Bodies in sequestered and non-sequestered aquatic environments: a comparative taphonomic study using decompositional scoring system.
The study of decomposition by using accumulated degree days (ADDs) has been suggested not only in terrestrial decay but also for water-related deaths. Previous studies have demonstrated that the accumulation of thermal energy as a function of the post-mortem submersion interval (PMSI) can be derived from a descriptive decompositional scoring system (DSS). In order to verify how useful can the total aquatic decomposition score (TADS) for ADD prediction be, a comparative taphonomic study has been performed between two series of bodies: 16 corpses found floating in shallower waters with a presumptive PMSI from 3 to 118 days and exposed to water temperatures (Tw) between 10.5 and 20.3 °C approximately equating from a minimum of 46 to 1.392 ADD; 52 bodies, all victims of a single shipwreck, found in sequestered environments and subjected to constant Tw of 4 °C for 210 days approximately equating to 840 ADD. The two series of bodies have revealed different stages of decay and a large DSS variability. In most of bodies, freshly formed adipocere was able to delay the appearance of later decompositional stages explaining why most of the bodies were in relatively good condition. Although promising, the accuracy of the TADS model can be affected by adipocere and animal activity. The TADS model suffers of the same limitations for ADD calculations as they can give a false perception of accuracy due to the complexity of integrating all changing factors affecting human decay in sequestered and non-sequestered marine environments (currents, animal activity, water temperatures, depth of submersion).


Standard diagnostics with and without urine-based lipoarabinomannan testing for tuberculosis disease in HIV-infected patients in a high-burden setting-A cost-effectiveness analysis.
Recent clinical findings reported the reduced mortality associated with treatment guided by sputum-based molecular test with urine-based lipoarabinomannan (LAM) assay for tuberculosis (TB) disease in HIV-infected individuals. We aimed to evaluate the cost-effectiveness of sputum-based Xpert tests with and without urine-based LAM assays among HIV-infected individuals with signs and symptoms of TB disease (TBD) from the perspective of South African healthcare providers. A one-year decision-analytic model was constructed to simulate TB-related outcomes of 7 strategies: Sputum smear microscope (SSM), Xpert, Xpert Ultra, Xpert with AlereLAM, Xpert Ultra with AlereLAM, Xpert with FujiLAM, and Xpert Ultra with FujiLAM, in a hypothetical cohort of adult HIV-infected individuals with signs and symptoms of TB. The model outcomes were TB-related direct medical cost, mortality, early treatment, disability-adjusted life-years (DALYs) and incremental cost per DALY averted (ICER). The model inputs were retrieved from literature and public data. Base-case analysis and sensitivity analysis were conducted. In the base-case analysis, the Xpert Ultra with FujiLAM strategy showed the highest incidence of early treatment (267.7 per 1000 tested) and lowest mortality (29.0 per 1000 tested), with ICER = 676.9 USD/DALY averted. Probabilistic sensitivity analysis of 10,000 Monte Carlo simulations showed the cost-effective probability of Xpert Ultra with FujiLAM was the highest of all 7 strategies at the willingness-to-pay (WTP) threshold >202USD/DALY averted. Standard sputum-based TB diagnostic Xpert Ultra with urine-based FujiLAM for TBD testing in HIV-infected individuals appears to be the preferred cost-effective strategy from the perspective of the health service provider of South Africa.


An unusual case of dengue fever in aneurysmal subarachnoid haemorrhage: diagnosis and management nuances.
Dengue fever is highly prevalent in the Asia-Pacific region. Here we present an unusual case of dengue fever in a patient with a ruptured cerebral aneurysm causing subarachnoid (SAH) and intraventricular haemorrhage (IVH) and discuss the implications of dengue-related thrombopathies on the management of SAH and its complications. A 56-year-old female with a two-day history of high-grade pyrexia and myalgia presented with sudden-onset drowsiness (presenting Glasgow Coma Scale, GCS: E1V1M4). Imaging revealed extensive SAH and IVH due to a ruptured right middle cerebral artery (MCA) aneurysm, with extensive vasospasm. Blood test revealed thrombocytopenia and a positive NS-1 antigen. She subsequently suffered from two episodes of re-rupture of the aneurysm and elevated intracranial pressure which required a decompressive craniectomy in addition to coilingof the MCA aneurysm. Cerebral perfusion and rheology were maintained with the triple-H therapy. Her GCS improved to E4V1M6, but remained aphasic. Thrombocytopenia and deranged platelet functions in dengue infection might affect the stability of clot and increase the risk of re-rupture of aneurysm. Immediate securement of the aneurysm was paramount. In cases of severe dengue, plasma leakage could lead to intravascular depletion, and coupled with haemoconcentration and hypotension would further increase the risk for vasospasm.


Genetic variation in the base excision repair pathway and bladder cancer risk.
Genetic polymorphisms in DNA repair genes may impact individual variation in DNA repair capacity and alter cancer risk. In order to examine the association of common genetic variation in the base-excision repair (BER) pathway with bladder cancer risk, we analyzed 43 single nucleotide polymorphisms (SNPs) in 12 BER genes (OGG1, MUTYH, APEX1, PARP1, PARP3, PARP4, XRCC1, POLB, POLD1, PCNA, LIG1, and LIG3). Using genotype data from 1,150 cases of urinary bladder transitional cell carcinomas and 1,149 controls from the Spanish Bladder Cancer Study we estimated odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for age, gender, region and smoking status. SNPs in three genes showed significant associations with bladder cancer risk: the 8-oxoG DNA glycosylase gene (OGG1), the Poly (ADP-ribose) polymerase family member 1 (PARP1) and the major gap filling polymerase-beta (POLB). Subjects who were heterozygous or homozygous variant for an OGG1 SNP in the promoter region (rs125701) had significantly decreased bladder cancer risk compared to common homozygous: OR (95%CI) 0.78 (0.63-0.96). Heterozygous or homozygous individuals for the functional SNP PARP1 rs1136410 (V762A) or for the intronic SNP POLB rs3136717 were at increased risk compared to those homozygous for the common alleles: 1.24 (1.02-1.51) and 1.30 (1.04-1.62), respectively. In summary, data from this large case-control study suggested bladder cancer risk associations with selected BER SNPs, which need to be confirmed in other study populations.


Comparison of the Easy Strutter Functional Orthosis System and axillary crutches during modified 3-point gait.
The Easy Strutter Functional Orthosis System (ESFOS) was designed to improve assistive device ambulatory efficiency. This crossover design study compared the ESFOS to axillary crutches during modified 3-point gait. Thirty-eight subjects (40-65 years of age) at > 1 year after unilateral total knee or hip replacement participated in this study. Heart rate, mean peak palmar and plantar force magnitude, and onset timing were monitored during self-directed pace ambulation. Between trials, subjects responded to questions on perceived exertion, stability/security, and comfort. One-way analyses of variance were used to evaluate condition differences for ratio or interval data (p < or = 0.01). Statistically significant differences were noted for mean peak palmar forces (reduced 45% and delayed 31%), mean peak plantar force onsets (delayed 30%), and energy expenditure index (EEI) (reduced 25%). Wilcoxon signed rank tests were used to evaluate condition differences for ordinal data. Subjects preferred the ESFOS to axillary crutches for comfort and security/stability on flat surfaces and stairs (p < or = 0.001). Results suggest greater ambulatory gait efficiency during ESFOS use. Further study is indicated with other patient populations.


Antibiotic consumption and resistance of gram-negative pathogens (collateral damage).
Antibiotics are commonly prescribed in community and hospital care. Overuse and misuse favors emergence and spread of resistant bacteria. The ATC/DDD methodology is commonly used for presenting the drug utilization data. In primary care, the consumption is usually expressed in DDD per 1,000 inhabitants per day, in hospital, preferably in DDD per 100 bed days and DDD per 100 admissions. The alternative metric is days of therapy (DOT), which needs IT support. Antibiotics have ecological adverse effects at individual and population level. Antibiotics select resistant bacteria among pathogens and normal flora. Broad-spectrum antibiotics, low dosage and prolonged antibiotic therapy favor the development of resistance. Although total use of antibiotics in hospital is much less than in the community, the intensity of use magnified by cross infection ensures a multitude of resistant bacteria in today's hospitals. Reversal of resistance is complex and might persist for many years despite the introduction of antimicrobial containment and stewardship programs.


Gastrointestinal Bleed from Erosive Gastritis and Duodenitis: A Sentinel Event of Invasive Lobular Carcinoma of the Breast and a Diagnostic Dilemma.
Metastasis from breast cancer to the gastrointestinal (GI) tract is uncommon, and such events presenting as GI bleeding are exceedingly rare. In some individuals, the absence of classical findings of primary breast cancer coupled with the non-specific nature of GI symptoms may make early detection and diagnosis challenging. Our patient is a 75-year-old female who presented with symptomatic anemia manifesting as progressive dizziness, weakness, and early satiety that developed eight days after right knee arthroplasty. She had a remote history of acid reflux disease and reported regular use of non-steroidal anti-inflammatory drugs (NSAIDs). Physical examination was notable for pallor and tachycardia; the cardiopulmonary examination was otherwise unremarkable and the abdominal examination was normal. A fecal occult blood test was positive. Subsequent esophagogastroduodenoscopy demonstrated significant erosive gastritis and duodenitis that was initially attributed to the patient's NSAID use. However, biopsy showed signet ring carcinoma. No gastric primary tumor was identified on work up. Extensive evaluation ultimately revealed invasive lobular carcinoma of the breast. Notably, no primary breast lesion had been detected on physical examination or breast mammography or magnetic resonance imaging (MRI). Therapy for invasive lobular carcinoma of the breast is substantially different from gastric carcinoma and thus it is important to accurately diagnose the condition early in its course to optimize patient outcomes.


Uptake of oral fluid-based HIV self-testing among men who have sex with men and transgender women in Thailand.
Suboptimal uptake of HIV testing remains a primary bottleneck to HIV prevention and treatment for men who have sex with men (MSM) and transgender women (TGW) in Thailand. The World Health Organization has recommended HIV self-testing (HIVST) as an additional strategic HIV service. However, HIVST has not been fully endorsed and implemented in many countries in Southeast Asia. The aim of this study was to assess the uptake of oral fluid-based HIVST in MSM and TGW populations in Thailand. During 2017 and 2018, we conducted a cross-sectional study using convenience sampling to enroll 2,524 participants from three major urban areas. Participants were recruited during outreach and online activities and were offered unassisted or assisted HIVST, or referral to HIV testing services. A descriptive analysis was performed for summarizing data. A total of 2,502 participants (1,422 MSM and 1,082 TGW) were included in the analysis with about one-third (36.1%) of them being first-time testers. Among all participants enrolled in the study, a total of 2,486 participants (99.3%) selected HIVST versus referral to HIV testing services. Of those who selected HIVST, 2,095 (84.3%) opted for assisted HIVST while the rest opted for unassisted HIVST: 1,148 of 1,411 MSM (81.4%) and 947 of 1,075 TGW (88.1%) selected assisted HIVST. While no serious adverse events were reported during the study, we found that among 179 participants who needed a confirmatory test and were referred to HIV testing services, 108 (60.3.4%) accessed these later services. This study demonstrated a high uptake of oral fluid-based HIVST among MSM and TGW populations in Thailand and that HIVST could be scaled up through the national epidemic control program. However, a better understanding of HIV testing-seeking behavior and innovative follow-up solutions are needed to improve and monitor linkages to services for people who undertake HIVST.


[Intractable vasculitis syndromes--incidence and epidemiology].
Incidence and epidemiology of various diseases related to vasculitis were mainly reviewed from recent studies carried out in the Research Committee of Intractable Vasculitis Syndrome supported by the Ministry of Health and Welfare of Japan. A relative higher proportion of patients with aortitis syndrome (Takayasu's arteritis), Buerger's disease was reported in Asia compared to Europe and the United States. Today, the incidence of these diseases is considered to indicate a trend to decrease in Japan. However, the number of patients studied by the Committee remained almost unchanged. The patients are reported from all districts of Japan, though the incidences varied with the prefecture. The Research Committee is continuing further careful epidemiological investigations by established diagnostic criteria from year to year.


The Effectiveness of Depression Treatment for Adults with ESKD: A Systematic Review.
Adults with dialysis-dependent ESKD experience higher rates of depression than the general population, yet efficacy of depression treatments in this population is not well understood. We conducted a systematic review of the benefits and harms of depression treatment in adults with ESKD. We searched multiple data sources through June 2020 for English-language, controlled trials that compared interventions for depression in adults with ESKD to another intervention, placebo, or usual care, and reported depression treatment-related outcomes. Observational studies were included for harms. Two investigators independently screened all studies using prespecified criteria. One reviewer abstracted data on study design, interventions, implementation characteristics, and outcomes, and a second reviewer provided confirmation. Two reviewers independently assessed study quality and resolved any discords through discussion or a third reviewer. Strength of evidence (SOE) was assessed and agreed upon by review-team consensus. We qualitatively analyzed the data and present syntheses in text and tables. We included 26 RCTs and three observational studies. SSRIs were the most studied type of drug and the evidence was largely insufficient. We found moderate SOE that long-term, high-dose vitamin D3 is ineffective for reducing depression severity. Cognitive behavioral therapy is more effective than (undefined) psychotherapy and placebo for depression improvement and quality of life (low SOE), and acupressure is more effective than usual care or sham acupressure in reducing depression severity (low SOE). There is limited research evaluating treatment for depression in adults with ESKD, and existing studies may not be generalizable to adults in the United States. Studies suffer from limitations related to methodologic quality or reporting. More research replicating studies of promising interventions in US populations, with larger samples, is needed. Systematic Review registry name and registration number: PROSPERO, CRD42020140227.


Comparison of serum and urine lead levels in opium addicts with healthy control group.
Lead-contaminated opium is one of the new sources of lead exposure in our region. As far as the literature review is concerned, there are limited comparative studies about comparison of blood lead level (BLL) in addict patients with healthy controls. We aimed to compare BLL and urine lead level (ULL) between opium addicts with the healthy control group. Forty opium addict subjects (mean age: 43 ± 10 years) as the patient group and 40 healthy subjects (mean age: 41 ± 9 years) as the control group participated. Three milliliter of whole blood and urine was obtained from both groups and lead level was assessed using atomic absorption spectrophotometry. The mean value of BLL in patient group was 7.14 ± 1.41 mcg/dL and that in the healthy control group was 5.42 ± 1.46 mcg/dL. The mean value of ULL was 2.62 ± 0.83 mcg/dL in the patient group and 2.50 ± 0.76 mcg/dL in the healthy control group.BLL was different in the two groups (p < 0.001), but ULL was not (p = 0.5). There was a significant correlation between BLL with duration of opium addiction in the patient group (r = -0.403, p = 0.01). BLL and ULL were significantly correlated in controls (r = 0.436, p = 0.005) and not in patients. It was observed that the BLL in opium addicts was significantly higher than that in the healthy control group. This can be due to use of adulterated opium with lead. Therefore, screening of blood lead concentration is helpful for opium-addict patients especially with nonspecific symptoms.


The effectiveness of health communication strategies in health education in Kushima, Japan.
Japan's 2008 health policy focuses more than ever on health education for behaviour change and outcome measures for physical health status. This is at odds with contemporary health promotion and health education, which frame health as a resource for everyday life and indicate that the evaluation of interventions should measure broader aspects of health rather than just physical aspects. The application of a combination of different health communication models and theories allows for a customized approach, depending on the types of change that are being sought, and can lead to increased relevance as well as a better fit when it comes to evaluating the achievement of broad health promotion goals. This article explores the application of the Outcome Model for Health Promotion to a two-year health education intervention in Kushima, Japan. This model measures program effectiveness from four aspects: physical health outcomes; intermediate health outcomes; health promotion outcomes; and health promotion actions. A quantitative and qualitative longitudinal, mixed model study design and methods were used for the analysis. Data was taken from health exams, structured interviews, and participant observations collected from 67 participants at four times over two years. This intervention relied primarily on health education and communication to achieve mental and social health outcomes more significantly and faster than physical health outcomes. The importance of moving outcome measurement beyond direct health achievements is discussed in light of the relationships between physical, mental, and social health and its determinants, and our results.


Novel treatments and therapies in development for pancreatic cancer.
Until recently, 5-fluorouracil was the most widely used treatment for non-resectable pancreatic cancer. This treatment, however, only resulted in a median survival time of approximately 4 months. In the last few years, gemcitabine has rapidly become the new treatment benchmark, due more to its superior clinical benefit rather than to it conferring an increased median survival (approximately 5-6 months). Thus, the outlook for patients with pancreatic cancer is still relatively bleak. A number of new treatment options are presently being investigated. Some of these are combination therapies involving gemcitabine and other chemotherapeutic agents or radiation. Other novel treatment strategies are also already being evaluated in clinical studies. Some of the more promising treatments in development are discussed and evaluated in this article.


Evaluation of the quality of cardiovascular surgery care using risk stratification analysis according to the EuroSCORE additive model.
Risk stratification according to the EuroSCORE additive model of 803 consecutive patients undergoing heart and thoracic aorta surgery using cardiopulmonary bypass from August 1994 to December 2000 was performed. The population was divided into 5 clinically relevant risk categories: 0-2% risk, 3-5% risk, 6-8% risk, 9-11% risk, and 12+% risk. Observed and predicted mortalities were compared within 3 groups of patients divided by year of operation (early: August 1994 to September 1996, n=260; middle: October 1996 to September 1998, n=259; late: October 1998 to December 2000, n=284). Overall hospital mortality was 4.5%; predicted mortality was 5.3% in the early, 5.1% in the middle, and 5.4% in the late period; observed mortality was 6.5%, 3.9%, and 3.2%, respectively (p=0.0024 in early vs late). In the early period, observed mortality was lower than predicted mortality in the 0-2% and 3-5% risk categories, but higher in the other categories. Moreover, observed mortality increased markedly with the increase in predicted mortality. In the late period, observed mortality was lower than predicted mortality in all 5 risk categories. The EuroSCORE is clinically relevant index for constructing a risk stratification scoring system for Japanese cardiovascular patients as well and shows that the quality of surgical care has improved gradually over the years.


Relationship between insulin sensitivity and insulin receptor substrate-1 mutations in non-diabetic relatives of NIDDM families.
Insulin receptor substrate-1 (IRS-1) occupies a key position in the insulin-signalling pathway. Two mutations of the IRS-1 gene (Gly(972)Arg and Ala(513)Pro) have been described, although their roles in the development of insulin resistance and non-insulin-dependent diabetes mellitus (NIDDM) remain controversial. Insulin resistance has been described in non-diabetic relatives of NIDDM families, suggesting that it may be due to an inherited defect of insulin action. We therefore examined the relationships between the two mutations and insulin sensitivity in 93 non-diabetic first degree relatives from North European families with 2 or more living NIDDM subjects. Anthropometric measurements, an oral glucose tolerance test, and an insulin tolerance test to assess insulin sensitivity (K(ITT)) were performed. Basal insulin sensitivity was assessed by homeostasis model assessment (HOMA). Comparisons were made between the following relative subgroups: with (n = 9) and without (n = 84) the 972 mutation; with (n = 5) and without (n = 88) the 513 mutation; and with either one or both mutations (n = 13) or without either (n = 80). General linear model analysis was used to compare K(ITT) and HOMA between the subgroups with the anthropometric variables known to influence insulin sensitivity as covariates. There were no significant differences between the subgroups for K(ITT) and HOMA. In conclusion, the 513 and 972 mutations, alone and in combination, are not associated with decreased insulin sensitivity in non-diabetic relatives of NIDDM families.


Digital Quadrupole Isolation and Electron Capture Dissociation on an Extended Mass Range Q-TOF Provides Sequence and Structure Information on Proteins and Protein Complexes.
Electron capture dissociation (ECD) is now a well-established method for sequencing peptides and performing top-down analysis on proteins of less than 30 kDa, and there is growing interest in using this approach for studies of larger proteins and protein complexes. Although much progress on ECD has been made over the past few decades, establishing methods for obtaining informative spectra still poses a significant challenge. Here we describe how digital quadrupole (DigiQ) ion isolation can be used for the mass selection of single charge states of proteins and protein complexes prior to undergoing ECD and/or charge reduction. First, we demonstrate that the DigiQ can isolate single charge states of monomeric proteins such as ubiquitin (8.6 kDa) and charge states of large protein complexes such as pyruvate kinase (234 kDa) using a hybrid quadrupole-TOF-MS (Agilent extended m/z range 6545XT). Next, we demonstrate that fragment ions resulting from ECD can be utilized to provide information about the sequence and structure of the cytochrome c/heme complex and the ubiquitin monomer. Lastly, an especially interesting result for DigiQ isolation and electron capture (EC) was noted; namely, the 16+ charge state of the streptavidin/biotin complex reveals different electron capture patterns for the biotinylated proteoforms of streptavidin. This result is consistent with previous reports that apo streptavidin exists in multiple conformations and that biotin binding shifts the conformational dynamics of the complex (Quintyn, R. Chem. Biol. 2015, 22 (55), 583-592).


Epigenetic regulation of epithelial-mesenchymal transition by hypoxia in cancer: targets and therapy.
Intratumoral hypoxia followed by stabilization/activation of hypoxia-inducible factor 1 (HIF-1) and its downstream transcriptional factors, is one of the most important mechanisms inducing epithelial-mesenchymal transition (EMT), which has been widely accepted as a crucial step to generate early stage of tumor metastasis. Accumulating evidence suggests that epigenetic mechanisms play important roles in hypoxia-induced EMT and metastasis. These epigenetic regulations are mediated by various players including chromatin modifiers, transcriptional co-regulators, microRNAs, etc. In this review, we discuss how his tone-modifying enzymes and transcriptional co-regulators regulate EMT under hypoxic conditions. Developed or potential anticancer agents targeting epigenetic molecules regulating hypoxia-induced EMT are also discussed.


SNPs in bone-related miRNAs are associated with the osteoporotic phenotype.
Biogenesis and function of microRNAs can be influenced by genetic variants in the pri-miRNA sequences leading to phenotypic variability. This study aims to identify single nucleotide polymorphisms (SNPs) affecting the expression levels of bone-related mature microRNAs and thus, triggering an osteoporotic phenotype. An association analysis of SNPs located in pri-miRNA sequences with bone mineral density (BMD) was performed in the OSTEOMED2 cohort (n = 2183). Functional studies were performed for assessing the role of BMD-associated miRNAs in bone cells. Two SNPs, rs6430498 in the miR-3679 and rs12512664 in the miR-4274, were significantly associated with femoral neck BMD. Further, we measured these BMD-associated microRNAs in trabecular bone from osteoporotic hip fractures comparing to non-osteoporotic bone by qPCR. Both microRNAs were found overexpressed in fractured bone. Increased matrix mineralization was observed after miR-3679-3p inhibition in human osteoblastic cells. Finally, genotypes of rs6430498 and rs12512664 were correlated with expression levels of miR-3679 and miR-4274, respectively, in osteoblasts. In both cases, the allele that generated higher microRNA expression levels was associated with lower BMD values. In conclusion, two osteoblast-expressed microRNAs, miR-3679 and miR-4274, were associated with BMD; their overexpression could contribute to the osteoporotic phenotype. These findings open new areas for the study of bone disorders.


School-based prevention of depressive symptoms in adolescents: a 6-month follow-up.
Depressive disorders in adolescents are a widespread problem with extensive psychosocial consequences. The authors designed a school-based program to prevent the increase in depressive symptoms. The authors expect the program to reduce dysfunctional automatic thoughts and improve social skills and thus prevent the increase in depressive symptoms. The design includes a training group and a nontreatment control group with pre- and post-measurement and 3- and 6-month follow-up. The authors followed up 324 eighth graders in both groups. School classes were randomly assigned to one of the two groups. The prevention program, LISA-T, is based on cognitive-behavioral therapy concepts and targets of cognitive and social aspects. It comprises 10 meetings of 1.5 hours in a regular school setting. Increases in depressive symptoms in nondepressed adolescents in the training group were prevented over a 6-month period. Furthermore, adolescents with subsyndromal depression in the training group reported fewer symptoms, whereas depressive symptoms within the control group did not change. However, the groups did not differ with regard to social skills, frequency of negative automatic thoughts, and depressive symptoms before the prevention program. LISA-T is an effective school-based prevention program for eighth graders with minimal to mild depressive symptoms, but further research is needed.


Adhesion characteristics of lactobacillus is a criterion of the probiotic choice.
A sampling of lactobacilli from the German National Collection of Microorganisms and L. fermentum 90 TS-4 (21) reference strain clone 3 (Russian Federation) were studied. The results indicate that the receptors on the surface of lactobacillus strains from the German collection had no structures complementary to type 1 fimbriae, though adhesins of some of them reacted with mannose and galactose receptors. Adhesion on a monolayer of continuous cell cultures showed that adhesion activity of lactobacilli was a function of many derivatives, and hence, the choice of a model for evaluation of the adhesion characteristics of the strain should be based on adhesins exhibiting universal properties in different test systems. One of them can be lectin-binding adhesin; its expression on the surface of cultures of lactobacilli from the German collection varies within the same range as was shown previously for lactobacilli, studied by the same criterion. The molecular weight of lectin-binding adhesin is 25-30 kDa, and the corresponding receptors are frequently present on various eukaryotic cells, and hence, cell models can be considered as the most adequate for studies of the competitive interactions between lactobacilli and adhesins of pathogenic microorganisms.


Effect of denaturants and stabilisers on protein adsorption at solid-liquid interfaces.
The adsorption isotherms of different proteins from aqueous solution to the surface of different solids have been compared in the presence of additives such as urea, surfactants and high concentration of various neutral salts. The adsorption isotherms of lysozyme on alumina are not affected much in the presence of 8 M urea showing the rigid structure of lysozyme whereas isotherms of hemoglobin show surface coagulation even in presence of 2 M urea. In presence of 8 M urea, adsorption isotherms of BSA on alumina show two distinct steps. The extent of protein adsorption in the presence of surfactants depends on the nature of surfactants as well as of the underlying surface. The adsorption isotherms of BSA and lysozyme in presence of 2 M concentration of different neutral salts have also been compared with each other. In the presence of denaturants such as NaI and LiCl, the proteins are adsorbed in unfolded beta-conformation whereas in the presence of protein stabilizers such as NaCl, KCl and Na2SO4, amount of protein adsorbed at saturation is zero or extremely small showing that unfolding of proteins at the interface is necessary for initial stage of protein adsorption. The standard free energy change (delta G degrees) per square meter of the surface, signifying relative affinity of adsorption at the state of monolayer saturation, have been calculated. The magnitude of standard free energy of transfer (delta G degrees B) of one mole of protein to the surface in presence of all the additives was found close to 40 kJ/mole.


Stiffening colloidal gels by solid inclusions.
The elastic properties of a soft matter material can be greatly altered by the presence of solid inclusions whose microscopic properties, such as their size and interactions, can have a dramatic effect. In order to shed light on these effects we use extensive rheology computer simulations to investigate colloidal gels with solid inclusions of different sizes. We show that the elastic properties vary in a highly non-trivial way as a consequence of the interactions between the gel backbone and the inclusions. In particular, we show that the key aspects are the presence of the gel backbone and its mechanical alteration originating from the inclusions. To confirm our observations and their generality, we performed experiments on an emulsion that presents strong analogies with colloidal gels and confirms the trends observed in the simulations.


Serum levels of phytoestrogens as biomarkers of intake in Mexican women.
Phytoestrogens have generated interest in human health in view of their potential effect to reduce the risk of developing chronic diseases. Serum levels of phytoestrogens have been proposed as an alternative to measure the exposure of phytoestrogens. We evaluated the use of serum as a biomarker of phytoestrogen's intake in healthy women. Phytoestrogens in serum (luteolin, kaempferol, equol, biochanin A, formononetin, quercetin, naringenin, coumestrol, secoisolariciresinol, genistein, matairesinol, enterolactone, enterodiol, daidzein, glycitein and resveratrol) were analyzed by HPLC-ESI-MS. Subjects were asked to recall all foods and beverages consumed the previous 24 h. Association of dietary intake and serum concentrations was performed by Spearman correlation. Correlations were found for naringenin (r = 0.47, p < 0.001), luteolin (r = 0.4 p < 0.001), genistein (r = 0.32, p < 0.01) enterolactone (r = 0.35, p = 0.0553), coumestrol (r = 0.26, p = 0.0835) and resveratrol (r = 0.29, p = 0.0517). Serum levels as biomarkers of intake along with a 24-h recall would be useful in order to investigate the relationship between phytoestrogens and health.


omega-Lsp-IA, a novel modulator of P-type Ca2+ channels.
A novel polypeptide, designated omega-Lsp-IA, which modulates P-type Ca(2+) channels, was purified from the venom of the spider Geolycosa sp. omega-Lsp-IA contains 47 amino acid residues and 4 intramolecular disulfide bridges. It belongs to a group of spider toxins affecting Ca(2+) channels and presumably forms the inhibitor cystine knot (ICK) fold. Peculiar structural features (a cluster of positively charged residues in the C-terminal loop of the peptide and a regular distribution of hydrophobic residues) that may play a decisive role in the omega-Lsp-IA mechanism of action were located. Recombinant omega-Lsp-IA was produced in prokaryotic expression system and was shown to be structurally and functionally identical to the native toxin. At saturating concentration (10nM), the peptide clearly slows down the activation kinetics and partially inhibits the amplitude of P-current in rat cerebellar Purkinje neurons. Prominent deceleration of the activation kinetics is manifested as the appearance of a five-fold slower component of the current activation. The specificity of action of omega-Lsp-IA on different Ca(2+) channel types was studied in isolated hippocampal neurons of rat. omega-Agatoxin IVA completely removed the effect of omega-Lsp-IA on the whole-cell Ca(2+) current. Therefore, omega-Lsp-IA appears to act specifically on P-type Ca(2+) channels.


High Throughput Screen Identifies the DNMT1 (DNA Methyltransferase-1) Inhibitor, 5-Azacytidine, as a Potent Inducer of PTEN (Phosphatase and Tensin Homolog): Central Role for PTEN in 5-Azacytidine Protection Against Pathological Vascular Remodeling.
Our recent work demonstrates that PTEN (phosphatase and tensin homolog) is an important regulator of smooth muscle cell (SMC) phenotype. SMC-specific PTEN deletion promotes spontaneous vascular remodeling and PTEN loss correlates with increased atherosclerotic lesion severity in human coronary arteries. In mice, PTEN overexpression reduces plaque area and preserves SMC contractile protein expression in atherosclerosis and blunts Ang II (angiotensin II)-induced pathological vascular remodeling, suggesting that pharmacological PTEN upregulation could be a novel therapeutic approach to treat vascular disease. Approach and Results: To identify novel PTEN activators, we conducted a high-throughput screen using a fluorescence based PTEN promoter-reporter assay. After screening ≈3400 compounds, 11 hit compounds were chosen based on level of activity and mechanism of action. Following in vitro confirmation, we focused on 5-azacytidine, a DNMT1 (DNA methyltransferase-1) inhibitor, for further analysis. In addition to PTEN upregulation, 5-azacytidine treatment increased expression of genes associated with a differentiated SMC phenotype. 5-Azacytidine treatment also maintained contractile gene expression and reduced inflammatory cytokine expression after PDGF (platelet-derived growth factor) stimulation, suggesting 5-azacytidine blocks PDGF-induced SMC de-differentiation. However, these protective effects were lost in PTEN-deficient SMCs. These findings were confirmed in vivo using carotid ligation in SMC-specific PTEN knockout mice treated with 5-azacytidine. In wild type controls, 5-azacytidine reduced neointimal formation and inflammation while maintaining contractile protein expression. In contrast, 5-azacytidine was ineffective in PTEN knockout mice, indicating that the protective effects of 5-azacytidine are mediated through SMC PTEN upregulation. Our data indicates 5-azacytidine upregulates PTEN expression in SMCs, promoting maintenance of SMC differentiation and reducing pathological vascular remodeling in a PTEN-dependent manner.


Intranuclear development of asexual and sexual generations of Eimeria hermani Farr, 1953, the coccidian parasite of geese.
Both merogonic and gamogonic stages of Eimeria hermani occurred within the nucleus of epithelial cells of the intestine of experimentally infected goslings (Anser anser domesticus L.). They were located within a parasitophorous vacuole. Several developing meronts were often observed in one host nucleus and each of them had its own parasitophorous vacuole. We suppose that two generations of meronts were formed by ectomerogony from 2 to 4 days post infection (DPI). During the gamogony (4-6 DPI), we observed invagination of the host cell nucleoplasm into the parasites and we suppose that this may be connected with the process of the parasite's feeding.


Antifungal properties of an actinomycin D-producing strain, Streptomyces sp. IA1, isolated from a Saharan soil.
An actinomycete strain named IA1, which produced an antimicrobial compound, was isolated from a Saharan soil in In Amenas, Algeria. The study of the 16S rDNA sequence of this strain permitted to relate it to Streptomyces mutabilis NBRC 12800(T) (99.93% of similarity). Strain IA1 exhibited strong activity against a wide range of plant pathogenic fungi. One bioactive compound produced in large amounts (46.7 mg L(-1) day(-1) ), named YA, was isolated and purified by TLC and reverse phase HPLC. The structure elucidation of the pure substance, using combined data from UV visible, NMR spectra, and mass spectrometry, permitted to identify it as actinomycin D, and was thus found for the first time in S. mutabilis related species. The biocontrol abilities of the strain IA1 and compound YA were evaluated through two diseases, i.e., chocolate spot of field bean and Fusarium wilt of flax. The occurrence of the two fungal diseases was effectively reduced. The reduction of chocolate spot disease symptoms reached 80 and 91.7% with IA1 and YA seedlings pretreatments, respectively. Soil pretreatment with IA1 or YA also allowed to reduce Fusarium wilt disease impact by almost 60%.


Prevention of drowning by community-based intervention: implications for low- and middle- income countries.
Drowning is a serious but neglected health problem in low-and middle-income countries. To describe the effectiveness of drowning prevention program on the reduction of drowning mortality rates in rural settings at the north of Iran, and guide its replication elsewhere. This interventional design included pre- and post-intervention observations in the rural area of the Caspian Sea coastline without a comparison community. Cross-sectional data were collected at pre- and post-intervention phases. Outcome evaluation was based on a four-year period (March 2005-March 2009) utilizing drowning registry data for the north of Iran. The implementation program increased the rate of membership in an organization responsible for promoting safety in high risk areas near the Caspian Sea. Compared to a WHO standardized population, drowning incidence in rural areas of the study demonstrated a continuous decrease in age-specific drowning rate among the oldest victims with a gradual decline during the implementation. In the study area, the epidemiological aspects of the study population were exposed and contributing factors were highlighted. This study showed that the promotion of passive interventions had a greater effect on drowning rate than that of active interventions.


Telemedicine in neuro-ophthalmology.
The COVID-19 public health emergency accelerated the adoption of telemedicine in neuro-ophthalmology. This review surveys the current telemedicine landscape and discusses associated limitations and opportunities. Logistic considerations and regulatory changes related to the COVID-19 pandemic have spurred a proliferation of tele-neuro-ophthalmic practice. One significant benefit of telemedicine is increased access to the limited number of neuro-ophthalmologists in the country. Certain elements of the neuro-ophthalmic examination can be ascertained during a video visit or through the use of mobile applications. However, data quality can be limited and more direct evaluation of the fundus currently requires the implementation of imaging techniques, such as fundus photography and/or optical coherence tomography. For cases that require it, a 'hybrid' model can be adopted in which patients physically present to designated locations for testing and subsequently participate in televisit with the physician to discuss the assessment and plan. Telemedicine provides an alternate pathway for patients to access the limited resource of neuro-ophthalmic care, and it will likely persist beyond the current COVID-19 pandemic. It has some limitations currently but continued progress in technologic, legal, and reimbursement strategies will hopefully facilitate further adoption.


Ochratoxin A cytotoxicity on Madin-Darby canine kidney cells in the presence of alpha-tocopherol: Effects on cell viability and tight junctions.
Ochratoxin A (OTA) is a potent nephrotoxic fungi metabolite that affects animal and human health. At the cellular level, OTA is able to alter functions and viability by several mechanisms of action. Several strategies to counteract its toxicity have been studied. We investigated the role of α-tocopherol in counteracting OTA oxidative damage in Madin-Darby canine kidney (MDCK) cells by pre-incubating the cells for 3 hr with the antioxidant (1 nm, 10 μm) and then adding OTA (0-1.2 μg/ml) for the following 24 hr. Cell viability, lactate dehydrogenase (LDH) release, TUNEL staining and occludin and Zo1 localization by immunofluorescence were determined. Here, 1 nm α-tocopherol was shown to significantly reduce (p < .05) the cytotoxicity, LDH release and apoptotic rate induced by OTA. The presence of the antioxidant at the same concentration maintained the localization of occludin and Zo1 in the rim of the MDCK cells after the 24-hr OTA exposure. These results indicate that a low concentration of α-tocopherol could block OTA toxicity, supporting its defensive role in the cellular membrane.


A Pentanucleotide ATTTC Repeat Insertion in the Non-coding Region of DAB1, Mapping to SCA37, Causes Spinocerebellar Ataxia.
Advances in human genetics in recent years have largely been driven by next-generation sequencing (NGS); however, the discovery of disease-related gene mutations has been biased toward the exome because the large and very repetitive regions that characterize the non-coding genome remain difficult to reach by that technology. For autosomal-dominant spinocerebellar ataxias (SCAs), 28 genes have been identified, but only five SCAs originate from non-coding mutations. Over half of SCA-affected families, however, remain without a genetic diagnosis. We used genome-wide linkage analysis, NGS, and repeat analysis to identify an (ATTTC)n insertion in a polymorphic ATTTT repeat in DAB1 in chromosomal region 1p32.2 as the cause of autosomal-dominant SCA; this region has been previously linked to SCA37. The non-pathogenic and pathogenic alleles have the configurations [(ATTTT)7-400] and [(ATTTT)60-79(ATTTC)31-75(ATTTT)58-90], respectively. (ATTTC)n insertions are present on a distinct haplotype and show an inverse correlation between size and age of onset. In the DAB1-oriented strand, (ATTTC)n is located in 5' UTR introns of cerebellar-specific transcripts arising mostly during human fetal brain development from the usage of alternative promoters, but it is maintained in the adult cerebellum. Overexpression of the transfected (ATTTC)58 insertion, but not (ATTTT)n, leads to abnormal nuclear RNA accumulation. Zebrafish embryos injected with RNA of the (AUUUC)58 insertion, but not (AUUUU)n, showed lethal developmental malformations. Together, these results establish an unstable repeat insertion in DAB1 as a cause of cerebellar degeneration; on the basis of the genetic and phenotypic evidence, we propose this mutation as the molecular basis for SCA37.


Construction and application of a promoter-trapping vector with methyl parathion hydrolase gene mpd as the reporter.
A facilitative and efficient promoter-trapping vector, pUC-mpd, was constructed with the promoterless methyl parathion hydrolase gene as the reporter. This reporter gene is easily used to clone promoters with different promoting strength on selective plates. Promoter regions of the ytkA and ywoF genes with strong promoting and signal peptide functions were cloned from the Bacillus subtilis 168 genomic promoter library with this vector.


Validity and reliability of the general well-being schedule with northern plains American Indians diagnosed with type 2 diabetes mellitus.
The General Well-being Schedule is a brief indicator of subjective feelings of psychological well-being and distress. It is easy to administer, reliable, and valid, although its validity with American Indians has not been established. This study then assessed reliability, validity, and factor structure for a sample of 88 diabetic American Indians, who sought care for diabetes at an Indian Health Service hospital. Cronbach alpha was .89. A factor analysis indicated four dimensions. Adequate concurrent and divergent validity were noted in association with scores on the Beck Depression Inventory-Second Edition, the depression scale on the Symptom Checklist-90-Revised, and Family-Adaptation, Partnership, Growth, Affection, & Resolve. These results suggest that the General Well-being Schedule is a reliable and valid measure of general well-being for this population of American Indians.


The evolution of the chicken sarcomeric myosin heavy chain multigene family.
This manuscript describes the chicken sarcomeric myosin heavy chain (MyHC) multigene family and how it differs from the sarcomeric MyHC multigene families of other vertebrates. Data is discussed that suggests the chicken fast MyHC multigene family has undergone recent expansion subsequent to the divergence of avians and mammals, and has been subjected to multiple gene conversion-like events. Similar to human and rodent MyHC multigene families, the chicken multigene family contains sarcomeric MyHC genes that are differentially regulated in developing embryonic, fetal, and neonatal muscles. However, unlike mammalian genes, chicken fast MyHC genes expressed in developing muscles are also expressed in mature muscle fibers as well. The potential significance of conserved and divergent sequences with the MyHC rod domain of five fast chicken isoforms that have been cloned and sequenced is also discussed.


KHF2, a mild and selective desilylating agent for phenol t-butyldimethylsilyl (TBDMS) ethers.
TBDMS (t-BuMe2Si, t-butyldimethylsilyl) ethers of a variety of phenols have been deprotected with KHF2 in MeOH, at room temperature. Carboxylic ester and labile phenolic acetate were unaffected under these conditions. In competition reactions between TBDMS ethers of a phenol and two primary benzylic alcohols, the phenolic ether underwent cleavage whereas the alcohol ethers remained intact. From a substrate containing both a phenolic hydroxyl group and a secondary, doubly benzylic hydroxyl group protected as TBDMS ethers, the phenol was rapidly and selectively released. Cleavage of TBDMS, TBDPS, and TIPS ethers of a phenol was also compared. TBDMS and TBDPS ethers underwent cleavage at room temperature within 30 min, whereas removal of the TIPS ether required 2.5 hours. Ease of cleavage appears to be TBDMS ≈ TBDPS > TIPS. At 60 °C, TBDMS ethers of primary benzylic, allylic, and unactivated alcohols can be efficiently desilylated over a prolonged period (13-17 h). Thus, KHF2 proves to be a mild and effective reagent for the selective desilylation of phenol TBDMS ethers at room temperature.


Selecting immunohistochemical cut-off scores for novel biomarkers of progression and survival in colorectal cancer.
Cut-off scores for determining positivity of biomarkers detected by immunohistochemistry are often set arbitrarily and vary between reports. To evaluate the performance of receiver operating characteristic (ROC) curve analysis in determining clinically important cut-off scores for a novel tumour marker, the receptor for hyaluronic acid mediated motility (RHAMM), and show the reproducibility of the selected cut-off scores in 1197 mismatch-repair (MMR) proficient colorectal cancers (CRC). Immunohistochemistry for RHAMM was performed using a tissue microarray of 1197 MMR-proficient CRC. Immunoreactivity was scored using a semi-quantitative scoring method by evaluating the percentage of positive tumour cells. ROC curve analysis was performed for T stage, N stage, tumour grade, vascular invasion and survival. The score with the shortest distance from the curve to the point with both maximum sensitivity and specificity, i.e. the point (0.0, 1.0), was selected as the cut-off score leading to the greatest number of tumours correctly classified as having or not having the clinical outcome. In order to determine the reliability of the selected cut-off scores, 100 bootstrapped replications were performed to resample the data. The cut-off score for T stage, N stage, tumour grade and vascular invasion was 100% and that for survival 90%. The most frequently selected cut-off score from the 100 resamples was also 100% for T stage, N stage, tumour grade, and vascular invasion and 90% for survival. ROC curve analysis can be used as an alternative method in the selection and validation of cut-off scores for determining the clinically relevant threshold for immunohistochemical tumour positivity.


Uncovering the Uncommon: An 81-Year-Old Woman With Elevated Carcinoembryonic Antigen (CEA) but Normal Calcitonin Levels Diagnosed With Medullary Thyroid Carcinoma.
Medullary thyroid carcinoma (MTC) is a rare neuroendocrine tumor. However, non-elevated calcitonin levels have been reported in the literature. We present the case of an 81-year-old woman with chronic elevations in carcinoembryonic antigen (CEA) levels for the past 15 years, despite normal calcitonin levels, who was ultimately diagnosed with MTC. The patient had a remote history of breast cancer and presented with symptoms of unintentional weight loss, fatigue, and joint pain. A positron emission tomography (PET) scan revealed low fluorodeoxyglucose (FDG) uptake in partially calcified thyroid nodules, and fine needle aspiration cytology was consistent with medullary carcinoma. The patient underwent total thyroidectomy, with pathology revealing a pT1aN0M0 medullary thyroid microcarcinoma with negative margins. After thyroidectomy, CEA levels decreased to within the normal range, and calcitonin levels remained normal. This case highlights the importance of considering MTC in patients with unexplained chronic elevations in CEA levels, even with normal calcitonin levels.


Eruptive Xanthomas as Cutaneous Manifestation of Familial Combined Dyslipidaemia in an Eleven-year-old: A Case Report.
Xanthomas are subcutaneous lipid deposits containing macrophages loaded with cholesterol and cholesterol esters. Although quite common in adults, xanthomas in pediatric population are infrequent and when present, may represent a cutaneous manifestation of underlying lipoprotein disorders which most often are familial. We report a case of an eleven-year-old female child, with multiple eruptive xanthomas of skin since two years of age, a positive family history and deranged lipid profile consistent with possible familial hypercholesterolemia.


Understanding intermolecular interactions of large systems in ground state and excited state by using density functional based tight binding methods.
A novel energy decomposition analysis scheme, named DFTB-EDA, is proposed based on the density functional based tight-binding method (DFTB/TD-DFTB), which is a semi-empirical quantum mechanical method based on Kohn-Sham-DFT for large-scale calculations. In DFTB-EDA, the total interaction energy is divided into three terms: frozen density, polarization, and dispersion. Owing to the small cost of DFTB/TD-DFTB, DFTB-EDA is capable of analyzing intermolecular interactions in large molecular systems containing several thousand atoms with high computational efficiency. It can be used not only for ground states but also for excited states. Test calculations, involving the S66 and L7 databases, several large molecules, and non-covalent bonding complexes in their lowest excited states, demonstrate the efficiency, usefulness, and capabilities of DFTB-EDA. Finally, the limits of DFTB-EDA are pointed out.


Effects of washing, soaking and domestic cooking on cadmium, arsenic and lead bioaccessibilities in rice.
The health risk of heavy metals such as cadmium (Cd), arsenic (As) and lead (Pb) in rice can be assessed by their concentration and bioaccessibility. In this work, japonica cultivar Xinfeng 2 and indica cultivar T-You 15 were washed, soaked and cooked using three common domestic cooking methods. The present study investigated the effects of washing, soaking, normal cooking, high-pressure cooking and microwave cooking on the concentration, bioaccessibility and health risk of Cd, As and Pb in rice. Washing significantly reduced concentrations of Cd, As and Pb, and all three types of cooking reduced bioaccessibilities of these elements. No significant differences in bioaccessibility were observed among rice prepared with different cooking methods. Concentrations and bioaccessibilities of Cd, As and Pb highly affected the values of average daily dose, hazard quotient and lifetime cancer risk. High concentration and bioaccessibility cause As to pose non-carcinogenic and carcinogenic health risks to adults and children. Moreover, compared with adults, children have a high chance of exposure to non-carcinogenic and carcinogenic health risks. Washing and cooking of rice lowered the health risk by reducing Cd, As and Pb concentrations and bioaccessibilities respectively. © 2018 Society of Chemical Industry.


Retroinfusion of embryonic endothelial progenitor cells attenuates ischemia-reperfusion injury in pigs: role of phosphatidylinositol 3-kinase/AKT kinase.
Adult endothelial progenitor cells (EPCs) reduce myocardial infarct size and improve postischemic myocardial function. We have recently shown that clonal embryonic EPCs (eEPCs), derived from 7.5-day-old mice, home specifically to hypoxic areas in tumor metastasis mouse models but spare normal organs and do not form carcinomas. Here, we assessed the potential of eEPCs to limit organ dysfunction after ischemia and reperfusion in a preclinical pig model. Pigs were subjected to ischemia (60-minute left anterior descending [LAD] artery occlusion) and reperfusion (7 days). At the end of ischemia, we applied medium with or without 5 x 10(6) eEPCs by either pressure-regulated retroinfusion or intravenous transfusion. One hour after reperfusion, 99Tc-labeled eEPCs engrafted to a 6-fold higher extent in the ischemic myocardium after retroinfusion than after intravenous application. Regional myocardial function (subendocardial segment shortening [SES] at 150/min, given in percent of nonischemic circumflex region) and infarct size (TTC viability and Methylene-blue exclusion) were determined 24 hours and 7 days later. Compared with medium-treated animals, retroinfusion of eEPCs decreased infarct size (35+/-4% versus 51+/-6%) and improved regional myocardial reserve of the apical LAD region (SES 31+/-4% versus 6+/-8%), whereas intravenous application displayed a less pronounced effect (infarct size 44+/-4%; SES 12+/-3%). Retroinfusion of an equal amount of neonatal coronary endothelial cells (rat) did not affect infarct size (49+/-5%) nor regional myocardial reserve (16+/-7%). The eEPC-dependent effect was detected at 24 hours of reperfusion (infarct size 34+/-7% versus 58+/-6%) and was sensitive to Wortmannin coapplication (50+/-5%). Our findings show that eEPCs reduce ischemia-reperfusion injury in a preclinical pig model. The rapid effect (as early as 24 hours) indicates a role for enzyme-mediated cardioprotection, which involves, at least in part, the phosphatidylinositol 3-kinase/AKT pathway.


Effects of the osteopontin gene variants on milk production traits in dairy cattle.
Osteopontin (OPN) is a highly phosphorylated glycoprotein whose gene has been cloned and sequenced in different species. Several whole genome scans have identified quantitative trait loci (QTL) affecting milk production traits on bovine chromosome 6 close to the osteopontin gene (OPN) location. The presence of OPN in milk and its elevated expression in mammary gland epithelial cells together with previous QTL studies have prompted us to investigate the effects of OPN variants on milk production traits in the Holstein dairy cattle population. A single nucleotide polymorphism in intron 4 (C/T) was detected and primers were designed to amplify genomic DNA from 1362 bulls obtained from Cooperative Dairy DNA Repository and from 214 cows from the University of Wisconsin herd. For the Repository population, the C allele was associated with an increase in milk protein percentage and milk fat percentage. Correlation between milk protein percentage and milk fat percentage was about 0.57. For the University of Wisconsin herd, the estimates of the effects of allele C were in the same direction as for the Repository population, although these estimates did not reach statistical significance. Our results are consistent with other studies that showed a significant association of the microsatellite markers in the region of OPN with milk protein percentage and other correlated traits.


The effect of secretin on colonic mucin secretion rate in the dog.
A method of quantitation of mucin using chondroitin sulfate A as a standard has been modified and applied to timed mucin collections from surgically created isolated colonic fistulas in 8 dogs. 25 experiments were conducted in which the effect of secretin was tested in 5. The mucin assay is precise and showed increased colonic mucin secretin in response to secretin. This model appears suitable for pharmacologic assessment of potential drugs for augmenting colonic mucin secretin in states of impaired colonic motility.


β-Adrenergic Stimulation Induces Histone Deacetylase 5 (HDAC5) Nuclear Accumulation in Cardiomyocytes by B55α-PP2A-Mediated Dephosphorylation.
Class IIa histone deacetylase (HDAC) isoforms such as HDAC5 are critical signal-responsive repressors of maladaptive cardiomyocyte hypertrophy, through nuclear interactions with transcription factors including myocyte enhancer factor-2. β-Adrenoceptor (β-AR) stimulation, a signal of fundamental importance in regulating cardiac function, has been proposed to induce both phosphorylation-independent nuclear export and phosphorylation-dependent nuclear accumulation of cardiomyocyte HDAC5. The relative importance of phosphorylation at Ser259/Ser498 versus Ser279 in HDAC5 regulation is also controversial. We aimed to determine the impact of β-AR stimulation on the phosphorylation, localization, and function of cardiomyocyte HDAC5 and delineate underlying molecular mechanisms. A novel 3-dimensional confocal microscopy method that objectively quantifies the whole-cell nuclear/cytoplasmic distribution of green fluorescent protein tagged HDAC5 revealed the β-AR agonist isoproterenol to induce β1-AR-mediated and protein kinase A-dependent HDAC5 nuclear accumulation in adult rat cardiomyocytes, which was accompanied by dephosphorylation at Ser259/279/498. Mutation of Ser259/Ser498 to Ala promoted HDAC5 nuclear accumulation and myocyte enhancer factor-2 inhibition, whereas Ser279 ablation had no such effect and did not block isoproterenol-induced nuclear accumulation. Inhibition of the Ser/Thr phosphatase PP2A blocked isoproterenol-induced HDAC5 dephosphorylation. Co-immunoprecipitation revealed a specific interaction of HDAC5 with the PP2A targeting subunit B55α, as well as catalytic and scaffolding subunits, which increased >3-fold with isoproterenol. Knockdown of B55α in neonatal cardiomyocytes attenuated isoproterenol-induced HDAC5 dephosphorylation. β-AR stimulation induces HDAC5 nuclear accumulation in cardiomyocytes by a mechanism that is protein kinase A-dependent but requires B55α-PP2A-mediated dephosphorylation of Ser259/Ser498 rather than protein kinase A-mediated phosphorylation of Ser279.


Anti-Apoptotic and Anti-Oxidant Effects of Caffeic Acid Phenethyl Ester on Cadmium-Induced Testicular Toxicity in Rats.
Cadmium (Cd) is a serious environmental and occupational contaminant and may represent a serious health hazard to humans and other animals. Cd is reported to induce the generation of reactive oxygen species, and induces testicular damage in many species of animals. The goal of our study was to examine the anti-apoptotic and anti-oxidant effects of caffeic acid phenethyl ester (CAPE) on Cd-induced oxidative stress, apoptosis, and testicular injury in rats. A total of 40 male Wistar albino rats were divided into four groups: control, CAPE alone, Cd-treated, and Cd-treated with CAPE; each group consisted of 10 animals. To induce toxicity, Cd (1 mg/kg body weight) was dissolved in normal saline and subcutaneously injected into rats for 30 days. The rats in CAPE-treated group were given a daily dose of 10 μmol/kg body weight of CAPE by using intraperitoneal injection. This application was continued daily for a total of 30 days. To date, no examinations of the anti-apoptotic and anti-oxidant properties of CAPE on Cd-induced apoptosis, oxidative damage, and testicular injury in rat testes have been reported. CAPE-treated animals showed an improved histological appearance and serum testosterone levels in Cd-treated group. Our data indicate a significant reduction in the number of apoptotic cells in testis tissues of the Cd-treated group with CAPE treatment. Moreover, CAPE significantly suppressed lipid peroxidation, compensated deficits in the anti-oxidant defenses in testes tissue resulted from Cd administration. These findings suggest that the protective potential of CAPE in Cd toxicity might be due to its anti-oxidant and anti-apoptotic properties, which could be useful for achieving optimum effects in Cd-induced testicular injury.


Severe Graves' ophthalmopathy after retrobulbar anesthesia for cataract extraction in a patient with mild stable thyroid eye disease.
It has been hypothesized that the distinct anatomic localization of the Graves' triad may be partially explained by pressure and trauma. While there are reports of local trauma clearly contributing to the pathogenesis of pretibial myxedema, direct evidence for a similar mechanism in Graves' ophthalmopathy (GO) has been lacking. We describe a 65-year-old male patient with stable mild Graves' ophthalmopathy of 24 years' duration in whom a retrobulbar block was administered prior to cataract removal. Three weeks after the procedure, he complained of rapidly progressive bilateral diplopia. In 6 months, there was moderate exophthalmos, exposure keratitis, almost complete ophthalmoplegia, and decreasing visual acuity requiring surgical decompression. Postdecompression, inflammatory signs and vision improved but there was complete ophthalmoplegia. The eye signs remained unchanged for the next 4 months but there was exacerbation of the disease within a week of receiving radioiodine despite concomitant steroid administration. Orbital irradiation was finally administered with rapid improvement in extraocular eye muscle function. We hypothesize that local inflammatory and immune responses stimulated by trauma and/or pressure in the retrobulbar compartment, triggered the development of severe ophthalmopathy in this patient. Thyroid-stimulating immunoglobulin (TSI) levels remained markedly elevated despite the clinical improvement suggesting that the beneficial effects of radiotherapy in this case were not mediated by suppressing TSI production.


Magic-angle lasers in nanostructured moiré superlattice.
Conventional laser cavities require discontinuity of material property or disorder to localize a light field for feedback. Recently, an emerging class of materials, twisted van der Waals materials, have been explored for applications in electronics and photonics. Here we propose and develop magic-angle lasers, where the localization is realized in periodic twisted photonic graphene superlattices. We reveal that the confinement mechanism of magic-angle lasers does not rely on a full bandgap but on the mode coupling between two twisted layers of photonic graphene lattice. Without any fine-tuning in structure parameters, a simple twist can result in nanocavities with strong field confinement and a high quality factor. Furthermore, the emissions of magic-angle lasers allow direct imaging of the wavefunctions of magic-angle states. Our work provides a robust platform to construct high-quality nanocavities for nanolasers, nano light-emitting diodes, nonlinear optics and cavity quantum electrodynamics at the nanoscale.


Visual Hallucinations and the Role of Medications in Parkinson's Disease: Triggers, Pathophysiology, and Management.
Visual hallucinations, which are part of the syndrome of Parkinson's disease (PD) psychosis, affect patients' quality of life and increase the likelihood of residential aged-care placement. The association between visual hallucinations and dopaminergic and other medications that are necessary for the symptomatic management of motor and other symptoms of PD is a common clinical dilemma. While dopaminergic medications have long been associated with PD psychosis, a clear causal link has not been established, and other neurotransmitter systems, particularly noradrenaline, serotonin, and acetylcholine, are implicated and important. A diverse range of demographic and disease-related risk factors, some being modifiable, highlight the complexity of potential underlying pathophysiological processes but also broaden practical options for prevention and treatment that can be multifaceted and individualized. The investigators reviewed the clinical features and epidemiology of visual hallucinations and PD, explored the pathological evidence for dysfunction of multiple neurotransmitter systems that may be relevant to these phenomena, and addressed the potential of medications commonly used in PD to either trigger or treat these symptoms.


(Mal)Adaptive Psychological Functioning of Students Utilizing University Counseling Services.
Background: University students confront psychological difficulties that can negatively influence their academic performance. The present study aimed to assess several areas of adaptive and maladaptive psychological functioning among university students who request counseling services. Method: One hundred eighty-four young female students seeking professional psychological help (Counseling seekers) and 185 young female students who have never asked for psychological help (Non-counseling seekers) were asked to complete the Adult Self-Report (ASR) to evaluate both their internalizing and externalizing problems through DSM-oriented scales as well as their adaptive functioning. Results: ANOVA results indicated worse psychological functioning for the students who sought counseling. They reported lower score in ASR Adaptive Functioning Scales (i.e., friends, jobs, family, education), and higher scores in DSM-oriented scales (i.e., Depressive, Anxiety, Somatic, Avoidant Personality, Attention Deficit/Hyperactivity symptoms) than the students who never asked psychological help. Furthermore, discriminant analysis successfully discriminated between the two groups of students on the basis of the ASR's adaptive and DSM-oriented scales. Conclusion: The study findings could be useful to guide university counseling services in their screening activities as well as useful for clinical practice.


Do rice water weevils and rice stem borers compete when sharing a host plant?
The rice water weevil (RWW) Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae) is an invasive insect pest of rice Oryza sativa L. in China. Little is known about the interactions of this weevil with indigenous herbivores. In the present study, adult feeding and population density of the weevil, injury level of striped stem borer Chilo suppressalis (Walker) (Lepidoptera: Pyralidae) and pink stem borer Sesamia inferens (Walker) (Lepidoptera: Noctuidae) to rice, as well as growth status of their host plants were surveyed in a rice field located in Southeastern Zhejiang, China, in 2004 with the objective to discover interspecific interactions on the rice. At tillering stage, both adult feeding of the weevil and injury of the stem borers tended to occur on larger tillers (bearing 5 leaves) compared with small tillers (bearing 2~4 leaves), but the insects showed no evident competition with each other. At booting stage, the stem borers caused more withering/dead hearts and the weevil reached a higher density on the plants which had more productive tillers and larger root system; the number of weevils per tiller correlated negatively with the percentage of withering/dead hearts of plants in a hill. These observations indicate that interspecific interactions exist between the rice water weevil and the rice stem borers with negative relations occurring at booting or earlier developmental stages of rice.


Structure of a bis-amidinium derivative of hoechst 33258 complexed to dodecanucleotide d(CGCGAATTCGCG)2: the role of hydrogen bonding in minor groove drug-DNA recognition.
The crystal structure is reported of a complex between the dodecanucleotide sequence d(CGCGAATTCGCG)2and an analogue of the DNA binding drug Hoechst 33258, in which the piperazine ring has been replaced by an amidinium group and the phenol ring by a phenylamidinium group. The structure has been refined to an R factor of 19.5% at 2.2 A resolution. The drug is held in the minor groove by five strong hydrogen bonds, together with bridging water molecules at both ends. There are few other contacts with the floor of the groove, indicating a lack of isohelicity with the groove and suggesting (i) that the observed high DNA affinity of this drug is primarily due to the array of hydrogen bonds and (ii) that these more than compensate for its poor isohelicity.


Cloning of DNA fragments complementary to tobacco nitrate reductase mRNA and encoding epitopes common to the nitrate reductases from higher plants.
Messenger RNAs encoding the nitrate reductase apoenzyme from tobacco can be translated in a cell-free system. Poly(A)+ mRNA fractions from the 23-32 S area of a sucrose gradient were used to build a cDNA library in the expression vector gt11 with an efficiency of cloning of approximately 10(4) recombinants/ng mRNA. Recombinant clones were screened with a rabbit polyclonal antibody directed against the corn nitrate reductase, which cross reacts specifically with the nitrate reductases from dicotyledons. Among 240000 recombinant plaques, eight clones were isolated containing inserts of sizes ranging from 1.6 kb to 2.1 kb and sharing sequence homologies. Seven of these clones contained a common internal 1.6 kb EcoRI fragment. The identity of these clones was confirmed as follows. A fusion protein of 170 kDa inducible by IPTG and recognized by the rabbit nitrate reductase antibody was expressed by a lysogen derived from one of the recombinants. The antibodies binding the fused protein were eluted and shown to be inhibitory to the catalytic activity of tobacco nitrate reductase. Two monoclonal antibodies directed against nitrate reductase were also able to bind the hybrid protein. The 1.6 kb EcoRI fragment was sequenced by the method of Sanger. The open reading frame corresponding to a translational fusion with the -galactosidase coding sequence of the vector shared strong homology at the amino acid level with the heme-binding domain of proteins of the cytochrome b5 superfamily and with human erythrocyte cytochrome b5 reductase. When the 1.6 kb EcoRI fragment was used as a probe for Northern blot experiments a signal corresponding to a 3.5 kb RNA was detected in tobacco and in Nicotiana plumbaginifolia mRNA preparations but no cross-hybridization with corn mRNAs was detected. The probe hybridized with low copy number sequences in genomic blots of tobacco DNA.


Fulminant pneumatosis intestinalis in a patient with diabetes mellitus and minimal change nephrotic syndrome.
We report a case of pneumatosis intestinalis in a diabetic patient with minimal change nephrotic syndrome, receiving immunosuppressive drugs and an alpha-glucosidase inhibitor. The patient was a 72-year-old female, who suffered from right lower abdominal pain. Abdominal CT showed massive air in the intestinal wall, compatible with pneumatosis intestinalis. Her general condition rapidly deteriorated with systemic inflammatory response syndrome. The patient had received respiratory support for a week, along with antimicrobial therapy and continuous hemofiltration, and then recovered. Even though pneumatosis intestinalis is generally recognized as a mild disease, careful attention is necessary when it follows a serious condition.


Inhibition of Shigella sonnei and Shigella flexneri in Hummus Using Citric Acid and Garlic Extract.
Hummus (chickpea dip) is a ready-to-eat product that may pose a significant risk to human if pathogens are present. Several organisms including Shigella spp. have been isolated from hummus. However, studies on the survival and inhibition of Shigella spp. in food are scarce. This study investigated the growth pattern of Sh. sonnei and Sh. flexneri in hummus at different temperatures (4, 10, and 24 °C). Additionally, the inhibitory activity of different concentrations of citric acid (CA) (0.5%, 1.0%, and 2.0%) and garlic extract (GE) (1.0%, 2.0%, and 3.0%) against Sh. sonnei and Sh. flexneri inoculated into hummus and stored at 4 and 10 °C was investigated. Both Shigella spp. survived well at 4 °C, while both grew to >7.0 log10 after 4 d at 10 °C or 1 d at 24 °C. At 4 °C, CA at 0.5% and 1.0% resulted in a slight reduction in the count (approximately 1.0 log10 ); a complete elimination of Sh. sonnei was attained by using 2.0% CA. However, approximately 3.0 log10 reduction in Sh. sonnei was obtained at 10 °C. For Sh. flexneri, CA at 0.5% and 1.0% resulted in a bacteriostatic inhibition. GE at 1.0% and 2.0% resulted in approximately 1.0 to 2.0 log10 reduction in Sh. sonnei count at 4 °C, while at 3.0% GE, approximately 4.0 and 3.0 log10 reductions were obtained at 4 and 10 °C, respectively. In comparison, the 2.0% and 3.0% GE resulted in a bacteriostatic effect against Sh. flexneri at 4 and 10 °C.


Hydrodynamics with triangle anomalies.
We consider the hydrodynamic regime of theories with quantum anomalies for global currents. We show that a hitherto discarded term in the conserved current is not only allowed by symmetries, but is in fact required by triangle anomalies and the second law of thermodynamics. This term leads to a number of new effects, one of which is chiral separation in a rotating fluid at nonzero chemical potential. The new kinetic coefficients can be expressed, in a unique fashion, through the anomaly coefficients and the equation of state. We briefly discuss the relevance of this new hydrodynamic term for physical situations, including heavy-ion collisions.


Spin-polarized electron tunneling in bcc FeCo/MgO/FeCo(001) magnetic tunnel junctions.
In combining spin- and symmetry-resolved photoemission, magnetotransport measurements and ab initio calculations we detangled the electronic states involved in the electronic transport in Fe(1-x)Co(x)(001)/MgO/Fe(1-x)Co(x)(001) magnetic tunnel junctions. Contrary to previous theoretical predictions, we observe a large reduction in TMR (from 530 to 200% at 20 K) for Co content above 25 atomic% as well as anomalies in the conductance curves. We demonstrate that these unexpected behaviors originate from a minority spin state with Δ(1) symmetry that exists below the Fermi level for high Co concentration. Using angle-resolved photoemission, this state is shown to be a two-dimensional state that occurs at both Fe(1-x)Co(x)(001) free surface, and more importantly at the interface with MgO. The combination of this interface state with the peculiar density of empty states due to chemical disorder allows us to describe in details the complex conduction behavior in this system.


[Establishment of pelvic nerve denervation modal in mice].
To establishment and verify pelvic nerve denervation (PND) model in mice. (1) Establishment of models. Seventy-two healthy male SPE class C57 mice with age of 7 weeks and body weight of (25±1) g were chosen. These 72 mice were randomly divided into PND group containing 36 mice and sham operation group containing 36 mice. Referring to the establishment method of PND rats, after anesthesia, a laparotomy was performed on the mouse with an abdominal median incision. Under the dissection microscope, the pelvic nerves behind and after each sides of the prostate gland were bluntly separated with cotton swabs and cut with a dissecting scissor. After the operation, the urination of mice was assisted twice every day. For the mice of sham operation group, the pelvic nerves were only exposed without cutting. (2) Detection of models. Colonic transit test was performed in 18 mice chosen randomly from each group to detect the colonic transit ratio (colored colon by methylene blue/ whole colon) and visceral sensitivity tests was performed in the rest mice to observe and record the changes of electromyogram. Three mice died of colonic transit test in each group. Uroschesis occurred in all the mice of PND group and needed bladder massage to assist the urination. Colonic transit test showed that the colonic transit ratios of sham operation group at postoperative day (POD) 1, 3 and 7 were (0.4950±0.3858)%, (0.6386±0.1293)% and (0.6470±0.1088)% without significant difference (F=0.3647, P=0.058), while in PND group, the colonic transit ratio at POD 7 [(0.6044±0.1768) %] was obviously higher than that both at POD 3[(0.3876±0.1364)%, P=0.022] and POD 1[(0.2542±0.0371)%, P=0.001], indicating a recovery trend of colonic transit function (F=9.143, P=0.004). Compared with the sham operation group, the colonic transit function in PND group decreased significantly at POD 1 and POD 3(both P<0.05), and at POD 7, there was no significant difference between two groups. Visceral sensitivity test showed that the visceral sensitivity of sham operation group at POD 1, 3 and 7 was 24.2808±9.5566, 33.6725±7.9548 and 43.9086±12.1875 with significant difference (F=5.722, P=0.014). The visceral sensitivity of PND group at POD 1, 3 and 7 was 11.7609±2.1049, 21.8415±8.1527 and 26.2310±4.2235 with significant difference as well (F=11.154, P=0.001). The visceral sensitivity at POD 3 and POD 7 was obviously higher than that at POD 1 (P=0.006, P<0.001), and there was no significant difference between POD 3 and POD 7 (P=0.183). Compared with sham operation group, the visceral sensitivity of PND group decreased significantly at POD 1, 3 and 7(all P<0.05). Denervation of pelvic nerves can obviously decrease the colonic transit function and the visceral sensitivity of mice, but these changes can recover over time, which suggests that the establishment of PND model in mice is successful.


Bacterial urinary tract infection in cyclosporine-A immunosuppressed renal transplant recipients.
Urinary tract infection and rejection in 48 renal transplant patients immunosuppressed with cyclosporine-A monotherapy were analysed. Urinary tract infection was diagnosed in 52% of the cases with Escherichia coli dominating. Urinary tract infection took a mild and relatively uncomplicated course as only one case of graft pyelonephritis caused graft nephrectomy and no influence on graft survival was observed (p greater than 0.05) in the infected cases in contrast to rejection episodes which caused a significantly reduced graft survival (p less than 0.01).


Phosphine-catalyzed allylic substitution of Morita-Baylis-Hillman acetates: synthesis of N-protected beta-aminophosphonic acid esters.
A series of N-protected beta-amino phosphonic acid esters have been prepared by phosphine-catalyzed allylic substitution of 2-(diethylphosphonyl)-substituted allylic acetates employing 4,5-dichlorophthalimide as nucleophilic partner. These organocatalytic allylic substitutions exhibit exceptionally high levels of regiospecificity by virtue of a tandem S(N)2'-S(N)2' mechanism.


Domain adaptive Sim-to-Real segmentation of oropharyngeal organs.
Video-assisted transoral tracheal intubation (TI) necessitates using an endoscope that helps the physician insert a tracheal tube into the glottis instead of the esophagus. The growing trend of robotic-assisted TI would require a medical robot to distinguish anatomical features like an experienced physician which can be imitated by utilizing supervised deep-learning techniques. However, the real datasets of oropharyngeal organs are often inaccessible due to limited open-source data and patient privacy. In this work, we propose a domain adaptive Sim-to-Real framework called IoU-Ranking Blend-ArtFlow (IRB-AF) for image segmentation of oropharyngeal organs. The framework includes an image blending strategy called IoU-Ranking Blend (IRB) and style-transfer method ArtFlow. Here, IRB alleviates the problem of poor segmentation performance caused by significant datasets domain differences, while ArtFlow is introduced to reduce the discrepancies between datasets further. A virtual oropharynx image dataset generated by the SOFA framework is used as the learning subject for semantic segmentation to deal with the limited availability of actual endoscopic images. We adapted IRB-AF with the state-of-the-art domain adaptive segmentation models. The results demonstrate the superior performance of our approach in further improving the segmentation accuracy and training stability.


[Landouzy-Dejerine syndrome. Evolution of the concept of facio-scapulo-humeral amyotrophia].
Detailed analysis of the literature and the study of personal cases have led the authors to propose a new concept for facio-scapulo-humeral dystrophy. They consider it to be a syndrome, embracing under the same clinical picture both muscular disease (classical hereditary muscular dystrophy, congenital and acquired myopathies) and neurological disease (in particular progressive pseudomyopathic amyotrophy).


Development of supported iron oxide catalyst for destruction of PCDD/F.
Studies on the development of supported iron oxide catalysts for PCDD/F decomposition using 2-monochlorophenol as a surrogate test compound are presented. Iron oxide catalysts supported on titania were prepared by two methods: impregnation and the sol-gel method. The latter preparation method resulted in better dispersion of iron oxide on the surface and the formation of gamma-Fe2O3. This is in contrast to the impregnated samples where alpha-Fe2O3 crystallites were formed. Formation of gamma-Fe2O3 resulted in improved reducibility of the active phase that favorably affected the catalytic oxidation properties of the catalyst, i.e., the light-off curves for the sol-gel samples were shifted toward lower temperature. Addition of calcium oxide to iron oxide catalyst further improved the performance of the system through stabilization and increase in the concentration of gamma-Fe2O3 in the sol-gel prepared samples. Addition of calcium oxide has a dual effect on the performance of the catalyst. First, it creates oxygen vacancies in the reduction-resistant Fe2O3 octahedral structures, thereby improving the reducibility of the active phase. Second, iron oxide can transform during decomposition of chlorinated hydrocarbons into iron chloride. Calcium oxide improved the chlorine transfer from the surface iron oxide species, thereby providing a relatively fresh surface for further catalytic oxidation. Comparison of TPR profiles with the position of light-off curves in 2-monochlorophenol decomposition led to the conclusion that Fe3O4 species are the active phase under conditions that facilitate redox cycling between Fe3+ and Fe2+ ions.


MicroRNA-433 targets AKT3 and inhibits cell proliferation and viability in breast cancer.
Breast cancer is the most frequently diagnosed malignancy in women. However, the molecular mechanisms underlying breast cancer pathogenesis are not fully understood. The present study examined the role of miR-433 in breast cancer and investigated its underlying molecular mechanisms of action. Reverse transcription-quantitative polymerase chain reaction and western blot analysis were performed to analyze the level of microRNA (miRNA/miR)/mRNA and protein expression, respectively. Additionally, MTT assay was used to determined cell proliferation and viability. Cell apoptosis was measured by flow cytometry. A dual-luciferase reporter assay was used to confirm the identity of the downstream target of miR-433. The results revealed that miR-433 was downregulated in breast cancer tissues and cell lines. Overexpression of miR-433 inhibited cell proliferation and cell viability in BT-549 cells, whereas downregulation of miR-433 increased cell proliferation and cell viability in MDA-MB-231 cells. Further flow cytometry analysis revealed that miR-433 was able to induce apoptosis and also alter the levels of proteins expression of B-cell lymphoma-2 and Bcl-associated X. Bioinformatics analysis showed that RAC-γ serine/threonine-protein kinase (AKT3) was one of the downstream targets of miR-433, and luciferase reporter assay further confirmed that AKT3 is a direct target of miR-433. The knockdown of AKT3 was able to inhibit proliferation and viability in BT-549 cells. Overexpression of AKT3 prevented the inhibitory effects of miR-433 on proliferation and viability in BT-549 cells. The level of AKT3 mRNA expression was upregulated in breast cancer tissues compared with normal tissues and was inversely correlated with miR-433 expression levels. In summary, the results of the present study results indicate that the tumor-suppressive role of miR-433 may be mediated by regulating AKT3. miR-433 may therefore serve as a potential therapeutic target for breast cancer.


Determination of electron-heated temperatures of petawatt laser-irradiated foil targets with 256 and 68 eV extreme ultraviolet imaging.
Measurements of plasma temperature at the rear surface of foil targets due to heating by hot electrons, which were produced in short pulse high intensity laser matter interactions using the 150 J, 0.5 ps Titan laser, are reported. Extreme ultraviolet (XUV) imaging at 256 and 68 eV energies is used to determine spatially resolved target rear surface temperature patterns by comparing absolute intensities to radiation hydrodynamic modeling. XUV mirrors at these two energies were absolutely calibrated at the Advanced Light Source at the Lawrence Berkeley Laboratory. Temperatures deduced from both imagers are validated against each other within the range of 75-225 eV.


Membrane localization, topology, and mutual stabilization of the rnfABC gene products in Rhodobacter capsulatus and implications for a new family of energy-coupling NADH oxidoreductases.
The rnf genes in Rhodobacter capsulatus are unique nitrogen fixation genes that encode potential membrane proteins (RnfA, RnfD, and RnfE) and potential iron-sulfur proteins (RnfB and RnfC). In this study, we first analyzed the localization and topology of the RnfA, RnfB, and RnfC proteins. By activity and immunoblot analysis of expression of translational fusions to Escherichia coli alkaline phosphatase, RnfA protein was shown to span the chromatophore membrane with its odd-numbered hydrophilic regions exposed to periplasm. By alkaline treatment of membrane fractions and following immunoblot analysis using antibodies against recombinant proteins expressed in E. coli, both RnfB and RnfC proteins were revealed to situate at the periphery of the chromatophore membranes. Second, mutual interaction of the Rnf proteins was analyzed by immunochemical determinations of RnfB and RnfC proteins in rnf mutants and their complemented derivatives. The contents in cellular fractions indicated that RnfB and RnfC stabilize each other and that the presence of RnfA is necessary for stable existence of both proteins. These results support a hypothesis that the Rnf products are subunits of a membrane complex. Finally, we detected homologs of rnf genes in Haemophilus influenzae and Vibrio alginolyticus by data base searches and in E. coli by cloning of a fragment of an rnfA homolog followed by a data base search. Close comparisons revealed that RnfC has potential binding sites for NADH and FMN which are similar to those found in proton-translocating NADH:quinone oxidoreductases and that RnfA, RnfD, and RnfE show similarity to subunits of sodium-translocating NADH:quinone oxidoreductases. We predict that the putative Rnf complex represents a novel family of energy-coupling NADH oxidoreductases.


Association of a polymorphism in the intron 7 of the SREBF1 gene with osteonecrosis of the femoral head in Koreans.
Reduction or disruption of the blood supply to the bone is involved in the pathogenesis of osteonecrosis of the femoral head (ONFH). An altered lipid metabolism is one of the major risk factors for ONFH. Sterol regulatory element binding protein, SREBF1 activates genes regulating lipid biosynthesis. The aim of this study was to examine the association between the polymorphisms of the SREBF1 gene and ONFH susceptibility in the Korean population. The SREBF1 gene in 24 unrelated Korean individuals was sequenced and two polymorphisms were detected. Two variants, IVS6 - 48 C > T and IVS7 + 117 A > G, were genotyped in 423 ONFH patients and 348 controls. The genotype frequency of IVS7 + 117 A > G in ONFH patients was significantly different from that of the control group with P value < 0.0001 (Adjusted OR; 6.88, 95% CI; 3.74-12.67). Moreover, the IVS7 + 117 A > G genotype showed an association with men, and further analysis stratified by etiological factors indicated that the genotype data was significantly associated with a high risk for patients with alcohol-induced ONFH (P < 0.0001). We found that the IVS7 + 117 A > G polymorphism of the SREBF1 gene is associated with an increased risk of ONFH in the Korean population.


Ceruloplasmin protects injured spinal cord from iron-mediated oxidative damage.
CNS injury-induced hemorrhage and tissue damage leads to excess iron, which can cause secondary degeneration. The mechanisms that handle this excess iron are not fully understood. We report that spinal cord contusion injury (SCI) in mice induces an "iron homeostatic response" that partially limits iron-catalyzed oxidative damage. We show that ceruloplasmin (Cp), a ferroxidase that oxidizes toxic ferrous iron, is important for this process. SCI in Cp-deficient mice demonstrates that Cp detoxifies and mobilizes iron and reduces secondary tissue degeneration and functional loss. Our results provide new insights into how astrocytes and macrophages handle iron after SCI. Importantly, we show that iron chelator treatment has a delayed effect in improving locomotor recovery between 3 and 6 weeks after SCI. These data reveal important aspects of the molecular control of CNS iron homeostasis after SCI and suggest that iron chelator therapy may improve functional recovery after CNS trauma and hemorrhagic stroke.


Dengue Virus Capsid Interacts with DDX3X-A Potential Mechanism for Suppression of Antiviral Functions in Dengue Infection.
Dengue virus is a pathogen of global concern and has a huge impact on public health system in low- and middle-income countries. The capsid protein of dengue virus is least conserved among related flavivirus and there is very limited information on the role of cytosolic proteins that interact with dengue virus capsid. We identified DEAD (Asp-Glu-Ala-Asp) Box Helicase 3, an X-Linked (DDX3X), cytosolic ATP-dependent RNA helicase as a dengue virus capsid-interacting protein. We show that the N-terminal region of capsid is important for interaction with DDX3X, while the N-terminal domain of DDX3X seems to be involved in interaction with dengue capsid. DDX3X was down-regulated in dengue virus infected cells at later stages of infection. Our results show that DDX3X is an antiviral protein as suppression of DDX3X expression by siRNA led to an increase in viral titers and overexpression of DDX3X led to inhibition of viral replication. Knock-down of DDX3X did not affect induction of type I interferon response upon infection suggesting that the effect of DDX3X knock-down is independent of the interferon-dependent pathways that DDX3X modulates under normal conditions. Thus, our study identifies DDX3X as a dengue virus capsid interacting protein and indicates a potential link between the antiviral functions of DDX3X and dengue capsid at later stages of dengue infection.


How Places Shape Identity: The Origins of Distinctive LBQ Identities in Four Small U.S. Cities.
Tools from the study of neighborhood effects, place distinction, and regional identity are employed in an ethnography of four small cities with growing populations of lesbian, bisexual, and queer-identified (LBQ) women to explain why orientations to sexual identity are relatively constant within each site, despite informants' within-city demographic heterogeneity, but vary substantially across the sites, despite common place-based attributes. The author introduces the concept of "sexual identity cultures"--and reveals the defining role of cities in shaping their contours. She finds that LBQ numbers and acceptance, place narratives, and newcomers' encounters with local social attributes serve as touchstones. The article looks beyond major categorical differences (e.g., urban/rural) to understand how and why identities evolve and vary and to reveal the fundamental interplay of demographic, cultural, and other city features previously thought isolatable. The findings challenge notions of identity as fixed and emphasize the degree to which self-understanding and group understanding remain collective accomplishments.


Heterogeneity and Stability in Foxp3+ Regulatory T Cells.
Foxp3+ regulatory T cells (Tregs) play an indispensable role in controlling tolerance and immunity against self- and foreign antigens. The failure of Tregs to properly function is the direct cause of systemic and chronic inflammation as well as immune suppression. It is now evident that Tregs are highly heterogeneous populations depending on the surface phenotypes, cytokine profiles, and anatomical locations. Yet, our understanding of the cellular and molecular pathways underlying such heterogeneity is very limited. Furthermore, some Tregs lose the phenotype (and suppressive functions) and instead acquire pathogenicity. Since utilizing Tregs as a tool for immunotherapy is being implemented in many clinical settings, it is of utmost importance to understand the precise mechanisms by which the loss of Treg phenotype (and function) is prevented. In this review, both cellular and molecular factors involved in Treg heterogeneity and stability are discussed.


Nurses' engagement levels in an Italian public healthcare trust: findings from a cross-sectional study.
Introduction. Assessing nursing engagement and designing strategies to improve engagement according to the specific needs of the staff have been considered essential to avoid losing nurses, mitigate future shortages and improve patients' outcomes. Objectives. To explore engagement levels of staff nurses working in an Italian public health-care trust comprising a general hospital, a rehabilitation hospital, district centers and mental health services, and their association with demographic and professional variables. Methods. The Health Care Advisory Board's Nurse Engagement Survey (NES) was used to measure 547 nurses' engagement levels. Results. Out of 499 nurses, 8% were engaged, 40% were content, 39% were ambivalent and 13% were disengaged. According to the multiple linear regression analysis which has showed R 27.3% (R2 7.5%) of the variance in the total score of NES, being older than 45 years was associated with an increased likelihood of being work-engaged (β 0.121, [Confidence of Interval] CI 95% 0.066 to 0.457); differently, having the intention to leave the unit in the next three months (β -0.168, CI 95% -0.552 to -0.179), and working at the hospital levels as compared to other settings (e.g., Mental Health Service, β -0.150, CI 95% -0.140 to -0.038) were negatively associated with the WE. Conclusions. Nursing leaders should prioritize strategies to increase Registered Nurses' engagement. Specific initiatives devoted to younger nurses and to those intending to leave the unit, as well as to those working at the hospital level, are needed given these groups have a higher likelihood to be not or poorly engaged.