Factors with the management of incontinence and promotion of continence in older people in care homes.
Review of intervention studies of associated factors with incontinence as the primary outcome in older people in care homes to identify and inform practice and future research. Incontinence is highly prevalent among care home populations. Previous reviews of descriptive and intervention studies have used urinary incontinence as the primary outcome. Systematic review and narrative summary. Electronic searches of English empirical studies undertaken using MEDLINE and CINAHL from January 1966-May 2010. All relevant empirical designs were selected from MEDLINE highly sensitive search strings from the Cochrane Incontinence Review Group, modified to exclude surgical and pharmacological studies The PRISMA statement was followed and established methods for systematic review to produce a narrative summary. Nine studies identified relating to associated factors with the management of incontinence in care homes. Factors included economic data, skin care, exercise studies, staff quality and prompted voiding adherence and the promotion of continence by the management of dehydration and incontinence. Managing incontinence and promoting continence in care homes is complex, requiring time and cost-efficient management procedures to contain the problem and deliver quality, achievable care. When developing and designing systems of care in care homes, it is important to also recognize the impact of associated factors. As with any healthcare intervention programme, resources are required to implement the protocols. Economic evaluation studies are limited, with further studies warranted alongside preventative studies to maintain long-term continence in these populations.


Neurocognitive aspects of pain perception.
The perception of pain is sensitive to various mental processes such as the feelings and beliefs that someone has about pain. It is therefore not exclusively driven by the noxious input. Attentional modulation involving the descending pain modulatory system has been examined extensively in neuroimaging studies. However, the investigation of neural mechanisms underlying more complex cognitive modulation is an emerging field in pain research. Recent findings indicate an engagement of the ventrolateral prefrontal cortex during more complex modulation, leading to a change or reappraisal of the emotional significance of pain. Taking placebo-induced analgesia as an example, we discuss the contribution of attention, expectation and reappraisal as three basic mechanisms that are important for the cognitive modulation of pain.


The use of conventional and invaginated autologous vein grafts for nerve repair by means of entubulation.
Nerve repair by entubulation has re-emerged recently as a possible means of enhancing the microenvironment at the site of repair by inclusion within the tube of various trophic factors. To this end, a modification of the vein-graft technique has been used by turning it inside out before repair, to expose the adventitial surface to the regenerating axons. A comparative study of standard vein grafting versus the inside-out technique was carried out in two equal-sized groups of inbred Lewis rats. Jugular vein isografts were derived from litter mates. The sciatic nerve was transected and repaired by entubulation using the standard vein graft in one group and the inside-out graft in the other group. Morpho-metric and electrophysiological assessment were carried out 3 months after repair. When the animals were assessed it was found that both the standard-vein-graft group and the inside-out group exhibited a reduction in all of the morphometric and electrophysiological variables when compared to normal nerves. The mean axon diameter, fibre diameter and myelin sheath thickness were, however, found to be greater in the group that underwent the inside-out repair. The superior morphometric results seen in the inside-out group were not matched by improved electrophysiological performance. It is concluded that the use of the inside-out technique confers no functional benefit over standard vein grafting.


Intraocular Pressure Effects and Mechanism of Action of Topical Versus Sustained-Release Bimatoprost.
To assess the intraocular pressure (IOP)-lowering effects of bimatoprost sustained-release implant (BimSR) in normotensive monkeys receiving topical bimatoprost. Six eyes from six female, normotensive, cynomolgus monkeys were treated with once-daily topical latanoprost 0.005% plus twice-daily fixed-combination dorzolamide 2%/timolol 0.5%. At week 5, topical latanoprost was switched to once-daily topical bimatoprost 0.03% and twice-daily dorzolamide 2%/timolol 0.5% was continued. At week 8, BimSR 20 μg was administered intracamerally to three eyes and topical therapy was continued in all eyes. At week 12, all topical therapy was discontinued and animals were monitored for another 4 weeks. IOP was measured with a TonoVet rebound tonometer in nonsedated animals weekly for 16 weeks. Average mean (standard deviation) IOP was 19.8 (1.6) mm Hg at baseline, 15.7 (0.9) mm Hg during treatment with topical latanoprost/dorzolamide/timolol from weeks 1 to 5, and 14.2 (0.5) mm Hg during weeks 6 to 8 after topical latanoprost was switched to topical bimatoprost. After BimSR was added, average mean IOP during weeks 9 to 12 was 10.8 (1.3) mm Hg, a decrease of 3.9 mm Hg compared with the topical-only arm. When topical therapy was discontinued, IOP in BimSR-treated eyes remained below that in unmedicated eyes (15.8 [0.9] vs. 20.2 [0.2] mm Hg at weeks 14-16). Intracameral BimSR has IOP-lowering effects additive to those of topical bimatoprost, suggesting an additional mechanism of action with intracameral drug delivery. Compared with topical bimatoprost, intracameral BimSR may have an additional mechanism of action of IOP lowering.


Aligning an interface terminology to the Logical Observation Identifiers Names and Codes (LOINC®).
Our study consists in aligning the interface terminology of the Bordeaux university hospital (TLAB) to the Logical Observation Identifiers Names and Codes (LOINC). The objective was to facilitate the shared and integrated use of biological results with other health information systems. We used an innovative approach based on a decomposition and re-composition of LOINC concepts according to the transversal relations that may be described between LOINC concepts and their definitional attributes. TLAB entities were first anchored to LOINC attributes and then aligned to LOINC concepts through the appropriate combination of definitional attributes. Finally, using laboratory results of the Bordeaux data-warehouse, an instance-based filtering process has been applied. We found a small overlap between the tokens constituting the labels of TLAB and LOINC. However, the TLAB entities have been easily aligned to LOINC attributes. Thus, 99.8% of TLAB entities have been related to a LOINC analyte and 61.0% to a LOINC system. A total of 55.4% of used TLAB entities in the hospital data-warehouse have been mapped to LOINC concepts. We performed a manual evaluation of all 1-1 mappings between TLAB entities and LOINC concepts and obtained a precision of 0.59. We aligned TLAB and LOINC with reasonable performances, given the poor quality of TLAB labels. In terms of interoperability, the alignment of interface terminologies with LOINC could be improved through a more formal LOINC structure. This would allow queries on LOINC attributes rather than on LOINC concepts only.


Failure to remap visuotactile space across the midline in the split-brain.
We examined the effect of posture change on the representation of visuotactile space in a split-brain patient using a cross-modal congruency task. Split-brain patient J.W. made speeded elevation discrimination responses (up versus down) to a series of tactile targets presented to the index finger or thumb of his right hand. We report congruency effects elicited by irrelevant visual distractors placed either close to, or far from, the stimulated hand. These cross-modal congruency effects followed the right hand as it moved within the right hemispace, but failed to do so when the hand crossed the midline into left hemispace. These results support recent claims that interhemispheric connections are required to maintain an accurate representation of visuotactile space.


Cyclosporine A Suppressed Glucose Oxidase Induced P53 Mitochondrial Translocation and Hepatic Cell Apoptosis through Blocking Mitochondrial Permeability Transition.
P53 is known as a transcription factor to control apoptotic cell death through regulating a series of target genes in nucleus. There is accumulating evidences show that p53 can directly induce cell apoptosis through transcription independent way at mitochondria. However, the mechanism by which p53 translocation into mitochondria in response to oxidative stress remains unclear. Here, glucose oxidase (GOX) was used to induce ROS generation in HepG2 cells and liver tissues of mice. The results showed that p53 was stabilized and translocated to mitochondria in a time and dose dependent manner after GOX exposure. Interestingly, as an inhibitor of mitochondrial permeability transition, cyclosporine A (CsA) was able to effectively reduce GOX mediated mitochondrial p53 distribution without influencing on the expression of p53 target genes including Bcl-2 and Bax. These indicated that CsA could just block p53 entering into mitochondria, but not affect p53-dependent transcription. Meanwhile, CsA failed to inhibit the ROS generation induced by GOX, which indicated that CsA had no antioxidant function. Moreover, GOX induced typical apoptosis characteristics including, mitochondrial dysfunction, accumulation of Bax and release of cytochrome C in mitochondria, accompanied with activation of caspase-9 and caspase-3. These processions were suppressed after pretreatment with CsA and pifithrin-μ (PFT-μ, a specific inhibitor of p53 mitochondrial translocation). In vivo, CsA was able to attenuate p53 mitochondrial distribution and protect mice liver against from GOX mediated apoptotic cell death. Taken together, these suggested that CsA could suppress ROS-mediated p53 mitochondrial distribution and cell apoptosis depended on its inhibition effect to mitochondrial permeability transition. It might be used to rescue the hepatic cell apoptosis in the patients with acute liver injury.


Recent progress in nanomaterials for nucleic acid delivery in cancer immunotherapy.
The combination of gene therapy and immunotherapy has the potential to systemically promote anti-tumor effects while reducing adverse reactions. Small interfering RNA (siRNA) has generated great interest in biology, engineering and medicine, especially for cancer treatment due to its ability to knock down genes of interest. Nanomaterials play significant roles in the design of delivery systems of siRNA, and nanomaterial-mediated siRNA delivery in cancer immunotherapy is one of the most important directions for future clinical cancer treatment. Here, we review the recent advances in nanomaterial mediated targeted delivery of siRNA to dendritic cells (DCs), tumor-associated macrophages (TAMs), immune checkpoint inhibitors, B lymphocytes, natural killer cells (NKs), and immunosuppressive cytokines. Fundamental challenges in nucleic acid delivery enabled by bio-barriers, its promising solution strategies and future directions are also reviewed.


Role of 24-h ambulatory blood pressure monitoring in children with chronic kidney disease.
Hypertension is common in children with chronic kidney disease (CKD) and is a major determinant of CKD progression. Ambulatory blood pressure monitoring (ABPM) has been proposed to be better in detecting hypertension as compared to casual blood pressure (CBP). This study aims to study the usefulness of ABPM in detecting masked hypertension, evaluating the adequacy of blood pressure (BP) control and predicting left ventricular hypertrophy (LVH) amongst children with CKD. A prospective cross-sectional study of 46 children with stage 3-5 CKD was conducted at the Pediatric Nephrology department of a tertiary hospital in South India. All children underwent CBP, ABPM and an echocardiography. Results were categorized as normal BP; confirmed hypertension; masked hypertension and white coat hypertension. Out of 46 children studied, 11 were undergoing dialysis. While 39.1% children had stage 3 and 4 CKD each, 21.7% had stage 5 CKD. Masked hypertension was detected in 19.6% and 21.7% had confirmed hypertension. Thirty-four (73.9%) children were already receiving antihypertensive medication. In these, CBP was elevated in 23.5% and ABP in 47%. Among children with hypertension as defined by ABPM, LVH was detected in 32.2%. We found that higher the number of abnormal ABPM indices (assessed by BP Index, nocturnal dipping and BP Load) higher the likelihood of LVH (P = 0.046). ABPM is better in detecting hypertension and monitoring adequacy of treatment in children with CKD. The high prevalence of masked hypertension and its association with LVH supports early echocardiography and ambulatory BP monitoring to evaluate cardiovascular risks in this population.


Prolactin receptor and uterine milk protein expression in the ovine endometrium during the estrous cycle and pregnancy.
Lactogenic hormones regulate epithelial proliferation, differentiation, and function in a variety of epitheliomesenchymal organs. During pregnancy, the ovine uterus is a potential site for endocrine and paracrine actions of lactogenic hormones in the form of pituitary prolactin (PRL) and placental lactogen (PL). These studies determined temporal and spatial alterations in PRL receptor (PRL-R) and expression of uterine milk proteins (UTMP), a marker of endometrial secretory activity, in the ovine endometrium during the estrous cycle and pregnancy. Slot-blot hybridization analysis indicated that steady-state levels of endometrial PRL-R mRNA increased during pregnancy. In situ hybridization and immunohistochemical analyses indicated that PRL-R mRNA and protein were exclusively expressed in the endometrial glandular epithelium (GE). No PRL-R mRNA expression was detected in luminal epithelium, stroma, myometrium, or conceptus trophectoderm. Reverse transcription-polymerase chain reaction analyses determined that the endometrial GE expressed both long and short alternative splice forms of the ovine PRL-R gene. Slot-blot hybridization analysis indicated that steady-state levels of intercaruncular endometrial UTMP mRNA increased about 3-fold between Days 20 and 60, increased another 3-fold between Days 60 and 80, and then declined slightly to Day 120. In pregnant ewes, UTMP mRNA expression was restricted to the endometrial GE in the stratum spongiosum (sGE), increased substantially between Days 15 and 17, and, between Days 17 to 50 of gestation, was markedly higher in upper than lower sGE. After Day 50, hyperplasia of the sGE was accompanied by increased UTMP mRNA expression by all sGE. Collectively, results indicate that 1) endometrial sGE is a primary target for actions of lactogenic hormones and 2) UTMP mRNA expression is correlated with PL production by the trophectoderm and state of sGE differentiation during pregnancy. It is proposed that activation of PRL-R signal transduction pathways by PRL and PL plays a major role in endometrial GE remodeling and differentiated function during pregnancy in support of conceptus growth and development.


Rapid dendritic morphogenesis in CA1 hippocampal dendrites induced by synaptic activity.
Activity shapes the structure of neurons and their circuits. Two-photon imaging of CA1 neurons expressing enhanced green fluorescent protein in developing hippocampal slices from rat brains was used to characterize dendritic morphogenesis in response to synaptic activity. High-frequency focal synaptic stimulation induced a period (longer than 30 minutes) of enhanced growth of small filopodia-like protrusions (typically less than 5 micrometers long). Synaptically evoked growth was long-lasting and localized to dendritic regions close (less than 50 micrometers) to the stimulating electrode and was prevented by blockade of N-methyl-D-aspartate receptors. Thus, synaptic activation can produce rapid input-specific changes in dendritic structure. Such persistent structural changes could contribute to the development of neural circuitry.


Quantitative flow cytometric identification of aberrant T cell clusters in erythrodermic cutaneous T cell lymphoma. Implications for staging and prognosis.
Assessment of peripheral blood tumour burden for staging of cutaneous T cells lymphoma is most often accomplished by flow cytometry (FC) using various non-standarised strategies. We report the results of calculating absolute Sezary cell counts (SCCs) by FC, based on the identification of aberrant T cell clusters on a virtual 6-dimensional space and independently of the expected immunophenotype (6D-FC SCC). 6D-FC SCCs were calculated on 65 peripheral blood specimens from 28 patients with erythrodermic cutaneous T cells lymphoma (stage III or IV). Comparisons were made with recommended FC strategies and correlations with overall mortality were studied. At first visit, 17 of 28 patients (61%) had 6D-FC SCCs meeting current criteria for Stage IV disease (≥1000 SC/μL); while only 2 patients (7%) met Stage IV criteria on other tissues. As defined by comprehensive staging using clinicomorphological criteria and 6D-FC SCCs, Stage IV disease identified a subgroup of patients with worse overall survival (p=0.0227). Residual non-aberrant CD4 T cells were markedly decreased in Stage IV disease (p=0.018). Among 65 specimens, discrepancies were observed between 6D-FC SCCs and usual FC thresholds for Stage IV disease, namely a CD4:CD8 ratio ≥10:1 (9 discrepancies, 14%), and ≥40% aberrant CD4 T cells (4 discrepancies, 6%). Surprisingly, 8 cases (12%) from 6 patients exhibited two distinctively separate clusters of aberrant CD4 T cells with different CD7 and/or CD26 expression. Visual 6-dimensional identification of aberrant T cell clusters by FC allows for the calculation of clinically significant SCCs. Simplified gating strategies and relative quantitative values might underestimate the immunophenotypical complexity of Sezary cells.


Diel Variation in Gene Expression of the CO2-Concentrating Mechanism during a Harmful Cyanobacterial Bloom.
Dense phytoplankton blooms in eutrophic waters often experience large daily fluctuations in environmental conditions. We investigated how this diel variation affects in situ gene expression of the CO2-concentrating mechanism (CCM) and other selected genes of the harmful cyanobacterium Microcystis aeruginosa. Photosynthetic activity of the cyanobacterial bloom depleted the dissolved CO2 concentration, raised pH to 10, and caused large diel fluctuations in the bicarbonate and O2 concentration. The Microcystis population consisted of three Ci uptake genotypes that differed in the presence of the low-affinity and high-affinity bicarbonate uptake genes bicA and sbtA. Expression of the bicarbonate uptake genes bicA, sbtA, and cmpA (encoding a subunit of the high-affinity bicarbonate uptake system BCT1), the CCM transcriptional regulator gene ccmR and the photoprotection gene flv4 increased at first daylight and was negatively correlated with the bicarbonate concentration. In contrast, genes of the two CO2 uptake systems were constitutively expressed, whereas expression of the RuBisCO chaperone gene rbcX, the carboxysome gene ccmM, and the photoprotection gene isiA was highest at night and down-regulated during daytime. In total, our results show that the harmful cyanobacterium Microcystis is very responsive to the large diel variations in carbon and light availability often encountered in dense cyanobacterial blooms.


Synthesis and screening of a library of Re/Tc-based amyloid probes derived from beta-breaker peptides.
Through the development and application of a unique approach for producing Re-metallopeptides, a new class of peptide-derived probes that are designed to target beta-amyloid plaques was developed. Derivatives of a class of beta-breaker peptides having the core sequence lvffa or affvl (lower case letters represent D-amino acids) and the single amino acid chelate quinoline (SAACQ) ligand which can bind Re and (99m)Tc were prepared on an automated peptide synthesizer. Both monomeric and dimeric peptides were synthesized in modest to good yields where in select examples a biotin-containing amino acid derivative was included to act as a linker point for further conjugation to carrier proteins. The Re complexes for all reported peptides were prepared similarly and screened for their ability to inhibit fibrillogenesis. Two of the reported compounds showed excellent inhibitory properties (8a: 40 +/- 5% amyloid formation versus control; 16: 40 +/- 4%) and warrant further investigation. For one of these leads, the (99m)Tc analogue was synthesized and the product showed high stability toward histidine and cysteine challenges, making it a viable candidate for in vivo biodistribution studies.


Modified osteotomy for symptomatic malunion of the humeral greater tuberosity.
Here, we describe a modified osteotomy for malunion of the greater tuberosity that facilitates bone union and prevents symptom recurrence. The 3 most important features of this technique are: (1) osteotomizing the displaced fragment that includes the bed of the fracture, (2) placing figure-of-eight sutures by passing suture threads from inside the medullary cavity through osseous holes made in the metaphysis, and (3) pushing the distal end of the osteotomized fragment into the medullary cavity and fixing it in place. This procedure was performed on 10 patients who complained of clinical symptoms derived primarily from greater tuberosity malunion after fractures of various morphologies. Eight of these patients were available for follow-up examinations over 2 postoperative years. Constant score ratios comparing the repaired side to the uninjured side ranged from 82% to 100%. These results support the use of this modified osteotomy in achieving favorable bone union and in creating sufficient subacromial space to resolve most symptoms caused by these malunited proximal humeral fractures.


The INSPIRE study: do personality traits predict general quality of life (Short form-36) in distressed patients with ulcerative colitis and Crohn's disease?
To assess the role of personality as a predictor of Short form-36 (SF-36) in distressed patients (perceived stress questionnaire, PSQ) with ulcerative colitis (UC) and Crohn's disease (CD). Fifty-four patients with CD and 55 with UC (age 18-60 years) who had relapsed in the previous 18 months, i.e. with an activity index (AI) for UC or CD> or =4, PSQ> or =60, and without severe mental or other major medical conditions, completed the Buss-Perry Aggression Questionnaire (BPA), the Neuroticism and Lie scales of the Eysenck Personality Questionnaire (EPQ-N and -L), the Multidimensional Health Locus of Control Scale (LOC) (Internal (I), Powerful Other (PO), Chance (C)), the Toronto Alexithymia Scale (TAS) and the SF-36. Multiple linear regression analyses controlling for gender, age and clinical disease activity (AI) in separate analyses for UC and CD showed that the mental and vitality subscales were predicted by neuroticism in both UC and CD. The highest explained variance was 43.8% on the "mental" subscale in UC. The social function subscale was related to alexithymia only in UC, while the role limitation and pain subscales were related to personality in CD only. The physical function subscale related differently to personality in UC and CD. While mental and vitality subscales were predicted by neuroticism in both UC and CD, other subscales had different relationships to personality, suggesting different psychobiological interactions in UC and CD.


Racial differences in adipose tissue distribution and risk of aggressive prostate cancer among men undergoing radiotherapy.
Although elevated body mass index (BMI) has been associated with increased risk of aggressive prostate cancer, the importance of adipose tissue distribution is not well understood. We examined associations between overall and visceral obesity and aggressive prostate cancer risk. Moreover, given racial differences in adipose tissue distribution, we examined whether race modified these associations. We conducted a cross-sectional analysis of 308 radiotherapy-treated patients with prostate cancer within the Durham VA from 2005 to 2011. Multivariable logistic regression examined the association between BMI categories and tertiles of waist circumference (WC), visceral fat area (VFA), and periprostatic adipose tissue area (PPAT) with high-grade prostate cancer risk (Gleason score ≥7 vs. ≤6). Models stratified by race examined whether these associations differed between black and nonblack men. Both elevated BMI (Ptrend = 0.054) and WC (Ptrend = 0.040) were associated with increased high-grade prostate cancer risk, with similar results between races, although the association with BMI was not statistically significant. In contrast, elevated VFA was associated with increased aggressive prostate cancer risk in black men (Ptrend = 0.002) but not nonblack men (Ptrend = 0.831), with a significant interaction between race and VFA (Pinteraction = 0.035). Though similar patterns were observed for PPAT, none was statistically significant. Among men undergoing radiotherapy for prostate cancer, visceral obesity is associated with increased aggressive prostate cancer risk, particularly among black men. If confirmed in future studies, these results suggest that adipose tissue distribution differences may contribute to prostate cancer racial disparity. These findings highlight the need to elucidate mechanisms contributing to racial differences in the association between visceral obesity and aggressive prostate cancer.


Endogenous opioids and addiction to alcohol and other drugs of abuse.
There is significant experimental evidence implicating the endogenous opioid system (opioid peptides and opioid receptors) with the processes of reward and reinforcement. Indeed, many behaviors associated with reward and reinforcement, for example feeding behavior, are controlled by distinct components of the endogenous opioid system located in relevant brain regions. It has also been shown that regardless of their initial site of action many drugs of abuse, such as morphine, nicotine, cocaine, alcohol and amphetamines, induce an increase in the extracellular concentration of dopamine in the nucleus accumbens. This, increased secretion of dopamine in the nucleus accumbens seems to be a common effect of many drugs of abuse, and it was proposed that may mediate their rewarding and reinforcing properties. Furthermore, activation of mu opioid receptors in the ventral tegmental area, or of mu and delta opioid receptors in the nucleus accumbens enhances the extracellular concentration of dopamine in the nucleus accumbens. Thus, stimulation of the activity of distinct components of the endogenous opioid system either by opioid or by other drugs of abuse, may mediate some of their reinforcing effects. In this review article, a brief description of the endogenous opioid system and its implication in the processes of reward and reinforcement of opioid and other drugs of abuse will be presented. Furthermore, the use of opioid antagonists in the treatment of drug addiction will be discussed. Special emphasis will be given to ethanol addiction, the drug mainly studied in my laboratory.


Quality of groundwater resources in Afghanistan.
Water is the main source of energy production and economy in Afghanistan where agriculture accounts for more than 50% of the country's gross domestic product (GDP). Access to safe drinking water is still a problem in the country, which has caused different health issues and even child mortality especially in rural areas. Groundwater is the main source of drinking water in the country. However, little knowledge is available about the quality of groundwater throughout the entire country, and its quality has not been investigated extensively yet like in other countries in the world. While most people think that consuming groundwater is a reliable and safe source of drinking water for health, the United Nations (UN) agencies report various kinds of waterborne diseases and even child mortalities due to drinking water quality in the country. In this article, significant geogenic and anthropogenic factors that play a vital role in groundwater contamination of the country are identified and explained. Different geogenic contaminations such as arsenic, fluoride, sulfate, and boron occur in several areas of Afghanistan that have a direct effect on human health. The water quality mapping for Afghanistan is completed for half of the country, which shows that groundwater is plagued by high levels of fluoride and arsenic in some areas. The water quality mapping of the other half of the country cannot be completed due to security concerns currently. Also, there are different kinds of waterborne diseases such as diarrhea, cholera, and dysentery that can be seen in different parts of the country because of anthropogenic activities which continuously deteriorate groundwater.


Endoscopic sphincterotomy for the palliation of ampullary carcinoma.
Palliative endoscopic sphincterotomy was performed on 17 patients with adenocarcinoma of the ampulla of Vater. An endoprosthesis was inserted immediately after the sphincterotomy in four of the patients. Fourteen patients made uncomplicated recoveries from the procedure and their jaundice resolved completely. Early complications developed in three patients. One patient died from haemorrhage. Two patients, both of whom had an endoprosthesis, developed cholangitis. The endoprosthesis was removed and another inserted in one patient and the other underwent surgery. Both thereafter made uncomplicated recoveries. Jaundice subsequently recurred in eight patients and further endoscopic treatment was successful in five of these patients. Eleven patients died between 4 days and 23 months after the sphincterotomy with a median survival of 12 months. Four patients remain alive between 3 and 17 months after treatment. The results indicate that reasonable palliation can be achieved safely by endoscopic sphincterotomy.


A unified nomenclature and amino acid numbering for human PTEN.
The tumor suppressor PTEN is a major brake for cell transformation, mainly due to its phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] phosphatase activity that directly counteracts the oncogenicity of phosphoinositide 3-kinase (PI3K). PTEN mutations are frequent in tumors and in the germ line of patients with tumor predisposition or with neurological or cognitive disorders, which makes the PTEN gene and protein a major focus of interest in current biomedical research. After almost two decades of intense investigation on the 403-residue-long PTEN protein, a previously uncharacterized form of PTEN has been discovered that contains 173 amino-terminal extra amino acids, as a result of an alternate translation initiation site. To facilitate research in the field and to avoid ambiguities in the naming and identification of PTEN amino acids from publications and databases, we propose here a unifying nomenclature and amino acid numbering for this longer form of PTEN.


Varietal influences on antihyperglycemia properties of freshly harvested apples using in vitro assay models.
The well-known health benefits of apples have been attributed in part to the presence of polyphenols and related antioxidant capacity. The consumption of apples could provide health benefits by reducing the risk for chronic diseases such as metabolic syndrome disease, including type 2 diabetes. Thus, the objective of this study was to investigate the phenolic-linked antihyperglycemia bioactive factors in aqueous and 12% ethanol extracts of peel and pulp from 10 different freshly harvested apple varieties commonly consumed in the United States. The extracts were analyzed for total soluble phenolics, 2,2-diphenyl-1-picrylhydrazyl-linked antioxidant activity, and their associated in vitro α-glucosidase and α-amylase inhibitory activities. In general, peel extracts had higher total soluble phenolic content and related antioxidant capacity than pulp extracts. Quercetin derivatives, protocatechuic acid, chlorogenic acid, and p-coumaric acid were detected, and the amount varied significantly between aqueous and ethanolic extracts. Honeycrisp and Red Delicious varieties had the highest total phenolic contents and a significant correlation with antioxidant capacity (r = 0.91). In addition, high α-amylase and α-glucosidase inhibitory activities in aqueous pulp extracts were found. However, the peel extracts had the highest α-glucosidase inhibitory activity along with low α-amylase inhibitory activity. No correlation between α-amylase inhibitory activity and total phenolic content was observed. However, positive correlations between α-glucosidase inhibitory activity and total phenolics in aqueous (r = 0.50) and ethanolic (r = 0.70) extracts were observed. This study provides the biochemical rationale for animal and clinical studies to determine the suitable varieties with optimum bioactive factors with antihyperglycemia potential.


Velocity measurement using laser speckle statistics.
A technique is presented which uses a laser beam to measure both vector components of the transverse velocity of a diffuse target. It is shown that the derivative of the spatio-temporal cross-correlation function of laser speckle intensity fluctuations, taken with respect to the time delay and evaluated at zero time delay, is directly proportional to the component of target velocity that is parallel to the spatial separation. Experimental results are presented which verify this linearity.


Toward a broader understanding of aldosterone in congestive heart failure.
Discovered some 50 years ago, aldosterone (ALDO) has come to be recognised as a mineralocorticoid hormone with well-known endocrine properties in epithelial cells that contribute to the pathophysiology of congestive heart failure. This includes Na+ resorption at the expense of K+ excretion in classic target tissues: kidneys, colon, sweat and salivary glands. Though less well known, Mg2+ excretion is likewise enhanced by ALDO, while adrenal ALDO secretion is regulated by extracellular Mg2+ ([Mg2+]o). An emerging body of information has and continues to identify other endocrine actions of ALDO receptor-ligand binding. They include: promoting an efflux of cytosolic free Mg2+, or [Mg2+]i, in exchange for Na+ in such non-epithelial cells as peripheral blood mononuclear cells; its influence on endothelial cell function; and its central actions that involve regulation of cerebrospinal fluid composition produced by epithelial cells of the choroid plexus, activity of the hypothalamic paraventricular nucleus involved in Na+ appetite, Na+ and H2O excretion and sympathetic nerve activity, and the regulation of TNF-alpha production from central and/or peripheral sources. Extra-adrenal steroidogenesis and auto/paracrine properties of ALDO generated de novo in the cardiovasculature are now under investigation and preliminary findings suggest they contribute to tissue repair. The past decade has witnessed a revival of interest in this steroid molecule. In years to come, an even broader understanding of ALDOs contribution to the pathophysiology of congestive heart failure will undoubtedly emerge.


Attaching and effacing locus of a Citrobacter freundii biotype that causes transmissible murine colonic hyperplasia.
Citrobacter freundii biotype 4280 produces attaching and effacing (AE) lesions in the large intestine of laboratory mice and is the causative agent of transmissible murine colonic hyperplasia. AE lesions are also produced by enteropathogenic Escherichia coli in humans. Southern analysis revealed that biotype 4280, but not 20 other strains of C. freundii, contained DNA homologous to the eae (E. coli attaching and effacing) gene which is necessary for AE activity by enteropathogenic E. coli in vitro. We have cloned and determined the nucleotide sequence of the C. freundii eae homolog. Our findings suggest that the eae locus of C. freundii biotype 4280 is necessary for AE activity and has a role in the pathogenesis of transmissible murine colonic hyperplasia.


Lipidomics analysis of juveniles' blue mussels (Mytilus edulis L. 1758), a key economic and ecological species.
Blue mussels (Mytilus edulis L. 1758) are important components of coastal ecosystems and in the economy of rural and coastal areas. The understanding of their physiological processes at key life stages is important both within food production systems and in the management of wild populations. Lipids are crucial molecules for bivalve growth, but their diversity and roles have not been fully characterised. In this study, traditional lipid profiling techniques, such as fatty acid (FA) and lipid class analysis, are combined to untargeted lipidomics to elucidate the lipid metabolism in newly settled spat fed on a range of diets. The evaluated diets included single strains treatments (Cylindrotheca fusiformis CCAP 1017/2 -CYL, Isochrysis galbana CCAP 927/1- ISO, Monodopsis subterranean CCAP 848/1 -MONO, Nannochloropsis oceanica CCAP 849/10- NANNO) and a commercial algae paste (SP). Spat growth was influenced by the diets, which, according to their efficacy were ranked as follows: ISO>NANNO/CYL>SP>MONO. A higher triacylglycerols (TG) content, ranging from 4.23±0.82 μg mgashfree Dry weight (DW)-1 at the beginning of the trial (T0) to 51±15.3 μg mgashfreeDW-1 in ISO, characterised significant growth in the spat, whereas, a reduction of TG (0.3±0.08 μg mgashfreeDW-1 in MONO), mono unsaturated FA-MUFA (from 8.52±1.02 μg mgFAashfreeDW-1 at T0 to 2.81±1.02 μg mgFAashfreeDW-1 in MONO) and polyunsaturated FA-PUFA (from 17.57±2.24 μg mgFAashfreeDW-1 at T0 to 6.19±2.49 μg mgFAashfreeDW-1 in MONO) content characterised poor performing groups. Untargeted lipidomics evidenced how the availability of dietary essential PUFA did not influence only neutral lipids but also the membrane lipids, with changes in lipid molecular species in relation to the essential PUFA provided via the diet. Such changes have the potential to affect spat production cycle and their ability to respond to the surrounding environment. This study evidenced the advantages of coupling different lipid analysis techniques, as each technique disclosed relevant information on nutritional requirements of M. edulis juveniles, expanding the existing knowledge on the physiology of this important species.


Health and Health Seeking in Mosul During ISIS Control and Liberation: Results From a 40-Cluster Household Survey.
ISIS seized Mosul in June 2014. This survey was conducted to assess health status, health needs, and health-seeking behavior during ISIS control and the subsequent Iraqi military campaign. Forty clusters were chosen: 25 from east Mosul and 15 from west Mosul. In each, 30 households were interviewed, representing 7559 persons. The start house for each cluster was selected using satellite maps. The survey in east Mosul was conducted from March 13-31, 2017, and in west Mosul from July 18-31, 2017. In the preceding 2 weeks, 265 (5.4%) adults reported being ill. Some 67 (25.3%) complaints were for emotional or behavioral issues, and 59 (22.3%) for noncommunicable diseases. There were 349 (13.2%) children under age 15 reportedly ill during this time. Diarrhea, respiratory complaints, and emotional and behavioral problems were most common. Care seeking among both children and adults was low, especially in west Mosul. During ISIS occupation, 640 (39.0%) women of childbearing age reported deliveries. Of these, 431 (67.3%) had received some antenatal care, and 582 (90.9%) delivered in a hospital. Complications were reported by 417 (65.2%). Communicable and noncommunicable diseases were reported for both children and adults, with a high prevalence of emotional and behavioral problems, particularly in west Mosul. Care-seeking was low, treatment compliance for noncommunicable diseases was poor, and treatment options for patients were limited. (Disaster Med Public Health Preparedness. 2019;13:758-766).


Infantile neuroaxonal dystrophy caused by uniparental disomy.
Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the phospholipase A2 group 6 (Pla2G6) gene. Affected individuals usually present between the ages of 6 months and 2 years with rapid cognitive and motor regression and axial hypotonia. Gait disturbance, limb spasticity, cerebellar signs, and optic atrophy are other common features associated with INAD. Although magnetic resonance imaging (MRI) can sometimes contribute towards the diagnosis, the confirmation of INAD is by Pla2G6 gene analysis. In this case report, we describe the first individual (female) with INAD due to a combination of uniparental heterodisomy and isodisomy; we discuss the possible underlying mechanism and highlight the importance of parental carrier testing in accurately predicting the recurrence risk in these families. We also confirm the recent report of hypertrophy of the clava (also known as the 'gracile tubercle') as a useful MRI sign in INAD.


Developmental trajectories of associative memory from childhood to adulthood: a behavioral and neuroimaging study.
Episodic memory refers to the capacity to bind multimodal memories to constitute a unique personal event. Most developmental studies on episodic memory focused on one specific component, i.e., the core factual information. The present study examines the relevance of a novel episodic paradigm to assess its developmental trajectories in a more comprehensive way according to the type of association (item-feature, item-location, and item-sequence associations) with measures of both objective and subjective recollection. We conducted a behavioral study aimed at testing the effects of age in a large sample of 160 children, adolescents, and young adults (6-23 years old). We confronted the behavioral data to the neural correlates in a subgroup of 30 children using voxel-based morphometry. Behavioral data outlined differential developmental trajectories according to the type of association, with a continuous increase of factual associative memory efficiency until 10 years, a linear increase of performance in spatial associative memory that pursues until early adulthood and an abrupt increase in temporal associative memory efficiency between 9 and 10. Regarding recollection, measures showed a more pronounced enhancement from 9 to 10 years. Hence, behavioral data highlight a peculiar period in late childhood (8-10 years old) crucial for the developmental time course of episodic memory. Regarding structural data, we found that the improvement of associative memory efficiency was related to a decrease in gray matter volume in a large cerebral network including the dorsolateral and ventrolateral prefrontal cortex (and superior and anterior temporal regions), and the hippocampus bilaterally. These data suggest that multimodal integration would probably be related to the maturation of temporal regions and modulated by a fronto-parietal network. Besides, our findings emphasize the relevance of the present paradigm to assess episodic memory especially in the clinical setting.


Ibuprofen prevents altitude illness: a randomized controlled trial for prevention of altitude illness with nonsteroidal anti-inflammatories.
Acute mountain sickness occurs in more than 25% of the tens of millions of people who travel to high altitude each year. Previous studies on chemoprophylaxis with nonsteroidal anti-inflammatory drugs are limited in their ability to determine efficacy. We compare ibuprofen versus placebo in the prevention of acute mountain sickness incidence and severity on ascent from low to high altitude. Healthy adult volunteers living at low altitude were randomized to ibuprofen 600 mg or placebo 3 times daily, starting 6 hours before ascent from 1,240 m (4,100 ft) to 3,810 m (12,570 ft) during July and August 2010 in the White Mountains of California. The main outcome measures were acute mountain sickness incidence and severity, measured by the Lake Louise Questionnaire acute mountain sickness score with a diagnosis of ≥ 3 with headache and 1 other symptom. Eighty-six participants completed the study; 44 (51%) received ibuprofen and 42 (49%) placebo. There were no differences in demographic characteristics between the 2 groups. Fewer participants in the ibuprofen group (43%) developed acute mountain sickness compared with those receiving placebo (69%) (odds ratio 0.3, 95% confidence interval 0.1 to 0.8; number needed to treat 3.9, 95% confidence interval 2 to 33). The acute mountain sickness severity was higher in the placebo group (4.4 [SD 2.6]) than individuals receiving ibuprofen (3.2 [SD 2.4]) (mean difference 0.9%; 95% confidence interval 0.3% to 3.0%). Compared with placebo, ibuprofen was effective in reducing the incidence of acute mountain sickness.


Strontium Ranelate Combined with Insulin Is as Beneficial as Insulin Alone in Treatment of Fracture Healing in Ovariectomized Diabetic Rats.
BACKGROUND Type 2 diabetes mellitus (T2DM) and estrogen deficiency both predispose fracture patients to increased risk of delayed union or nonunion. The present study investigated the effects of strontium ranelate (SR) on fracture healing in ovariectomized (OVX) diabetic rats. MATERIAL AND METHODS A mid-shaft fracture was established in female normal control (CF), diabetic (DF), and OVX diabetic (DOF) rats. Treated DOF rats received either insulin alone (DOFI) or combined with SR (DOFIS). All rats were euthanized at 2 or 3 weeks after fracture. Fracture healing was evaluated using radiological, histological, immunohistochemical, and micro-computed tomography analyses. RESULTS At 3 weeks after fracture, radiological and histological evaluations demonstrated delayed fracture healing in the DF group compared with the CF group, which was exacerbated by OVX, as indicated by the significantly lower X-ray score, BMD, BV/TV, and Md.Ar/Ps.Cl.Ar, and the markedly decreased OCN and Col I expression in the DOF group. All these changes were prevented by insulin alone or combined with SR treatment. In comparison with the DOFI group, DOFIS rats displayed markedly higher OCN expression at 2 weeks after fracture and Col I expression at 2 and 3 weeks after fracture. CONCLUSIONS These results demonstrated delayed fracture healing with preexisting estrogen deficiency and T2DM. While insulin alone and combined with SR were both effective in promoting bone fracture healing in this model, their combined treatment showed significant improvement in promoting osteogenic marker expression, but not of the radiological appearance, compared with insulin alone.


Are more restrictive food cadmium standards justifiable health safety measures or opportunistic barriers to trade? An answer from economics and public health.
In the past, Cd regulations have imposed trade restrictions on foodstuffs from some developing countries seeking to access markets in the developed world and in recent years, there has been a trend towards imposing more rigorous standards. This trend seems to respond more to public and private sectors strategies in some developed countries to create disguised barriers to trade and to improve market competitiveness for their industries, than to scientifically justified health precautions (sanitary and phytosanitary measures) and/or technical barriers to trade acceptable under the Uruguay Round Agreement of the WTO. Applying more rigorous Cd standards in some developed countries will not only increase production costs in developing countries but it will also have a large impact on their economies highly dependent on international agricultural markets. In the current literature there are large uncertainties in the cause-effect relationship between current levels of Cd intakes and eventual health effects in human beings; even the risk of Cd to kidney function is under considerable debate. Recent works on the importance of zinc:Cd ratio rather than Cd levels alone to determine Cd risk factors, on the one hand, and on the declining trends of Cd level in foods and soils, on the other, also indicate a lack of scientific evidence justifying more restrictive cadmium standards. This shows that developing countries should fight for changing and making more transparent the current international structures and procedures for setting sanitary and phytosanitary measures and technical barriers to trade.


Pulmonary lymphoma in Sjögren's syndrome.
Sjögren's syndrome (SS) is an immunologic disease characterized by progressive destruction of the exocrine glands that causes mucosal and conjunctival dryness. In addition to the common pulmonary complications of diffuse interstitial lung disease, airways obstruction, desiccation of the upper respiratory tract, localized parenchymal nodules, recurrent tracheobronchitis, bronchiectasis, interstitial pneumonitis, and pleural effusion, patients with SS have a high risk of developing non-Hodgkin's lymphoma that may affect the lungs. Among 50 patients with SS and associated lymphoma, 10 had pulmonary involvement by lymphoma. The mean age of these 10 patients was 59.7 years, and 8 were women. The mean duration of SS was 7.2 years, and the mean interval between the onset of SS and lymphoma was 5.4 years. Cough and slowly progressive dyspnea were the most common pulmonary symptoms, and chest roentgenographic findings varied. Lung biopsies revealed a spectrum of low-to high-grade lymphomas, and high-grade lymphomas were associated with increased mortality. Of the 10 patients, 4 died from 8 to 48 months after lymphoma was diagnosed. We conclude that pulmonary involvement is common in patients with lymphoma associated with SS; thus, lymphoma should be considered in the differential diagnosis of pulmonary lesions in patients with SS.


Decreased expression of HLA-DQ and HLA-DR on cells of the monocytic lineage in cystic fibrosis.
We studied HLA class II molecules on blood monocyte subsets, blood dendritic cells, sputum macrophages, and monocyte-derived macrophages at the protein (flow cytometry) and mRNA level (RT-PCR) in adult patients with cystic fibrosis (CF) and healthy control subjects as putative contributors to the CF phenotype. In healthy donors, we found a high average HLA-DQ expression of 4.35 mean specific fluorescence intensity units (ΔMnI) on classical blood monocytes. In F508del homozygous CF patients, the average ΔMnI was low (1.80). Patients were divided into two groups, in which 14 of these patients had HLA-DQ expression above 2 ΔMnI (average 3.25 ΔMnI, CF-DQ(group1)) and 36 below (average 1.24 ΔMnI, CF-DQ(group2)). Also, the CD16-positive monocyte subset and blood dendritic cells showed much lower levels of HLA-DQ for the CF-DQ(group2) patients compared with healthy controls. In macrophages from sputum and derived from monocytes, in vitro HLA-DQ expression was dramatically decreased to background levels in CF-DQ(group2). MHC class II transcripts were reduced in CF with a sevenfold decrease in HLA-DQβ1 for CF-DQ(group2) patients. Higher levels of the inflammation marker CRP were associated with low HLA-DQ protein expression, and in vitro treatment with the inflammatory molecule lipopolysaccharide reduced HLA-DQ expression. Interferon γ (IFNγ) could overcome this effect in healthy donor cells while, in CF, the IFNγ-induced activation was impaired. Our data demonstrate a pronounced reduction of HLA-DQ expression in CF, which is associated with inflammation and a reduced response to IFNγ. • CF patients show a reduced expression of MHCII molecules in monocytes and macrophages. • HLA-DQ and HLA-DR transcript levels are also reduced in CF patients. • CF patient C-reactive protein levels correlate with low HLA-DQ expression. • Reduced expression of MHC class II molecules appears to be linked to inflammation. • CF patients exhibit an impaired response to IFNgamma.


Prevalence of the metabolic syndrome and its components in Northwest Russia: the Arkhangelsk study.
The metabolic syndrome (MetS) is a cluster of risk factors associated with morbidity from cardiovascular disease (CVD) and associated mortality. Russia has one of the highest CVD mortality rates in the world. However, the prevalence of MetS in Russia remains largely unknown. The aim of this study is to estimate the prevalence of MetS and its components in an urban Russian setting. Altogether, 3705 Russian adults aged 18-90 years were enrolled in a cross-sectional study in Arkhangelsk (Northwest Russia). All subjects completed a questionnaire and underwent a physical examination. Blood samples were taken and analyzed in TromsØ, Norway. Three separate modified definitions of MetS were used, namely, the National Education Cholesterol Education Program Adult Treatment Panel III (NCEP), the American Heart Association/National Heart, Lung and Blood Institute (AHA/NHLBI) and the International Diabetes Federation (IDF). To ensure comparability of the findings, the prevalence data were standardized using world and European standard populations and Russian population. The age-standardized (Segi's world standard population) prevalence rates of the MetS among women were 19.8% (95% CI: 18.1-21.5), 20.6% (95% CI: 18.9-22.3) and 23.1% (95% CI: 21.3-24.9) by the NCEP, AHA/NHLBI and IDF criteria, respectively. The corresponding rates for men were 11.5% (95% CI: 10.1-12.9), 13.7% (95% CI: 12.2-15.2) and 11.0% (95% CI: 9.7-12.4). Among subjects with MetS, central obesity was more common among women, while elevated triglycerides and blood glucose were more common among men. Almost perfect agreement was found between the NCEP and AHA/NHLBI criteria (kappa = 0.94). There was less agreement between the used definitions of MetS in men than in women. While the prevalence of MetS among Russian women is comparable to the data for Europe and the U.S., the prevalence among Russian men is considerably lower than among their European and North-American counterparts. Our results suggest that MetS is unlikely to be a major contributor to the high cardiovascular mortality among Russian men. Further studies of MetS determinants and associated cardiovascular risk are needed for a better understanding of the mechanisms leading to the exceptionally high cardiovascular mortality in Russia.


Multi-criteria analysis towards the new end use of recycled water for household laundry: a case study in Sydney.
This paper aims to put forward several management alternatives regarding the application of recycled water for household laundry in Sydney. Based on different recycled water treatment techniques such as microfiltration (MF), granular activated carbon (GAC) or reverse osmosis (RO), and types of washing machines (WMs), five alternatives were proposed as follows: (1) do nothing scenario; (2) MF+existing WMs; (3) MF+new WMs; (4) MF-GAC+existing WMs; and (5) MF-RO+existing WMs. Accordingly, a comprehensive quantitative assessment on the trade-off among a variety of issues (e.g., engineering feasibility, initial cost, energy consumption, supply flexibility and water savings) was performed over the alternatives. This was achieved by a computer-based multi-criteria analysis (MCA) using the rank order weight generation together with preference ranking organization method for enrichment evaluation (PROMETHEE) outranking techniques. Particularly, the generated 10,000 combinations of weights via Monte Carlo simulation were able to significantly reduce the man-made errors of single fixed set of weights because of its objectivity and high efficiency. To illustrate the methodology, a case study on Rouse Hill Development Area (RHDA), Sydney, Australia was carried out afterwards. The study was concluded by highlighting the feasibility of using highly treated recycled water for existing and new washing machines. This could provide a powerful guidance for sustainable water reuse management in the long term. However, more detailed field trials and investigations are still needed to effectively understand, predict and manage the impact of selected recycled water for new end use alternatives.


Medroxyprogesterone acetate impairs memory and alters the GABAergic system in aged surgically menopausal rats.
In women, medroxyprogesterone acetate (MPA) is the most commonly used progestin component of hormone therapy (HT). In vitro, MPA negatively impacts markers of neuronal health and exacerbates experimentally-induced neurotoxicity. There is in vitro evidence that these factors are driven by GABAergic and neurotrophic systems. Whether these effects translate to a negative impact on brain function has not been tested in vivo, clinically or preclinically. Here we evaluate the mnemonic and neurobiological effects of MPA in the surgically menopausal rat. Aged ovariectomized (OVX) rats were given subcutaneous vehicle, natural progesterone, low-dose MPA or high-dose MPA. Multiple cognitive domains were analyzed via the water radial-arm maze (WRAM) and Morris maze (MM). Cognitive brain regions were assayed for changes in the GABAergic system by evaluating GAD protein, the synthesizing enzyme for GABA, and neurotrophins. On the WRAM, both progestin types impaired learning. Further, high-dose MPA impaired delayed memory retention on the WRAM, and exacerbated overnight forgetting on the MM. While neurotrophins were not affected by progesterone or MPA treatment, both progestin types altered GAD levels. MPA significantly and progesterone marginally decreased GAD levels in the hippocampus, and both MPA and progesterone significantly increased GAD levels in the entorhinal cortex. These findings suggest that MPA, the most commonly used progestin in HT, is detrimental to learning and two types of memory, and modulates the GABAergic system in cognitive brain regions, in aged surgically menopausal rats. These findings, combined with in vitro evidence that MPA is detrimental to neuronal health, indicates that MPA has negative effects for brain health and function.


Contraceptive Use and Uptake of HIV-Testing among Sub-Saharan African Women.
Despite improved availability of simple, relatively inexpensive, and highly effective antiretroviral treatment for HIV/AIDS, the disease remains a major public health challenge for women in sub-Saharan Africa (SSA). Given the numerous barriers in access to care for women in this region, every health issue that brings them into contact with the health system should be optimized as an opportunity to integrate HIV/AIDS prevention. Because most non-condom forms of modern contraception require a clinical appointment for use, contraception appointments could provide a confidential opportunity for access to HIV counseling, testing, and referral to care. This study sought to investigate the relationship between contraceptive methods and HIV testing among women in SSA. Data from the Demographic and Health Survey from four African countries-Congo, Mozambique, Nigeria, and Uganda-was used to examine whether modern (e.g., pills, condom) or traditional (e.g., periodic abstinence, withdrawal) forms of contraception were associated with uptake of HIV testing. Data for the current analyses were restricted to 35,748 women with complete information on the variables of interest. Chi-square tests and logistic regression models were used to assess the relationship between uptake of HIV testing and respondents' baseline characteristics and contraceptive methods. In the total sample and in Mozambique, women who used modern forms of contraception were more likely to be tested for HIV compared to those who did not use contraception. This positive association was not demonstrated in Congo, Nigeria, or Uganda. That many women who access modern contraception are not tested for HIV in high HIV burden areas highlights a missed opportunity to deliver an important intervention to promote maternal and child health. Given the increasing popularity of hormonal contraception methods in low-income countries, there is an urgent need to integrate HIV counseling, testing, and treatment into family planning programs. Women on hormonal contraceptives should be encouraged to continue to use condoms for HIV-prevention.


Evaluation of the Effectiveness of a Novel Brain and Vestibular Rehabilitation Treatment Modality in PTSD Patients Who have Suffered Combat-Related Traumatic Brain Injuries.
Blast-related head injuries are among the most prevalent injuries suffered by military personnel deployed in combat and mild traumatic brain injury (mTBI) or concussion on the battlefield in Iraq/Afghanistan has resulted in its designation as a "signature injury." Vestibular complaints are the most frequent sequelae of mTBI, and vestibular rehabilitation (VR) has been established as the most important treatment modality for this group of patients. We studied the effectiveness of a novel brain and VR treatment post-traumatic stress disorder (PTSD) in subjects who had suffered combat-related traumatic brain injuries in terms of PTSD symptom reduction. The trial was registered as ClinicalTrials.gov Identifier: NCT02003352. (http://clinicaltrials.gov/ct2/show/NCT02003352?term=carrick&rank=6). We analyzed the difference in the Clinician Administered DSM-IV PTSD Scale (CAPS) scores pre- and post-treatment using our subjects as their own matched controls. The study population consisted of 98 combat veterans maintaining an alpha of <0.05 and power of 80%. Prior to treatment, 75 subjects representing 76.53 % of the sample were classified in the 2 most severe categories of PTSD. Forty-one subjects, representing 41.80 % of the total sample, were classified in the extreme category of PTSD and 34 subjects, representing 34.70 % of the total sample, were classified in the severe category of PTSD. After treatment, we observed a large reduction in CAPS severity scores with both statistical and substantive significance. Treatment of PTSD as a physical injury rather than a psychiatric disorder is associated with strong statistical and substantive significant outcomes associated with a decrease of PTSD classification. The stigma associated with neuropsychiatric disorders may be lessened when PTSD is treated with brain and VR with a potential decrease in suffering of patients, family, and society.


Brain Structure and Function Associated with Younger Adults in Growth Hormone Receptor-Deficient Humans.
Growth hormone receptor deficiency (GHRD) results in short stature, enhanced insulin sensitivity, and low circulating levels of insulin and insulin-like growth factor 1 (IGF-1). Previous studies in mice and humans suggested that GHRD has protective effects against age-related diseases, including cancer and diabetes. Whereas GHRD mice show improved age-dependent cognitive performance, the effect of GHRD on human cognition remains unknown. Using MRI, we compared brain structure, function, and connectivity between 13 people with GHRD and 12 unaffected relatives. We assessed differences in white matter microstructural integrity, hippocampal volume, subregional volumes, and cortical thickness and surface area of selected regions. We also evaluated brain activity at rest and during a hippocampal-dependent pattern separation task. The GHRD group had larger surface areas in several frontal and cingulate regions and showed trends toward larger dentate gyrus and CA1 regions of the hippocampus. They had lower mean diffusivity in the genu of the corpus callosum and the anterior thalamic tracts. The GHRD group showed enhanced cognitive performance and greater task-related activation in frontal, parietal, and hippocampal regions compared with controls. Furthermore, they had greater functional synchronicity of activity between the precuneus and the rest of the default mode network at rest. The results suggest that, compared with controls, GHRD subjects have brain structure and function that are more consistent with those observed in younger adults reported in previous studies. Further investigation may lead to improved understanding of underlying mechanisms and could contribute to the identification of treatments for age-related cognitive deficits.SIGNIFICANCE STATEMENT People and mice with growth hormone receptor deficiency (GHRD or Laron syndrome) are protected against age-related diseases including cancer and diabetes. However, in humans, it is unknown whether cognitive function and brain structure are affected by GHRD. Using MRI, we examined cognition in an Ecuadorian population with GHRD and their unaffected relatives. The GHRD group showed better memory performance than their relatives. The differences in brain structure and function that we saw between the two groups were not consistent with variations typically associated with brain deficits. This study contributes to our understanding of the connection between growth genes and brain aging in humans and provides data indicating that GHR inhibition has the potential to protect against age-dependent cognitive decline.


The Neuroscience of Dance: A Conceptual Framework and Systematic Review.
Ancient and culturally universal, dance pervades many areas of life and has multiple benefits. In this article, we provide a conceptual framework and systematic review, as a guide for researching the neuroscience of dance. We identified relevant articles following PRISMA guidelines, and summarised and evaluated all original results. We identified avenues for future research in: the interactive and collective aspects of dance; groove; dance performance; dance observation; and dance therapy. Furthermore, the interactive and collective aspects of dance constitute a vital part of the field but have received almost no attention from a neuroscientific perspective so far. Dance and music engage overlapping brain networks, including common regions involved in perception, action, and emotion. In music and dance, rhythm, melody, and harmony are processed in an active, sustained pleasure cycle giving rise to action, emotion, and learning, led by activity in specific hedonic brain networks. The neuroscience of dance is an exciting field, which may yield information concerning links between psychological processes and behaviour, human flourishing, and the concept of eudaimonia.


Predictors of Mortality Among U.S. Veterans With Streptococcus Pneumoniae Infections.
Serious Streptococcus pneumoniae infections, encompassing pneumonia, bacteremia, and meningitis, are a major cause of mortality. However, literature regarding mortality is often limited to invasive pneumococcal disease, excluding pneumonia. This study sought to identify predictors of mortality among adults with serious pneumococcal disease, including pneumonia and invasive pneumococcal disease. This was a nested case-control study of unvaccinated older Veterans with positive S. pneumoniae cultures (blood, cerebrospinal fluid, respiratory) admitted to Veterans Affairs medical centers nationally between 2002 and 2011. Patients vaccinated against pneumococcal disease were excluded. Using multivariable logistic regression, predictors of 30-day mortality were identified, including patient demographics, comorbidities during admission, and medical history within the previous year. Among 9,468 patients, there were 9,730 serious pneumococcal infections; 1,764 (18.6%) resulted in death within 30 days (cases), whereas 7,966 did not (controls). Pneumonia accounted for half (49.4%, n=871) of all deaths. Mortality predictors consistent with vaccine recommendations included dialysis (during hospitalization, OR=3.35, 95% CI=2.37, 4.72), moderate to severe liver disease (during hospitalization, OR=2.47, 95% CI=1.53, 3.99; within 1 year, OR=1.49, 95% CI=1.01, 2.20), and neutropenia (during hospitalization, OR=2.67, 95% CI=1.32, 5.42). Predictors not included in current recommendations included dementia (during hospitalization, OR=1.8, 95% CI=1.23, 2.61) and neurologic disorders (during hospitalization, OR=1.86, 95% CI=1.42, 2.45; within 1 year, OR=1.28, 95% CI=1.02, 1.59). Several mortality predictors among unvaccinated Veterans with serious pneumococcal disease were consistent with pneumococcal vaccine recommendations, including organ or immune system dysfunction-related conditions. Other predictors, including neurologic disorders or dementia, may warrant expanded vaccination recommendations.


Listmania. How lists can open up fresh possibilities for research in the history of science.
Anthropologists, linguists, cultural historians, and literary scholars have long emphasized the value of examining writing as a material practice and have often invoked the list as a paradigmatic example thereof. This Focus section explores how lists can open up fresh possibilities for research in the history of science. Drawing on examples from the early modern period, the contributors argue that attention to practices of list making reveals important relations between mercantile, administrative, and scientific attempts to organize the contents of the world. Early modern lists projected both spatial and temporal visions of nature: they inventoried objects in the process of exchange and collection; they projected possible trajectories for future endeavor; they publicized the social identities of scientific practitioners; and they became research tools that transformed understandings of the natural order.


Assessing third-year medical students' ability to address a patient's spiritual distress using an OSCE case.
To inform curricular development by assessing the ability of third-year medical students to address a patient's spiritual distress during an acute medical crisis in the context of an objective structured clinical examination (OSCE) case. During March and April 2010, 170 third-year medical students completed an eight-station videotaped OSCE at Albert Einstein College of Medicine of Yeshiva University. One of the standardized patients (SPs) was a 65-year-old man with acute chest pain who mentioned his religious affiliation and fear of dying. If prompted, he revealed his desire to speak with a chaplain. The SP assessed students' history taking, physical examination, and communication skills. In a postencounter written exercise, students reported their responses to the patient's distress via four open-ended questions. Analysis of the postencounter notes was conducted by three coders for emergent themes. Clinical skills performance was compared between students who reported making chaplain referral and those who did not. A total of 108 students (64%) reported making a chaplain referral; 4 (2%) directly addressed the patient's religious/spiritual beliefs. Students' clinical performance scores showed no significant association with whether they made a chaplain referral. Findings suggest that the majority of medical students without robust training in addressing patients' spiritual needs can make a chaplain referral when faced with a patient in spiritual crisis. Yet, few students explicitly engaged the patient in a discussion of his beliefs. Thus, future studies are needed to develop more precise assessment measures that can inform development in spirituality and medicine curricula.


The effect of different amounts of calcium intake on bone metabolism and arterial calcification in ovariectomized rats.
Low calcium (Ca) intake is the one of risk factors for both bone loss and medial elastocalcinosis in an estrogen deficiency state. To examine the effect of different amounts of Ca intake on the relationship between bone mass alteration and medial elastocalcinosis, 6-wk-old female SD rats were randomized into ovariectomized (OVX) control or OVX treated with vitamin D(3) plus nicotine injection (VDN) groups. The OVX treated with VDN group was then divided into 5 groups depending on the different Ca content in their diet, 0.01%, 0.1%, 0.6%, 1.2%, and 2.4% Ca intakes. After 8 wk of experimentation, the low Ca intake groups of 0.01% and 0.1% showed a low bone mineral density (BMD) and bone properties significantly different from those of the other groups, whereas the high Ca intake groups of 1.2% and 2.4% showed no difference compared with the OVX control. Only in the 0.01% Ca intake group, a significantly higher Ca content in the thoracic artery was found compared with that of the OVX control. Arterial tissues of the 0.01% Ca intake group showed an increase of bone-specific alkaline phosphatase (BAP) activity, a marker of bone mineralization, associated with arterial Ca content. However, the high Ca intake did not affect arterial Ca content nor arterial BAP activity. These results suggested that a low Ca intake during periods of rapid bone loss caused by estrogen deficiency might be one possible cause for the complication of both bone loss and medial elastocalcinosis.


Community based maternal and child health nutrition project, uttar pradesh: an innovative strategy focusing on "at risk" families.
Use of community based volunteers, frequently reaching and counseling a selected group of prioritized families, can make a substantial difference in improving maternal and child care practices and in reducing child undernutrition. Program Rural Uttar Pradesh, India. A comparison of baseline and endline surveys following 4 years of community based project intervention. "At risk" undernutrition families comprising mothers of under twos, newlyweds, and severely undernourished children below 6 years. Mapping and counseling of "at risk" families. Measuring impact on maternal-child care practices, underweight status. Trained community mobilizers identified and counseled selected "at risk" families. Following 4 years of implementation in 907 villages of 8 blocks of four districts, significant improvement was noted in practices of early initiation of breastfeeding, feeding colostrum, timely introduction of complementary feeding, and washing the hands after defecation. Percentage of mothers exclusively breastfeeding at 6 months was only 2.1% with 78% receiving prelacteal feeds. A small increase in normal and mild malnutrition and a significant reduction of 43% in severe malnutrition was noted. Frequently counseling by accredited social health activists by focusing on selected defined "at risk" families of under twos and those with severe malnourished children could result in increasing acceptability of correct child health, feeding, and care practices and in contributing to improving nutritional status scenario.


Herpesviruses carrying a Brainbow cassette reveal replication and expression of limited numbers of incoming genomes.
Whether all the infectious herpesvirus particles entering a cell are able to replicate and/or express their genomes is not known. Here, we developed a general method to determine the number of viral genomes expressed in an infected cell. We constructed and analysed fluorophore expression from a recombinant pseudorabies virus (PRV263) carrying a Brainbow cassette (Cre-conditional expression of different fluorophores). Using three isogenic strains derived from PRV263, each expressing a single fluorophore, we analysed the colour composition of cells infected with these three viruses at different multiplicities. We estimate that fewer than seven incoming genomes are expressed per cell. In addition, those templates that are expressed are the genomes selected for replication and packaging into virions. This finite limit on the number of viral genomes that can be expressed is an intrinsic property of the infected cell and may be influenced by viral and cellular factors.


Tolerance of lesions in E. coli: Chronological competition between Translesion Synthesis and Damage Avoidance.
Lesion tolerance pathways allow cells to proceed with replication despite the presence of replication-blocking lesions in their genome. Following transient fork stalling, replication resumes downstream leaving daughter strand gaps opposite replication-blocking lesions. The existence and repair of these gaps have been know for decades and are commonly referred to as postreplicative repair [39,38] (Rupp, 2013; Rupp and Howard-Flanders, 1968). This paper analyzes the interaction of the pathways involved in the repair of these gaps. A key repair intermediated is formed when RecA protein binds to these gaps forming ssDNA.RecA filaments establishing the so-called SOS signal. The gaps are either "repaired" by Translesion Synthesis (TLS), a process that involves the transient recruitment of a specialized DNA polymerase that copies the lesion with an intrinsic risk of fixing a mutation opposite the lesion site, or by Damage Avoidance, an error-free pathway that involves homologous recombination with the sister chromatid (Homology Directed Gap Repair: HDGR). We have developed an assay that allows one to study the partition between TLS and HDGR in the context of a single replication-blocking lesion present in the E. coli chromosome. The level of expression of the TLS polymerases controls the extent of TLS. Our data show that TLS is implemented first with great parsimony, followed by abundant recombination-based tolerance events. Indeed, the substrate for TLS, i.e., the ssDNA.RecA filament, persists for only a limited amount of time before it engages in an early recombination intermediates (D-loop) with the sister chromatid. Time-based competition between TLS and HDGR is set by mere sequestration of the TLS substrates into early recombination intermediates. Most gaps are subsequently repaired by Homology Directed Gap Repair (HDGR), a pathway that involves RecA. Surprisingly, however, in the absence of RecA, some cells manage to divide and form colonies at the expense of losing the damage-containing chromatid.


Bacterial Exposure Mediates Developmental Plasticity and Resistance to Lethal Vibrio lentus Infection in Purple Sea Urchin (Strongylocentrotus purpuratus) Larvae.
Exposure to and colonization by bacteria during development have wide-ranging beneficial effects on animal biology but can also inhibit growth or cause disease. The immune system is the prime mediator of these microbial interactions and is itself shaped by them. Studies using diverse animal taxa have begun to elucidate the mechanisms underlying the acquisition and transmission of bacterial symbionts and their interactions with developing immune systems. Moreover, the contexts of these associations are often confounded by stark differences between "wild type" microbiota and the bacterial communities associated with animals raised in conventional or germ-free laboratories. In this study, we investigate the spatio-temporal kinetics of bacterial colonization and associated effects on growth and immune function in larvae of the purple sea urchin (Strongylocentrotus purpuratus) as a model for host-microbe interactions and immune system development. We also compare the host-associated microbiota of developing embryos and larvae raised in natural seawater or exposed to adult-associated bacteria in the laboratory. Bacteria associated with zygotes, embryos, and early larvae are detectable with 16S amplicon sequencing, but 16S-FISH indicates that the vast majority of larval bacterial load is acquired after feeding begins and is localized to the gut lumen. The bacterial communities of laboratory-cultured embryos are significantly less diverse than the natural microbiota but recapitulate its major components (Alphaproteobacteria, Gammaproteobacteria, and Bacteroidetes), suggesting that biologically relevant host-microbe interactions can be studied in the laboratory. We also demonstrate that bacterial exposure in early development induces changes in morphology and in the immune system. In the absence of bacteria, larvae grow larger at the 4-arm stage. Additionally, bacteria-exposed larvae are significantly more resistant to lethal infection with the larva-associated pathogen Vibrio lentus suggesting that early exposure to high levels of microbes, as would be expected in natural conditions, affects the immune state in later larvae. These results expand our knowledge of microbial influences on early sea urchin development and establish a model in which to study the interactions between the developing larval immune system and the acquisition of larval microbiota.


Photosynthesis: Temperate and Tropical Characteristics within a Single Grass Genus.
Leaves of two subgenera of Panicum differ in photosynthetic physiology and bundle sheath characteristics. Species of the subgenus Eupanicum, like other tropical grasses, had high phosphoenolpyruvate carboxylase (E.C.126.96.36.199) activity, had specialized chloroplasts within the parenchyma bundle sheath cells, and lacked phatorespiration. The pattern for the temperate subgenus Dichanthelium was opposite.


Therapeutic potential of pterostilbene against pancreatic beta-cell apoptosis mediated through Nrf2.
Nuclear factor erythroid 2-related factor 2 (Nrf2) is considered to be a 'master regulator' of the antioxidant response as it regulates the expression of several genes including phase II metabolic and antioxidant enzymes and thus plays an important role in preventing oxidative stress-mediated disorders, including diabetes. In this study, for the first time, we investigated the protective properties of a naturally available antioxidant, pterostilbene (PTS), against pancreatic beta-cell apoptosis and the involvement of Nrf2 in its mechanism of action. Immunoblotting and quantitative reverse transcriptase (qRT)-PCR analysis were performed to identify PTS-mediated nuclear translocation of Nrf2 protein and the following activation of target gene expression, respectively, in INS-1E cells. In addition, an annexin-V binding assay was carried out to identify the apoptotic status of PTS-treated INS-1E cells, while confirming the anti-apoptotic potential of Nrf2 by qRT-PCR analysis of the expressions of both pro- and anti-apoptotic genes. PTS induced significant activation of Nrf2, in dose- and time-dependent manner, in streptozotocin-treated INS-1E rat pancreatic beta-cells. Furthermore, PTS increased the expression of target genes downstream of Nrf2, such as heme oxygenase 1 (HO1), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), that confer cellular protection. PTS also up-regulated the expression of anti-apoptotic gene, Bcl-2, with a concomitant reduction in pro-apoptotic Bax and caspase-3 expression. Collectively, our findings indicate the therapeutic potential of Nrf2 activation by PTS as a promising approach to safeguard pancreatic beta-cells against oxidative damage in diabetes.


Providing Palliative Care in a Swedish Support Home for People Who Are Homeless.
Despite high frequencies of multiple, life-limiting conditions relating to palliative care needs, people who are homeless are one of the most underserved and rarely encountered groups in palliative care settings. Instead, they often die in care places where palliative competence is not available. In this qualitative single-case study, we explored the conditions and practices of palliative care from the perspective of staff at a Swedish support home for homeless people. Interpretive description guided the research process, and data were generated from repeated reflective conversations with staff in groups, individually, and in pairs. The findings disclose a person-centered approach to palliative care, grounded in the understanding of the person's health/illness and health literacy, and how this is related to and determinant on life as a homeless individual. Four patterns shape this approach: building trustful and family-like relationships, re-dignifying the person, re-considering communication about illness and dying, and re-defining flexible and pragmatic care solutions.


α1-Microglobulin Protects Against Bleeding-Induced Oxidative Damage in Knee Arthropathies.
Knee injury increases the risk of developing knee osteoarthritis (OA). Recent evidence suggests involvement of oxidative stress induced by inflammation and bleeding in the joint. This study investigates the role in this process of α1-microglobulin (A1M), a plasma and tissue antioxidant protein with reducing function, and heme- and radical-binding properties. We studied matched knee synovial fluid (sf) and serum (s) samples from 122 subjects (mean age 40 years, 31% females): 10 were knee healthy references, 13 had acute inflammatory arthritis (AIA), 79 knee injury 0-10 years prior to sampling, and 20 knee OA. Using immunoassays, we measured sf-A1M and s-A1M, sf-hemoglobin (sf-Hb), sf-total free heme (sf-Heme), and sf-carbonyl groups (sf-Carbonyl). We explored associations by partial correlation, or linear regression models with adjustments for age, sex and diagnosis, and evaluated diagnostic capacity by area under the receiver operator characteristics curve (AUC). The AIA group had 1.2- to 1.7-fold higher sf-A1M and s-A1M concentrations compared to the other diagnostic groups; other biomarkers showed no between-group differences. sf-A1M and s-A1M were with AUC of 0.76 and 0.78, respectively, diagnostic for AIA. In the injury group, the amount of bleeding in the joint was inversely correlated to time after injury when measured as sf-Heme (r = -0.41, p < 0.001), but not when measured as sf-Hb (r = -0.19, p = 0.098). A similar inverse association with time after injury was noted for sf-A1M (r = -0.30, p = 0.007), but not for s-A1M and sf-Carbonyl. Linear regression models showed that sf-Heme was more strongly associated with sf-A1M and sf-Carbonyl than sf-Hb. Independent of diagnosis, sf-Heme explained 5.7% of the variability in sf-A1M and 3.0% in the variability in sf-Carbonyl, but appeared unrelated to s-A1M. High sf-A1M and low sf-Heme or sf-Hb were independently associated with low sf-Carbonyl. In conclusion, our results demonstrate that independent of disease, Hb and heme within a knee joint correlates with an increased sf-A1M concentration that appears to be protective of oxidative damage, i.e., a reduction in carbonyl groups. High concentrations of A1M in synovial fluid and serum was further diagnostic for AIA.


Inframammary crease ligament.
This study was designed to clarify and define the anatomic components of the inframammary crease in the female breast. Thirteen blunt dissections of the female breast were performed in cadavers and one dissection was performed in a living patient undergoing mastectomy. During the course of these dissections, a ligament was identified. This ligament originates from the fifth rib periosteum medially and the fascia between the fifth and sixth ribs laterally. The ligament inserts distally into the deep dermis of the inframammary skin fold. Histologic sections confirmed the proximal bony origin of this structure. In three cadavers, the contralateral breast was studied as it pertains to transaxillary subpectoral mammaplasty using the Agis-Dingman dissector (Padgett Instruments, Kansas City, Mo.). If too forceful a sweep were made in the inferior portion of the dissection, the ligament would be disrupted. This separation of the ligament from its origin could lead to the "double-bubble" phenomenon. Further, the horizontal position of this ligament determines the medial versus lateral fall of the ptotic breast.


Block of A1 astrocyte conversion by microglia is neuroprotective in models of Parkinson's disease.
Activation of microglia by classical inflammatory mediators can convert astrocytes into a neurotoxic A1 phenotype in a variety of neurological diseases1,2. Development of agents that could inhibit the formation of A1 reactive astrocytes could be used to treat these diseases for which there are no disease-modifying therapies. Glucagon-like peptide-1 receptor (GLP1R) agonists have been indicated as potential neuroprotective agents for neurologic disorders such as Alzheimer's disease and Parkinson's disease3-13. The mechanisms by which GLP1R agonists are neuroprotective are not known. Here we show that a potent, brain-penetrant long-acting GLP1R agonist, NLY01, protects against the loss of dopaminergic neurons and behavioral deficits in the α-synuclein preformed fibril (α-syn PFF) mouse model of sporadic Parkinson's disease14,15. NLY01 also prolongs the life and reduces the behavioral deficits and neuropathological abnormalities in the human A53T α-synuclein (hA53T) transgenic mouse model of α-synucleinopathy-induced neurodegeneration16. We found that NLY01 is a potent GLP1R agonist with favorable properties that is neuroprotective through the direct prevention of microglial-mediated conversion of astrocytes to an A1 neurotoxic phenotype. In light of its favorable properties, NLY01 should be evaluated in the treatment of Parkinson's disease and related neurologic disorders characterized by microglial activation.


Mechanochemical and solvent-free assembly of zirconium-based metal-organic frameworks.
We develop the first mechanochemical and solvent-free routes for zirconium metal-organic frameworks, making the frameworks UiO-66 and UiO-66-NH2 accessible on the gram scale without strong acids, high temperatures or excess reactants. The frameworks form either by milling, or spontaneous self-assembly by simply exposing solid mixtures of reactants to organic vapour. The generated frameworks exhibit high porosity and catalytic activity in the hydrolysis of model nerve agents, on par with their solvothermally generated counterparts.


Validation of a population pharmacokinetic model of adalimumab in a cohort of patients with inflammatory bowel disease.
therapeutic monitoring of anti-TNF drugs and anti-drug antibody levels are useful for clinical decision-making, via the rationalization and optimization of the use of anti-TNF treatments. The objective of the present study was to validate the model of Ternant et al., in a cohort of patients with inflammatory bowel diseases (IBD). This model was originally established for patients with rheumatoid arthritis and was used in this study to optimize the adalimumab (ADA) dose and predict ADA trough levels (ATL). this study used concentration data points from 30 IBD patients who received ADA treatment between 2014 and 2015. A goodness-of-fit of the model was determined by evaluating the relationship between the observed ATL values and population model-predicted values (PRED) or individual model-predicted values (IPRED). a total of 51 ADA concentration points were analyzed. The bias of the model was 2.39 (95% CI, 1.63-3.15) for PRED and 0.63 (95% CI, 0.23-1.03) for IPRED. The precision was 3.57 (95% CI, 2.90-4.13) and 1.53 (95% CI, 1.22-1.80), respectively. therapeutic drug monitoring involving ATL may allow the optimization of the treatment of IBD patients. The validation results of the phamacokinectic (PK) model for ADA in IBD patients are inadequate. However, additional studies will strengthen the bias and precision of the model.


Structural Basis for the Limited Response to Oxidative and Thiol-Conjugating Agents by Triosephosphate Isomerase From the Photosynthetic Bacteria Synechocystis.
In plants, the ancestral cyanobacterial triosephosphate isomerase (TPI) was replaced by a duplicated version of the cytosolic TPI. This isoform acquired a transit peptide for chloroplast localization and functions in the Calvin-Benson cycle. To gain insight into the reasons for this gene replacement in plants, we characterized the TPI from the photosynthetic bacteria Synechocystis (SyTPI). SyTPI presents typical TPI enzyme kinetics profiles and assembles as a homodimer composed of two subunits that arrange in a (β-α)8 fold. We found that oxidizing agents diamide (DA) and H2O2, as well as thiol-conjugating agents such as oxidized glutathione (GSSG) and methyl methanethiosulfonate (MMTS), do not inhibit the catalytic activity of SyTPI at concentrations required to inactivate plastidic and cytosolic TPIs from the plant model Arabidopsis thaliana (AtpdTPI and AtcTPI, respectively). The crystal structure of SyTPI revealed that each monomer contains three cysteines, C47, C127, and C176; however only the thiol group of C176 is solvent exposed. While AtcTPI and AtpdTPI are redox-regulated by chemical modifications of their accessible and reactive cysteines, we found that C176 of SyTPI is not sensitive to redox modification in vitro. Our data let us postulate that SyTPI was replaced by a eukaryotic TPI, because the latter contains redox-sensitive cysteines that may be subject to post-translational modifications required for modulating TPI's enzymatic activity.


Climate-phenology-hydrology interactions in northern high latitudes: Assessing the value of remote sensing data in catchment ecohydrological studies.
We assessed the hydrological implications of climate effects on vegetation phenology in northern environments by fusion of data from remote-sensing and local catchment monitoring. Studies using satellite data have shown earlier and later dates for the start (SOS) and end of growing seasons (EOS), respectively, in the Northern Hemisphere over the last 3 decades. However, estimates of the change greatly depend on the satellite data utilized. Validation with experimental data on climate-vegetation-hydrology interactions requires long-term observations of multiple variables which are rare and usually restricted to small catchments. In this study, we used two NDVI (normalized difference vegetation index) products (at ~25 & 0.5 km spatial resolutions) to infer SOS and EOS for six northern catchments, and then investigated the likely climate impacts on phenology change and consequent effects on catchment water yield, using both assimilated data (GLDAS: global land data assimilation system) and direct catchment observations. The major findings are: (1) The assimilated air temperature compared well with catchment observations (regression slopes and R2 close to 1), whereas underestimations of summer rainstorms resulted in overall underestimations of precipitation (regression slopes of 0.3-0.7, R2 ≥ 0.46). (2) The two NDVI products inferred different vegetation phenology characteristics. (3) Increased mean pre-season temperature significantly influenced the advance of SOS and delay of EOS. The precipitation influence was weaker, but delayed SOS corresponding to increased pre-season precipitation at most sites can be related to later snow melting. (4) Decreased catchment streamflow over the last 15 years could be related to the advance in SOS and extension of growing seasons. Greater streamflow reductions in the cold sites than the warm ones imply stronger climate warming impacts on vegetation and hydrology in colder northerly environments. The methods used in this study have potential for better understanding interactions between vegetation, climate and hydrology in observation-scarce regions.


Toward Shared Working Space of Human and Robotic Agents Through Dipole Flow Field for Dependable Path Planning.
Recent industrial developments in autonomous systems, or agents, which assume that humans and the agents share the same space or even work in close proximity, open for new challenges in robotics, especially in motion planning and control. In these settings, the control system should be able to provide these agents a reliable path following control when they are working in a group or in collaboration with one or several humans in complex and dynamic environments. In such scenarios, these agents are not only moving to reach their goals, i.e., locations, they are also aware of the movements of other entities to find a collision-free path. Thus, this paper proposes a dependable, i.e., safe, reliable and effective, path planning algorithm for a group of agents that share their working space with humans. Firstly, the method employs the Theta* algorithm to initialize the paths from a starting point to a goal for a set of agents. As Theta* algorithm is computationally heavy, it only reruns when there is a significant change of the environment. To deal with the movements of the agents, a static flow field along the configured path is defined. This field is used by the agents to navigate and reach their goals even if the planned trajectories are changed. Secondly, a dipole field is calculated to avoid the collision of agents with other agents and human subjects. In this approach, each agent is assumed to be a source of a magnetic dipole field in which the magnetic moment is aligned with the moving direction of the agent. The magnetic dipole-dipole interactions between these agents generate repulsive forces to help them to avoid collision. The effectiveness of the proposed approach has been evaluated with extensive simulations. The results show that the static flow field is able to drive agents to the goals with a small number of requirements to update the path of agents. Meanwhile, the dipole flow field plays an important role to prevent collisions. The combination of these two fields results in a safe path planning algorithm, with a deterministic outcome, to navigate agents to their desired goals.


Barriers and facilitators with medication use during the transition from hospital to home: a qualitative study among patients.
During transitions from hospital to home, up to half of all patients experience medication-related problems, such as adverse drug events. To reduce these problems, knowledge of patient experiences with medication use during this transition is needed. This study aims to identify the perspectives of patients on barriers and facilitators with medication use, during the transition from hospital to home. A qualitative study was conducted in 2017 among patients discharged from two hospitals using a semi-structured interview guide. Patients were asked to identify all barriers they experienced with medication use during transitions from hospital to home, and facilitators needed to overcome those barriers. Data were analyzed following thematic content analysis and visualized using an "Ishikawa" diagram. In total, three focus groups were conducted with 19 patients (mean age: 70.8 (SD 9.3) years, 63% female). Three barriers were identified; lack of personalized care in the care continuum, insufficient information transfer (e.g. regarding changes in pharmacotherapy), and problems in care organization (e.g. medication substitution). Facilitators to overcome these barriers included a personal medication-counselor in the care continuum to guide patients with medication use and overcome communication barriers, and post-discharge follow-up care (e.g. home visits from healthcare providers). During transitions from hospital to home patients experience individual-, healthcare provider- and organization level barriers. Future research should focus on personal-medication counselors in the care continuum and post-discharge follow-up care as it may overcome communication, emotional, information and organization barriers with medication use.