Evaluation of a Diabetes Prevention Program Lifestyle Intervention in Older Adults: A Randomized Controlled Study in Three Senior/Community Centers of Varying Socioeconomic Status.
Purpose The purpose of this study is to evaluate the feasibility and effectiveness of an adapted Diabetes Prevention Program (DPP) lifestyle program, DPP Group Lifestyle Balance (GLB), delivered in 3 economically diverse senior/community centers. Methods The DPP-GLB was implemented in 3 senior/community centers in Allegheny County, PA. A 6-month delayed control intervention design was used. Participants were randomized to begin the DPP-GLB immediately (immediate) or after a 6-month delay (delayed). Adults (n = 134; mean age = 62.8 years) with BMI ≥24 kg/m2 and prediabetes and/or the metabolic syndrome took part. Weight, physical activity (PA), and diabetes and cardiovascular disease (CVD) risk factors were assessed at 6, 12, and 18 months from baseline. Results At 6 months, the immediate group demonstrated greater mean weight loss than the delayed control group as well as significantly greater improvements in PA, A1C, fasting insulin, and waist circumference. In pre-post analyses, both randomized groups showed similar success that was maintained at 18 months. Conclusions The DPP-GLB delivered in economically diverse community centers was effective in this group of older adults. These findings support provision of coverage for prevention programs in older adults at risk for diabetes/CVD, which is important considering the large number of individuals who will be Medicare eligible in the near future.


Reassortants of H5N1 influenza viruses recently isolated from aquatic poultry in Hong Kong SAR.
The H5N1 virus (H5N1/97) that caused the bird flu incident in Hong Kong in 1997 has not been isolated since the poultry slaughter in late 1997. But the donor of its H5 hemagglutinin gene, Goose/Guangdong/1/96-like (Gs/Gd/96-like) virus, established a distinct lineage and continued to circulate in geese in the area. In 2000, a virus from the Goose/Guangdong/1/96 lineage was isolated for the first time from domestic ducks. Subsequently, it has undergone reassortment, and these novel reassortants now appear to have replaced Gs/Gd/96-like viruses from its reservoir in geese and from ducks. The internal gene constellation is also different from H5N1/97, but these variants have the potential for further reassortment events that may allow the interspecies transmission of the virus.


Treatment of aqueous bisphenol A using nano-sized zero-valent iron in the presence of hydrogen peroxide and persulfate oxidants.
Bisphenol A (BPA) is an industrial pollutant considered as one of the major endocrine-disrupting chemicals found in natural waters. In the present study, the use of a commercial, air-stable, zero-valent iron (ZVI) powder, consisting of Fe0 surface stabilized nanoparticles was examined for the treatment of 20 mg/L, aqueous BPA solutions. The influence of pH (3, 5, 7), addition of hydrogen peroxide (HP) and persulfate (PS) oxidants (0.0, 1.25 and 2.5 mM) as well as temperature (25 and 50 °C) was studied for BPA treatment with 1 g/L ZVI. ZVI coupled with HP or PS provided an effective treatment system, which was based on rapid ZVI-mediated decomposition of the above-mentioned oxidants, resulting in complete BPA as well as significant total organic carbon (TOC) (88%) removals, in particular when PS was employed as the oxidant. Increasing the PS concentration and reaction temperature dramatically enhanced PS decomposition and BPA removal rates, whereas HP was not very effective in TOC removals and at elevated temperatures. According to the bioassays conducted with Vibrio fischeri and Pseudokirchneriella subcapitata, the acute toxicity of aqueous BPA fluctuated at first but decreased appreciably at the end of ZVI/PS treatment.


Chimeric Hepatitis B core antigen virus-like particles displaying the envelope domain III of dengue virus type 2.
Dengue is a global public health problem for which no drug or vaccine is available. Currently, there is increasing interest in developing non-replicating dengue vaccines based on a discrete antigenic domain of the major structural protein of dengue viruses (DENVs), known as envelope domain III (EDIII). The use of bio-nanoparticles consisting of recombinant viral structural polypeptides, better known as virus-like particles (VLPs), has emerged as a potential platform technology for vaccine development. This work explores the feasibility of developing nanoparticles based on E. coli-expressed recombinant Hepatitis B virus core antigen (HBcAg) designed to display EDIII moiety of DENV on the surface. We designed a synthetic gene construct encoding HBcAg containing an EDIII insert in its c/e1 loop. The fusion antigen HBcAg-EDIII-2 was expressed in E. coli, purified to near homogeneity using Ni+2 affinity chromatography and demonstrated to assemble into discrete 35-40 nm VLPs by electron microscopy. Competitive ELISA analyses showed that the EDIII-2 moieties of the VLPs are accessible to anti-EDIII-2-specific monoclonal and polyclonal antibodies, suggesting that they are surface-displayed. The VLPs were highly immunogenic eliciting high titer anti-EDIII-2 antibodies that were able to recognize, bind and neutralize infectious DENV based on ELISA, immunofluorescence and virus-neutralization assays. This work demonstrates that HBcAg-derived nanoparticles can serve as a useful platform for the display of DENV EDIII. The EDIII-displaying nanoparticles may have potential applications in diagnostics/vaccines for dengue.


Derivation of HLA-A11/Kb transgenic mice: functional CTL repertoire and recognition of human A11-restricted CTL epitopes.
Transgenic mice expressing chimeric human (alpha1 and alpha2 HLA-A11 domains) and murine (alpha3, transmembrane, and cytoplasmic H-2Kb domains) class I molecules were derived. These mice were used as a model system to study the immunogenicity of human CTL epitopes and also to examine the aspects of Ag processing differences of mice vs man. Immunization of these mice with seven known HLA-A11-restricted CTL epitopes emulsified in IFA resulted in vigorous specific CTL responses. A larger panel of 45 A11-binding peptides was used to examine the relationship between immunogenicity in the HLA-A11/Kb transgenic mice and HLA-A11 binding capacity. Twenty-one of 28 (75%) peptides with high binding affinities (50% inhibitory concentration (IC50), 2-50 nM) and 7 of 13 (54%) intermediate binding peptides (IC50, 50-500 nM range) were immunogenic. In parallel, 19 of these peptides were used for in vitro primary immunizations of PBMC derived from HLA-A11 healthy human donors. It was found that 8 of 8 peptides that were able to elicit CTL in primary human in vitro cultures were also immunogenic in HLA-A11/Kb mice. Finally, HLA-A11/Kb transgenic mice were found to generate an A11/Kb restricted CTL response following immunization with influenza virus A/PR/8/34, suggesting that, at least to some extent, A11 epitopes are generated by transgenic mice as a result of natural in vivo processing and presentation.


Breastfeeding is associated with increased lung function at 18 years of age: a cohort study.
Breastfeeding has been linked with increased forced vital capacity (FVC) in children but not in older adolescents. Our aim was to investigate the effects of breastfeeding duration and infant weight gain on FVC in both developmental periods. In a birth cohort, information on breastfeeding duration was collected at 1 and 2 yrs; spirometric tests were conducted at 10 and 18 yrs. To estimate the effect of breastfeeding duration on FVC at 18 yrs of age, we used linear models; to analyse repeated FVC measurements at 10 and 18 yrs of age, we used linear mixed models. Links between breastfeeding, infant weight gain and FVC at 10 and 18 yrs of age were analysed through path analyses. Among 808 breastfed children, 49% were breastfed for ≥ 4 months. At 18 yrs of age the augmenting effect of breastfeeding on FVC was reduced with increased height. Linear mixed models identified that breastfeeding duration was associated with increased FVC. Path analysis suggested a direct effect of breastfeeding on FVC at 10 yrs of age, but an indirect effect at 18 yrs of age via FVC at 10 yrs of age. Although inversely related to breastfeeding, a higher weight gain in infants led to taller adolescents and, in turn, resulted in increased FVC. In conclusion, a longer duration of breastfeeding contributes to lung health in childhood and adolescence.


Evaluation of a commercial integrating sphere setup for the determination of absolute photoluminescence quantum yields of dilute dye solutions.
The commercial availability of stand-alone setups for the determination of absolute photoluminescence quantum yields (Phi(f)) in conjunction with the increasing use of integrating sphere accessories for spectrofluorometers is expected to have a considerable influence not only on the characterization of chromophore systems for use in optical and opto-electronic devices, but also on the determination of this key parameter for (bio)analytically relevant dyes and functional luminophores. Despite the huge potential of systems measuring absolute Phi(f) values and the renewed interest in dependable data, evaluated protocols for even the most elementary case, the determination of the fluorescence quantum yield of transparent dilute solutions of small organic dyes with integrating sphere methods, are still missing. This encouraged us to evaluate the performance and sources of uncertainty of a simple commercial integrating sphere setup with dilute solutions of two of the best characterized fluorescence quantum yield standards, quinine sulfate dihydrate and rhodamine 101, strongly differing in spectral overlap between absorption and emission. Special attention is dedicated to illustrate common pitfalls of this approach, thereby deriving simple procedures to minimize measurement uncertainties and improve the comparability of data for the broad community of users of fluorescence techniques.


Analysis of the autoimmune response against BP180 in patients with Alzheimer's disease.
Current epidemiological studies suggest a significant correlation between Alzheimer's disease (AD) and bullous pemphigoid (BP). However, the autoimmune response against BP180 in patients with AD has not been fully understood. investigated. We randomly enrolled 48 patients with AD and 50 sex- and age-matched healthy controls. We detected the presence/absence and the level of anti-BP180/BP230 immunoglobulin G (IgG) autoantibodies in the patients' serum to determine whether said antibodies possess reactivity against the BP180 protein in the human brain and skin. The enzyme-linked immunosorbent assay (ELISA) results revealed that the positive rate of anti-BP180 autoantibodies in patients with AD (23/48, 47.9%) was significantly higher than that in controls (4/50, 8.0%; P<0.0001). These ELISA-positive patients were further examined through immunoblotting. Sera from nine patients with AD (9/23, 39.1%) and one control (1/4, 25.0%) reacted with human cutaneous recombinant full-length BP180 and BP180-noncollagenous 16A (NC16A). Sera from 11 (11/23, 47.8%) patients with AD reacted with a 180-kDa protein from the human brain extract, but none of the controls' sera recognized the corresponding protein band. The majority of the patients in the anti-BP180-positive AD group were men (14/23, 60.9%) who were older (74.0 years) compared with those in the control group (6/25, 24.0%; P<0.05) (72.2 years; P<0.01). Anti-BP180 autoantibodies are present in AD and recognize human recombinant full-length BP180 and a 180-kDa protein from the human brain extract, suggesting that BP180 is a shared autoantigen in AD and BP and may help clarify the mechanism to explain why a high risk of BP exists in AD. Elderly male patients with AD are significantly more likely to develop BP180 serum autoreactivity compared with other patients with AD.


Responses of the sympathetic nervous system and the hypothalamic-pituitary-adrenal axis to interleukin-6: a pilot study in fibromyalgia.
To determine whether deficient activity of the hypothalamic corticotropin-releasing hormone (CRH) neuron, which stimulates the hypothalamic-pituitary-adrenal (HPA) axis and the central control nuclei of the sympathetic nervous system and inhibits ascending pain pathways, may be pathogenic in patients with fibromyalgia (FM). We administered interleukin-6 (IL-6; 3 microg/kg of body weight subcutaneously), a cytokine capable of stimulating hypothalamic CRH release, and measured plasma levels of adrenocorticotropic hormone (ACTH), cortisol, and catecholamines and their metabolites and precursors. Thirteen female FM patients and 8 age- and body mass index-matched female controls were studied. The diagnosis of FM was made according to American College of Rheumatology criteria. Tender points were quantitated by pressure algometry. All subjects had HPA axis studies. Seven FM patients and 7 controls also had catecholamine measurements. After IL-6 injection, delayed ACTH release was evident in the FM patients, with peak levels at 96.9 +/- 6.0 minutes (mean +/- SEM; control peak 68.6 +/- 10.3 minutes; P = 0.02). Plasma cortisol responses to IL-6 did not differ significantly between patients and controls. Basal norepinephrine (NE) levels were higher in the FM patients than in the controls. While a small, although not significant, rise in NE levels occurred after IL-6 injection in the controls, NE levels dramatically increased over basal levels in the FM patients between 60 and 180 minutes after IL-6 injection. Both peak NE levels (mean +/- SEM 537.6 +/- 82.3 versus 254.3 +/- 41.6 pg/ml; P = 0.0001) and time-integrated NE responses (93.2 +/- 16.6 pg/ml x minutes(-3) versus 52.2 +/- 5.7 pg/ml x minutes(-3); P = 0.038) were greater in FM patients than in controls. Heart rate was increased by IL-6 injection in FM patients and controls, but rose to significantly higher levels in the FM patients from 30 minutes to 180 minutes after IL-6 injection (P < 0.03). Exaggerated NE responses and heart rate increases, as well as delayed ACTH release, were observed among female FM patients compared with age-matched female controls. Delayed ACTH release after IL-6 administration in FM is consistent with a defect in hypothalamic CRH neuronal function. Exaggerated NE release may reflect abnormal regulation of the sympathetic nervous system, perhaps secondary to chronically deficient hypothalamic CRH. The excessive heart rate response after IL-6 injection in FM patients may be unrelated to the increase in NE, or it may reflect an alteration in the sensitivity of cardiac beta-adrenoceptors to NE. These responses to a physiologic stressor support the notion that FM may represent a primary disorder of the stress system.


The representation of occluded image regions in area V1 of monkeys and humans.
Neuronal activity in the primary visual cortex (V1) is driven by feedforward input from within the neurons' receptive fields (RFs) and modulated by contextual information in regions surrounding the RF. The effect of contextual information on spiking activity occurs rapidly and is therefore challenging to dissociate from feedforward input. To address this challenge, we recorded the spiking activity of V1 neurons in monkeys viewing either natural scenes or scenes where the information in the RF was occluded, effectively removing the feedforward input. We found that V1 neurons responded rapidly and selectively to occluded scenes. V1 responses elicited by occluded stimuli could be used to decode individual scenes and could be predicted from those elicited by non-occluded images, indicating that there is an overlap between visually driven and contextual responses. We used representational similarity analysis to show that the structure of V1 representations of occluded scenes measured with electrophysiology in monkeys correlates strongly with the representations of the same scenes in humans measured with functional magnetic resonance imaging (fMRI). Our results reveal that contextual influences rapidly alter V1 spiking activity in monkeys over distances of several degrees in the visual field, carry information about individual scenes, and resemble those in human V1. VIDEO ABSTRACT.


Real-Time Risk Prediction on the Wards: A Feasibility Study.
Failure to detect clinical deterioration in the hospital is common and associated with poor patient outcomes and increased healthcare costs. Our objective was to evaluate the feasibility and accuracy of real-time risk stratification using the electronic Cardiac Arrest Risk Triage score, an electronic health record-based early warning score. We conducted a prospective black-box validation study. Data were transmitted via HL7 feed in real time to an integration engine and database server wherein the scores were calculated and stored without visualization for clinical providers. The high-risk threshold was set a priori. Timing and sensitivity of electronic Cardiac Arrest Risk Triage score activation were compared with standard-of-care Rapid Response Team activation for patients who experienced a ward cardiac arrest or ICU transfer. Three general care wards at an academic medical center. A total of 3,889 adult inpatients. The system generated 5,925 segments during 5,751 admissions. The area under the receiver operating characteristic curve for electronic Cardiac Arrest Risk Triage score was 0.88 for cardiac arrest and 0.80 for ICU transfer, consistent with previously published derivation results. During the study period, eight of 10 patients with a cardiac arrest had high-risk electronic Cardiac Arrest Risk Triage scores, whereas the Rapid Response Team was activated on two of these patients (p < 0.05). Furthermore, electronic Cardiac Arrest Risk Triage score identified 52% (n = 201) of the ICU transfers compared with 34% (n = 129) by the current system (p < 0.001). Patients met the high-risk electronic Cardiac Arrest Risk Triage score threshold a median of 30 hours prior to cardiac arrest or ICU transfer versus 1.7 hours for standard Rapid Response Team activation. Electronic Cardiac Arrest Risk Triage score identified significantly more cardiac arrests and ICU transfers than standard Rapid Response Team activation and did so many hours in advance.


Rates of hexadehydro-Diels-Alder (HDDA) cyclizations: impact of the linker structure.
The rates of the hexadehydro-Diels-Alder (HDDA) reaction of substrates containing, minimally, a 1,3,8-triyne subunit are reported. Several series of related substrates, differing in the nature of the three-atom tether that links the 1,3-diyne and diynophile, were examined. Seemingly small changes in substrate structure result in large differences in cyclization rate, spanning more than 8 orders of magnitude. The reactivity trends revealed by these studies should prove useful in guiding substrate design and choice of reaction conditions in future applications.


Differential expression of molecular markers of synaptic plasticity in the hippocampus, prefrontal cortex, and amygdala in response to spatial learning, predator exposure, and stress-induced amnesia.
We have studied the effects of spatial learning and predator stress-induced amnesia on the expression of calcium/calmodulin-dependent protein kinase II (CaMKII), brain-derived neurotrophic factor (BDNF) and calcineurin in the hippocampus, basolateral amygdala (BLA), and medial prefrontal cortex (mPFC). Adult male rats were given a single training session in the radial-arm water maze (RAWM) composed of 12 trials followed by a 30-min delay period, during which rats were either returned to their home cages or given inescapable exposure to a cat. Immediately following the 30-min delay period, the rats were given a single test trial in the RAWM to assess their memory for the hidden platform location. Under control (no stress) conditions, rats exhibited intact spatial memory and an increase in phosphorylated CaMKII (p-CaMKII), total CaMKII, and BDNF in dorsal CA1. Under stress conditions, rats exhibited impaired spatial memory and a suppression of all measured markers of molecular plasticity in dorsal CA1. The molecular profiles observed in the BLA, mPFC, and ventral CA1 were markedly different from those observed in dorsal CA1. Stress exposure increased p-CaMKII in the BLA, decreased p-CaMKII in the mPFC, and had no effect on any of the markers of molecular plasticity in ventral CA1. These findings provide novel observations regarding rapidly induced changes in the expression of molecular plasticity in response to spatial learning, predator exposure, and stress-induced amnesia in brainregions involved in different aspects of memory processing.


One-step hydrophobization of tannic acid for antibacterial coating on catheters to prevent catheter-associated infections.
Catheter-associated infections (CAIs) caused by bacterial colonization are significant problems in clinics. Thus, effective antibacterial coatings for biomedical catheters to prevent bacterial infections are urgently needed. Ideal coatings should include the advantage of potent antibacterial properties and being easily and economically modified on the catheter surface. Due to their advantages of adhesive capability on various substrates, an increasing number of coatings based on plant polyphenols have been developed. However, the hydrophilicity of plant polyphenols limits their utilization in coatings. Herein, hydrophobic tannic acid (TA) was synthesized via the one-step electrostatic assembly of TA and benzalkonium chloride (BAC) with the green solvent water as the medium. The as-prepared hydrophobic TA (TBA) facilely formed a stable and colorless coating on the luminal and outer surface of biomedical catheters with broad-spectrum antibacterial activity and biocompatiblity. It was demonstrated that the TBA-coated surfaces displayed excellent bactericidal activity toward Gram-positive Staphylococcus aureus (S. aureus) and Gram-negative Escherichia coli (E. coli), and more than 99% of the above bacteria were killed by the TBA-coated films. The test of the coated catheters in vitro also showed the excellent antibacterial activity of both the outer and luminal surfaces of the catheter. Moreover, in an in vivo mouse model, the coated catheters relatively prevented bacterial colonization compared to the uncoated catheters. Meantime, no significant cytotoxicity and host response for Cell Counting Kit-8 (CCK-8) and tissue compatibility in vivo were observed, indicating the better biocompatibility of the TBA coating. This preparation method overcomes the limitation of the traditional hydrophilic tannic acid as a coating and provides a new method for preventing medical indwelling device-associated infections.


Reprogramming the chromatin landscape: interplay of the estrogen and glucocorticoid receptors at the genomic level.
Cross-talk between estrogen receptors (ER) and glucocorticoid receptors (GR) has been shown to contribute to the development and progression of breast cancer. Importantly, the ER and GR status in breast cancer cells is a significant factor in determining the outcome of the disease. However, mechanistic details defining the cellular interactions between ER and GR are poorly understood. We investigated genome-wide binding profiles for ER and GR upon coactivation and characterized the status of the chromatin landscape. We describe a novel mechanism dictating the molecular interplay between ER and GR. Upon induction, GR modulates access of ER to specific sites in the genome by reorganization of the chromatin configuration for these elements. Binding to these newly accessible sites occurs either by direct recognition of ER response elements or indirectly through interactions with other factors. The unveiling of this mechanism is important for understanding cellular interactions between ER and GR and may represent a general mechanism for cross-talk between nuclear receptors in human disease.


[Spontaneous bacterial peritonitis in patients with decompensated liver cirrhosis and "tense" ascites].
In the study 52 patients with decompensated liver cirrhosis and "tense" ascites were included. According to the clinical picture, ascites cultures and the number of polymorphonuclears in cmm of the ascitic fluid, all patients were selected in one of the following groups: 1. group of patients with sterile ascites (28), 2. group of patients with spontaneous peritonitis (16), and 3. group of patients with bacterascites (8). The results have shown that the incidence of spontaneous peritonitis is much higher in the group of "tense" ascites patients than in the group of all patients with ascites, the ratio being 30.7% compared to 6% in all cirrhotic patients with ascites. Spontaneous bacterial peritonitis correlates with increased polymorphonuclears in the ascitic fluid (p less than 0.05), decreased pH values (p less than 0.0), and increased amounts of total proteins in the ascitic fluid (p less than 0.05). The lethality rate in the group of spontaneous peritonitis and sterile ascites was 43.7% and 7.1% respectively. Early diagnosis and, of course, adequate therapy are the main points in spontaneous bacterial peritonitis.


Preoperative use of anti-tumor necrosis factor therapy in Crohn's disease: promises and pitfalls.
Recent advances in medical and surgical therapy were achieved during the last two decades in the management of Crohn's disease (CD). Anti-tumor necrosis factor (anti-TNF) agents are widely used worldwide. However, a significant proportion of patients still need surgical resections. The impact of previous exposure to these agents on the perioperative and postoperative outcomes is still controversial. In this critical review, we aimed to position the strategy of intentional preoperative use of anti-TNF agents in the management of CD. The indications and contraindications for this strategy are detailed, and despite scarce evidence, the possible advantages and disadvantages of the intentional use of anti-TNF agents before abdominal surgery in CD are discussed.


Inflammatory response to abdominal irradiation stimulates hemopoiesis.
The connection between inflammation and hemopoiesis was studied in the context of abdominal irradiation. Male C57BL6/J mice received localized irradiation of 20 Gy either to 70% of the liver or to the intestine (most of ileum and caecum). Irradiation of liver induced a rapid increase in intercellular adhesion molecule-1 mRNA expression in the liver. In serum/plasma, an increase in positive acute phase proteins (serum amyloid-P and fibrinogen) and a decrease in albumin occurred during the second and third week following liver irradiation. Similarly, intestinal irradiation induced an increase in plasma fibrinogen level. A transient elevation in neutrophil and platelet counts was observed that was maximal during the second and third week with similar kinetics for intestinal and liver irradiation. Moreover, intestinal irradiation enhanced hemopoietic progenitors in bone marrow. IL-6, which is known to be an agonist in the regulation of acute phase protein expression as well as hemopoietic cell production, was increased in plasma from intestinal- and liver-irradiated mice. Administration of an anti-IL-6 mAb to intestinal-irradiated mice abrogated the elevation of fibrinogen and the increase in hemopoietic progenitors. Abdominal irradiation provokes an inflammatory response which in turn stimulates hemopoiesis. IL-6 may play a major role in controlling these events.


Electronic Structure of Above-Room-Temperature van der Waals Ferromagnet Fe3GaTe2.
Fe3GaTe2, a recently discovered van der Waals ferromagnet, demonstrates intrinsic ferromagnetism above room temperature, necessitating a comprehensive investigation of the microscopic origins of its high Curie temperature (TC). In this study, we reveal the electronic structure of Fe3GaTe2 in its ferromagnetic ground state using angle-resolved photoemission spectroscopy and density functional theory calculations. Our results establish a consistent correspondence between the measured band structure and theoretical calculations, underscoring the significant contributions of the Heisenberg exchange interaction (Jex) and magnetic anisotropy energy to the development of the high-TC ferromagnetic ordering in Fe3GaTe2. Intriguingly, we observe substantial modifications to these crucial driving factors through doping, which we attribute to alterations in multiple spin-splitting bands near the Fermi level. These findings provide valuable insights into the underlying electronic structure and its correlation with the emergence of high-TC ferromagnetic ordering in Fe3GaTe2.


Prevalence and Correlates of Everyday Discrimination among U.S. Latinos.
OBJECTIVES: This study reports on the prevalence and correlates of perceived discrimination among a national sample of Latinos in the U.S. Understanding the prevalence and correlates of discrimination can help us better address disparities in the healthcare system. We define perceived discrimination as self-reported everyday experiences of unfair treatment. METHODS: Logistic regression analyses were used to assess rates of perceived discrimination among Latinos and identify correlates of discrimination. Data came from the National Latino and Asian American Study (NLAAS). RESULTS: The prevalence of perceived discrimination among Latinos was 30%. Cubans and Latinos with high ethnic identity were less likely to perceive discrimination compared to other Latino subgroups or Latinos with low ethnic identity. U.S.-born Latinos and Latinos arriving to the U.S. at younger ages were more likely to perceive discrimination compared to immigrants arriving at older ages. CONCLUSIONS: Perceived discrimination among Latinos is less prevalent than what has been reported for other minorities. Variations in perceived discrimination are related to sociodemographic and cultural differences across ethnic subgroups.


Horizontal gene transfer plays a major role in the pathological convergence of Xanthomonas lineages on common bean.
Host specialization is a hallmark of numerous plant pathogens including bacteria, fungi, oomycetes and viruses. Yet, the molecular and evolutionary bases of host specificity are poorly understood. In some cases, pathological convergence is observed for individuals belonging to distant phylogenetic clades. This is the case for Xanthomonas strains responsible for common bacterial blight of bean, spread across four genetic lineages. All the strains from these four lineages converged for pathogenicity on common bean, implying possible gene convergences and/or sharing of a common arsenal of genes conferring the ability to infect common bean. To search for genes involved in common bean specificity, we used a combination of whole-genome analyses without a priori, including a genome scan based on k-mer search. Analysis of 72 genomes from a collection of Xanthomonas pathovars unveiled 115 genes bearing DNA sequences specific to strains responsible for common bacterial blight, including 20 genes located on a plasmid. Of these 115 genes, 88 were involved in successive events of horizontal gene transfers among the four genetic lineages, and 44 contained nonsynonymous polymorphisms unique to the causal agents of common bacterial blight. Our study revealed that host specificity of common bacterial blight agents is associated with a combination of horizontal transfers of genes, and highlights the role of plasmids in these horizontal transfers.


Intestinal glucose and sodium transport and its relation to hypertension.
Final carbohydrate digestion by brush disaccharidases is closely linked to the transport of the resulting monosaccharides. A bifunctional carrier operates within the brush-border membrane of intestinal mucosal epithelial cells translocating glucologues and sodium due to a down-hill Na+ -gradient. Inhibition of final carbohydrate digestion by an inhibitor of a-glucoside-hydrolase activity results in reduction of glucose absorption from sucrose and even more marked inhibition of Na+ and water absorption. Modulation of the kinetic of carbohydrate absorption may be important in the control of post-prandial hyperglycemia of the diabetic, but no evidence exists that retardation of Na+ -absorption may be of importance in the hypertensive patient.


Metformin alters the gut microbiome of individuals with treatment-naive type 2 diabetes, contributing to the therapeutic effects of the drug.
Metformin is widely used in the treatment of type 2 diabetes (T2D), but its mechanism of action is poorly defined. Recent evidence implicates the gut microbiota as a site of metformin action. In a double-blind study, we randomized individuals with treatment-naive T2D to placebo or metformin for 4 months and showed that metformin had strong effects on the gut microbiome. These results were verified in a subset of the placebo group that switched to metformin 6 months after the start of the trial. Transfer of fecal samples (obtained before and 4 months after treatment) from metformin-treated donors to germ-free mice showed that glucose tolerance was improved in mice that received metformin-altered microbiota. By directly investigating metformin-microbiota interactions in a gut simulator, we showed that metformin affected pathways with common biological functions in species from two different phyla, and many of the metformin-regulated genes in these species encoded metalloproteins or metal transporters. Our findings provide support for the notion that altered gut microbiota mediates some of metformin's antidiabetic effects.


Safety Assessment of PEGylated Alkyl Glycerides as Used in Cosmetics.
The Expert Panel for Cosmetic Ingredient Safety (Panel) assessed the safety of 60 PEGylated alkyl glycerides. PEGylated alkyl glycerides are mono-, di-, and/or triglycerides that have been modified with ethylene glycol repeat units (in the starting material form as epoxide). Most of the PEGylated alkyl glycerides are reported to function as skin-conditioning agents or surfactants. The Panel reviewed the available animal and clinical data as well as data from the 1999 report for the 5 polyethylene glycol (PEG) glyceryl cocoates and the 2012 report of PEGylated oils, to determine the safety of these ingredients. The Panel concluded these ingredients are safe in the current practices of use and concentration when formulated to be nonirritating; this conclusion supersedes the 1999 conclusion issued on 5 PEG glyceryl cocoate ingredients.


[Food habits of the white-tailed deer, Odocoileus virginianus (Artiodactyla: Cervidae) in Nanchititla Natural Park, Mexico].
White-tailed deer is a species with a large behavioral plasticity and adaptation to different habitats, including their food habits. This study was conducted with the aim to determine the food habits of this species in the cloud (BMM) and pine-oak (BPE) forests. Deer scats and plant samples were obtained following standard methods, from Sierra Nanchititla Park in the State of Mexico, from June 1990 to May 1992. A total of 104 deer pellet-groups were collected, and histological analysis for herbivores was used and compared with stock samples of plant tissues collected from the study area. We applied the Spearman correlation and Morisita index to determine alimentary preference. The results showed that the deer consumes 79.44% of plant species from BMM and 20.56% of the BPE. There is a selectivity tendency for 12 of the 14 plant species located in the BMM, while for BPE no tendency was observed. Key species that are part of the elemental diet of the deer in these areas were: Acalypha setosa, Smilax pringlei, Psidium sartorianum and Dendropanax arborea. The consumption of plants did not differ significantly between the dry and rainy seasons in terms of biological form, however, during the dry season there is a tendency to consume trees, and by the end of the rainy season to consume herbs. The data indicate that the deer can be selective with BMM plants, while for the BPE tends to be opportunistic.


Senior first, junior second.
The seniority system exists in most companies, including in healthcare industries. Seniority often plays an essential role in the organizational success and career advance of employees. However, there are pros and cons in the application of the seniority system in all organizations, especially in the healthcare industry. This article prompts a discussion about seniority in nursing and provides some particular concerns and recommendations for consideration, and this begs the question, should senior be first and junior second?


The effects of weight loss on adipokines and markers of inflammation in dogs.
Evidence suggests that adipose tissue-derived adipokines induce mild inflammation and may play a role in insulin resistance associated with diabetes. The present study was designed to examine a series of adipokines and markers of inflammation in dogs before and after a successful weight loss. The study included fasting serum samples from twenty-five dogs before and after a weight-loss programme. Serum C-reactive protein (CRP) and monocyte chemoattractant protein-1 (MCP-1) were measured as indicators of chronic inflammation, while serum adipokines including total adiponectin, high-molecular-weight (HMW) adiponectin, resistin and leptin were also examined. Medians for CRP (before, 10.0 (interquartile range 5.4-15.0) μg/ml; after, 5.6 (interquartile range 3.8-7.0) μg/ml) and MCP-1 (before, 212 (interquartile range 157-288) ng/ml; after, 185 (interquartile range 143-215) ng/ml) decreased significantly after weight loss. Medians for resistin showed a mild, yet significant reduction (before, 67.1 (interquartile range 44.4-88.5) pg/ml; after, 60.5 (interquartile range 32.3-67.1) pg/ml), while leptin showed a dramatic decrease after weight loss (before, 18.9 (interquartile range 10.8-35.4) ng/ml; after, 6.6 (interquartile range 3.9-10.2) ng/ml). Serum total adiponectin and HMW adiponectin were unchanged on all analyses performed. These data suggest that weight loss can decrease chronic inflammation; however, the clinical implications of this decrease are not well elucidated in dogs. Surprisingly, there was no increase in total or HMW serum adiponectin after weight loss, as observed previously in human subjects. The lack of change in total and HMW adiponectin might explain why insulin resistance and type 2 diabetes are less prevalent in obese dogs when compared with humans and cats.


Provision of the progestogen-only pill by community pharmacies as bridging contraception for women receiving emergency contraception: the Bridge-it RCT.
Unless women start effective contraception after using emergency contraception, they remain at risk of unintended pregnancy. Most women in the UK obtain emergency contraception from community pharmacies that are unable to provide ongoing contraception (apart from barrier methods which have high failure rates). This means that women need an appointment with a general practitioner or at a sexual and reproductive health clinic. We conducted a pragmatic cluster randomised cohort crossover trial to determine whether or not pharmacist provision of a bridging supply of a progestogen-only pill plus the invitation to attend a sexual and reproductive health clinic resulted in increased subsequent use of effective contraception (hormonal or intrauterine). Twenty-nine pharmacies in three UK cities recruited women receiving emergency contraception (levonorgestrel). In the intervention, women received a 3-month supply of the progestogen-only pill (75 µg of desogestrel) plus a card that provided rapid access to a local sexual and reproductive health clinic. In the control arm, pharmacists advised women to attend their usual contraceptive provider. The primary outcome was reported use of an effective contraception (hormonal and intrauterine methods) at 4 months. Process evaluation was also conducted to inform any future implementation. The study took place December 2017 and June 2019 and recruited 636 women to the intervention (n = 316) and control groups (n = 320). There were no statistically significant differences in demographic characteristics between the groups. Four-month follow-up data were available for 406 participants: 63% (198/315) of the control group and 65% (208/318) of the intervention group. The proportion of participants reporting use of effective contraception was 20.1% greater (95% confidence interval 5.2% to 35.0%) in the intervention group (58.4%, 95% confidence interval 48.6% to 68.2%) than in the control group (40.5%, 95% confidence interval 29.7% to 51.3%) (adjusted for recruitment period, treatment arm and centre; p = 0.011). The proportion of women using effective contraception remained statistically significantly larger, when adjusted for age, current sexual relationship and history of past use of effective contraception, and was robust to the missing data. There were no serious adverse events. Provision of a bridging supply of the progestogen-only pill with emergency contraception from a pharmacist and the invitation to a sexual and reproductive health clinic resulted in a significant increase in self-reported subsequent use of effective contraception. This simple intervention has the potential to prevent more unintended pregnancies for women after emergency contraception. Current Controlled Trials ISRCTN70616901. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 27. See the NIHR Journals Library website for further project information.


Noncredible cognitive performance in the context of severe brain injury.
In two litigating patients with histories of severe brain injury (i.e., coma > or =2 days and residual brain imaging abnormalities), noncredible cognitive symptomatology was demonstrated by: (1) "failed" performance on multiple cognitive "effort" tests, (2) noncredible performance on standard neuropsychological instruments, (3) questionable validity of personality inventory profiles, and (4) marked inconsistency in test performance across testing evaluations or marked inconsistency between test scores and activities of daily living documented through surveillance videotapes. Some patients with severe traumatic brain injury show substantial, if not full recovery, and in a litigating context, may feign cognitive symptoms. These cases indicate that tests to verify cognitive effort should be routinely administered to all patients in litigation or who have other motive to feign symptoms, not just patients with mild or questionable brain injury.


The effect of nondamaging intensity laser irradiation on the immune system.
Data on in vitro studies of the effect of nondamaging laser irradiation on peripheral blood lymphoid cells of donors and cancer patients are reported including the results of experimental investigations carried out in patients with breast cancer and malignant melanoma. Laser irradiation is demonstrated to potentiate the immunological parameters both in healthy individuals and patients, the effect being more marked in cancer patients. A different action of red and blue laser irradiation on the immune system was revealed. The evidence obtained may be useful in working out the immunotherapeutic methods in cancer management.


Studies into postural hypotension in elderly patients.
Postural hypotension is common in elderly people. A study of 247 patients in Wellington showed an incidence of 33.1 percent. The causative factors included drugs such as diuretics and antihypertensive agents; the consequences of cerebrovascular accidents and peripheral neuropathies; and in a small number, the dysfunction of the autonomic nervous system. The test for autonomic function were difficult to apply to patients and any results likely to be unsatisfactory.


Electrostatic interactions in the hairpin ribozyme account for the majority of the rate acceleration without chemical participation by nucleobases.
Molecular dynamics simulations using a combined quantum mechanical/molecular mechanical potential are used to determine the two-dimensional free energy profiles for the mechanism of RNA transphosphorylation in solution and catalyzed by the hairpin ribozyme. A mechanism is explored whereby the reaction proceeds without explicit chemical participation by conserved nucleobases in the active site. The ribozyme lowers the overall free energy barrier by up to 16 kcal/mol, accounting for the majority of the observed rate enhancement. The barrier reduction in this mechanism is achieved mainly by the electrostatic environment provided by the ribozyme without recruitment of active site nucleobases as acid or base catalysts. The results establish a baseline mechanism that invokes only the solvation and specific hydrogen-bonding interactions present in the ribozyme active site and provide a departure point for the exploration of alternate mechanisms where nucleobases play an active chemical role.


The prevalence and correlates of depression before and after the COVID-19 pandemic declaration among urban refugee adolescents and youth in informal settlements in Kampala, Uganda: A longitudinal cohort study.
There is scant research examining urban refugee youth mental health outcomes, including potential impacts of the COVID-19 pandemic. We examine prevalence and ecosocial risk factors of depression in the periods before and after the COVID-19 pandemic declaration among urban refugee youth in Kampala, Uganda. Data from a cohort of refugee youth (n = 367) aged 16-24 years were collected in periods before (February 2020) and after (December 2020) the WHO COVID-19 pandemic declaration. We developed crude and adjusted generalized estimating equation logistic regression models to examine demographic and ecosocial factors (food insecurity, social support, intimate partner violence) associated with depression, and include time-ecosocial interactions to examine if associations differed before and after the pandemic declaration. The prevalence of depression was high, but there was no significant difference before (27.5%), and after (28.9%) the pandemic declaration (P = .583). In adjusted models, food insecurity (aOR: 2.54; 95% CI: 1.21-5.33) and experiencing violence (aOR: 2.53; 95% CI: 1.07-5.96) were associated with increased depression, and social support was associated with decreased depression (aOR: 0.85; 95% CI: 0.81-0.89). These findings highlight the urgent need for interventions to address chronic depression, food insecurity, and ongoing effects of violence exposure among urban refugee youth in Kampala.


MHC class I upregulation is not sufficient to rescue neonatal alpha motoneurons after peripheral axotomy.
Associated with neuronal death, profound synaptic changes occur in the spinal cord during the apoptotic process triggered after axotomy in neonatal rats. With respect to this, the major histocompatibility complex of class I (MHC class I) has recently emerged as a new mechanism related to synaptic stripping and plasticity. The present study investigated the impact of upregulating MHC class I expression by treatment with beta interferon (beta INF) on motoneuron survival, synaptic plasticity and astrogliosis after neonatal sciatic nerve injury. P2 rats were subjected to unilateral axotomy followed by three days of beta INF treatment. The results were analyzed by counting Nissl stained motoneurons, immunohistochemistry (anti-synaptophysin, MHC class I, GFAP and Iba-1) and transmission electron microscopy. INF treatment induced an increased expression of MHC class I, which resulted in a stronger synaptic elimination process in the spinal cord, as seen by the synaptophysin labeling. GFAP and Iba-1 upregulation were not significantly altered by the INF treatment, displaying the same degree of enhanced reactivity as compared to the placebo group. The ultrastructural analysis showed that, apart from the overall reduction of inputs in the neuropil, no statistical differences were present when comparing the INF and placebo treated animals. Also, neuronal survival was not altered by cytokine administration. The present results provide evidence that MHC class I upregulation after neonatal injury does not change the fate of lesioned motoneurons. In this way, the lack of neurotrophic support may cause broader synaptic loss, which superposes the more subtle effects of the upregulation of MHC class I.


The Cuban Strategy for Combatting the COVID-19 Pandemic.
The emerging SARS-CoV-2, a novel human coronavirus, caused the COVID-19 pandemic, with more than 9.5 million cases and 484 000 known fatalities to date (June 24th, 2020). In several regions, healthcare systems have collapsed whereas interventions applied to slow the viral spreading have had major social and economic impacts. After China, Europe, and the United States, Latin America has emerged as the new epicenter of the pandemic. By late-June, the region accounted for roughly 50% of global daily deaths (Gardner, 2020). The evolution of the COVID-19 pandemic in the region has been heterogenous as several countries are currently experiencing exponential growth of their daily cases and fatalities, while others have successfully controlled their corresponding outbreaks. Cuba confi rmed its fi rst COVID-19 cases in mid-March. After a three-month outbreak, the country recently began to move to a post-epidemic phase. This dispatch details some relevant aspects of the strategy deployed in Cuba to face the COVID-19 pandemic and to decrease the impact of this emerging disease in the country. In addition, it describes the evolution of some epidemiological variables which allowed the country to de-escalate some of the non-pharmaceutical interventions applied during the outbreak.


The role of the surface energy of water in the conformational changes of the human erythrocyte glucose transporter.
There is now strong experimental evidence that the red cell glucose transporter protein operates by a conformational change which has the effect of presenting a sugar binding site to the outside and inside medium of the cells in an alternating manner, but the way in which this is brought about is still unknown. Kinetic evidence that the conformational changes which create the inward and outward facing modes can occur in the absence of a sugar substrate has been put on a firmer experimental basis by Appleman and Lienhard (1989). Conformational changes of the magnitude envisaged are too large to be attributed only to spontaneous thermal agitation in the protein. Theoretical considerations show that the surface energy of water could be an alternative source of energy which, in a suitable reciprocating cycle of activity, could sustain the conformational changes throughout the existence of the transporter.


Tumor Infiltrating Effector Memory Antigen-Specific CD8+ T Cells Predict Response to Immune Checkpoint Therapy.
Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs post-ICT that correlate with successful responses have not been well characterized. Here, we studied murine tumor models with dichotomous responses to ICT. We tracked tumor antigen-specific CTL frequencies and phenotype before and after ICT in responding and non-responding animals. Tumor antigen-specific CTLs increased within tumor and draining lymph nodes after ICT, and exhibited an effector memory-like phenotype, expressing IL-7R (CD127), KLRG1, T-bet, and granzyme B. Responding tumors exhibited higher infiltration of effector memory tumor antigen-specific CTLs, but lower frequencies of regulatory T cells compared to non-responders. Tumor antigen-specific CTLs persisted in responding animals and formed memory responses against tumor antigens. Our results suggest that increased effector memory tumor antigen-specific CTLs, in the presence of reduced immunosuppression within tumors is part of a successful ICT response. Temporal and nuanced analysis of T cell subsets provides a potential new source of immune based biomarkers for response to ICT.


Pediatric primary care provider practices, knowledge, and attitudes of human immunodeficiency virus screening among adolescents.
To evaluate pediatric primary care provider (PCP) HIV screening practices, knowledge, and attitudes. Anonymous cross-sectional, internet-based survey of pediatric PCPs from 29 primary care practices. Survey items assessed current HIV screening practices and knowledge, attitudes, and perceived barriers towards screening. Provider demographics and practice characteristics were analyzed for associations with screening through logistic regression. Of 190 PCPs, there were 101 evaluable responses (response rate: 53.2%). PCPs reported a screening rate for HIV of 39.6% ("most" or "all of the time") during routine adolescent visits compared with violence (60.4%), substance abuse (92.1%), and depression (94.1%) (P < .001). Less than 10% of PCPs correctly answered questions related to Centers for Disease Control and Prevention and state HIV screening recommendations. Of 20 potential HIV screening barriers assessed, mean number of reported barriers was 4.8 (SD ± 2.9); with most concerns related to confidentiality, time for counseling, and follow-up. In a multivariable model, the only factor significantly associated with HIV screening "most" or "all of the time" during routine adolescent visits was urban practice site (aOR 9.8, 95% CI 2.9, 32.9). Provider type, sex, years since training, HIV screening guideline knowledge, and endorsing ≤5 barriers were not associated with HIV screening. Although providers practicing in urban areas were more likely to report screening adolescents for HIV than those in suburban areas, overall self-reported screening rates were low, and several barriers were identified commonly. Future interventions should target increasing providers' knowledge and addressing concerns about confidentiality, requirements and counseling time, and follow-up of results.


Solution conformation of Lys63-linked di-ubiquitin chain provides clues to functional diversity of polyubiquitin signaling.
Diverse cellular events are regulated by post-translational modification of substrate proteins via covalent attachment of one or a chain of ubiquitin molecules. The outcome of (poly)ubiquitination depends upon the specific lysine residues involved in the formation of polyubiquitin chains. Lys48-linked chains act as a universal signal for proteasomal degradation, whereas Lys63-linked chains act as a specific signal in several non-degradative processes. Although it has been anticipated that functional diversity between alternatively linked polyubiquitin chains relies on linkage-dependent differences in chain conformation/topology, direct structural evidence in support of this model has been lacking. Here we use NMR methods to determine the structure of a Lys63-linked di-ubiquitin chain. The structure is characterized by an extended conformation, with no direct contact between the hydrophobic residues Leu8, Ile44, and Val70 on the ubiquitin units. This structure contrasts with the closed conformation observed for Lys48-linked di-ubiquitin wherein these residues form the interdomain interface (Cook, W. J., Jeffrey, L. C., Carson, M., Zhijian, C., and Pickart, C. M. (1992) J. Biol. Chem. 267, 16467-16471; Varadan, R., Walker, O., Pickart, C., and Fushman, D. (2002) J. Mol. Biol. 324, 637-647). Consistent with the open conformation of the Lys(63)-linked di-ubiquitin, our binding studies show that both ubiquitin domains in this chain can bind a ubiquitin-associated domain from HHR23A independently and in a mode similar to that for mono-ubiquitin. In contrast, Lys48-linked di-ubiquitin binds in a different, higher affinity mode that has yet to be determined. This is the first experimental evidence that alternatively linked polyubiquitin chains adopt distinct conformations.


The four-step total synthesis of (-)-chaetominine.
The total synthesis of the alkaloid (-)-chaetominine (1) has been achieved in four steps with an overall yield of 33.4%. Key features of our strategy include a one-pot cascade indole epoxidation - epoxide ring-opening cyclization - lactamization reaction sequence, and the use of a nitro group as a latent amino group for the one-pot construction of the quinazolinone ring. This constitutes a step economical, redox economical and protecting group-free total synthesis.


Decelerating mortality rates in older ages and its prospects through Lee-Carter approach.
The present study attempts to study the age pattern mortality and prospects through Lee-Carter approach. The objectives of the study are to examine the trend of mortality decline and life expectancy. Contemporaneously, we have projected life expectancy up to 2025, projecting ASDR using Lee-Carter method. Life table aging rate (LAR) used to estimate the rate of mortality deceleration. Overtime, LAR increased and during recent decade it remained more or less unchanged. By age, LAR significant increased in the oldest of old. The slope is steepest in the oldest of old in the recent decade. The rates of mortality increased in oldest of old as the age group is more vulnerable to chronic disease and vulnerable to identifiable risk factors for virtually every disease, marked by senility. The analysis revealed that the level of mortality is not declining but rate of acceleration is declining and is further expected to decline. By the year 2025, the age specific death rates for the age group 5-9 and 10-14 will go below one per thousand.Life expectancy will attained as high as 73 and 79 years for male and female and is further expected to increase linearly. 71 percent of total female birth and 57 percent of total male birth will survive up to age 70+. Also the findings revealed that mortality rate is declining with constant rate up to age 70 and thereafter, the mortality rate accelerates and this holds true for both sexes.


The Pacific Biosciences de novo assembled genome dataset from a parthenogenetic New Zealand wild population of the longhorned tick, Haemaphysalis longicornis Neumann, 1901.
The longhorned tick, Haemaphysalis longicornis, feeds upon a wide range of bird and mammalian hosts. Mammalian hosts include cattle, deer, sheep, goats, humans, and horses. This tick is known to transmit a number of pathogens causing tick-borne diseases, and was the vector of a recent serious outbreak of oriental theileriosis in New Zealand. A New Zealand-USA consortium was established to sequence, assemble, and annotate the genome of this tick, using ticks obtained from New Zealand's North Island. In New Zealand, the tick is considered exclusively parthenogenetic and this trait was deemed useful for genome assembly. Very high molecular weight genomic DNA was sequenced on the Illumina HiSeq4000 and the long-read Pac Bio Sequel platforms. Twenty-eight SMRT cells produced a total of 21.3 million reads which were assembled with Canu on a reserved supercomputer node with access to 12 TB of RAM, running continuously for over 24 days. The final assembly dataset consisted of 34,211 contigs with an average contig length of 215,205 bp. The quality of the annotated genome was assessed by BUSCO analysis, an approach that provides quantitative measures for the quality of an assembled genome. Over 95% of the BUSCO gene set was found in the assembled genome. Only 48 of the 1066 BUSCO genes were missing and only 9 were present in a fragmented condition. The raw sequencing reads and the assembled contigs/scaffolds are archived at the National Center for Biotechnology Information.


Protein-protein interactions of tandem affinity purification-tagged protein kinases in rice.
Forty-one rice cDNAs encoding protein kinases were fused to the tandem affinity purification (TAP) tag and expressed in transgenic rice plants. The TAP-tagged kinases and interacting proteins were purified from the T1 progeny of the transgenic rice plants and identified by mass spectrometry. Ninety-five percent of the TAP-tagged kinases were recovered. Fifty-six percent of the TAP-tagged kinases were found to interact with other rice proteins. A number of these interactions were consistent with known protein complexes found in other species, validating the TAP-tag method in rice plants. Phosphorylation sites were identified on four of the kinases that interacted with either 14-3-3 proteins or cyclins.


[The regulation of medical practice in Mexico].
The recent evolution and present situation of the regulation of medical practice in Mexico is discussed. In part one the regulation function is defined in the context of the main functions of a health system. In part two, sanitary regulation and health care regulation are distinguished and discussed. Finally, the present situation of the regulation of medical practice in Mexico is discussed in detail in part three, more specifically, two of the most developed forms of regulation: i) legal regulation and ii) regulation through licensing and certification of general practitioners and medical specialists, respectively. A set of measures to develop a mixed and participatory regulatory system is presented in the section on conclusions.


Telehealth personalized cancer risk communication to motivate colonoscopy in relatives of patients with colorectal cancer: the family CARE Randomized controlled trial.
The rate of adherence to regular colonoscopy screening in individuals at increased familial risk of colorectal cancer (CRC) is suboptimal, especially among rural and other geographically underserved populations. Remote interventions may overcome geographic and system-level barriers. We compared the efficacy of a telehealth-based personalized risk assessment and communication intervention with a mailed educational brochure for improving colonoscopy screening among at-risk relatives of patients with CRC. Eligible individuals age 30 to 74 years who were not up-to-date with risk-appropriate screening and were not candidates for genetic testing were recruited after contacting patients with CRC or their next of kin in five states. Enrollees were randomly assigned as family units to either an active, personalized intervention that incorporated evidence-based risk communication and behavior change techniques, or a mailed educational brochure. The primary outcome was medically verified colonoscopy within 9 months of the intervention. Of the 481 eligible and randomly assigned at-risk relatives, 79.8% completed the outcome assessments within 9 months; 35.4% of those in the personalized intervention group and 15.7% of those in the comparison group obtained a colonoscopy. In an intent-to-treat analysis, the telehealth group was almost three times as likely to get screened as the low-intensity comparison group (odds ratio, 2.83; 95% CI, 1.87 to 4.28; P < .001). Persons residing in rural areas and those with lower incomes benefitted at the same level as did urban residents. Remote personalized interventions that consider family history and incorporate evidence-based risk communication and behavior change strategies may promote risk-appropriate screening in close relatives of patients with CRC.


Immunization of mice with components of Pasteurella multocida.
Log-phase cells of Pasteurella multocida strain P-1059 were used to prepare isolated culture filtrate, cell wall, and cytoplasmic components. Culture filtrate was further separated by column chromatography. A portion of cytoplasm and culture filtrate was conjugated to ferritin by means of metaxylylene diisocyanate. Cell walls induced more protection in mice than the conjugated or unconjugated cytoplasm or culture filtrate. The cell walls caused edema and erythema when given intradermally in rabbits, whereas cytoplasm and culture filtrate produced dermal necrosis. The first of four chromatographically separated fractions of culture filtrate was possibly more immunogenic in mice than cell walls. This fraction was less reactive intradermally in rabbits than cell walls but more reactive than the other fractions.


MADS-box out of the black box.
The compelling elegance of using genome-wide scans to detect the signature of selection is difficult to resist, but is countered by the low demonstrated efficacy of pinpointing the actual genes and traits that are the targets of selection in nonmodel species. While the difficulty of going from a suggestive signature to a functional nucleotide polymorphism should not prevent researchers from using genome scans, it does lessen their long-term utility within and across study systems. In a new study published in this issue of Molecular Ecology (Mariac et al. 2011), researchers have gone a long way towards increasing the relevance of genome-wide scans for selection via two approaches: (i) they tailored the markers used in the scan to target a family of developmental genes that were good candidates for controlling a trait of interest and (ii) they used an independent mapping population to confirm the association of the gene with polymorphism in the trait of interest. All of this was completed in the nonmodel system of pearl millet (Pennisetum glaucum) and may provide a road map for other researchers hoping to pin down solid candidate genes for selected traits in natural or cultivated systems. Outside of these broad methodological innovations, the paper specifically focuses on a trait (flowering time) that varies across an environmental gradient (rainfall). This environmental gradient potentially serves as a model for environmental change over time, and allele frequencies at the gene can therefore be used to track how populations of pearl millet will adapt to future climate shifts at the genetic level.


[Cancer incidence estimation by hospital discharge flow as compared with cancer registries data].
the study evaluates the accuracy of an algorithm based on hospital discharge data (HDD) in order to estimate breast cancer incidence in three italian regions (Emilia-Romagna, Toscana and Veneto) covered by cancer registries (CR). The evolution of computer-based information systems in health organization suggests automatic processing of HDD as a possible alternative to the time-consuming methods of CR. The study intends to verify whether HDD quickly provides reliable cancer incidence estimates for diagnosis and therapy evaluations. an algorithm based on discharge diagnosis and surgical therapy of hospitalized breast cancer patients was developed in order to provide breast cancer incidence. Results were compared with the corresponding incidence data of cancer registries. The accuracy of the automatic method was also verified by a direct record-linkage between HDD output and registries' files. The overall survival of cases lost to "HDD method" was analyzed. in the period covered by the study (3,125,425 person/year) CR enrolled 6,079 incident cases, compared to 6,000 cases recorded through the HDD flow. Incidence rates of the two methods (CR 194.5; HDD 192.0 x 100.000) showed no statistical differences. However, matched cases by the two methods were only 5,038. The sensitivity of the HDD algorithm was 82.9% and its predictive positive value (PPV) was 84.0%. False positive cases were 9.9%. On the other hand, 12.3% CR incident cases were not identified by the algorithm: these were mainly made up of older women, not eligible for surgical therapy. Their three-years survival was 62.0% vs 88.8% of the whole incidence group. HDD flow performance was similar to observations reported in the literature. The agreement between HDD and CR incidence rates is a result of a cross effect of both sensitivity and specificity limitations of the HDD algorithm. This can seriously impair the reliability of the latter method with regard to the evaluation of diagnostic and therapeutic strategies in cohort studies (i.e. the most effective approach to health setting in oncology).s.


Risk factors for vascular disease and arteriovenous fistula dysfunction in hemodialysis patients.
Vascular access dysfunction is an important cause of morbidity for dialysis patients and a major contributor to hemodialysis cost. Thrombosis is a leading cause of vascular access failure, and usually results from stenotic lesions in the venous outflow system. This study was designed to explore the impact of serum levels of various risk factors for thrombosis and accelerated fibrointimal hyperplasia on progressive stenosis, and the subsequent thrombosis of hemodialysis fistula. A cross-sectional and 2-yr prospective pilot study was performed in 30 nondiabetic hemodialysis patients with primary arteriovenous fistula. Venous dialysis pressure, urea recirculation, color Doppler sonography, and angiography were used to monitor vascular access patency. Eleven patients (37%) developed a progressive stenosis in the venous circuit, which was complicated by thrombosis in three patients. Compared with the patients without fistula dysfunction, these patients had higher serum levels of monocyte chemoattractant protein-1 and interleukin-6, two cytokines that regulate the proliferation of vascular smooth muscle cells, which is the key mechanism in the pathogenesis of fistula stenosis. In addition, they had hyperinsulinemia, hyperlipidemia, and increased plasma levels of two hemostasis-derived risk factors for thrombosis: plasminogen activator inhibitor type 1 and factor VII. Monocyte chemoattractant protein-1, interleukin-6, plasminogen activator inhibitor type 1, factor VII, triglycerides, and the ratios for cholesterol/HDL-cholesterol, apolipoprotein (apo) A-I/ apo C-III, apo A-I/apo B, and glucose/insulin were independent predictors of fistula dysfunction. This study demonstrates the influece of cytokines, hemostasis-derived vascular risk factor, hyperinsullnemia, and abnormallties of lipids and apolipoproteins on primary fistula survival. The assessment of these factors might be useful for the identification of the patients at risk of fistula stenosis and thrombosis.


The acid-tolerant microbiota associated with plaque from initial caries and healthy tooth surfaces.
The intent of this study was to compare the inherent acid tolerance of bacteria in samples of dental plaque from tooth sites in subjects with and without initial caries. Plaque was collected from approximal surfaces showing early enamel caries and from healthy tooth surfaces in the same subjects, as well as from enamel surfaces of caries-free individuals. In addition to plating on blood agar, the plaque samples were plated directly on non-selective solid agar medium buffered to pH 7.0, 6.0, 5.5, 5.0, 4.5 and 4.0 to avoid any loss of adaptation to acid during primary isolation of plaque bacteria. The results showed that approximately 50% of the total cultivable plaque microbiota from caries, as well as healthy tooth sites, was able to grow at pH 5.5 and 1% at pH 5.0, pH values regarded as critical for the demineralization of tooth enamel. At pH 5.0, members of the genus Streptococcus were the dominant group, but mutans streptococci accounted for less than half of the streptococcal viable count. The other acid-tolerant streptococcal isolates included Streptococcus anginosus, Streptococcus constellatus, Streptococcus gordinii, Streptococcus intermedius, Streptococcus mitis, Streptococcus oralis, Streptococcus salivarius and SStreptococcus sanguis. Analysis of the results indicated that the mutans streptococci in dental plaque were highly variable with respect to acid tolerance, and that both caries and healthy sites harboured significant numbers of mutans streptococci that were not acid-tolerant.


Adaptive testing for psychological assessment: how many items are enough to run an adaptive testing algorithm?
Although the principles of adaptive testing were established in the psychometric literature many years ago (e.g., Weiss, 1977), and practice of adaptive testing is established in educational assessment, it not yet widespread in psychological assessment. One obstacle to adaptive psychological testing is a lack of clarity about the necessary number of items to run an adaptive algorithm. The study explores the relationship between item bank size, test length and measurement precision. Simulated adaptive test runs (allowing a maximum of 30 items per person) out of an item bank with 10 items per ability level (covering .5 logits, 150 items total) yield a standard error of measurement (SEM) of .47 (.39) after an average of 20 (29) items for 85-93% (64-82%) of the simulated rectangular sample. Expanding the bank to 20 items per level (300 items total) did not improve the algorithm's performance significantly. With a small item bank (5 items per ability level, 75 items total) it is possible to reach the same SEM as with a conventional test, but with fewer items or a better SEM with the same number of items.


Prevalence and Pattern of Late-Stage Presentation in Women with Breast and Cervical Cancers in Lagos University Teaching Hospital, Nigeria.
Cervical and breast cancers are the most common cancers among women in developing countries contributing to high morbidity and mortality. Even though both these cancers have a better prognosis if caught early; however, studies conducted in Nigeria still show a large incidence of late tumor stage presentation. This study aimed at identifying the patient and disease characteristics of women with breast and cervical cancers presenting at a tertiary medical facility in Nigeria, with emphasis on the prevalence of late-stage presentation and reasons for late-stage presentation. This cross-sectional study recruited women at Lagos University Teaching Hospital (LUTH) with breast and cervical cancers from April to June 2016; an interviewer-based questionnaire was administered to 105 patients who seen to elicit information needed to achieve the set objectives. The mean age of patients was 51.09 (±11.70) years; majority had no known family history and no health insurance. Most cervical cancer patients were unaware of their human papillomavirus status. About 72.81% of all patients presented late, surprisingly 87.6% of patients presented in an appropriate health-care facility as place of the first contact, but still presented in LUTH at late stages of their disease mostly due to misdiagnosis. Reasons for late presentation included fear, misconceptions, misdiagnosis, ignorance, and prolonged investigation time. As late-stage presentation was associated with both poor health-seeking behavior and health system delays; interventions should not only include increased awareness for the early detection and diagnosis but also measures to ensure improvements in health service delivery to ensure timely diagnosis and the management of breast and cervical cancers.


Pneumoperitoneum and signs of peritonitis from a pleuroperitoneal shunt.
Pleuroperitoneal shunting has become an increasingly popular therapeutic option for the control of intractable pleural effusions. However, there exists a paucity of information regarding institutional and individual experiences with this technique. We report an unusual complication of a Denver pleuroperitoneal shunt that resulted in pneumoperitoneum and a clinical picture of diffuse peritonitis from a ruptured abdominal viscus. The cause of this condition was continuous decompression of a pneumothorax into the peritoneal cavity, through the shunt.


Antimicrobial resistance profiles of microorganisms isolated from hospitalized patients in Dominican Republic.
To define the antimicrobial resistance profiles of the microorganisms most commonly isolated from hospitalized adult patients in Dominican Republic (DR). A retrospective, cross-sectional study of phenotypic antimicrobial susceptibility patterns was conducted using data from 3 802 clinical microbiology reports specifying positive bacterial cultures in samples collected from patients admitted to the clinical, surgery, and intensive care units (ICU) at three tertiary-level care hospitals in the city of Santiago de los Caballeros from 1 January 2016 - 31 December 2017. Descriptive statistics and chi-square test (P ≤ 0.05) were used to analyze the qualitative variables. At the three hospitals, there were 932, 1 090, and 1 780 microbiology reports analyzed. Of the total, 1274 were from the ICU, 1 042 from the surgery unit, and 1 486 from the clinical unit. Methicillin resistance was found in 57.3% of the Staphylococcus aureus isolates and 75.3% of the coagulase-negative staphylococci. Third-generation cephalosporin resistance was detected in 54.4% of isolates identified as members of the Enterobacteriaceae family, 67.3% of the Acinetobacter spp., and 91.7% of the Pseudomonas, while carbapenem resistance was shown by 8.0%, 23.8%, and 51.0% of these, respectively. Most of the resistant Acinetobacter spp. isolates were found in just one hospital and the prevalence of Enterobacteriaceae resistant to carbapenems was highest in the ICU. Antimicrobial resistance levels are high among hospitalized patients in Dominican Republic and may cause enhanced risk factors that impact clinical outcomes. Urgent measures are needed to address antimicrobial resistance in DR.


Integrated Metabolomic and Transcriptomic Analysis Reveals Differential Mechanism of Flavonoid Biosynthesis in Two Cultivars of Angelica sinensis.
Angelica sinensis is a traditional Chinese medicinal plant that has been primarily used as a blood tonic. It largely relies on its bioactive metabolites, which include ferulic acid, volatile oils, polysaccharides and flavonoids. In order to improve the yield and quality of A. sinensis, the two cultivars Mingui 1 (M1), with a purple stem, and Mingui 2 (M2), with a green stem, have been selected in the field. Although a higher root yield and ferulic acid content in M1 than M2 has been observed, the differences of flavonoid biosynthesis and stem-color formation are still limited. In this study, the contents of flavonoids and anthocyanins were determined by spectrophotometer, the differences of flavonoids and transcripts in M1 and M2 were conducted by metabolomic and transcriptomic analysis, and the expression level of candidate genes was validated by qRT-PCR. The results showed that the contents of flavonoids and anthocyanins were 1.5- and 2.6-fold greater in M1 than M2, respectively. A total of 26 differentially accumulated flavonoids (DAFs) with 19 up-regulated (UR) and seven down-regulated (DR) were obtained from the 131 identified flavonoids (e.g., flavonols, flavonoid, isoflavones, and anthocyanins) in M1 vs. M2. A total 2210 differentially expressed genes (DEGs) were obtained from the 34,528 full-length isoforms in M1 vs. M2, and 29 DEGs with 24 UR and 5 DR were identified to be involved in flavonoid biosynthesis, with 25 genes (e.g., CHS1, CHI3, F3H, DFR, ANS, CYPs and UGTs) mapped on the flavonoid biosynthetic pathway and four genes (e.g., RL1, RL6, MYB90 and MYB114) belonging to transcription factors. The differential accumulation level of flavonoids is coherent with the expression level of candidate genes. Finally, the network of DAFs regulated by DEGs was proposed. These findings will provide references for flavonoid production and cultivars selection of A. sinensis.


Common genetic variants near the Brittle Cornea Syndrome locus ZNF469 influence the blinding disease risk factor central corneal thickness.
Central corneal thickness (CCT), one of the most highly heritable human traits (h(2) typically>0.9), is important for the diagnosis of glaucoma and a potential risk factor for glaucoma susceptibility. We conducted genome-wide association studies in five cohorts from Australia and the United Kingdom (total N = 5058). Three cohorts were based on individually genotyped twin collections, with the remaining two cohorts genotyped on pooled samples from singletons with extreme trait values. The pooled sample findings were validated by individual genotyping the pooled samples together with additional samples also within extreme quantiles. We describe methods for efficient combined analysis of the results from these different study designs. We have identified and replicated quantitative trait loci on chromosomes 13 and 16 for association with CCT. The locus on chromosome 13 (nearest gene FOXO1) had an overall meta-analysis p-value for all the individually genotyped samples of 4.6x10(-10). The locus on chromosome 16 was associated with CCT with p = 8.95x10(-11). The nearest gene to the associated chromosome 16 SNPs was ZNF469, a locus recently implicated in Brittle Cornea Syndrome (BCS), a very rare disorder characterized by abnormal thin corneas. Our findings suggest that in addition to rare variants in ZNF469 underlying CCT variation in BCS patients, more common variants near this gene may contribute to CCT variation in the general population.


Critical function for the Ras-GTPase activating protein RASA3 in vertebrate erythropoiesis and megakaryopoiesis.
Phenotype-driven approaches to gene discovery using inbred mice have been instrumental in identifying genetic determinants of inherited blood dyscrasias. The recessive mutant scat (severe combined anemia and thrombocytopenia) alternates between crisis and remission episodes, indicating an aberrant regulatory feedback mechanism common to erythrocyte and platelet formation. Here, we identify a missense mutation (G125V) in the scat Rasa3 gene, encoding a Ras GTPase activating protein (RasGAP), and elucidate the mechanism producing crisis episodes. The mutation causes mislocalization of RASA3 to the cytosol in scat red cells where it is inactive, leading to increased GTP-bound Ras. Erythropoiesis is severely blocked in scat crisis mice, and ~94% succumb during the second crisis (~30 d of age) from catastrophic hematopoietic failure in the spleen and bone marrow. Megakaryopoiesis is also defective during crisis. Notably, the scat phenotype is recapitulated in zebrafish when rasa3 is silenced. These results highlight a critical, conserved, and nonredundant role for RASA3 in vertebrate hematopoiesis.


Ureteral obstruction of solitary kidneys by iliac artery aneurysms.
Two patients with solitary kidneys had ureteral obstruction caused by iliac artery aneurysms. Both patients were treated successfully with ureterolysis and temporary proximal diversion. Iliac artery aneurysms generally remain asymptomatic; however, patients may have urologic complaints (such as hematuria, flank pain, anuria, or a pulsatile urinary stream), and severe complications may develop as a result of an obstructive uropathy. Diagnosis is confirmed by cystoscopy when a mass is present, intravenous pyelography, retrograde pyelography, and arteriography. Treatment must be individualized with consideration of the etiology of the aneurysm and condition of the patient. Surgical correction of the aneurysm may be appropriate. Ureterolysis, with proximal diversion as a temporary safety valve, is a useful procedure particularly when the patient has a solitary kidney.


The effect of peat components on endocrine and immunological parameters and on trace elements--results of two pilot studies.
Peat and different peat preparations are successfully used in clinical therapies for different indications (as, for instance, in the field of gynecology). New studies show the biochemical effects of peat components which they have aside from their physical-thermal effects. This is of extraordinary interest with regard to the medical use of peat, because considerable concentrations of trace elements and heavy metals have been found in different kinds of peat. By means of atomic spectrometry it was investigated in 17 female patients with irritable bladder whether and how variations of the concentration of special trace elements and heavy metals (lead, cadmium, copper, manganese) could be measured within 24-hour urine after vaginal peat-mush treatments had been applied serially. Additionally, the effect of peat-mush baths compared to the effect of water baths (n=6) - both of which were applied to 17 female patients with degenerative diseases - was examined with regard to their special endocrinological parameters. The results concerning safety did not show any changes of the concentration of the trace-elements or heavy metals within the 24-hour urine. These results can be explained by the chelating features of the peat components, which are the reason for the absorption of the trace elements. Examinations done to compare the effects of peat-mush baths and water baths have shown that peat components - independent from their thermal effects - are the reason for the occurrence of special effects. This applies in particular to the parameter soluble interleukin-2-receptor. As regards estradiol, a significant increase could be measured after peat-mush baths had been applied to 17 postmenopausal female patients (n=11). Comparing these results with those of the group of patients treated with water baths, we noticed that the increase of estradiol was remarkably lower and not significant. The effect of the peat components is thought to be the reason for this.


The clinical outcome of abdominoplasty performed under conscious sedation: increased use of fentanyl correlated with longer stay in outpatient unit.
The objective of this study was to present data supporting the effectiveness of performing mini and full abdominoplasties under conscious sedation with local anesthesia. The authors performed 20 such operations between 1994 and 1996, using a combination of midazolam (Versed) and fentanyl instead of general anesthesia (without an anesthesiologist or nurse anesthetist present). At 5- to 10-minute intervals, the surgeon would order the injection of 1 cc (1 mg/ml) of midazolam and 1 cc (50 microg/ml) of fentanyl. The amount and the interval varied based on the patient's level of sedation. Blood pressure, oxygen saturation, and the patient's response to verbal and physical stimuli were used to assess the sedation level. Average operating time was 147.5 minutes, and mean length of stay in the outpatient recovery room was 235.5 minutes. The average amounts of midazolam and fentanyl used were 9.4 mg (6 to 12.5 mg) and 532 microg (300 to 800 microg), respectively. The average age of patients in this group was 41.7 years (28 to 63 years). Nineteen patients were discharged the same day. There were no surgical complications and no complication related to the sedation (such as respiratory or cardiac compromise). The average follow-up of these patients was 1.2 years (range, 3 to 21 months). Correlation coefficient rates and regression rates were calculated. The longer the procedure, the more midazolam was used intraoperatively (r = 0.5, p = 0.03). However, there was no correlation between the length of the procedure and the amount of fentanyl used. Rather, there was a positive correlation demonstrating that patients who received more fentanyl stayed longer in the outpatient recovery area after surgery (r = 0.6, p < 0.01). The age of the patients and the amount of midazolam did not correlate with how fast they went home from the outpatient area. In conclusion, full and mini abdominoplasties can be performed safely using conscious sedation without compromising patient care or surgical outcome. Second, the survey revealed that patient satisfaction with these procedures performed under conscious sedation was very high. Third, the increased use of fentanyl, not midazolam, resulted in a longer stay in the outpatient unit after surgery. Nausea is a known side effect of narcotic analgesics, and it correlated with a higher dose of fentanyl administration in the patients. The authors are now routinely administering a dose of either droperidol or odansetron (Zofran) preoperatively (both are antiemetics). Previously, the ratio of midazolam and fentanyl injection was 1:1 every 5 to 10 minutes, but now it is 2: 1 to 4: 1 every 5 to 10 minutes (a smaller dose of fentanyl is administered). The conscious sedation technique should be an option for patients and plastic surgeons in academic and community hospital settings if they desire.


Androgen and estrogen treatment, alone or in combination, differentially influences bone maturation and hypothalamic mechanisms that time puberty in the male rhesus monkey (Macaca mulatta).
In higher primates, the mechanisms that govern the ontogeny of gonadotropin-releasing hormone pulse generator activity and that, therefore, dictate the timing of the onset of puberty remain intriguingly elusive. Groups of three infant agonadal male monkeys were treated with sex steroids [17beta-estradiol (E(2)), testosterone (T), or dihydrotestosterone (DHT)] for the first year of life to advance bone age (BA). E(2) and T resulted in a significant advancement of BA, and a pubertal BA of 130 wk was attained at a mean chronological age of 64 and 67 wk, respectively. In contrast, DHT failed to advance BA during treatment but stimulated linear growth. All animals exhibited a pubertal resurgence in LH secretion, but the timing of this developmental event did not differ between treatment and control groups (the mean for all animals was 117.7 +/- 8.9 wk). Two of the three T-treated animals, however, displayed a pubertal LH resurgence at a remarkably young age (70 and 76 wk of age) that coincided with T withdrawal. During the period of steroid treatment, all three groups were significantly heavier than the controls. The rate of body weight gain was most rapid in the DHT-treated group. Steroid treatments also resulted in accelerated linear growth. Body weight gain and linear growth continued at the same rate as controls after withdrawal of treatment. These data indicate that attainment of a pubertal BA may be a necessary but not a sufficient factor to trigger the onset of puberty. The results not only are consistent with the view that androgen-induced skeletal maturation in males is mediated by estrogen receptor activity but also indicate that androgen receptor activity contributes to the pubertal growth spurt in males.


Atomic-scale structure evolution in a quasi-equilibrated electrochemical process of electrode materials for rechargeable batteries.
Lithium-ion batteries have proven to be extremely attractive candidates for applications in portable electronics, electric vehicles, and smart grid in terms of energy density, power density, and service life. Further performance optimization to satisfy ever-increasing demands on energy storage of such applications is highly desired. In most of cases, the kinetics and stability of electrode materials are strongly correlated to the transport and storage behaviors of lithium ions in the lattice of the host. Therefore, information about structural evolution of electrode materials at an atomic scale is always helpful to explain the electrochemical performances of batteries at a macroscale. The annular-bright-field (ABF) imaging in aberration-corrected scanning transmission electron microscopy (STEM) allows simultaneous imaging of light and heavy elements, providing an unprecedented opportunity to probe the nearly equilibrated local structure of electrode materials after electrochemical cycling at atomic resolution. Recent progress toward unraveling the atomic-scale structure of selected electrode materials with different charge and/or discharge state to extend the current understanding of electrochemical reaction mechanism with the ABF and high angle annular dark field STEM imaging is presented here. Future research on the relationship between atomic-level structure evolution and microscopic reaction mechanisms of electrode materials for rechargeable batteries is envisaged.


The effectiveness of simethicone in improving visibility during colonoscopy.
In colonoscopy examination, luminal visibility is frequently limited due to intraluminal bubbles. In present study was evaluated factors affecting bubble formation and the effects of simethicone in preventing bubble formation during colonoscopy. Consecutive patients (n=164) who received polyethylene glycol or sodium phosphate for bowel preparation were prospectively enrolled. Before colonoscopy, 57 patients took 80 mg simethicone after ingestion of bowel preparation solution and 107 did not to determine whether simethicone decreased bubble formation. Intraluminal gas bubbles were assessed and graded as follows: 0, minimal or none; 1, covering less than half the lumen; 2, covering at least half the lumen or the entire circumference. Grade 2 bubbles were regarded as significant, limiting visibility. Sodium phosphate preparation tended to have more bubbles than the polyethylene glycol. Significant bubbles were more likely to occur in males than females (p = 0.020). Significant bubbles were noted in 34.6% of patients without simethicone and 7% of patients with simethicone. Simethicone significantly lowered the incidence of bubbles during colonoscopy when given after a preparation solution (p < 0.05), The present study findings indicate that taking simethicone after an oral polyethylene glycol or sodium phosphate preparation can improve colonic visibility by diminishing colonic bubbles.


alpha-Fetoprotein levels in fullterm and very low birthweight infants.
Plasma alpha-fetoprotein (alpha-FP) levels were determined in fullterm and very low birthweight (VLBW) infants in the first week of life and serially in a cohort of VLBW infants for the first 24 weeks after delivery. A rapid decline in alpha-FP levels was observed in both the fullterm and VLBW infants initially. Beyond 2 weeks of age, there was a gradual, linear decline until 6 weeks, followed by a more rapid period of decline from 6 to 16 weeks. The decline in the ensuing weeks demonstrated an asymptotic pattern. The half-life of alpha-FP was 7.5 days in the first week of life in both fullterm and preterm infants, 28.7 days from 2 to 6 weeks of life and 11.9 days from 6 to 16 weeks of life in VLBW infants.


The Effect of SLT Laser Application on Iris to Treat Sectorial Heterochromia: A Promising Technique.
The purpose of this study is to report a new and promising method for changing iris color in a sectorial heterochromia iridis patient. A 22-year-old man with a complaint of innate color disparity between his eyes presented to our clinic to seek medical advice. He underwent a comprehensive ophthalmic examination, including visual acuity, biomicroscopy, fundoscopy, intraocular pressure measurements, endothelial cell count, and evaluation of iridocorneal angle. The causes of acquired heterochromia were excluded. After a detailed explanation of the procedure and probable side effects, the patient underwent an application with a laser device that produces a frequency-doubled 532 nm wavelength Nd:YAG laser beam with a spot size of 400 μm (selective laser trabeculoplasty laser device). The heterochromic areas (brown) were divided into zones and a gradual treatment pattern was performed to avoid inflammation and flare. The patient showed no side effects such as increased intraocular pressure, pain, corneal edema, hypopyon formation, decrease in visual acuity, synechia, or iris defect. After two complete sessions, the color difference disappeared and a solid eye color was achieved.


Endocrine and antineoplastic actions of growth hormone-releasing hormone antagonists.
Potent antagonists of growth hormone-releasing hormone (GHRH) have been developed for the treatment of disorders caused by excessive GHRH or growth hormone (GH) production and for therapy of cancers. GHRH antagonists suppressed the release of GH and insulin-like growth factor (IGF)-I in transgenic mice overexpressing human (h) GHRH gene, an animal model of human acromegaly. It was also shown in GH3 rat pituitary tumor cells overexpressing the human pituitary GHRH receptor (pGHRH-R) that GHRH antagonists can inhibit c-AMP production and GH secretion through the human receptor. These observations indicate that GHRH antagonists could be used clinically in disorders characterized by excessive GHRH/GH secretion. Many recent studies demonstrate that GHRH antagonists can inhibit tumor growth by several mechanisms. By indirect action through pGHRH-Rs these antagonists suppress circulating GH/IGF-I level, which results in the inhibition of cancers that depend on GH and/or IGF-I as growth factors. However, GHRH antagonists are also effective inhibitors of tumor IGF-II production, which is a potent mitogen but independent of GH. GHRH antagonists can inhibit tumor cell proliferation by direct action on tumor cell receptors, suppressing the IGF-II and other growth factor production of tumor cells. In addition, various human tumors and tumor cell lines secrete GHRH peptide and respond to GHRH with proliferation. This finding suggests that GHRH functions as an autocrine growth factor and that GHRH antagonists can block its effects on tumor growth. Recently, we demonstrated the expression of hGHRH-R and its splice variants in various human cancers. Antiproliferative action of GHRH antagonists on these cancers indicates that the direct inhibitory effects of GHRH antagonists are mediated by tumoral GHRH receptors.


Genetic variations and haplotypes of CYP2C19 in a Japanese population.
Forty-eight single nucleotide variations, including 27 novel ones, were found in the 5'- regulatory region, all of the exons and their surrounding introns of CYP2C19 in 253 Japanese subjects (134 diabetic patients and 119 healthy volunteers). Identified novel variations were as follows: -2772G>A, 2767_-2760delGGTGAACA, -2720T>C, -2547delG, -2545G>T, -2545_-2544 delGC, and -2040C>T in the enhancer region; -778C>T, -777G>A, -529G>C, -189C>A, and -185A>G in the promoter region; 151A>G (S51G), 481G>C (A161P), 986G>A (R329H), 1078G>A (D360N), and 1119C>T (D373D) in the exons, and IVS1+128T>A, IVS3+163G>A, IVS4+271A>G, IVS5-49A>G, IVS6-210C>T, IVS6-196T>A, IVS6-32T>A, IVS7+84G>A, IVS7-174C>T, and IVS8+64C>T in the introns. Since we found no significant differences in the variation frequencies between healthy volunteers and diabetic patients, the data for all subjects were treated as one group in further analysis. The allele frequencies were 0.265 for IVS6-196T>A, 0.045 for -2772G>A and -2720T>C, 0.024 for -2040C>T, 0.014 for IVS7-174C>T, 0.010 for -529G>C, 0.006 for IVS1+128T>A and 481G>C (A161P), 0.004 for -2767_-2760delGGTGAACA and IVS6-210C>T, and 0.002 for the other 17 variations. In addition, the two known nonsynonymous single nucleotide polymorphisms, 681G>A (splicing defect, (*)2 allele) and 636G>A (W212X; (*)3 allele) were detected at 0.267 and 0.128 frequencies, respectively. No variation was detected in the known binding sites for constitutive androstane receptor and glucocorticoid receptor. Linkage disequilibrium analysis showed several close linkages of variations throughout the gene. By using the variations, thirty-one haplotypes of CYP2C19 and their frequencies were estimated. Our results would provide fundamental and useful information for genotyping CYP2C19 in the Japanese and probably other Asian populations.