Combining markers into haplotypes can improve population structure inference.
High-throughput genotyping and sequencing technologies can generate dense sets of genetic markers for large numbers of individuals. For most species, these data will contain many markers in linkage disequilibrium (LD). To utilize such data for population structure inference, we investigate the use of haplotypes constructed by combining the alleles at single-nucleotide polymorphisms (SNPs). We introduce a statistic derived from information theory, the gain of informativeness for assignment (GIA), which quantifies the additional information for assigning individuals to populations using haplotype data compared to using individual loci separately. Using a two-loci-two-allele model, we demonstrate that combining markers in linkage equilibrium into haplotypes always leads to nonpositive GIA, suggesting that combining the two markers is not advantageous for ancestry inference. However, for loci in LD, GIA is often positive, suggesting that assignment can be improved by combining markers into haplotypes. Using GIA as a criterion for combining markers into haplotypes, we demonstrate for simulated data a significant improvement of assigning individuals to candidate populations. For the many cases that we investigate, incorrect assignment was reduced between 26% and 97% using haplotype data. For empirical data from French and German individuals, the incorrectly assigned individuals can, for example, be decreased by 73% using haplotypes. Our results can be useful for challenging population structure and assignment problems, in particular for studies where large-scale population-genomic data are available.


Country ownership and capacity building: the next buzzwords in health systems strengthening or a truly new approach to development?
During the last decade, donor governments and international agencies have increasingly emphasized the importance of building the capacity of indigenous health care organizations as part of strengthening health systems and ensuring sustainability. In 2009, the U.S. Global Health Initiative made country ownership and capacity building keystones of U.S. health development assistance, and yet there is still a lack of consensus on how to define either of these terms, or how to implement "country owned capacity building". Concepts around capacity building have been well developed in the for-profit business sector, but remain less well defined in the non-profit and social sectors in low and middle-income countries. Historically, capacity building in developing countries has been externally driven, related to project implementation, and often resulted in disempowerment of local organizations rather than local ownership. Despite the expenditure of millions of dollars, there is no consensus on how to conduct capacity building, nor have there been rigorous evaluations of capacity building efforts. To shift to a new paradigm of country owned capacity building, donor assistance needs to be inclusive in the planning process and create true partnerships to conduct organizational assessments, analyze challenges to organizational success, prioritize addressing challenges, and implement appropriate activities to build new capacity in overcoming challenges. Before further investments are made, a solid evidence base should be established concerning what works and what doesn't work to build capacity. Country-owned capacity building is a relatively new concept that requires further theoretical exploration. Documents such as The Paris Declaration on Aid Effectiveness detail the principles of country ownership to which partner and donor countries should commit, but do not identify the specific mechanisms to carry out these principles. More evidence as to how country-owned capacity building plays out in practice is needed to guide future interventions. The Global Health Initiative funding that is currently underway is an opportunity to collect evaluative data and establish a centralized and comprehensive evidence base that could be made available to guide future country-owned capacity building efforts.


A mouse beta-globin mutant that is an exact model of hemoglobin Rainier in man.
A mutation induced by ethylnitrosourea in a spermatogonial stem cell of a 101/H mouse has resulted in a structurally altered beta-diffuse major globin in one of his offspring. The mutant hemoglobin is associated with polycythemia, rubor, increased oxygen affinity and decreased hem-hem interaction. The mutant haplotype has been designated Hbbd4, polycythemia. Amino acid analysis of the mutant globin has shown that a single substitution beta 145 Tyr----Cys has occurred, and it is proposed that ethylnitrosourea induced an A----G transition in the tyrosine codon (TAC----TGC). This murine polycythemia is homologous with hemoglobin Rainier in man, in which the amino acid substitution is also beta 145 Tyr----Cys and which is associated with similar physiological consequences.


Interpreting nonverbal cues to deception in real time.
When questioning the veracity of an utterance, we perceive certain non-linguistic behaviours to indicate that a speaker is being deceptive. Recent work has highlighted that listeners' associations between speech disfluency and dishonesty are detectable at the earliest stages of reference comprehension, suggesting that the manner of spoken delivery influences pragmatic judgements concurrently with the processing of lexical information. Here, we investigate the integration of a speaker's gestures into judgements of deception, and ask if and when associations between nonverbal cues and deception emerge. Participants saw and heard a video of a potentially dishonest speaker describe treasure hidden behind an object, while also viewing images of both the named object and a distractor object. Their task was to click on the object behind which they believed the treasure to actually be hidden. Eye and mouse movements were recorded. Experiment 1 investigated listeners' associations between visual cues and deception, using a variety of static and dynamic cues. Experiment 2 focused on adaptor gestures. We show that a speaker's nonverbal behaviour can have a rapid and direct influence on listeners' pragmatic judgements, supporting the idea that communication is fundamentally multimodal.


Development and initial psychometric validation of the Brief-Caffeine Expectancy Questionnaire (B-CaffEQ).
Caffeine is the most widely available and consumed psychoactive substance in the United States. Extant work indicates that across substances, use expectancies play a marked role in the development and maintenance of consumption patterns. Despite a burgeoning line of etiological and intervention-oriented research focused on expectancies (e.g., alcohol), there is a limited literature regarding caffeine use effect expectancies, specifically. To facilitate this work, the Caffeine Expectancy Questionnaire (CaffEQ) was developed and psychometrically validated; however, the length of the CaffEQ (i.e., 47 items) may hinder widespread adoption of this tool. As such, the current study provides an initial psychometric validation of a brief, 20-item version-the Brief-Caffeine Expectancy Questionnaire (B-CaffEQ)-in a multiethnic sample of undergraduate students (N = 975). Results showed that the B-CaffEQ replicated the 7-factor structure of the original CaffEQ using both constrained (confirmatory factor analysis) and less constrained (exploratory structural equation modeling) structural models and evidenced good internal consistency across subscales. The B-CaffEQ also demonstrated concurrent validity with caffeine use frequency indices, replicated and extended convergent validity between caffeine expectancy subscales and related behavioral and psychological constructs, and demonstrated discriminant validity with other related, but notably distinct, stimulant use metrics (e.g., cocaine, Ritalin). Lastly, the B-CaffEQ appears to provide an invariant measure of expectancies across types of caffeine users. These findings indicate that the B-CaffEQ is a reliable assessment of caffeine use effect expectancies, with acceptable-to-good psychometric properties-comparable in length to other substance use expectancies measures-that may be more readily incorporated into research and clinical settings. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Urea transporter expression in aging kidney and brain during dehydration.
Aging is commonly associated with defective urine-concentrating ability. The present study examined how the kidney and the brain of senescent (30-mo-old) female WAG/Rij rats respond to dehydration induced by 2 days of water deprivation in terms of urea transporter (UT) regulation. In euhydrated situation, senescent rats exhibited similar vasopressin plasma level but lower urine osmolality and papillary urea concentration and markedly reduced kidney UT-A1, UT-A3, and UT-B1 abundances compared with adult (10-mo-old) rats. Senescent rats responded to dehydration similarly to adult rats by a sixfold increase in vasopressin plasma level. Their papillary urea concentration was doubled, without, however, attaining that of dehydrated adult rats. Such an enhanced papillary urea sequestration occurred with a great fall of both UT-A1 and UT-A3 abundances in the tip of inner medulla and an increased UT-A1 abundance in the base of inner medulla. UT-A2 and UT-B1 were unchanged. These data suggest that the inability of control and thirsted senescent rats to concentrate urine as much as their younger counterparts derives from lower papillary urea concentration. In aging brain, UT-B1 abundance was increased twofold together with a fourfold increase in aquaporin-4 abundance. Dehydration did not alter the abundance of these transporters.


Advancing the Role of Proton Therapy for Spine Metastases Through Diagnostic Scan-Based Planning.
Many patients with metastatic cancer live years beyond diagnosis, and there remains a need to improve the therapeutic ratio of metastasis-directed radiation for these patients. This study aimed to assess a process for delivering cost-effective palliative proton therapy to the spine using diagnostic scan-based planning (DSBP) and prefabricated treatment delivery devices. We designed and characterized a reusable proton aperture system that adjusts to multiple lengths for spine treatment. Next, we retrospectively identified 10 patients scan treated with thoracic proton therapy who also had a diagnostic computed tomography within 4 months of simulation. We contoured a T6-T9 target volume on both the diagnostic scans (DS) and simulation scans (SS). Using the aperture system, we generated proton plans on the DS using a posterior-anterior beam with no custom range compensator to treat T6-T9 to 8 Gy × 1. Plans were transferred to the SS to compare coverage and normal tissue doses, followed by robustness analysis. Finally, we compared normal tissue doses and costs between proton and photon plans. Results were compared using the Wilcoxon signed-rank test. Median D95% on the DS plans was 101% (range, 100%-102%) of the prescription dose. Median Dmax was 107% (range, 105%-108%). When transferred to SS, coverage and hot spots remained acceptable for all cases. Heart and esophagus doses did not vary between the DS and SS proton plans (P >.2). Robustness analysis with 5 mm X/Y/Z shifts showed acceptable coverage (D95% > 98%) for all cases. Compared with the proton plans, the mean heart dose was higher for both anterior-posterior/posterior-anterior and volumetric modulated arc therapy plans (P < .01). Cost for proton DSBP was comparable to more commonly used photon regimens. Proton DSBP is technically feasible and robust, with superior sparing of the heart compared with photons. Eliminating simulation and custom devices increases the value of this approach in carefully selected patients.


Platelet activation during exercise induced asthma: effect of prophylaxis with cromoglycate and salbutamol.
Peak expiratory flow (PEF) and plasma concentrations of platelet factor 4 and beta thromboglobulin were measured before and after exercise in nine asthmatic patients and 12 non-asthmatic volunteers. Exercise was preceded by administration in random order of either placebo, salbutamol 200 micrograms, or sodium cromoglycate 2 mg from a pressurised inhaler. In control subjects there were minimal changes in PEF and plasma concentrations of platelet factor 4 and beta thromboglobulin. In the asthmatic patients the typical changes in PEF were seen on exercise; plasma concentrations of platelet factor 4 and beta thromboglobulin rose significantly in parallel, the rise preceding the fall in PEF. The changes in peak flow and platelet activation induced by exercise were attenuated by prior administration of salbutamol or cromoglycate. These results indicate that exercise induced asthma is associated with a rise in platelet release products similar to that observed in antigen induced asthma.


Childlessness, parental mortality and psychiatric illness: a natural experiment based on in vitro fertility treatment and adoption.
Childlessness increases the risk of premature mortality and psychiatric illness. These results might, however, be confounded by factors that affect both the chance of parenthood as well as the risk of premature death and psychiatric illness. Using population-based health and social registers, we conducted a follow-up study of 21 276 childless couples in in vitro fertility treatment. The crude death rate ratio in women who become mothers to a biological child is 0.25 (95% CI 0.16 to 0.39). In other words, childless women experience a fourfold higher rate of death, that is, 4.02 (2.56 to 6.31). The analogous death rate in fathers is approximately halved: 0.51 (0.39 to 0.68) and 0.55 (0.32 to 0.96) associated with having a biological child and an adopted child, respectively. With substance use disorders being the exception, none of the crude rates of psychiatric illness in parents of a biological child were statistically distinguishable from the rates in the childless. These findings were slightly confounded by age, calendar year, income, education, somatic comorbidity and marital breakup. Mindful that association is not causation, our results suggest that the mortality rates are higher in the childless. Rates of psychiatric illness do not appear to vary with childlessness, but the rate of psychiatric illness in parents who adopt is decreased.


Stimulus generalization of conditioned suppression.
A tone ending in unavoidable electric shock was periodically presented to pigeons while they pecked a key for food. When pecking was completely disrupted by tone, shock was disconnected, and the training tone and tones having new frequencies were presented. Initially the gradient of generalization was broad; as testing proceeded, however, the gradient narrowed severely.


Comparison of complete blood counts in samples obtained from healthy dogs and cats by use of standard and microsample blood collection tubes.
To compare results of a CBC performed on blood samples obtained from healthy dogs and cats by use of standard and microsample collection tubes. Evaluation study. 29 healthy client-owned animals (14 dogs and 15 cats). A blood sample (3 mL) was collected from each animal; 2.5 mL was transferred into a vacuum tube that contained sodium EDTA, and 0.5 mL was transferred into a microsample tube that contained sodium EDTA. Variables evaluated were total numbers of RBCs and WBCs, hemoglobin concentration, Hct, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration (MCHC), mean platelet volume, and plasma total protein concentration as well as neutrophil, lymphocyte, monocyte, eosinophil, basophil, and platelet counts. Results for the 2 types of tube in each species were compared by use of Pearson correlation coefficients, Passing-Bablok regression analysis, and Bland-Altman analysis. The Pearson correlation coefficient was low for basophil count in cats and moderate, high, or very high for all other variables. Constant and proportional biases were identified for MCHC in dogs by use of Passing-Bablok regression analysis, although the mean difference between types of blood collection tubes was small. No evidence of constant or proportional bias for any other variable was revealed by regression analysis or Bland-Altman analysis. Samples obtained from healthy dogs and cats by use of microsample blood collection tubes provided clinically equivalent CBC results, compared with results for samples obtained by use of standard blood collection tubes, and minimized the total sample volume collected for diagnostic testing.


Breastfeeding Education and Support Services Provided to Family Medicine and Obstetrics-Gynecology Residents.
Breastfeeding education is known to be insufficient in pediatric (PEDS) training and is, in part, responsible for suboptimal rates of breastfeeding. No recent studies about the level of education provided to family medicine (FM) and obstetrics-gynecology (OB) residency trainees are available. This study was conducted to investigate breastfeeding education and support services provided to FM and OB residents in the United States. The results were compared with a 2011 study of PEDS residents. A cross-sectional study was conducted using a web-based survey emailed to program directors (PDs) of FM and OB residency programs in the United States. Eighteen percent of PDs (95 of 515) completed the survey. Of these, 88% answered questions regarding education and support services provided. A median of 23 hours of breastfeeding education is provided to OB residents (4-year program) and 8 hours provided to FM residents (3-year program). In comparison, PEDS programs reported a median of 9 hours. The most commonly used settings included lectures with faculty and lactation consultants, similar to the PEDS study. Approximately 75% of respondents cited barriers to educating residents, with limited resident time being the most common. Eighty-one percent of respondents identified breastfeeding rooms as the service most frequently provided to residents who breastfeed. FM and PEDS residents are provided similar amounts of breastfeeding education, while OB programs provide more education, but in different settings. Reported barriers to this education are similar in all specialties. Support services are more commonly provided in PEDS programs.


[Antibiotic use in the pediatric population: factors to consider].
The aim of this retrospective study was to analyze the use of antibiotics in pediatrics in the Canary Islands during the period 2001-2005. We used the defined daily dose (DDD) as a technical unit of measurement as well as the DDD/1000 habitants/day (DHD), following the ATC classification system. The demographic data were obtained from individual patient health cards assigned to the primary care pediatricians. During the period 2001-2005, the total number of prescriptions for antibiotics in pediatrics was 1,207,726 at a cost of 6,119,679 Euros to the Canarian Health Service in Tenerife and 4,808,654 Euros in Las Palmas. The annual number of DHD in the Canary Islands decreased from 103,044 in 2001 to 68,168 in 2005. The cost for 1000 inhabitants/day (CHD) was 27,686 Euros and 19,183 Euros in Tenerife and Las Palmas, respectively. In analyzing the therapeutic classes of antibiotics, we found that the consumption of broad-spectrum penicillins (amoxicillin) in Tenerife decreased, while in Las Palmas it remained stable. There was also a significant decrease in the use of tetracyclines in both provinces. The DHD of beta-lactamase inhibitors was more significantly reduced in Tenerife than in LPA. The consumption of cephalosporins, mainly cefixime, was high in Tenerife, while in Las Palmas the second-generation cephalosporins (cefuroxime and cefaclor) were widely consumed. The use of macrolide antibiotics gradually decreased. Interestingly, there were 7,939 prescriptions for fluoroquinolones (mainly ciprofloxacin) in Tenerife and 4,846 in Las Palmas (mainly norfloxacin and ciprofloxacin). There were differences in the prescribing practices between Tenerife and Gran Canaria that don't coincide with changes in the microbiological spectrum. Prescribing practices in Las Palmas are based on scientific data, probably because of the continuing education courses on antibiotherapy that began in 2003.


A noncoding RNA gene on chromosome 10p15.3 may function upstream of hTERT.
We attempted to clone candidate genes on 10p 14-15 which may regulate hTERT expression, through exon trapping using 3 BAC clones covering the region. After obtaining 20 exons, we examined the function of RGM249 (RGM: RNA gene for miRNAs) we cloned from primary cultured human hepatocytes and hepatoma cell lines. We confirmed approximately 20 bp products digested by Dicer, and investigated the function of this cloned gene and its involvement in hTERT expression by transfecting the hepatoma cell lines with full-length dsRNA, gene-specific designed siRNA, and shRNA-generating plasmid. RGM249 showed cancer-dominant intense expression similar to hTERT in cancer cell lines, whereas very weak expression was evident in human primary hepatocytes without telomerase activity. This gene was predicted to be a noncoding precursor RNA gene. Interestingly, RGM249 dsRNA, siRNA, and shRNA inhibited more than 80% of hTERT mRNA expression. In contrast, primary cultured cells overexpressing the gene showed no significant change in hTERT mRNA expression; the overexpression of the gene strongly suppressed hTERT mRNA in poorly differentiated cells. These findings indicate that RGM249 might be a microRNA precursor gene involved in the differentiation and function upstream of hTERT.


Adenosine neuromodulation and traumatic brain injury.
Adenosine is a ubiquitous signaling molecule, with widespread activity across all organ systems. There is evidence that adenosine regulation is a significant factor in traumatic brain injury (TBI) onset, recovery, and outcome, and a growing body of experimental work examining the therapeutic potential of adenosine neuromodulation in the treatment of TBI. In the central nervous system (CNS), adenosine (dys)regulation has been demonstrated following TBI, and correlated to several TBI pathologies, including impaired cerebral hemodynamics, anaerobic metabolism, and inflammation. In addition to acute pathologies, adenosine function has been implicated in TBI comorbidities, such as cognitive deficits, psychiatric function, and post-traumatic epilepsy. This review presents studies in TBI as well as adenosine-related mechanisms in co-morbidities of and unfavorable outcomes resulting from TBI. While the exact role of the adenosine system following TBI remains unclear, there is increasing evidence that a thorough understanding of adenosine signaling will be critical to the development of diagnostic and therapeutic tools for the treatment of TBI.


Safety and efficacy of dermal fibroblast conditioned medium (DFCM) fortified collagen hydrogel as acellular 3D skin patch.
Skin substitutes are one of the main treatments for skin loss, and a skin substitute that is readily available would be the best treatment option. However, most cell-based skin substitutes require long production times, and therefore, patients endure long waiting times. The proteins secreted from the cells and tissues play vital roles in promoting wound healing. Thus, we aimed to develop an acellular three-dimensional (3D) skin patch with dermal fibroblast conditioned medium (DFCM) and collagen hydrogel for immediate treatment of skin loss. Fibroblasts from human skin samples were cultured using serum-free keratinocyte-specific media (KM1 or KM2) and serum-free fibroblast-specific medium (FM) to obtain DFCM-KM1, DFCM-KM2, and DFCM-FM, respectively. The acellular 3D skin patch was soft, semi-solid, and translucent. Collagen mixed with DFCM-KM1 and DFCM-KM2 showed higher protein release compared to collagen plus DFCM-FM. In vitro and in vivo testing revealed that DFCM and collagen hydrogel did not induce an immune response. The implantation of the 3D skin patch with or without DFCM on the dorsum of BALB/c mice demonstrated a significantly faster healing rate compared to the no-treatment group 7 days after implantation, and all groups had complete re-epithelialization at day 17. Histological analysis confirmed the structure and integrity of the regenerated skin, with positive expression of cytokeratin 14 and type I collagen in the epidermal and dermal layer, respectively. These findings highlight the possibility of using fibroblast secretory factors together with collagen hydrogel in an acellular 3D skin patch that can be used allogeneically for immediate treatment of full-thickness skin loss.


[Occurrence of antibodies anti-Neospora caninum in dogs of Botucatu range Micro region, State of São Paulo, Brazil].
Neosporosis is a parasitic disease caused by a protozoon Neospora caninum, which is recognized as an important cause of bovine abortion and canine neuropathy. Considering the isolation of N. caninum and the frequent serology in bovines of our region, the objectives of the present trial were to evaluate the occurrence of antibodies anti-N. caninum in dogs of the Botucatu range micro region, in the State of São Paulo, and its association with gender, age and origin (urban area--exclusively from the city; rural area--only farms and cottages; and periurban area--access to the urban and rural areas) of the dogs studied. A total of 963 dogs of defined breeds or non-defined breeds, of both genders and different ages, showing no clinical symptoms, were analyzed. Animals were randomly selected during the anti-rabies vaccination campaign in the region, from May to September 1998. Serum samples obtained from the animals were evaluated by means of the Indirect Fluorescent Antibody Test (IFAT) using as antigen N. caninum, standard strain NC-1. A total of 245 animals were reagent (25.4% positive results), with 161 (27.5%) males and 84 (22.3%) females. According to the origin--urban, rural and periurban areas--223 (25.8%), 11(16.9%) and 11(33.3%) dogs were, respectively, reagent to the IFAT. All of the 11 cities in this region presented seropositive dogs with occurrence rates ranging from 53.5 to 8.9%. The lower positive percentage was observed in dogs below 1 year old (16.2%) when compared with animals from 1 to 4 years old and more than 4 years old (28.4% and 28.0% respectively), which did not present any differences between them. Results obtained characterized the seropositivity for N. caninum in dogs from all Municipalities in the Botucatu micro region showing the wide distribution of the agent in the region.


The effects of endotoxemia and bacteremia on gastrointestinal drug absorption in mice and rats.
Endotoxin [lipopolysaccharide (LPS)] from four Gram-negative bacteria injected i.v. delayed absorption of drugs administered in solution by gastric tube to mice and rats. Salicylate and guinine absorption was delayed at LPS doses from 50 to 400 mug/kg. Salicylate absorption was delayed by LPS when drug was given by gastric tube, while LPS did not affect drug levels when salicylate was given i.p. or intraduodenally. Bethanechol prevented the LPS effect and LPS pretreatment also protected against delayed absorption. LPS- treated rats retained more drugs in their stomachs after 30 minutes and their plasma salicylate levels were lowered. Everted intestinal sacs from LPS-treated rats transferred salicylate as well as controls. Thus, LPS delays gastrointestinal drug absorption solely by retarding gastric emptying. Escherichia coli urinary tract infection did not reproduce LPS delay of drug absorption, but the effects of systemic bacteria were similar to those of endotoxemia.


Normal and anomalous heating rate effects on thermoluminescence of Ce-doped ZnB2O4.
The effect of heating rate (HR) on thermoluminescence (TL) glow curves of 1%, 4%, and 10% Ce3 + doped ZnB2O4 phosphors was investigated in detail. The glow peaks are examined and, activation energy (E) and frequency factor (s) are determined by using various heating rate (VHR) method. In the obtained glow curves with nine different HRs between 2 and 10°C/s, it was observed that the TL intensities of the first peaks of all three samples and the second peak of 10% Ce3 + doped sample decrease with increasing HR. The decrease in TL intensity was investigated whether it may be due to the presence of thermal quenching or not. On the other hand, the second glow peaks of 1, 4% Ce3 + doped ZnB2O4 phosphors show an anomalous TL behavior, which the probability of the radiative processes increases due to recombination of free electrons, so the TL intensity increases with the HR. The graphs of full width at the half maximum (FWHM) versus HR were also plotted to evaluate the influence of HR on TL intensity. In this paper, we suggest that the non-localized Schön - Klasens model may give an explanation for the second peaks of 1, 4% Ce3 + doped ZnB2O4 phosphors showing an unexpected increase with the increasing HR. In addition, the calculated E values of all doped phosphors were found similar in the range of 0.47-0.53eV for peak 1 and 0.61-0.66eV for peak 2. However, s values of Ce3 + doped ZnB2O4 phosphors were found slightly different according to the dopant amount and the equation used. Furthermore, different amount of Ce3 + doped samples indicate the similar properties for the repeated cycles of 5Gy in the same irradiation conditions.


Cellular glutathione redox homeostasis plays an important role in the brassinosteroid-induced increase in CO2 assimilation in Cucumis sativus.
Brassinosteroids (BRs) play a vital role in plant growth, stress tolerance and productivity. Here, the involvement of BRs in the regulation of CO(2) assimilation and cellular redox homeostasis was studied. The effects of BRs on CO(2) assimilation were studied in cucumber (Cucumis sativus) through the analysis of the accumulation of H(2)O(2) and glutathione and photosynthesis-related enzyme activities using histochemical and cytochemical detection or a spectrophotometric assay, and Rubisco activase (RCA) using western blot analysis and immunogold labeling. Exogenous BR increased apoplastic H(2)O(2) accumulation, the ratio of reduced to oxidized glutathione (GSH:GSSG) and CO(2) assimilation, whereas a BR biosynthetic inhibitor had the opposite effects. BR-induced CO(2) assimilation was decreased by a H(2)O(2) scavenger or inhibition of H(2)O(2) generation, GSH biosynthesis and the NADPH-generating pentose phosphate pathway. BR-, H(2)O(2) - or GSH-induced CO(2) assimilation was associated with increased activity of enzymes in the Benson-Calvin cycle. Immunogold labeling and western blotting showed that BR increased the content of RCA and this effect was blocked by inhibitors of redox homeostasis. These results strongly suggest that BR-induced photosynthesis involves an H(2)O(2) -mediated increase in the GSH:GSSG ratio, which may positively regulate the synthesis and activation of redox-sensitive enzymes in carbon fixation.


Lung deposition of budesonide from a pressurized metered-dose inhaler attached to a spacer.
The absolute systemic availability and pulmonary deposition of budesonide inhaled from a pressurized metered-dose inhaler (pMDI) attached to a Nebuhaler spacer was determined in 15 healthy subjects. The study was of an open cross-over design. Each subject randomly received three single doses of budesonide on separate days: 0.5 mg given intravenously and 1.0 mg (0.2 mg x 5) by inhalation from a pMDI with a Nebuhaler, with or without concomitant oral charcoal intake to prevent gastrointestinal absorption. Charcoal intake did not significantly affect the systemic availability or deposition of budesonide. The systemic availability was 36+/-14% (metered dose, mean+/-SD) with charcoal and 35+/-10% without. The pulmonary deposition was 36+/-14% with charcoal and 34+/-11% without. Erroneous administration, in which the canister was shaken only before the first of the five actuations, halved the systemic availability. In conclusion, the pulmonary deposition of budesonide from a pressurized metered-dose inhaler with Nebuhaler is high under optimum conditions. The small discrepancy between the systemic availability and pulmonary deposition indicates that the contribution from deposition in the oropharynx and subsequent absorption from the gastrointestinal tract is negligible. The marked reduction in the systemic availability of budesonide with the unshaken canisters confirms that the performance of a pressurized metered-dose inhaler is very much dependent on proper handling.


Ethnic Diversity and Increasing Resistance Patterns of Hospitalized Community-Acquired Urinary Tract Infections in Southern Israel: A Prospective Study.
Little is known about the incidence of urinary tract infections (UTI) in the dispersed Bedouin population. UTIs are routinely treated empirically according to local resistance patterns, which is important when evaluating the risk factors and antibiotic resistance patterns in the Bedouin population. To analyze risk factors, pathogens, and antibiotic resistance patterns of UTIs in the Bedouin population compared to the general population in southern Israel. To compare data from this study to that from a previous study conducted at our center. We prospectively followed all patients hospitalized with community acquired UTIs during a 4 month period at Soroka Medical Center. We also compared results from this study to those from a study conducted in 2000. The study comprised 223 patients: 44 Bedouin (19.7%), 179 (80.3) non-Bedouin; 158 female (70.9%), 65 male (29.1). The Bedouin were younger (51.7 vs. 71.1 years of age, P < 0.001) and had a lower Charlson Comorbidity Index (2.25 vs. 4.87, P < 0.001). Enterobacteriaceae were the most common pathogens identified, and Escherichia coli (E. coli) was the most common with 156 (70%) strains identified, followed by Klebsiella spp. with 29 (13%), Proteus spp. with 18 (8%), pseudomonas with 9 (4%), and other bacteria including enterococci with 11 (5%). The prevalence of E. coli increased significantly from 56% in 2000 to 70% in this study. We also noted an increase in community acquired extended spectrum beta lactamase (ESBL) pathogens from 4.5% in 2000 to 25.5% in the present study. No statistically significant difference was observed between the Bedouin and general populations in the causal pathogens, resistance to antibiotics, length of therapy, and readmission rate within 60 days. The Bedouin population hospitalized for UTIs is younger and presents with fewer co-morbidities. Isolated pathogens were similar to those found in the general population as was the presence of drug resistant infections. Overall, a substantial percentage of pathogens were resistant to standard first-line antibiotics, driving the need to change from empiric therapy to aminoglycoside therapy.


Raman spectroscopy of graphite.
We present a review of the Raman spectra of graphite from an experimental and theoretical point of view. The disorder-induced Raman bands in this material have been a puzzling Raman problem for almost 30 years. Double-resonant Raman scattering explains their origin as well as the excitation-energy dependence, the overtone spectrum and the difference between Stokes and anti-Stokes scattering. We develop the symmetry-imposed selection rules for double-resonant Raman scattering in graphite and point out misassignments in previously published works. An excellent agreement is found between the graphite phonon dispersion from double-resonant Raman scattering and other experimental methods.


Role of US in acute scrotal pain.
The acute scrotum is a common emergency department (ED) presentation and can be defined as any condition of the scrotum or intrascrotal contents requiring emergent medical or surgical intervention. Although rarely fatal, acute scrotal pathology can result in testicle infarction and necrosis, testicular atrophy, infertility, and significant morbidity. Scrotal US is best performed with a linear 7.5- to 12-MHz transducer. In addition to imaging in the longitudinal and transverse planes, it is helpful to obtain simultaneous images of both testes for comparison. Color Doppler is used to evaluate for abnormalities of flow and to differentiate vascular from nonvascular lesions. Attention to appropriate color Doppler settings to optimize detection of slow flow is critical. The evaluation of acute scrotal pain can be challenging for the clinician initially examining and triaging the patient. Acute scrotal conditions due to traumatic, infectious, vascular, or neoplastic etiologies can all present with pain as the initial complaint. Additionally, the laboratory and physical examination findings in such conditions may overlap; this, coupled with potential patient guarding and lack of collaboration, may result in a limited, non-specific physical examination. Therefore, scrotal ultrasound has emerged to play a central role in the evaluation of the patient presenting with acute scrotal pain. In conclusion, we are firmly convinced that a scrotal ultrasound should always be performed in the presence of acute scrotal pain. Moreover, urologist should be able to perform a scrotal ultrasound but, if imaging does not supply a clear diagnosis, surgical exploration is still mandatory.


Telomere lengths at birth in trisomies 18 and 21 measured by Q-FISH.
Trisomies 18 and 21 are genetic disorders in which cells possess an extra copy of each of the relevant chromosomes. Individuals with these disorders who survive birth generally have a shortened life expectancy. As telomeres are known to play an important role in the maintenance of genomic integrity by protecting the chromosomal ends, we conducted a study to determine whether there are differences in telomere length at birth between individuals with trisomy and diploidy, and between trisomic chromosomes and normal chromosomes. We examined samples of peripheral blood lymphocytes (PBLs) from 31 live neonates (diploidy: 10, trisomy 18: 10, trisomy 21: 11) and estimated the telomere length of each chromosome arm using Q-FISH. We observed that the telomeres of trisomic chromosomes were neither shorter nor longer than the mean telomere length of chromosomes as a whole among subjects with trisomies 18 and 21 (intra-cell comparison), and we were unable to conclude that there were differences in telomere length between 18 trisomy and diploid subjects, or between 21 trisomy and diploid subjects (inter-individual comparison). Although it has been reported that telomeres are shorter in older individuals with trisomy 21 and show accelerated telomere shortening with age, our data suggest that patients with trisomies 18 and 21 may have comparably sized telomeres. Therefore, it would be advisable for them to avoid lifestyle habits and characteristics such as obesity, cigarette smoking, chronic stress, and alcohol intake, which lead to marked telomere shortening.


Surgical release of the pediatric trigger thumb.
The spontaneous recovery rate for locked pediatric trigger thumb (PTT) has recently been reported at between 24% and 66%; these studies concluded that a conservative approach for this condition could be adopted. The aims of this study were to review our results of surgical release of the PTT and to survey pediatric hand surgeons regarding their practice patterns for treatment of the PTT. After institutional review board approval, we retrospectively reviewed 173 consecutive patients with 217 thumbs treated surgically at our institution. An e-mail survey of 27 pediatric hand surgeons questioned treatment of a 2-year-old child with a 6-month history of a locked trigger thumb and of an intermittently triggering thumb. The retrospective review demonstrated that preoperative range of motion averaged 36° loss of extension (range, 0° to 90°; SD, 22°); postoperative range of motion averaged 1° loss of extension (range, 0° to 30°; SD, 7°) at 27-day follow-up. Using a parent questionnaire at an average follow-up of 4.2 years, there were no major complications or recurrences identified. Five thumbs developed minor skin complications that healed with conservative management. There were no secondary surgeries. The practice pattern survey demonstrated that 85% of pediatric hand surgeons would treat a locked PTT in a 2-year-old with surgical release and 52% would treat an intermittently triggering thumb in a 2-year-old with continued observation if the triggering thumb was not painful. The surgical results reported in this study, along with the practice pattern survey, confirm that surgical release is a short, safe, and effective procedure when performed by specialty trained hand surgeons, and it is the treatment of choice for a locked PTT.


The effect of Kisspeptin-10 on mesenchymal stem cells migration in vitro and in vivo.
Kisspeptins (kp) activate a receptor coupled to a Gαq subunit (GPR54 or KiSS-1R) receptor to perform a variety of functions, including inhibition of cell motility, chemotaxis, and metastasis. In this study we have investigated whether kp-10, the most potent member of the kisspeptin family, can modulate CXCR4 (C-X-C chemokine receptor type 4) expression and mesenchymal stem cells (MSCs) migration that may influence the development of tumors. We compared the directional migration of MSCs treated with 10-100 or 500 nM kp-10 for 24 hours and no treated cells using an in vitro transmembrane migration assay. In addition, Chloromethylbenzamido Dialkylacarbocyanine (CM-Dil) labeled adipose-derived mesenchymal stem cells treated with 10-100 or 500 nM kp-10 and no treated cells were transfused via the tail vein to the melanoma tumor bearing C57BL/6 mice. After 24 hours, the mice were scarified, the tumors were dissected, and the tumor cell suspensions were analyzed by flow cytometry for detection of CM-Dil(+) MSCs. We have found that kp-10 increased the MSCs migration at 100 nM, while it decreased the MSCs migration at 500 nM, both in vitro and in vivo, with a significant increase of CXCR4 expression at 100 nM kp-10 compared to the no treated cells, but it had no significant difference between the various concentrations of kp-10. Thus, our data showed that kp-10 can differently affect MSCs migration in various concentrations, probably through different effects on CXCR4 expression in various concentrations.


Bio-organism sensing via surface enhanced Raman spectroscopy on controlled metal/polymer nanostructured substrates.
A new class of nonlithographically prepared surface enhanced Raman spectroscopy (SERS) substrates based on metalized, nanostructured poly(p-xylylene) films has been developed and optimized for surface plasmon response with a view to applications of SERS detection of microbial pathogens, specifically, bacteria and viruses. The main emphasis has been on achieving high spot to spot, sample to sample reproducibility of the SERS signals while maintaining useful enhancement factors. The use of these surfaces, metalized with either Ag or Au, provides a noninvasive and nondestructive method for spectral fingerprint analyses of both bacteria and viruses. Examples are given for the detection of bacteria (E. coli and B. cereus) and viruses (respiratory syncytial virus and Coxsackievirus). Our method is able to distinguish Gram positive from Gram negative bacterial strains as well as enveloped and nonenveloped viruses. The results demonstrate the development of a new class of SERS substrates which can provide rapid, selective identification of infectious agents without amplification of cultures.


Immunologic sensitization in recipients of left ventricular assist devices.
Left ventricular assist device implantation is associated with an increased risk of development of circulating anti-HLA class I and II antibodies (sensitization). We investigated the impact of sensitization on posttransplantation outcomes in 105 consecutive left ventricular assist device recipients. Five hundred twenty-one consecutive adult cardiac allograft recipients between 1992 and 1999 were retrospectively studied. Of these, 105 were supported with a left ventricular assist device. Pretransplantation and posttransplantation antibody production, time to transplantation after listing, rejection, freedom from transplant coronary artery disease, and survival were evaluated by Kaplan-Meier analysis. Among sensitized left ventricular assist device recipients, 26 were treated with a pretransplantation immunomodulatory regimen consisting of intravenous immunoglobulin and cyclophosphamide. There were no significant differences between left ventricular assist device recipients and nonbridged recipients with respect to pretransplantation demographic characteristics and ABO and HLA matching. Among left ventricular assist device recipients, 66% (69/105) were sensitized before transplantation; in contrast, only 6% (24/399) of nonbridged recipients were sensitized (P <.001). Sensitized untreated left ventricular assist device recipients had both a prolongation of waiting time to transplantation and an increased risk of acute rejection. Pretransplantation immunomodulatory therapy reduced both the increased waiting time and the increased risk of acute rejection. However, sensitization or the use of immunomodulatory therapy in left ventricular assist device-bridged recipients did not influence posttransplantation survival relative to nonbridged recipients. Left ventricular assist device recipients have survival outcomes similar to those of nonbridged recipients after cardiac transplantation, despite their significantly higher immunologic risk. The reduced rate of transplantation and the increased incidence of rejection observed in sensitized left ventricular assist device recipients are prevented by immunomodulatory therapy. Sensitization will remain an important issue with increased use of left ventricular assist devices, and improved understanding of this is essential to achieve better outcomes in the management of patients with end-stage heart failure.


Intraluminally injected oil induces changes in vascular permeability in the 'sensitized' and 'non-sensitized' uterus of the mouse.
After suitable sensitization of ovariectomized mice with progesterone and oestradiol, the intrauterine instillation of oil produces a massive decidual cell reaction. Vascular permeability, as reflected by the extra-vascular accumulation of 125I-labelled human serum albumin, increased after oil instillation and was maintained at 2-3 times control values for at least the next 3 days. Although oil instillation did not produce a decidual response in females treated with progesterone alone, an increase in vascular permeability (about 2 times control levels) still occurred. This response peaked 8 h after oil instillation and was not maintained. These results indicate that the progesterone-dominated uterus which has not been sensitized with oestradiol cannot be viewed as completely unresponsive to the stimulus of oil and demonstrate that a marked increase in vascular permeability is not itself sufficient to induce decidualization of progesterone-dominated uterine stromal cells. The uterine extravascular accumulation of 125I-labelled albumin was increased both in association with tribromoethanol anaesthesia and after oestradiol treatment of progesterone-primed animals. In pregnant mice, the appearance of Pontamine Sky Blue spots provided an earlier indication of implantation than did determination of total uterine extravascular 125I-labelled albumin accumulation.


Identification of metal sensitization in sarcoid-like metal-exposed patients by the MELISA® lymphocyte proliferation test - a pilot study.
Pulmonary function is often affected by the inhalation of metal particles. The resulting pathology might trigger various lung diseases, e.g., parenchymal lung fibrosis and granulomatous lung disorders. We previously demonstrated that 6 % of tissue-proven sarcoid patients had a positive beryllium lymphocyte proliferation test (BeLPT), thus correcting the diagnosis to chronic beryllium disease. The aim of this study was to examine if MEmory Lymphocyte Immnuno Stimulation Assay (MELISA®), currently used for non-pulmonary diseases, can identify metals other than beryllium that can also trigger sensitization and induce granulomatous disease. This pilot study included 13 sarcoid-like patients who underwent MELISA®. Eleven patients also underwent BeLPT. Biopsy samples were tested for metal content by scanning electron microscope. Eleven study patients had been exposed to metals at the workplace and 2 had silicone implants. Two patients who had undergone BeLPT were positive for beryllium. MELISA® detected 9 patients (9/13, 69 %) who were positive for at least one of the tested metals: 4 reacted positively to nickel, 4 to titanium, 2 to chromium, 2 to beryllium, 2 to silica, and one each to palladium, mercury and lead. It is proposed that MELISA® can be exploited to also identify specific sensitization in individuals exposed to inhaled particles from a variety of metals.


Digital and Mobile Technologies to Promote Physical Health Behavior Change and Provide Psychological Support for Patients Undergoing Elective Surgery: Meta-Ethnography and Systematic Review.
Digital technology has influenced many aspects of modern living, including health care. In the context of elective surgeries, there is a strong association between preoperative physical and psychological preparedness, and improved postoperative outcomes. Health behavior changes made in the pre- and postoperative periods can be fundamental in determining the outcomes and success of elective surgeries. Understanding the potential unmet needs of patients undergoing elective surgery is central to motivating health behavior change. Integrating digital and mobile health technologies within the elective surgical pathway could be a strategy to remotely deliver this support to patients. This meta-ethnographic systematic review explores digital interventions supporting patients undergoing elective surgery with health behavior changes, specifically physical activity, weight loss, dietary intake, and psychological support. A literature search was conducted in October 2019 across 6 electronic databases (International Prospective Register of Systematic Reviews [PROSPERO]: CRD42020157813). Qualitative studies were included if they evaluated the use of digital technologies supporting behavior change in adult patients undergoing elective surgery during the pre- or postoperative period. Study quality was assessed using the Critical Appraisal Skills Programme tool. A meta-ethnographic approach was used to synthesize existing qualitative data, using the 7 phases of meta-ethnography by Noblit and Hare. Using this approach, along with reciprocal translation, enabled the development of 4 themes from the data. A total of 18 studies were included covering bariatric (n=2, 11%), cancer (n=13, 72%), and orthopedic (n=3, 17%) surgeries. The 4 overarching themes appear to be key in understanding and determining the effectiveness of digital and mobile interventions to support surgical patients. To successfully motivate health behavior change, technologies should provide motivation and support, enable patient engagement, facilitate peer networking, and meet individualized patient needs. Self-regulatory features such as goal setting heightened patient motivation. The personalization of difficulty levels in virtual reality-based rehabilitation was positively received. Internet-based cognitive behavioral therapy reduced depression and distress in patients undergoing cancer surgery. Peer networking provided emotional support beyond that of patient-provider relationships, improving quality of life and care satisfaction. Patients expressed the desire for digital interventions to be individually tailored according to their physical and psychological needs, before and after surgery. These findings have the potential to influence the future design of patient-centered digital and mobile health technologies and demonstrate a multipurpose role for digital technologies in the elective surgical pathway by motivating health behavior change and offering psychological support. Through the synthesis of patient suggestions, we highlight areas for digital technology optimization and emphasize the importance of content tailored to suit individual patients and surgical procedures. There is a significant rationale for involving patients in the cocreation of digital health technologies to enhance engagement, better support behavior change, and improve surgical outcomes.


Optimal positive-end expiratory pressure weaning in acute respiratory distress syndrome patients.
Positive-end expiratory pressure (PEEP) is a tool in managing acute respiratory distress syndrome (ARDS). In this review, we discuss the various approaches to weaning PEEP after the acute phase of ARDS. There is a paucity of research specifically looking at the differences between PEEP weaning protocols. Data in some populations though, particularly those with elevated BMI, suggest that a physiologic approach to PEEP weaning may be helpful. Use of various tools to optimize PEEP prior to and during spontaneous breathing trials (SBTs) may allow for improved alveolar recruitment and respiratory outcomes. Although further prospective studies are warranted, we should consider using a physiologic approach to PEEP weaning in ARDS rather than a one size fits all model, which is currently the standard used in many clinical trials and throughout many ICUs.


Plant trichomes and a single gene GLABRA1 contribute to insect community composition on field-grown Arabidopsis thaliana.
Genetic variation in plants alters insect abundance and community structure in the field; however, little is known about the importance of a single gene among diverse plant genotypes. In this context, Arabidopsis trichomes provide an excellent system to discern the roles of natural variation and a key gene, GLABRA1, in shaping insect communities. In this study, we transplanted two independent glabrous mutants (gl1-1 and gl1-2) and 17 natural accessions of Arabidopsis thaliana to two localities in Switzerland and Japan. Fifteen insect species inhabited the plant accessions, with the insect community composition significantly attributed to variations among plant accessions. The total abundance of leaf-chewing herbivores was negatively correlated with trichome density at both field sites, while glucosinolates had variable effects on leaf chewers between the sites. Interestingly, there was a parallel tendency for the abundance of leaf chewers to be higher on gl1-1 and gl1-2 than on their different parental accessions, Ler-1 and Col-0, respectively. Furthermore, the loss of function in the GLABRA1 gene significantly decreased the resistance of plants to the two predominant chewers; flea beetles and turnip sawflies. Overall, our results indicate that insect community composition significantly varies among A. thaliana accessions across two distant field sites, with GLABRA1 playing a key role in altering the abundance of leaf-chewing herbivores. Given that such a trichome variation is widely observed in Brassicaceae plants, the present study exemplifies the community-wide effect of a single plant gene on crucifer-feeding insects in the field.


Hesperidin-CAMKIV interaction and its impact on cell proliferation and apoptosis in the human hepatic carcinoma and neuroblastoma cells.
Calcium/calmodulin-dependent protein kinase IV (CAMKIV) is a key regulatory molecule of cell signaling, and thereby controls its growth and proliferation, including expression of certain genes. The overexpression of CAMKIV is directly associated with the development of different types of cancers. Hesperidin is abundantly found in citrus fruits and exhibits wide range of pharmacological activities including anti-inflammatory, antibacterial and anticancerous effects. We have investigated binding mechanism of hesperidin with the CAMKIV using molecular docking methods followed by fluorescence quenching and isothermal titration calorimetric assays. An appreciable binding affinity of hesperidin was observed with CAMKIV during fluorescence quenching and isothermal titration calorimetric studies. Efficacy of hesperidin to inhibit the growth of human hepatic carcinoma (HepG2) and neuroblastoma (SH-SY5Y) cancer cell lines were investigated. Hesperidin has significantly reduced the proliferation of HepG2 and SH-SY5Y cells and induces apoptosis by activating the caspase-3-dependent intrinsic pathway through the upregulation of proapoptotic Bax protein. Hesperidin treatment reduces the mitochondrial membrane potential of HepG2 and SH-SY5Y cells. All these observations clearly anticipated hesperidin a potent inhibitor of CAMKIV which may be further exploited a newer therapeutic approach for the management of different cancer types.


The Utility of Preoperative Venous Testing for Lower Extremity Flap Planning in Patients with Lower Extremity Wounds.
Although venous thrombosis is a leading cause of flap failure, the majority of lower extremity free flap planning is centered on arterial system evaluation. Preoperative identification of relevant abnormality in lower extremity venous systems by means of duplex ultrasound may aid in the diagnosis of clinically important abnormality that could affect lower extremity flap outcomes. Between November of 2014 and August of 2017, 57 patients underwent preoperative lower extremity venous duplex imaging and free tissue transfer for lower extremity wounds. A retrospective review was performed to describe lower extremity venous pathologic findings, relevant patient demographic data, comorbid conditions, and outcomes. Discovery of venous abnormality helped guide recipient vein selection. Fifty-seven consecutive patients underwent 59 free flap operations to treat chronic lower extremity wounds. Venous duplex ultrasonography detected venous insufficiency (defined as >0.5 second of reflux) in 23 patients (39.0 percent), including 16 (27.2 percent) with deep thigh reflux, six (10.2 percent) with superficial calf reflux, and four (6.78 percent) with deep calf reflux. Deep venous thrombosis was found in four patients (6.78 percent) and treated with anticoagulation. The flap success rate was 98.3 percent. Five patients (8.47 percent) progressed to amputation. At a mean follow-up time of 15.1 ± 9.51 months (range, 1.67 to 35.2 months), 53 patients (89.8 percent) were able to continue community ambulation. Lower extremity venous duplex testing before free tissue transfer may be useful for optimizing flap recipient vessel selection and for detecting potentially unknown venous abnormality. Development of free flap planning protocols incorporating preoperative vascular imaging is important to achieving good functional outcomes in this comorbid patient population. Diagnostic, IV.


Cellular receptors and hantavirus pathogenesis.
Hantaviruses cause two potentially lethal diseases, HPS and HFRS, and both diseases result in defects in vascular permeability and platelet function. Human beta 3 integrins confer cellular susceptibility to HPS- and HFRS-causing hantaviruses, a fact directly linking platelets, endothelial cells, and hantavirus diseases to the use of [figure: see text] cellular receptors that maintain capillary integrity and regulate platelet function. The role of vitronectin, PAI-1, uPAR, and complement cascades in hantavirus pathogenesis are unstudied but may contribute to specific disease syndromes effected by hantaviruses. The divergence of hantavirus surface glycoproteins and common beta 3-integrin usage provides further insight into the interaction of hantaviruses with cells. G1 and G2 glycoprotein variation is likely to contribute to additional interactions that determine pathogenic responses to individual viruses. beta 3-integrin usage also suggests that common elements exist on G1 or the more highly conserved G2 surface glycoprotein, which mediate viral attachment to integrins. Although there is currently no data defining the virion attachment protein, the development of antibodies that recognize the hantavirus attachment protein and block integrin interactions is of interest since it is likely to provide an additional point for therapeutic intervention and vaccine development. There are a plethora of effects that could be elicited by hantavirus regulation of cellular beta 3 integrins and their ligands that are consistent with hantavirus diseases. Since beta 3 integrins are critical adhesive receptors on platelets and endothelial cells and regulate both vascular permeability and platelet activation and adhesion, the use of these receptors by hantaviruses is likely to be fundamental to hantavirus pathogenesis. The lack of an animal model for hantavirus pathogenesis has prevented a systematic analysis of immune and cellular responses to hantavirus infections, and it impedes our ability to study protective or therapeutic approaches to hantavirus diseases. However, recent findings suggest that human beta 3 integrins within transgenic mice may provide animal models of hantavirus pathogenesis and have the potential to radically alter the ability to investigate hantavirus disease.


Factors associated with syrinx size in pediatric patients treated for Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium.
Factors associated with syrinx size in pediatric patients undergoing posterior fossa decompression (PFD) or PFD with duraplasty (PFDD) for Chiari malformation type I (CM-I) with syringomyelia (SM; CM-I+SM) are not well established. Using the Park-Reeves Syringomyelia Research Consortium registry, the authors analyzed variables associated with syrinx radiological outcomes in patients (< 20 years old at the time of surgery) with CM-I+SM undergoing PFD or PFDD. Syrinx resolution was defined as an anteroposterior (AP) diameter of ≤ 2 mm or ≤ 3 mm or a reduction in AP diameter of ≥ 50%. Syrinx regression or progression was defined using 1) change in syrinx AP diameter (≥ 1 mm), or 2) change in syrinx length (craniocaudal, ≥ 1 vertebral level). Syrinx stability was defined as a < 1-mm change in syrinx AP diameter and no change in syrinx length. The authors identified 380 patients with CM-I+SM who underwent PFD or PFDD. Cox proportional hazards modeling revealed younger age at surgery and PFDD as being independently associated with syrinx resolution, defined as a ≤ 2-mm or ≤ 3-mm AP diameter or ≥ 50% reduction in AP diameter. Radiological syrinx resolution was associated with improvement in headache (p < 0.005) and neck pain (p < 0.011) after PFD or PFDD. Next, PFDD (p = 0.005), scoliosis (p = 0.007), and syrinx location across multiple spinal segments (p = 0.001) were associated with syrinx diameter regression, whereas increased preoperative frontal-occipital horn ratio (FOHR; p = 0.007) and syrinx location spanning multiple spinal segments (p = 0.04) were associated with syrinx length regression. Scoliosis (HR 0.38 [95% CI 0.16-0.91], p = 0.03) and smaller syrinx diameter (5.82 ± 3.38 vs 7.86 ± 3.05 mm; HR 0.60 [95% CI 0.34-1.03], p = 0.002) were associated with syrinx diameter stability, whereas shorter preoperative syrinx length (5.75 ± 4.01 vs 9.65 ± 4.31 levels; HR 0.21 [95% CI 0.12-0.38], p = 0.0001) and smaller pB-C2 distance (6.86 ± 1.27 vs 7.18 ± 1.38 mm; HR 1.44 [95% CI 1.02-2.05], p = 0.04) were associated with syrinx length stability. Finally, younger age at surgery (8.19 ± 5.02 vs 10.29 ± 4.25 years; HR 1.89 [95% CI 1.31-3.04], p = 0.01) was associated with syrinx diameter progression, whereas increased postoperative syrinx diameter (6.73 ± 3.64 vs 3.97 ± 3.07 mm; HR 3.10 [95% CI 1.67-5.76], p = 0.003), was associated with syrinx length progression. PFD versus PFDD was not associated with syrinx progression or reoperation rate. These data suggest that PFDD and age are independently associated with radiological syrinx improvement, although forthcoming results from the PFDD versus PFD randomized controlled trial (NCT02669836, clinicaltrials.gov) will best answer this question.


[Can cross-allergic reactions to food antigens be the cause of recurrent pancreatitis in children with food allergies?].
Drug and food allergy in 80% of cases are the cause of duodenal inflammation disrupting the function of the pancreatic ducts. However, in some cases, elimination diet in patients with food allergy does not provide a sufficient effect. The article shows the effect of cross-allergic reactions on recurrent pancreatitis in 28 children with food allergy (mean age 11.7 +/- 2.9 years). As an additional diagnostic criterion the coefficient of degranulation of mast cell in the intestinal mucosa (the ratio of degranulated forms to granulated) was determined, through which the effect of cross-allergic reactions (between food antigens and drugs of animal origin) on the duration and frequency of exacerbations of chronic pancreatitis in children with food sensitization has been shown. The exception of enzyme preparations for children with sensitization to pork and exception of eubiotics prepared using sucrose-gelatin-milk medium for children with sensitization to cow's milk and beef led to feel better in a shorter time (2-3 days) and to reduce the frequency of relapses. Catamnesis observation for 3 years showed that the incidence of recurrent exacerbations of the disease in 11 children with excepted cross-allergic reactions in the first year of follow-up was 9.1%, in the second year--9.1% and in the third year--0%, while in control group (17 children) the frequency of exacerbations was respectively 23.5; 35.3; 35.3%. In patients of the main group there was a slight overall increase of mast cells in the intestinal mucosa from 211.7 to 230.2 mm2 (p > 0.05) with decreasing of degranulated forms from 163.6 to 138.71 mm2 (p > 0.05) and significant increase of granulated forms from 47.41 to 91.51 mm2 (p < 0.05), resulting in a significant decrease in mast cells degranulation coefficient from 3.2 +/- 0.62/mm2 to 1.24 +/- 0.26/mm2 (p < 0.0001). Thus, duodenal etiology of recurrent pancreatitis caused by exposure to food antigens or cross-allergic reactions can be diagnosed with an additional diagnostic criterion--the coefficient of mast cell degranulation, whose exponents greater than 1.5 indicate evidence of antigenic exposure to the mucosa of the duodenum and allergic inflammation.


Impact of vaccination against severe COVID-19 in the French population aged 50 years and above: a retrospective population-based study.
Given the widespread implementation of COVID-19 vaccination to mitigate the pandemic from the end of 2020, it is important to retrospectively evaluate its impact, in particular by quantifying the number of severe outcomes prevented through vaccination. We estimated the number of hospitalizations, intensive care unit (ICU) admissions and deaths directly averted by vaccination in France, in people aged ≥ 50 years, from December 2020 to March 2022, based on (1) the number of observed events, (2) vaccination coverage, and (3) vaccine effectiveness. We accounted for the effect of primary vaccination and the first booster dose, the circulating variants, the age groups, and the waning of vaccine-induced protection over time. An estimated 480,150 (95% CI: 260,072-582,516) hospitalizations, 132,156 (50,409-157,767) ICU admissions and 125,376 (53,792-152,037) deaths were directly averted by vaccination in people aged ≥ 50 years, which corresponds to a reduction of 63.2% (48.2-67.6), 68.7% (45.6-72.4) and 62.7% (41.9-67.1) respectively, compared to what would have been expected without vaccination over the study period. An estimated 5852 (2285-6853) deaths were directly averted among the 50-59 years old, 16,837 (6568-19,473) among the 60-69 years old, 32,136 (13,651-36,758) among the 70-79 years old and 70,551 (31,288-88,953) among the ≥ 80 years old. The vaccination campaign in France considerably reduced COVID-19 morbidity and mortality, as well as stress on the healthcare system.


Review of magnetic resonance imaging and spectroscopy studies in children with bipolar disorder.
Pediatric bipolar disorder is a serious condition that affects a child's ability to function normally during important developmental stages. Pediatric bipolar disorder often presents with a different symptom complex than adult-onset bipolar disorder, including higher rates of irritability and rapid cycling. Due to these differences, it is important to understand the neural substrates of the disease as it presents in children, especially when compared with adults. Understanding the brain abnormalities associated with pediatric bipolar disorder may provide much needed markers useful in diagnosing childhood-onset bipolar disorder, give insight into the neurobiological etiology of the disorder and lead to more effective treatments. Currently, there has been little neuroimaging research into pediatric bipolar disorder, specifically with regards to brain function. This review summarizes the neurobiological research that has been conducted on childhood- and adolescent-onset bipolar disorder using magnetic resonance technology. Future directions of research needed in this area also are discussed in the context of the existing literature.


Correlation of cardiovascular autonomic function tests, magnetic resonance brain imaging and clinical features in suspect cases of multiple system atrophy.
Nine patients presenting with parkinsonian features and no other clinical abnormalities were studied. These patients were evaluated for dopaminergic responsiveness, for cardiovascular reflex autonomic function, and underwent high field magnetic resonance scan. A 0 to 5 point probability score was used to evaluate the possibility that parkinsonian signs were the presenting symptoms of multiple system atrophy (MSA). Five patients were considered at risk for having MSA: three of them were classified as possible MSA cases (score 2-3), two of them were classified as probable cases of MSA (score 4-5). In patients at risk for MSA, no specific pattern of combination of clinical and laboratory data was found; all patients had different combinations of positive findings.


Immunohistochemical detection of 4-hydroxynonenal protein adducts in Parkinson disease.
There is growing evidence that oxidative stress and mitochondrial respiratory failure with attendant decrease in energy output are implicated in nigral neuronal death in Parkinson disease (PD). It is not known, however, which cellular elements (neurons or glial cells) are major targets of oxygen-mediated damage. 4-Hydroxy-2-nonenal (HNE) was shown earlier to react with proteins to form stable adducts that can be used as markers of oxidative stress-induced cellular damage. We report here results of immunochemical studies using polyclonal antibodies directed against HNE-protein conjugates to label the site of oxidative damage in control subjects (ages 18-99 years) and seven patients that died of PD (ages 57-78 years). All the nigral melanized neurons in one of the midbrain sections were counted and classified into three groups according to the intensity of immunostaining for HNE-modified proteins--i.e., no staining, weak staining, and intensely positive staining. On average, 58% of nigral neurons were positively stained for HNE-modified proteins in PD; in contrast only 9% of nigral neurons were positive in the control subjects; the difference was statistically significant (Mann-Whitney U test; P < 0.01). In contrast to the substantia nigra, the oculomotor neurons in the same midbrain sections showed no or only weak staining for HNE-modified proteins in both PD and control subjects; young control subjects did not show any immunostaining; however, aged control subjects showed weak staining in the oculomotor nucleus, suggesting age-related accumulation of HNE-modified proteins in the neuron. Our results indicate the presence of oxidative stress within nigral neurons in PD, and this oxidative stress may contribute to nigral cell death.


Platelets from children are hyper-responsive to activation by thrombin receptor activator peptide and adenosine diphosphate compared to platelets from adults.
Platelets are crucial subcellular elements of haemostasis at sites of vascular injury and are also known to be immune mediators in pathological thrombosis. Despite the integral role of platelets in many disease processes, there is very little information available on platelet function and response to agonists in healthy children. We recently reported important differences in the interaction of platelets with monocytes in the circulation, including increased formation of monocyte-platelet aggregates (MPAs) without concomitant increase in P-selectin expression. Our current study investigates parameters of platelet activation (PAC-1 binding and P-selectin expression) and MPA formation in response to a range of physiologically relevant platelet agonists in healthy children compared to healthy adults. All parameters were significantly higher in children in response to sub-maximal concentrations of thrombin receptor activator peptide and adenosine diphosphate, reflecting an age-specific difference in agonist-stimulated platelet reactivity in children. The results of our study challenge the general assumption that platelet reactivity in children is similar to adults. This finding is fundamental to investigating the role of platelets in diseases of childhood and pathogenesis of adult-based diseases that have their origins in childhood. Our findings underscore the need for age-specific reference ranges for platelet function in children rather than extrapolation from adult data.


DNMT3B mutations and DNA methylation defect define two types of ICF syndrome.
ICF syndrome is a rare autosomal recessive disease characterized by variable immunodeficiency, centromeric instability, and facial abnormalities. Mutations in the catalytic domain of DNMT3B, a gene encoding a de novo DNA methyltransferase, have been recognized in a subset of patients. ICF syndrome is a genetic disease directly related to a genomic methylation defect that mainly affects classical satellites 2 and 3, both components of constitutive heterochromatin. The variable incidence of DNMT3B mutations and the differential methylation defect of alpha satellites allow the identification of two types of patients, both showing an undermethylation of classical satellite DNA. This classification illustrates the specificity of the methylation process and raises questions about the genetic heterogeneity of the ICF syndrome.


Phenotypic and genotypic differences of the vancomycin-resistant Enterococcus faecium isolates from humans and poultry in Korea.
A total of 98 vancomycin-resistant Enterococcus faecium (VREF) isolates (58 isolates from patients and 40 isolates from poultry) were compared based on their antimicrobial susceptibility, Tn1546 element organization, and pulsed-field gel electrophoresis (PFGE) patterns. This comparison aided in determining the relationships between the groups of isolates. All the VREF isolates harbored the vanA gene; however, 29 (29.6%) of the isolates exhibited the VanB phenotype-vanA genotype. Furthermore, the VREF isolates from humans and poultry exhibited distinct antimicrobial resistance patterns. The PCR mapping of the Tn1546 elements exhibited 12 different transposon types (A to L). The VREF isolates of poultry were classified into types A to D, whereas the human isolates were classified into types E to L. A PFGE analysis demonstrated a high degree of clonal heterogeneity in both groups of isolates; however, the distinct VREF clones appeared in each group of isolates. The deletion of the vanX-vanY genes or insertion of IS1216V in the intergenic region from the vanX-vanY genes is directly associated with the incongruence of the VanB phenotype-vanA genotype in human VREF isolates. These data suggest that the VREF isolates exhibit distinct phenotypic and genotypic traits according to their origins, which suggests that no evidence exists to substantiate the clonal spread or transfer of vancomycin resistance determinants between humans and poultry.


A non-reflecting wave equation through directional wave-field suppression and its finite difference implementation.
The acoustic wave equation describes wave propagation directly from basic physical laws, even in heterogeneous acoustic media. When numerically simulating waves with the wave equation, contrasts in the medium parameters automatically generate all scattering effects. For some applications - such as propagation analysis or certain wave-equation based imaging techniques - it is desirable to suppress these reflections, as we are only interested in the transmitted wave-field. To achieve this, a modification to the constitutive relations is proposed, yielding an extra term that suppresses waves with reference to a preferred direction. The scale-factor [Formula: see text] of this extra term can either be interpreted as a penetration depth or as a typical decay time. This modified theory is implemented using a staggered-grid, time-domain finite difference scheme, where the acoustic Poynting-vector is used to estimate the local propagation direction of the wave-field. The method was successfully used to suppress reflections in media with bone tissue (medical ultrasound) and geophysical subsurface structures, while introducing only minor perturbations to the transmitted wave-field and a small increase in computation time.


Efficiency of coding in macaque vocal communication.
A key characteristic of human language efficiency is that more frequently used words tend to be shorter in length-the 'law of brevity'. To date, no test of this relationship between frequency of use and length has been carried out on non-human animal vocal communication. We show here that the vocal repertoire of the Formosan macaque (Macaca cyclopis) conforms to the pattern predicted by the law of brevity, with an inverse relationship found between call duration and rate of utterance. This finding provides evidence for coding efficiency in the vocal communication system of this species, and indicates commonality in the basic structure of the coding system between human language and vocal communication in this non-human primate.


Comparison of the skin microbiota in acne and rosacea.
Acne and rosacea, despite their similar clinical presentations, follow distinct clinical courses, suggesting that fundamental differences exist in their pathophysiology. We performed a case-control study profiling the skin microbiota in rosacea and acne patients compared to matched controls. Nineteen rosacea and eight acne patients were matched to controls by age ± 5 years, sex and race. DNA was extracted from facial skin swabs. The V3V4 region of the bacterial 16S rRNA gene was sequenced using Illumina MiSeq and analysed using QIIME/Metastats 2.0 software. The mean relative abundance of Cutibacterium acnes in rosacea with inflammatory papules and pustules (20.454% ±16.943%) was more similar to that of acne (19.055% ±15.469%) than that of rosacea without inflammatory papules and pustules (30.419% ±21.862%). C acnes (P = .048) and Serratia marcescens (P = .038) were significantly enriched in individuals with rosacea compared to acne. Investigating the differences between the skin microbiota in acne and rosacea can provide important clues towards understanding the disease progression in each condition.


Learning exceptions to category rules varies across the menstrual cycle.
Ways in which ovarian hormones affect cognition have been long overlooked despite strong evidence of their effects on the brain. To address this gap, we study performance on a rule-plus-exception category learning task, a complex task that requires careful coordination of core cognitive mechanisms, across the menstrual cycle (N = 171). Results show that the menstrual cycle distinctly affects exception learning in a manner that parallels the typical rise and fall of estradiol across the cycle. Participants in their high estradiol phase outperform participants in their low estradiol phase and demonstrate more rapid learning of exceptions than a male comparison group. A likely mechanism underlying this effect is estradiol's impact on pattern separation and completion pathways in the hippocampus. These results provide novel evidence for the effects of the menstrual cycle on category learning, and underscore the importance of considering female sex-related variables in cognitive neuroscience research.


In vitro evaluation of human cytochrome P450 and P-glycoprotein-mediated metabolism of some phytochemicals in extracts and formulations of African potato.
African potato (Hypoxis hemerocallidea, AP) is a traditional herbal medicine widely used as an immune booster and also for the treatment of various ailments such as urinary diseases, prostrate hypertrophy and cancer. Amongst the chemical components contained in AP, the norlignan glycoside, hypoxoside (HYP) is purported to be the most important phytochemical in terms of AP's medicinal value. Additional constituents in AP include the sterols, beta-sitosterol (BSS), stigmasterol (STG), and the stanol, stigmastanol (STN). The potential of extracts of AP, AP formulations as well as HYP, its aglycone rooperol (ROP) and the sterols to inhibit in vitro metabolism of drug marker substrates by human cytochrome P450 (CYP) enzymes such as CYP3A4, 3A5 and CYP19 were investigated. Samples were also assessed for their effect on drug transport proteins such as P-glycoprotein (P-gp). The effects on CYP-mediated metabolism were studied by fluorometric microtitre plate assay. The potential interaction with P-gp was investigated by measuring the efflux of the fluorescent dye rhodamine 123 (Rh 123) in the CaCo-2 (colon carcinoma) cell line. Various extracts of AP, AP formulations, only STG and the norlignans, in particular the aglycone ROP, exhibited inhibitory effects on CYP3A4-, 3A5- and 19-mediated metabolism. The extracts and the formulations that contained a significant amount of HYP showed high induction of P-gp compared to the positive control, ritonavir. Whilst extrapolation of the current in vitro findings to clinical effects may well be considered speculative, these in vitro data should be heeded as a signal of possible in vivo interactions. Appropriate measures are therefore necessary to explore the possibility of such in vitro-in vivo correlations.


Type 2 diabetes among North American children and adolescents: an epidemiologic review and a public health perspective.
To review the magnitude, characteristics, and public health importance of type 2 diabetes in North American youth. Among 15- to 19-year-old North American Indians, prevalence of type 2 diabetes per 1000 was 50.9 for Pima Indians, 4.5 for all US American Indians, and 2.3 for Canadian Cree and Ojibway Indians in Manitoba. From 1967-1976 to 1987-1996, prevalence increased 6-fold for Pima Indian adolescents. Among African Americans and whites aged 10 to 19 years in Ohio, type 2 diabetes accounted for 33% of all cases of diabetes. Youth with type 2 diabetes were generally 10 to 19 years old, were obese and had a family history of type 2 diabetes, had acanthosis nigricans, belonged to minority populations, and were more likely to be girls than boys. At follow-up, glucose control was often poor, and diabetic complications could occur early. Type 2 diabetes is an important problem among American Indian and First Nation youth. Other populations have not been well studied, but cases are now occurring in all population groups, especially in ethnic minorities. Type 2 diabetes among youth is an emerging public health problem, for which there is a great potential to improve primary and secondary prevention.


Somatic cells regulate maternal mRNA translation and developmental competence of mouse oocytes.
Germ cells divide and differentiate in a unique local microenvironment under the control of somatic cells. Signals released in this niche instruct oocyte reentry into the meiotic cell cycle. Once initiated, the progression through meiosis and the associated programme of maternal messenger RNA translation are thought to be cell autonomous. Here we show that translation of a subset of maternal mRNAs critical for embryo development is under the control of somatic cell inputs. Translation of specific maternal transcripts increases in oocytes cultured in association with somatic cells and is sensitive to EGF-like growth factors that act only on the somatic compartment. In mice deficient in amphiregulin, decreased fecundity and oocyte developmental competence is associated with defective translation of a subset of maternal mRNAs. These somatic cell signals that affect translation require activation of the PI(3)K-AKT-mTOR pathway. Thus, mRNA translation depends on somatic cell cues that are essential to reprogramme the oocyte for embryo development.


Integration of the genetic map and genome assembly of fugu facilitates insights into distinct features of genome evolution in teleosts and mammals.
The compact genome of fugu (Takifugu rubripes) has been used widely as a reference genome for understanding the evolution of vertebrate genomes. However, the fragmented nature of the fugu genome assembly has restricted its use for comparisons of genome architecture in vertebrates. To extend the contiguity of the assembly to the chromosomal level, we have generated a comprehensive genetic map of fugu and anchored the scaffolds of the assembly to the 22 chromosomes of fugu. The map consists of 1,220 microsatellite markers that provide anchor points to 697 scaffolds covering 86% of the genome assembly (http://www.fugu-sg.org/). The integrated genome map revealed a higher recombination rate in fugu compared with other vertebrates and a wide variation in the recombination rate between sexes and across chromosomes of fugu. We used the extended assembly to explore recent rearrangement events in the lineages of fugu, Tetraodon, and medaka and compared them with rearrangements in three mammalian (human, mouse, and opossum) lineages. Between the two pufferfishes, fugu has experienced fewer chromosomal rearrangements than Tetraodon. The gene order is more highly conserved in the three teleosts than in mammals largely due to a lower rate of interchromosomal rearrangements in the teleosts. These results provide new insights into the distinct patterns of genome evolution between teleosts and mammals. The consolidated genome map and the genetic map of fugu are valuable resources for comparative genomics of vertebrates and for elucidating the genetic basis of the phenotypic diversity of ~25 species of Takifugu that evolved within the last 5 My.


Feasibility, reliability, and validity of a smartphone based application for the assessment of cognitive function in the elderly.
While considerable knowledge has been gained through the use of established cognitive and motor assessment tools, there is a considerable interest and need for the development of a battery of reliable and validated assessment tools that provide real-time and remote analysis of cognitive and motor function in the elderly. Smartphones appear to be an obvious choice for the development of these "next-generation" assessment tools for geriatric research, although to date no studies have reported on the use of smartphone-based applications for the study of cognition in the elderly. The primary focus of the current study was to assess the feasibility, reliability, and validity of a smartphone-based application for the assessment of cognitive function in the elderly. A total of 57 non-demented elderly individuals were administered a newly developed smartphone application-based Color-Shape Test (CST) in order to determine its utility in measuring cognitive processing speed in the elderly. Validity of this novel cognitive task was assessed by correlating performance on the CST with scores on widely accepted assessments of cognitive function. Scores on the CST were significantly correlated with global cognition (Mini-Mental State Exam: r = 0.515, p<0.0001) and multiple measures of processing speed and attention (Digit Span: r = 0.427, p<0.0001; Trail Making Test: r = -0.651, p<0.00001; Digit Symbol Test: r = 0.508, p<0.0001). The CST was not correlated with naming and verbal fluency tasks (Boston Naming Test, Vegetable/Animal Naming) or memory tasks (Logical Memory Test). Test re-test reliability was observed to be significant (r = 0.726; p = 0.02). Together, these data are the first to demonstrate the feasibility, reliability, and validity of using a smartphone-based application for the purpose of assessing cognitive function in the elderly. The importance of these findings for the establishment of smartphone-based assessment batteries of cognitive and motor function in the elderly is discussed.


Large-scale identification of core-fucosylated glycopeptide sites in pancreatic cancer serum using mass spectrometry.
Glycosylation has significant effects on protein function and cell metastasis, which are important in cancer progression. It is of great interest to identify site-specific glycosylation in search of potential cancer biomarkers. However, the abundance of glycopeptides is low compared to that of nonglycopeptides after trypsin digestion of serum samples, and the mass spectrometric signals of glycopeptides are often masked by coeluting nonglycopeptides due to low ionization efficiency. Selective enrichment of glycopeptides from complex serum samples is essential for mass spectrometry (MS)-based analysis. Herein, a strategy has been optimized using LCA enrichment to improve the identification of core-fucosylation (CF) sites in serum of pancreatic cancer patients. The optimized strategy was then applied to analyze CF glycopeptide sites in 13 sets of serum samples from pancreatic cancer, chronic pancreatitis, healthy controls, and a standard reference. In total, 630 core-fucosylation sites were identified from 322 CF proteins in pancreatic cancer patient serum using an Orbitrap Elite mass spectrometer. Further data analysis revealed that 8 CF peptides exhibited a significant difference between pancreatic cancer and other controls, which may be potential diagnostic biomarkers for pancreatic cancer.


Pharmacokinetics of oral sustained release clonidine in humans.
Tablet cores of clonidine (Catapres) showing varying rates of in vitro dissolution were administered in a crossover study with intravenous clonidine to determine the rate of absorption into the systemic circulation in humans. Excellent bioavailability (0.87-0.96) was obtained in all 12 subjects for each of the formulations. When peak concentration and time to peak are compared for the standard immediate release cores and the cores designed to be slowly dissolving there was a significant difference (p less than 0.05). Absorption rate plots for each formulation in each subject were obtained using the Loo-Riegelman procedure of comparing the oral pharmacokinetic profile with the intravenous profile. As the release from the cores were formulated to be slower, the in vivo absorption rate of clonidine approached zero order input. Incorporating combinations of sustained release and immediate release cores into a capsule (Perlonget) gave predictable absorption rates, permitting the formulation scientist to control the plasma levels obtained from oral dosing of clonidine. The intravenous pharmacokinetics of clonidine after a 0.2 mg infusion followed a tri-exponential decline with a final phase half-life of 13.6 h (harmonic mean). Following the intravenous infusion 42.3% of the dose was excreted unchanged in the urine with a renal clearance of 10.05 +/- 0.65 1/h (167 ml/min).


Student learning: what has instruction got to do with it?
A seemingly unending controversy in the field of instruction science concerns how much instructional guidance needs to be provided in a learning environment. At the one extreme lies the claim that it is important for students to explore and construct knowledge for themselves, which is often called discovery learning, and at the other extreme lies the claim that providing direct instruction is more beneficial than withholding it. In this article, evidence and arguments that support either of the approaches are reviewed. Also, we review how different instructional approaches interact with other instructional factors that have been known to be important, such as individual difference, self-explanation, and comparison. The efforts to combine different instructional approaches suggest alternative ways to conceive of learning and to test it.


Comparison of mobile health education messages verses face-to-face consultation for weight reduction among overweight female adolescents in Thailand.
Background: Obesity is considered a significant public health problem in Thailand. This study was conducted to compare the impact of mobile health education messages verses face-to-face consultation on weight reduction among overweight female university students. Methods: This Quasi-experimental study comprised three groups: a control group, a group receiving mobile health education, and a group receiving face-to-face consultation. Each group contained 26 participants taking part over a period of 12 weeks, with a 12-week follow-up thereafter. The data analysis used two-way repeated measures ANOVA with least significant difference testing. The study was ethically approved at Chulalongkorn University, Thailand. Results: The results revealed that the intervention found significant results in weight reduction among the respondents ( p < 0.05). In addition, both intervention groups significantly improved their health belief, social support, and health behavior scores in comparison to the control group ( p < 0.001). The results show that the average scores for social support for eating and exercise at baseline were significantly lower than at post-intervention or follow-up ( p < 0.001). In addition, the results of both aspects of social support showed that the average social support score at post-intervention was significantly higher than at follow-up. Furthermore, the health behavior score measured post-intervention was higher than at follow-up. There was a statistically significant difference in average metabolism during physical activity ( p < 0.001) but no statistical difference in average eating behavior score. Conclusion: The study found that the use of mobile health education to deliver health programs facilitates communication between the healthcare provider and individual, and can empower adolescent females in their pursuit of weight loss by improving their attitudes and knowledge, leading to better health behavior. Keywords Electronic health education, Facebook, health education, health belief model, social support, obesity, Thailand, health behaviors.


[Use of affinity chromatography for the purification of specific endonuclease Eco RI and Bg1 II].
The highly active preparations of specific endonucleases Eco RI and Bgl II were purified by affinity chromatography from E. coli and Bacillus globiggii cells, respectively. The isolation and purification procedures included cell disruption by ultrasonication, ultracentrifugation and chromatography. Blue dextrane-Sepharose, folate-Sepharose and phenyl-Sepharose were used as affinity adsorbents. The optimal conditions for the adsorption and elution of the endonucleases excluding intermediate steps of dialysis and concentration were selected. A high degree of purification was achieved by a consecutive use of adsorbents with different ligands. The purified enzyme does not contain non-specific nucleases or phosphatases, is sufficiently concentrated and can be used for specific hydrolysis of DNA.


An examination of factorial invariance of the Asthma Control Questionnaire among adults with severe asthma.
The Asthma Control Questionnaire (ACQ) is used to assess asthma symptom control. The relationship between the questionnaire items and symptom control has not been fully studied in severe asthmatic patients, and its validity for making comparisons between subgroups of patients is unknown. Data was obtained from patients in the United Kingdom Severe Asthma Registry whose symptom control was assessed using the five-item ACQ (ACQ5) (n = 2,951). Confirmatory factor analysis determined whether a latent factor for asthma symptom control, as measured by the ACQ5, was consistent with the data. Measurement invariance was examined in relation to ethnicity, sex and age; this included testing for approximate measurement invariance using Bayesian Structural Equation Modelling (BSEM). The fitted models were used to estimate the internal consistency reliability of the ACQ5. Invariance of factor means across subgroups was assessed. A one-factor construct with residual correlations for the ACQ5 was an excellent fit to the data in all subgroups (Root Mean Square Error Approximation 0.03 [90%CI 0.02,0.05], p-close fit 0.93, Comparative Fit Index 1.00, Tucker Lewis Index 1.00}. Expected item responses were consistent for Caucasian and non-Caucasian patients with the same absolute level of symptom control. There was some evidence that females and younger adults reported wakening more frequently during the night than males and older adults respectively with the same absolute level of symptom control (p<0.001). However approximate measurement invariance was tenable and any failure to observe strong measurement invariance had minimal impact when comparing mean levels of asthma symptom control between patients of different sexes or ages. Average levels of asthma symptom control were lower for non-Caucasians (p = 0.001), females (p<0.01)and increased with age (p<0.01). Reliability of the instrument was high (over 88%) in all subgroups studied. The ACQ5 is informative in comparing levels of symptom control between severe asthmatic patients of different ethnicities, sexes and ages. It is important that analyses are replicated in other severe asthma registries to determine whether measurement invariance is observed.


Discovery and characterization of tRNAIle lysidine synthetase (TilS).
In the bacterial decoding system, the AUA codon is deciphered as isoleucine by tRNA(Ile) bearing lysidine (L, 2-lysyl-cytidine) at the wobble position. Lysidine is an essential modification that determines both the codon and amino acid specificities of tRNA(Ile). We identified an enzyme named tRNA(Ile) lysidine synthetase (TilS) that catalyzes lysidine formation by using lysine and ATP as substrates. Biochemical studies revealed a molecular mechanism of lysidine formation that consists of two consecutive reactions involving the adenylated tRNA intermediate. In addition, we deciphered how Escherichia coli TilS specifically discriminates between tRNA(Ile) and the structurally similar tRNA(Met), which bears the same anticodon loop. Recent structural studies unveiled tRNA recognition by TilS, and a molecular basis of lysidine formation at atomic resolution.