Phone Calls to Retain Research Participants and Determinants of Reachability in an African Setting: Observational Study.
Long-term retention of research participants in studies is challenging. In research in sub-Saharan Africa, phone calls are the most frequently used method to distantly engage with participants. We aimed to get insight into the effectiveness of phone calls to retain contact with participants and evaluated determinants of reachability. A cross-sectional study was performed using the databases of two randomized controlled trials investigating different kinds of antiretroviral therapy in HIV-positive patients. One trial finished in 2018 (study 1), and the other finished in 2015 (study 2). A random sample size of 200 participants per study was obtained. There were up to 3 phone numbers available per participant collected during the studies. Participants received a maximum of 3 phone calls on every available number on different days and at different times. Voicemails were left, and emails sent wherever possible. We documented how many calls were answered, who answered, as well as after how many attempts participants were reached. To further increase our understanding of reachability, we conducted a short questionnaire assessing factors contributing to reachability. The study was approved by the Research Ethics Committee of the University of Witwatersrand, Johannesburg, South Africa (reference number M1811107). In our sample size of n=200 per study, study 1, with a median time of 11 months since the last visit at the research site, had a response rate of 70.5% (141/200) participants while study 2, with a median duration of 55 months since the last visit, had a response rate of 50.0% (100/200; P<.001). In study 1, 61.5% (123/200) of calls were answered directly by the participant while this was 36.0% (72/200) in study 2 (P=.003). The likelihood of reaching a participant decreased with time (odds ratio [OR] 0.73, 95% CI 0.63 to 0.84) for every year since the last face-to-face visit. Having more phone numbers per participant increased reachability (OR 2.32, 95% CI 1.24 to 4.36 for 2 phone numbers and OR 3.03, 95% CI 1.48 to 6.22 for 3 phone numbers compared with 1 number). A total of 141 of 241 reached participants responded to the questionnaire. Of the 93 participants who had changed phone numbers, 5% (50/93) had changed numbers because their phone was stolen. The most preferred method of being contacted was direct calling (128/141) with participants naming this method followed by WhatsApp (69/141). Time since last visit and the number of phone numbers listed were the only determinants of reachability. Longer follow-up time is accompanied with a decrease in reachability by phone while more listed phone numbers increases the likelihood that someone can be reached. ClinicalTrials.gov NCT02671383; https://clinicaltrials.gov/ct2/show/NCT02671383 and ClinicalTrials.gov NCT02670772; https://clinicaltrials.gov/ct2/show/NCT02670772.


Membrane properties and aging: in vivo and in vitro effects of ethanol on synaptosomal gamma-aminobutyric acid (GABA) release.
It has been reported previously that biological membranes from aged mice are disordered less by ethanol as compared with membranes from younger animals. The purpose of this study was to determine whether those age differences would be associated with changes in membrane transport as measured by release of gamma-aminobutyric acid (GABA). GABA release in the presence and absence of ethanol was measured in synaptosomes from young (4 months), middle (14 months) and aged (28 months) C57BL/ 6NNIA male mice. In addition, the effects of chronic ethanol administration on GABA release was examined in young and aged mice. GABA release was inhibited more by ethanol in synaptosomes from young mice as compared with older mice. The IC50 for ethanol was significantly lower for the younger mice than for the older mice. GABA release in the presence of ethanol was affected by chronic ethanol administration. Inhibition of release was significantly less for young ethanol-tolerant as compared with young control animals. Release did not differ significantly between the old ethanol and old control groups. Inhibition of GABA release was found to be highly related to the membrane/buffer partition coefficient of n-alcohols. The results of the present study are consistent with our earlier finding that membranes from aged mice are disordered less by ethanol as compared with younger mice.


The favorable impact of PIK3CA mutations on survival: an analysis of 2587 patients with breast cancer.
The phosphatidylinositol-3 kinase(PI3K) pathway regulates a number of cellular processes, including cell survival, cell growth, and cell cycle progression. Consequently, this pathway is commonly deregulated in cancer. In particular, mutations in the gene PIK3CA that encodes the p110α catalytic subunit of the PI3K enzymes result in cell proliferation and resistance to apoptosis in vitro and induce breast tumors in transgenic mice. These data underscore the role of this pathway during oncogenesis. Thus, an ongoing, large-scale effort is underway to develop clinically active drugs that target elements of the PI3K pathway. However, conflicting data suggest that gain-of-function PIK3CA mutations may be associated with either a favorable or a poor clinical outcome, compared with the wild-type PIK3CA gene. In the current study, we performed a systematic review of breast cancer clinical studies. Upon evaluation of 2587 breast cancer cases from 12 independent studies, we showed that patients with tumors harboring a PIK3CA mutation have a better clinical outcome than those with a wild-type PIK3CA gene. Importantly, this improved prognosis may pertain only to patients with mutations in the kinase domain of p110α and to postmenopausal women with estrogen receptor-positive breast cancer. We propose three potential explanations for this paradoxical observation. First, PIK3CA mutations may interfere with the metastasis process or may induce senescence, which results in a better outcome for patients with mutated tumors. Secondly, we speculate that PIK3CA mutations may increase early tumor diagnosis by modification of the actin cytoskeleton in tumor cells. Lastly, we propose that PIK3CA mutations may be a favorable predictive factor for response to hormonal therapy, giving a therapeutic advantage to these patients. Ultimately, an improved understanding of the clinical impact of PIK3CA mutations is critical for the development of optimally personalized therapeutics against breast cancer and other solid tumors. This effort will be important to prevent or explain therapeutic failures and select patients who are most likely to respond to new therapies that inhibit the PI3K pathway.


Prediction of Phenotypic Antimicrobial Resistance Profiles From Whole Genome Sequences of Non-typhoidal Salmonella enterica.
Surveillance of antimicrobial resistance (AMR) in non-typhoidal Salmonella enterica (NTS), is essential for monitoring transmission of resistance from the food chain to humans, and for establishing effective treatment protocols. We evaluated the prediction of phenotypic resistance in NTS from genotypic profiles derived from whole genome sequencing (WGS). Genes and chromosomal mutations responsible for phenotypic resistance were sought in WGS data from 3,491 NTS isolates received by Public Health England's Gastrointestinal Bacteria Reference Unit between April 2014 and March 2015. Inferred genotypic AMR profiles were compared with phenotypic susceptibilities determined for fifteen antimicrobials using EUCAST guidelines. Discrepancies between phenotypic and genotypic profiles for one or more antimicrobials were detected for 76 isolates (2.18%) although only 88/52,365 (0.17%) isolate/antimicrobial combinations were discordant. Of the discrepant results, the largest number were associated with streptomycin (67.05%, n = 59). Pan-susceptibility was observed in 2,190 isolates (62.73%). Overall, resistance to tetracyclines was most common (26.27% of isolates, n = 917) followed by sulphonamides (23.72%, n = 828) and ampicillin (21.43%, n = 748). Multidrug resistance (MDR), i.e., resistance to three or more antimicrobial classes, was detected in 848 isolates (24.29%) with resistance to ampicillin, streptomycin, sulphonamides and tetracyclines being the most common MDR profile (n = 231; 27.24%). For isolates with this profile, all but one were S. Typhimurium and 94.81% (n = 219) had the resistance determinants blaTEM-1,strA-strB, sul2 and tet(A). Extended-spectrum β-lactamase genes were identified in 41 isolates (1.17%) and multiple mutations in chromosomal genes associated with ciprofloxacin resistance in 82 isolates (2.35%). This study showed that WGS is suitable as a rapid means of determining AMR patterns of NTS for public health surveillance.


Evaluation of dried blood spots as an alternative sample matrix for equine antidoping analysis.
Controlling the abuse of prohibited substances such as anabolic steroids, selective androgen receptor modulators, β-adrenoceptor agonists, and blood doping agents is of great interest to racing authorities. The use of dried blood spots (DBS) as an alternative sampling approach may be a feasible approach for controlling the use of these agents. To assess the feasibility of using DBS in equine blood, an 11-min liquid chromatography-mass spectrometry method was developed on a triple quadrupole mass spectrometer following extraction from Whatman 903 DBS cards. A total of 50 compounds across multiple compound classes were detectable with reproducible results. The stability was assessed with good results after almost 3 months of storage at ambient temperatures. These results suggest that the use of DBS may be a feasible alternative sampling approach in equine drug testing.


[Motives and interpersonal functions of aggression].
In this review, the author theoretically and empirically examined motives and interpersonal functions of aggression. A factor-analysis of Averill's questionnaire items on anger revealed that motives involved in aggressive responses were clustered into two groups: the hostile and the instrumental. It was also clarified that an individual is likely to engage in aggression particularly when some hostile motives are evoked. Concerning the interpersonal functions, the author proposed that aggression might serve four principal goals. (1) Aggression can be generated as an avoidance response to an aversive stimulus, such as frustration, annoyance, or pain, and so on. It depends on the severity of the stimulus. It was however emphasized that aggression is also mediated by social cognition, such as an attribution of intent to a harm-doer. (2) Aggression can be used as a means of coercing the other person into doing something. An individual is likely to use such a power strategy if he/she is lacking in self-confidence or a perspective for influencing the target person by more peaceful strategies. (3) Aggression can be interpreted as a punishment when it is directed toward a transgressor. In this case, aggression is motivated by restoration of a social justice, and thus its intensity is determined by the perceived moral responsibility of the transgressor. Further, it was indicated that aggression is intensified if it is justified as a sanctional conduct against the immoral. (4) Aggression can be also evoked when an individual's social identity is threatened. It was suggested that impression management motives are involved in aggression by an unexpected finding that the presence of audience or the identifiability rather facilitated retaliative aggression. The aggression-inhibition effect of apology was also explained in terms of impression management. In conclusion, it was presented that aggression is a behavioral strategy as an attempt to resolve interpersonal conflicts including physical or psychological annoyance, the other person's disobedience, perceived injustice, and a threat to one's social identity. Whether one's aggression is performed or not depends on a number of intra- and inter-personal determinants, particularly on social cognitive processes such as attribution, inference, prediction and other judgements.


Drug therapy of post-traumatic stress disorder.
Post-traumatic stress disorder (PTSD) is a recently introduced diagnosis. The disorder is quite common, yet often unrecognised, and leads to significant morbidity or mortality. Effective treatment often entails use of psychotropic medication. Only recently has this become apparent, and awareness of the role of drug therapy in PTSD remains limited. A number of studies have indicated efficacy for antidepressant, mood-stabilising, anticonvulsant and antianxiety medications. This review describes the role of pharmacotherapy, by examining issues of diagnosis and recognition of PTSD, the theoretical basis for drug use, goals of drug treatment, dose ranges, and clinical application of psychotropic drugs.


Higher-achieving children are better at estimating the number of books at home: Evidence and implications.
The number of books at home is commonly used as a proxy for socioeconomic status in educational studies. While both parents' and students' reports of the number of books at home are relatively strong predictors of student achievement, they often disagree with each other. When interpreting findings of analyses that measure socioeconomic status using books at home, it is important to understand how findings may be biased by the imperfect reliability of the data. For example, it was recently suggested that especially low-achieving students tend to underestimate the number of books at home, so that use of such data would lead researchers to overestimate the association between books at home and achievement. Here we take a closer look at how students' and parents' reports of the number of books at home relate to literacy among fourth grade students, by analyzing data from more than 250,000 students in 47 countries participating in 2011 PIRLS. Contrary to prior claims, we find more downward bias in estimates of books at home among high-achieving students than among low-achieving students, but unsystematic errors appear to be larger among low-achieving students. This holds within almost every country. It also holds between countries, that is, errors in estimates of books at home are larger in low-achieving countries. This has implications for studies of the association between books at home and achievement: the strength of the association will generally be underestimated, and this problem is exacerbated in low-achieving countries and among low-achieving students.


Pharmacological modulation of edema induced by Lys-49 and Asp-49 myotoxic phospholipases A2 isolated from the venom of the snake Bothrops asper (terciopelo).
The pharmacological modulation of edema-forming activity of Bothrops asper myotoxins II and III, Lys-49 and Asp-49 phospholipases A2, respectively, was studied plethysmographically in the mouse foot pad model. Myotoxin III had phospholipase A2 activity, whereas myotoxin II was devoid of enzymatic activity when tested on egg yolk phosphatidylcholine. Both toxins induced a dose-dependent edema of rapid onset. Chemical modification of myotoxin III with p-bromophenacyl bromide abrogated enzymatic activity and significantly reduced edemat-forming activity, although a residual effect remained. Pre-treatment of animals with diphenhydramine, dexamethasone, indomethacin and prazosin significantly reduced the effect of both myotoxins. It is concluded that (a) these myotoxins are important edema-forming components of B. asper venom, (b) enzymatic activity is not a strict requirement to exert this effect, although in the case of myotoxin III it contributes to its development, and (c) several inflammatory mediators participate in mouse foot pad edema induced by these myotoxins.


Immunohistochemical analysis of inflammation in primary sclerosing cholangitis.
There are only limited data about the nature of the mononuclear infiltrate surrounding the affected biliary canaliculi in primary sclerosing cholangitis (PSC). The aim of this study was to characterize the composition of the mononuclear infiltrate and to detect signs of activation/ proliferation among the various subpopulations involved. Furthermore the putative role of the biliary epithelium as antigen presenting cells (APC) was assessed. Liver biopsies of 14 PSC patients were analysed. Seven liver specimens of non-inflammatory liver disease (NIL) patients with hepatocellular carcinoma or metastasis from colorectal carcinoma, as well as eight liver biopsies of primary biliary cirrhosis (PBC) patients, served as controls. Paraffin embedded material was stained with GB7, anti-CD3, anti-CD20, anti-CD45RO. Deep frozen sections were stained with anti-CD4, anti-CD8, anti-CD25, anti-CD86, anti-HLA-DR, anti-IFNgamma, anti-IL4, anti-ICAM1 and anti-alpha4beta7. Stainings were scored by two pathologists using a semiquantitative scale. The portal infiltrate was found to consist mainly of CD3+CD45RO+ cells. Few cells expressed activation or proliferation markers in any of the liver specimens. In the PSC-material, significantly more of the infiltrative lymphocytes were positive for the integrin alpha4beta7, as compared to hardly any positive cells in the NIL-group (P < 0.001) and < 10% in the PBC-specimens (P < 0.01). Variable HLA-DR expression of the biliary epithelium was observed in all groups, however, without co-expression of ICAM1 or B7.2. The portal infiltrate in PSC liver histology specimens appears to consist mainly of non-activated memory T-lymphocytes, a substantial proportion of which expresses the gut-homing integrin alpha4beta7. An antigen-presenting role for the biliary epithelium could not be demonstrated.


Mobile applications in medical education: A systematic review and meta-analysis.
This review evaluates the effectiveness of smartphone applications in improving academic performance and clinical practice among healthcare professionals and students. This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Articles were retrieved from PubMed, Scopus, and Cochrane library through a comprehensive search strategy. Studies that included medical, dental, nursing, allied healthcare professional, undergraduates, postgraduates, and interns from the same disciplines who used mobile applications for their academic learning and/or daily clinical practice were considered. 52 studies with a total of 4057 learner participants were included in this review. 33 studies (15 RCTs, 1 cluster RCT, 7 quasi-experimental studies, 9 interventional cohort studies and 1 cross-sectional study) reported that mobile applications were an effective tool that contributed to a significant improvement in the knowledge level of the participants. The pooled effect of 15 studies with 962 participants showed that the knowledge score improved significantly in the group using mobile applications when compared to the group who did not use mobile applications (SMD = 0.94, 95% CI = 0.57 to1.31, P<0.00001). 19 studies (11 RCTs, 3 quasi-experimental studies and 5 interventional cohort studies) reported that mobile applications were effective in significantly improving skills among the participants. Mobile applications are effective tools in enhancing knowledge and skills. They can be considered as effective adjunct tools in medical education by considering their low expense, high versatility, reduced dependency on regional or site boundaries, online and offline, simulation, and flexible learning features of mobile apps.


Variance estimation for stratified propensity score estimators.
Propensity score methods are increasingly used to estimate the effect of a treatment or exposure on an outcome in non-randomised studies. We focus on one such method, stratification on the propensity score, comparing it with the method of inverse-probability weighting by the propensity score. The propensity score--the conditional probability of receiving the treatment given observed covariates--is usually an unknown probability estimated from the data. Estimators for the variance of treatment effect estimates typically used in practice, however, do not take into account that the propensity score itself has been estimated from the data. By deriving the asymptotic marginal variance of the stratified estimate of treatment effect, correctly taking into account the estimation of the propensity score, we show that routinely used variance estimators are likely to produce confidence intervals that are too conservative when the propensity score model includes variables that predict (cause) the outcome, but only weakly predict the treatment. In contrast, a comparison with the analogous marginal variance for the inverse probability weighted (IPW) estimator shows that routinely used variance estimators for the IPW estimator are likely to produce confidence intervals that are almost always too conservative. Because exact calculation of the asymptotic marginal variance is likely to be complex, particularly for the stratified estimator, we suggest that bootstrap estimates of variance should be used in practice.


Developing a Biomechanical Testing Setup of the Pelvis-Part II: Experimental Testing.
Biomechanical testbench emulating the physiological loading of the pelvis is crucial in developing reconstructive implants for fragility fractures of the pelvis. Additionally, it will help understand the influence of the common daily loading on the pelvic ring. However, most reported experimental studies were mainly comparative with simplified loading and boundary conditions. In Part I of our study, we described the concept of the computational experiment design to design and construct a biomechanical testbench emulating the gait movement of the pelvis. The 57 muscles and joints' contact forces were reduced to four force actuators and one support, producing a similar stress distribution. The experimental setup is explained in this paper and some experimental results are presented. In addition, a series of repeatability and reproducibility tests were conducted to assess the test stand capabilities of replicating the gait physiological loading. The calculated stresses and the experimentally recorded strains showed that the pelvic ring response to the loading always follows the loaded leg side during the gait cycle. Furthermore, the experimental results of the pelvis displacement and strain at selected locations match the numerical ones. The developed test stand and the concept of computational experiment design behind it provide guidelines on how to design biomechanical testing equipment with physiological relevance.


Resveratrol addiction: to die or not to die.
Resveratrol, a polyphenol derived from red grapes, berries, and peanuts, has been shown to mediate death of a wide variety of cells. The mechanisms by which resveratrol mediates cell death include necrosis, apoptosis, autophagy, and others. While most studies suggest that resveratrol kills tumor cells selectively, evidence is emerging that certain normal cells such as endothelial cells, lymphocytes, and chondrocytes are vulnerable to resveratrol. Cell killing by this stilbene may be mediated through any of numerous mechanisms that involve activation of mitochondria and of death caspases; upregulation of cyclin-dependent kinase inhibitors, tumor suppressor gene products, or death-inducing cytokines and cytokine receptors; or downregulation of cell survival proteins (survivin, cFLIP, cIAPs, X-linked inhibitor of apoptosis protein (XIAP), bcl-2, bcl-XL) or inhibition of cell survival kinases (e.g., mitogen-activiated protein kinases (MAPKs), AKT/phosphoinositide 3-kinase (PI3K), PKC, EGFR kinase) and survival transcription factors (nuclear factor-kappaB (NF-kappaB), activating protein 1 (AP-1), HIF-1alpha, signal transducer and activator of transcription (STAT3)). Induction of any of these pathways by resveratrol leads to cell death. While cell death is a hallmark of resveratrol, this polyphenol also has been linked with suppression of inflammation, arthritis, and cardiovascular diseases and delaying of aging. These attributes of resveratrol are discussed in detail in this review.


Detecting mineral content in turbid medium using nonlinear Raman imaging: feasibility study.
Osteoporosis is a bone disease characterized by reduced mineral content with resulting changes in bone architecture, which in turn increases the risk of bone fracture. Raman spectroscopy has an intrinsic sensitivity to the chemical content of the bone, but its application to study bones in vivo is limited due to strong optical scattering in tissue. It has been proposed that Raman excitation with photoacoustic detection can successfully address the problem of chemically specific imaging in deep tissue. In this report, the principal possibility of photoacoustic imaging for detecting mineral content is evaluated.


Interhospital transport of patients with ongoing intraaortic balloon pumping.
During a 5-year period (1979 to 1983), 50 consecutive patients undergoing continuous intraaortic balloon (IAB) pumping were transferred from Evanston Hospital to Northwestern Memorial Hospital (16 miles), where they underwent cardiac operation. All patients had cardiac catheterization before transfer. Indications for IAB were cardiogenic shock (9 patients), postinfarction angina (18 patients), unstable angina (9 patients), evolving myocardial infarction (3 patients), accelerating angina or hemodynamic instability during cardiac catheterization (9 patients) and prophylactic insertion for high-grade left main stenosis (2 patients). Transportation after stabilization was uneventful in all patients. All patients underwent operative coronary revascularization. There was concomitant mitral valve replacement in 3 patients, acute ventricular septal defect repair in 1 patient, aortic valve replacement in 1, and ventricular aneurysmectomy in 1. Three patients (5%) died postoperatively. Nine patients (20%) had complications directly related to IAB insertion. One patient required femoral-femoral arterial bypass preoperatively, 4 patients had postoperative lower limb ischemia treated by IAB removal or thrombectomy and 1 patient had thrombocytopenia (less than 60,000/mm3), 1 false aneurysm, 1 anterior compartment syndrome and 1 prolonged bleeding at the insertion site. Interhospital transfer with IAB pumping in progress should not be restricted to patients with cardiogenic shock, but can be effectively used for all patients who require preoperative IAB insertion.(ABSTRACT TRUNCATED AT 250 WORDS)


[Effects of some extenders and monoamines on sperm cryopreservation in tree shrews (Tupaia belangeri)].
The tree shrew may be an important experimental animal for disease models in humans. The effects of some extenders and momamines on sperm cryopreservation will provide helpful data for experimentation of strains and conservation of genetic resources in tree shrews. Epididymal sperm were surgically harvested from male tree shrews captured around Kunming, China and sperm motility, acrosome integrity and fertility were assessed during cryopreservation. In Experiment 1 eight extenders (TTE, TCG, TCF, TTG, BWW, BTS, DM, and SR) supplemented with 0.4 mol/L DMSO were used to dilute the sperm: only TTE, DM and SR showed no differences in motility and acrosome integrity compared to fresh controls after equilibration. After freezing and thawing, sperm in any extender showed lower motility than fresh control and sperm in DM showed higher motility than other groups. However, BWW produced the lowest motility. For acrosome integrity, TTE and DM showed higher than BWW, BTS and SR after equilibration. The parameter in DM was higher than other groups (except TTE) after thawing. In Experiment 2 four penetrating cryoprotectant agents (CPA) [dimethyl-formamide (DF), formamide (F), dimethylacetamide (DA), and acetamide (A)] at 0.2 mol/L, 0.4 mol/L, 0.8 mol/L, and 1.2 mol/L, respectively were added to the DM extender. Motility showed no difference among CPA groups and non-CPA group (control) after equilibration, but all thawed sperm showed lower values in motility and acrosome integrity than pre-freezing groups. However, sperm in 0.8 mol/L DF and 0.4 mol/L DMSO showed higher values in both parameters than that in other CPA groups (P>0.05). In Experiment 3 the fertilization rate of oocytes inseminated with 0.4mol/L DMSO (50%) were higher than that with 0.8mol/L DF (16%). In conclusion, non-ion extenders supplemented with egg yolk may be better for sperm cryopreservation in tree shrews and cryoprotectant effects of monoamines agents should be further studied in this species.


The influence of glucose, succinate, pH of the medium and higher temperature on the cytotoxic activity of the preparation Ukrain.
Cells of ascitic forms of Ehrlich's carcinoma and sarcoma 37 transplanted into C57BI/6 mice were used to study the influence of glucose, succinate, and pH of the medium on the cytotoxic activity of the preparation Ukrain. Viability of cells was estimated by the method of intravital staining with tripan blue after the incubation of cell suspension in the presence of the preparation (1.05 x 10(-5) mol and 1.69 x 10(-4) mol). It was established that glucose (5 mmol) reduces the cytotoxic activity of Ukrain, while succinate (5 mmol) increases it. The activity of the preparation was practically absent at pH 6.1-6.7 of the incubation medium and was at a maximum at pH 7.3-8.0. A temperature of 41.5 degrees C has no influence on the effectiveness of Ukrain.


Fertility preservation in a family with a novel NR5A1 mutation.
The common phenotype of nuclear receptor superfamily 5, group A, member 1 (NR5A1) gene mutations in 46,XY is gonadal dysgenesis without adrenal deficiency. Though the phenotype of gonadal dysgenesis is variable, ranging from complete female to normal male genitalia, an asymptomatic 46,XY male is rare. Preserved fertility has so far been described in only three affected 46,XY males with different mutations, but no functional analysis of these mutations has been performed. Here, we report on male siblings with hypospadias and their asymptomatic father in whom we identified a heterozygous NR5A1 mutation of c.910G>A, p.E304K. Western blotting and subcellular localization revealed no significant difference between the wild type (WT) and E304K. Electrophoretic mobility shift assay experiments showed that E304K abrogated DNA-binding ability. E304K reduced transactivation and had no dominant negative effect. In conclusion, we report on a novel hypomorphic NR5A1 mutation, which may be associated with the phenotype of the family.


Quantification of CH-π Interactions Using Calix[4]pyrrole Receptors as Model Systems.
We describe the use of two series of aryl-extended calix[4]pyrrole receptors bearing two and four electronically tunable phenyl groups, respectively, in their meso-positions as model systems for the quantification of CH-π interactions in solution. The "four-wall" and the "two-wall" receptors formed thermodynamically stable 1:1 complexes in acetonitrile solution with both trimethylamine N-oxide and trimethylphosphine P-oxide as guests. The complexes were mainly stabilized by the formation of four convergent hydrogen bonds between the oxygen atom of the guests and the pyrrole NHs of the host. In general, the N-oxide produced thermodynamically more stable hydrogen bonding interactions than the P-oxide. Upon guest binding, the receptors adopted the cone conformation and the methyl groups of the included guests engaged in CH-π interactions with the aromatic walls. We show that the modification of the electronic properties of the aromatic surfaces, in any of the receptor series, did not have a significant impact in the measured binding affinities for a given guest. However, the larger binding affinities determined for the "four-wall" receptors in comparison to the "two-wall" counterparts supported the importance of CH-π interactions on guest complexation. The strength of the CH-π interactions present in the inclusion complexes was quantified employing the octamethyl calix[4]pyrrole as reference. We determined an average magnitude of ~1 kcal·mol(-1) for each CH-π interaction. The CH-π interactions featured a reduced electrostatic nature and thus dispersion forces were assigned as main contributors of their strength.


Structural and conformational features determining selective signal transduction in the beta 3-adrenergic receptor.
With respect to the beta 1- and beta 2-adrenergic receptors (ARs), the beta 3-AR induces specific physiological effects in a few target tissues and exhibits atypical pharmacological properties that distinguish it unambiguously from its counterparts. Therefore, the beta 3-AR represents a suitable model to study the molecular mechanism responsible for receptor subtype selectivity and specificity. Potent beta 3-AR ligands newly characterized in Chinese hamster ovary cells expressing the beta 3-AR were also evaluated in Chinese hamster ovary cells expressing beta 1- and beta 2-ARs and were classified into three groups according to their pharmacological properties. Among the beta 1/beta 2/beta 3 agonists BRL 37344 and LY 79771 exhibit beta 3 selectivity in stimulating adenylyl cyclase; among the beta 1/beta 2 antagonists displaying beta 3 agonistic effects ICI 201651 exhibits beta 3-AR binding selectivity, whereas among the beta 1/beta 2/beta 3 antagonist class bupranolol is the most efficient (but not selective) beta 3-AR antagonist. The structures of these ligands were simulated and compared using computer-generated molecular modeling. Structure-activity relationship analysis indicates that potent or selective beta 3-AR compounds, in addition to possessing a pharmacophore common to all beta-AR ligands, contain a long and bulky alkylamine substituent moiety, which is able to adopt and exchange extended and stacked conformations. Computerized three-dimensional models of the beta 1-, beta 2-, and beta 3-AR binding sites show that more bulky amino acid side chains point inside the groove of the beta 1 and beta 2 sites, compared with the beta 3 site, in a region implicated in signal processing. The long alkylamine chain of compounds behaving as beta 1/beta 2 antagonists and beta 3 agonists may thus adopt either a stacked conformation in the encumbered beta 1- and beta 2-AR sites, leading to antagonistic effects, or an extended conformation in the less encumbered beta 3 site, thus interacting with specific residues implicated in signal transduction.


Childhood Trauma in Persons With Schizophrenia and a History of Interpersonal Violence.
Childhood trauma is a risk factor for psychosis as well for violent behavior and offending later in life. Childhood trauma comprises subdomains of abuse and neglect that may be differently related to later violence among patients with schizophrenia. The aim of this study was to map the subdomains of childhood trauma associated with violent offending in schizophrenia. Information on childhood trauma from predominantly male patients with a DSM-IV diagnosis of schizophrenia and a history of violent offending (interpersonal violence) (SCZ-V, n = 19), schizophrenia patients without a history of violence (SCZ-NV, n = 34), and healthy controls (HC, n = 66) was obtained with the Childhood Trauma Questionnaire (CTQ). Differences between groups in total maltreatment scores and the five subdomains including physical, emotional, and sexual abuse, as well as physical and emotional neglect were analyzed. SCZ-V had the highest median CTQ scores for all sub-domains. SCZ-V reported significantly higher total CTQ scores than SCZ-NV and HC. SCZ-V had significantly higher scores than HC on all subdomains, and significantly higher than SCZ-NV on physical and emotional neglect. SCZ-NV had higher scores on all domains except sexual abuse compared to HC. SCZ-V patients had higher exposure to childhood trauma than SCZ-NV, and both schizophrenia groups had higher exposure than HC. The results suggest that childhood physical and emotional neglect may be of specific importance to later violence in schizophrenia.


Reduced KIR2DL1 recognition of MHC class I molecules presenting phosphorylated peptides.
As initially described by K. Karre and colleagues in the missing self hypothesis, cells expressing self-MHC class I proteins are protected from NK cells attack. In contrast, reduction in the expression of MHC class I molecules due to viral infection or tumor transformation result in the killing of these "abnormal" cells by NK cells via NK-activating receptors. Thus, NK killing of target cells is determined by both negative signals coming from MHC class I proteins and by positive signals derived from the activating ligands. The bound peptide in MHC class I play an important role in the balanced recognition of NK cells. The peptide stabilizes the MHC complex and interacts directly with the NK inhibitory receptors, thus participating in the determination of the fate of the target cells. In this study we demonstrate that posttranslational modifications such as phosphorylation of the presented peptide altered the ability of NK cells to recognize MHC class I molecules. By using a consensus peptide (QYDDAVYKL) that binds HLA-Cw4 in which different positions in the bound peptide were modified by serine phosphorylation, we observed a reduction in KIR2DL1 binding that led to decreased protection from NK killing. Therefore, it might be possible that alteration in the phosphorylation pattern during tumor transformation or viral infection may result in less inhibition and, consequently, improved NK cell killing.


Influence of calf genotype on colostral immunoglobulins in Bos taurus and Bos indicus cows and serum immunoglobulins in their calves.
Purebred Bos indicus calves are documented to have lower survival rates than Bos taurus calves. Thus, this study was designed to investigate the possibility that this decreased survival rate may be attributed to dam colostral immunoglobulin (Ig) concentrations and subsequent calf serum Ig concentrations. The specific objective was to determine the effect of breed type of calf on colostrum production, immunoglobulin concentrations in colostrum and calf serum, and availability and absorption efficiency of Ig. Brahman (B) and Angus (A) cattle were reciprocally mated to produce calves of the following types: A x A (n = 8), A x B (n = 9), B x B (n = 11), and B x A (n = 11). At birth, calves were separated from their dams and a blood sample was collected before feeding pooled colostrum (30 mL/kg birth weight) at 1 and 6 h of age. From 6 to 12 h of age, each calf was placed in a box that allowed interaction with the dam but prevented suckling. At 12 h of age, each calf was fed its dam's colostrum and placed with the dam. Additional blood samples were collected at 12, 24, and 48 h after birth. Serum and colostrum samples were analyzed for IgG, IgG1, IgG2, IgM, and IgA using single radial immunodiffusion (RID) assay techniques. The cows were hand-milked after induction of milk letdown with oxytocin at 1 and 12 h after calving. Colostrum volume was recorded, and samples were collected. Brahman cows produced more (P < .001) colostrum at 1 and 12 h than A cows. Total Ig concentrations were obtained by summing IgG, IgG1, IgG2, IgM, and IgA concentrations. Total Ig (P < .02), IgG (P < .005), and IgA (P < .01) concentrations in colostrum were greater in cows producing crossbred calves. Total Ig (P < .006), IgG (P < .02), IgG1 (P < .004), and IgG2 (P < .02) available in colostrum were affected by B x B and A x B breed types of calf. Brahman cows had more Ig available at 1 and 12 h than A cows due to increased production of colostrum. Breed type influenced colostral Ig in cattle. Serum concentrations of total Ig, IgG, IgG1, IgG2, IgM, and IgA in the calf and efficiency of absorption at 6 and 12 h were not affected by breed type, sex of calf, or any interaction.


Substance P and adrenocorticotropic hormone do not affect T-lymphocyte adhesion to vascular endothelium or surface expression of adhesion receptors.
Substance P (SP) and adrenocorticotropic hormone (ACTH) are peptides that have been shown to have both neurological and immunological effects. Because of the demonstrated effects upon immune function, we examined the effects of these peptides on T-lymphocyte adhesion to vascular endothelium and surface adhesion receptor expression. Neither the adhesion assays nor the expression assays showed any statistically significant effect of SP (10 microM) or ACTH (1 microM) for any incubation period used. We conclude that, while SP and ACTH have a variety of immunomodulatory effects, direct modulation of T-lymphocyte adhesion to vascular endothelium is probably not one of them.


Capacity building of district health management teams in the era of provincial health administration reform in the Democratic Republic of Congo: a realist evaluation protocol.
In 2006, the Congolese Ministry of Health developed a health system strengthening strategy focusing on health district development. This strategy called for reforming the provincial health administration in order to better support the health district development through leadership and management capacity building of district health management teams. The implementation is currently underway, yet, more evidence on how, for whom and under what conditions this capacity building works is needed. The proposed research aims to address this gap using a realist evaluation approach. We will follow the cycle of the realist evaluation. First, we will elicit the initial programme theory through a scoping review (completed in December 2022, using MEDLINE, Health Systems Evidence, Wiley Online Library, Cochrane Library, Google Scholar and grey literature), a review of health policy documents (completed in March 2023), and interviews with key stakeholders (by June 2023). Second, we will empirically test the initial programme theory using a multiple-embedded case study design in two provincial health administrations and four health districts (by March 2024). Data will be collected through document reviews, in-depth interviews, non-participant observations, a questionnaire, routine data from the health information management system and a context mapping tool. We will analyse data using the Intervention-Context-Actor-Mechanism-Outcome configuration heuristic. Last, we will refine the initial programme theory based on the results of the empirical studies and develop recommendations for policymakers (by June 2024). The Institutional Review Board of the Institute of Tropical Medicine and the Medical Ethics Committee of the University of Lubumbashi approved this study. We will also seek approvals from provincial-level and district-level health authorities before data collection in their jurisdictions. We will disseminate the study findings through the publication of articles in peer-reviewed academic journals, policy briefs for national policymakers and presentations at national and international conferences.


Synchrotron-Based Techniques Shed Light on Mechanisms of Plant Sensitivity and Tolerance to High Manganese in the Root Environment.
Plant species differ in response to high available manganese (Mn), but the mechanisms of sensitivity and tolerance are poorly understood. In solution culture, greater than or equal to 30 µm Mn decreased the growth of soybean (Glycine max), but white lupin (Lupinus albus), narrow-leafed lupin (Lupin angustifolius), and sunflower (Helianthus annuus) grew well at 100 µm Mn. Differences in species' tolerance to high Mn could not be explained simply by differences in root, stem, or leaf Mn status, being 8.6, 17.1, 6.8, and 9.5 mmol kg(-1) leaf fresh mass at 100 µm Mn. Furthermore, x-ray absorption near edge structure analyses identified the predominance of Mn(II), bound mostly to malate or citrate, in roots and stems of all four species. Rather, differences in tolerance were due to variations in Mn distribution and speciation within leaves. In Mn-sensitive soybean, in situ analysis of fresh leaves using x-ray fluorescence microscopy combined with x-ray absorption near edge structure showed high Mn in the veins, and manganite [Mn(III)] accumulated in necrotic lesions apparently through low Mn sequestration in vacuoles or other vesicles. In the two lupin species, most Mn accumulated in vacuoles as either soluble Mn(II) malate or citrate. In sunflower, Mn was sequestered as manganite at the base of nonglandular trichomes. Hence, tolerance to high Mn was ascribed to effective sinks for Mn in leaves, as Mn(II) within vacuoles or through oxidation of Mn(II) to Mn(III) in trichomes. These two mechanisms prevented Mn accumulation in the cytoplasm and apoplast, thereby ensuring tolerance to high Mn in the root environment.


The thoracic sympathetic neurons of the chick: normal development and the effects of nerve growth factor.
The generation and degeneration of sympathetic neurons in the third thoracic ganglion (segment 19) of the chick were studied between embryonic days (E) 7-18 using 3H-Thymidine autoradiography and routine cell counts. Cumulative radiolabelling experiments indicated that few sympathetic neurons were generated on E6-7. 10% of the sympathetic neurons were generated on E8 and a further 20% on E9. The final 70% of neurons completed the mitotic cycle between E10-12. Cell counts demonstrated that the neuronal population increased from 10,166 +/- 423 (mean +/- SEM) to 22,291 +/- 767 between E8-10 and remained stable up to E14. The population subsequently declined by 37%, to 14,157 +/- 831, by E18. Pyknotic neurons were found at all stages of development, but were most apparent between E7-15. The effects of Nerve Growth Factor (NGF) on the number of both surviving and pyknotic neurons in the ganglion were also examined. E9 embryos treated with NGF from E5-8 showed a 57% increase in the number of sympathetic neurons. This increase therefore occurred prior to the decline in neuronal number and was not accompanied by a decrease in the number of visibly pyknotic neurons. It is therefore possible that early NGF treatment increases the number of sympathetic neurons through a mechanism other than the attenuation of cell death.


Synthesis, analysis and cytotoxic evaluation of some hydroxypyridinone derivatives on HeLa and K562 cell lines.
A range of iron bidentae ligands containing the chelating moiety 3- hydroxypyridin-4-ones (HPOs) have been synthesized via a single or a three-step synthetic pathway. In the single-step reaction, maltol was directly reacted by suitable primary amine and in the second synthetic method; benzylated maltol was reacted with related amines to give 1-substuted-2-methyl-3-benzyloxypyridin-4-one derivatives. Finally, removal of the benzyl group under acidic conditions was performed by catalytic hydrogenation to yield the favored bidentate chelators as HCl salt. The partition coefficient of the free ligands and their iron (III) complexes between an aqueous phase buffered at pH 7.4 and 1-octanol were also determined. The cytotoxic effects of these iron chelators against HeLa and K562 cell lines were evaluated using MTT assay and the results showed that cytotoxicity was closely related to the lipophilicity of compounds so that the most lipophilic compound (4g) revealed the highest activity and compound 4e as a more hydrophilic agent (Kpart; 0.05) showed the lowest cytotoxic effect.


Cultivation-based characterization of biliary microbiota in bile samples collected during routine endoscopic retrograde cholangiography: 10 years of experience at a tertiary center.
Bile has long been considered sterile. Recent studies show that bacteria can frequently be detected in bile and certain bacterial species are associated with bile duct-associated liver disease. To detect bacterial species and antibiotic resistance in bile in bile duct-associated liver disease. To evaluate microbiological findings of bile samples obtained during ERCP at a tertiary center from 2009 to 2019. There were 1885 bile samples from 992 patients examined by cultural microbiological analysis. Germs were detected in 91% of the samples. Most bile samples (n) were obtained from patients who had undergone liver transplantation (LTX; n = 556), followed by patients with primary sclerosing cholangitis (PSC; n = 287). Enterococci were detected in 67% of samples, followed by E. coli (32.2%) and Klebsiella (28.2%). Of 1151 enterococci detected, 13.1% were vancomycin (VRE)s and of 216 staphylococci detected, 10% were ORSA. The proportion of VRE increased with the number of tests performed during ERCPs ( P < 0.01; chi-square) and increased 2.5-fold over 10 years, whereas the detection of ORSA remained stable. Patients with cholecystolithiasis were significantly more likely to have evidence of VRE in bile compared to LTX and PSC patients ( P = 0.02, P < 0.01; chi-square). The most abundant bacterial genera showed highly statistically significant differences in their levels of liver enzymes and c-reactive protein ( P < 0.001). Knowledge of the bacterial composition of bile in various bile duct-associated liver diseases may allow more targeted antibiotic use in the future.


A cross-national study of depression in preclinical dementia: A COSMIC collaboration study.
Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to diagnosis. The association between years to dementia diagnosis and successive depressive states was assessed using a mixed effect logistic regression model. A generic inverse variance method was used to group study results, construct forest plots, and generate heterogeneity statistics. A common trajectory was observed showing an increase in the incidence of depression as the time to dementia diagnosis decreased despite cross-national variability in depression rates. The results support the hypothesis that depression occurring in the preclinical phases of dementia is more likely to be attributable to dementia-related brain changes than environment or reverse causality.


Carbohydrate cytochemistry by transmission and scanning electron microscopy.
Macromolecules containing abundant carbohydrate moieties occur widely distributed on cell surfaces and in cell organelles. Extension to the ultrastructural level of light microscopic cytochemical methods for demonstrating the complex carbohydrates has provided extensive information about the precise location of a great diversity of glycoconjugates in various cell types affording, accordingly, an improved insight into the biologic significance of the chemical nature of some components. The available methods of ultrastructural carbohydrate cytochemistry are reviewed in this tutorial, and the applicability of these methods to demonstration of glycoconjugates by scanning electron microscopy is considered. Backscattered electron imaging was carried out on specimens of trachea stained by methods for demonstrating glycoconjugates by transmission electron microscopy. This approach provided a means of localizing sites of abundant complex carbohydrate by scanning electron microscopy. Further extension of carbohydrate cytochemical methods to demonstration of glycoconjugates by scanning electron microscopy appears feasible and offers a promise of providing valuable information for carbohydrate cytochemistry.


DNA ploidy in bronchopulmonary carcinoid tumours.
Fifty three bronchopulmonary carcinoid tumours were studied to assess the significance of DNA ploidy, determined by flow cytometry of paraffin embedded tissue. Twenty eight were typical carcinoid tumours and 25 well differentiated neuroendocrine carcinomas. Twenty seven were DNA diploid and 26 DNA aneuploid. DNA aneuploidy was significantly associated with histological features of increased malignant potential. Survival data were available for 43 patients. Of the 19 with DNA diploid tumours, 16 survived five years, compared with 14 of 24 with DNA aneuploid tumours--the difference being at the borderline of statistical significance. In a Cox multivariate regression analysis with other histological variables, DNA ploidy did not confer independent prognostic information. It is concluded that, although DNA aneuploidy as determined by flow cytometry is an indicator of increased malignant potential in bronchopulmonary carcinoid tumours, it does not provide clinically useful information additional to the results of routine histological examination.


Broadening the horizon--level 2.5 of the HUPO-PSI format for molecular interactions.
Molecular interaction Information is a key resource in modern biomedical research. Publicly available data have previously been provided in a broad array of diverse formats, making access to this very difficult. The publication and wide implementation of the Human Proteome Organisation Proteomics Standards Initiative Molecular Interactions (HUPO PSI-MI) format in 2004 was a major step towards the establishment of a single, unified format by which molecular interactions should be presented, but focused purely on protein-protein interactions. The HUPO-PSI has further developed the PSI-MI XML schema to enable the description of interactions between a wider range of molecular types, for example nucleic acids, chemical entities, and molecular complexes. Extensive details about each supported molecular interaction can now be captured, including the biological role of each molecule within that interaction, detailed description of interacting domains, and the kinetic parameters of the interaction. The format is supported by data management and analysis tools and has been adopted by major interaction data providers. Additionally, a simpler, tab-delimited format MITAB2.5 has been developed for the benefit of users who require only minimal information in an easy to access configuration. The PSI-MI XML2.5 and MITAB2.5 formats have been jointly developed by interaction data producers and providers from both the academic and commercial sector, and are already widely implemented and well supported by an active development community. PSI-MI XML2.5 enables the description of highly detailed molecular interaction data and facilitates data exchange between databases and users without loss of information. MITAB2.5 is a simpler format appropriate for fast Perl parsing or loading into Microsoft Excel.


Ovarian Hormone Influences on Dysregulated Eating: A Comparison of Associations in Women with versus without Binge Episodes.
Changes in ovarian hormones predict changes in emotional eating across the menstrual cycle. However, prior studies have not examined whether the nature of associations varies across dysregulated eating severity. The current study determined whether the strength and/or nature of hormone/dysregulated eating associations differ based on the presence of clinically diagnosed binge episodes (BEs). Participants included 28 women with BEs and 417 women without BEs who provided salivary hormone samples, ratings of emotional eating, and BE frequency for 45 days. Results revealed stronger associations between dysregulated eating and ovarian hormones in women with BEs as compared to women without BEs. The nature of associations also differed, as progesterone moderated the effects of lower estradiol levels on dysregulated eating in women with BEs only. Although hormone/dysregulated eating associations are present across the spectrum of pathology, the nature of associations may vary in ways that have implications for etiological models and treatment.


What is Mooren's ulcer?
It is probable that the traditional definition of Mooren's ulcer involving relentless progression should be modified. Many eyes have been seen with corneal ulcers which have the clinical diagnosis of Mooren's ulcer but respond to varying medications and to conjunctival excision. The ulcers can progress, however, in spite of all therapy, and in these cases, we recommend removal of the remaining corneal stroma, followed by penetrating corneal transplantation. Patients with Mooren's ulcer exhibit both cell-mediated and humoral immunological phenomena but, in a small series, did not respond to immunotherapy.


Prevalence of beta-thalassaemia and sickle cell traits in premarital screening in Al-Qassim, Saudi Arabia.
To study the prevalence of beta-thalassaemia and sickle cell traits in the Al-Qassim region, Saudi Arabia. The Ministry of Health of Saudi Arabia launched a countrywide programme in February 2004 to allow all Saudis planning marriage to screen their carrier status for beta-thalassaemia and sickle cell traits. This population survey of mandatory premarital screening for beta-thalassaemia and sickle cell heterozygotes provided an opportunity to estimate the prevalence of these traits in the Al-Qassim region. From February 2004 to October 2006 all individuals attending for premarital screening in that region were screened. For each subject, venous blood was taken to determine complete blood count, red cell indices and hemoglobin electrophoresis. Subjects were considered to have beta-thalassaemia trait if mean corpuscular volume was <79 fl, mean corpuscular haemoglobin <27 pg and haemoglobin A2 level >3.5%; and sickle cell trait if sickle cell haemoglobin amounted to 35 to 45% and sickling test was positive. Totally 38,153 individuals were screened during the study period. The prevalence rates of beta-thalassaemia and sickle cell traits were 0.165% (63/38,153) and 0.252% (96/38,153) respectively. Compared with results of previous studies carried out in this region on the same issue, the prevalence of sickle cell heterozygotes seems to be the same but the frequency of beta-thalassaemia carriers is substantially higher. Screening for carriers both of beta-thalassaemia and sickle cell traits is important to prevent at risk marriages through genetic counseling.


The problems of interprofessional healthcare practice in hospitals.
This article outlines the problems of interprofessional practice in the hospital setting. It examines the difficulties associated with competing ideologies and aims, inequalities in power relations, communication and role confusion and overlap. Within the hospital setting such problems often arise although the roots of the problem may go unacknowledged. The ways in which the problems occur in the hospital setting are considered, as is the underlying cause of such problems. Case studies will be used to analyse how the problems arise and ways in which they might be addressed.


Determinants of cancer screening frequency: the example of screening for cervical cancer.
Cancer screening frequency should be based on the rate of progression of the disease and the sensitivity of the screening test. A common misconception is that a person's risk of getting the disease determines how often they should be screened. We describe algebraically the theoretical interaction of disease progression rate and screening test sensitivity determining the portion of invasive cancers prevented by screening. After discussing the assumptions and limitations of the model, we apply this model to the example of screening for cervical cancer. Actual data from large screening programs assembled by the International Agency for Research on Cancer (IARC) are used to test the assumptions of the model. A simple formula can express the relation between disease progression rate, sensitivity of the screening test, screening frequency, and screening error. Disease prevalence does not figure in this equation. The IARC data suggest that, at least for cervical cancer, as screening frequency increases, incremental sensitivity of the test decreases or remaining undetected cases progress more rapidly so that anticipated benefits from more frequent screening are not realized. Rate of disease progression and sensitivity of the screening test are the proper determinants of cancer screening frequency. Because these factors can vary depending on screening frequency, however, the optimal screening interval for a particular cancer must be determined by clinical trials.


Vesicle-micelle transition in mixtures of dioctadecyldimethylammonium chloride and bromide with nonionic and zwitterionic surfactants.
We have investigated the effect of mixing spontaneously formed dispersions of the cationic vesicle-forming dioctadecyldimethylammonium chloride and bromide (DODAX, with X being anions Cl- (C) or Br- (B)) with solutions of the micelle-forming nonionic ethylene oxide surfactants penta-, hepta-, and octaethyleneglycol mono-n-dodecyl ether, C12E(n) (n = 5, 7, and 8), and the zwitterionic 3-(N-hexadecyl-N,N-dimethylammonio)propane sulfonate (HPS). We used for this purpose differential scanning calorimetry (DSC), turbidity, and steady-state fluorescence spectroscopy to investigate the vesicle-micelle (V-M) transition yielded by adding C12E(n) and HPS to 1.0 mM vesicle dispersions of DODAC and DODAB. The addition of these surfactants lowers the gel-to-liquid crystalline phase transition temperature (T(m)) of DODAC and DODAB, and the transition becomes less cooperative, that is, the thermogram transition peak shifts to lower temperature and broadens to disappear when the V-M transition is complete, the vesicle bilayer becomes less organized, and the T(m) decreases, in agreement with measurements of the fluorescence quantum yield of trans-diphenylpolyene (t-DPO) fluorescence molecules incorporated in the vesicle bilayer. Turbidity data indicate that the V-M transition comes about in three stages: first surfactants are solubilized into the vesicle bilayer; after saturation, the vesicles are ruptured, and, finally, the vesicles are completely solubilized and only mixed micelles are formed. The critical points of bilayer saturation and vesicle solubilization were obtained from the turbidity and fluorescence curves, and are reported in this communication. The solubility of DODAX is stronger for C12E(n) than it is for HPS, meaning that C12E(n) solubilizes DODAX more efficiently than does HPS. The surfactant solubilization depends slightly on the counterion, and varies according to the sequence C12E5 > C12E7 > C12E8 > HPS.


The impact of family socioeconomic status and parenting styles on children's academic trajectories: A longitudinal study comparing migrant and urban children in China.
The positive development of migrant children in China is hampered due to their unequal accessibility to quality urban education resources. This research aimed at exploring the developmental trajectories of migrant and urban children's literacy and mathematics performance, as well as the impact of family socioeconomic status (SES) and parenting styles, including the mediating effect of parenting styles, by comparing migrant children with their urban counterparts. Growth mixture modeling identified distinguishable trajectories of mathematics development for migrant children (i.e., "falling behind" and "keeping pace" groups) and urban children (i.e., "catching up" and "keeping pace" groups), as well as distinguishable trajectories of literacy development for migrant children (i.e., "jumpstarting" and "keeping pace" groups) and urban children ("falling behind" and "steadily progressing" groups). Multinomial logistic regression analyses further clarified that authoritative parenting increased the likelihood of favorable trajectories of migrant children's mathematics development and urban children's literacy and mathematics development. Family SES enhanced migrant children's mathematics development. Family SES contributed to urban children's literacy development through authoritative parenting, yet such a mediating effect was not observed for migrant children. This study highlights the importance of focusing on distinct trajectories of migrant and urban children's literacy and mathematics in improving their school achievement.


Occurrence of Aerobic and Anaerobic Bacteria in the Consumer End of a Water Distribution System.
In this study, mixed species biofilm formation including sulphate-reducing bacteria (SRB) on polypropylene surface and bacteriology of network water were investigated in a model water distribution system during a nine-month period. Water and biofilm samples were analyzed for the enumeration of aerobic heterotrophic bacteria (AHB), anaerobic heterotrophic bacteria (ANHB) and SRB. The number of live/dead bacteria was also analyzed by epifluorescence microscopy. In addition, extracellular polysaccharide substances (EPS) extraction, carbohydrate analysis and scanning electron microscope observation were performed. A biofilm with heterogeneous structure formed on the polypropylene surface of the model water distribution system. Live/dead staining data indicated that biofilm matured in the first month. It was observed that especially AHB entered into a viable but not culturable state because of the temperature decrease. It was also noted that temperature is an important environmental factor especially for planktonic SRB. The quantity of carbohydrate significantly decreased according to the temperature.


α-Synuclein phosphorylation as a therapeutic target in Parkinson's disease.
Phosphorylation is a key post-translational modification necessary for normal cellular signaling and, therefore, lies at the heart of cellular function. In neurodegenerative disorders, abnormal hyperphosphorylation of pathogenic proteins is a common phenomenon that contributes in important ways to the disease process. A prototypical protein that is hyperphosphorylated in the brain is α-synuclein (α-syn) - found in Lewy bodies and Lewy neurites - the pathological hallmarks of Parkinson's disease (PD) and other α-synucleinopathies. The genetic linkage of α-syn to PD as well as its pathological association in both genetic and sporadic cases have made it the primary protein of interest. In understanding how α-syn dysfunction occurs, increasing focus is being placed on its abnormal aggregation and the contribution of phosphorylation to this process. Studies of both the kinases and phosphatases that regulate α-syn phosphorylation are beginning to reveal the roles of this post-translational modification in disease pathogenesis. Modulation of α-syn phosphorylation may ultimately prove to be a viable strategy for disease-modifying therapeutic interventions. In this review, we explore mechanisms related to α-syn phosphorylation, its biophysical and functional consequences, and its role in neurodegeneration.


Effect of clinician advice and patient preparedness to quit on subsequent quit attempts in hospitalized smokers.
Although smoking cessation counseling for cardiac inpatients is a quality measure, little data exist regarding postdischarge quit attempts in a primarily urban, African American, underserved population. This study aimed to assess preparedness to quit smoking and quit behaviors. Smokers on the cardiology service were asked to rate preparedness using the 10-step Contemplation Ladder. During phone surveys given 30-days postdischarge, patients reported whether they made quit attempts, method and success of attempts, and recall of receiving advice to quit. From February 2006 through July 2007, 2906 of 3364 of inpatients were interviewed. Fifteen percent (436/2906) were current smokers and 415/436 completed the inpatient assessment. Of these, 75% (310/415) indicated they were prepared to quit. At the 1-month follow-up, 67% (276/415) were interviewed and 71% of those patients (195/276) reported making a quit attempt, with most (76%) reporting quitting "cold turkey" (without aid). Compared with less prepared patients, prepared patients were more likely to report making a quit attempt after discharge (77% [163/212] vs. 50% [32/64], P < 0.001) and were successful in that attempt (43% [90/212] vs. 25% [16/64], P = 0.010). The majority of smokers hospitalized with cardiac disease reported being prepared to quit smoking. Those prepared, and who received advice to quit, were more likely to make a quit attempt and report abstinence than those less prepared. However, most quit attempts were made using the least effective methods. Future studies in a population of primarily African American patients should assess preparedness to quit and target prepared patients with more effective interventions.


Sunscreens in the management of photodermatoses.
Key to the management of photodermatoses is photoprotection, which includes seeking shade; wearing photoprotective clothing, wide brimmed hats, and sunglasses; and applying sunscreens. The process of selecting the most effective sunscreen depends on identification of the wavelengths of photons that are responsible for inducing the sensitivity reaction, which can be determined through assessment of patient history or by phototesting. Sunscreens with sun protection factor (SPF) >30 that incorporate photostable or photostabilized ultraviolet A (UVA) filters (labeled as 'broad spectrum' in the US) are usually the appropriate choice for adequate photoprotection.


Short-term outcomes of enhanced recovery after surgery protocol in robotic-assisted McKeown esophagectomy for esophageal cancer: a single-center retrospective cohort study.
This study aimed to evaluate the short-term outcomes of enhanced recovery after surgery (ERAS) protocol in perioperative robotic-assisted McKeown esophagectomy (RAME) among esophageal cancer patients. For this retrospective study, all patients who had undergone RAME with esophageal cancer using ERAS protocol and conventional management strategy at the surgery center of our hospital from February 2019 to March 2022 were performed for analysis. A total of 211 patients were included. Compared to the conventional group, the ERAS group has shorter median operative time [207 (147.5-267.5) vs. 244 (183-305), P<0.001], time to first flatus (P<0.001), time to out-of-bed activity (P=0.045), and time to liquid diet (P<0.001). In addition, the ERAS group has lower postoperative pain scores (3.62 ± 0.87 vs. 4.54 ± 0.91), shorter duration of analgesia pump [2 (1-3) vs. 3 (2.5-5.5)], shorter postoperative hospital stay [(9 (6-47) vs. 11 (6-79)], shorter postoperative hospital stay within neoadjuvant treated patients [8 (7-43) vs. 13 (8-67], shorter postoperative ICU stay [1 (0-7) vs. 2 (0-15)], and less reoperation rate (7.6% vs. 16.8%). Furthermore, the overall complication rate was significantly lower in the ERAS group (26.1%) than in the conventional group (50.4%). Notably, the ERAS group had lower thoracic fluid drainage volume than the conventional group on postoperative 2-7 days (P<0.05). The application of ERAS protocol in esophageal cancer patients treated with RAME showed advantages of quick postoperative recovery in contrast to the conventional management strategy.


[Surgical Repair of Kommerell's Diverticulum with Right Sided Aortic Arch;Report of a Case].
A 54-year-old woman was referred for assessment of dysphagia and extrinsic compression of the esophagus detected by upper gastrointestinal endoscopy. Computed tomography revealed the rightsided aortic arch with mirror image branching and Kommerell's diverticulum. To relieve the esophageal compression, surgical intervention was indicated. Descending aortic replacement with a Dacron graft was performed through right thoracotomy under partial cardiopulmonary bypass. The patient was discharged without any complication, and her dysphagia disappeared.


Achieving effective health promotion for women with disabilities.
The field of health promotion has yet to acknowledge the unique needs of women with disabilities, a population representing approximately 1 of 5 women in the United States. Compared with women without disabilities, women with disabilities have critical needs for evidence-based health promotion services. Women with disabilities face a lack of access to multitudinous opportunities for maintaining and improving their overall health. Inaccessible exercise equipment and other disability-related barriers discourage women with physical disabilities from engaging in health-promoting behaviors. This article identifies 10 essential elements for achieving effective health promotion research and interventions for women in this population.


Serotonergic genotypes, neuroticism, and financial choices.
Life financial outcomes carry a significant heritable component, but the mechanisms by which genes influence financial choices remain unclear. Focusing on a polymorphism in the promoter region of the serotonin transporter gene (5-HTTLPR), we found that individuals possessing the short allele of this gene invested less in equities, were less engaged in actively making investment decisions, and had fewer credit lines. Short allele carriers also showed higher levels of the personality trait neuroticism, despite not differing from others with respect to cognitive skills, education, or wealth. Mediation analysis suggested that the presence of the 5-HTTLPR short allele decreased real life measures of financial risk taking through its influence on neuroticism. These findings show that 5-HTTLPR short allele carriers avoid risky and complex financial choices due to negative emotional reactions, and have implications for understanding and managing individual differences in financial choice.


Transcriptional Reprogramming of the Mycoparasitic Fungus Ampelomyces quisqualis During the Powdery Mildew Host-Induced Germination.
Ampelomyces quisqualis is a mycoparasite of a diverse range of phytopathogenic fungi associated with the powdery mildew disease. Among them are several Erysiphaceae species with great economic impact on high-value crops such as grape. Due to its ability to parasitize and prevent the spread of powdery mildews, A. quisqualis has received considerable attention for its biocontrol potential. However, and in sharp contrast to the extensively studied biocontrol species belonging to the genus Trichoderma, little is known about the biology of A. quisqualis at the molecular and genetic levels. We present the first genome-wide transcription profiling in A. quisqualis during host-induced germination. A total of 1,536 putative genes showed significant changes in transcription during the germination of A. quisqualis. This finding denotes an extensive transcriptional reprogramming of A. quisqualis induced by the presence of the host. Several upregulated genes were predicted to encode for putative mycoparasitism-related proteins such as secreted proteases, virulence factors, and proteins related to toxin biosynthesis. Our data provide the most comprehensive sequence resource currently available for A. quisqualis in addition to offering valuable insights into the biology of A. quisqualis and its mycoparasitic lifestyle. Eventually, this may improve the biocontrol capacity of this mycoparasite.


Myeloid-derived NF-κB negative regulation of PU.1 and c/EBP-β-driven pro-inflammatory cytokine production restrains LPS-induced shock.
Sepsis is a life-threatening event predominantly caused by Gram-negative bacteria. Bacterial infection causes a pronounced macrophage (MΦ) and dendritic cell activation that leads to excessive pro-inflammatory cytokine IL-1β, IL-6 and TNF-α production (cytokine storm), resulting in endotoxic shock. Previous experimental studies have revealed that inhibiting NF-κB signaling ameliorates disease symptoms; however, the contribution of myeloid p65 in endotoxic shock remains elusive. In this study, we demonstrate increased mortality in mice lacking p65 in the myeloid lineage (p65Δmye) compared with wild type mice upon ultra-pure LPS challenge. We show that increased susceptibility to LPS-induced shock was associated with elevated serum level of IL-1β and IL-6. Mechanistic analyses revealed that LPS-induced pro-inflammatory cytokine production was ameliorated in p65-deficient bone marrow-derived MΦs; however, p65-deficient 'activated' peritoneal MΦs exhibited elevated IL-1β and IL-6. We show that the elevated pro-inflammatory cytokine secretion was due, in part, to increased accumulation of IL-1β mRNA and protein in activated inflammatory MΦs. The increased IL-1β was linked with heightened binding of PU.1 and CCAAT/enhancer binding protein-β to Il1b and Il6 promoters in activated inflammatory MΦs. Our data provide insight into a role for NF-κB in the negative regulation of pro-inflammatory cytokines in myeloid cells.


Worst headache and subarachnoid hemorrhage: prospective, modern computed tomography and spinal fluid analysis.
This study investigated the hypothesis that modern computed tomographic (CT) imaging is sufficient to exclude subarachnoid hemorrhage (SAH) in patients with severe headache. All 38,730 adult patients who presented to Hermann Hospital in Houston, Texas, during a 16-month period were prospectively screened to detect those with "the worst headache of my life." Two neuroradiologists blinded to the study hypothesis interpreted the CT scans. Patients with negative scans underwent comprehensive cerebrospinal fluid (CSF) analysis including cell count in first and last tubes, visual and spectrophotometric detection of xanthochromia, and CSF D-dimer assay. A chief complaint of headache was elicited in 455 patients, and 107 of these had "worst headache" and were enrolled in the study. CT-confirmed SAH was found in 18 of the 107 (17%). Only 2 patients (2.5%, 95% confidence interval, .3% to 8.8%) had SAH detected by CSF analysis among those with negative CT imaging result. CSF spectrophotometric detection was the most sensitive test for blood. Three patients with less than 6 red blood cells in tube 1 had positive spectrophotometric results, but in all 3, tube 4 was negative on spectrophotometric analysis, suggesting a high false-positive rate. Modern CT imaging is sufficient to exclude 97.5% of SAH in patients presenting to the ED with "worst headache" symptoms.


Caloric restriction causes a distinct reorganization of the lipidome in quiescent and non-quiescent cells of budding yeast.
After budding yeast cells cultured in a nutrient-rich liquid medium with 0.2% glucose (under caloric restriction conditions) or 2% glucose (under non-caloric restriction conditions), ferment glucose to ethanol and then consume ethanol, they enter the stationary phase. The process of their chronological aging begins. At that point, the yeast culture starts to accumulate quiescent and non-quiescent cells. Here, we purified the high- and low-density populations of quiescent and non-quiescent cells from the yeast cultures limited in calorie supply or not. We then employed mass spectrometry-based quantitative lipidomics to assess the aging-associated changes in high- and low-density cells' lipidomes. We found that caloric restriction, a geroprotective dietary intervention, alters the concentrations of many lipid classes through most of the chronological lifespan of the high- and low-density populations of quiescent and non-quiescent cells. Specifically, caloric restriction decreased triacylglycerol, increased free fatty acid, elevated phospholipid and amplified cardiolipin concentrations. Based on these findings, we propose a hypothetical model for a caloric restriction-dependent reorganization of lipid metabolism in budding yeast's quiescent and non-quiescent cells. We also discovered that caloric restriction creates lipidomic patterns of these cells that differ from those established by two other robust geroprotectors, namely the tor1Δ mutation and lithocholic acid.


Recommendations for the Appropriate Structure, Communication, and Investigation of Tobacco Harm Reduction Claims. An Official American Thoracic Society Policy Statement.
The tobacco harm reduction literature is replete with vague language, far-reaching claims, and unwarranted certainty. The American Thoracic Society has increasingly recognized the need for a framework for reliably making such claims. Evidence-based standards improving the scientific value and transparency of harm reduction claims are expected to improve their trustworthiness, clarity, and consistency. Experts from relevant American Thoracic Society committees identified key topic areas for discussion. Literature search strategy included English language articles across Medline, Google Scholar, and the Cochrane Collaborative databases, with expanded search terms including tobacco, addiction, smoking, cigarettes, nicotine, and harm reduction. Workgroup members synthesized their evidentiary summaries into a list of candidate topics suitable for inclusion in the final report. Breakout groups developed detailed content maps of each topic area, including points to be considered for suggested recommendations. Successive draft recommendations were modified using an iterative consensus process until unanimous approval was achieved. Patient representatives ensured the document's relevance to the lay public. Fifteen recommendations were identified, organized into four framework elements dealing with: estimating harm reduction among individuals, making claims on the basis of population impact, appropriately careful use of language, and ethical considerations in harm reduction. This statement clarifies important principles guiding valid direct and inferential harm reduction claims. Ideals for effective communication with the lay public and attention to unique ethical concerns are also delineated. The authors call for formal systems of grading harm reduction evidence and regulatory assurances of longitudinal surveillance systems to document the impact of harm reduction policies.


Numerical simulation of hot-melt extrusion processes for amorphous solid dispersions using model-based melt viscosity.
Simulation of HME processes is a valuable tool for increased process understanding and ease of scale-up. However, the experimental determination of all required input parameters is tedious, namely the melt rheology of the amorphous solid dispersion (ASD) in question. Hence, a procedure to simplify the application of hot-melt extrusion (HME) simulation for forming amorphous solid dispersions (ASD) is presented. The commercial 1D simulation software Ludovic® was used to conduct (i) simulations using a full experimental data set of all input variables including melt rheology and (ii) simulations using model-based melt viscosity data based on the ASDs glass transition and the physical properties of polymeric matrix only. Both types of HME computation were further compared to experimental HME results. Variation in physical properties (e.g. heat capacity, density) and several process characteristics of HME (residence time distribution, energy consumption) among the simulations and experiments were evaluated. The model-based melt viscosity was calculated by using the glass transition temperature (Tg) of the investigated blend and the melt viscosity of the polymeric matrix by means of a Tg-viscosity correlation. The results of measured melt viscosity and model-based melt viscosity were similar with only few exceptions, leading to similar HME simulation outcomes. At the end, the experimental effort prior to HME simulation could be minimized and the procedure enables a good starting point for rational development of ASDs by means of HME. As model excipients, Vinylpyrrolidone-vinyl acetate copolymer (COP) in combination with various APIs (carbamazepine, dipyridamole, indomethacin, and ibuprofen) or polyethylene glycol (PEG 1500) as plasticizer were used to form the ASDs.


Pseudomonas aeruginosa exotoxin Y-mediated tau hyperphosphorylation impairs microtubule assembly in pulmonary microvascular endothelial cells.
Pseudomonas aeruginosa uses a type III secretion system to introduce the adenylyl and guanylyl cyclase exotoxin Y (ExoY) into the cytoplasm of endothelial cells. ExoY induces Tau hyperphosphorylation and insolubility, microtubule breakdown, barrier disruption and edema, although the mechanism(s) responsible for microtubule breakdown remain poorly understood. Here we investigated both microtubule behavior and centrosome activity to test the hypothesis that ExoY disrupts microtubule dynamics. Fluorescence microscopy determined that infected pulmonary microvascular endothelial cells contained fewer microtubules than control cells, and further studies demonstrated that the microtubule-associated protein Tau was hyperphosphorylated following infection and dissociated from microtubules. Disassembly/reassembly studies determined that microtubule assembly was disrupted in infected cells, with no detectable effects on either microtubule disassembly or microtubule nucleation by centrosomes. This effect of ExoY on microtubules was abolished when the cAMP-dependent kinase phosphorylation site (Ser-214) on Tau was mutated to a non-phosphorylatable form. These studies identify Tau in microvascular endothelial cells as the target of ExoY in control of microtubule architecture following pulmonary infection by Pseudomonas aeruginosa and demonstrate that phosphorylation of tau following infection decreases microtubule assembly.


Quantum trajectory dynamics in arbitrary coordinates.
The quantum trajectory approach is generalized to arbitrary coordinate systems, including curvilinear coordinates. This allows one to perform an approximate quantum trajectory propagation, which scales favorably with system size, in the same framework as standard quantum wave packet dynamics. The trajectory formulation is implemented in Jacobi coordinates for a nonrotating triatomic molecule. Wave packet reaction probabilities are computed for the O(3P) + H2 --> OH + H reaction using the approximate quantum potential. The latter is defined by the nonclassical component of the momentum operator expanded in terms of linear and exponential functions. Unlike earlier implementations with linear functions, the introduction of the exponential function provides an accurate description of asymptotic dynamics for this system and gives good agreement of approximate reaction probabilities with accurate quantum calculations.


Immunohistochemical Characterization of Immune Infiltrate in Tumor Microenvironment of Glioblastoma.
Glioblastoma (GBM) is the most common primary malignant brain cancer in adults, with very limited therapeutic options. It is characterized by a severe immunosuppressive milieu mostly triggered by suppressive CD163+ tumor-associated macrophages (TAMs). The efficacy of immune checkpoint inhibitor interventions aimed at rescuing anti-tumor immunity has not been proved to date. Thus, it is critically important to investigate the immunomodulatory mechanisms acting within the GBM microenvironment for the better design of immunotherapeutic strategies. The immunohistochemical analysis of a panel of immune biomarkers (CD3, FoxP3, CD163, IDO, PDL-1, PD-1 and TIGIT) was performed in paired samples of the tumor core (TC) and peritumoral area (PTA) of nine GBM patients. CD163+ cells were the most common cell type in both the PTA and TC. IDO and PDL-1 were expressed in most of the TC samples, frequently accompanied by TIGIT expression; on the contrary, they were almost absent in the PTA. CD3+ cells were present in both the TC and PTA, to a lesser extent than CD163+ cells; they often were accompanied by PD-1 expression, especially in the TC. FoxP3 was scarcely present. Distinct inhibitory mechanisms can act simultaneously in both the TC and PTA to contribute to the strong immunosuppression observed within the GBM microenvironment. Nevertheless, the PTA shows strongly reduced immunosuppression when compared to the TC, thus representing a potential target for immunotherapies. Moreover, our results support the working hypothesis that immunosuppression and T-cell exhaustion can be simultaneously targeted to rescue anti-tumor immunity in GBM patients.


The isolation and characterization of a colony stimulating factor from human lung.
Serum-free conditioned medium from human lung obtained at autopsy provides a rich source of colony stimulating factor which stimulates granulocytic and macrophagic colony growth in both mouse and human bone marrow. The appearance of the factor is enhanced by endotoxin and inhibited by either puromycin or actinomycin D. Human lung colony stimulating factor is stable at the pH range of 6.5-10 and temperature of 56 degrees C for 30 min. It is resistant to trypsin and neuraminidase but is sensitive to subtilisin, chymotrypsin and periodate. It shows heterogeneity on Sephadex gel filtration with two activity peaks having molecular weight of 200 000 and 40 000, respectively. Upon gel electrophoresis, human lung colony stimulating factor migrates in the alpha-globulin post-albumin region. Using the combination procedures of hydroxyapatite chromatography and preparative polyacrylamide gel electrophoresis a 600-fold purification was achieved with a final specific activity of 6-10(5) units per mg protein. The purified colony stimulating factor is very labile; however, the activity can be stabilized by the addition of gelatin or bovine serum albumin at the concentration of 0.1% and 0.2 mg/ml, respectively.


Folklore and traditional ecological knowledge of geckos in Southern Portugal: implications for conservation and science.
Traditional Ecological Knowledge (TEK) and folklore are repositories of large amounts of information about the natural world. Ideas, perceptions and empirical data held by human communities regarding local species are important sources which enable new scientific discoveries to be made, as well as offering the potential to solve a number of conservation problems. We documented the gecko-related folklore and TEK of the people of southern Portugal, with the particular aim of understanding the main ideas relating to gecko biology and ecology. Our results suggest that local knowledge of gecko ecology and biology is both accurate and relevant. As a result of information provided by local inhabitants, knowledge of the current geographic distribution of Hemidactylus turcicus was expanded, with its presence reported in nine new locations. It was also discovered that locals still have some misconceptions of geckos as poisonous and carriers of dermatological diseases. The presence of these ideas has led the population to a fear of and aversion to geckos, resulting in direct persecution being one of the major conservation problems facing these animals. It is essential, from both a scientific and conservationist perspective, to understand the knowledge and perceptions that people have towards the animals, since, only then, may hitherto unrecognized pertinent information and conservation problems be detected and resolved.


Enzymatically degradable, starch-based layer-by-layer films: application to cytocompatible single-cell nanoencapsulation.
The build-up and degradation of cytocompatible nanofilms in a controlled fashion have great potential in biomedical and nanomedicinal fields, including single-cell nanoencapsulation (SCNE). Herein, we report the fabrication of biodegradable films of cationic starch (c-ST) and anionic alginate (ALG) by electrostatically driven layer-by-layer (LbL) assembly technology and its application to the SCNE. The [c-ST/ALG] multilayer nanofilms, assembled either on individual Saccharomyces cerevisiae or on the 2D flat gold surface, degrade on demand, in a cytocompatible fashion, via treatment with α-amylase. Their degradation profiles are investigated, while systematically changing the α-amylase concentration, by several surface characterization techniques, including quartz crystal microbalance with dissipation monitoring (QCM-D) and ellipsometry. DNA incorporation in the LbL nanofilms and its controlled release, upon exposure of the nanofilms to an aqueous α-amylase solution, are demonstrated. The highly cytocompatible nature of the film-forming and -degrading conditions is assessed in the c-ST/ALG-shell formation and degradation of S. cerevisiae. We envisage that the cytocompatible, enzymatic degradation of c-ST-based nanofilms paves the way for developing advanced biomedical devices with programmed dissolution in vivo.


Validated stability-indicating HPLC method for the determination of mesna in presence of its degradation products.
A rapid and simple stability-indicating liquid chromatographic method was developed and validated for analysis of mesna in the presence of its degradation products in drug substance and drug products in a run time not >5 min. The separation was achieved on a RP amide C16 column at room temperature using methanol-phosphate buffer (10:90, v/v, pH 3.0) as mobile phase at a flow rate of 1 mL min(-1) and UV detection at 210 nm. The detector response for mesna was linear over the selected concentration range from 50 to 1000 µg mL(-1) with a correlation coefficient 0.9998. The limit of detection and the limit of quantitation were 7.5 and 22.7 µg mL(-1), respectively. The solution was stable for at least 5 days. Baseline resolution between mesna and its degradation products was achieved. Diode array detection peak purity tests showed no peak interfered with mesna peak. Moreover, the method was successfully applied for the determination of mesna in two different commercially available drug products.


Intake of artificially sweetened soft drinks and risk of preterm delivery: a prospective cohort study in 59,334 Danish pregnant women.
Sugar-sweetened soft drinks have been linked to a number of adverse health outcomes such as high weight gain. Therefore, artificially sweetened soft drinks are often promoted as an alternative. However, the safety of artificial sweeteners has been disputed, and consequences of high intakes of artificial sweeteners for pregnant women have been minimally addressed. We examined the association between intakes of sugar-sweetened and artificially sweetened soft drinks and preterm delivery. We conducted prospective cohort analyses of 59,334 women from the Danish National Birth Cohort (1996-2002). Soft drink intake was assessed in midpregnancy by using a food-frequency questionnaire. Preterm delivery ( lt 37 wk) was the primary outcome measure. Covariate information was assessed by telephone interviews. There was an association between intake of artificially sweetened carbonated and noncarbonated soft drinks and an increased risk of preterm delivery (P for trend: le 0.001, both variables). In comparison with women with no intake of artificially sweetened carbonated soft drinks, the adjusted odds ratio for women who consumed ge 1 serving of artificially sweetened carbonated soft drinks/d was 1.38 (95% CI: 1.15, 1.65). The corresponding odds ratio for women who consumed ge 4 servings of artificially sweetened carbonated soft drinks/d was 1.78 (95% CI: 1.19, 2.66). The association was observed for normal-weight and overweight women. A stronger increase in risk was observed for early preterm and moderately preterm delivery than with late-preterm delivery. No association was observed for sugar-sweetened carbonated soft drinks (P for trend: 0.29) or for sugar-sweetened noncarbonated soft drinks (P for trend: 0.93). Daily intake of artificially sweetened soft drinks may increase the risk of preterm delivery. Further studies are needed to reject or confirm these findings.


Eligibility and patient barriers to peritoneal dialysis in patients with advanced chronic kidney disease.
The burden of chronic kidney disease (CKD) is increasing in Kenya and is a significant cause of morbidity and mortality. While definitive treatment is renal transplantation, many patients require kidney replacement therapy with haemodialysis (HD) or peritoneal dialysis (PD). The predominant modality utilized in Kenya is currently HD. There is a need to explore why PD remains underutilized and whether patient factors may be contributory to barriers that limit the uptake of PD. This was a descriptive cross-sectional study where patients with advanced CKD were assessed by a multidisciplinary team for PD eligibility using a standardized tool. Contraindications and barriers to the modality were recorded as was the presence or absence of support for the provision of PD. Demographic and clinical data were recorded using a standardized questionnaire. The impact of support on PD eligibility was determined. We found that 68.9% patients were eligible for PD. Surgery-related abdominal scarring was the most common contraindication. Barriers to PD were identified in 45.9% and physical barriers were more common than cognitive barriers. Presence of support was associated with a significant increase in PD eligibility (p < 0.001). The rate of eligibility for PD in this study was similar to that found in other populations. Surgical-related factors were the most commonly identified contraindication. Physical and cognitive barriers were commonly identified and may be overcome by the presence of support for PD.


Time course of panic disorder and posttraumatic stress disorder onsets.
Posttraumatic stress disorder (PTSD) often co-occurs with panic disorder (PD), with some etiological models positing a causal role of panic reactivity in PTSD onset; however, data addressing the temporal ordering of these conditions are lacking. The aim of this study was to examine the bi-directional associations between PD and PTSD in a nationally representative, epidemiologic sample of trauma-exposed adults. Participants were community-dwelling adults (62.6% women; Mage = 48.9, SD 16.3) with lifetime DSM-IV PTSD criterion A trauma exposure drawn from the 2001/2 National Epidemiologic Survey on Alcohol and Related Conditions (NESARC) and re-interviewed in 2004/5 (N = 12,467). Cox discrete-time proportional hazards models with time-varying covariates were used to investigate the bi-directional associations between lifetime PD and PTSD, accounting for demographic characteristics, trauma load, and lifetime history of major depression, generalized anxiety disorder, and social anxiety disorder. PD was significantly associated with subsequent onset of PTSD (HR 1.210, 95%CI = 1.207-1.214, p < .001), and PTSD was significantly associated with onset of PD (HR 1.601, 95% CI 1.597-1.604, p < .001). The association between PTSD and subsequent PD was stronger in magnitude than that between PD and subsequent PTSD (Z = - 275.21, p < .01). Men evidenced stronger associations between PD and PTSD compared to women. Results were consistent with a bidirectional pathway of risk, whereby PD significantly increased risk for the development of PTSD, and PTSD significantly increased risk for PD. Given the association between PTSD and subsequent PD, particularly among men, clinicians may consider supplementing PTSD treatment with panic-specific interventions, such as interoceptive exposure, to prevent or treat this disabling comorbidity.