Results of drug screening from a producer's view.
The dairy industry is faced with increasing governmental and public concern about the safety of the nation's milk supply. New regulations under the Grade A Pasteurized Milk Ordinance require that prescription drugs be properly labeled and that all tanker loads of milk be tested for beta-lactam antimicrobial residues. Concern over the use of animal drugs in an extralabel manner has prompted the National Milk Producers Federation and the American Veterinary Medical Association to develop a quality assurance program for on-farm residue prevention known as the Dairy Quality Assurance 10-Point Milk and Dairy Beef Residue Prevention Protocol. The program promotes the concept of Hazard Analysis Critical Control Points, applied to a pre-harvest farm environment. Screening limitations at point of milk receipt necessitates widespread adoption of the Dairy Quality Assurance protocol to address controlled use of all animal medications under a valid relationship among veterinarian, client, and animals, thus minimizing the potential for violative residues in the milk and meat supply.


Series of open-framework aluminoborates containing [B5O10] clusters.
Three new open-framework aluminoborates (ABOs), Rb2AlB5O10·4H2O (), [C5N2H16]AlB5O10 (, C5N2H16 = N-ethyl-1,3-diaminopropane) and [H2dap][(CH3)2NH]AlB5O10 (, dap = 1,2-diaminopropane) have been made under solvothermal conditions and characterized by elemental analysis, IR, TGA, UV-vis, powder XRD, single-crystal XRD, fluorescence spectra and NLO determination, respectively. These three ABOs display two structural types: and are isostructural and crystallize in acentric space groups C2221 and P212121 respectively, showing intersecting helical channels and good NLO properties; while, crystallizes in the centrosymmetric space group Pbca and has CrB4 topology, exhibiting intersecting 8-, 11- and 14-ring channels. UV-vis spectral investigation indicates that they are wide-band-gap semiconductors.


Ecological breastfeeding and child spacing.
Until the 2nd and 3rd decades of this century, breastfeeding was essential for infant survival. In that period, spacing of children was generally about 2 years. Later, improved modified cow's milk preparations became commercially available and were well tolerated by most infants. As a result, near cessation of ecological breastfeeding occurred toward the middle of the century. The decline in ecological breastfeeding was associated with early postpartum ovulation and shortened child-spacing of about 1 year. The endocrinology of breastfeeding is now known in considerable detail. Prolactin is secreted promptly in response to nipple stimulation and is a reliable marker of the endocrine alterations occurring postpartum. Success of lactation in suppression of ovulation was found to occur when infants sucked frequently and when only small amounts of selected foods were introduced gradually after the infants were about 6 months of age.


Health Status of Gulf War and Era Veterans Serving in the US Military in 2000.
This research describes Gulf War and era veterans enrolled in the Millennium Cohort Study, who were sampled from US military personnel serving in 2000, and compares health characteristics of this sample to a Department of Veterans Affairs study sampled from the complete population. Demographics characteristics of this sample were described. Self-reported health characteristics were compared between the two studies. Gulf War and era veterans in the Millennium Cohort were generally healthier than in the VA study; they had fewer medical conditions and mental health disorders and better self-reported health. In both studies, Gulf War veterans had poorer health outcomes than era veterans. The Millennium Cohort Study is a unique resource for examining the long-term health effects of Gulf War deployment, particularly comparing deployed and nondeployed personnel and examining illnesses with long latencies.


Epigenetic Modifications of the Liver Tumor Cell Line HepG2 Increase Their Drug Metabolic Capacity.
Although human liver tumor cells have reduced metabolic functions as compared to primary human hepatocytes (PHH) they are widely used for pre-screening tests of drug metabolism and toxicity. The aim of the present study was to modify liver cancer cell lines in order to improve their drug-metabolizing activities towards PHH. It is well-known that epigenetics is strongly modified in tumor cells and that epigenetic regulators influence the expression and function of Cytochrome P450 (CYP) enzymes through altering crucial transcription factors responsible for drug-metabolizing enzymes. Therefore, we screened the epigenetic status of four different liver cancer cell lines (Huh7, HLE, HepG2 and AKN-1) which were reported to have metabolizing drug activities. Our results showed that HepG2 cells demonstrated the highest similarity compared to PHH. Thus, we modified the epigenetic status of HepG2 cells towards 'normal' liver cells by 5-Azacytidine (5-AZA) and Vitamin C exposure. Then, mRNA expression of Epithelial-mesenchymal transition (EMT) marker SNAIL and CYP enzymes were measured by PCR and determinate specific drug metabolites, associated with CYP enzymes by LC/MS. Our results demonstrated an epigenetic shift in HepG2 cells towards PHH after exposure to 5-AZA and Vitamin C which resulted in a higher expression and activity of specific drug metabolizing CYP enzymes. Finally, we observed that 5-AZA and Vitamin C led to an increased expression of Hepatocyte nuclear factor 4α (HNF4α) and E-Cadherin and a significant down regulation of Snail1 (SNAIL), the key transcriptional repressor of E-Cadherin. Our study shows, that certain phase I genes and their enzyme activities are increased by epigenetic modification in HepG2 cells with a concomitant reduction of EMT marker gene SNAIL. The enhancing of liver specific functions in hepatoma cells using epigenetic modifiers opens new opportunities for the usage of cell lines as a potential liver in vitro model for drug testing and development.


[The effect of stress on blood levels of vitamin A and E in piglets].
In five trials with 99 suckling or weaned piglets, the effects of the increased adrenocortical function, caused by cold, weaning from the sow or fasting or by stimulation with exogenous adrenocorticotrophic hormone (ACTH) were studied as exerted on vitamin A and vitamin E concentrations in the blood serum. Three hours after an exposure of three-day and four-day piglets to the temperature of 8-12 degrees C, a small drop of the concentrations of both vitamins occurred. In four-week weanling piglets a decrease in vitamin E concentration was observed in two days, the trend being slight in vitamin A concentration. At the same time some sibs were left fasting, which considerably reduced the concentrations of both vitamins. The situation was similar in two hours after ACTH administration to suckling piglets, however the difference was insignificant in vitamin E concentrations. In seventeen hours elapsing from two administrations of the adrenocorticotrophic hormone (ACTH) when the increased secretion of corticosteroids was fading out, only the vitamin A concentration in suckling piglets was found to drop. The response in weanling piglets was negligible. The suppressive effects of stress on vitamin A concentrations were usually observed when the levels of circulating corticosteroids were high or in the period immediately following this status. The changes in nutrition after early weaning exert large negative effects on vitamin E concentrations in the blood serum. The differences in the response of the organism to the two vitamins may be due to various types of transport mechanisms in the blood circulation. The specific effects of stress factors are mentioned.


Development of a prognostic index based on an immunogenomic landscape analysis of papillary thyroid cancer.
Papillary thyroid cancer (PTC) is the most common subtype of thyroid cancer, and inflammation relates significantly to its initiation and prognosis. Systematic exploration of the immunogenomic landscape therein to assist in PTC prognosis is therefore urgent. The Cancer Genome Atlas (TCGA) project provides a large number of genetic PTC samples that enable a comprehensive and reliable immunogenomic study. We integrated the expression profiles of immune-related genes (IRGs) and progression-free intervals (PFIs) in survival in 493 PTC patients based on the TCGA dataset. Differentially-expressed and survival-associated IRGs in PTC patients were estimated a computational difference algorithm and COX regression analysis. The potential molecular mechanisms and properties of these PTC-specific IRGs were also explored with the help of computational biology. A new prognostic index based on immune-related genes was developed by using multivariable COX analysis. A total of 46 differentially expressed immune-related genes were significantly correlated with clinical outcome of PTC patients. Functional enrichment analysis revealed that these genes were actively involved in a cytokine-cytokine receptor interaction KEGG pathway. A prognostic signature based on RGs (AGTR1, CTGF, FAM3B, IL11, IL17C, PTH2R and SPAG11A) performed moderately in prognostic predictions and correlated with age, tumor stage, metastasis, number of lesions, and tumor burden. Intriguingly, the prognostic index based on IRGs reflected infiltration by several types of immune cells. Together, our results screened several IRGs of clinical significance, revealed drivers of the immune repertoire, and demonstrated the importance of a personalized, IRG-based immune signature in the recognition, surveillance, and prognosis of PTC.


The perceptions of individuals with anorexia nervosa regarding their family's understanding of their illness, treatment, and recovery.
The current study explores how affected individuals understand their family's perceptions of anorexia nervosa (AN). Perceptions of individuals with AN regarding their family's understanding of the illness may influence their ability to accept family support. Thematic analysis was used on qualitative data of 19 individuals with AN undergoing inpatient treatment. Participants perceived that families: (a) considered AN a problem with food rather than a mental illness; and (b) viewed treatment as time limited, and complete recovery as achievable. Family-based interventions are needed to facilitate understanding about AN, as well as the behavioral and psychological adjustments required during treatment and recovery.


Over-expression of vitronectin correlates with impaired survival in gastric cancers.
Over-expression of vitronectin (VN) is associated with tumorigenesis. The present study aimed to evaluate the prognostic value of VN expression in gastric cancer.The least absolute shrinkage and selection operator analysis was performed to screen the hub gene from The Cancer Genome Atlas gastric cancer patients with complete follow-up data, and 347 patients were finally included. Moreover, 102 patients were enrolled from the Affiliated Fuzhou First Hospital of Fujian Medical University. VN expression in paired gastric cancer and adjacent gastric normal tissues was detected using immunohistochemistry, and the clinicopathological significance of VN expression was evaluated. The prognostic significance of VN expression in gastric cancer patients was evaluated using by Kaplan-Meier method and Cox regression analysis and confirmed using Oncomine.VN was the prognosis relative gene which screened by The Cancer Genome Atlas dataset. Moreover, we identified the VN expression in an external dataset by immunohistochemistry. The result demonstrated that VN expression was remarkedly elevated in gastric cancer tissues (P < .001). High VN expression correlated with higher pathological Tumor-Node-Metastasis stage, and poorer survival outcomes. Cox regression analysis showed that VN expression was independently predictive of overall survival (OS) and disease-free survival (P = .004, P < .001, respectively). A prognostic risk score for OS was built based on VN expression. A meta-analysis from Oncomine datasets revealed that significantly lower VN mRNA levels in gastric cancer correlated with poorer OS.VN expression could be a prognostic marker of gastric cancer.


[Genetic variation of main restorer lines of hybrid rice in China was revealed by microsatellite markers].
A total of thirty-five restorer lines of hybrid rice (Oryza sativa L.) were analyzed by twenty-five SSR (simple sequence repeats) primer pairs, which disperse on 12 chromosomes in rice. Those primers detected 65 alleles among 35 restorer lines of hybrid rice. Per primer pair detected 2.6 alleles on the average. PIC (polymorphism index content) values ranged from 0.206 to 0.682. PIC value is 0.414 on the average. The result from cluster analysis shows that hybrid rice restorer lines have abundant resource in China, but the genetic diversity is small and the genetic background is vulnerable among them. The utilization of rice heterosis was limited seriously.


Evidence-Based Dietary Practices to Improve Osteoarthritis Symptoms: An Umbrella Review.
While there is some research investigating whole foods or diets that are easily understood and accessible to patients with osteoarthritis, specific nutrients or nutraceuticals are more commonly identified. Unfortunately, guidelines and evidence surrounding individual nutrients, extracts, and nutraceuticals are conflicting and are more difficult to interpret and implement for patients with osteoarthritis. The purpose of this umbrella review is to provide a comprehensive understanding of the existing evidence of whole foods and dietary patterns effects on osteoarthritis-related outcomes to inform evidence-based recommendations for healthcare professionals and identify areas where more research is warranted. A literature search identified relevant systematic reviews/meta-analyses using five databases from inception to May 2022. Five systematic reviews/meta-analyses were included in the current umbrella review. Most evidence supported the Mediterranean diet improving osteoarthritis-related outcomes (e.g., pain, stiffness, inflammation, biomarkers of cartilage degeneration). There was little to no evidence supporting the effects of fruits and herbs on osteoarthritis-related outcomes; however, there was some suggestion that specific foods could potentiate symptom improvement through antioxidative mechanisms. The overall lack of homogeneity between the studies limits the conclusions that can be made and highlights the need for quality research that can identify consumer-accessible foods to improve osteoarthritis-related symptoms.


The insulin receptor: both a prototypical and atypical receptor tyrosine kinase.
Unlike prototypical receptor tyrosine kinases (RTKs), which are single-chain polypeptides, the insulin receptor (InsR) is a preformed, covalently linked tetramer with two extracellular α subunits and two membrane-spanning, tyrosine kinase-containing β subunits. A single molecule of insulin binds asymmetrically to the ectodomain, triggering a conformational change that is transmitted to the cytoplasmic kinase domains, which facilitates their trans-phosphorylation. As in prototypical RTKs, tyrosine phosphorylation in the juxtamembrane region of InsR creates recruitment sites for downstream signaling proteins (IRS [InsR substrate] proteins, Shc) containing a phosphotyrosine-binding (PTB) domain, and tyrosine phosphorylation in the kinase activation loop stimulates InsR's catalytic activity. For InsR, phosphorylation of the activation loop, which contains three tyrosine residues, also creates docking sites for adaptor proteins (Grb10/14, SH2B2) that possess specialized Src homology-2 (SH2) domains, which are dimeric and engage two phosphotyrosines in the activation loop.


Dialysis access: issues related to conversion from peritoneal dialysis to hemodialysis and vice versa.
ABSTRACTHemodialysis (HD) and peritoneal dialysis (PD) represent two complementary modalities of renal replacement therapy (RRT) for end-stage renal disease patients. Conversion between the two modalities is frequent and more likely to happen from PD to HD. Every year, 10% of PD patients convert to HD, suggesting the need for recommendations on how to proceed with the creation of a vascular access in these patients. Criteria for selecting patients who would likely fail PD, and therefore take advantage of a backup access, are undefined. Creating backup fistulas at the time of PD treatment start to allow emergency access for HD has proved to be inefficient, but it may be considered in patients with progressive difficulty in achieving adequate depuration and/or peritoneal ultrafiltration. A big challenge is represented by patients switching from PD to HD for unexpected infectious complications. Those patients need to start HD with a central venous catheter (CVC), but an alternative approach might be using an early cannulation graft, provided that infection has been cleared by the circulation. An early cannulation graft might also be used to considerably shorten the time spent using a CVC. In patients who need a conversion from HD to PD, urgent-start PD is now an accepted and well-established approach.


Substrate recognition by the human fatty-acid synthase.
The human fatty-acid synthase (HFAS) is a potential target for anti-tumor drug discovery. As a prelude to the design of compounds that target the enoyl reductase (ER) component of HFAS, the recognition of NADPH and exogenous substrates by the ER active site has been investigated. Previous studies demonstrate that modification of Lys-1699 by pyridoxal 5'-phosphate results in a specific decrease in ER activity. For the overall HFAS reaction, the K1699A and K1699Q mutations reduced kcat and kcat/KNADPH by 8- and 600-fold, respectively (where KNADPH indicates the Km value for NADPH). Thus, Lys-1699 contributes 4 kcal/mol to stabilization of the rate-limiting transition state following NADPH binding, while also stabilizing the most stable ground state after NADPH binding by 3 kcal/mol. A similar effect of the mutations on the ER partial reaction was observed, in agreement with the proposal that Lys-1699 is located in the ER NADPH-binding site. Most unexpectedly, however, both kcat and kcat/KNADPH for the beta-ketoacyl reductase (BKR) reaction were also impacted by the Lys-1699 mutations, raising the possibility that the ER and BKR activities share a single active site. However, based on previous data indicating that the two reductase activities utilize distinct cofactor binding sites, mutagenesis of Lys-1699 is hypothesized to modulate BKR activity via allosteric effects between the ER and BKR NADPH sites.


Formation of tungsten oxide nanowires by ion irradiation and vacuum annealing.
Here we reported the fabrication of tungsten oxide (WO3-x ) nanowires by Ar+ ion irradiation of WO3 thin films followed by annealing in vacuum. The nanowire length increases with increasing irradiation fluence and with decreasing ion energy. We propose that the stress-driven diffusion of the irradiation-induced W interstitial atoms is responsible for the formation of the nanowires. Comparing to the pristine film, the fabricated nanowire film shows a 106-fold enhancement in electrical conductivity, resulting from the high-density irradiation-induced vacancies on the oxygen sublattice. The nanostructure exhibits largely enhanced surface-enhanced Raman scattering effect due to the oxygen vacancy. Thus, ion irradiation provides a powerful approach for fabricating and tailoring the surface nanostructures of semiconductors.


Expression of candidate marker genes of sugar starvation is upregulated in growth-suppressed parthenocarpic cucumber fruit. Novel gene markers for sugar starvation in growth-suppressed cucumber fruit.
To examine the physiological change in the growth suppression and abortion of parthenocarpic cucumber fruit, the expression of candidate marker genes of sugar starvation in relation to growth activity was examined. Fruits that failed to start exponential growth seemed to eventually abort. Hexose concentration of fruits was low in growth-suppressed fruit and increased in normally growing fruit consistent with the vacuolization. The correlation matrix indicated that the transcript levels of the genes, except CsaV3_6G046050 and CsaV3_5G032930, had a highly significant negative correlation with the relative growth rate in fruit length and had highly significant mutual positive correlations, suggesting that the asparagine synthetase gene, Cucumis sativus putative CCCH-type zinc finger protein CsSEF1, C. sativus BTB/POZ domain-containing protein At1g63850-like, CsaV3_3G000800, CsaV3_3G041280, and CsaV3_7G032930 are good markers of sugar starvation in cucumber fruit. The expression of candidate marker genes together with the hexose analysis strongly suggests that severe sugar starvation is occurring in growth-suppressed fruit.


Nucleoside analogue delivery systems in cancer therapy.
Nucleoside analogues (NAs) are important agents in the treatment of hematological malignancies. They are prodrugs that require activation by phosphorylation. Their rapid catabolism, cell resistance and overdistribution in the body jeopardize nucleoside analogue chemotherapy. Accordingly, therapeutic doses of NAs are particularly high and regularly have to be increased, resulting in severe toxicity and narrow therapeutic index. The major challenge is to concentrate the drug at the tumour site, avoiding its distribution to normal tissues. New drug carriers and biomaterials are being developed to overcome some of these obstacles. This review highlights novel NA delivery systems and discusses new technologies that could improve NA cancer therapy.


Time-, concentration-, and age-dependent inhibition of muscarinic receptor-stimulated phosphoinositide metabolism by ethanol in the developing rat brain.
We have previously reported that administration of ethanol (EtOH; 4 g/Kg/day) to rats from postnatal day 4 to day 10 causes microencephaly and decreases muscarinic receptor-stimulated inositol metabolism on days 7 and 10. An identical exposure to EtOH of adult rats, which resulted in similar blood EtOH concentrations, did not have any effect on the same system. Initial in vitro studies have shown the presence of a differential sensitivity to EtOH of the phosphoinositide system coupled to muscarinic receptors during development. In the present study we have expanded these findings by investigating the concentration-, time-, and age-dependent effects of EtOH on accumulation of [3H]inositol phosphates ([3H]InsPs) in brain slices. EtOH caused a dose-dependent inhibition of carbachol-stimulated phosphoinositide metabolism in cerebral cortex slices from 7 day-old rats. When the time of incubation with EtOH was increased to 90 minutes, concentrations as low as 50 mM, which are reached following in vivo administration of EtOH, significantly inhibited the muscarinic response. The effect of EtOH was rather specific for the muscarinic receptors, since, even with longer incubation times, the accumulation of [3H]InsPs induced by norepinephrine or serotonin was inhibited only at concentrations of 150-500 mM. The effect of EtOH was more pronounced in cerebral cortex, hippocampus and cerebellum, and less in the brainstem. The potency of EtOH in inhibiting carbachol-stimulated phosphoinositide metabolism was also dependent on the age of the animals. Its effect was maximal in the 7-day-old rat and less pronounced in younger and older animals.(ABSTRACT TRUNCATED AT 250 WORDS)


Venture capital, control rights, and family enterprise growth.
This research explores and explains the path of family enterprise venture capital equity financing from the perspective of endogenous family control rights. We adopted unbalanced panel data on Chinese listed companies from 2007 to 2018. Empirical research shows that there are significant differences in the impact of venture capital on the growth performance of family enterprises and non-family enterprises. Venture capital negatively affects the growth performance of family enterprises, while the negative impact of venture capital on family enterprises is not significant. In addition, family control positively moderates the negative impact of venture capital on family enterprise growth performance.


Outcome of conservatively managed early-onset breast cancer by BRCA1/2 status.
Management of early-stage breast cancer in young women with mutations in BRCA1 or BRCA2 remains controversial. This study assessed the long-term risks of ipsilateral and contralateral breast cancer in a cohort of young women who underwent breast-conserving surgery followed by radiotherapy. Between 1975 and 1998, 290 women with breast cancer diagnosed at age 42 years or younger underwent lumpectomy followed by radiotherapy at our hospital. We recruited 127 of these women for complete sequencing of BRCA1 and BRCA2. Demographic, clinical, pathological, and outcome data were recorded. The primary endpoints were rates of ipsilateral and contralateral breast cancer, in relation to germline BRCA1/2 status. 105 women were classified as having sporadic disease (94 with wild-type or known polymorphisms and 11 with variants of unclear significance) and 22 as having genetic predisposition (deleterious mutations in BRCA1 [15] or BRCA2 [seven]). At 12 years of follow-up, the genetic group had significantly higher rates of ipsilateral (49% vs 21%, p=0.007) and contralateral events (42% vs 9%, p=0.001) than the sporadic group. The majority of events were classified as second primary tumours. No patient in the genetic group had undergone oophorectomy or was taking prophylactic agents such as tamoxifen. Patients with germline mutations in BRCA1 or BRCA2 have a high risk of developing late ipsilateral and contralateral second primary tumours. With breast-conserving therapy, chemoprophylaxis or other interventions to reduce the rate of second cancers may be valuable. Alternatively, bilateral mastectomy may be considered, to minimise the risk of second tumours in the breasts.


Scary gas: intravascular, intracranial, and intraspinal ectopic gas (part III).
While ectopic gas can be a sign of dangerous disease requiring immediate medical or surgical intervention, it can also be an incidental and benign finding. Intravenous gas and spinal vacuum gas are common and almost always benign. Intravascular gas is most often related to instrumentation and, if intraarticular, can cause end-organ ischemia; however, treatment is usually supportive. Pneumocephalus arises from a communication with paranasal sinuses or mastoids more often than from meningeal infection and can usually be managed nonoperatively. In part 3 of this series, the different causes of ectopic gas in the vessels, skull, and spine are reviewed, as are the imaging features that can help to narrow the differential diagnosis.


Ferritin - another tumor marker for testicular malignancies.
On the basis of results obtained with other malignancies, the usefulness of serum ferritin as a tumor marker in the diagnosis of testicular tumors was studied. In 68 patients with malignant testicular tumors and 22 patients with benign testicular processes, serial determinations of beta-human chorionic gonadotropin (beta-HCG), alpha-fetoprotein (AFP) and serum ferritin were performed. The serum ferritin values showed no relationship to tumor stage, and no difference in nonseminomatous and seminomatous tumors. In particular, no diagnostic improvement was achieved in those cases in which the conventional markers AFP and beta-HCG were unsuccessful (falsely negative results). Furthermore, serum ferritin values were influenced by hepatic factors and anemia, so that serum ferritin - on the basis of the present material-could not be considered a useful tumor marker in testicular malignancies. Further studies on the determination of carcinofetal isoferritin and other new tumor markers are warranted.


Crystal and solution structures of fragments of the human leucocyte common antigen-related protein.
Leucocyte common antigen-related protein (LAR) is a post-synaptic type I transmembrane receptor protein that is important for neuronal functionality and is genetically coupled to neuronal disorders such as attention deficit hyperactivity disorder (ADHD). To understand the molecular function of LAR, structural and biochemical studies of protein fragments derived from the ectodomain of human LAR have been performed. The crystal structure of a fragment encompassing the first four FNIII domains (LARFN1-4) showed a characteristic L shape. SAXS data suggested limited flexibility within LARFN1-4, while rigid-body refinement of the SAXS data using the X-ray-derived atomic model showed a smaller angle between the domains defining the L shape compared with the crystal structure. The capabilities of the individual LAR fragments to interact with heparin was examined using microscale thermophoresis and heparin-affinity chromatography. The results showed that the three N-terminal immunoglobulin domains (LARIg1-3) and the four C-terminal FNIII domains (LARFN5-8) both bound heparin, while LARFN1-4 did not. The low-molecular-weight heparin drug Innohep induced a shift in hydrodynamic volume as assessed by size-exclusion chromatography of LARIg1-3 and LARFN5-8, while the chemically defined pentameric heparin drug Arixtra did not. Together, the presented results suggest the presence of an additional heparin-binding site in human LAR.


Ocular demodicidosis as a risk factor of adult recurrent chalazion.
To report Demodex infestation in adult recurrent chalazion and its clinical response to weekly lid scrub with 50% tea tree oil (TTO) and daily lid scrub with tea tree shampoo. This is a retrospective review of 30 adult patients (48 eyes) who presented with recurrent chalazion within 6 months after conventional treatment. Demodex was detected by random lash sampling and microscopic examination. Patients with confirmed ocular Demodex infestation were treated with weekly lid scrub with 50% TTO and daily lid scrub with tea tree shampoo. The study is limited by the lack of a control group. The mean age of patients was 39.1 ± 10.2 years (range 18-69). The mean follow-up of patients is 10.0 ± 3.0 months (range 6-24 months). Among 48 eyes with recurrent chalazion, Demodex mites were found in 35 (72.9%). Recurrent chalazion was found to be associated with ocular demodicidosis (Fisher exact test, p = 0.017). Tea tree oil treatment was given to 31 eyes with recurrent chalazion associated with Demodex infestation. Among the treatment group, all cases except one had no recurrence after the TTO treatment. The success rate of preventing recurrence is 96.8%. Treatment of TTO was found to be associated with preventing recurrence of chalazion associated with Demodex infestation (Fisher exact test, p = 0.002). The possibility of demodicidosis should be considered in adults presenting with recurrent chalazia. Tea tree oil eyelid scrubs is an effective treatment in preventing recurrence.


Regional Contrast-Enhanced Ultrasonography (CEUS) Characteristics of Breast Cancer and Correlation with Microvessel Density (MVD).
BACKGROUND The aim of this study was to investigate the perfusion characteristics of different breast lesion regions in contrast-enhanced ultrasonography (CEUS). MATERIAL AND METHODS A total of 161 malignant and benign breast lesion cases were subjected to CEUS. Perfusion parameters were analyzed and compared between the central and peripheral lesion regions, and surrounding tissue. Mass section was marked with methylene blue. Samples were subjected to immunohistochemistry, and microvessel density (MVD) was calculated. RESULTS There were significant differences in perfusion performance between the central and peripheral lesion regions, and surrounding tissue. In the malignant tumors, the fast-in and fast-out pattern was the most common type in the peripheral region (57.98%), while the slow-in and slow-out patterns were the major types in the central region and surrounding tissue (49.58% and 57.98%, respectively). Compared with the surrounding tissue, the peripheral region in the cancers exhibited hyperechoic enhancement and fast-in and slow-out pattern, with large area under the curve (AUC), while the central region showed isoechoic enhancement and equally-in and slow-out pattern, with large AUC. In the benign lesions, the peripheral region exhibited hyperechoic enhancement and fast-in and fast-out pattern, with small AUC, while the central region showed isoechoic enhancement and equally-in and -out pattern, with the same AUC value. Moreover, the perfusion parameters in the central and peripheral regions were significantly associated with MVD. CONCLUSIONS It is more objective to evaluate the perfusion performance of breast lesions with the reference of surrounding tissue. Compared with the central region, the peripheral region could better reflect the perfusion characteristics of malignant lesions.


Oncogenic roles of astrocyte elevated gene-1 (AEG-1) in osteosarcoma progression and prognosis.
Astrocyte elevated gene-1 (AEG-1) is overexpressed in several cancers and plays an important role in cancer progression. However, AEG-1 expression, biological function, and clinical significance in osteosarcoma have not been uncovered. Utilizing manipulated human osteosarcoma cell lines and osteosarcoma tissues, we found that increasing expression of AEG-1 enhanced osteosarcoma cell proliferation and invasion in vitro, and knockdown of AEG-1 significantly attenuated osteosarcoma cell malignancy. Moreover, AEG-1 was overexpressed in osteosarcoma tissues, and overexpression of AEG-1 was strongly associated with gender (p = 0.018), clinical stages (p < 0.001), classification (p < 0.001), metastasis (p = 0.013), differentiation (p < 0.001), and poor survival (p = 0.021). Mechanistic studies conducted in vitro and in vivo revealed that AEG-1-mediated carcinogenesis and invasiveness might be through upregulating MMP-2. Taken together, our data strongly suggest that AEG-1 plays a crucial role in osteosarcoma progression through MMP-2, and AEG-1 could be a useful biomarker for the prediction of osteosarcoma progression and prognosis.


Experience of harm from others' drinking and support for stricter alcohol policies: Analysis of the Australian National Drug Strategy Household Survey.
Previous research indicates that those who have experienced alcohol-related harm from others are more likely to support stricter alcohol control policies. This study investigates the association between types of harm experienced because of others' drinking and support for stricter alcohol control policies. Data from 20,570 Australians aged 18 and over who completed the 2013 National Drug Strategy Household Survey was used. Questions about experience of alcohol-related harm from others - being put in fear and abuse (verbal or physical) - were asked. Support for stricter alcohol control policies was quantified by a mean policy support score across 18 alcohol policy questions. Twenty seven percent of respondents reported harm from someone's drinking. Respondents who were put in fear had a higher level of support for stricter alcohol control policies than respondents who were not harmed (p<0.001), regardless of whether they were abused or not. Conversely, respondents who experienced abuse but were not put in fear did not significantly differ in their support for stricter policies from those who experienced no harm. It is the apprehension of harm (i.e. having been put in fear), and not the experience of harm itself (i.e. abuse), which is related to people's support for stricter alcohol policies. These findings suggest that perceiving others' intoxication as dangerous to oneself may motivate support for stricter alcohol policies.


Treatment Options for Amelobastic Carcinoma of the Mandible: A Case Series and Review of the Literature.
We retrospectively review the only three cases in the Irish National Maxillofacial Unit over a 12-year period. Methods involved retrospectively reviewing clinical notes, radiology and histopathology of three cases. Case one was an 80-year-old male presenting with mandibular swelling, who received radiotherapy alone. Case two was a 26-year-old male with swelling and odynophagia. He underwent left hemimandibulectomy and fibular free flap reconstruction. Case three was a 64-year-old female with mental nerve involvement who underwent a right hemimandibulectomy. The cases presented here illustrate a diverse sample regarding patient demographics and management approaches. Surgery usually necessitates en bloc resection, free flap reconstruction and 1-1.5 cm margins. Adjuvant radiotherapy may be required for close margins.


ERBB2 in cat mammary neoplasias disclosed a positive correlation between RNA and protein low expression levels: a model for erbB-2 negative human breast cancer.
Human ERBB2 is a proto-oncogene that codes for the erbB-2 epithelial growth factor receptor. In human breast cancer (HBC), erbB-2 protein overexpression has been repeatedly correlated with poor prognosis. In more recent works, underexpression of this gene has been described in HBC. Moreover, it is also recognised that oncogenes that are commonly amplified or deleted encompass point mutations, and some of these are associated with HBC. In cat mammary lesions (CMLs), the overexpression of ERBB2 (27%-59.6%) has also been described, mostly at the protein level and although cat mammary neoplasias are considered to be a natural model of HBC, molecular information is still scarce. In the present work, a cat ERBB2 fragment, comprising exons 10 to 15 (ERBB2_10-15) was achieved for the first time. Allelic variants and genomic haplotype analyses were also performed, and differences between normal and CML populations were observed. Three amino acid changes, corresponding to 3 non-synonymous genomic sequence variants that were only detected in CMLs, were proposed to damage the 3D structure of the protein. We analysed the cat ERBB2 gene at the DNA (copy number determination), mRNA (expression levels assessment) and protein levels (in extra- and intra protein domains) in CML samples and correlated the last two evaluations with clinicopathological features. We found a positive correlation between the expression levels of the ERBB2 RNA and erbB-2 protein, corresponding to the intracellular region. Additionally, we detected a positive correlation between higher mRNA expression and better clinical outcome. Our results suggest that the ERBB2 gene is post-transcriptionally regulated and that proteins with truncations and single point mutations are present in cat mammary neoplastic lesions. We would like to emphasise that the recurrent occurrence of low erbB-2 expression levels in cat mammary tumours, suggests the cat mammary neoplasias as a valuable model for erbB-2 negative HBC.


Comparison of results of treatment of hydrocele and epididymal cysts by surgery and injection.
A comparison has been made between a series of hydroceles and cysts of epididymis treated by surgery with a complication rate of at least 17% haematoma and 10% sepsis, an average hospital stay of five days, and a much longer time off work, and a series treated by tapping and injection (described in detail) requiring one to three visits to outpatients, an almost negligible complication rate, and no failures in those completing treatment.


The emergence of beta-lactamase resistance in respiratory pathogens.
Bacteria have evolved a variety of mechanisms to express resistance to beta-lactam antibiotics. beta-Lactamase-induced hydrolysis of the beta-lactam ring is the principal and most important mediator of clinically significant resistance. Almost 200 beta-lactamases have now been identified, of which class 1 chromosomal beta-lactamases, class 2b plasmid-mediated beta-lactamases (especially TEM-1) and class 2be extended-spectrum beta-lactamases (ESBLs) are among the most important in respiratory pathogens. The combination of enzymatic and non-enzymatic resistance mechanisms has led to a steady rise in the prevalence of resistance to beta-lactams among isolates of the major respiratory pathogens, and, in turn, increasing rates of treatment failure, increased mortality, and prolonged morbidity. The combination of a beta-lactam antibiotic with a beta-lactamase inhibitor such as sulbactam, which protects the antibiotic from beta-lactamase destruction and so restores its activity, provides an innovative solution to this problem.


[The locomotor system in irreversible renal failure treated with regular dialysis].
Changes of the locomotor apparatus in prolonged uraemia with regular dialyzation treatment determine the quality of life with all its consequences for the patient. The greatest impact on osteodystrophic disease (the most typical finding on the skeleton) is exerted by the length of dialyzation treatment. Of 216 patients having regular dialyzation treatment in 1979 to 1992 the authors observed osteodystrophic disease in 25, i.e. 11.6%. As to other most frequently observed changes they recorded osteoporosis in 12.9%, only very rarely osteomalacia and even osteopetrosis (1.8%). Carpal tunnel syndrome was recorded in 17.4% as a symptom of so-called dialyzation amyloidosis and in one man they observed the development of typical rheumatoid arthritis shortly after the onset of haemodialyzation. This is a rare observation not described in the literature so far. Crystalline arthropathy, incl. typical attacks of gout, were recorded only in 11 patients (5%). Changes on the locomotor apparatus in conjunction with irreversible renal failure with regular dialyzation treatment were recorded in 45%. It is important to differentiate findings which are not associated with uraemia and haemodialysis. This applies in particular to osteoarthritis deformans of the joints and spine. In major uraemic changes participates in particular secondary hyperparathyroidism. These changes comprise in particular osteolysis or even spontaneous absorption, erosive changes and destructive spondylopathy. Contemporary findings on the locomotor apparatus are so varied that they must be classified.(ABSTRACT TRUNCATED AT 250 WORDS)


Children with comorbid speech sound disorder and specific language impairment are at increased risk for attention-deficit/hyperactivity disorder.
This study focuses on the comorbidity between attention-deficit/hyperactivity disorder (ADHD) symptoms and speech sound disorder (SSD). SSD is a developmental disorder characterized by speech production errors that impact intelligibility. Previous research addressing this comorbidity has typically used heterogeneous groups of speech-language disordered children. This study employed more precise speech-language diagnostic criteria and examined ADHD symptomatology in 108 SSD children between the ages of 4 and 7 years old with specific language impairment (SLI) (n = 23, 14 males, 9 females) and without SLI (n = 85, 49 males, 36 females). We also examined whether a subcategory of SSD, persistent (n = 39, 25 males, 14 females) versus normalized SSD (n = 67, 38 males, 29 females), was associated with ADHD and/or interacted with SLI to predict ADHD symptomatology. Results indicated that participants in the SSD + SLI group had higher rates of inattentive ADHD symptoms than those in the SSD-only and control groups. In addition, an unexpected interaction emerged such that children with SLI and normalized-SSD had significantly higher ADHD inattentive ratings than the other subgroups. A proposed explanation for this interaction is discussed.


Determination of anabolic steroids by gas chromatography/negative-ion chemical ionization mass spectrometry and gas chromatography/negative-ion chemical ionization tandem mass spectrometry with heptafluorobutyric anhydride derivatization.
A gas chromatography/mass spectrometry (GC/MS) method is described which uses negative ion chemical ionization (NCI) and tandem mass spectrometry (MS/MS) for the determination of eight anabolic steroids in human urine. Eight anabolic steroids were derivatized by heptafluorobutyric anhydride (HFBA), and were determined using GC/NCI-MS and GC/NCI-MS/MS. The linear correlation coefficients for calibration in NCI-MS/MS were in the range 0.9880-0.9988. This method of derivatization with HFBA for use with GC/NCI was useful in determinations of 19-norandrosterone, boldenone, 19-noretiocholanolone, 2-methylandrosterone, nandrolone, 1-methyleneandrosterone, 1-methylandrosterone, 4-dihydroboldenone and mesterolone. The detection limits of this procedure were 5-20 ppb at a signal-to-noise (S/N) ratio of 3.


Physiological variables in association with spreading depolarizations in the late phase of ischemic stroke.
Physiological effects of spreading depolarizations (SD) are only well studied in the first hours after experimental stroke. In patients with malignant hemispheric stroke (MHS), monitoring of SDs is restricted to the postoperative ICU stay, typically day 2-7 post-ictus. Therefore, we investigated the role of physiological variables (temperature, intracranial pressure, mean arterial pressure and cerebral perfusion pressure) in relationship to SD during the late phase after MHS in humans. Additionally, an experimental stroke model was used to investigate hemodynamic consequences of SD during this time window. In 60 patients with MHS, the occurrence of 1692 SDs was preceded by a decrease in mean arterial pressure (-1.04 mmHg; p = .02) and cerebral perfusion pressure (-1.04 mmHg; p = .03). Twenty-four hours after middle cerebral artery occlusion in 50 C57Bl6/J mice, hypothermia led to prolonged SD-induced hyperperfusion (+2.8 min; p < .05) whereas hypertension mitigated initial hypoperfusion (-1.4 min and +18.5%Δ rCBF; p < .01). MRI revealed that SDs elicited 24 hours after experimental stroke were associated with lesion progression (15.9 vs. 14.8 mm³; p < .01). These findings of small but significant effects of physiological variables on SDs in the late phase after ischemia support the hypothesis that the impact of SDs may be modified by adjusting physiological variables.


Impact of Pathologists and Evaluation Methods on Performance Assessment of the Kidney Injury Biomarker, Kim-1.
Attempts to characterize and formally qualify biomarkers for regulatory purposes have raised questions about how histological and histopathological methods impact the evaluation of biomarker performance. A group of pathologists was asked to analyze digitized images prepared from rodent kidney injury experiments in studies designed to investigate sources of variability in histopathology evaluations. Study A maximized variability by using samples from diverse studies and providing minimal guidance, contextual information, or opportunities for pathologist interaction. Study B was designed to limit interpathologist variability by using more uniform image sets from different locations within the same kidneys and allowing pathologist selected interactions to discuss and identify the location and injury to be evaluated but without providing a lexicon or peer review. Results from this study suggest that differences between pathologists and across models of disease are the largest sources of variability in evaluations and that blind evaluations do not generally make a significant difference. Results of this study generally align with recommendations from both industry and the U.S. Food and Drug Administration and should inform future studies examining the effects of common lexicons and scoring criteria, peer review, and blind evaluations in the context of biomarker performance assessment.


Toll-Like Receptors in Natural Killer Cells and Their Application for Immunotherapy.
Innate immunity represents the first barrier for host defense against microbial infection. Toll-like receptors (TLRs) are the most well-defined PRRs with respect to PAMP recognition and induction of innate immune responses. They recognize pathogen-associated molecular patterns (PAMPs) and trigger innate immune responses by inducing inflammatory cytokines, chemokines, antigen-presenting molecules, and costimulatory molecules. TLRs are expressed either on the cell surface or within endosomes of innate immune cells. NK cells are one of the innate immune cells and also express TLRs to recognize or respond to PAMPs. TLRs in NK cells induce the innate immune responses against bacterial and viral infections via inducing NK cytotoxicity and cytokine production. In this review, we will discuss the expression and cellular function of TLRs in NK cells and also introduce some therapeutic applications of TLR agonists for NK cell-mediated immunotherapy.


A trend analysis of antimicrobial resistance in commensal Escherichia coli from several livestock species in Belgium (2011-2014).
A temporal trend analysis was performed on antimicrobial resistance data collected over 4 consecutive years (2011-2014) in the official Belgian antimicrobial resistance monitoring programme. Commensal Escherichia coli strains were isolated from faecal samples of four livestock categories (veal calves, young beef cattle, broiler chickens and slaughter pigs) and the trends of resistance profiles were analysed. The resistance prevalence remained high (>50%) during the study period for ampicillin in veal calves and chickens, for ciprofloxacin and nalidixic acid in chickens, for sulfamethoxazole in veal calves, chickens and pigs and for tetracycline in veal calves. Using logistic regression and Generalized Estimating Equation and after p value adjustment for multiple testing (Linear step-up method), statistically significant decreasing temporal trends were observed for several of the 11 tested antimicrobials in several livestock categories: in veal calves (10/11), in chickens (6/11) and in pigs (5/11). A significant increasing trend was observed for the prevalence of resistance to ciprofloxacin in chickens. Multi-resistance, considered as the resistance to at least three antimicrobials of different antibiotic classes, was observed in the four livestock categories but was significantly decreasing in veal calves, chickens and pigs. Overall, the prevalence of resistance and of multi-resistance was lowest in the beef cattle livestock category and highest in broiler chickens. These decreasing temporal trends of antimicrobial resistance might be due to a decrease of the total antimicrobial consumption for veterinary use in Belgium which was reported for the period between 2010 and 2013. The methodology and statistical tools developed in this study provide outputs which can detect shifts in resistance levels or resistance trends associated with particular antimicrobial classes and livestock categories. Such outputs can be used as objective evidence to evaluate the possible efficacy of measures taken by animal health authorities and stakeholders in the livestock sector to limit antimicrobial resistance occurrence.


Therapeutic Effect, Rheological Properties and α-Amylase Resistance of a New Mixed Starch and Xanthan Gum Thickener on Four Different Phenotypes of Patients with Oropharyngeal Dysphagia.
Thickened fluids are a therapeutic strategy for oropharyngeal dysphagia (OD). However, its therapeutic effect among different phenotypes of OD patients has not yet been compared. We aimed to assess the therapeutic effect and α-amylase resistance of a mixed gum/starch thickener [Fresubin Clear Thickener® (FCT)] on four phenotypes of OD patients: G1) 36 older; G2) 31 head/neck cancer (HNC); G3) 30 Parkinson's disease; and G4) 31 chronic post-stroke. Therapeutic effect of FCT was assessed during videofluoroscopy using the Penetration-Aspiration Scale (PAS), for 5/20 mL boluses, at four levels of shear-viscosity (<50, 250, 1000 and 2000 mPa·s). The effect of α-amylase was assessed after 30 s of oral incubation. Patients had high prevalence of VFS signs of impaired efficacy (98.44%) and safety (70.31%) of swallow with a severe PAS score (4.44 ± 0.20). Most severe OD was in HNC (80.6% unsafe swallows). FCT showed a strong therapeutic effect on the safety of swallow at a range between 250-1000 mPa·s (74.19-96.67%, safe swallows in G1, G3, G4, and 58.06% in G2), without increasing pharyngeal residue. Viscosity was unaffected by α-amylase. Increasing shear-viscosity with FCT causes a strong viscosity-dependent therapeutic effect on the safety of swallow. This effect depends on the phenotype and is similar among older, Parkinson's and post-stroke patients.


Docosahexaenoic acid and arachidonic acid are fundamental supplements for the induction of neuronal differentiation.
Cell replacement therapy is being investigated for the treatment of neurodegenerative disorders. Adult autologous bone marrow-derived mesenchymal stem cells (MSCs) have been induced to differentiate into neuron-like cells harboring a variety of neuronal markers and transcription factors. Neural tissue characteristically contains high proportions of docosahexaenoic acid (DHA) and arachidonic acid (AA). In this study, evaluation of the fatty acid profile of differentiated neuron-like cells revealed a very low level of DHA, similar to that in MSCs but different from typical neurons. Supplementation of the medium with DHA alone resulted in increased levels of DHA but concomitant low levels of AA. However, supplementation with both DHA and AA yielded a fatty acid profile resembling that of neural tissue. It also resulted in enhanced outgrowth of neurite-like processes, hallmarks of neuronal differentiation. These findings demonstrate the essentiality of DHA and AA supplementation in the process of induced neuronal differentiation and have important implications for the development of cell replacement strategies of neural repair.


Inhibition of cathepsin L-like cysteine proteases by cytotoxic T-lymphocyte antigen-2 beta.
The protein sequence of cytotoxic T-lymphocyte antigen-2 beta (CTLA-2 beta) is 36% identical to the proregion of mouse cathepsin L (Denizot, F., Brunet, J.F., Roustan, P., Harper, K., Suzan, M., Luciani, M. F., Mattei, M. G., and Goldstein, P. (1989) Eur. J. Immunol. 19, 631-635). Here we report the expression, purification, and characterization of recombinant murine CTLA-2 beta. The protein was purified by consecutive gel-filtration, anion-exchange, and reverse-phase (C4) chromatography. Purified CTLA-2 beta exists in solution primarily as a dimer but also as a disulfide-linked tetramer as judged by size exclusion chromatography. Circular dichroism studies suggest that the dimeric form of the protein contains 8% alpha-helix, 67% beta-sheet, and 21% random coil and also indicates that there is a conformational change upon formation of the tetramer. The protein is a competitive inhibitor of certain cysteine proteases including papain (Ki = 25 nM), cathepsins L (Ki = 24 nM) and H (IC50 = 67 nM) but not cathepsin B. CTLA-2 beta forms a noncovalent complex with cathepsin L and has a stoichiometry of binding to papain of 1 mol of CTLA-2 beta/mol of papain. There is no homology between CTLA-2 beta and any of the known cysteine protease inhibitors, including the kininogens and cystatins. Therefore, CTLA-2 beta represents a novel class of cysteine protease inhibitor that is specific for the cathepsin L family of proteases.


Glycoprotein Ia-IIa (VLA-2) and glycoprotein Ib-IX complexes are processed independently during thrombin-induced platelet activation.
We have previously shown that when human platelets are stimulated by thrombin, glycoprotein Ib-IX (GP Ib-IX) complexes are cleared to the surface-connected canalicular system (Blood 1990;76:1503). The question arose as to whether GP Ia-IIa complexes (VLA-2), another adhesion receptor thought to be linked to the membrane cytoskeleton, behaved similarly. Monoclonal antibodies to GP Ia-IIa were used in either (1) immunofluorescence procedures and flow cytometry or (2) immunogold staining and electron microscopy. In flow cytometry, VLA-2 was shown to have a low but variable expression in the platelets of different donors. Immunogold staining showed that the complexes were regularly distributed over the platelet surface. This was best seen after staining of paraformaldehyde-fixed whole mounts, where bound antibodies were often visualized in small clusters. The surface expression of VLA-2 receptors increased somewhat after thrombin stimulation, the receptors coming from a small intracellular pool revealed by flow cytometric analysis of Triton X-100-permeabilized cells. Immunogold staining showed that after activation the receptors were equally as present on pseudopods as on the peripheral zone of the platelet. Down-regulation, as seen with GP Ib-IX complexes, was not observed. Our results therefore show that two-way trafficking of adhesion receptors can occur during platelet activation. This would imply that GP Ib-IX and VLA-2 are attached to different elements within the membrane cytoskeleton.


The Role of Angiogenesis and Pro-Angiogenic Exosomes in Regenerative Dentistry.
Dental surgeries can result in traumatic wounds that provoke major discomfort and have a high risk of infection. In recent years, density research has taken a keen interest in finding answers to this problem by looking at the latest results made in regenerative medicine and adapting them to the specificities of oral tissue. One of the undertaken directions is the study of angiogenesis as an integrative part of oral tissue regeneration. The stimulation of this process is intended to enhance the local availability of stem cells, oxygen levels, nutrient supply, and evacuation of toxic waste. For a successful stimulation of local angiogenesis, two major cellular components must be considered: the stem cells and the vascular endothelial cells. The exosomes are extracellular vesicles, which mediate the communication between two cell types. In regenerative dentistry, the analysis of exosome miRNA content taps into the extended communication between these cell types with the purpose of improving the regenerative potential of oral tissue. This review analyzes the stem cells available for the dentistry, the molecular cargo of their exosomes, and the possible implications these may have for a future therapeutic induction of angiogenesis in the oral wounds.


Induction of lactose transport in Escherichia coli during the absence of phospholipid synthesis.
Induction of lactose transport and of beta-galactosidase synthesis was examined in two Escherichia coli strains that require exogenous glycerol for phospholipid synthesis and growth. No preferential inhibition of lactose transport induction was observed when phospholipid synthesis was restricted to 5 to 10% of the normal rate. We conclude that the lactose transport system does not require concurrent phospholipid synthesis for its functional assembly.


Gold(I)-Catalyzed Cycloisomerization of ortho-(Propargyloxy)arenemethylenecyclopropanes Controlled by Adjacent Substituents at Aromatic Rings.
Gold(I)-catalyzed cycloisomerization of ortho-(propargyloxy)arenemethylenecyclopropanes afforded two different types of products, that is, products of methylenecyclopropane migration and cycloisomerization products of the methylenecyclopropane moiety, controlled jointly by electronic and steric effects of the adjacent substituents. Furthermore, the corresponding cycloisomerization products could be also produced in an enantiomerically enriched manner.


Dissociation as a Transdiagnostic Indicator of Self-Injurious Behavior and Suicide Attempts: A Focus on Posttraumatic Stress Disorder and Borderline Personality Disorder.
Dissociative symptoms and suicidality are transdiagnostic features of posttraumatic stress disorder (PTSD) and borderline personality disorder (BPD). The primary objective of this study was to examine associations between dissociation (i.e., depersonalization and derealization) and suicidality (i.e., self-harm and suicide attempts) among individuals with PTSD and BPD. We analyzed data from the 2012-2013 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III; N = 36,309). The Alcohol Use Disorder and Associated Disabilities Interview Schedule for DSM-5 was used to assess lifetime PTSD and BPD. Estimated rates of self-harm among individuals who endorsed dissociation were 15.5%-26.2% for those with PTSD and 13.7%-23.5% for those with BPD, and estimates of suicide attempts among individuals who endorsed dissociation were 34.5%-38.1% for those with PTSD and 28.3%-33.1% for those with BPD. Multiple logistic regressions were conducted to examine the associations between dissociation (derealization, depersonalization, and both) and both self-harm and suicide attempts among respondents with PTSD and BPD. The results indicated that dissociation was associated with self-harm and suicide attempts, especially among individuals with BPD, aORs = 1.39-2.66; however, this association may be driven in part by a third variable, such as other symptoms of PTSD or BPD (e.g., mood disturbance, PTSD or BPD symptom severity). These results may inform risk assessments and targeted interventions for vulnerable individuals with PTSD, BPD, or both aimed at mitigating the risk of self-harm and suicide.


Angiogenic profiling and comparison of immortalized endothelial cells for functional genomics.
Genomics efforts of the past decade have resulted in the identification of numerous genes with putative roles in disease processes, including tumor angiogenesis. To functionally validate these genes, cultured endothelial cells are indispensable tools, though these may not completely mimic the phenotype of tissue endothelial cells as the proper microenvironment is lacking. To obtain experimental data representative of normal physiology, the use of primary endothelial cells is preferred. However, these cells are usually limited in passage number, can be difficult to obtain and show great interindividual variety. Furthermore, transfection efficiency is very limited in primary cells, hampering applications in functional genomics and gene function analysis. The use of properly characterized alternative endothelial cell sources is therefore warranted. Here, we compared immortalized endothelial cells - HMEC, RF24 and EVLC2 - with primary HUVEC. We show that RF24, and to a slightly lesser extent HMEC, resembles primary HUVEC most on all facets examined. RF24, in contrast to EVLC2, express the endothelial markers CD31, CD34, CD105, vWF and VE-cadherin, and are capable of migration and tube formation in vitro. Furthermore, the expression levels of angiogenic growth factors and their receptors are comparable to that of primary EC. In addition, whereas primary HUVEC are resistant to transfection using common lipophilic transfection reagents, HMEC and RF24 could be readily transfected. Hence, these cells pose a valuable tool for functional genomics in angiogenesis research.


Effect of naproxen and acetaminophen on blood pressure lowering by ramipril, valsartan and aliskiren in hypertensive patients.
Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently used for reducing pain and other symptoms in osteoarthritis (OA). NSAIDs have been associated with an increase in blood pressure (BP) in both normotensive and hypertensive individuals and a blunting effect on various anti-hypertensive medications. Acetaminophen effects on anti-hypertensive treatment, instead, are still a matter of debate. To assess the effect of naproxen versus acetaminophen on ramipril, valsartan and aliskiren therapy in hypertensive patients with OA in a double-blind, cross-over study, by measuring clinic, ambulatory BP and heart rate (HR). One hundred seventy four patients were randomly treated with ramipril, valsartan or aliskiren for 8 weeks and 135 patients with normalized BP were randomized to receive naproxen or acetaminophen for 2 weeks. Naproxen significantly increased clinic and ambulatory systolic/diastolic BP (SBP/DBP) values in patients treated with ramipril (p < 0.01) or valsartan (p < 0.05), but did not affect aliskiren effects. Also acetaminophen slightly but significantly affected clinic and ambulatory SBP/DBP in all three groups and, surprisingly, it also produced a slight increase in HR (+3.1, +3.3 and +3.4 b/min day-time HR values, for ramipril, valsartan and aliskiren, respectively; p < 0.05). Both naproxen and acetaminophen can affect anti-hypertensive therapy with ramipril, valsartan or aliskiren with a different extent. When acetaminophen is chosen for OA management in subjects with hypertension, patients should be evaluated as carefully as when traditional NSAIDs are given.


Synthesis of racemic β-chamigrene, a spiro[5.5]undecane sesquiterpene [corrected].
The present paper describes a total synthesis of racemic β-chamigrene, a sesquiterpene with a spiro[5.5]undecane carbon framework. Compared with previously reported β-chamigrene syntheses, we were able to reduce the total number of reaction steps, which also resulted in a significant improvement of the overall yield. The commercially available ketone 6-methylhept-5-en-2-one was transformed by known simple procedures into 3,3-dimethyl-2-methylenecyclohexanone. This reacted with isoprene by a Diels-Alder reaction to give a spiro ketone. An olefination reaction on this compound gave the target molecule.


A preclinical evaluation of alternative site for islet allotransplantation.
The bone marrow cavity (BMC) has recently been identified as an alternative site to the liver for islet transplantation. This study aimed to compare the BMC with the liver as an islet allotransplantation site in diabetic monkeys. Diabetes was induced in Rhesus monkeys using streptozocin, and the monkeys were then divided into the following three groups: Group1 (islets transplanted in the liver with immunosuppressant), Group 2 (islets transplanted in the tibial BMC), and Group 3 (islets transplanted in the tibial BMC with immunosuppressant). The C-peptide and blood glucose levels were preoperatively measured. An intravenous glucose tolerance test (IVGTT) was conducted to assess graft function, and complete blood cell counts were performed to assess cell population changes. Cytokine expression was measured using an enzyme-linked immune sorbent assay (ELISA) and MILLIPLEX. Five monkeys in Group 3 exhibited a significantly increased insulin-independent time compared with the other groups (Group 1: 78.2 ± 19.0 days; Group 2: 58.8 ± 17.0 days; Group 3: 189.6 ± 26.2 days) and demonstrated increases in plasma C-peptide 4 months after transplantation. The infusion procedure was not associated with adverse effects. Functional islets in the BMC were observed 225 days after transplantation using the dithizone (DTZ) and insulin/glucagon stains. Our results showed that allogeneic islets transplanted in the BMC of diabetic Rhesus monkeys remained alive and functional for a longer time than those transplanted in the liver. This study was the first successful demonstration of allogeneic islet engraftment in the BMC of non-human primates (NHPs).


Synj1 haploinsufficiency causes dopamine neuron vulnerability and alpha-synuclein accumulation in mice.
Synaptojanin1 (synj1) is a phosphoinositide phosphatase with dual SAC1 and 5'-phosphatase enzymatic activities in regulating phospholipid signaling. The brain-enriched isoform has been shown to participate in synaptic vesicle (SV) recycling. More recently, recessive human mutations were identified in the two phosphatase domains of SYNJ1, including R258Q, R459P and R839C, which are linked to rare forms of early-onset Parkinsonism. We now demonstrate that Synj1 heterozygous deletion (Synj1+/-), which is associated with an impaired 5'-phosphatase activity, also leads to Parkinson's disease (PD)-like pathologies in mice. We report that male Synj1+/- mice display age-dependent motor function abnormalities as well as alpha-synuclein accumulation, impaired autophagy and dopaminergic terminal degeneration. Synj1+/- mice contain elevated 5'-phosphatase substrate, PI(4,5)P2, particularly in the midbrain neurons. Moreover, pharmacological elevation of membrane PI(4,5)P2 in cultured neurons impairs SV endocytosis, specifically in midbrain neurons, and further exacerbates SV trafficking defects in Synj1+/- midbrain neurons. We demonstrate down-regulation of SYNJ1 transcript in a subset of sporadic PD brains, implicating a potential role of Synj1 deficiency in the decline of dopaminergic function during aging.


Results of target tracking with a Musca domestica inspired sensor.
As a follow-up to previous work done at the University of Wyoming (and presented at a previous Rocky Mountain Bioengineering Symposium), this paper discusses the results of using a Musca domestica based sensor platform as a target tracking mechanism for the measurement of wing deflection of fixed-wing aircraft. The testing of the sensor hardware and accompanying software is described, and the results are analyzed. Work remains to be done to improve robustness and adaptability, but given specific operating conditions, the sensor is a viable alternative to other technologies, and provides results with improved efficiency, speed, and computational load.


Morphology of the endothelium over atherosclerotic plaques in human coronary arteries.
The right coronary arteries of six hearts removed from patients with atherosclerosis, who were undergoing cardiac transplantation, were perfused with 2% buffered glutaraldehyde for 20 minutes before preparation for scanning electron microscopy. Perfusion was started within five minutes of explanation. In two patients the artery was angiographically normal, in one it was irregular in outline, and three had focal segments with significant stenosis. None of the patients had concentrations of plasma lipids above 5.5 mmol/l. The endothelial surface showed widespread focal abnormalities ranging from adhesion and migration of monocytes to loss of individual endothelial cells. Larger areas of endothelial denudation with exposure of underlying collagen were also seen consistently. Loss of endothelial cells was associated with accumulation of monocytes, on and deep to the surface, as well as adhesion of platelets to the exposed subendothelial tissue. These results accord with the endothelial damage and platelet adhesion seen in hyperlipidaemic animals fed a high lipid diet.


Feeding performance of juvenile hatchery-reared spotted seatrout Cynoscion nebulosus.
The feeding performance of individual hatchery-reared (HR) and wild juvenile spotted seatrout Cynoscion nebulosus was compared across a series of six 1·5 h feeding exposures over a 3 day period in a controlled experiment. The predation cycle served as a context for discerning feeding performance elements. The experimental design facilitated assessments of the effects of experience, motivation due to hunger or satiation and prey density and encounter frequency. Although feeding success improved significantly across successive trials for both groups of C. nebulosus, wild C. nebulosus successfully captured and consumed significantly more Palaemonetes spp. prey and completed most performance metrics more efficiently than HR C. nebulosus. Total exposure time decreased with experience for both groups of C. nebulosus; however, HR C. nebulosus took longer to complete feeding exposures. Underpinning this difference was the time spent by HR C. nebulosus in non-search mode and for completing various foraging behaviours. Nevertheless, juvenile HR C. nebulosus exhibited sufficient foraging plasticity to switch from a pelleted diet to live novel prey.


Effects of Bending Radii on the Characteristics of Flexible Organic Solar Cells Investigated by Impedance Analysis.
Flexible organic solar cells (OSCs) were fabricated on an indium-tin-oxide (ITO)/poly(ethylene terephthalate) (PET) substrate and were subjected to bending tests with various bending radii. We observed that the photovoltaic properties of the OSCs precipitously deteriorated at a bending radius ≤ 0.75 cm. In order to investigate the effects of the bending test, the changes in the surface morphology and the sheet resistance of the ITO-coated PET samples were investigated, and the photovoltaic properties of bent and unbent OSCs were evaluated. Thereafter, equivalent circuits for the OSCs were assumed and the change in their parameters, such as resistance and capacitance, was observed.


Coronary artery bypass surgery versus coronary stenting: risk-adjusted survival rates in 5,619 patients.
We used the Texas Heart Institute Cardiovascular Research Database to retrospectively identify patients who had undergone their 1st revascularization procedure with coronary artery bypass surgery (CABG; n=2,826) or coronary stenting (n=2,793) between January 1995 and December 1999. Patients were classified into 8 anatomic groups according to the number of diseased vessels and presence or absence of proximal left anterior descending coronary artery disease. Mortality rates were adjusted with proportional hazards methods to correct for baseline differences in severity of disease and comorbidity. We found that in-hospital mortality was significantly greater in patients undergoing CABG than in those undergoing stenting (3.6% vs 0.75%; adjusted OR 8.4; P < 0.0001). At a mean 2.5-year follow-up, risk-adjusted survival was equivalent (CABG 91%, stenting 95%; adjusted OR 1.26; P = 0.06). When subgroups matched for severity of disease were compared, no differences in risk-adjusted survival were seen. A survival advantage of stenting was noted in 3 categories of patients: those >65 years of age (OR 1.33, P = 0.049), those with non-insulin-requiring diabetes (OR 2.06, P = 0.002), and those with any noncoronary vascular disease (OR 1.59, P = 0.009). In this nonrandomized observational study, CABG had a higher periprocedural mortality rate than did percutaneous stenting. At 2.5 years, however, the survival advantage of stenting was no longer evident. These data suggest that there is no intermediate-term survival advantage of CABG over stenting in patients who have multivessel disease with lesions that can be treated percutaneously.


[Barium meal after pancreatic surgery (author's transl)].
After duodenopancreatectomy the roentgenpattern of the upper gastrointestinal tract resembles the pattern after Billroth I- or Billroth II- resection. A different aspect results after Y-Roux anastomosis. The follow-up of pseudocysts drained into the stomach poses no problems. The follow-up of pseudocysts drained into the small bowel demands a roentgenexamination with duodenal intubation. The use of hypotonia is advisable in the diagnosis of malignancy. Problems may arise in roentgendiagnostics after palliative operations.


A reconsideration of the clinical work of Harold Searles.
A rereading of the work of Harold Searles in light of the more contemporary paradigm of dissociation refreshes our insights into transference and countertransference phenomena with patients who rely heavily on dissociation. Searles's perspective on the dependence of the analyst (therapist) on his or her patients, the reality of patients' projections, and patients' need to cure their analyst can be helpful in resolving conundrums and impasses in the treatment of dissociative disordered patients. The reciprocity of dissociative phenomena between patients and therapists, wherein therapists must own the reality of their own dissociative processes in the therapeutic transaction, recontextualizes Searles's clinical contributions.


Phylogenetic and geographical relationships of hantavirus strains in eastern and western Paraguay.
Recently, we reported the discovery of several potential rodent reservoirs of hantaviruses in western (Holochilus chacarius) and eastern Paraguay (Akodon montensis, Oligoryzomys chacoensis, and O. nigripes). Comparisons of the hantavirus S- and M-segments amplified from these four rodents revealed significant differences from each another and from other South American hantaviruses. The ALP strain from the semiarid Chaco ecoregion clustered with Leguna Negra and Rio Mamore (LN/RM), whereas the BMJ-NEB strain from the more humid lower Chaco ecoregion formed a clade with Oran and Bermejo. The other two strains, AAI and IP37/38, were distinct from known hantaviruses. With respect to the S-segment sequence, AAI from eastern Paraguay formed a clade with ALP/LN/RM, but its M-segment clustered with Pergamino and Maciel, suggesting a possible reassortment. AAI was found in areas experiencing rapid land cover fragmentation and change within the Interior Atlantic Forest. IP37/38 did not show any strong association with any of the known hantavirus strains.


Extractive acetonobutylic fermentation by coupling ultrafiltration and distillation.
An extractive acetonobutylic fermentation process is developed by integrating bioproduction, Ultrafiltration, and distillation, providing simultaneous retention of biomass, selective removal of inhibitors from the permeate, as well as separation and purification of acetone-butanol-ethanol solvents. Successive batch fermentations were performed with normal pressure distillation (98 degrees C), which permitted prolonging and enhancing (by a factor of 3) solvent production, with very few volume exchanges of medium (average dilution rate ws 0.002 h(-1)), and recovering on-line concentrated solvents. Different operating conditions were also tested in order to study the presence of extracellular autolytic enzymes as inhibition factors: It was shown that, (1) extracellular autolytic activity remains low during the larger part of fermentations, even without enzyme-inactivating thermotreatment in the distillation boiler, and (2) high-temperature distillation causes deleterious effects to the culture medium for long duration treatments. Progressive improvements of the process were achieved, first, by managing continuous runs, providing a minimum renewal of the culture medium and, mainly, by decreasing temperature and pressure of distilation. Solvent productivity then reached 2.6 g/L h for a 0.036 h(-1) average dilution rate, corresponding to a feed concentration of 156 g/L glucose actually consumed.


[Clinical picture of urogenital tuberculosis].
On the basis of a survey on 28 cases with ascertained urogenital tuberculosis from 1971 to 1975 clinical picture and findings of the examinations are discussed. The cases in question are not a representative cross-section, since primarily ascertained cases of urogenital tuberculosis are treated in special departments. On account of the participation of the bladder which - compared with former cases - seems to be less frequent in interest of the early diagnosis is referred to the importance of the urinary findings and the excretion urography.


Health policy in nursing curriculum.
This article presents the findings of a study on how health policy is integrated into the nursing curriculum at both the graduate and undergraduate levels, with particular emphasis on type of coursework, faculty preparation, and teaching strategies. The sample for the study included 210 randomly selected schools of nursing: 150 with undergraduate programs only and 60 with both graduate and undergraduate programs. The findings indicate that health policy has not yet received optimal placement in the curriculum at either the undergraduate or graduate level of nursing preparation. Recommendations are made based upon the findings of the study, a review of the literature, and the collective experience of the authors.


A practical development protocol for evidence-based digital integrative arts therapy content in public mental health services: digital transformation of mandala art therapy.
The fundamentals of digital transformation include the conversion of the traditional method into a digital format to develop a standardized system that collects, analyzes, and processes quantitative data. This study aims to provide a comprehensive understanding of the development process and key elements of evidence-based digital integrative arts therapy. The "Digital Mandala" service in the "Mental Health App" produced as part of a national public mental health project for personalized depression management is adopted to explain how to convert the existing mandala art therapy into digital format. A living lab approach has been applied, which can be used to address the nation's mental health challenges by promoting collaboration, innovation, and evidence-based solutions. Evidence-based digital content requires evidence that covers the structural process, the effects of existing methods, and the components and meanings of each detailed scene. In this section, we provide five stages of the development process, including preliminary research, design, development, commercialization, and advancement. Consequently, clinical elements, integrative arts therapy features, and data factors are defined as the key principles of evidence-based digital integrative arts therapy. Based on the data factors found in this study, it will be possible to create an evaluation dataset of digital integrative arts therapy content for managing depression. Additionally, the large-scale public data can be analyzed through artificial intelligence technology, which is expected to be used as a basis for deriving significant results in a new form, going further than the existing evaluation method. This research is significant because it establishes the foundation for digital transformation in the field of art therapy for public mental health services and investigates its potential.


The impact of Caesarean delivery on paracetamol and ketorolac pharmacokinetics: a paired analysis.
Pharmacokinetics is a first, but essential step to improve population-tailored postoperative analgesia, also after Caesarean delivery. We therefore aimed to quantify the impact of caesarean delivery on the pharmacokinetics of intravenous (iv) paracetamol (2 g, single dose) and iv ketorolac tromethamine (30 mg, single dose) in 2 cohorts eachof 8 women at caesarean delivery and to compare these findings with postpartum to quantify intrapatient changes. We documented a higher median paracetamol clearance at delivery when compared to 10-15 weeks postpartum (11.7 to 6.4 L/h·m², P < 0.01), even after correction for weight-related changes. Similar conclusions were drawn for ketorolac: median clearance was higher at delivery with a subsequent decrease (2.03 to 1.43 L/h·m², P < 0.05) in postpartum (17-23 weeks). These differences likely reflect pregnancy- and caesarean-delivery-related changes in drug disposition. Moreover, postpartum paracetamol clearance was significantly lower when compared to estimates published in healthy young volunteers (6.4 versus 9.6 L/h·m²), while this was not the case for ketorolac (1.43 versus 1.48 L/h·m²). This suggests that postpartum is another specific status in young women that merits focused, compound-specific pharmacokinetic evaluation.


Gryllotalpicola reticulitermitis sp. nov., isolated from a termite gut.
Strain TS-56(T) was isolated from the gut of a wood-feeding termite, Reticulitermes chinensis Snyder. Phylogenetic analyses based on 16S rRNA gene sequences revealed that the strain represented a member of the genus Gryllotalpicola of the family Microbacteriaceae, with sequence similarities to other species of the genus ranging from 96.6 % to 97.8 %. The isolate was Gram-stain-positive, non-motile, with light yellow colonies and irregular short rod-shaped cells (0.4-0.6 µm in diameter, 0.6-1.0 µm in length). Growth of TS-56(T) occurred at 20-35 °C (optimum, 30 °C) and at pH 4.0-8.0 (optimum, pH 5.0). The peptidoglycan of TS-56(T) contained ornithine, glutamic acid, alanine, homoserine and glycine. The acyl type was acetyl. The most abundant cellular fatty acid of TS-56(T) was cyclohexyl-C17 : 0 (88.79 %). The respiratory menaquinone was MK-11. The polar lipid profile contained disphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol and two unknown glycolipids. DNA of the type strain had a G+C content of 67.4 mol%. On the basis of the phylogenetic properties and phenotypic distinctiveness, TS-56(T) represents a novel species of the genus Gryllotalpicola, for which the name Gryllotalpicola reticulitermitis sp. nov. is proposed. The type strain is TS-56(T) ( = CGMCC 1.10363(T) = NBRC 109838(T)).


Classical molecular-dynamics simulation of the hydroxyl radical in water.
We have studied the hydration and diffusion of the hydroxyl radical OH0 in water using classical molecular dynamics. We report the atomic radial distribution functions, hydrogen-bond distributions, angular distribution functions, and lifetimes of the hydration structures. The most frequent hydration structure in the OH0 has one water molecule bound to the OH0 oxygen (57% of the time), and one water molecule bound to the OH0 hydrogen (88% of the time). In the hydrogen bonds between the OH0 and the water that surrounds it the OH0 acts mainly as proton donor. These hydrogen bonds take place in a low percentage, indicating little adaptability of the molecule to the structure of the solvent. All hydration structures of the OH0 have shorter lifetimes than those corresponding to the hydration structures of the water molecule. The value of the diffusion coefficient of the OH0 obtained from the simulation was 7.1x10(-9) m2 s(-1), which is higher than those of the water and the OH-.


Imaging white matter microstructure with gradient-echo phase imaging: Is ex vivo imaging with formalin-fixed tissue a good approximation of the in vivo brain?
Ex vivo imaging is a commonly used approach to investigate the biophysical mechanism of orientation-dependent signal phase evolution in white matter. Yet, how phase measurements are influenced by the structural alteration in the tissue after formalin fixation is not fully understood. Here, we study the effects on magnetic susceptibility, microstructural compartmentalization, and chemical exchange measurement with a postmortem formalin-fixed whole-brain human tissue. A formalin-fixed, postmortem human brain specimen was scanned with multiple orientations to the main magnetic field direction for robust bulk magnetic susceptibility measurement with conventional quantitative susceptibility imaging models. White matter samples were subsequently excised from the whole-brain specimen and scanned in multiple rotations on an MRI scanner to measure the anisotropic magnetic susceptibility and microstructure-related contributions in the signal phase and to validate the findings of the whole-brain data. The bulk isotropic magnetic susceptibility of ex vivo whole-brain imaging is comparable to in vivo imaging, with noticeable enhanced nonsusceptibility contributions. The excised specimen experiment reveals that anisotropic magnetic susceptibility and compartmentalization phase effect were considerably reduced in the formalin-fixed white matter specimens. Formalin-fixed postmortem white matter exhibits comparable isotropic magnetic susceptibility to previous in vivo imaging findings. However, the measured phase and magnitude data of the fixed white matter tissue shows a significantly weaker orientation dependency and compartmentalization effect. Alternatives to formalin fixation are needed to better reproduce the in vivo microstructural effects in postmortem samples.


Bovine WC1+ and WC1neg γδ T Lymphocytes Influence Monocyte Differentiation and Monocyte-Derived Dendritic Cell Maturation during In Vitro Mycobacterium avium Subspecies paratuberculosis Infection.
During early Mycobacterium avium subspecies paratuberculosis (Map) infection, complex interactions occur between the bacteria, cells from the mononuclear phagocyte system (MPS) including both resident (macrophages and dendritic cells) and recruited (monocytes) cells, and other mucosal sentinel cells such as γδ T lymphocytes. Though the details of early host-pathogen interactions in cattle remain largely underexplored, our hypothesis is that these significantly influence development of host immunity and ultimate success or failure of the host to respond to Map infection. The aims of the present study were to first characterize monocyte-derived MPS cells from young calves with respect to their immunophenotype and function. Then, we set out to investigate the effects of WC1+ and WC1neg γδ T lymphocytes on (1) the differentiation of autologous monocytes and (2) the maturation of autologous monocyte-derived dendritic cells (MDDCs). To achieve this, peripheral blood WC1+ or WC1neg γδ T lymphocytes were cocultured with either autologous freshly isolated peripheral blood-derived monocytes or autologous immature MDDCs (iMDDCs). We began by measuring several markers of interest on MPS cells. Useful markers to distinguish monocyte-derived macrophages (MDMs) from MDDCs include CD11b, CD163, and CD172a, which are expressed significantly higher on MDMs compared with MDDCs. Function, but not phenotype, was influenced by WC1neg γδ T lymphocytes: viability of Map harvested from monocytes differentiated in the presence of WC1neg γδ T lymphocytes (dMonWC1neg) was significantly lower compared to MDMs and MDDCs. With respect to DC maturation, we first showed that mature MDDCs (mMDDCs) have significantly higher expression of CD11c, CD80, and CD86 compared with iMDDCs, and the phagocytic capacity of mMDDCs is significantly reduced compared to iMDDCs. We then showed that γδ T lymphocyte subsets induce functional (reduced phagocytosis) but not phenotypic (surface marker expression) iMDDC maturation. These data collectively show that γδ T lymphocytes influence differentiation, maturation, and ultimately the function of monocytes during Map infection, which has significant implications on survival of Map and success of host defense during early Map infection.


[Elastase and its inhibitors in the pathogenesis of benign ovarian tumors].
Activities of elastase and its inhibitors were studied in blood serum and tissues of patients with ovary benign tumors. Two peaks of the enzyme activation were detected during the menstrual cycle: at periovulatory period and at the second step of the cycle. In blood serum and tissues of the patients a decrease in the elastase activity was found, which was most distinct in papillary and mucinosis tumors. These alterations in the elastase activity appears to be responsible for impairments in the blood vessel wall structure, which may limit in penetration of estrogens into circulation and cause prolongation of effects of steroids on ovary tissue.


Ineffective platelet production in thrombocytopenic human immunodeficiency virus-infected patients.
Thrombocytopenia has been characterized in six patients infected with human immunodeficiency virus (HIV) with respect to the delivery of viable platelets into the peripheral circulation (peripheral platelet mass turnover), marrow megakaryocyte mass (product of megakaryocyte number and volume), megakaryocyte progenitor cells, circulating levels of endogenous thrombopoietin (TPO) and platelet TPO receptor number, and serum antiplatelet glycoprotein (GP) IIIa49-66 antibody (GPIIIa49-66Ab), an antibody associated with thrombocytopenia in HIV-infected patients. Peripheral platelet counts in these patients averaged 46 +/- 43 x 10(3)/microL (P = . 0001 compared to normal controls of 250 +/- 40x 10(3)/microL), and the mean platelet volume (MPV) was 10.5 +/- 2.0 fL (P > 0.3 compared with normal control of 9.5 +/- 1.7 fL). The mean life span of autologous 111In-platelets was 87 +/- 39 hours (P = .0001 compared with 232 +/- 38 hours in 20 normal controls), and immediate mean recovery of 111In-platelets injected into the systemic circulation was 33% +/- 16% (P = .0001 compared with 65% +/- 5% in 20 normal controls). The resultant mean peripheral platelet mass turnover was 3.8 +/- 1.5 x 10(5) fL/microL/d versus 3.8 +/- 0.4 x 10(5) fL/microL/d in 20 normal controls (P > .5). The mean endogenous TPO level was 596 +/- 471 pg/mL (P = .0001 compared with 95 +/- 6 pg/mL in 98 normal control subjects), and mean platelet TPO receptor number was 461 +/- 259 receptors/platelet (P = .05 compared with 207 +/- 99 receptors/platelet in nine normal controls). Antiplatelet GPIIIa49-66Ab levels in sera were uniformly increased in HIV thrombocytopenic patients (P < .001). In this cohort of thrombocytopenic HIV patients, marrow megakaryocyte number was increased to 30 +/- 15 x 10(6)/kg (P = .02 compared with 11 +/- 2.1 x 10(6)/kg in 20 normal controls), and marrow megakaryocyte volume was 32 +/- 0.9 x 10(3) fL (P = .05 compared with 28 +/- 4.5 x 10(3) fL in normal controls). Marrow megakaryocyte mass was expanded to 93 +/- 47 x 10(10) fL/kg (P = .007 compared with normal control of 31 +/- 5.3 x 10(10) fL/kg). Marrow megakaryocyte progenitor cells averaged 3.3 (range, 0.4 to 7.3) CFU-Meg/1,000 CD34(+) cells compared with 27 (range, 0.1 to 84) CFU-Meg/1,000 CD34(+) cells in seven normal subjects (P = .02). Thus, thrombocytopenia in these HIV patients was caused by a combination of shortening of platelet life span by two thirds and doubling of splenic platelet sequestration, coupled with ineffective delivery of viable platelets to the peripheral blood, despite a threefold TPO-driven expansion in marrow megakaryocyte mass. We postulate that this disparity between circulating platelet product and marrow platelet substrate results from direct impairment in platelet formation by HIV-infected marrow megakaryocytes.


Time-restricted feeding for prevention and treatment of cardiometabolic disorders.
The soaring prevalence of obesity and diabetes is associated with an increase in comorbidities, including elevated risk for cardiovascular diseases (CVDs). CVDs continue to be among the leading causes of death and disability in the United States. While increased nutritional intake from an energy-dense diet is known to disrupt metabolic homeostasis and contributes to the disease risk, circadian rhythm disruption is emerging as a new risk factor for CVD. Circadian rhythms coordinate cardiovascular health via temporal control of organismal metabolism and physiology. Thus, interventions that improve circadian rhythms are prospective entry points to mitigate cardiometabolic disease risk. Although light is a strong modulator of the neural circadian clock, time of food intake is emerging as a dominant agent that affects circadian clocks in metabolic organs. We discovered that imposing a time-restricted feeding (TRF) regimen in which all caloric intakes occur consistently within ≤ 12 h every day exerts many cardiometabolic benefits. TRF prevents excessive body weight gain, improves sleep, and attenuates age- and diet-induced deterioration in cardiac performance. Using an integrative approach that combines Drosophila melanogaster (fruit fly) genetics with transcriptome analyses it was found that the beneficial effects of TRF are mediated by circadian clock, ATP-dependent TCP/TRiC/CCT chaperonin and mitochondrial electron transport chain components. Parallel studies in rodents have shown TRF reduces metabolic disease risks by maintaining metabolic homeostasis. As modern humans continue to live under extended periods of wakefulness and ingestion events, daily eating pattern offers a new potential target for lifestyle intervention to reduce CVD risk.


Genetic Variability of Chrysodeixis Includens Nucleopolyhedrovirus (ChinNPV) and the Insecticidal Characteristics of Selected Genotypic Variants.
Genetic variation in baculoviruses is recognized as a key factor, not only due to the influence of such variation on pathogen transmission and virulence traits, but also because genetic variants can form the basis for novel biological insecticides. In this study, we examined the genetic variability of Chrysodeixis includens nucleopolyhedrovirus (ChinNPV) present in field isolates obtained from virus-killed larvae. Different ChinNPV strains were identified by restriction endonuclease analysis, from which genetic variants were isolated by plaque assay. Biological characterization studies were based on pathogenicity, median time to death (MTD), and viral occlusion body (OB) production (OBs/larva). Nine different isolates were obtained from eleven virus-killed larvae collected from fields of soybean in Mexico. An equimolar mixture of these isolates, named ChinNPV-Mex1, showed good insecticidal properties and yielded 23 genetic variants by plaque assay, one of which (ChinNPV-R) caused the highest mortality in second instars of C. includens. Five of these variants were selected: ChinNPV-F, ChinNPV-J, ChinNPV-K, ChinNPV-R, and ChinNPV-V. No differences in median time to death were found between them, while ChinNPV-F, ChinNPV-K, ChinNPV-R and ChinNPV-V were more productive than ChinNPV-J and the original mixture of field isolates ChinNPV-Mex1. These results demonstrate the high variability present in natural populations of this virus and support the use of these new genetic variants as promising active substances for baculovirus-based bioinsecticides.


Perceptions of physical activity and walking in an early stage after stroke or acquired brain injury.
Physical activity has been established as being highly beneficial for health after stroke. There are considerable global efforts to find rehabilitation programs that encourage increased physical activity for persons with stroke. However, many persons with stroke or acquired brain injury do not reach recommended levels of physical activity and increased knowledge about why is needed. We aimed to explore views and experiences of physical activity and walking among persons with stroke or acquired brain injury. A qualitative study was conducted, among persons with stroke (n = 8) or acquired brain injury (n = 2) from a rehabilitation unit at Sahlgrenska University Hospital in Sweden. Semi-structured in-depth interviews were held about perceptions and experiences of walking and physical activity in general. Data were analyzed using qualitative content analysis, with categories that were determined inductively. Physical activity in general and walking ability more specifically were considered very important by the participants. However, physical activity was, regardless of exercising habits pre-injury, associated with different kinds of negative feelings and experiences. Commonly reported internal barriers in the current study were; fatigue, fear of falling or getting hurt in traffic, lack of motivation and depression. Reported external barriers were mostly related to walking, for example; bad weather, uneven ground, lack of company or noisy or too busy surroundings. Persons with stroke or acquired brain injury found it difficult to engage in and sustain an eligible level of physical activity. Understanding individual concerns about motivators and barriers surrounding physical activity may facilitate the work of forming tailor-made rehabilitation for these groups, so that the levels of physical activity and walking can increase.