Peeping at TOMs-Diverse Entry Gates to Mitochondria Provide Insights into the Evolution of Eukaryotes.
Mitochondria are essential for eukaryotic life and more than 95% of their proteins are imported as precursors from the cytosol. The targeting signals for this posttranslational import are conserved in all eukaryotes. However, this conservation does not hold true for the protein translocase of the mitochondrial outer membrane that serves as entry gate for essentially all precursor proteins. Only two of its subunits, Tom40 and Tom22, are conserved and thus likely were present in the last eukaryotic common ancestor. Tom7 is found in representatives of all supergroups except the Excavates. This suggests that it was added to the core of the translocase after the Excavates segregated from all other eukaryotes. A comparative analysis of the biochemically and functionally characterized outer membrane translocases of yeast, plants, and trypanosomes, which represent three eukaryotic supergroups, shows that the receptors that recognize the conserved import signals differ strongly between the different systems. They present a remarkable example of convergent evolution at the molecular level. The structural diversity of the functionally conserved import receptors therefore provides insight into the early evolutionary history of mitochondria.


Effects of barium graded doses on redox status, membrane bound ATPases and histomorphological aspect of the liver in adult rats.
Nowadays, liver diseases constitute a major health problem in the world. The objective of the present study was to elucidate the hepatotoxicity induced by barium chloride (BaCl2) administered at graded doses in order to evaluate redox state and membrane-bound ATPases in the liver of adult rats. Our results showed, after 21 days of treatment with barium at doses 67 150 and 300 ppm, an increase in hepatic biomarkers such as AST, ALT and GGT activities and in bilirubin and albumin levels. A significant increase in MDA, LOOHs, H2O2, AOPP and PCO levels in liver of treated rats with graded doses of BaCl2 was also observed suggesting the implication of oxidative stress with a significant relation between dose and response. Moreover, LDH activity increased in plasma and decreased in liver of all treated groups. Antioxidant activities of glutathione peroxidase and catalase decreased, especially with the highest dose of barium, indicating a failure of antioxidant system defense. Additionally, the activities of Na+K+-ATPase and Mg2+-ATPase significantly decreased in all treated groups. Our biochemical findings were supported by histological observations. These results highlight the subchronic hepatotoxicity of barium.


Prognostic factors in critically ill patients with solid tumours admitted to an oncological intensive care unit.
The mortality and prognostic factors for patients admitted to the intensive care unit (ICU) with solid tumours are unclear The aim of this study was to describe demographic, clinical and survival data and to identify factors associated with mortality in critically ill patients with solid tumours. A prospective observational cohort study of 177 critically ill patients with solid tumours admitted to a medical-surgical oncological ICU was undertaken. There were no interventions. Among the admissions, 66% were surgical, 79.7% required mechanical ventilation during their stay in the ICU and 31.6% presented with severe sepsis or septic shock. In a multivariate analysis, independent prognostic factors for in-ICU death were the need for vasopressors (OR: 22.66, 95% confidence interval: 6.09 to 82.22, P < 0.001) and the acute physiology and chronic health evaluation (APACHE) II score (OR: 1.92, 95% confidence interval: 1.43 to 2.58, P < 0.001). Cox multivariate analysis identified the length of stay in the ICU, Charlson comorbidity index score greater than 2, and the need for vasopressors as independent predictors of death after ICU discharge. The mortality rate in the ICU was 21.4%. Improved outcomes in critically ill cancer patients extended to the subgroup of patients with solid tumours. Independent prognostic factors for in-ICU death were the need for vasopressors and the APACHE IL score, while the length of stay in the ICU, Charlson comorbidity index score >2, and the need for vasopressors were independent predictors of death after ICU discharge.


Seventy Years of Asthma in Italy: Age, Period and Cohort Effects on Incidence and Remission of Self-Reported Asthma from 1940 to 2010.
It is well known that asthma prevalence has been increasing all over the world in the last decades. However, few data are available on temporal trends of incidence and remission of asthma. To evaluate the rates of asthma incidence and remission in Italy from 1940 to 2010. The subjects were randomly sampled from the general Italian population between 1991 and 2010 in the three population-based multicentre studies: ECRHS, ISAYA, and GEIRD. Individual information on the history of asthma (age at onset, age at the last attack, use of drugs for asthma control, co-presence of hay-fever) was collected on 35,495 subjects aged 20-84 and born between 1925-1989. Temporal changes in rates of asthma incidence and remission in relation to age, birth cohort and calendar period (APC) were modelled using Poisson regression and APC models. The average yearly rate of asthma incidence was 2.6/1000 (3,297 new cases among 1,263,885 person-years). The incidence rates have been linearly increasing, with a percentage increase of +3.9% (95%CI: 3.1-4.5), from 1940 up to the year 1995, when the rates begun to level off. The stabilization of asthma incidence was mainly due to a decrease in the rates of atopic asthma after 1995, while non-atopic asthma has continued to increase. The overall rate of remission was 43.2/1000person-years, and it did not vary significantly across generations, but was associated with atopy, age at asthma onset and duration of the disease. After 50 years of a continuous upward trend, the rates of asthma incidence underwent a substantial stabilization in the late 90s. Despite remarkable improvements in the treatment of asthma, the rate of remission did not change significantly in the last seventy years. Some caveats are required in interpreting our results, given that our estimates are based on self-reported events that could be affected by the recall bias.


Perceived mental health at the start of dialysis as a predictor of morbidity and mortality in patients with end-stage renal disease (CALVIDIA Study).
Health-related quality of life may affect morbidity and survival in end-stage renal disease, but it is not clear whether coexisting comorbidity and other known prognostic variables could account for such an association. To study the relationship between health-related quality of life and morbidity and survival, we carried out an inception cohort study in patients starting chronic dialysis, mostly diabetics, with a follow-up of 1-3 years in 34 Spanish hospitals. Health-related quality of life was measured by the SF-36 Health Survey and Karnofsky scale. Charlson age-comorbidity index and other prognostic clinical variables were measured concurrently. The primary outcome variable was time until death and the secondary outcome was hospitalization days. Of 318 patients enrolled (208 diabetics), with a median follow-up of 771 days, 80 died. In the unadjusted analysis, all-cause mortality was associated with lower SF-36 physical and mental component scores and Karnofsky scale. In the adjusted analysis, SF-36 mental component score predicted all-cause mortality (hazard ratio for a 10 point decrease: 1.28; 95% confidence interval: 1.05-1.56). The SF-36 mental component score also predicted more hospitalization days (adjusted risk ratio of each additional hospital day associated with every 10 point decrease: 1.25; 95% confidence interval: 1.08-1.45). Among diabetics, both the SF-36 physical and mental components predicted mortality and hospitalization days. In end-stage renal disease, perceived mental health is an independent predictor of mortality and morbidity, mainly among diabetics patients.


Amphetamine locomotor sensitization and conditioned place preference in adolescent male and female rats neonatally treated with quinpirole.
Neonatal quinpirole treatment has been shown to produce an increase in dopamine D2-like receptor sensitivity that persists throughout the subject's lifetime. The objective was to analyze the effects of neonatal quinpirole treatment on effects of amphetamine in adolescent rats using locomotor sensitization and conditioned place preference procedures. Sprague-Dawley rats were treated with quinpirole (1 mg/kg) or saline from postnatal days (P)1 to P11 and raised to adolescence. For locomotor sensitization, subjects were given amphetamine (1 mg/kg) or saline every second day from P35 to P47 and were placed into a locomotor arena. In female rats, neonatal quinpirole treatment enhanced amphetamine locomotor sensitization compared with quinpirole-free controls sensitized to amphetamine. Male rats demonstrated sensitization to amphetamine, although this was muted compared with female rats, and were unaffected by neonatal quinpirole. For conditioned place preference, subjects were conditioned for 8 consecutive days (P32-39) with amphetamine (1 mg/kg) or saline and a drug-free preference test was conducted at P40. Rats treated with neonatal quinpirole enhanced time spent in the amphetamine-paired context compared with quinpirole-free controls conditioned with amphetamine, but only female controls conditioned with amphetamine spent more time in the drug-paired context compared with saline-treated controls. Increased D₂-like receptor sensitivity appears to have enhanced the behavioral effects of amphetamine, but these effects were more prevalent in adolescent female rats compared with male rats.


Potentiation of glucose-induced insulin release in islets by desHis1[Glu9]glucagon amide.
Glucagon and secretin and some of their hybrid analogs potentiate glucose-induced release of insulin from isolated mouse pancreatic islets. It was recently shown that the synthetic glucagon analog, desHis1[Glu9]glucagon amide, does not stimulate the formation of cyclic adenosine monophosphate in the rat hepatocyte membrane, but binds well to the glucagon receptor and is a good competitive antagonist of glucagon. In the present study the effect of this analog on isolated islets was examined. desHis1-[Glu9]glucagon amide at 3 x 10(-7) M, in the presence of 0.01 M D-glucose, increased the release of insulin by 30% and maintained that level for the full 30-min test period. The rate of insulin release returned to the glucose-induced base line after removal of the peptide. The same insulin level was produced by 3 x 10(-9) M glucagon, and at 3 x 10(-7) M glucagon insulin release was enhanced 290% above the glucose base line.


Atherosclerosis and Epigenetic Modifications in Chronic Kidney Disease.
Chronic kidney disease (CKD) is one of the most common chronic diseases worldwide, with prevalence currently projected at 10% and rising. Cardiovascular disease is the leading cause of morbidity and mortality in CKD patients and is integrally linked with atherogenesis and vascular stiffness. Estimated glomerular filtration rate and the level of proteinuria are not only markers of kidney function but of cardiovascular risk, as well. Despite the efforts, CKD patients still experience excessive cardiovascular burden. MicroRNAs (miRNAs) are small (18-24 nucleotides), single-stranded non-coding RNAs that regulate gene expression by blocking messenger RNA (mRNA) translation and initiating degradation of mRNA. Studies have confirmed the imperative role of miRNA dysregulation in the pathophysiology of several diseases, including atherosclerosis and CKD. This article summarizes what is currently known about the role of miRNAs in CKD patients.


Preparation of cross-linked dimers of pancreatic ribonuclease.
The cross-linking reaction between diimido esters and ribonuclease has been studied in terms of the yield of cross-linked dimer with optimum activity toward double-stranded RNA. With dimethyl suberimidate the most satisfactory conditions were condensation for 15 min at pH 7.5-8.0 at 21 degrees C with 1.25 mol equiv of the diimido ester and a protein concentration of 6%. The dimer (yield 20%) had 19 unmodified NH2 groups out of a theoretical 20 for a molecule in which two such groups are involved in the cross-linkage; the activity toward poly(A)-poly(U) in 0.14 M salt solution by spectrophotometric assay was 8.5 times that of the monomeric enzyme toward the same substrate.


Treatment of dental anxiety disorders. Outcome related to DSM-IV diagnoses.
In this study we evaluated treatment effects in 70 consecutively admitted patients in a specialized university clinic for treatment of dental fear. Thirty-three (47%) of the patients fulfilled the diagnostic criteria for Specific Phobia alone (Dental Phobia, DP), 24 (33%) had severe dental anxiety without fulfilling the criteria for phobia (ND), and 13 (19%) fulfilled the criteria for multiple DSM-IV diagnoses (MD). Dental anxiety was measured prior to, immediately after and at follow-up (mean = 19 months) using Corah's Dental Anxiety Scale and Dental Fear Survey. Dental attitudes were measured by Getz' Dental Beliefs Survey. Dental attendance and everyday functioning were measured by self-report. DP patients received significantly more treatment-sessions as compared to the ND group. Despite significant overall reductions in scores on all psychometric instruments from pretreatment to follow up, patients in the MD group reported significantly more severe anxiety at pre- and post-treatment and at follow-up as compared to patients in the ND group. There was no interaction between diagnostic group and assessment occasion (pre treatment, post treatment and follow up) on the self-reported anxiety. Patients reported significant improvements in self-esteem, social relations and everyday functioning, regardless of diagnostic group. Sixty-three percentage of the respondents had been to the dentist within 1 year after completed treatment. Patients treated by dentists who had received supervised training in exposure treatment had significantly more often seen the dentist at follow-up.


Macrophages Derived From Human Induced Pluripotent Stem Cells Are Low-Activated "Naïve-Like" Cells Capable of Restricting Mycobacteria Growth.
In peripheral tissues, immune protection critically depends on the activity of tissue resident macrophages, which makes our understanding of the biology of these cells of great significance. Until recently, human macrophage studies were largely based on the analysis of monocyte-derived macrophages that differ from tissue resident macrophages by many characteristics. To model tissue resident macrophages, methods of generating macrophages from pluripotent stem cells have been developed. However, the immunological properties of macrophages derived from pluripotent stem cells remain under-investigated. In this study, we aimed to perform the multifarious immunological characteristics of macrophages generated from human induced pluripotent stem cells (iMϕs), including an analysis of their phenotype, secretory and antibacterial activities, as well as their comparison with macrophages derived from blood monocytes and infected lung tissue. We report that iMϕs displayed the morphology and the CD11b+CD45+CD14+ phenotype typical for mononuclear phagocytes. The cells co-expressed markers known to be associated with classically (CD80, CD86, CCR5) and alternatively (CD163 and CD206) activated macrophages, with a bias toward a higher expression of the latter. iMϕs secreted pro-inflammatory (IL-6, CXCL8, CCL2, CCL4, CXCL1, CXCL10) and anti-inflammatory (IL-10, IL-1RA, CCL22) cytokines with a high IL-10/IL-12p70 index (>20). iMϕs were phagocytic and restricted Mycobacterium tuberculosis growth in vitro by >75%. iMϕs differed from blood monocytes/macrophages by a lower expression level of HLA-DR and the CD14+CD16int phenotype and shared several phenotypic characteristics with lung macrophages. In response to LPS, iMϕs up-regulated HLA-DR and produced TNF-α. IFN-γ increased iMϕ reactivity to LPS, but did not increase iMϕ mycobactericidal capacity. The results characterize iMϕs as differentiated but low-activated/low-polarized "naïve-like" macrophages that are capable of mounting inflammatory and antibacterial responses when exposed to inflammatory stimuli or pathogens. iMϕs represent a valuable model for studying antibacterial responses of tissue resident macrophages and for developing approaches to modulating macrophage activity.


Isolation of CONSTANS as a TGA4/OBF4 interacting protein.
Members of the TGA family of basic domain/leucine zipper transcription factors regulate defense genes through physical interaction with NON-EXPRESSOR OF PR1 (NPR1). Of the seven TGA family members, TGA4/octopine synthase (ocs)-element-binding factor 4 (OBF4) is the least understood. Here we present evidence for a novel function of OBF4 as a regulator of flowering. We identified CONSTANS (CO), a positive regulator of floral induction, as an OBF4-interacting protein, in a yeast two-hybrid library screen. OBF4 interacts with the B-box region of CO. The abundance of OBF4 mRNA cycles with a 24 h rhythm under both long-day (LD) and short-day (SD) conditions, with significantly higher levels during the night than during the day. Electrophoretic mobility shift assays revealed that OBF4 binds to the promoter of the FLOWERING LOCUS T (FT) gene, a direct target of CO. We also found that, like CO and FT, an OBF4:GUS construct was prominently expressed in the vascular tissues of leaf, indicating that OBF4 can regulate FT expression through the formation of a protein complex with CO. Taken together, our results suggest that OBF4 may act as a link between defense responses and flowering.


Industrial hygiene is a viable profession.
All of the criteria selected to measure the performance of our profession are positive and collectively proclaim our profession to be very viable. Phenomenal successes have occurred during its less than a century emergence. It is especially important that the next decades of practice continue this acceleration and not level off into complacency, a period of expanded practice but, essentially, in applying the same already-established methods of practice. Such stagnation could seriously hinder our effectiveness, our technical growth in the application of our special knowledge and skills, and our outreach to newer technologies and their milieu. Should this happen, newer sciences and professionals will emerge to fill the void instead of our profession solving attendant problems. As discussed under the section on definition, our practice is extending beyond plant boundaries. Programs such as identifying asbestos and other hazardous construction material with their removal and decontamination, radon identification and control in homes, and indoor contamination problems are areas where industrial hygiene techniques and procedures are directly involved. Industrial hygienists are obviously participating in these programs, and without fanfare. Should newer areas be more formally recognized and incorporated into the definition of industrial hygiene practice, it is appropriate to ask if the term industrial hygiene is sufficiently and firmly established to identify such to public, legislative, and other bodies, or could another more suitable term be used? We should keep in mind that protecting worker health is the mainstay of our profession. Our science and supporting bodies which have brought us to our present recognition and state of excellence should remain intact both in fact and in principle.(ABSTRACT TRUNCATED AT 250 WORDS)


Short communication: analysis of health and survival in a population of Ontario Holstein heifer calves.
The objective of the present study was to investigate health and survival in heifer calves, from 16 farms in southwestern Ontario. Research technicians visited the farms on a weekly schedule for 16 mo, starting in January 2008, and collected blood samples and various measurements to determine the overall health status of the calves. Data of 1,588 Holstein heifer calves from birth until 90 to 120 d of age were analyzed. Initially, a survival analysis was carried out to determine which factors surrounding birth increased a calf's risk of mortality. The factors examined were type of birth, calving ease, season of birth, serum total protein, weight during first week of life, treatment status during first week of life, total number of treatments, and bovine respiratory disease status. In general, calves born in fall (October-December), low serum total protein, low weight, and calves treated for illness during the first week of life, increasing number of treatments, and being treated for bovine respiratory disease all increased a calf's risk of mortality. Genetic parameters for requiring treatment for illness, survival, bovine respiratory disease, other diseases, height, and weight were estimated. Heritabilities for treatment, survival, and diseases were low, ranging from 0.04 to 0.07, and were not significant. Moderate and significant heritabilities were found for height (0.33 to 0.45) and weight (0.24 to 0.44). Treatment and survival to 90 to 120 d of age were favorably correlated, indicating that calves requiring less treatment have a higher survival rate and vice versa. Further, body weight was found to have a tendency of favorable genetic correlation (-0.22 to -0.53) with treatment for diseases, indicating that calves with higher body weight in their first month of life were genetically more resistant to diseases than those with average body weight. Overall, our results show the potential of using data on calfhood disease and survival in future dairy cattle breeding programs. Further investigation and improved data collection are required to determine the full impact of genetics on health and survival in dairy heifer calves.


Immunological hyperresponsiveness in HTLV-I LTR-env-pX transgenic rats: a prototype animal model for collagen vascular and HTLV-I-related inflammatory diseases.
We have earlier reported that diverse collagen vascular diseases, including arthritis, arteritis, thrombosis, myocarditis, myositis, sialo-/dacryoadenitis and dermatitis develop with the advent of autoantibodies in transgenic rats carrying the LTR-env-pX gene of human T lymphocyte virus type I (LTR-env-pX rats). To clarify the pathogenesis of these collagen vascular diseases, immunological features of LTR-env-pX rats were examined. In LTR-env-pX rats affected with these diseases, expression of CD80/86 on both tissue-infiltrating and peripheral T cells increased, compared with findings in non-transgenic rats with experimental inflammatory diseases. CD80/86 was also upregulated on peripheral T cells in LTR-env-pX rats prior to the development of diseases. Lymphocytes from LTR-env-pX rats showed an increase in autologous proliferation and were hyperreactive against several mitogens, including concanavalin A, immobilized anti-CD3 antibodies, and superantigens in vitro. Antigen-specific immune response was also enhanced in LTR-env-pX rats. The collective evidence indicates that lymphocytes of LTR-env-pX rats constitutively express surface molecules related to T cell activation and are immunologically hyperresponsive. Bone marrow cell transfer from LTR-env-pX rats to lethally irradiated non-transgenic rats revealed that these immunologically pre-activated and hyperresponsive lymphocytes play a critical role in the pathogenesis of several collagen vascular diseases, especially of dermatitis in LTR-env-pX rats.


Disease managing capacities and mechanisms of host effects of lactic acid bacteria.
Consumption of lactic acid bacteria (LAB) has been suggested to confer health-promoting effects on the host. However, effects of LABs have been reported to be species- and strain-specific and the mechanisms involved are subjects of discussion. Here, the possible mechanisms by which LABs induce antipathogenic, gut barrier enhancing and immune modulating effects in consumers are reviewed. Specific strains for which it has been proven that health is improved by these mechanisms are discussed. However, most strains probably act via several or combinations of mechanisms depending on which effector molecules they express. Current insight is that these effector molecules are either present on the cell wall of LAB or are excreted. These molecules are reviewed as well as the ligand binding receptors in the host. Also postbiotics are discussed. Finally, we provide an overview of the efficacy of LABs in combating infections caused by Helicobacter pylori, Salmonella, Escherichia coli, Streptococcus pneumoniae, and influenza virus, in controlling gut inflammatory diseases, in managing allergic disorders, and in alleviating cancer.


[Opportunistic pulmonary infections: immunologic principles].
In patients suffering from an immunosuppressive state pneumonia is a common manifestation of infection. In these patients the radiological appearance of pneumonia is influenced by the still existing immunocompetent reaction and not by the germ itself. Basic defense mechanisms in known underlying disease, clinical condition and the influence of epidemiology on the occurrence of pneumonia are discussed briefly.


Concurrent and discriminant validity of DSM-IV symptoms of impaired control over alcohol consumption in adolescents.
Little research has examined impaired control over alcohol consumption in adolescents. This study examined the concurrent and discriminant validity of two DSM-IV dependence criteria that reflect impaired control over drinking: "using more or longer than intended" (Larger/Longer) and "persistent desire or unsuccessful efforts to quit or cut down" (Quit/Cut Down). Adolescent drinkers, ages 13-19 (N = 173), were recruited from addictions treatment (76%) and community sources (24%). A modified SCID that included assessment of alcohol craving and questionnaires measuring dependence severity, attempts to limit drinking, and impulsivity were administered. Larger/Longer had higher prevalence and an earlier onset than Quit/Cut Down, suggesting that the symptoms respectively represent milder and more severe manifestations of impaired control over drinking. Both symptoms were associated with drinking frequency, dependence severity, episodes of passing out, and an independent measure of unsuccessful attempts to limit drinking. Alcohol craving was associated with both Larger/Longer and Quit/Cut Down. Impulsivity was correlated with Larger/Longer but not Quit/Cut Down. Larger/Longer and Quit/Cut Down demonstrated adequate concurrent validity. The two symptoms were distinguished by severity and differential relations with impulsivity, suggesting that Larger/Longer and Quit/Cut Down reflect different types of impaired control over alcohol consumption. Results suggest the need for improved description and scaling of the impaired control construct in adolescents.


Studies on the preparation and controlled release of redox/pH-responsive zwitterionic nanoparticles based on poly-L-glutamic acid and cystamine.
The enhancement of tumor intracellular drug uptake and resistance against nonspecific protein adsorption are essential for an injectable anticancer drug carrier. In the present study, a new type of redox/pH-responsive zwitterionic nanoparticles (NPs) was prepared using poly-L-glutamic acid and cystamine in aqueous solutions under mild conditions. The NPs showed surface charge convertible feature in response to pH change of the solutions. The NPs demonstrated excellent anti nonspecific protein adsorption. In vitro release profiles of the NPs, they showed redox/pH dual sensitivities in vitro release. The effective intracellular delivery behaviors were verified through investigation of cell viability, and confocal laser scanning microscopy observation of HeLa cells after incubation with the DOX-loaded NPs. The NPs were non-cytotoxic and would have potential applications as a drug delivery vehicle for enhancing intracellular uptake of anticancer drugs.


Heart block following topical latanoprost treatment.
The authors report a case of second degree heart block associated with topical latanoprost treatment. The authors discuss the possibility of a causative effect as the cessation of this treatment resulted in improvement of the arrhythmia. The authors highlight previous reports and research in humans and animals which demonstrate an association of arrhythmias with prostaglandin analogues. This report draws attention to the possibility that an extremely commonly prescribed topical drug may trigger arrhythmias in susceptible individuals. It is important that prescribers are aware of this possible side-effect.


Highly Luminescent and Ultrastable CsPbBr3 Perovskite Quantum Dots Incorporated into a Silica/Alumina Monolith.
We successfully prepared QDs incorporated into a silica/alumina monolith (QDs-SAM) by a simple sol-gel reaction of an Al-Si single precursor with CsPbBr3 QDs blended in toluene solution, without adding water and catalyst. The resultant transparent monolith exhibits high photoluminescence quantum yields (PLQY) up to 90 %, and good photostability under strong illumination of blue light for 300 h. We show that the preliminary ligand exchange of didodecyl dimethyl ammonium bromide (DDAB) was very important to protect CsPbBr3 QDs from surface damages during the sol-gel reaction, which not only allowed us to maintain the original optical properties of CsPbBr3 QDs but also prevented the aggregation of QDs and made the monolith transparent. The CsPbBr3 QDs-SAM in powder form was easily mixed into the resins and applied as color-converting layer with curing on blue light-emitting diodes (LED). The material showed a high luminous efficacy of 80 lm W-1 and a narrow emission with a full width at half maximum (FWHM) of 25 nm.


Turning a Blind Eye: Public Support of Emergency Housing Policies for Sex Offenders.
In this study, we examine the influences of citizen decision making in the context of four policy scenarios that would affect the living conditions of sex offenders (SOs) residing at an "emergency shelter" budget motel. We surveyed 773 citizens in an online survey about their support for four policy scenarios that would improve the living conditions of SOs: (a) at no cost to the respondent, (b) in exchange for a US$100 tax increase, and (c) by relocating SOs within the respondent's neighborhood (i.e., "in my backyard"/IMBY scenario). The fourth scenario involved moving nearby SOs into substandard housing located far away from the respondent (i.e., "not in my backyard"/NIMBY). While prior research finds that the public overwhelmingly supports punitive SO policies, we find that indifference is a mainstay of public opinion about improving SO housing conditions. That is, we find only modest levels of average support for any of the policy scenarios, and policy support decreased when increased taxes would be involved, compared with a "no cost" scenario. While no respondent characteristics significantly predicted policy support consistently across all four scenarios, some scenarios showed stark differences in support when considering specific respondent characteristics. Overall, these results suggest that what does affect support depends on the details of the policy being proposed, as well as who is considering the policy. We end by discussing the policy implications of our study for both policymakers and the public.


Relationship between left atrial appendage peak flow velocity and nonvalvular atrial fibrillation recurrence after cryoablation.
Previous studies revealed the connection between left atrial appendage peak flow velocity (LAA-PEV) and postoperative persistent atrial fibrillation (AF) recurrence. Yet, this association is not necessarily generalizable to persistent AF patients undergoing initial cryoballoon ablation due to current gaps in the literature. We prospectively studied 74 consecutive individuals with persistent atrial fibrillation undergoing a cryoballoon ablation for the first time between January 2018 and January 2020. Before ablation, LAA-PEV was documented by transesophageal echocardiography (TEE). Subsequently, demographic information and other clinical characteristics of these participants were collected. A 96-h continuous cardiac monitor was reviewed regularly for recurrence of atrial fibrillation. Cox proportional hazards regression was used to investigate LAA-PEV as well as other clinical characteristics as a predictor of AF recurrence. Our study found that AF recurrences had lower LAA-PEV than those without AF recurrence. A nonlinear relationship between the LAA-PEV and AF recurrence was observed in this study, which had an inflection point of 34.9. Subgroup analysis of female participants showed that LAA-PEV had a positive correlation with AF recurrence [β = 0.8, 95% CI (0.7, 0.9), p < 0.05]. A low LAA-PEV is related to recurrence of atrial fibrillation and may predict AF recurrence after initial cryoballoon ablation for persistent atrial fibrillation. This finding may help improve treatment and care strategies for patients with persistent atrial fibrillation.


Using amino-cerv after cervical LEEP.
To evaluate the ability of Amino-Cerv to promote healing of the cervix following loop electrical excision procedure (LEEP) of the cervix for cervical intraepithelial neoplasia. A randomized study was conducted on 48 women in a private office setting. Patients were divided into two groups, to use or not use Amino-Cerv intravaginally for two weeks after the procedure. Statistical analysis of the findings were performed using the chi 2 test. Twenty of 24 (83%) of women using Amino-Cerv had completely healed tissue at four weeks, whereas 12 of 24 (50%) in the untreated group had healed tissue at four weeks. Findings were not statistically significant at two weeks but were statistically significant (P < .005, power = .55) at four weeks after the procedure. Amino-Cerv after LEEP of the cervix promotes healing.


Human herpesvirus 6 encephalitis followed by acute disseminated encephalomyelitis in an immunocompetent adult.
A 26-year-old, otherwise healthy man presented with visual abnormality followed by loss of consciousness and convulsion. The patient then developed headache and fever 14 days later. Brain MRI showed hyperintensities in the left cingulate cortex. The cerrebrospinal fluid examinations showed mononuclear pleocytosis and positive PCR results for human herpesvirus 6 (HHV-6). A diagnosis of HHV-6 encephalitis and symptomatic epilepsy was made. The patient's clinical symptoms improved promptly following acyclovir treatment. However, 3 months later the patient noticed dysesthesia in the trunk, the left upper limb and the right lower limb. Brain and spine MRI showed multiple brain white matter lesions, the middle cerebellar peduncle and cervical spinal lesions. The symptoms resolved following methylprednisolone pulse therapy only. We report an adult patient with HHV-6 encephalitis followed by acute disseminated encephalomyelitis whose initial presentation was epilepsy. HHV-6 encephalitis should be included in the differential diagnosis of encephalitis of unknown etiology in an immunocompetent adult.


Experimental determination of the heat of hydrogenation of phenylcyclobutadiene.
The heat of hydrogenation of phenylcyclobutadiene (DeltaH degrees (hyd) = 57.4 +/- 4.9 kcal mol(-1)) was determined via a thermodynamic cycle by carrying out gas-phase measurements on 1-phenylcyclobuten-3-yl cation. This leads to an antiaromatic destabilization energy of 27 +/- 5 kcal mol(-1), a difference of 9.6 +/- 4.9 kcal mol(-1) for the first and second C-H bond dissociation energies of 1-phenylcyclobutene, and an estimate of 96 +/- 5 kcal mol(-1) for the heat of formation of cyclobutadiene. These results are compared to G3, G3(MP2), and B3LYP computations and represent the first experimental measurements of the energy of a monocyclic cyclobutadiene.


Boolean network identification from perturbation time series data combining dynamics abstraction and logic programming.
Boolean networks (and more general logic models) are useful frameworks to study signal transduction across multiple pathways. Logic models can be learned from a prior knowledge network structure and multiplex phosphoproteomics data. However, most efficient and scalable training methods focus on the comparison of two time-points and assume that the system has reached an early steady state. In this paper, we generalize such a learning procedure to take into account the time series traces of phosphoproteomics data in order to discriminate Boolean networks according to their transient dynamics. To that end, we identify a necessary condition that must be satisfied by the dynamics of a Boolean network to be consistent with a discretized time series trace. Based on this condition, we use Answer Set Programming to compute an over-approximation of the set of Boolean networks which fit best with experimental data and provide the corresponding encodings. Combined with model-checking approaches, we end up with a global learning algorithm. Our approach is able to learn logic models with a true positive rate higher than 78% in two case studies of mammalian signaling networks; for a larger case study, our method provides optimal answers after 7min of computation. We quantified the gain in our method predictions precision compared to learning approaches based on static data. Finally, as an application, our method proposes erroneous time-points in the time series data with respect to the optimal learned logic models.


Metabotropic glutamate receptor subtypes in axon terminals of projection fibers from the main and accessory olfactory bulbs: a light and electron microscopic immunohistochemical study in the rat.
Localization of metabotropic glutamate receptor subtypes, mGluR1, mGluR1alpha, mGluR2/3, mGluR4a, mGluR5, mGluR7a, mGluR7b, and mGluR8, was examined in some of the target areas of projection fibers from the main and accessory olfactory bulbs (MOB and AOB) by using subtype-specific antibodies. The superficial layer of the olfactory tubercle and layer Ia of the piriform cortex, the target areas of MOB, showed marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-like immunoreactivities (-LI), and rather weak mGluR2/3-LI. The periamygdaloid cortical region including the target areas of both MOB and AOB showed intense mGluR2/3-LI as well as marked mGluR1-, mGluR5-, mGluR7a-, and mGluR8-LI. No significant mGluR1alpha-, mGluR4a-, or mGluR7b-LI was seen in these regions. After transection of the lateral olfactory tract, mGluR2/3-, mGluR7a-, and mGluR8-LI were reduced markedly in the target regions on the side ipsilateral to the transection; no significant changes were detected in mGluR1- or mGluR5-LI. Double labeling experiments indicated light and electron microscopically colocalization of mGluR7a- and mGluR8-LI in axon terminals on dendritic shafts of presumed interneurons in the superficial layer of the olfactory tubercle and layer Ia of the piriform cortex. Electron microscopically mGluR2/3-LI was seen in preterminal and terminal portions of axons, whereas mGluR7a- and mGluR8-LI were associated with presynaptic membrane specialization. Immunolabeled axon terminals were filled with round synaptic vesicles and constituted asymmetric synapses with dendritic profiles. The results suggest that glutamate release from axon terminals of projection fibers from MOB and AOB is regulated presynaptically and differentially through mGluR2/3, mGluR7a, and/or mGluR8.


A Seven-Gene Signature with Close Immune Correlation Was Identified for Survival Prediction of Lung Adenocarcinoma.
BACKGROUND Lung adenocarcinoma is the most life-threatening malignancy with high incidence and poor long-term survival. The crucial role of tumor immunity reveals the significance of exploring immune-related prognostic predictors in lung adenocarcinoma. MATERIAL AND METHODS Immune-related genes were screened out applying the ESTIMATE algorithm. The Cancer Genome Atlas Lung Adenocarcinoma (TCGA-LUAD) dataset was trained for the construction of Cox proportional hazard model. Univariate Cox and Lasso regression analysis was conducted to reduce the overfitting of model. Nomogram integrated the signature and clinicopathological characteristics was established for prognosis prediction of LUAD. The GSE30219, GSE41271, and GSE42127 datasets were analyzed for external validation. LUAD patients were separated into low-risk and high-risk subgroups based on the optimum cutoff threshold of calculated risk score. The predictive value of the signature was evaluated using Kaplan-Meier survival analysis, Harrell's C-index, and receiver operating characteristic (ROC) curve analysis and calibration curve. Clinical- and immune-correlation of the signature was further performed. Gene Set Enrichment Analysis (GSEA) was performed for functional exploration. RESULTS An immune-related signature containing 7 genes was identified. The signature exhibited reliable performance in the prediction of overall survival for LUAD with the C-index being 0.72. The areas under the curve (AUCs) of the model in 1-year risk prediction were 0.781, 0.797, 0.659, and 0.822 for TCGA-LUAD, GSE30219, GSE41271, and GSE42127 datasets, respectively. In all datasets, the signature proved to an independent risk factor for LUAD. Correlation analyses and GSEA further revealed the close relationship between the predictive biomarker and tumor immunity. CONCLUSIONS A Cox proportional hazard model consisting of 7 genes was identified for prognostic prediction of LUAD. The signature was highly correlated with immunity and deserves further exploration.


Windows of Opportunity for Lifestyle Interventions to Prevent Gestational Diabetes Mellitus.
Gestational diabetes mellitus (GDM) is linked with several acute maternal health risks and long-term development of type 2 diabetes, metabolic syndrome, and cardiovascular disease. Intrauterine exposure to GDM similarly increases offspring risk of early-life health complications and later disease. GDM recurrence is common, affecting 40 to 73% of women, and augments associated maternal/fetal/child health risks. Modifiable and independent risk factors for GDM include maternal excessive gestational weight gain and prepregnancy overweight and obesity. Lifestyle interventions that target diet, activity, and behavioral strategies can effectively modify body weight. Randomized clinical trials testing the effects of lifestyle interventions during pregnancy to reduce excessive gestational weight gain have generally shown mixed effects on reducing GDM incidence. Trials testing the effects of postpartum lifestyle interventions among women with a history of GDM have shown reduced incidence of diabetes and improved cardiovascular disease risk factors. However, the long-term effects of interpregnancy or prepregnancy lifestyle interventions on subsequent GDM remain unknown. Future adequately powered and well-controlled clinical trials are needed to determine the effects of lifestyle interventions to prevent GDM and identify pathways to effectively reach reproductive-aged women across all levels of society, before, during, and after pregnancy.


A facile approach to synthesize alumina nanostructures at room temperature.
Alumina nanostructures, nanowires, and semicolumn nanotubes with high aspect ratios were synthesized by the chemical etching of porous alumina membranes (PAMs) in phosphoric acid solution. The morphology and structure of alumina nanostructures were analyzed by scanning electron microscopy (SEM), energy dispersive spectrum (EDS), and X-ray diffraction (XRD), respectively. The results showed that the typical features of highly flexible nanostructures were around 20-40 nm in diameter and around 100 microm in length. EDS analysis indicated that the nanostructures were constructed by aluminum oxide. The crystalline structure of the alumina nanostructures was amorphous, which was in accordance with that of the PAMs. Furthermore, the morphology of the PAMs was characterized in detail by atomic force microscope (AFM) and SEM. On the basis of AFM and SEM observations, a possible formation mechanism of alumina nanostructures was discussed, and the inhomogeneous dissolution between the triple points and the side walls was considered to be the essential factor deciding the formation of nanostructures.


Portrait of glial scar in neurological diseases.
Fibrosis is formed after injury in most of the organs as a common and complex response that profoundly affects regeneration of damaged tissue. In central nervous system (CNS), glial scar grows as a major physical and chemical barrier against regeneration of neurons as it forms dense isolation and creates an inhibitory environment, resulting in limitation of optimal neural function and permanent deficits of human body. In neurological damages, glial scar is mainly attributed to the activation of resident astrocytes which surrounds the lesion core and walls off intact neurons. Glial cells induce the infiltration of immune cells, resulting in transient increase in extracellular matrix deposition and inflammatory factors which inhibit axonal regeneration, impede functional recovery, and may contribute to the occurrence of neurological complications. However, recent studies have underscored the importance of glial scar in neural protection and functional improvement depending on the specific insults which involves various pivotal molecules and signaling. Thus, to uncover the veil of scar formation in CNS may provide rewarding therapeutic targets to CNS diseases such as chronic neuroinflammation, brain stroke, spinal cord injury (SCI), traumatic brain injury (TBI), brain tumor, and epileptogenesis. In this article, we try to describe the new portrait of glial scar and trending of research in neurological diseases to readers.


[Reverse or inverse reaction - a present-day point].
The reversal or inversal reactions, well studied in some research centers, is still imperfectly known, even contested or denied. This lack of knowledge has been one of the hindrances in the understanding of the mechanism of the hansenic neuritis. The evolution of the concepts about this question is studied, starting with Souza Lima and Souza Campos (1950), followed by Tajiri (1955), up to the present "I reaction" of Jopling, involving the "up grading" and "down grading" reactions. An interpretation of the reactional mechanism is given, with better possibilities for the understanding of clinical aspects and for therapy.


Characterization of IL-21-expressing recombinant hepatitis B virus (HBV) as a therapeutic agent targeting persisting HBV infection.
Chronic infection by hepatitis B virus (HBV) is associated with high risks of liver fibrosis, cirrhosis and hepatocellular carcinoma. In mouse models of HBV persistence, interleukin 21 (IL-21) has been identified as a potent inducer of viral clearance. Strict hepatotropism makes recombinant HBV (rHBV) vectors ideal for liver-targeting gene delivery. Previously, we established an rHBV vector termed 5c3c, which is highly replicative by itself, but requires HBV envelope proteins provided in trans to produce virions. 5c3c-based rHBV virions are capable of delivering cargo gene expression driven by HBV Sp1 promoter into infected hepatocytes. In this work, we explore the feasibility of using 5c3c-derived rHBV for liver-specific delivery of IL-21 as treatment of chronic HBV infection. Methods: 5c3c-derived rHBV replicons harboring mouse or human IL-21 genes (termed 5c3c-mIL-21 and 5c3c-hIL-21 respectively) were constructed and then tested for the production of rHBV virions in vitro and in vivo. 5c3c-mIL-21's anti-HBV effects were determined in chronic HBV mouse model. Furthermore, superinfection by rHBV virions was analysed using HBV-infected HepG2/NTCP cells and human liver chimeric mice. Results: 5c3c-mIL-21 and 5c3c-hIL-21 were efficiently replicative and produced enveloped virions when provided with envelope proteins, both in vitro and in vivo. In mouse model of HBV persistence, IL-21 expressed from injected 5c3c-mIL-21 replicon induced complete viral clearance. 5c3c-mIL-21 and 5c3c-hIL-21 virions could infect HepG2/NTCP cells and engender sustained IL-21 expression. Most importantly, IL-21-expressing rHBV virions could superinfect HBV-infected HepG2/NTCP cells and human hepatocytes in human liver chimeric mice, and engender sustained IL-21 expression and rHBV production. Conclusion: These data suggest the high potential of 5c3c-derived IL-21-expressing rHBV as a novel therapeutic against chronic HBV infection.


Introducing Short Interpulse Intervals in High-Rate Pulse Trains Enhances Binaural Timing Sensitivity in Electric Hearing.
Common envelope-based stimulation strategies for cochlear implants (CIs) use relatively high carrier rates in order to properly encode the speech envelope. For such rates, CI listeners show poor sensitivity to interaural time differences (ITDs), which are important for horizontal-plane sound localization and spatial unmasking of speech. Based on the findings from previous studies, we predicted that ITD sensitivity can be enhanced by including pulses with short interpulse intervals (SIPIs), to a 1000-pulses-per-second (pps) reference pulse train. We measured the sensitivity of eight bilateral CI listeners to ITD while systematically varying both the rate at which SIPIs are introduced ("SIPI rate") and the time interval between the two pulses forming a SIPI ("SIPI fraction"). Results showed largely enhanced ITD sensitivity relative to the reference condition, with the size of the improvement increasing with decreasing SIPI rate and decreasing SIPI fraction. For the lowest SIPI fraction, insertion of extra pulses brought ITD sensitivity to the level measured for low-rate pulse trains with rates matching the SIPI rates. The results appear promising for the goal of enhancing ITD sensitivity with envelope-based CI strategies by inserting SIPI pulses at strategic times in speech stimuli.


The unimodal distribution of sub-threshold, ongoing activity in cortical networks.
The characterization of the subthreshold, ongoing activity in cortical neurons has been the focus of numerous studies. This activity, described as spontaneous slow waves in membrane potential, has been observed in a span of species in diverse cortical and subcortical areas. We here characterized membrane potential fluctuations in motor and the frontal association cortices cortical neurons of ketamine-xylazine anesthetized rats. We recorded from 95 neurons from a range of cortical depths to unravel the network and cellular mechanisms that shape the subthreshold ongoing spontaneous activity of these neurons. We define a unitary event that generates the subthreshold ongoing activity: giant synaptic potentials (GSPs). These events have a duration of 87 ± 50 ms and an amplitude of 19 ± 6.4 mV. They occur at a frequency of 3.7 ± 0.8 Hz and involve an increase in conductance change of 22 ± 21%. GSPs are mainly due to excitatory activity that occurs throughout all cortical layers, unaffected by the intrinsic properties of the cells. Indeed, blocking the GABAA receptors, a procedure that had a profound effect on cortical activity, did not alter these unitary events. We propose that this unitary event is composed of individual, excitatory synaptic potentials that appear at different levels of synchrony and that the level of synchrony determines the shape of the subthreshold activity.


Non-invasive Intraocular pressure monitoring with contact lens.
Glaucoma is the second leading cause of blindness in the world and the first leading cause of irreversible vision loss. Currently, the primary methodology of testing for the intraocular pressure (IOP) is during clinical office hours, which only provide a limited amount of information on the trends and fluctuations of the IOP. Therefore, a continuous monitoring system is required to properly determine the peaks of pressure and to negate any false results obtained by sparse, clinic hour testing. The objective of this study is to determine the ability of a newly designed contact lens with an embedded microchannel, to accurately measure the fluctuations in the IOP. Experimentation was completed on fresh enucleated porcine eyes. The contact lens was placed on the porcine eye and utilising a camera the fluid movement, within the microchannel in the contact lens, was recorded. A micro-pressure catheter, threaded into the centre of the vitreous chamber, recorded the true IOP and was compared with the displacement of the indicator fluid within the microchannel. The contact lenses showed a consistent linear responsiveness to changes in IOP and robust to the effects of anatomical differences among eyes. The indicator fluid had an average fluid movement of 28 um/mm Hg between all the trials. Additionally, the devices showed the ability to measure both increases and decreases in IOP during cyclical fluctuations. The described inexpensive and non-invasive sensor is able to reliably monitor the IOP changes based on porcine eye model.


[Preparation and evaluation of multidentate ligand-bonded silica chromatographic medium].
Iminodisuccinic acid (IDS), a green environment-friendly multidentate chelating agent, was used as a ligand to synthesize IDS-Silica stationary phase under the optimized conditions. The binding capacity of IDS on the stationary phase was measured by potentiometric titration. The chromatographic properties and metal chelating property on IDS-Silica column were investigated. Three standard protein mixtures were separated successfully with IDS-Silica column. The results showed that the IDS-Silica column displayed a typical cation exchange property. The binding characteristics of six different metal ions on IDS-Silica stationary phase were examined by inductively coupled plasma-atomic emission spectroscopy (ICP-AES). The results validated that the variation of binding capacities of metal ions on the stationary phase were consistent with the chelating stability order of the IDS-Silica column for metal ions. Compared with the other silica columns bonded with the three different aminocarboxyl ligands, the bonding amounts of Cu2+ on IDS-Silica column was the largest, which indicated that IDS had stronger chelating ability for metal ions. This characteristic lays the foundation for IDS as a good chromatographic packing used in the field of immobilized metal affinity chromatography (IMAC), thus probably provides an effective solution to reduce the leaking problem of metal ion from IMAC column during protein elution with one competitive agent.


Clinico-Epidemiological Patterns of Cutaneous Leishmaniasis Patients Attending the Anuradhapura Teaching Hospital, Sri Lanka.
Cutaneous leishmaniasis (CL) caused by Leishmania donovani is an endemic vector-borne disease in Sri Lanka. Over 2,500 cases have been reported since 2000 and the number of CL cases has dramatically increased annually. Total 57 clinically suspected CL patients attending the dermatology clinic in Anuradhapura Teaching Hospital were recruited from January to June 2015. Slit skin smears and skin biopsies were taken from each of the subjects. Clinical and epidemiological data were obtained using interviewer administered questionnaire. Forty-three (75.4%) patients among 57 were confirmed positive for L. donovani. The majority of infected patients was males (P=0.005), and the most affected age group was 21-40 years. Soldiers in security forces, farmers, and housewives were identified as high risk groups. The presence of scrub jungles around the residence or places of occupation (P=0.003), the presence of sandflies (P=0.021), and working outsides more than 6 hr per day (P=0.001) were significantly associated with CL. The number of lesions ranged from 1-3, and the majority (76%) of the patients had a single lesion. Upper and lower extremities were the prominent places of lesions, while the wet type of lesions were more prevalent in females (P=0.022). A nodular-ulcerative type lesion was common in both sexes. The presence of sandflies, scrub jungles, and outdoor activities contributed to spread of Leishmania parasites in an endemic pattern. Implementation of vector control programs together with health education with regard to transmission and prevention of CL are necessary to control the spread of this infection.


Additional information obtained from mucosal biopsies is limited after pan-enteric capsule endoscopy in patients with suspected Crohn's disease.
Background and study aims Pan-enteric capsule endoscopy (CE) is an emerging alternative to ileo-colonoscopy for diagnosing Crohn's disease (CD). However, CE does not offer the opportunity to take biopsies to support the diagnosis. This study examined the additional information obtained with mucosal biopsies and the feasibility of CE as a single diagnostic procedure. Patients and methods This retrospective study was based on a prospective, blind multicenter trial in which patients with suspected CD were examined with ileo-colonoscopy plus segmental biopsies and CE. Histopathological findings were compared to the result of CE. Results A total of 107 patients with a complete CE were included in the analysis. CE was consistent with CD in 44 patients (41.1%) and ulcerative colitis in 10 patients (9.3%). Histopathology confirmed the result of CE in 39.3% of patients and added new diagnostic information in 6.5% of patients. A CE consistent with CD was histologically confirmed in 20.5% of patients. Biopsies most often showed non-specific inflammation (61.4%). Only one patient with a normal CE had a specific histological diagnosis (microscopic colitis). Biopsies altered the diagnosis of ulcerative colitis to CD in two patients, and in two patients with a normal CE, biopsies showed CD or ulcerative colitis. In one patient with lymphoma in the terminal ileum and cecum, CE was misinterpreted as CD. Conclusions In patients with suspected CD and an evident result of CE, the additional information obtained from biopsies is limited, and CE as a single diagnostic procedure might be feasible in selected patients. Biopsies are warranted, however, in patients with an atypical endoscopic appearance or suspected malignancy.


Decline of gustatory sensitivity with the progression of Alzheimer's disease.
Patients with Alzheimer's disease (AD) manifest various impairments in eating behavior. However, few previous studies have directly investigated the gustatory function of AD patients, and results have been inconsistent. Thirty-two AD patients (Clinical Dementia Rating (CDR) 0.5/1/2, respectively 11/15/6 patients) and 22 normal control participants were examined to measure detection and recognition thresholds of the four elemental tastes (sweet, salty, sour, and bitter), and their ability to discriminate between tastes. Effects of demographic and clinical factors (age, sex, histories of alcohol and tobacco consumption, and CDR grade) on gustatory threshold were examined using ordinal logistic regression analysis. Performance was compared between AD and control groups. Total threshold values (the sum of threshold grades for the four tastes) for detection and recognition of tastes were significantly higher in the AD group. Detection thresholds for sweet, salty, and bitter, and recognition thresholds for sweet and sour, were also significantly higher in the AD group. Ordinal logistic regression analysis revealed that CDR grade was the only factor that significantly affected both total threshold values. Regarding taste discrimination, there were no significant differences between the AD group and control group. These findings suggest that progression of dementia severity accompanies gustatory decline. Although it seemingly paradoxical, weight loss and preference for sweet tastes are frequently, often simultaneously, observed in AD. Gustatory dysfunction may be partially involved in these symptoms. Thus, the nutritional care of patients with AD could be improved by making the taste of meals stronger, while controlling calorie and mineral intake.


Multiple-complete-digest restriction fragment mapping: generating sequence-ready maps for large-scale DNA sequencing.
Multiple-complete-digest mapping is a DNA mapping technique based on complete-restriction-digest fingerprints of a set of clones that provides highly redundant coverage of the mapping target. The maps assembled from these fingerprints order both the clones and the restriction fragments. Maps are coordinated across three enzymes in the examples presented. Starting with yeast artificial chromosome contigs from the 7q31.3 and 7p14 regions of the human genome, we have produced cosmid-based maps spanning more than one million base pairs. Each yeast artificial chromosome is first subcloned into cosmids at a redundancy of x15-30. Complete-digest fragments are electrophoresed on agarose gels, poststained, and imaged on a fluorescent scanner. Aberrant clones that are not representative of the underlying genome are rejected in the map construction process. Almost every restriction fragment is ordered, allowing selection of minimal tiling paths with clone-to-clone overlaps of only a few thousand base pairs. These maps demonstrate the practicality of applying the experimental and software-based steps in multiple-complete-digest mapping to a target of significant size and complexity. We present evidence that the maps are sufficiently accurate to validate both the clones selected for sequencing and the sequence assemblies obtained once these clones have been sequenced by a "shotgun" method.


Expression of CHODL in hepatocellular carcinoma affects invasion and migration of liver cancer cells.
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-associated death. Due to rapid progression and metastasis, the long-term survival remains poor for most patients. Thus, it is important to discover and develop novel preventive strategies and therapeutic approaches for HCC. Recent data show that chondrolectin (CHODL) is commonly overexpressed in the majority of lung cancers, indicating a possible correlation between CHODL and metastasis of lung cancer cells. Our investigation shows that the expression of CHODL is significantly decreased in HCC clinical samples and in HCC cell lines. Overexpression of CHODL in SMMC7721 cells with a lentiviral vector increased SMMC7721 cell migration and invasion. Our findings establish for the first time an association between human CHODL and HCC metastasis.


Performance of new adjustments to the TRISS equation model in developed and developing countries.
The Trauma and Injury Severity Score (TRISS) has been criticized for being based on data from the USA and Canada-high-income countries-and therefore, it may not be applicable to low-income and middle-income countries. The present study evaluated the accuracy of three adjustments to the TRISS equation model (NTRISS-like; TRISS SpO2; NTRISS-like SpO2) in a high-income and a middle-income country to compare their performance when derived and applied to different groups. This was a retrospective study of trauma patients admitted to two institutions: a university medical center in São Paulo, Brazil (a middle-income country), and a level 1 university trauma center in San Diego, USA (a high-income country). Patients were admitted between January 1, 2006, and December 31, 2010. The subjects were 2416 patients from Brazil and 8172 patients from the USA. All equations had adjusted coefficients for São Paulo and San Diego and for blunt and penetrating trauma. Receiver operating characteristic (ROC) curves were used to evaluate performance of the models. Regardless of the population where the equation was generated, it performed better when applied to patients in the USA (AUC from 0.911 to 0.982) compared to patients in Brazil (AUC from 0.840 to 0.852). When the severity was considered and homogenized, the performance of equations were similar to both application in the USA and Brazil. Survival probability models showed better performance when applied in data collected in the high-income countries (HIC) regardless the country they were derived. The severity is an important factor to consider when using non-adjusted survival probability models for the local population. Adjusted models for severely traumatized patients better predict survival probability in less severely traumatized populations. Other factors besides physiological and anatomical data may impact final outcomes and should be identified in each environment if they are to be used in the development of the trauma care performance improvement process in middle-income countries.


Early access for innovative oncology medicines: a different story in each nation.
As innovative oncology medicines are rapidly developed, there is increasing pressure on payers to offer patients timely access to life-saving therapies. The uncertainty surrounding these therapies when phase III clinical trials are pending has necessitated new, adapted pathways to market access, with timelines that greatly vary by country. Understanding differences between pathways may identify opportunities to expedite patient access universally. To describe early access pathways for new oncology medicines among selected countries with established health technology assessment (HTA) frameworks and publicly funded health systems, with a special focus on real-world evidence (RWE). We reviewed the HTA agency websites of the selected OECD countries: National Institute for Health and Care Excellence (NICE) for England and Wales; Haute Autorité de Santé (HAS) for France; IQWiG and G-BA for Germany; Agenzia Italiana del Farmaco (AIFA) for Italy; Pharmaceutical Benefits Advisory Committee (PBAC) for Australia; and CADTH and Institut National d'Excellence en Santé et Services Sociaux (INESSS) for Canada as the primary source of evidence. Processes for early patient access to innovative oncology therapies varied across selected countries; however, most countries have an established pathway for publicly funded early access (England and Wales, France, Germany, Italy, and Australia). The utilization of RWE to support earlier access (coverage with evidence) also varied by country, with some HTA organizations being actively engaged in these agreements (NICE, AIFA, and HAS) and others having no established processes in place (G-BA and CADTH/INESSS). This review of early access pathways for novel oncology medicines found substantial variability between countries of interest. Coverage with evidence frameworks may provide a unique opportunity for industry and payers to collaborate on earlier access to innovative cancer therapies with life-saving potential.


Factors associated with risky sun exposure behaviors among operating engineers.
The objective of this study was to determine the factors associated with sun exposure behaviors among Operating Engineers (heavy equipment operators). Operating Engineers (N = 498) were asked to complete a cross-sectional survey. Linear and logistic regression analyses were used to determine health behavioral, perceptional, and demographic factors associated with sun exposure behavior (sun burns, blistering, use of sunscreen, and interest in sun protection services). Almost half reported two or more sunburns/summer and the median times blistering was 2 with a range of 0-100. About one-third never used sun block, while just over one-third rarely used sun block. Almost one-quarter were interested in sun protection guidance. Multivariate analyses showed that perceptions of skin type, alcohol problems, fruit intake, BMI, sleep quality, age, sex, and race were significantly associated with at least one of the outcome variables (P < 0.05). Operating Engineers are at high risk for skin cancer due to high rates of exposure to ultraviolet light and low rates of sun block use. Subgroups of Operating Engineers are particularly at risk for sun damage. Interventions are needed to decrease sun exposure among Operating Engineers.


Effect of total motile sperm count in intra-uterine insemination on ongoing pregnancy rate.
In a descriptive retrospective cohort study, we determined the cumulative pregnancy rate for couples undergoing intra-uterine insemination (IUI) with at least one total motile sperm count (TMC) <1 million compared to couples with a TMC consistently >1 million. Eight hundred and ninety-five cycles in 273 couples were studied from 2006 to 2009. In 895 cycles, ovarian stimulation was performed through recFSH injections. IUI was scheduled 38 ± 2 h after the administration of HCG when at least one follicle measured >18 mm. The cumulative pregnancy rate according to the TMC was calculated. The cumulative pregnancy rate after four cycles of IUI was 17.3% in couples with at least one TMC <1 million and 25.5% in couples with a TMC consistently >1 million. It is concluded that the TMC does not significantly influence cumulative pregnancy rates after 4 IUI cycles. Couples with a low TMC could benefit from IUI. This could be considered before IVF.


Microbes on a Bottle: Substrate, Season and Geography Influence Community Composition of Microbes Colonizing Marine Plastic Debris.
Plastic debris pervades in our oceans and freshwater systems and the potential ecosystem-level impacts of this anthropogenic litter require urgent evaluation. Microbes readily colonize aquatic plastic debris and members of these biofilm communities are speculated to include pathogenic, toxic, invasive or plastic degrading-species. The influence of plastic-colonizing microorganisms on the fate of plastic debris is largely unknown, as is the role of plastic in selecting for unique microbial communities. This work aimed to characterize microbial biofilm communities colonizing single-use poly(ethylene terephthalate) (PET) drinking bottles, determine their plastic-specificity in contrast with seawater and glass-colonizing communities, and identify seasonal and geographical influences on the communities. A substrate recruitment experiment was established in which PET bottles were deployed for 5-6 weeks at three stations in the North Sea in three different seasons. The structure and composition of the PET-colonizing bacterial/archaeal and eukaryotic communities varied with season and station. Abundant PET-colonizing taxa belonged to the phylum Bacteroidetes (e.g. Flavobacteriaceae, Cryomorphaceae, Saprospiraceae-all known to degrade complex carbon substrates) and diatoms (e.g. Coscinodiscophytina, Bacillariophytina). The PET-colonizing microbial communities differed significantly from free-living communities, but from particle-associated (>3 μm) communities or those inhabiting glass substrates. These data suggest that microbial community assembly on plastics is driven by conventional marine biofilm processes, with the plastic surface serving as raft for attachment, rather than selecting for recruitment of plastic-specific microbial colonizers. A small proportion of taxa, notably, members of the Cryomorphaceae and Alcanivoraceae, were significantly discriminant of PET but not glass surfaces, conjuring the possibility that these groups may directly interact with the PET substrate. Future research is required to investigate microscale functional interactions at the plastic surface.


Midterm results after septal reshaping for anteroseptal scars.
Midterm clinical and morphologic results of the septal-reshaping exclusion of anteroseptal dyskinetic or akinetic areas were evaluated. From January to June 2003, 44 patients with myocardial infarction following left anterior descending coronary artery (LAD) occlusion underwent septal reshaping. The mean (+/- SD) New York Heart Association (NYHA) class of the patients at admission was 2.7 +/- 0.9. Angina was referred in 21 cases. The incision was started at the apex and directed parallel to the LAD toward the base of the heart. The septum was rebuilt with 1 or 2 U-stitches passed from the inside to join the anterior wall to the septum by starting as high as possible where the scar began and continuing in an oblique direction toward the new apex. An oval polyethylene terephthalate fiber (Dacron) patch was then sutured from the septum (at the end of the direct suture through the border with the inferior septum) to the anterior wall (between the healthy wall and the scarred wall) and up to the new apex. The 30-day mortality rate was 2.2% (1 patient, due to the failure of a previously implanted defibrillator). Three patients experienced acute renal failure. No patient had restrictive syndrome. After a mean follow-up period of 8.5 +/- 4.9 months (range, 4-22 months), the mean NYHA class improved from 2.7 +/- 0.9 to 1.6 +/- 0.5 (P < .001). The 18- month survival rate and the probability of being alive in NYHA class I or II were 93.2% +/- 2.0% and 90.9% +/- 4.3%, respectively. Echocardiographic results showed reductions in the left ventricle volume with a normalization of the stroke volume. The diastolic longitudinal length remained unchanged, and the diastolic sphericity index was reduced but not significantly. At 1 year after surgery, the good clinical and morphologic results demonstrate the safety and effectiveness of septal reshaping for anteroseptal scars.


Causal effects of specific gut microbiota on musculoskeletal diseases: a bidirectional two-sample Mendelian randomization study.
Recent observational studies and clinical trials demonstrated an association between gut microbiota and musculoskeletal (MSK) diseases. Nonetheless, whether the gut microbiota composition has a causal effect on the risk of MSK diseases remains unclear. Based on large-scale genome-wide association studies (GWAS), we performed a two-sample Mendelian randomization (MR) analysis to investigate the causal relationship between gut microbiota and six MSK diseases, namely osteoporosis (OP), fracture, sarcopenia, low back pain (LBP), rheumatoid arthritis (RA), and ankylosing spondylitis (AS). Instrumental variables for 211 gut microbiota taxa were obtained from the largest available GWAS meta-analysis (n = 18,340) conducted by the MiBioGen consortium. And the summary-level data for six MSK diseases were derived from published GWAS. The inverse-variance weighted (IVW) method was conducted as a primary analysis to estimate the causal effect, and the robustness of the results was tested via sensitivity analyses using multiple methods. The Bonferroni-corrected test was used to determine the strength of the causal relationship between gut microbiota and various MSK diseases. Finally, a reverse MR analysis was applied to evaluate reverse causality. According to the IVW method, we found 57 suggestive causal relationships and 3 significant causal relationships between gut microbiota and MSK diseases. Among them, Genus Bifidobacterium (β: 0.035, 95% CI: 0.013-0.058, p = 0.0002) was associated with increased left handgrip strength, Genus Oxalobacter (OR: 1.151, 95% CI: 1.065-1.245, p = 0.0003) was correlated with an increased risk of LBP, and Family Oxalobacteraceae (OR: 0.792, 95% CI: 0.698-0.899, p = 0.0003) was linked with a decreased risk of RA. Subsequently, sensitivity analyses revealed no heterogeneity, directional pleiotropy, or outliers for the causal effect of specific gut microbiota on MSK diseases (p > 0.05). Reverse MR analysis showed fracture may result in a higher abundance of Family Bacteroidales (p = 0.030) and sarcopenia may lead to a higher abundance of Genus Sellimonas (p = 0.032). Genetic evidence suggested a causal relationship between specific bacteria taxa and six MSK diseases, which highlights the association of the "gut-bone/muscle" axis. Further exploration of the potential microbiota-related mechanisms of bone and muscle metabolism might provide novel insights into the prevention and treatment of MSK diseases.


Combined transcriptomic and proteomic analysis of cold stress induced sugar accumulation and heat shock proteins expression during postharvest potato tuber storage.
Plant species differ greatly in their ability to acclimatise to and survive, cold stress. Normally, potato tubers are stored at low temperatures (below 10 °C) to delay sprouting. In this research, combined transcriptomic and proteomic analysis was conducted on potato tubers stored at 15 °C, 4 °C and 0 °C to investigate the mechanism of cold responses during postharvest storage. Results showed that soluble sugars were accumulated under low temperatures, regulating by granule-bound starch synthase 1, beta-amylase, invertase inhibitor and fructokinase. In addition, fifteen heat shock proteins (Hsps), including three Hsp70s, two Hsp80s, one Hsp90, one Hsp100 and eight small Hsps, were induced by low temperatures, which may act individually or synergistically to prevent physiological or cellular damage from cold stress in postharvest potato tubers. This research provided general information of sugar accumulation and defense response in potato tuber under cold storage.


Is 2020 the year when primatologists should cancel fieldwork?
Year 2020 has brought the greatest global pandemic to hit the world since the end of the First World War. The severe acute respiratory syndrome coronavirus 2 and the resulting disease named coronavirus disease 2019 has brought the world to its knees both financially and medically. The American Society of Primatologists has postponed their annual meetings from the end of May 2020 until the end of September 2020, while the International Primatological Society have postponed their biennial congress from August 2020 to August 2021, which has also resulted in their 2022 meetings in Malaysia being pushed back until 2023. Here, I explore the potential dangers of pursuing any primate fieldwork during this pandemic on our study species, their ecosystems, and local peoples. I believe that the risk of bringing this virus into our study ecosystems is too great and that primatologists should cancel all field research until the pandemic ends or a vaccine/reliable treatment is widely available. This is the year we all must become One Health practitioners!


The risk of placenta accreta following primary elective caesarean delivery: a case-control study.
To evaluate the risk of placenta praevia accreta following primary (first) elective or primary emergency caesarean section in a pregnancy complicated by placenta praevia. Retrospective matched case-control study, employing variable matching. Tertiary referral centre between 1993 and 2008. Sixty-five cases and 102 controls were used for the analysis from a total of 82 667 births during the study period. Relevant data were abstracted from clinical records. Matching of cases with controls was based on co-existing placenta praevia, number of previous caesarean sections, and age, with one or two controls per case. Results are presented as odds ratios (ORs) with 95% confidence intervals (95% CIs). Placenta accreta in a pregnancy complicated by placenta praevia following a primary elective or emergency caesarean section, and morbidity associated with pregnancies complicated by placenta accreta. Significantly more cases than controls had an elective caesarean section for their primary caesarean delivery (46.2 versus 18.6%; P < 0.001). There were no differences between groups for previous pregnancy loss, uterine surgery, and vaginal delivery, before or after the primary caesarean section. Compared with primary emergency caesarean section, primary elective caesarean section significantly increased the risk of placenta accreta in a subsequent pregnancy in the presence of placenta praevia (OR 3.00; 95% CI 1.47-6.12; P = 0.025). Our results suggest that women with a primary elective caesarean section without labour are more likely, compared with those undergoing primary emergency caesarean section with labour, to develop an accreta in a subsequent pregnancy with placenta praevia.


Protein A, avidin, and biotin in immunohistochemistry.
Conjugated and unlabeled peroxidase antibody methods have proven to be quite satisfactory in localizing sites of antigen-antibody reaction. The use of avidin-biotin-peroxidase complex (ABC), as well as protein A, can contribute significantly to the field of immunohistochemistry. The sensitivity and specificity of several immunohistochemical methods is compared. In general, the ABC method produced the most intense staining and the least background staining of any method tested. The unlabeled antibody (peroxidase-antiperoxidase: PAP) method also yielded satisfactory results, but it was less intense than the ABC method. In comparison to the PAP method, the indirect conjugated method presented slightly inferior staining intensities and significantly higher background staining. Protein A techniques produced a range of staining sensitivities similar to or inferior to the PAP technique. The main disadvantage in using protein A is that it reacts with intrinsic immunoglobulin (Ig) G, thus producing an intense background. Therefore, its use is not recommended on tissues that have either abundant immunoglobulins in their interstitium or numerous IgG-containing plasma cells.


[Late recurrences in Hodgkin's disease following radiotherapy].
1. From 1950 to 1970, 92 patients with Hodgkin's disease stage I and II were treated by irradiation at the Universitäts-Strahlenklinik Marburg. Staging was performed without diagnostic laparotomy. More than a third might be staged wrong. 2. The over-all survival rates for both, stage I and II, are 65% after five years, 40% after ten years. 15% of the patients are expected to be cured. 3. Three late recurrences after 12 or 13 years are contradictory to the definition of cure in Hodgkin's disease, as a ten years lasting relapse-free interval after primary treatment. In two further cases lymphogranulomatosis developed 7 and 12 years after operation and irradiation of mediastinal tumors, which were histologically classified as lymphadenitis and polymorphcellular sarcoma, but here and there showed the features of lymphogranulomatosis. Two further cases of lymphogranulomatosis were seen with extraordinary long remissions of 11 and 17 years. 4. On the understanding that the primary tumor disease had been cured, we can look at the recurrences as at second tumor disease. Then a tumor-disposition in these patients must be discussed. 5. The occurrence of the prognostically advantageous histologic type of nodular sclerosis, the age of the patients between 27 and 37 years at the first manifestation of the disorder, and the tolerance of peripheral localisation of the tumor disease lead to the conclusion that histologic type and course show the ratio between tumor disease and immunologic situation of the patient. Probably, the histologic features might be the expression of this situation.


A model morphology of the pulmonary acinus.
A variation of a mathematical model of the structure of a pulmonary ventilatory unit is used to generate its internal ductal tree and associated alveolar architecture. The model unit comprises a space-filling block of regular polyhedra; ducts and alveoli were formed by opening specific common faces between polyhedra. The model employs a physically reasonable optimization strategy of maximizing gas exchange while minimizing the mean transit time to ventilate the ventilatory unit (assumed to be proportional to the mean path length) in order to create the ductal tree. The sensitivity of the global architecture to the competitive optimization parameters used and the tree structure are compared with independently published measurements. The study concludes that it is possible to model the detailed architecture of a unit using a simple space-invariant uniform modular structure for both alveoli and ductal parts. The close similarity between model and experimental measurement strongly suggests that the optimization used to create the unit is a likely one from a functional biological standpoint. The insensitivity of the architecture to the competition between the optimization parameters supports the belief that it is not important to consider the detailed measured size distribution of alveoli when considering how the large structure of the ventilatory unit is built up.


Cerebral clearance of human amyloid-beta peptide (1-40) across the blood-brain barrier is reduced by self-aggregation and formation of low-density lipoprotein receptor-related protein-1 ligand complexes.
Soluble amyloid-beta peptide (Abeta) exists in the form of monomers and oligomers, and as complexes with Abeta-binding molecules, such as low-density lipoprotein receptor-related protein-1 (LRP-1) ligands. The present study investigated the effect of self-aggregation and LRP-1 ligands on the elimination of human Abeta(1-40) [hAbeta(1-40)] from the rat brain across the blood-brain barrier. Incubation of [(125)I]hAbeta(1-40) monomer resulted in time-dependent and temperature-dependent dimer formation, and the apparent elimination rate of [(125)I]hAbeta(1-40) dimer was significantly decreased by 92.7% compared with that of [(125)I]hAbeta(1-40) monomer. Pre-incubation with LRP-1 ligands, such as activated alpha2-macroglobulin (alpha2M), apolipoprotein E2 (apoE2), apoE3, apoE4, and lactoferrin, reduced the elimination of [(125)I]hAbeta(1-40). By contrast, pre-administration of the same concentration of these molecules in the rat brain did not significantly inhibit [(125)I]hAbeta(1-40) monomer elimination. Purified [(125)I]hAbeta(1-40)/activated alpha2M complex and [(125)I]activated alpha2M were not significantly eliminated from the rat brain up to 60 min. MEF-1 cells, which have LRP-1-mediated endocytosis, exhibited uptake of [(125)I]activated alpha2M, and enhancement of [(125)I]hAbeta(1-40) uptake upon pre-incubation with apoE, suggesting that [(125)I]activated alpha2M and [(125)I]hAbeta(1-40)/apoE complex function as LRP-1 ligands. These findings indicate that dimerization and LRP-1-ligand complex formation prevent the elimination of hAbeta(1-40) from the brain across the blood-brain barrier.


Characterization of insulin-like growth factor binding proteins produced in the rat central nervous system.
Insulin-like growth factor binding proteins (IGFBP) are thought to modulate the biological actions of the insulin-like growth factors (IGF), including possible regulatory roles in the growth and differentiation of the central nervous system. Extracellular fluids usually contain a mixture of IGFBPs, three of which have been cloned, sequenced, and designated IGFBP-1, -2, and -3. We used Western ligand blotting, immunoprecipitation, and competitive binding analysis to characterize IGFBPs found in fetal and adult rat cerebrospinal fluid (CSF) and IGFBPs produced by cultures of neonatal rat choroid plexus, astrocytes, and C6 glial cells. Pooled rat CSF contains primarily IGFBP-2 (a narrow band at Mr = 29,000), lesser quantities of IGFBP-3 (a multicomponent broad band at Mr = 37,500-43,000), and trace amounts of low mol wt IGFBPs. Conditioned medium from cultures of choroid plexus cells contained a single binding protein corresponding to IGFBP-2, whereas C6 cells made predominately an IGFBP corresponding to IGFBP-3. Astrocytes secreted two IGFBPs corresponding to IGFBP-2 and -3, primarily IGFBP-3. Neonatal CSF contained substantially more binding activity corresponding to IGFBP-2 than did adult CSF. In all samples showing Western ligand binding profiles corresponding to IGFBP-2, identification was established by immunoprecipitation. Competitive binding analysis performed on choroid plexus IGFBP showed preferential high affinity binding for IGF-II compared with that for IGF-I. In conclusion, CSF contains a mixture of distinct IGFBPs, primarily IGFBP-2. The other IGFBPs found in CSF are capable of being synthesized locally within the central nervous system by glial cells and neurons, suggesting that they are not derived from plasma by transport across the blood-brain barrier.


A laboratory-based multifunctional near ambient pressure X-ray photoelectron spectroscopy system for electrochemical, catalytic, and cryogenic studies.
A versatile multifunctional laboratory-based near ambient pressure x-ray photoelectron spectroscopy (XPS) instrument is presented. The entire device is highly customized regarding geometry, exchangeable manipulators and sample stages for liquid- and solid-state electrochemistry, cryochemistry, and heterogeneous catalysis. It therefore delivers novel and unique access to a variety of experimental approaches toward a broad choice of functional materials and their specific surface processes. The high-temperature (electro)catalysis manipulator is designed for probing solid state/gas phase interactions for heterogeneous catalysts including solid electrolyzer/fuel cell electrocatalysts at pressures up to 15 mbar and temperatures from room temperature to 1000 °C. The liquid electrochemistry manipulator is specifically designed for in situ spectroscopic investigations of polarized solid/liquid interfaces using aqueous electrolytes and the third one for experiments for ice and ice-like materials at cryogenic temperatures to approximately -190 °C. The flexible and modular combination of these setups provides the opportunity to address a broad spectrum of in situ and operando XPS experiments on a laboratory-based system, circumventing the limited accessibility of experiments at synchrotron facilities.


Antigen presentation between T cells drives Th17 polarization under conditions of limiting antigen.
T cells form immunological synapses with professional antigen-presenting cells (APCs) resulting in T cell activation and the acquisition of peptide antigen-MHC (pMHC) complexes from the plasma membrane of the APC. They thus become APCs themselves. We investigate the functional outcome of T-T cell antigen presentation by CD4 T cells and find that the antigen-presenting T cells (Tpres) predominantly differentiate into regulatory T cells (Treg), whereas T cells that have been stimulated by Tpres cells predominantly differentiate into Th17 pro-inflammatory cells. Using mice deficient in pMHC uptake by T cells, we show that T-T antigen presentation is important for the development of experimental autoimmune encephalitis and Th17 cell differentiation in vivo. By varying the professional APC:T cell ratio, we can modulate Treg versus Th17 differentiation in vitro and in vivo, suggesting that T-T antigen presentation underlies proinflammatory responses in conditions of antigen scarcity.


Analysis of the association between polymorphisms in the vitamin D receptor (VDR) gene and dental caries in a Chinese population.
Environmental influences on the development and progression of dental caries are well known; however, there is little evidence of a genetic component imparting susceptibility to dental caries. The aim of this study was to investigate the relationship between a single nucleotide polymorphism in the vitamin D receptor TaqI locus and dental caries susceptibility in a Chinese population. This case-control study was conducted with a case group (264 patients with dental caries from northwestern China) and a control group (219 individuals without dental caries or systemic disease from the same area). DNA was extracted from the peripheral venous blood of the study participants; the distribution of TaqI locus genotypes and allele frequencies was determined via polymerase chain reaction-restriction fragment length polymorphism. The data obtained were statistically analyzed using the Hardy-Weinberg equilibrium and Chi-square test. The frequency of the Tt genotype in the case group (14.0%) was significantly higher than that in the control group (4.3%), as determined using the genotype TT as the reference. The risk of dental caries was increased 3.8-fold in individuals with the heterozygous Tt genotype compared to that in the individuals with the TT genotype. The proportion of the 't' allele in the case group (7.0%) and the control group (2.1%) was observed to be significantly different [P = 0.0003; OR = 3.592, confidence interval 95% (1.790-7.208)]. Our results therefore suggested that the allele 't' might be a genetic factor determining dental caries susceptibility in individuals from the northwest of China.


Comparison of Short-Term Effects of Diquafosol and Rebamipide on Mucin 5AC Level on the Rabbit Ocular Surface.
To investigate the short-term effects of 2 new secretagogue eye drops for dry eye, 3% diquafosol tetrasodium ophthalmic solution (diquafosol) and 2% rebamipide ophthalmic suspension (rebamipide), on the concentration of mucin 5AC (MUC5AC) in rabbit tear fluid and conjunctival goblet cells. One dose of artificial tears, diquafosol or rebamipide, was instilled into 8 eyes of Japanese white rabbits. MUC5AC concentration in the tear fluid was examined using the enzyme-linked immunosorbent assay 15 min after instillation and compared with 8 untreated controls. Impression cytology was performed to measure the number of periodic acid Schiff (PAS)-positive cells and the ratio of the PAS-positive area using image analysis software. Statistical comparison was performed using ANOVA with post hoc analysis with the Tukey's test. After 15 min, only diquafosol significantly (P ≤ 0.01) increased the MUC5AC level in the tear fluid. Although no drug affected the number of PAS-positive cells, the ratio of the PAS-positive area decreased significantly (P ≤ 0.01) only in the diquafosol group. These data indicated that more PAS-positive MUC5AC was released into the tear fluid from the goblet cells by diquafosol than by rebamipide. There is a difference in the induction pattern of MUC5AC into the tears from the goblet cells between these eye drops.


Non-exclusivity in adolescent girls' romantic relationships.
As adolescents develop intimate relationships skills, they might change romantic partners often. Little is known about this developmental phenomenon. The goal was to determine the frequency of non-exclusive romantic relationships in girls, the variables associated with non-exclusive relationships, and the variables associated with having sexual intercourse in a non-exclusive relationship. Girls (12-15 years of age) participated in a longitudinal study (3 y, 7 visits) of romantic relationships. Seventy-two of 160 girls had a non-exclusive relationship, and of these, 23 girls had intercourse in an outside relationship. Younger age, belief that the boyfriend had an outside relationship, and less parental indirect monitoring was associated with the girl having an outside relationship. A longer time being sexually experienced and less direct parental monitoring was associated with having intercourse in the outside relationship. Non-exclusivity in adolescence is common but does not always include sexual intercourse. Healthcare providers can address non-exclusivity with adolescents directly.


Hmga2 regulation of tooth formation and association with Sox2 and Nanog expression.
Tooth formation is accomplished under strict genetic programs. Although patients with chromosome 12q14 aberration shows tooth phenotype including the size and eruption timing with bone growth anomaly, its etiology is uncertain. Here, we examined expression of Hmga2, which is encoded at chromosome 12q14, in mouse tooth germs and analyzed the involvement in lower first molar (M1) and mandibular bone development. Hmga2 expression was immunohistochemically detected at enamel organ and the surrounding mesenchyme of the M1 germs. The expression was dynamically changed with gestation and rapidly decreased in postnatal mice. In Hmga2-/- mice, the M1 germs and crowns were diminished in size, and formation and eruption of molars were delayed with mandibular bone growth retardation. Hmga2 cDNA or siRNA transfection showed that Hmga2 transcriptionally up-regulates expression of stem cell factors, Sox2 and Nanog. They were co-localized with Hmga2 in the germs, but differentially distributed at enamel organ and mesenchyme in Hmga2-/- mice. These results demonstrate that Hmga2 expressed in tooth germs regulates the growth, sizing and eruption and stem cell factor expression in different compartment of the germ and associates with mandibular bone growth. Although future studies are needed, the present study demonstrates HMGA2 regulation of tooth genesis with skeletal development.


[Antibiotic stewardship: Measures for optimization of antibacterial therapy].
Because the development of resistance is steadily increasing, especially among Gram-negative pathogens and new developments in antibiotics are lacking, a rational antibiotic therapy is necessary now more than ever. A continuing uncritical and non-guideline-conform use of antibiotics leads to selection of multidrug-resistant pathogens, which can colonize patients and as instigators of infections make treatment more difficult. A prerequisite for targeted antibiotic therapy is a critical testing of the suspected infection diagnosis based on a guideline-conform microbiological preanalytical procedure. To promote a guideline-conform antibiotic therapy in hospitals with respect to choice of substance, dosage and duration, in December 2013 so-called antibiotic stewardship (ABS) measures were summarized in a so-called S3-guideline from the Association of the Scientific Medical Societies in Germany (AWMF) under the auspices of the German Society for Infectious Diseases (DGI). With a strategy of targeted antibiotic therapy and infection prevention it is possible to achieve optimum treatment results and to minimize the development of resistance.