains, including those of the aforementioned NSAIDs. An in silico model, consistent with the observed broad side chain tolerance, is presented. Importantly, the SsADH-10 enzyme could be conveniently recycled by exploiting the differential solubility of the organic substrate/product at 80 degrees C and at rt. Pleasingly, SsADH-10 could be taken through several "thermal cycles," without erosion of ee, suggesting this as a generalizable approach to enzyme recycling for hyperthermophilic enzymes. Moreover, the robustness of this hyperthermophilic DH, in terms of both catalytic activity and stereochemical fidelity, speaks for greater examination of such archaeal enzymes in asymmetric synthesis.


Experimental study of coil embolization using a new atelocollagen spring coil.
Spring steel coils have been used to occlude abnormal vessels in patients with a congenital heart malformation. However, long-term adverse effects of steel spring coils remain uncertain, although some long-term results appear to be good. The purpose of this study was to evaluate the angiographic and histologic results of coil embolization experimentally using a biodegradable atelocollagen coil that we have recently developed. The spring coil was made from a 30% atelocollagen solution mixed with a contrast medium. The delivery system consisted of a 5-F end-hole catheter and a 3-F modified biotome catheter as a catch and release system. Coil embolization was percutaneously attempted in 12 dogs, and only one coil was placed in each dog so that a variety of endothelial coverage could be evaluated both in complete and incomplete occlusion. At 1 wk to 5 mo after the procedure, the occluded vessels were resected and examined histologically. Postprocedural angiography showed complete occlusion in 6 of the 12 vessels and partial occlusion in 6. Follow-up angiography showed complete occlusion in 8 and incomplete occlusion in 4. Histologic examination revealed that diffuse thrombosis around the coil loops and the exchange between blood and contrast medium were detectable as early as 7 d after embolization. Atelocollagen was gradually replaced with fibrous tissue and became markedly degraded by 5 mo. Atelocollagen spring coils can be used to occlude abnormal vessel effectively and safely. The histologic reactions and the fate of the coil seem to be within tolerable limits. This experimental study supports the feasibility of a clinical trial of this coil embolization in patients with an aorticopulmonary collateral artery.


Major carotenoid isolated from Paracoccus schoinia NBRC 100637T is adonixanthin diglucoside.
The structure of a novel major carotenoid glycoside (nearly 80% of total carotenoids) from a newly isolated bacterium, Paracoccus schoinia NBRC 100637T, was determined to be adonixanthin diglucoside using spectral data. By contrast, carotenoid diglycosides are rare and are usually minor carotenoids in nature. The minor carotenoids in this bacterium included astaxanthin diglucoside, zeaxanthin diglucoside, canthaxanthin, echinenone, zeaxanthin, beta-cryptoxanthin, and beta-carotene.


Differential efficacy profile of aldosterone receptor antagonists, depending on the type of chronic heart failure, whether with reduced or preserved left ventricular ejection fraction-results of a meta-analysis of randomized controlled trials.
Because of renin-angiotensin-aldosterone system (RAAS) activation, the patients with chronic heart failure (CHF) manifest increased ventricular stress, with impaired left ventricular function, and a slowing down in systemic venous drainage. More importantly, a reduction of the patient's life expectancy has been proven in the case of RAAS overstimulation. For these reasons, huge efforts have been made to obtain molecules able to efficaciously antagonize the RAAS overstimulation, such as aldosterone receptor antagonists (ARAs). These drugs have been shown to improve clinical outcomes in patients with heart failure with reduced left ventricular ejection fraction (HFREF), but not in those with preserved left ventricular ejection fraction (HFpEF). In order to study this topic more deeply, we carried out a meta-analysis of selective and nonselective ARAs in HFREF and HFpEF. Only randomized controlled trials (RCTs) were incorporated in our meta-analysis. Studies were included if they satisfied the following criteria: experimental groups included patients with CHF treated with ARAs in addition to the conventional therapy; control groups included patients with CHF receiving conventional therapy without ARAs. Outcomes of interest were all-cause mortality, cardiovascular hospitalizations, hyperkalemia, or gynecomastia. Overall, 15 RCTs including a total of 15,671 patients were eligible for inclusion in the meta-analysis. ARA use in patients with heart failure was associated with a significant reduction in adverse outcomes. Indeed, a significant reduced odds of all-cause death among CHF patients treated with ARAs compared to controls was found [odds ratio (OR) =0.79; 95% CI: 0.73-0.87]. Subgroup analysis based on the heart failure (HF) type revealed a statistically significant benefit as regards all- cause death for patients with HFREF (OR =0.77; 95% confidence interval (CI): 0.69-0.84), but not for those with HFpEF (OR =0.91; 95% CI: 0.76-1.1). Furthermore reduced odds of CV hospitalizations was detected in the entire group of CHF patients under treatment with ARAs (OR =0.73; 95% CI: 0.61-0.89) as well as among HFREF patients treated with ARAs, compared to controls (OR =0.66; 95% CI: 0.51-0.85). Hyperkalemia was significantly more frequent with ARA use. Besides, ARA use was shown to be associated with the occurrence of gynecomastia. In particular, selective ARAs didn't induce significant amounts of gynecomastia compared to controls (OR =0.74; 95% CI: 0.43-1.27), while nonselective ARAs did (OR =8.22; 95% CI: 4.9-13.81). Based on this meta-analysis, ARAs should be systematically used in patients with HFREF, in whom these drugs proved to reduce all-cause mortality and hospitalizations from cardiac cause. Conversely, ARA usage in HFpEF patients is questionable since in this CHF setting no significant improvement in clinical endpoints has been demonstrated so far. New selective ARAs are devoid of the risk of gynecomastia, while are similar to nonselective ARAs with regard to the efficacy profile as well as to the risk of eliciting hyperkalemia.


Fundamental frequency from classical molecular dynamics.
We give a theoretical validation for calculating fundamental frequencies of a molecule from classical molecular dynamics (MD) when its anharmonicity is small enough to be treated by perturbation theory. We specifically give concrete answers to the following questions: (1) What is the appropriate initial condition of classical MD to calculate the fundamental frequency? (2) From that condition, how accurately can we extract fundamental frequencies of a molecule? (3) What is the benefit of using ab initio MD for frequency calculations? Our analytical approaches to those questions are classical and quantum normal form theories. As numerical examples we perform two types of MD to calculate fundamental frequencies of H2O with MP2/aug-cc-pVTZ: one is based on the quartic force field and the other one is direct ab initio MD, where the potential energies and the gradients are calculated on the fly. From those calculations, we show comparisons of the frequencies from MD with the post vibrational self-consistent field calculations, second- and fourth-order perturbation theories, and experiments. We also apply direct ab initio MD to frequency calculations of C-H vibrational modes of tetracene and naphthalene. We conclude that MD can give the same accuracy in fundamental frequency calculation as second-order perturbation theory but the computational cost is lower for large molecules.


[Comparative evaluation of serum HCV RNA by Roche Monitor Assay. Versions 1.0 and 2.0; as a predictive marker of subsequent response to IFN therapy].
Quantitative measurement of serum hepatitis C virus(HCV) RNA is important in predicting and monitoring interferon(IFN) therapy. We compared the sensitivity of HCV RNA measurement of different HCV genotypes between two available assays, Roche Monitor 1.0(v1.0) and Roche Monitor 2.0(v2.0). We also evaluated serum level of HCV RNA as the predictors of a long-term response to IFN therapy by distinguishing the complete responders(CR), partial responders(PR) and non-responders(NR) for IFN therapy. We quantified the serum HCV RNA levels in 151 patients and determined the genotypes; 96(64%) with genotype 1b(1b), 42(28%) with genotype 2a(2a), and 6(4%) was not identified. The relationship between the genotype and effects of IFN treatment was as follows: 23CR(1b:11, 2a:9), 15PR(1b:8, 2a:7), 20NR(1b:14, 2a:6). The RNA levels of 2a measured by v2.0 were significantly higher than those by v1.0(p < 0.05), although no significant difference was found in 1b between two assays. By using v2.0, when the cut-off level was set at 200 x 10(3) IU/ml before IFN therapy, CR was discriminated from PR, NR with a predicting efficiency of 88%. HCV RNA levels before IFN therapy were significantly lower in patients who became HCV RNA negative within 2 weeks than in patients who did at 4 weeks or longer. These results suggest that v2.0 is more sensitive and accurate than v1.0 for the quantification of 2a. Using v2.0 assay, it was shown that low viral titre at pretreatment and loss of viraemia within 2 weeks after treatment might be important markers for a long-term response to IFN therapy, irrespective of viral genotype. The v2.0 assay was found to be more useful in predicting effectiveness of IFN therapy.


Chronic and acute effects of stress on energy balance: are there appropriate animal models?
Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight.


Klotho sensitizes human lung cancer cell line to cisplatin via PI3k/Akt pathway.
Klotho was first identified in 1997 and has been considered as an anti-aging gene. Emerging evidence demonstrates that klotho has a close relationship with cancers, including lung cancer, breast cancer, etc, by inhibiting the proliferation and promoting apoptosis of cancer cells. Cisplatin has been the most widely used drug in the first-line chemotherapy. However, the increase in cisplatin-resistant cancer cells has become a major obstacle in clinical management of cancers. In our study, we for the first time demonstrated that klotho could attenuate the resistance of lung cancer to cisplatin based chemotherapy and the apoptosis of the resistant cells with klotho overexpression was markedly increased. However, klotho knockdown cells showed enhanced resistance to chemotherapy. Further analysis showed that inhibition of PI3K/Akt pathway with specific inhibitor (LY294002) attenuated the promotive effects on cancer growth following interfering with klotho shRNA. Moreover, we demonstrated that klotho modulated the resistance to cisplatin in a xenograft nude mice model. These observations suggested that klotho could improve the resistance of lung cancer cells to chemotherapy and may serve as a potential target for the gene therapy of lung cancers resistant to cisplatin based chemotherapy.


Increasing HDL cholesterol with extended-release nicotinic acid: from promise to practice.
The inverse relation between high-density lipoprotein cholesterol (HDL-C) and cardiovascular (CV) disease underscores the need for clinical evaluation of the effect of HDL-C increasing drugs on the prevalence of CV disease. We review the efficacy of Niaspan on serum lipids and the occurrence of side effects either alone or in combination with statins, in randomised controlled trials (RCT) and comparative cohort trials (CCT). In four RCTs, low-density lipoprotein cholesterol (LDL-C), triglycerides (TG) and lipoprotein(a) (Lp(a)) were decreased by 13, 26, and 17%, respectively, whereas HDL-C increased by 18%. In four CCTs a combination of Niaspan and statins showed an additional 22% reduction in LDL-C, 8% in TG and 6% in Lp(a) levels, compared with Niaspan monotherapy. Statin therapy had a minor additional effect of 1% on a total of 25% HDL-C increase during Niaspan treatment. Flushes occurred in 69% of the patients without any additional toxicity during combination therapy. Niaspan effectively raises HDL-C with concomitant beneficial effects on TG and LDL-C. Niaspan can be combined safely with statins and is also effective in patients with combined dyslipidaemia and type 2 diabetes mellitus. Trials on CV endpoints evaluating the effect of statins with Niaspan are urgently needed to settle whether this combination can confirm the high expectations for cardiovascular outcome.


Age-related changes of genital systems in the female Crj:CD (SD) IGS rats during sexual maturation.
The age-related changes of vaginal opening, body weight, the weights of the uterus and ovary, together with histological examination, serum 17beta-estradiol (E2) and progesterone levels were examined in intact female Crj:CD (SD) IGS rats between 21 and 36 days of age to understand the basic biological profile of changes of the female genital system during sexual maturation in the rat for female pubertal assays. With the beginning of the elevation of serum E2 level from 28 days of age, all parameters except body weight started to show drastic change until 31 days of age. The highest incidence of vaginal opening was recorded at 34 days of age. On macroscopic examinations, a number of rats showed uterine imbibition but vaginal opening. Immediately after the confirmation of the vaginal opening, the genital systems of three rats were observed microscopically. Both ovaries already had multiple corpora lutea, and degeneration of endometrial epithelial cells was observed. In conclusion, we obtained essential data on genital tract development of female Crj:CD (SD) IGS rats for in vivo screening assays that will contribute to detect potential endocrine active chemicals. In addition, it is assumed that the first ovulation precedes or occurs simultaneously with vaginal opening.


Three dimensional modeling of biologically relevant fluid shear stress in human renal tubule cells mimics in vivo transcriptional profiles.
The kidney proximal tubule is the primary site for solute reabsorption, secretion and where kidney diseases can originate, including drug-induced toxicity. Two-dimensional cell culture systems of the human proximal tubule cells (hPTCs) are often used to study these processes. However, these systems fail to model the interplay between filtrate flow, fluid shear stress (FSS), and functionality essential for understanding renal diseases and drug toxicity. The impact of FSS exposure on gene expression and effects of FSS at differing rates on gene expression in hPTCs has not been thoroughly investigated. Here, we performed RNA-sequencing of human RPTEC/TERT1 cells in a microfluidic chip-based 3D model to determine transcriptomic changes. We measured transcriptional changes following treatment of cells in this device at three different fluidic shear stress. We observed that FSS changes the expression of PTC-specific genes and impacted genes previously associated with renal diseases in genome-wide association studies (GWAS). At a physiological FSS level, we observed cell morphology, enhanced polarization, presence of cilia, and transport functions using albumin reabsorption via endocytosis and efflux transport. Here, we present a dynamic view of hPTCs response to FSS with increasing fluidic shear stress conditions and provide insight into hPTCs cellular function under biologically relevant conditions.


AMPK: Therapeutic Target for Diabetes and Cancer Prevention.
AMP-activated protein kinase (AMPK) is a protein kinase that maintains homeostasis in cells and organs. As a master regulator of metabolism, AMPK coordinates many metabolic reactions. AMPK is a key factor in diabetes and metabolic syndrome associated with dysregulation of the metabolic status. Recently, AMPK has also attracted attention as a tumor suppressor. The aim of this article is to discuss about the role of AMPK in diabetes as well as cancer and to evaluate its effectiveness in treatment and prevention of these diseases. We reviewed studies of signaling mechanism involving AMPK and research on the role of AMPK in human disease including diabetes and cancer. In particular, we focused our attention on clinical trials about cancer treatment and prevention targeting AMPK. Many experimental studies reported the relation of AMPK and various metabolic reactions, mainly regulating energy homeostasis. Recent studies showed effect of AMPK on arrest of cell cycle as well as suppression of inflammation, which are important factors for carcinogenesis. Although some clinical studies investigated cancer treatment and prevention targeting AMPK, the effective yields in clinical trial have been limited. AMPK activation as represented by metformin showed to improve disorders associated with diabetes and metabolic syndrome and became a well-established treatment strategy for these diseases. The increasing evidence suggests that AMPK is a promising target in the treatment and prevention of cancer. Further investigation including long-term clinical trials with large sample size is needed.


Subunit II of yeast QH2:cytochrome-c oxidoreductase. Nucleotide sequence of the gene and features of the protein.
The nucleotide sequence of a 2.5 X 10(3)-base segment of yeast nuclear DNA, containing the structural gene for the 40-kDa subunit II of the ubiquinol:cytochrome-c oxidoreductase, has been determined. The region contains only one single reading frame of length sufficient to encode a protein of the size of subunit II. The mature protein is predicted to have a length of 352 amino acids, with a molecular mass of 38714 Da. It is predominantly hydrophilic, with an overall polarity of 45%. Comparison of the sequence of the reading frame with that derived from direct sequence analysis of the N terminus of the mature 40-kDa protein shows that subunit II is synthesized as a longer precursor and shows that the extension is N-terminal. The presequence is 16 amino acids long and it contains a number of positively charged residues and lacks acidic ones. It is also rich in neutral, polar amino acids. S1 nuclease protection analysis of DNA X RNA hybrids identifies two major and one minor transcript of the gene, whose 5' termini map approximately 55, 65 and 75 nucleotides upstream of the initiation codon. Sequences 5' of these termini lack obvious homology to the regulatory sequences of other imported mitochondrial proteins, whose synthesis is controlled by oxygen and by catabolite repression. A mutant lacking a functional subunit II gene has been constructed by a one-step gene-disruption procedure. This mutant grows only slowly on glycerol and still displays a low level of QH2: cytochrome-c oxidoreductase activity (approx. 5% of that of wild type). The implications of this finding for the possible role of subunit II in the complex are discussed.


Ultrastructure Variability of the Exosporium Layer of Clostridium difficile Spores from Sporulating Cultures and Biofilms.
The anaerobic sporeformer Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea in developed and developing countries. The metabolically dormant spore form is considered the morphotype responsible for transmission, infection, and persistence, and the outermost exosporium layer is likely to play a major role in spore-host interactions during recurrent infections, contributing to the persistence of the spore in the host. A recent study (M. Pizarro-Guajardo, P. Calderón-Romero, P. Castro-Córdova, P. Mora-Uribe, and D. Paredes-Sabja, Appl Environ Microbiol 82:2202-2209, 2016, http://dx.doi.org/10.1128/AEM.03410-15) demonstrated by transmission electron microscopy the presence of two ultrastructural morphotypes of the exosporium layer in spores formed from the same sporulating culture. However, whether these distinct morphotypes appeared due to purification techniques and whether they appeared during biofilm development remain unclear. In this communication, we demonstrate through transmission electron microscopy that these two exosporium morphotypes are formed under sporulation conditions and are also present in spores formed during biofilm development. In summary, this work provides definitive evidence that in a population of sporulating cells, spores with a thick outermost exosporium layer and spores with a thin outermost exosporium layer are formed. Clostridium difficile spores are recognized as the morphotype of persistence and transmission of C. difficile infections. Spores of C. difficile are intrinsically resistant to all known antibiotic therapies. Development of spore-based removal strategies requires a detailed knowledge of the spore surface for proper antigen selection. In this context, in this work we provide definitive evidence that two types of spores, those with a thick outermost exosporium layer and those with a thin outermost exosporium layer, are formed in the same C. difficile sporulating culture or during biofilm development.


Examining the correlates of psychological aggression among a community sample of couples.
In this study, the authors examined the correlates of psychological aggression victimization and perpetration among a community sample of 145 heterosexual couples. For both women and men, psychological aggression victimization was associated with greater psychological distress, anxiety, and physical health symptoms beyond the effects of physical aggression. Psychological aggression victimization was also uniquely associated with higher levels of depression for women. Trait anger and poor relationship adjustment were the strongest correlates of psychological aggression perpetration across genders. Childhood father-to-child and father-to-mother aggressions were associated with psychological aggression perpetration for men only, suggesting possible distinct etiologies across genders. These data highlight the importance of the further development of models for psychological aggression in both women and men.


[Administration Order of FEC-DOC in Breast Cancer Adjuvant Chemotherapy Has an Effect on Toxicity].
Sequential administration of anthracycline - and taxane-based regimens has been established as standard adjuvant chemotherapy for breast cancer. In our hospital, FEC(5-FU/EPI/CPA) followed by docetaxel therapy has been used for this indication. Recently, we changed the sequence of FEC and docetaxel to reduce skin toxicities during the docetaxel phase. Since the effect of the administration order on efficacy and toxicity is not clear, we retrospectively compared the toxicities and relative dose intensity (RDI) of the administration orders. From January to December of 2012, 46 patients received FEC followed by docetaxel (AT group), while 42 patients underwent docetaxel followed by FEC during the same period in 2013(TA group). The incidence of severe hematological and major non-hematological toxicities was similar in the two groups. There was no significant difference in RDI between groups. However, grade 2 or higher hand-foot syndrome(HFS)during the docetaxel phase, which can be a reason for dose reduction or treatment termination, was more frequently observed in the AT group than in the TA group(54% vs 33%, p<0.05). Our data shows that the risk of HFS was reduced when the taxane was administered first. Interestingly, HFS significantly increased in the winter, regardless of the administration order(p<0.01).


Parental provisioning, nestling departure decisions and prefledging mass recession in Cassin's auklets.
We investigated how parental provisioning and nestling departure behaviour interact to produce prefledging mass recession in Cassin's auklets, Ptychoramphus aleuticus. Under our hypothesis, auklet parents are reluctant provisioners and should be increasingly likely to terminate or reduce provisioning of their single nestling as it matures. For the nestling, remaining in the nest presents a risk of losing mass (if the parent does not provision) but also a possibility of additional provisioning. As the nestling matures and becomes increasingly capable of independence, the benefits of remaining in the nest decrease and nestlings should be increasingly likely to fledge. Nestlings also should be more likely to fledge when the expectation of additional provisioning is low. Data on parental provisioning (based on growth increments) and nestling departure were consistent with our hypothesis. Older and heavier nestlings had smaller growth increments than younger and lighter nestlings, suggesting that parents were reluctant to provision old and heavy nestlings. Older and heavier nestlings also were increasingly likely to fledge. We hypothesized that nestlings might use the intensity of mass loss to gauge parental reluctance to provision, and accordingly, nestlings were increasingly likely to fledge after experiencing a greater amount of mass loss. Copyright 1999 The Association for the Study of Animal Behaviour.


Meniscal Ramp Lesions and Root Tears: A Review of the Current Literature.
The importance of the menisci in providing joint stability and their role in load transmission within the knee are well understood. A growing body of literature has emerged on 2 distinct injury patterns to these crucial anatomic structures, ramp lesions and root tears. Ramp lesions may be characterized as tears at the posterior meniscocapsular junction, while root tears involve bony or soft tissue avulsion of the meniscal insertions at the anterior or posterior intercondylar regions. In this 2-part review, we present an overview of the current available literature on ramp lesions and meniscal root tears, summarizing the unique anatomic considerations, etiology, biomechanics, management decisions, clinical outcomes pertinent to these very distinct injuries.


Effect of excess food nutrient on producer-grazer model under stoichiometric and toxicological constraints.
Accurately assessing the risks of contaminants requires more than an understanding of the effects of contaminants on individual organism, but requires further understanding of complex ecological interactions, elemental cycling, and the interactive effects of natural stressors, such as resource limitations, and contaminant stressors. There is increasing evidence that organisms experience interactive effects of contaminant stressors and food conditions, such as resource stoichiometry, availability and excess of nutrient. Here, we develop and analyze the first producer-grazer population model that incorporates the effects of excess nutrients, as well as nutrient limitations on grazer exposed to toxicants. We use analytical, numerical and bifurcation analysis to reduce and exploremodel parameterized for an aquatic system of algae and zooplankton exposed to methylmercury under varying phosphorus conditions. Under certain environmental conditions, our models predict higher toxicity than previous models that neglect the consequences excess nutrient conditions can have on grazer populations.


Sequential action of JNK genes establishes the embryonic left-right axis.
The establishment of the left-right axis is crucial for the placement, morphogenesis and function of internal organs. Left-right specification is proposed to be dependent on cilia-driven fluid flow in the embryonic node. Planar cell polarity (PCP) signalling is crucial for patterning of nodal cilia, yet downstream effectors driving this process remain elusive. We have examined the role of the JNK gene family, a proposed downstream component of PCP signalling, in the development and function of the zebrafish node. We show jnk1 and jnk2 specify length of nodal cilia, generate flow in the node and restrict southpaw to the left lateral plate mesoderm. Moreover, loss of asymmetric southpaw expression does not result in disturbances to asymmetric organ placement, supporting a model in which nodal flow may be dispensable for organ laterality. Later, jnk3 is required to restrict pitx2c expression to the left side and permit correct endodermal organ placement. This work uncovers multiple roles for the JNK gene family acting at different points during left-right axis establishment. It highlights extensive redundancy and indicates JNK activity is distinct from the PCP signalling pathway.


The Optimal Cut-Points for Weight and Non-Weight Quantitative Ultrasound of the Calcaneus to Screen Osteoporosis in Postmenopausal Women.
To determine the optimal cut-off point of quantitative ultrasound (QUS) of the calcaneus, and optimized position for QUS of the calcaneus, between non-weight (sitting) and weight (standing) position, to screen osteoporosis in postmenopausal women. A cross-sectional study of postmenopausal women aged 65 years or older who came for bone mineral density (BMD) evaluation at the menopause unit, Department of Obstetrics and Gynecology, Ramathibodi Hospital between April 2013 and October 2015. Bone tissue was measured by using QUS of the calcaneus in the standard sitting (non-weight position) and in standing (weight position) consecutively of non-dominant calcaneus to compared with BMD that measured by dual energy X-ray absorptiometry (DXA) of lumbar spine and hip within the same visit of QUS measurement. The area under Receiver Operating Characteristic (ROC) curve and optimal of diagnostic properties to diagnosed osteoporosis were analyzed by sensitivity, specificity, positive and negative likelihood ratio (LR +/-). One hundred sixty one postmenopausal women were enrolled, median age was 70 (65, 94) years old, median time since menopause was 22 (10, 55) years. Ten point five percent of subjects had history of osteoporotic fracture at wrist. The prevalence of osteoporosis was 23% at lumbar spine and 30% at femoral neck respectively. Area under ROC curve for diagnosed osteoporosis was 0.73 in the non-weight QUS of the calcaneus and correlated well with using DXA at neck of femur (gold standard). However the weight or standing position did not improve the diagnostic power of QUS of the calcaneus. The optimal cut-point value of QUS of the calcaneus to screen osteoporosis at stiffness index was determined by T-score of ≤ -2.6 with 81.42%, 45.83%, 1.5, and 0.41 for the sensitivity, specificity, LR +/- respectively. QUS of the calcaneus was acceptable and promising to be alternative tool for screening osteoporosis in postmenopausal woman age older than 65 years by the optimal cut-point of stiffness index T-score at ≤ -2.6 measured in standard position or non-weight method.


Standardized analyses of correction of astigmatism with the visian toric phakic implantable collamer lens.
To demonstrate the methodology described by the American National Standards Institute (ANSI) Standard Subcommittee on Astigmatism Analysis reporting a standardized method of presenting astigmatism data by laser systems that reshape the cornea also applies to toric phakic intraocular lens (IOL) data. The U.S. Food and Drug Administration trial of the Visian Toric Implantable Collamer Lens comprised 210 eyes of 124 study patients. The mean preoperative manifest refraction spherical equivalent for the study cohort was -9.36 +/- 2.66 diopters (D) (range: -19.50 to -2.38 D). The mean preoperative manifest refractive cylinder was 1.94 +/- 0.84 D (range: 1.00 to 4.00 D). Data were arrayed using the 11 tables and 4 figures suggested in the Subcommittee paper. Interpretation of the data from a toric phakic IOL study was similar to that of laser refractive procedures. The addition of a table of manifest refractive cylinder (in the spectacle plane) over time, which provides a direct clinical measure of clinical efficacy, is suggested. Mean postoperative manifest refractive cylinder was 0.51 +/- 0.48 D (range: 0 to 3.00 D) with 65.6% of eyes having < or = 0.50 D of refractive cylinder at 12 months. A table of observed stability of the toric phakic IOL orientation within the eye obtained by slit-lamp examination also is recommended, which is a useful table not applicable in laser refractive procedures. The data presented demonstrate that the methodology developed by the ANSI Standard Subcommittee on Astigmatism Analysis, with some minor additions, accurately characterizes the efficacy of toric phakic IOLs in treating astigmatism.


[Extensive interactions between eating and weight disorder, major depression, pain, and sarcoidosis - case 5/2012].
We report on a 41-year-old female patient suffering from obesity, binge eating more than twice a week with loss of control, eating rapidly and feeling guilty after eating, dyspnoea and chronic pain in the whole body, especially in her arms, legs and in both ankles. Furthermore, subdued mood, loss of interest and pleasure, fatigue and impaired concentration could be recognized. In the past, weight increase had been observed when corticosteroids were given against exacerbations of sarcoidosis. In the case of our patient, the beginning of sarcoidosis and increase of weight and pain correlated with augmentation of depression and psychosocial stress. Dysfunctional behavioral features and multiple interactions between diseases could be observed. We diagnosed obesity, binge eating disorder, major depression, chronic pain disease with somatic and psychical components and sarcoidosis. The patient was treated in a multimodal therapy program including psychotherapy, pharmacotherapy and psychopharmacotherapy, nutritionist advice and therapeutic exercise. A weight loss of 7.9 kg (5.9 %), well-balanced diet, reduction of binge eating and of pain intensity, mood stabilization as well as perception and expression of emotions and coping strategies in chronic diseases were achieved. Interdisciplinary treatment of patients suffering from psychosomatic, somatic and mental diseases is crucial for a good outcome.


Assessments of arterial stiffness and endothelial function using pulse wave analysis.
Conventionally, the assessments of endothelial function and arterial stiffness require different sets of equipment, making the inclusion of both tests impractical for clinical and epidemiological studies. Pulse wave analysis (PWA) provides useful information regarding the mechanical properties of the arterial tree and can also be used to assess endothelial function. PWA is a simple, valid, reliable, and inexpensive technique, offering great clinical and epidemiological potential. The current paper will outline how to measure arterial stiffness and endothelial function using this technique and include discussion of validity and reliability.


Three-dimensional ab initio potential-energy surface and rovibrational spectra of the H2-Kr complex.
We report a three-dimensional ab initio potential-energy surface for the H2-Kr complex calculated using a supermolecular method. The electronic calculations were performed at the coupled-cluster singles and doubles level with noniterative inclusion of connected triples levels with a large basis set including midbond functions and the full counterpoise correction for the basis-set superposition error. The intermolecular potential energy between the H2 molecule and the Kr atom were evaluated at five potential-optimized discrete variable representation (DVR) grid points generated from the potential-energy curve of H2. The potential for other bond lengths of H2 could be deduced using polynomial interpolations. The complex is found to have a linear preferred structure with a rather flat energy barrier. The three-dimensional DVR method and the Lanczos propagation algorithm were employed to calculate the rovibrational states without separating the inter- and intramolecular nuclear motions. In addition, the rovibrational spectra from the H2 fundamental vibrational band were calculated. The calculated shift for the band origin is -1.50 cm-1, which is in good agreement with the experimental value of -1.706 cm-1, and the calculated transition frequencies in Q1(0) and S1(0) bands are within 3% of the observed values.


Patients' perceptions of nasopharyngeal aspiration in the emergency department of a teaching hospital in Hong Kong.
Nasopharyngeal aspiration (NPA) is the preferred method for collecting specimens for viral culture in patients with respiratory tract infection. As virus identification may influence admission and treatment decisions, it is important to perform NPA in the emergency department. The test may be uncomfortable and poorly tolerated. This prospective study investigated patients' perceptions of NPA. Patients in the emergency department with upper respiratory tract infection undergoing NPA between 9 March 2005 and 12 August 2005 were included. 86 patients (mean (SD) age 47 (23) years; 49 women) were recruited. 22 (26%) patients complained that NPA was very uncomfortable, 59 (69%) reported that it was mildly uncomfortable and 5 (6%) patients reported no discomfort. On a 10-point scale, the median discomfort score was 4. 29 (34%) patients stated that NPA was more uncomfortable than blood taking, 19 (22%) patients felt that both were similar and 38 (44%) patients felt that NPA was less uncomfortable (p value not significant). NPA performed in the emergency department is well tolerated and should be considered in emergency departments when results may influence patient management.


Dishevelled Segment Polarity Protein 3: A Novel Prognosis-related Marker in Pan-driver-gene-negative Lung Adenocarcinoma.
Purpose: In this study, we aimed to investigate the potential prognostic molecular marker in patients with "pan-driver-gene-negative" lung adenocarcinoma (PDGN-LUAD). LUAD patients who were negative for mutations in EGFR, KRAS, BRAF, HER2, MET, ALK, RET and ROS1 were identified as PDGN-LUAD. Methods: In the screening phase, we profiled the mRNA expression levels in 52 paired PDGN-LUAD tumor tissues and adjacent normal tissues using a genome-wide microarray, and the results revealed that the expression level of dishevelled segment polarity protein 3 (DVL3) was higher in PDGN-LUAD tumor tissues than in normal lung tissues. Then, we enrolled 626 PDGN-LUAD patients from three independent hospital centers and divided them into a training cohort, an internal validation cohort and two external validation cohorts. In the training cohort, tissue microarrays (TMAs) were used to confirm the protein expression level of DVL3. Statistical methods were applied to explore the prognostic role of DVL3. Results: The results indicated that the level of DVL3 could be used to classify patients with PDGN-LUAD in the training cohort into a high-risk group (high expression level of DVL3) and a low-risk group (low expression level of DVL3). In the training cohort, high-risk patients had shorter overall survival (OS) times (hazard ratio [HR] 2.27; 95% CI, 1.57-2.97; p<0.001) than low-risk patients. In the validation phase, the performance of DVL3 as a prognostic marker was successfully validated in the internal and external cohorts. Conclusions: In conclusion, DVL3 is an important prognostic indicator for PDGN-LUAD and may provide new insights into the treatment of PDGN-LUAD.


Polyomavirus microRNAs circulating in biological fluids during viral persistence.
Increasing evidence suggests that microRNA-mediated gene silencing, detected during exosome intercellular communication between cells, may be exploited by persistent human viruses. Recently, it has been reported that human polyomaviruses encode microRNAs that downregulate large T expression and target host factors, helping the virus to escape immune elimination. Consequently, viral microRNAs and their genetic variability may have roles in the induction of polyomavirus reactivation, the success of persistence or replication and the development of diseases. In vitro experiments have detected polyomavirus JC (JCPyV) microRNAs in exosomes obtained from cell supernatants after viral infection and showed that they can be carried into uninfected cells. JCPyV and BKPyV microRNAs have been sought in clinical samples obtained from patients with or at risk of severe polyomavirus-associated diseases and from healthy subjects. Variable expressions of JCPyV and BKPyV microRNAs circulating in blood, urine, and cerebrospinal fluid samples were found in patients who were polyomavirus DNA positive and were also observed in negative subjects. Differences in the relationship between the JCPyV and BKPyV microRNA expressions and viral DNA load have been observed. All the data point towards a potential role of polyomavirus exosome microRNAs in viral persistence and suggest that further work is warranted to define their role in viral reactivation and to identify potential new antiviral strategies targeting these viruses.


Direct Growth of van der Waals Tin Diiodide Monolayers.
Two-dimensional (2D) van der Waals (vdW) materials have garnered considerable attention for their unique properties and potentials in a wide range of fields, which include nano-electronics/optoelectronics, solar energy, and catalysis. Meanwhile, challenges in the approaches toward achieving high-performance devices still inspire the search for new 2D vdW materials with precious properties. In this study, via molecular beam epitaxy, for the first time, the vdW SnI2 monolayer is successfully fabricated with a new structure. Scanning tunneling microscopy/spectroscopy characterization, as corroborated by the density functional theory calculation, indicates that this SnI2 monolayer exhibits a band gap of ≈2.9 eV in the visible purple range, and an indirect- to direct-band gap transition occurs in the SnI2 bilayer. This study provides a new semiconducting 2D material that is promising as a building block in future electronics/optoelectronics.


Selection of High-Yielding and Stable Genotypes of Barley for the Cold Climate in Iran.
The interaction between genotypes and environments plays an important role in selecting superior genotypes for target locations. The main objectives of the present study were to analyze the effect of the genotype-by-environment interaction (GEI) and identify superior, newly developed, and promising barley genotypes for cold regions in Iran. For these purposes, a set of genotypes obtained from breeding programs for cold climates in Iran, along with two reference genotypes, were investigated at eight research stations (Tabriz, Ardabil, Arak, Miandoab, Mashhad, Jolge Rokh, Karaj, and Hamadan) during two consecutive growing seasons (2019-2020 and 2020-2021). The results of the freezing test (LT50) showed that most of the tested genotypes had significant cold tolerance at the seedling stage. Based on the additive main effect and multiplicative interaction (AMMI) analysis, environment (E) and GEI effects explained 49.44% and 16.55% of the total variation in grain yield, respectively. Using AMMI1 and AMMI2 models, G2 and G20 were found to be superior genotypes in terms of grain yield and stability. Moreover, AMMI-based stability parameters considered the G20 genotype to be the ideal genotype. A two-plot analysis of the genotype-by-environment interaction (GGE) biplot showed that the 16 experimental environments were grouped into 2 mega-environments. Of the test environments, ARK1 and KAJ2 had the highest discriminating power and representativeness ability, and these were identified as ideal environments for testing advanced genotypes for yield and stability performance during early barley breeding practices in cold areas in Iran. In conclusion, both AMMI and GGE biplot models identified several superior genotypes, among which G20, with a high average yield relative to the overall average yield and the lowest IPC1 score, was found to have high yield stability and is recommended for inclusion in breeding programs for cold climates in Iran.


Proximal Femur Volumetric Bone Mineral Density and Mortality: 13 Years of Follow-Up of the AGES-Reykjavik Study.
Bone mineral density (BMD) has been linked to mortality, but little is known about the independent contribution of each endosteal bone compartment and also the rate of bone loss to risk of mortality. We examined the relationships between (1) baseline trabecular and cortical volumetric BMD (vBMD) at the proximal femur, and (2) the rate of trabecular and cortical bone loss and all-cause mortality in older adults from the AGES-Reykjavik study. The analysis of trabecular and cortical vBMD and mortality was based on the baseline cohort of 4654 participants (aged ≥66 years) with a median follow-up of 9.4 years; the association between rate of bone loss and mortality was based on 2653 participants with bone loss data (median follow-up of 5.6 years). Analyses employed multivariable Cox-proportional models to estimate hazard ratios (HRs) with time-varying fracture status; trabecular and cortical variables were included together in all models. Adjusted for important confounders, Cox models showed that participants in the lowest quartile of trabecular vBMD had an increased risk of mortality compared to participants in other quartiles (HR = 1.12; 95% confidence interval (CI), 1.01 to 1.25); baseline cortical vBMD was not related to mortality (HR = 1.08; 95% CI, 0.97 to 1.20). After adjustment for time-dependent fracture status, results were attenuated and not statistically significant. A faster loss (quartile 1 versus quartiles 2-4) in both trabecular and cortical bone was associated with higher mortality risk (HR = 1.37 and 1.33, respectively); these associations were independent of major potential confounders including time-dependent incident fractures (HR = 1.32 and 1.34, respectively). Overall, data suggest that faster bone losses over time in both the trabecular and cortical bone compartments are associated with mortality risk and that measurements of change in bone health may be more informative than single-point measurements in explaining mortality differences in older adults. © 2017 American Society for Bone and Mineral Research.


Solid pseudopapillary neoplasm-diagnostic approach and post-surgical follow up: Three case reports and review of literature.
Solid pseudopapillary neoplasm (SPN) is a rare tumor that was first described by Frantz in 1959. Although this tumor is benign, some may have malignant potential that can be predicted based on demographics, imaging characteristics, and pathologic evaluation. This case series presents 3 SPN cases with discussion on gender differences, preoperative predictors of malignancy, and a suggested algorithm for diagnostic approach as well as post-surgical follow up. Three adult patients in a tertiary hospital found to have SPN, one elderly male and two young females. Each of the cases presented with abdominal pain and were discovered incidentally. Two cases underwent endoscopic ultrasound with fine needle aspiration and biopsy to assess tumor markers and immuno-histochemical staining (which were consistent with SPN before undergoing surgery), and one case underwent surgery directly after imaging. The average tumor size was 5 cm. Diagnosis was confirmed by histology. Two patients had post-surgical complications requiring intervention. Demographic and imaging characteristics can be sufficient to establish diagnosis for SPN, while malignant cases require pre-operative evaluation with endoscopic ultrasound fine needle aspiration/fine needle biopsy.


Characterization of cell-cell junction changes associated with the formation of a strong endothelial barrier.
A principal function of endothelial cells is the formation of a barrier between the blood and tissues. This barrier arises from the physical connections at cell-cell junctions, which includes cytoskeletal tight junction and adherens junction proteins. Methods that alter barrier function must therefore affect these cell-cell connections. The blood brain barrier (BBB) represents perhaps the most selective endothelial barrier, which arises from endothelial cell interactions with astrocytes and pericytes. Even in non-central nervous system (CNS) endothelial cells, barrier properties can be enhanced, mimicking the BBB, through induction of intercellular junctions, by either direct co-culture with astrocytes, supplementation with astrocyte conditioned medium (ACM) and/or pharmacologic enhancement of cAMP. To understand how cell-cell junctions change during endothelial barrier enhancement, we examined the effects of ACM and/or cAMP donors added to standard media on human umbilical vein endothelial cells (HUVEC). HUVEC cultured with cAMP-elevating agents had the most enhanced barrier function as measured by Electric Cell-substrate Impedance Sensing (ECIS®), a real-time, label-free, impedance based method of studying cell barrier properties. However, subtle differences in actin and cell-cell junction proteins were seen across all four culture conditions. cAMP-elevating agents also triggered the redistribution of ZO-1 and VE-cadherin to cell-cell junctions, and intensified the actin microfilament network at the cell cortex. Using a VE-cadherin FRET-force sensor, we observed a decrease in VE-cadherin force in HUVEC cultured with ACM with cAMP donors. Our data indicate cAMP elevation induces both junctional strengthening and reduced VE-cadherin forces. Additionally, treatment with an inhibitor of formin, which reduced actin stress fibers, enhanced barrier function. These data suggest that barrier function is modulated both through the trafficking of proteins to cell-cell junctions, and through the modulation and a relaxation of mechanical force through adherens junctions as intercellular junctional complexes become established.


Antimicrobial Secondary Metabolites from the Mangrove Plants of Asia and the Pacific.
Microbes such as the White Spot Syndrome Virus account for severe losses in the shrimp farming industry globally. This review examines the literature on the mangrove plants of Asia and the Pacific with antibacterial, antifungal, or antiviral activities. All of the available data published on this subject were collected from Google Scholar, PubMed, Science Direct, Web of Science, ChemSpider, PubChem, and a library search from 1968 to 2022. Out of about 286 plant species, 119 exhibited antimicrobial effects, and a total of 114 antimicrobial natural products have been identified including 12 with MIC values below 1 µg/mL. Most of these plants are medicinal. The mangrove plants of Asia and the Pacific yield secondary metabolites with the potential to mitigate infectious diseases in shrimp aquaculture.


Tuberculosis knowledge among injecting drug users visiting syringe exchange programme in Tallinn, Estonia.
The purpose of the current study was to describe tuberculosis (TB) knowledge, beliefs, and experience with TB services among injecting drug users. Participants for this anonymous, cross-sectional study were recruited from a community based syringe exchange programme in Tallinn, Estonia. A structured questionnaire was completed and included information on socio-demographics, health history, drug use, and knowledge about TB and HIV. The study included 407 people (79% male, mean age 27.9 years, mean injection drug use 9.4 years). 32.9% of participants reported HIV infection and 1.7% lifetime history of TB. 26.4% participants (n=106) reported symptoms suggestive of TB. 93% of participants recognized correctly that TB is air-borne infection and 91% that HIV is a risk factor for TB. Only 40% of the participants knew that TB diagnostics and treatment in Estonia are free of charge for everybody and 58% reported they knew where to get health care services in case they suspected that they had TB. TB transmission and treatment adherence knowledge was better among those in contact with either health care or harm reduction services, e.g the community based syringe exchange programme. Similar to HIV services, TB prevention and education should be integrated into harm reduction and drug treatment programmes to facilitate early diagnosis and treatment of TB among injecting drug users.


[Shortening the stimulus T time: indicator for physical activity in patients with demand modulated cardiac pacemakers].
Activity-modulated pacemakers detect body vibrations and increase their pacing rate. As the body vibrations are not always related to physical activity, we studied in 20 patients with the activity-modulated pacemaker Legend (Medtronic) whether a second physiological signal, the paced QT duration, can help to verify exercise. At rest, pacing rate was programmed from 60 ppm to 130 ppm in steps of 10 ppm which shortened the QT duration from 467 +/- 32 ms (60 ppm) to 391 +/- 24 ms (130 ppm). During treadmill exercise, pacing rate increased from 62 +/- 1 ppm to 98 +/- 9 ppm and the QT duration decreased from 450 +/- 25 ms to 372 +/- 27 ms. Compared to rest, the exercise-induced QT shortening was significantly shorter for pacing rates > or = 70 ppm. To simulate artificial sensor activation, an electrical razor was put onto the pulse generator. Pacing rate increased to 81 +/- 7 ppm, but the QT duration shortening was similar to the measurement at rest with 80 ppm. In conclusion, the paced QT duration is able to confirm whether body vibrations are related to physical exercise.


Postural sway, working years and BMI in healthy truck drivers: an observational study.
The following study analyses the influence of risk factors among the occupational group of truck drivers on postural control and body mass index (BMI). Observational study. One motorway station close to several highways in Germany. 180 truck drivers (177 male/3 female), aged 21-65 years old, took part in this study. Postural control was examined using a pressure plate. In order to examine the influence of body weight (BMI) and working years on postural control, subjects were divided into samples of five and three groups, respectively. Furthermore, it was evaluated whether the subjects suffered from back pain. For data analysis, the Kruskal-Wallis test was used as the data were not normally distributed. Once the p value of the Kruskal-Wallis test was p≤0.05, the Conover-Iman comparison and afterwards the Bonferroni-Holm correction were used. The significance level was set at α ≤0.05. Regarding the number of working years, a significant increase of frontal (p≤0.04) and sagittal (p≤0.001) sway were observed. The correlation of the five BMI groups with the number of working years demonstrates that an increase of the working years leads to an increase of BMI (p≤0.03). Furthermore, the majority of truck drivers participating in this study suffered from back pain (61.7%). BMI and musculoskeletal impairment are indicators of health risk factors. In this study, it is shown that an increasing number of working years and an increasing BMI lead to a decrease in frontal and sagittal postural sway. In addition, the number of working years correlates with body weight and back pain.


Characterization of two RNAs transcribed from the cis-regulatory region of the abd-A domain within the Drosophila bithorax complex.
The infra-abdominal (iab) regions of the biothorax complex are thought to cis-regulate expression of the abdominal-A (abd-A) and Abdominal-B (Abd-B) transcripts. These large cis-regulatory regions are also actively transcribed. Here we present a detailed analysis of the transcription products of the iab-4 region. During early embryogenesis a 6.8-kilobase (kb) RNA is transcribed and processed to yield 1.7- and 2.0-kb poly(A)+ RNAs. These RNAs are expressed from the time of cellular blastoderm formation to germ-band shortening and are localized in parasegments 8-14 (the posterior second through the anterior ninth abdominal segments). Sequence analysis of the two RNAs suggests that they may not be translated. We discuss some possible functions of the 1.7/2.0-kb iab RNAs and the significance of their similarity to the bithoraxoid (bxd) RNAs and other transcripts from the iab regions of the abd-A and Abd-B domains.


Comprehensive Transcriptome Analysis Reveals the Role of lncRNA in Fatty Acid Metabolism in the Longissimus Thoracis Muscle of Tibetan Sheep at Different Ages.
Long noncoding RNA (lncRNA) plays an important regulatory role in mammalian adipogenesis and lipid metabolism. However, their function in the longissimus thoracis (LT) muscle of fatty acid metabolism of Tibetan sheep remains undefined. In this study, fatty acid and fat content in LT muscle of Tibetan sheep were determined, and RNA sequencing was performed to reveal the temporal regularity of lncRNA expression and the effect of lncRNA-miRNA-mRNA ceRNA regulatory network on lipid metabolism of LT muscle in Tibetan sheep at four growth stages (4-month-old, 4 m; 1.5-year-old, 1.5 y; 3.5-year-old, 3.5 y; 6-year-old, 6 y). The results indicated that the intramuscular fat (IMF) content was highest at 1.5 y. Moreover, the monounsaturated fatty acid (MUFA) content in 1.5 y of Tibetan sheep is significantly higher than those of the other groups (P < 0.05), and it was also rich in a variety of polyunsaturated fatty acids (PUFA). A total of 360 differentially expressed lncRNAs (DE lncRNAs) were identified from contiguous period transcriptome comparative groups of 4 m vs. 1.5 y, 1.5 y vs. 3.5 y, 3.5 y vs. 6 y, and 4 m vs. 6 y, respectively. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis found that the target genes in lncRNA trans-mRNA were significantly related to the protein digestion, absorption, and fatty acid biosynthesis pathways (P < 0.05), which demonstrated that DE lncRNA trans-regulated the target genes, and further regulated the growth and development of the LT muscle and intramuscular fatty acid metabolism in Tibetan sheep. We further analyzed the role of the lncRNA-miRNA-mRNA regulatory network in the lipid metabolism of Tibetan sheep. Additionally, GPD2, LIPE (lipase E hormone-sensitive enzyme), TFDP2, CPT1A, ACACB, ADIPOQ, and other mRNA related to fatty acid and lipid metabolism and the corresponding lncRNA-miRNA regulatory pairs were identified. The enrichment analysis of mRNA in the regulatory network found that the AMPK signaling pathway was the most significantly enriched (P = 0.0000112361). Comprehensive transcriptome analysis found that the LIPE, ADIPOQ, ACACB, and CPT1A that were regulated by lncRNA might change the formation of energy metabolism in Tibetan sheep muscle through the AMPK signaling pathway, and oxidized muscle fibers are transformed into glycolytic muscle fibers, reduced IMF content, and the fatty acid profile also changed.


From the first to the second domain of gelsolin: a common path on the surface of actin?
We present the 2.6 A resolution crystal structure of a complex formed between G-actin and gelsolin fragment Met25-Gln160 (G1+). The structure differs from those of other gelsolin domain 1 (G1) complexes in that an additional six amino acid residues from the crucial linker region into gelsolin domain 2 (G2) are visible and are attached securely to the surface of actin. The linker segment extends away from G1 up the face of actin in a direction that infers G2 will bind along the same long-pitch helical strand as the actin bound to G1. This is consistent with a mechanism whereby G2 attaches gelsolin to the side of a filament and then directs G1 toward a position where it would disrupt actin-actin contacts. Alignment of the sequence of the structurally important residues within the G1-G2 linker with those of WH2 (WASp homology domain 2) domain protein family members (e.g. WASp (Wiscott-Aldridge syndrome protein) and thymosin beta4) suggests that the opposing activities of filament assembly and disassembly may exploit a common patch on the surface of actin.


[Glucagon-like peptide-1 (GLP-1) mimetics: a new treatment for Alzheimer's disease?].
The glucagon-like peptide-1 (GLP-1) mimetics are an established therapeutic option for patients with type 2 diabetes. However, the properties of the GLP-1 mimetics go beyond the strict metabolic control of the patients with diabetes. The neuroprotective effects of GLP-1 have been shown in recent studies opening new areas of research in neurodegenerative diseases such as Alzheimer's disease (AD), among others. AIM. Systematic review including experimental studies and human clinical trials demonstrating the neuroprotective properties of GLP-1 mimetics in AD. The experimental studies that have been conducted in rodent models of AD have demonstrated the neuroprotective properties of GLP-1 in the central nervous system reducing beta-amyloid plaques, the oxidative stress and the inflammatory brain response. Clinical trials in patients with cognitive impairment and AD testing the effects of GLP-1 analogs have recently started. The GLP-1 analogs have neuroprotective properties. Considering that type 2 diabetes is a risk factor for cognitive impairment and dementia, the benefits of GLP-1 mimetics on cognition must be considered. Likewise, the GLP-1 mimetics represent a promising treatment for neurodegenerative diseases such as AD.


Confidence response times: Challenging postdecisional models of confidence.
Even though the nature of confidence computations has been the topic of intense interest, little attention has been paid to what confidence response times (cRTs) reveal about the underlying confidence computations. Several previous studies found cRTs to be negatively correlated with confidence in the group as a whole and consequently hypothesized the existence of an intrinsic relationship of cRT with confidence for all subjects. This hypothesis was further used to support postdecisional models of confidence that predict that cRT and confidence should always be negatively correlated. Here we test the alternative hypothesis that cRT is driven by the frequency of confidence responses such that the most frequent confidence ratings are inherently made faster regardless of whether they are high or low. We examined cRTs in three large data sets from the Confidence Database and found that the lowest cRTs occurred for the most frequent confidence rating. In other words, subjects who gave high confidence ratings most frequently had negative confidence-cRT relationships, whereas subjects who gave low confidence ratings most frequently had positive confidence-cRT relationships. In addition, we found a strong across-subject correlation between response time and cRT, suggesting that response speed for both the decision and the confidence rating is influenced by a common factor. Our results show that cRT is not intrinsically linked to confidence and strongly challenge several postdecisional models of confidence.


Direct and metal-free arylsulfonylation of alkynes with sulfonylhydrazides for the construction of 3-sulfonated coumarins.
A novel and metal-free procedure has been developed for the construction of 3-sulfonated coumarins via the direct difunctionalization of alkynoates with sulfonylhydrazides. The present protocol, which simply utilizes TBAI as the catalyst and TBHP as the oxidant, provides a convenient and highly efficient approach to construct a series of sulfonated coumarins with high regioselectivity and good functional group tolerance.


Novel Analytics Framework for Universal Healthcare Insurance Database.
Medical insurance claims data is one of the most useful data sources that can offer a big-picture view of a nation-wide healthcare system. Form the viewpoint of medical policy planning, Japan's Ministry of Health, Labour and Welfare has been continuously collecting claims data. However, claims data in Japan has an ordered nested tuple format, and a method for describing the logic to analyze this form in a simple and clear manner has not been established yet. In the present work, we construct a novel analytics framework based on previous analyses that we conducted with medical researchers and design a UI that facilitates the construction of the processing logic in a simple and clear manner. By showing the execution result of typical analyses of claim data, we demonstrate the effectiveness of the developed tool.


Phenol abatement using persulfate activated by nZVI, H2O2 and NaOH and development of a kinetic model for alkaline activation.
Three persulfate (PS) activation methods (nanoparticles of zero-valent iron (nZVI), hydrogen peroxide and alkali) were compared using phenol as target pollutant. Firstly, four experiments were conducted at 25°C in a batch way using the same initial phenol and oxidant concentrations (10 mM and 420 mM, respectively), being the molar ratio activator/PS fixed to 0.005 with nZVI (mass ratio 0.0011 nZVI/PS), to 2 using hydrogen peroxide and to 2 and 4 with NaOH. Phenol and PS conversions and aromatic byproducts profiles during 168 h reaction time were measured and compared, as well as mineralization and ecotoxicity of the samples. It was found that both phenol and aromatic byproducts (catechol and hydroquinone) totally disappeared using PS activated by alkali before 24 h, while a significant amount of aromatic intermediates was obtained with nZVI and H2O2. Additional runs were carried out using shorter times (0-2 h) to discriminate the oxidation route and the kinetic model of phenol abatement by using PS activated by alkali. Different initial concentrations of phenol (5-15 mM), PS (210 and 420 mM) and molar ratio NaOH/PS (2 and 4) were employed. The kinetic model obtained predicts accurately the evolution of phenol, persulfate, hydroquinone and catechol.


A hot aldehyde-peroxide fixation method for electron microscopy of the free-living nematode Caenorhabditis elegans.
An improved method for the fixation of the third and fourth larval stages and adults of Caenorhabditis elegans has been developed. Worms are placed in a mixture of 1.5% paraformaldehyde and 1.0% glutaraldehyde at pH 7.0 and 70 C and the suspension promptly cooled in a water bath at 20 C for 1 hr. The fixed worms are then immersed in a mixture of 5% glutaraldehyde and hydrogen peroxide at 4 C for 1 hr, stained en bloc in uranyl acetate, and embedded in resin for electron microscopy. The procedure results in superior fixation, particularly of microfilaments and microtubules. The high temperature of the initial fixation straightens the worms and thus facilitates serial sectioning.


Menstrual cycle affects bladder pain sensation in subjects with interstitial cystitis.
Using psychophysical methods we compared the effect of the menstrual cycle on bladder sensation in subjects with the diagnosis of interstitial cystitis (IC) and in controls. Female participants with normal menstrual cycles, including 7 with IC and 8 healthy controls, were recruited into this study. They completed daily diaries related to bladder pain and other body pain, and tracked daily micturition frequency. In a subset formal psychophysical testing of thermal and ischemic pain was performed at 2 times of the menstrual cycle, corresponding to the luteal and follicular phases. Cystometrograms were performed at the same time. Subjects with IC had higher pain scores and frequency than controls throughout the entire menstrual cycle. Pain scores were highest in the perimenstrual period in subjects with IC and controls. Micturition frequency was highest in the perimenstrual period in subjects with IC. Cystometric evaluation of a first need to void and the evocation of bladder pain demonstrated that lower intravesical volume and pressure were necessary to evoke bladder pain during the follicular period than during the luteal period in subjects with IC, although there was no effect on the first need to void. These findings are consistent with clinical lore that suggests a perimenstrual flare in pain in subjects with IC. To our knowledge it also demonstrates for the first time a menstrual cycle effect on bladder sensory function in subjects with IC. This suggests a potential role of gonadal hormones on bladder sensory processing and, therefore, a potential role for hormonal modulation as a therapeutic modality in this patient population.


Diagnostic trinity: Graves' disease on F-18 FDG PET.
A 31-year-old man underwent a whole-body F-18 fluorodeoxyglucose (FDG) positron emission tomography (PET) scan for cancer screening. There was no history of diabetes, thyroid disease, or noticeable exercise before imaging. The results demonstrated diffusely increased uptake of F-18 FDG in the thyroid and thymus. In addition, there was symmetrically increased uptake of F-18 FDG in skeletal muscles, especially in the psoas and limb muscles. The concurrent appearance of these characteristics led to a diagnosis of Graves' disease.


Clostridium indicum sp. nov., a novel anaerobic bacterium isolated from the sludge of an industrial effluent.
A strictly anaerobic bacterial strain, designated as PI-S10-A1B, was isolated from a sludge sample collected from an industrial effluent dump site at Hyderabad, India. Cells stained Gram-positive and contained terminal endospores. Optimal growth was observed at 30 °C and pH 7.0. It showed negative reactions to catalase and oxidase activities. Phylogenetic analysis of the 16S rRNA gene led to strain PI-S10-A1BT being assigned to the genus Clostridium. It displayed high sequence similarity to species of cluster XIVa including Clostridium amygdalinumBR-10T (99.84 %), Clostridium saccharolyticum WM1T (98.93 %) and Clostridium indolis DSM 755T (98.31 %). It formed a coherent cluster with members of cluster XIVa. Despite high 16S rRNA gene sequence similarity, strain PI-S10-A1BT displayed only 25.3 % identity in DNA-DNA hybridization tests with C. amygdalinum BR-10T. A draft genome exhibited low values for average nucleotide identity and in silico DNA-DNA hybridization with strains of cluster XIVa. The DNA G+C content was 42.3 mol%. Major lipids were phosphatidylglycerol and diphosphatidylglycerol, with an abundance of phosphoglycolipids. Further, analysis of the draft genome revealed genomic insights against functional aspects. Considering the phenotypic differences and low genomic identity with phylogenetic relatives, strain PI-S10-A1BT is concluded to represent a new species of the genus Clostridium, for which the name Clostridiumindicum sp. nov. is proposed with type strain PI-S10-A1BT (=MTCC 12282T=DSM 24996T=JCM 32788T).


Nonoperative Comminuted Hamate Fracture.
A US Navy sailor was seen at an emergency department after falling on her outstretched hand. A computed tomography (CT) scan demonstrated a comminuted, nondisplaced dorsal hamate fracture. After 8 weeks of cast immobilization, a CT scan revealed no healing and physical therapy was initiated. Following 4 weeks of physical therapy, a third CT scan was performed and demonstrated partial fracture healing without displacement, so physical therapy continued. J Orthop Sports Phys Ther 2019;49(7):557. doi:10.2519/jospt.2019.8514.


Near real-time bedside detection of spinal cord ischaemia during aortic repair by microdialysis of the cerebrospinal fluid.
Spinal cord ischaemia (SCI) remains the most devastating complication after thoraco-abdominal aortic aneurysm (TAAA) repair. Its early detection is crucial if therapeutic interventions are to be successful. Cerebrospinal fluid (CSF) is readily available and accessible to microdialysis (MD) capable of detecting metabolites involved in SCI [i.e. lactate, pyruvate, the lactate/pyruvate ratio (LPR), glucose and glycerol] in real time. Our aim was to evaluate the feasibility of CSF MD for the real-time detection of SCI metabolites. In a combined experimental and translational approach, CSF MD was evaluated (i) in an established experimental large animal model of SCI with 2 arms: (a) after aortic cross-clamping (AXC, N = 4), simulating open TAAA repair and (b) after total segmental artery sacrifice (Th4-L5, N = 8) simulating thoracic endovascular aortic repair. The CSF was analysed utilizing MD every 15 min. Additionally, CSF was collected hourly from 6 patients undergoing open TAAA repair in a high-volume aortic reference centre and analysed using CSF MD. In the experimental AXC group, CSF lactate increased 3-fold after 10 min and 10-fold after 60 min of SCI. Analogously, the LPR increased 5-fold by the end of the main AXC period. Average glucose levels demonstrated a 1.5-fold increase at the end of the first (preconditioning) AXC period (0.60±0.14 vs 0.97±0.32 mmol/l); however, they decreased below (to 1/3 of) baseline levels (0.60±0.14 vs 0.19±0.13 mmol/l) by the end of the experiment (after simulated distal arrest). In the experimental segmental artery sacrifice group, lactate levels doubled and the LPR increased 3.3-fold within 30 min and continued to increase steadily almost 5-fold 180 min after total segmental artery sacrifice (P < 0.05). In patients undergoing TAAA repair, lactate similarly increased 5-fold during ischaemia, reaching a maximum at 6 h postoperatively. In 2 patients with intraoperative SCI, indicated by a decrease in the motor evoked potential of >50%, the LPR increased by 200%. CSF is widely available during and after TAAA repair, and CSF MD is feasible for detection of early anaerobic metabolites of SCI. CSF MD is a promising new tool combining bedside availability and real-time capacity to potentially enable rapid detection of imminent SCI, thereby maximizing chances to prevent permanent paraplegia in patients with TAAA.


Binding of tetramethylammonium to polyether side-chained aromatic hosts. Evaluation of the binding contribution from ether oxygen donors.
A set of macrocyclic and open-chain aromatic ligands endowed with polyether side chains has been prepared to assess the contribution of ether oxygen donors to the binding of tetramethylammonium (TMA), a cation believed incapable of interacting with oxygen donors. The open-chain hosts consisted of an aromatic binding site and side chains possessing a variable number of ether oxygen donors; the macrocyclic ligands were based on the structure of a previously investigated host, the dimeric cyclophane 1,4-xylylene-1,4-phenylene diacetate (DXPDA), implemented with polyether-type side chains in the backbone. Association to tetramethylammonium picrate (TMAP) was measured in CDCl(3) at T = 296 K by (1)H NMR titrations. Results confirm that the main contribution to the binding of TMA comes from the cation-pi interaction established with the aromatic binding sites, but they unequivocally show that polyether chains participate with cooperative contributions, although of markedly smaller entity. Water is also bound, but the two guests interact with aromatic rings and oxygen donors in an essentially noncompetitive way. An improved procedure for the preparation of cyclophanic tetraester derivatives has been developed that conveniently recycles the oligomeric ester byproducts formed in the one-pot cyclization reaction. An alternative entry to benzylic diketones has also been provided that makes use of a low-order cyanocuprate reagent to prepare in fair yields a class of compounds otherwise uneasily accessible.


Tumor-Targeted Gene Silencing IDO Synergizes PTT-Induced Apoptosis and Enhances Anti-tumor Immunity.
Background: Photothermal therapy (PTT) has been demonstrated to be a promising cancer treatment approach because it can be modulated to induce apoptosis instead of necrosis via adjusting irradiation conditions. Recently, an abscopal anti-tumor immunity has been highlighted, in which PTT on the primary tumor also induced repression of distant tumors. In PTT cancer treatments, the mechanism and the role of immune checkpoints to enhance anti-tumor immunity needs to be investigated. Methods: We prepared a multi-functional gold nanorod reagent, GMPF-siIDO, that is composed of gold nanorods (GNRs) that act as the nano-platform and photothermal sensitizer; folic acid (FA) as the tumor-targeting moiety; and IDO-specific RNA (siIDO) as an immune-stimulator functionality for inducing anti-tumor immunity. For this study, we adjusted the irradiation condition of PTT to induce apoptosis and to silence the immune checkpoint indoleamine 2,3 dioxygeonase (IDO), simultaneously. Results: Our studies provide evidence that photothermal effects kill tumor cells mainly via inducing apoptosis, which can significantly improve antitumor immunity when IDO was down-regulated in TME through significant increases of localized CD8+ and CD4+ lymphocytes in tumor tissue, the downregulation of CD8+ and CD4+ lymphocyte apoptosis, and the upregulation of antitumor cytokines, TNF-α and IFN-γ. Conclusion: In this study, we, for the first time, validated the role of IDO as a negative regulator for both PTT-induced tumor cell apoptosis and anti-tumor immunity; IDO is a critical immune checkpoint that impedes PTT while combination of gene knockdown of IDO in TME enhances anti-tumor efficacy of PTT.


Assessing behavioral health using OASIS: Part 1: Depression and suicidality.
This article is the first of a two-part series on assessing behavioral health in adult and elderly patients using OASIS. Direct questioning about emotional and behavioral symptoms in addition to observation, reports from family members, and input from other team members are used. This approach improves assessment information and increases nurse confidence and accuracy when making referrals for further psychiatric evaluation and treatment.


Single nucleotide polymorphism within arylsulfatase D gene (ARSD) is associated with selected kinematic parameters of sperm motility in Holstein-Friesian bulls.
The aim of the study was to find out whether the single nucleotide polymorphism (SNP) within arylsulfatase D (ARSD) gene is associated with kinematic parameters of sperm motility in Holstein-Friesian bulls. 367 Holstein-Friesian bulls kept in one AI center were included in the study. Point mutation C/T at position 139037255 on chromosome X (rs42207167) was identified by PCR-RFLP method (Pflm I). Significant associations were found between ARSD genotypes and CASA-derived sperm motility parameters: average TM (Total Motility), average VSL (Straight Velocity), average VCL (Curvilinear Velocity) and for fraction of sperms showing progressive motility (a) of sperms (VSLa, VCLa and BCFa -Beat Cross Frequency). Most significant differences were observed between alternative homozygotes (CC vs TT). Our results suggest new role of arylsulfatase D gene as being involved in sperm motility.


Prevalence of methicillin-resistant Staphylococcus haemolyticus in companion animals: a cross-sectional study.
Among coagulase-negative staphylococci, Staphylococcus haemolyticus is the second most frequently isolated species from human blood cultures and has the highest level of antimicrobial resistance. This species has zoonotic character and is prevalent both in humans and animals. Recent studies have indicated that methicillin-resistant S. haemolyticus (MRSH) is one of the most frequent isolated Staphylococcus species among neonates in intensive care units. The aim of this study was to determine the presence of MRSH in different groups of companion animals and to characterize isolates according their antimicrobial resistance. Samples (n = 754) were collected from healthy and diseased dogs and cats, female dogs in pure-breed kennels, healthy horses, and kennel owners. Classical microbiological tests along with molecular testing including PCR and 16S rRNA sequencing were performed to identify MRSH. Clonality of the isolates was assessed by Pulsed Field Gel Electrophoresis using the SmaI restriction enzyme. Antimicrobial susceptibility testing was performed using the broth micro-dilution method. Detection of genes encoding antimicrobial resistance was performed by PCR. Statistical analysis was performed using the R Project of Statistical Computing, "R 1.8.1" package. From a total of 754 samples tested, 12 MRSH isolates were obtained. No MRSH were found in horses and cats. Eleven isolates were obtained from dogs and one from a kennel owner. Ten of the dog isolates were detected in pure-breed kennels. The isolates demonstrated the same clonality only within separate kennels.The most frequent resistances of MRSH isolates was demonstrated to benzylpenicillin (91.7%), erythromycin (91.7%), gentamicin (75.0%), tetracycline (66.7%), fluoroquinolones (41.7%) and co-trimoxazole (41.7%). One isolate was resistant to streptogramins. All isolates were susceptible to daptomycin, rifampin, linezolid and vancomycin. The clone isolated from the kennel owner and one of the dogs was resistant to beta-lactams, macrolides, gentamicin and tetracycline. Pure-breed kennels keeping 6 or more females were determined to be a risk factor for the presence of MRSH strains. MRSH isolated from companion animals were frequently resistant to some classes of critically important antimicrobials, although they remain susceptible to antibiotics used exclusively in human medicine.