Does the technique employed for skin temperature assessment alter outcomes? A systematic review.
Skin temperature is an important physiological measure that can reflect the presence of illness and injury as well as provide insight into the localised interactions between the body and the environment. The aim of this systematic review was to analyse the agreement between conductive and infrared means of assessing skin temperature which are commonly employed in in clinical, occupational, sports medicine, public health and research settings.Full-text eligibility was determined independently by two reviewers. Studies meeting the following criteria were included in the review: (1) the literature was written in English, (2) participants were human (in vivo), (3) skin surface temperature was assessed at the same site, (4) with at least two commercially available devices employed-one conductive and one infrared-and (5) had skin temperature data reported in the study.A computerised search of four electronic databases, using a combination of 21 keywords, and citation tracking was performed in January 2015. A total of 8,602 were returned.Methodology quality was assessed by two authors independently, using the Cochrane risk of bias tool.A total of 16 articles (n = 245) met the inclusion criteria.Devices are classified to be in agreement if they met the clinically meaningful recommendations of mean differences within ±0.5 °C and limits of agreement of ±1.0 °C.Twelve of the included studies found mean differences greater than ±0.5 °C between conductive and infrared devices. In the presence of external stimulus (e.g. exercise and/or heat) five studies found exacerbated measurement differences between conductive and infrared devices.This is the first review that has attempted to investigate presence of any systemic bias between infrared and conductive measures by collectively evaluating the current evidence base. There was also a consistently high risk of bias across the studies, in terms of sample size, random sequence generation, allocation concealment, blinding and incomplete outcome data.This systematic review questions the suitability of using infrared cameras in stable, resting, laboratory conditions. Furthermore, both infrared cameras and thermometers in the presence of sweat and environmental heat demonstrate poor agreement when compared to conductive devices. These findings have implications for clinical, occupational, public health, sports science and research fields.


The influence of culture, structure, and human agency on interprofessional learning in a neurosurgical practice learning setting: a case study.
The World Health Organization supports the notion that interprofessional learning (IPL) improves healthcare outcomes and contributes to safe, effective, and high-quality care. Consequently, IPL is an integral component within most UK undergraduate healthcare programs. Although much is written about IPL, research to date has mainly focused on the classroom or simulation lab as a setting for IPL. Less is known about how the practice learning environment influences the experiences and outcomes for those involved. A case study research design, situated within a critical realist framework, was undertaken which aimed to better understand how IPL was facilitated for undergraduate healthcare students within a neurosurgical practice learning setting. Interviews, non-participatory observations, and secondary documentary data were used as the methods of data collection to inform the case. Thematic analysis was undertaken, and the findings clustered into overarching themes of culture, structure, and human agency, facilitating a more in-depth exploration of the complex interplay between the factors influencing IPL in the study setting. IPL was supported within the setting which operated as an 'interprofessional community of practice,' facilitating student engagement and investing in its staff for the benefit of the patients who had complex neurological needs. A practice-based IPL Multi-Dimensional Assessment Tool was also created to enable colleagues in practice learning environments worldwide to better understand their capability and capacity for the facilitation of practice-based IPL.


Cellular uptake of aminoglycosides, guanidinoglycosides, and poly-arginine.
Aminoglycosides (including neomycin B and tobramycin) exhibit poor uptake by eukaryotic cell lines. When the amines of these natural products are converted into guanidine groups, their cellular uptake is dramatically enhanced. We have synthesized BODIPY-containing aminoglycosides and guanidinoglycosides to evaluate their cellular uptake properties. Fluorescence activated cell sorting (FACS) and fluorescence microscopy are used to compare the membrane translocation and the cellular localization of these compounds. Upon guanidinylation, the cellular uptake efficiencies of tobramycin and neomycin B are enhanced by 10-fold and 20-fold, respectively. Guanidino-neomycin B exhibits a highly efficient uptake, superior to a fluorescent poly-arginine peptide. Interestingly, the cellular uptake of this common transduction peptide is inhibited by guanidine-neomycin B, suggesting a similar uptake mechanism for both the arginine-rich peptides and the guanidinoglycosides.


Reducing the risk of adverse drug events in older adults.
Adverse drug events occur in 15 percent or more of older patients presenting to offices, hospitals, and extended care facilities. These events are potentially preventable up to 50 percent of the time. Common serious manifestations include falls, orthostatic hypotension, heart failure, and delirium. The most common causes of death are gastrointestinal or intracranial bleeding and renal failure. Antithrombotic and antidiabetic medications, diuretics, and nonsteroidal anti-inflammatory drugs cause most of the preventable hospital admissions due to adverse drug events. Strategies to reduce the risk of adverse drug events include discontinuing medications, prescribing new medications sparingly, reducing the number of prescribers, and frequently reconciling medications. The Beers, STOPP (screening tool of older persons' potentially inappropriate prescriptions), and START (screening tool to alert doctors to right treatment) criteria can help identify medications causing adverse drug events. Not all potentially inappropriate medications can be avoided. Clinicians should involve patients in shared decision making and individualize prescribing decisions based on medical, functional, and social conditions; quality of life; and prognosis.


Vitamin B(12) and folate in relation to the development of Alzheimer's disease.
To explore the associations of low serum levels of vitamin B(12) and folate with AD occurrence. A population-based longitudinal study in Sweden, the Kungsholmen A random sample of 370 nondemented persons, aged 75 years and older and not treated with B(12) and folate, was followed for 3 years to detect incident AD cases. Two cut-off points were used to define low levels of vitamin B(12) (< or =150 and < or =250 pmol/L) and folate (< or =10 and < or =12 nmol/L), and all analyses were performed using both definitions. AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria. When using B(12) < or =150 pmol/L and folate < or =10 nmol/L to define low levels, compared with people with normal levels of both vitamins, subjects with low levels of B(12) or folate had twice higher risks of developing AD (relative risk [RR] = 2.1, 95% CI = 1.2 to 3.5). These associations were even stronger in subjects with good baseline cognition (RR = 3.1, 95% CI = 1.1 to 8.4). Similar relative risks of AD were found in subjects with low levels of B(12) or folate and among those with both vitamins at low levels. A comparable pattern was detected when low vitamin levels were defined as B(12) < or =250 pmol/L and folate < or =12 nmol/L. This study suggests that vitamin B(12) and folate may be involved in the development of AD. A clear association was detected only when both vitamins were taken into account, especially among the cognitively intact subjects. No interaction was found between the two vitamins. Monitoring serum B(12) and folate concentration in the elderly may be relevant for prevention of AD.


Human immunodeficiency virus 1 downregulates cell surface expression of the non-classical major histocompatibility class I molecule HLA-G1.
Human immunodeficiency virus 1 (HIV-1) downregulates cell surface expression of HLA-A and HLA-B but not HLA-C or HLA-E to ultimately escape immune defences. Here, it is shown that cell surface expression of the non-classical HLA-G1 is also downregulated by HIV-1, by using co-transfection experiments and infection with cell-free HIV-1 of HLA-G1-expressing U87 glioma cells or macrophages in primary culture. Moreover, co-transfection experiments using proviruses deleted in either nef or vpu or plasmids encoding HIV-1 Nef and Vpu mixed together with a HLA-G1-expressing construct demonstrated that HLA-G1 downregulation is Nef-independent and Vpu-dependent, contrasting with the Nef- and Vpu-dependent HLA-A2 downregulation. Together, these results show that the decrease of HLA-A2 and HLA-G1 caused by HIV-1 occurs through distinct mechanisms.


Chondrogenitor cells and gene therapy.
The development of isolation and culture techniques for mesenchymal progenitor cells from various tissues has promoted interest in the use of these cells for repair and regeneration of musculoskeletal tissues. The chondrogenic differentiation of these pluripotential cells seems to be mediated by numerous cytokines most of which belong to the transforming growth factor-beta superfamily. Strategies to repair articular cartilage have focused on delivery of these cytokines or progenitor cells to the area of damage. More recently, with the development of gene transfer techniques, these cells have become the target of in vivo gene therapy, which involves direct injection of viral and nonviral vectors carrying transgenes. Furthermore, they are viewed as potential carriers of the transgenes for ex vivo gene therapy, in which the gene transfer is done in vitro with culture-expanded cells that then are implanted or injected. In vitro data suggest that the chondrogenic potential of these cells is maintained with virally mediated ex vivo gene transfer. By transducing these cells with chondroinductive factors, the bioactive factors and the target cells are delivered to the repair site.


Analyzing proteasomal subunit expression reveals Rpt4 as a prognostic marker in stage II colorectal cancer.
Colorectal cancer is a leading cause of cancer-related deaths worldwide. Early diagnosis and treatment of colorectal cancer is the key to improving survival rates and as such a need exists to identify patients who may benefit from adjuvant chemotherapy. The dysregulation of the ubiquitin-proteasome system (UPS) has been implicated in oncogenesis and cancer cell survival, and proteasome inhibitors are in clinical use for a number of malignancies including multiple myeloma. In our study, we examined the protein expression of several key components of the UPS in colorectal cancer using immunohistochemistry to determine expression levels of ubiquitinylated proteins and the proteasomal subunits, 20S core and Rpt4 in a cohort of 228 patients with colon cancer. Multivariate Cox analysis revealed that neither the intensity of either ubiquitinylated proteins or the 20S core was predictive in either Stage II or III colon cancer for disease free survival or overall survival. In contrast, in Stage II patients increased Rpt4 staining was significantly associated with disease free survival (Cox proportional hazard ratio 0.605; p = 0.0217). Our data suggest that Rpt4 is an independent prognostic variable for Stage II colorectal cancer and may aid in the decision of which patients undergo adjuvant chemotherapy.


The neural selection and integration of actions and objects: an fMRI study.
There is considerable evidence that there are anatomically and functionally distinct pathways for action and object recognition. However, little is known about how information about action and objects is integrated. This study provides fMRI evidence for task-based selection of brain regions associated with action and object processing, and on how the congruency between the action and the object modulates neural response. Participants viewed videos of objects used in congruent or incongruent actions and attended either to the action or the object in a one-back procedure. Attending to the action led to increased responses in a fronto-parietal action-associated network. Attending to the object activated regions within a fronto-inferior temporal network. Stronger responses for congruent action-object clips occurred in bilateral parietal, inferior temporal, and putamen. Distinct cortical and thalamic regions were modulated by congruency in the different tasks. The results suggest that (i) selective attention to action and object information is mediated through separate networks, (ii) object-action congruency evokes responses in action planning regions, and (iii) the selective activation of nuclei within the thalamus provides a mechanism to integrate task goals in relation to the congruency of the perceptual information presented to the observer.


Effect of hormone therapy and calcitriol on serum lipid profile in postmenopausal older women: association with estrogen receptor-α genotypes.
The aim of this study was to examine the effect of conjugated equine estrogens alone (ET), conjugated equine estrogens + medroxyprogesterone (EPT), calcitriol alone, calcitriol + EPT/ET, or placebo on serum lipid profile and analyze the interaction with estrogen receptor-α gene single nucleotide polymorphisms (ESR-α SNPs) on the response to therapy. A total of 489 postmenopausal women older than 65 years were enrolled into a 3-year double-blind, placebo-controlled clinical trial. In both intent-to-treat and complier (>80% adherent) analysis, there was a significant increase in serum high-density lipoproteins and a significant decrease in serum low-density lipoproteins (LDLs) and the LDL/high-density lipoprotein ratio in all hormone treatment groups compared with placebo (P < 0.05). However, serum triglycerides and very low-density lipoproteins increased in the EPT and ET + calcitriol groups versus placebo (P < 0.05). ESR-α SNPs PvuII and XbaI seemed to have a significant effect on the response to treatment. Genotypes containing the p allele showed a significantly greater decrease in serum cholesterol and very low-density lipoprotein than those having the P allele in the ET + calcitriol group (P < 0.05), and those with the x allele had a significantly greater decrease in serum cholesterol in the hormone therapy + calcitriol group at the end of 3 years versus the X allele, and a greater decrease in serum LDL in alleles x versus the X in the ET + calcitriol group (P < 0.05). ET with or without progesterone had a favorable effect on lipid profile in postmenopausal older women, and this was dependent on estrogen receptor SNPs--PvuII and XbaI. However, this interaction with ESR-α SNPs needs to be confirmed in larger studies.


Using a bacterial fucose-rich polysaccharide as encapsulation material of bioactive compounds.
The potential of a bacterial exopolysaccharide named FucoPol, produced by the bacterium Enterobacter A47, as encapsulation matrix was explored. Spherical capsules with a smooth surface were produced by spray drying. The obtained microcapsules had average diameters ranging from 0.5 to 26.7μm and presented thin walls (thickness from 222 to 1094nm). The capsules were loaded with two bioactive compounds: gallic acid (GA) and oregano essential oil (OEO). Both bioactive materials were encapsulated in FucoPol particles, retaining their antioxidant activity after the drying process. Release studies showed that GA release in simulated gastric and intestinal fluids was faster than that of OEO, envisaging that the latter had established stronger interactions with the polymer matrix. These results suggest that FucoPol has a good potential for use as encapsulating material of bioactive compounds for application in several areas, including food, cosmetic or pharmaceutical products.


A two-year follow-up study of cotransplantation with neural stem/progenitor cells and mesenchymal stromal cells in ischemic stroke patients.
Stem cell therapy is an emerging therapeutic modality in the treatment of stroke. We assessed the safety and feasibility of the cotransplantation of neural stem/progenitor cells (NSPCs) and mesenchymal stromal cells (MSCs) in patients with ischemic stroke. Eight patients were enrolled in this study. All patients had a hemisphere with infarct lesions located on one side of the territories of the cerebral middle or anterior arteries as revealed with cranial magnetic resonance imaging (MRI). The patients received one of the following two types of treatment: the first treatment involved four intravenous injections of MSCs at 0.5 × 10(6)/kg body weight; the second treatment involved one intravenous injection of MSCs at 0.5 × 10(6)/kg weight followed by three injections of MSCs at 5 × 10(6)/patient and NSPCs at 6 × 10(6)/patient through the cerebellomedullary cistern. The patients' clinical statuses were evaluated with the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel index (BI). Six patients were given four cell transplantations. The most common side effect of stem cell transplantation in these six cases was low fever that usually lasted 2-4 days after each therapy. One patient exhibited minor dizziness. All side effects appeared within the first 2-24 h of cell transplantation, and they resolved without special treatment. There was no evidence of neurological deterioration or neurological infection. Most importantly, no tumorigenesis was found at a 2-year follow-up. The neurological functions, disability levels, and daily living abilities of the patients in this study were improved. While these observations support the use of the combination transplantation of NSPCs and MSCs as a safe and feasible method of improving neurological function, further studies that include larger samples, longer follow-ups, and control groups are still needed. This manuscript is published as part of the International Association of Neurorestoratology (IANR) special issue of Cell Transplantation.


Factors contributing to epidemic MRSA clones replacement in a hospital setting.
The mechanisms governing the epidemiology dynamics and success determinants of a specific healthcare-associated methicillin-resistant S. aureus (HA-MRSA) clone in hospital settings are still unclear. Important epidemiological changes have occurred in Europe since 2000 that have been related to the appearance of the ST22-IV clone. Between 2006 and 2010, we observed the establishment of the ST22-IV clone displacing the predominant Italian clone, ST228-I, in a large Italian university hospital. To investigate the factors associated with a successful spread of epidemic MRSA clones we studied the biofilm production, the competitive behavior in co-culture, the capacity of invasion of the A549 cells, and the susceptibility to infection in a murine model of acute pneumonia of the two major HA-MRSA clones, ST22-IV and ST228-I. We showed that persistence of ST22-IV is associated with its increased biofilm production and capacity to inhibit the growth of ST228-I in co-culture. Compared to ST228-I, ST22-IV had a significantly higher capacity to invade the A549 cells and a higher virulence in a murine model of acute lung infection causing severe inflammation and determining death in all the mice within 60 hours. On the contrary, ST228-I was associated with mice survival and clearance of the infection. ST22-IV, compared with ST228-I, caused a higher number of persistent, long lasting bacteremia. These data suggest that ST22-IV could have exploited its capacity to i) increase its biofilm production over time, ii) maintain its growth kinetics in the presence of a competitor and iii) be particularly invasive and virulent both in vitro and in vivo, to replace other well-established MRSA clones, becoming the predominant European clone.


HIV-1 Tat Inhibits Autotaxin Lysophospholipase D Activity and Modulates Oligodendrocyte Differentiation.
White matter injury has been frequently reported in HIV+ patients. Previous studies showed that HIV-1 Tat (transactivator of transcription), a viral protein that is produced and secreted by HIV-infected cells, is toxic to young, immature oligodendrocytes (OLGs). Adding Tat to the culture medium reduced the viability of immature OLGs, and the surviving OLGs exhibited reduced process networks. OLGs produce and secrete autotaxin (ATX), an ecto-enzyme containing a lysophospholipase D (lysoPLD) activity that converts lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a lipid signaling molecule that stimulates OLG differentiation. We hypothesized that Tat affects OLG development by interfering with the ATX-LPA signaling pathway. Our data show that Tat treatment leads to changes in the expression of OLG differentiation genes and the area of OLG process networks, both of which can be rescued by LPA. Tat-treated OLGs showed no change in LPA receptor expression but significantly decreased extracellular ATX levels and lysoPLD activity. In Tat transgenic mice, expression of Tat in vivo leads to decreased OLG ATX secretion. Furthermore, co-immunoprecipitation experiments revealed a potential physical interaction between Tat and ATX. Together, these data strongly suggest two functional implications of Tat blocking ATX's lysoPLD activity. On one hand, it attenuates OLG differentiation, and on the other hand it interferes with the protective effects of LPA on OLG process morphology.


Inositols: From Established Knowledge to Novel Approaches.
Myo-inositol (myo-Ins) and D-chiro-inositol (D-chiro-Ins) are natural compounds involved in many biological pathways. Since the discovery of their involvement in endocrine signal transduction, myo-Ins and D-chiro-Ins supplementation has contributed to clinical approaches in ameliorating many gynecological and endocrinological diseases. Currently both myo-Ins and D-chiro-Ins are well-tolerated, effective alternative candidates to the classical insulin sensitizers, and are useful treatments in preventing and treating metabolic and reproductive disorders such as polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and male fertility disturbances, like sperm abnormalities. Moreover, besides metabolic activity, myo-Ins and D-chiro-Ins deeply influence steroidogenesis, regulating the pools of androgens and estrogens, likely in opposite ways. Given the complexity of inositol-related mechanisms of action, many of their beneficial effects are still under scrutiny. Therefore, continuing research aims to discover new emerging roles and mechanisms that can allow clinicians to tailor inositol therapy and to use it in other medical areas, hitherto unexplored. The present paper outlines the established evidence on inositols and updates on recent research, namely concerning D-chiro-Ins involvement into steroidogenesis. In particular, D-chiro-Ins mediates insulin-induced testosterone biosynthesis from ovarian thecal cells and directly affects synthesis of estrogens by modulating the expression of the aromatase enzyme. Ovaries, as well as other organs and tissues, are characterized by a specific ratio of myo-Ins to D-chiro-Ins, which ensures their healthy state and proper functionality. Altered inositol ratios may account for pathological conditions, causing an imbalance in sex hormones. Such situations usually occur in association with medical conditions, such as PCOS, or as a consequence of some pharmacological treatments. Based on the physiological role of inositols and the pathological implications of altered myo-Ins to D-chiro-Ins ratios, inositol therapy may be designed with two different aims: (1) restoring the inositol physiological ratio; (2) altering the ratio in a controlled way to achieve specific effects.


Diabetes Outpatient Care and Acute Complications Before and After High-Deductible Insurance Enrollment: A Natural Experiment for Translation in Diabetes (NEXT-D) Study.
High-deductible health plans (HDHPs) have expanded under the Affordable Care Act and are expected to play a major role in the future of US health policy. The effects of modern HDHPs on chronically ill patients and adverse outcomes are unknown. To determine the association of HDHP with high-priority diabetes outpatient care and preventable acute complications. Controlled interrupted-time-series study using a large national health insurer database from January 1, 2003, to December 31, 2012. A total of 12 084 HDHP members with diabetes, aged 12 to 64 years, who were enrolled for 1 year in a low-deductible (≤$500) plan followed by 2 years in an HDHP (≥$1000) after an employer-mandated switch were included. Patients transitioning to HDHPs were propensity-score matched with contemporaneous patients whose employers offered only low-deductible coverage. Low-income (n = 4121) and health savings account (HSA)-eligible (n = 1899) patients with diabetes were subgroups of interest. Data analysis was performed from February 23, 2015, to September 11, 2016. Employer-mandated HDHP transition. High-priority outpatient visits, disease monitoring tests, and outpatient and emergency department visits for preventable acute diabetes complications. In the 12 084 HDHP members included after the propensity score match, the mean (SD) age was 50.4 (10.0) years; 5410 of the group (44.8%) were women. The overall, low-income, and HSA-eligible diabetes HDHP groups experienced increases in out-of-pocket medical expenditures of 49.4% (95% CI, 40.3% to 58.4%), 51.7% (95% CI, 38.6% to 64.7%), and 67.8% (95% CI, 47.9% to 87.8%), respectively, compared with controls in the year after transitioning to HDHPs. High-priority primary care visits and disease monitoring tests did not change significantly in the overall HDHP cohort; however, high-priority specialist visits declined by 5.5% (95% CI, -9.6% to -1.5%) in follow-up year 1 and 7.1% (95% CI, -11.5% to -2.7%) in follow-up year 2 vs baseline. Outpatient acute diabetes complication visits were delayed in the overall and low-income HDHP cohorts at follow-up (adjusted hazard ratios, 0.94 [95% CI, 0.88 to 0.99] for the overall cohort and 0.89 [95% CI, 0.81 to 0.98] for the low-income cohort). Annual emergency department acute complication visits among HDHP members increased by 8.0% (95% CI, 4.6% to 11.4%) in the overall group, 21.7% (95% CI, 14.5% to 28.9%) in the low-income group, and 15.5% (95% CI, 10.5% to 20.6%) in the HSA-eligible group. Patients with diabetes experienced minimal changes in outpatient visits and disease monitoring after an HDHP switch, but low-income and HSA-eligible HDHP members experienced major increases in emergency department visits for preventable acute diabetes complications.


Stream specificity and asymmetries in feature binding and content-addressable access in visual encoding and memory.
Human memory is content addressable-i.e., contents of the memory can be accessed using partial information about the bound features of a stored item. In this study, we used a cross-feature cuing technique to examine how the human visual system encodes, binds, and retains information about multiple stimulus features within a set of moving objects. We sought to characterize the roles of three different features (position, color, and direction of motion, the latter two of which are processed preferentially within the ventral and dorsal visual streams, respectively) in the construction and maintenance of object representations. We investigated the extent to which these features are bound together across the following processing stages: during stimulus encoding, sensory (iconic) memory, and visual short-term memory. Whereas all features examined here can serve as cues for addressing content, their effectiveness shows asymmetries and varies according to cue-report pairings and the stage of information processing and storage. Position-based indexing theories predict that position should be more effective as a cue compared to other features. While we found a privileged role for position as a cue at the stimulus-encoding stage, position was not the privileged cue at the sensory and visual short-term memory stages. Instead, the pattern that emerged from our findings is one that mirrors the parallel processing streams in the visual system. This stream-specific binding and cuing effectiveness manifests itself in all three stages of information processing examined here. Finally, we find that the Leaky Flask model proposed in our previous study is applicable to all three features.


Diffuse Lewy body disease: clinical features in nine cases without coexistent Alzheimer's disease.
To further elucidate the relation between diffuse Lewy body disease and Parkinson's disease. The clinical features of nine cases of pure diffuse Lewy body disease without pathological evidence of coexisting Alzheimer's neuritic pathology were reported. All patients were aged less than 70 years at onset (mean 62 years). Five patients presented with clinical features, which included assymetric resting tremor had levodopa responsiveness, which were initially indistinguishable from idiopathic Parkinson's disease. All five patients later became demented (mean of three years after presentation). Two further patients presented with parkinsonism and dementia and two patients presented with dementia and developed parkinsonism at a later stage. Hallucinations appeared 2.5-9 years after the onset of symptoms in six patients and were a presenting feature in one patient. All patients met the pathological criteria of idiopathic Parkinson's disease, with respect to the midbrain changes, in addition to having diffuse cortical Lewy bodies. Diffuse Lewy body disease may present a parkinsonism, dementia, or both depending on whether the Lewy body pathology begins in the midbrain, the cortex, or both together. When it begins in the midbrain, diffuse Lewy body disease is indistinguishable initially from idiopathic Parkinson's disease. Diffuse Lewy body disease may be a common cause of dementia complicating Parkinson's disease.


Linkages between stratospheric ozone, UV radiation and climate change and their implications for terrestrial ecosystems.
Exposure of plants and animals to ultraviolet-B radiation (UV-B; 280-315 nm) is modified by stratospheric ozone dynamics and climate change. Even though stabilisation and projected recovery of stratospheric ozone is expected to curtail future increases in UV-B radiation at the Earth's surface, on-going changes in climate are increasingly exposing plants and animals to novel combinations of UV-B radiation and other climate change factors (e.g., ultraviolet-A and visible radiation, water availability, temperature and elevated carbon dioxide). Climate change is also shifting vegetation cover, geographic ranges of species, and seasonal timing of development, which further modifies exposure to UV-B radiation. Since our last assessment, there has been increased understanding of the underlying mechanisms by which plants perceive UV-B radiation, eliciting changes in growth, development and tolerances of abiotic and biotic factors. However, major questions remain on how UV-B radiation is interacting with other climate change factors to modify the production and quality of crops, as well as important ecosystem processes such as plant and animal competition, pest-pathogen interactions, and the decomposition of dead plant matter (litter). In addition, stratospheric ozone depletion is directly contributing to climate change in the southern hemisphere, such that terrestrial ecosystems in this region are being exposed to altered patterns of precipitation, temperature and fire regimes as well as UV-B radiation. These ozone-driven changes in climate have been implicated in both increases and reductions in the growth, survival and reproduction of plants and animals in Antarctica, South America and New Zealand. In this assessment, we summarise advances in our knowledge of these and other linkages and effects, and identify uncertainties and knowledge gaps that limit our ability to fully evaluate the ecological consequences of these environmental changes on terrestrial ecosystems.


Use of a decision aid to help caregivers discuss terminal disease status with a family member with cancer: a randomized controlled trial.
We tested whether a decision aid explaining how to discuss the approach of death with a family member with cancer would help family caregivers decide to discuss a terminal prognosis. We randomly assigned caregivers of terminally ill patients with cancer to a group that received a video and a companion workbook that showed either how they can discuss the prognosis with their patient (experimental arm) or how cancer pain can be controlled (control arm). At baseline and 1 month, we evaluated the decision to discuss terminal prognosis as the primary outcome. At 0, 1, 3, and 6 months, we assessed the caregivers' decisional conflict and satisfaction as secondary outcomes using a Decision Conflict Scale (DCS). We found no difference in changes in the decision to discuss terminal prognosis between the two groups. Conflict (P = .003), uncertainty (P = .019), and value clarity (P = .007) subscale scores and total DCS score (P = .008) improved from baseline to 1 month significantly more in the experimental arm than in the control arm. Over 6 months, the significant between-group differences continued for the conflict (P = .031), uncertainty (P = .014), and value clarity (P = .039) subscale scores and total DCS score (P = .040). Decision aids can help caregivers, with the aid of trained professionals, to communicate with patients about their terminal illness.


First mid-term results after cancellous allograft vitalized with autologous bone marrow for infected femoral non-union.
Surgical treatment of infected femoral non-union is challenging. Only few reports exist including autologous bone grafting (ABG) from the iliac crest promoting union. Vitalized allogeneic bone grafting (VABG) is an alternative promoting osseous healing and reconstructing bone defects. VABG contains allogeneic cancellous bone, impregnated with autologous bone marrow puncture harvested from the iliac crest. Yet, no systematic trial exists summarizing the results of septic femoral non-union using VABG analyzing the infection eradication rate, rate of osseous integration with union, and osseous remodeling. In this prospective non-randomized cohort study, 18 patients treated by nailing or plating for femur fractures that subsequently developed a septic non-union were included. The surgical intervention included a standardized protocol by eradicating infection first, followed by implantation VABG to promote osseous union. Main outcome measurements were radiographic union and clinical parameters. Mean follow-up was 5.9 years (range: 2-8 years). Infection eradication was achieved for all patients, while union was achieved in 15 out of 18 cases (83.3 %). Mean time for union took 16.9 weeks (range: 12-24). Radiographic analysis proved osseous remodeling and full integration of VABG within 12 months for 15 patients. No infection recurrence occurred at final follow-up. VABG demonstrated a high union rate without donor site morbidity as the main advantage over ABG. Sufficient osseous integration within 3 months and remodeling within 12 months are promising aspects, as no late fatigue fractures occurred. However, further trials are necessary due to the limitations of this study.


American College of Sports Medicine Roundtable Report on Physical Activity, Sedentary Behavior, and Cancer Prevention and Control.
The American College of Sports Medicine convened an International Multidisciplinary Roundtable on Exercise and Cancer in March 2018 to evaluate and translate the evidence linking physical activity and cancer prevention, treatment, and control. This article discusses findings from the Roundtable in relation to the biologic and epidemiologic evidence for the role of physical activity in cancer prevention and survival. The evidence supports that there are a number of biologically plausible mechanisms, whereby physical activity can influence cancer risk, and that physical activity is beneficial for the prevention of several types of cancer including breast, colon, endometrial, kidney, bladder, esophageal, and stomach. Minimizing time spent in sedentary behavior may also lower risk of endometrial, colon and lung cancers. Conversely, physical activity is associated with higher risk of melanoma, a serious form of skin cancer. Further, physical activity before and after a cancer diagnosis is also likely to be relevant for improved survival for those diagnosed with breast and colon cancer; with data suggesting that postdiagnosis physical activity provides greater mortality benefits than prediagnosis physical activity. Collectively, there is consistent, compelling evidence that physical activity plays a role in preventing many types of cancer and for improving longevity among cancer survivors, although the evidence related to higher risk of melanoma demonstrates the importance of sun safe practices while being physically active. Together, these findings underscore the importance of physical activity in cancer prevention and control. Fitness and public health professionals and health care providers worldwide are encouraged to spread the message to the general population and cancer survivors to be physically active as their age, abilities, and cancer status will allow.


A narrow window of cortical tension guides asymmetric spindle positioning in the mouse oocyte.
Cell mechanics control the outcome of cell division. In mitosis, external forces applied on a stiff cortex direct spindle orientation and morphogenesis. During oocyte meiosis on the contrary, spindle positioning depends on cortex softening. How changes in cortical organization induce cortex softening has not yet been addressed. Furthermore, the range of tension that allows spindle migration remains unknown. Here, using artificial manipulation of mouse oocyte cortex as well as theoretical modelling, we show that cortical tension has to be tightly regulated to allow off-center spindle positioning: a too low or too high cortical tension both lead to unsuccessful spindle migration. We demonstrate that the decrease in cortical tension required for spindle positioning is fine-tuned by a branched F-actin network that triggers the delocalization of myosin-II from the cortex, which sheds new light on the interplay between actin network architecture and cortex tension.


The effect of the PostureJac on deep cervical flexor endurance: implications in the management of cervicogenic headache and mechanical neck pain.
The convergence of cervical and trigeminal afferents on second-order neurons in the trigeminocervical nucleus may refer pain from the upper cervical spine into the head and face. Furthermore, "bi-directional interactions" between trigeminal and upper cervical afferents may also explain neck symptoms of trigeminal origin (e.g., migraine). It is known that cervicogenic headache sufferers present with several musculoskeletal changes including poor endurance of the deep cervical flexor muscles. These intrinsic muscles of the neck contribute to stabilization and protection of the cervical spine and are critical for the control of both intervertebral motion and the cervical lordosis. The purpose of this study was to determine whether the use of the PostureJac (SomatoCentric Systems, Inc., Toronto, Ontario, Canada), a posture support and exercise jacket, was effective in enhancing deep cervical muscle endurance. Forty-five (45) female subjects, between the ages of 18 and 40 years, were randomly assigned to three groups consisting of the no-treatment control, the treatment-control (table stabilization), and the experimental (PostureJac) group. The outcome measure of deep cervical flexor muscle endurance was based on the Flexor Endurance Test and was recorded in seconds. The results indicated that the PostureJac group was superior to the no-treatment control (p=.001) and the treatment-control (p=.004) groups in terms of increasing endurance of the deep cervical flexors. Consequently, the PostureJac may be a useful therapeutic tool in the management of cervicogenic headache and mechanical neck pain.


Chaotic stimulated Brillouin scattering near the threshold in a fiber.
We investigate the nonlinear dynamic behavior of stimulated Brillouin scattering (SBS) near threshold in the absence of feedback. When a cw Nd:YAG laser is injected into a single-mode optical fiber, the SBS signal exhibits intermittently appearing irregular self-pulsations near the threshold. By examining the time series of the SBS signals, we verify that the irregular SBS signal is one of the chaotic phenomena appearing near the bifurcation point.


Neurocognitive improvement after carotid artery stenting in patients with chronic internal carotid artery occlusion and cerebral ischemia.
Chronic cerebral hypoperfusion may lead to impairment in neurocognitive performance in patients with chronic internal carotid artery occlusion, and the effects of carotid artery stenting on neurocognitive function have been unclear. We prospectively enrolled 20 chronic internal carotid artery occlusion patients with objective ipsilateral hemisphere ischemia, in whom carotid artery stenting was attempted. Functional assessments, including the National Institutes of Health Stroke Scale, Barthel Index, and a battery of neuropsychological tests, including the Mini-Mental State Examination, Alzheimer Disease Assessment Scale-Cognitive Subtest, verbal fluency, and Color Trail Making A and B, were administered before and 3 months after intervention. Successful recanalization was achieved in 12 of 20 patients (60%). There was no procedural or new cerebral ischemic event, except for 1 intracranial hemorrhage, which occurred during the procedure and had neurologic sequelae; this case was excluded from analysis. The demographics and baseline cognitive performance were similar between the group with a successful outcome (group 1, n=12) and patients who did not (group 2, n=7). Ten of 12 patients in group 1 had improvement in ipsilateral brain perfusion after the procedure, but none in group 2 had improvement. Significant improvement in the scores on the Alzheimer Disease Assessment Scale-Cognitive Subtest (before, 7.7±8.9 versus after, 5.7±7.1; P=0.024), Mini-Mental State Examination (before, 25.8±3.8 versus after, 27.7±2.7; P=0.015), and Color Trail Making A (before, 123.2±68.6 versus after, 99.3±51.5; P=0.017) were found in group 1 but not in group 2. Successful carotid artery stenting improves global cognitive function as well as attention and psychomotor processing speed in patients with chronic internal carotid artery occlusion.


Optical forces induced behavior of a particle in a non-diffracting vortex beam.
An interaction between a light field with complex field spatial distribution and a micro-particle leads to forces that drag the particle in space and may confine it in a stable position or a trajectory. The particle behavior is determined by its size with respect to the characteristic length of the spatially periodic or symmetric light field distribution. We study theoretically and experimentally the behavior of a microparticle near the center of an optical vortex beam in a plane perpendicular to the beam propagation. We show that such particle may be stably trapped either in a dark spot on the vortex beam axis, or in one of two points placed off the optical axis. It may also circulate along a trajectory having its radius smaller or equal to the radius of the first bright vortex ring.


Epidemiology of soybean vein necrosis-associated virus.
Soybean vein necrosis-associated virus has been linked to an emerging soybean disease in the United States and Canada. Virus distribution and population structure in major growing areas were evaluated. Data were employed to design and develop sensitive detection protocols, able to detect all virus isolates available in databases. The host range for the virus was assessed and several species were found to sustain virus replication, including ivyleaf morning glory, a common weed species in soybean-growing areas in the United States. Koch's postulates were fulfilled using soybean thrips and transmission efficiency was determined. This article provides significant insight into the biology of the most widespread soybean virus in the United States.


How cancer metabolism is tuned for proliferation and vulnerable to disruption.
Cancer metabolism has received a substantial amount of interest over the past decade. The advances in analytical tools have, along with the rapid progress of cancer genomics, generated an increasingly complex understanding of metabolic reprogramming in cancer. As numerous connections between oncogenic signalling pathways and metabolic activities emerge, the importance of metabolic reprogramming in cancer is being increasingly recognized. The identification of metabolic weaknesses of cancer cells has been used to create strategies for treating cancer, but there are still challenges to be faced in bringing the drugs that target cancer metabolism to the clinic.


Hyperbaric oxygen therapy for chronic antibiotic-refractory ischemic pouchitis.
Hyperbaric oxygen therapy (HBOT) has been shown to be efficacious in treating various conditions, including perianal Crohn's disease. Here we present a case of a 59-year-old male with a history of ulcerative colitis, who underwent a total proctocolectomy and two-stage J-pouch construction. He later developed chronic antibiotic-refractory pouchitis with endoscopic features of ischemia. At the completion of HOBT-a total of 20 sessions of 100% oxygen at 2.5-3.0 atmospheres absolute for 60-90 minutes per session-a repeat pouchoscopy showed marked improvement of endoscopic mucosal inflammation. HBOT is known to increase tissue oxygenation, reduce tissue hypoxia, alter inflammatory pathways and promote tissue healing. This case demonstrated the therapeutic role of HBOT as well as the possible disease mechanism in chronic antibiotic-refractory pouchitis.


Effect of preoperative angina pectoris on cardiac outcomes in patients with previous myocardial infarction undergoing major noncardiac surgery (data from ACS-NSQIP).
The impact of preoperative stable angina pectoris on postoperative cardiovascular outcomes in patients with previous myocardial infarction (MI) who underwent major noncardiac surgery is not well studied. We studied patients with previous MI who underwent elective major noncardiac surgeries within the American College of Surgeons-National Surgical Quality Improvement Program (2005 to 2011). Primary outcome was occurrence of an adverse cardiac event (MI and/or cardiac arrest). Multivariable logistic regression models evaluated the impact of stable angina on outcomes. Of 1,568 patients (median age 70 years; 35% women) with previous MI who underwent major noncardiac surgery, 5.5% had postoperative MI and/or cardiac arrest. Patients with history of preoperative angina had significantly greater incidence of primary outcome compared to those without anginal symptoms (8.4% vs 5%, p = 0.035). In secondary outcomes, reintervention rates (22.5% vs 11%, p <0.001) and length of stay (median 6-days vs 5-days; p <0.001) were also higher in patients with preoperative angina. In multivariable analyses, preoperative angina was a significant predictor for postoperative MI (odds ratio 2.49 [1.20 to 5.58]) and reintervention (odds ratio 2.40 [1.44 to 3.82]). In conclusion, our study indicates that preoperative angina is an independent predictor for adverse outcomes in patients with previous MI who underwent major noncardiac surgery, and cautions against overreliance on predictive tools, for example, the Revised Cardiac Risk Index, in these patients, which does not treat stable angina and previous MI as independent risk factors during risk prognostication.


Indium-catalyzed intramolecular hydroarylation of aryl propargyl ethers.
Indium(III) halides catalyze efficiently the intramolecular hydroarylation (IMHA) of aryl propargyl ethers. The reaction proceeds regioselectively with terminal and internal alkynes bearing electron-rich and electron-deficient substituents in the benzenes and alkynes affording only the 6-endo dig cyclization product. Additionally, a sequential indium-catalyzed IMHA and palladium-catalyzed Sonogashira coupling can be performed in one reaction vessel. Experiments with deuterium support a mechanism through electrophilic aromatic substitution.


Substrate-mediated effects in photothermal patterning of alkanethiol self-assembled monolayers with microfocused continuous-wave lasers.
In recent years, self-assembled monolayers (SAMs) have been demonstrated to provide promising new approaches to nonlinear laser processing. Most notably, because of their ultrathin nature, indirect excitation mechanisms can be exploited in order to fabricate subwavelength structures. In photothermal processing, for example, microfocused lasers are used to locally heat the substrate surface and initiate desorption or decomposition of the coating. Because of the strongly temperature-dependent desorption kinetics, the overall process is highly nonlinear in the applied laser power. For this reason, subwavelength patterning is feasible employing ordinary continuous-wave lasers. The lateral resolution, generally, depends on both the type of the organic monolayer and the nature of the substrate. In previous studies we reported on photothermal patterning of distinct types of SAMs on Si supports. In this contribution, a systematic study on the impact of the substrate is presented. Alkanethiol SAMs on Au-coated glass and silicon substrates were patterned by using a microfocused laser beam at a wavelength of 532 nm. Temperature calculations and thermokinetic simulations were carried out in order to clarify the processes that determine the performance of the patterning technique. Because of the strongly temperature-dependent thermal conductivity of Si, surface-temperature profiles on Au/Si substrates are very narrow ensuring a particularly high lateral resolution. At a 1/e spot diameter of 2 µm, fabrication of subwavelength structures with diameters of 300-400 nm is feasible. Rapid heat dissipation, though, requires high laser powers. In contrast, patterning of SAMs on Au/glass substrates is strongly affected by the largely distinct heat conduction within the Au film and in the glass support. This results in broad surface temperature profiles. Hence, minimum structure sizes are larger when compared with respective values on Au/Si substrates. The required laser powers, though, are more than one order of magnitude lower. Also, the laser power needed for patterning decreases with decreasing Au layer thickness. These results demonstrate the impact of the substrate on the overall patterning process and provide new perspectives in photothermal laser patterning of ultrathin organic coatings.


Fatal Fulminant Pneumonia Caused by Methicillin-Sensitive Staphylococcus aureus Negative for Major High-Virulence Factors Following Influenza B Virus Infection.
Increasing evidence has indicated that Staphylococcus aureus pneumonia complicated with influenza virus infection is often fatal. In these cases, disease severity is typically determined by susceptibility to antimicrobial agents and the presence of high-virulence factors that are produced by Staphylococcus aureus, such as Panton-Valentine leukocidin (PVL). We describe a rare case of fatal community-acquired pneumonia caused by methicillin-sensitive Staphylococcus aureus (MSSA), which did not secrete major high-virulence factors and coexisted with influenza type B infection. The 32-year-old previously healthy male patient presented with dyspnea, high fever, and cough. His roommate had been diagnosed with influenza B virus infection 3 days earlier. Gram-positive clusters of cocci were detected in the patient's sputum; therefore, he was diagnosed with severe pneumonia and septic shock, and was admitted to the intensive care unit. Despite intensive antibiotic and antiviral treatment, he died of multiple organ failure 5 days after admission. His blood culture from the admission was positive for MSSA, and further analysis revealed that the strain was negative for major high-virulence factors, including PVL and enterotoxins, although influenza B virus RNA was detected by PCR. Physicians should pay special attention to patients with pneumonia following influenza and Staphylococcus aureus infection, as it may be fatal, even if the Staphylococcus aureus strain is PVL-negative and sensitive to antimicrobial agents.


Ethnographic study of ICT-supported collaborative work routines in general practice.
Health informatics research has traditionally been dominated by experimental and quasi-experimental designs. An emerging area of study in organisational sociology is routinisation (how collaborative work practices become business-as-usual). There is growing interest in the use of ethnography and other in-depth qualitative approaches to explore how collaborative work routines are enacted and develop over time, and how electronic patient records (EPRs) are used to support collaborative work practices within organisations. Following Feldman and Pentland, we will use 'the organisational routine' as our unit of analysis. In a sample of four UK general practices, we will collect narratives, ethnographic observations, multi-modal (video and screen capture) data, documents and other artefacts, and analyse these to map and compare the different understandings and enactments of three common routines (repeat prescribing, coding and summarising, and chronic disease surveillance) which span clinical and administrative spaces and which, though 'mundane', have an important bearing on quality and safety of care. In a detailed qualitative analysis informed by sociological theory, we aim to generate insights about how complex collaborative work is achieved through the process of routinisation in healthcare organisations. Our study offers the potential not only to identify potential quality failures (poor performance, errors, failures of coordination) in collaborative work routines but also to reveal the hidden work and workarounds by front-line staff which bridge the model-reality gap in EPR technologies and via which "automated" safety features have an impact in practice.


Quality goal attainment and maintenance in patients with type II diabetes mellitus initiated on canagliflozin or a glucagon-like peptide-1 receptor agonist in an actual practice setting.
To compare achievement of quality goals (HbA1c, weight loss/body mass index [BMI], systolic blood pressure [SBP]), including maintaining HbA1c, between patients with type 2 diabetes mellitus (T2DM) treated with canagliflozin 300 mg (CANA) or a GLP-1 in an actual practice setting. Adults with T2DM newly initiated on CANA or a GLP-1 were identified from the IQVIATM Real-World Data Electronic Medical Records-US database (2012Q2-2016Q1). To account for differences in baseline characteristics, inverse probability of treatment weighting was used. Outcomes were compared using Cox models (hazard ratios [HRs] and 95% confidence intervals [CIs]) and Kaplan-Meier analyses. CANA (n = 11,435) and GLP-1 (n = 11,582) cohorts had similar attainment of HbA1c < 8.0% (64 mmol/mol) and HbA1c < 9.0% (75 mmol/mol; HbA1c < 8.0%: HR [CI] = 0.98 [0.91-1.06]; HbA1c < 9.0%: HR [CI] = 1.02 [0.93-1.12]), while GLP-1 patients were 10% more likely to achieve HbA1c < 7.0% (53 mmol/mol). CANA and GLP-1 patients were similar in maintaining HbA1c < 7.0%, < 8.0%, or <9.0%, achieving weight loss ≥5% (HR [CI] = 1.05 [0.99-1.12]), achieving BMI <30 kg/m2 (HR [CI] = 1.11 [0.98-1.27]), and achieving SBP <140 mmHg (HR [CI] = 1.07 [0.98-1.17]). CANA patients were 30% less likely to discontinue treatment, 28% less likely to have a prescription for a new anti-hyperglycemic, and 17-21% less likely to fail to maintain HbA1c < 8.0% or 9.0% or have a prescription for a new anti-hyperglycemic (composite outcome) vs GLP-1. No significant difference was observed for the composite outcome using the HbA1c < 7.0% threshold. This retrospective study in an actual practice setting showed that CANA patients were generally as likely as GLP-1 patients to achieve HbA1c, weight, and blood pressure thresholds, and to maintain glycemic control while being less likely to discontinue treatment and/or have a new anti-hyperglycemic prescribed.


Corals sustain growth but not skeletal density across the Florida Keys Reef Tract despite ongoing warming.
Through the continuous growth of their carbonate skeletons, corals record information about past environmental conditions and their effect on colony fitness. Here, we characterize century-scale growth records of inner and outer reef corals across ~200 km of the Florida Keys Reef Tract (FKRT) using skeletal cores extracted from two ubiquitous reef-building species, Siderastrea siderea and Pseudodiploria strigosa. We find that corals across the FKRT have sustained extension and calcification rates over the past century but have experienced a long-term reduction in skeletal density, regardless of reef zone. Notably, P. strigosa colonies exhibit temporary reef zone-dependent reductions in extension rate corresponding to two known extreme temperature events in 1969-1970 and 1997-1998. We propose that the subtropical climate of the FKRT may buffer corals from chronic growth declines associated with climate warming, though the significant reduction in skeletal density may indicate underlying vulnerability to present and future trends in ocean acidification.


Effect of spineboard and headblocks on the image quality of head CT scans.
Trauma patients at risk for, or suspected of, spinal injury are frequently transported to hospital using full spinal immobilisation. At the emergency department, immobilisation is often maintained until radiological work-up is completed. In this study, we examined how these devices for spinal stabilization influence visual image quality. Image quality was judged for both patient CT scans and phantom CT scans. CT scans of 217 patients were assessed retrospectively by two radiologists for visual scoring of image quality, scoring both quantity and impact of artifacts caused by the immobilization devices. For the phantom CT scans, eight set-ups were made, using a vacuum mattress without headblocks and a rigid and a soft-layered spineboard without headblocks, with standard soft-foam headblocks, or with new design headblocks. Overall, artifacts were found in 67 % of CT scans of patients on immobilization devices, which hampered diagnosis in 10 % of the cases. In the phantom CT scans, artifacts were present in all set-ups with one or more devices present and were seen in 20 % of all scan slices. The presence of headblocks resulted in more artifacts in both the patient CT scans and the phantom CT scans. Considerable effort should therefore be made to adjust the design of the immobilization devices and to remove the headblocks before CT scans are made.


Changes in DNA polymerase alpha, beta, gamma activities during early development of the teleost fish Misgurnus fossilis (loach).
DNA polymerase alpha, beta, gamma activities were determined after fractionation of loach (Misgurnus fossilis) cell extracts in glycerol gradients. The extracts of mature eggs, liver and testes cells yielded similar specific activities of DNA polymerase gamma (9-15 units/g protein) but differed markedly in the specific activities of DNA polymerases alpha and beta. A high activity of DNA polymerase alpha was revealed in the egg extract (2.0 X 10(3) units/g protein), while no DNA polymerase alpha activity was detected in liver cells. The specific beta-polymerase activity in the extract of mature eggs was extremely low (3.6 units/g protein), about two orders of magnitude lower than the enzyme activity in the extracts of liver or testes cells. The specific activity of DNA polymerases alpha and gamma changes insignificantly during oocyte maturation and embryogenesis up to the stage of hatching (50 h at 21.5 degrees C). As the mass of oocytes and embryos remains virtually unchanged at the stages studied, no substantial changes were observed in the alpha and gamma-polymerase activities per egg or embryo. The specific beta-polymerase activity in embryo cells increases about threefold by the completion of epiboly (20 h).


Demographic history influences spatial patterns of genetic diversityin recently expanded coyote (Canis latrans) populations.
Human-mediated range expansions have increased in recent decades and represent unique opportunities to evaluate genetic outcomes of establishing peripheral populations across broad expansion fronts. Over the past century, coyotes (Canis latrans) have undergone a pervasive range expansion and now inhabit every state in the continental United States. Coyote expansion into eastern North America was facilitated by anthropogenic landscape changes and followed two broad expansion fronts. The northern expansion extended through the Great Lakes region and southern Canada, where hybridization with remnant wolf populations was common. The southern and more recent expansion front occurred approximately 40 years later and across territory where gray wolves have been historically absent and remnant red wolves were extirpated in the 1970s. We conducted a genetic survey at 10 microsatellite loci of 482 coyotes originating from 11 eastern U.S. states to address how divergent demographic histories influence geographic patterns of genetic diversity. We found that population structure corresponded to a north-south divide, which is consistent with the two known expansion routes. Additionally, we observed extremely high genetic diversity, which is atypical of recently expanded populations and is likely the result of multiple complex demographic processes, in addition to hybridization with other Canis species. Finally, we considered the transition of allele frequencies across geographic space and suggest the mid-Atlantic states of North Carolina and Virginia as an emerging contact zone between these two distinct coyote expansion fronts.


Trajectories of childhood aggression and inattention/hyperactivity: differential effects on substance abuse in adolescence.
Aggression and hyperactivity/inattention each are linked to risk of alcohol use disorder (AUD), but their unique contributions remain ambiguous. The present study disaggregated these two domains developmentally and examined the relation between childhood behavior trajectories and adolescent substance use. A total of 335 children of alcoholic and nonalcoholic fathers were studied prospectively. Parallel process latent trajectory class analysis was developed with behavioral ratings by parents and teachers of aggression and inattention/hyperactivity across ages 7 to 16. Membership in the four latent classes was used as a predictor for problem adolescence alcohol use and substance onset. Youths in the four latent trajectory classes differed in number of alcohol problems at age 16: healthy class (39% of sample, mean 2.1 alcohol-related problems), inattentive/hyperactive but not aggressive (33%; mean 2.7 problems), aggressive but not inattentive/hyperactive (4%, mean 5.0 problems), and comorbid (24%; mean 4.0 problems). Survival analysis revealed that the aggressive, comorbid, and inattentive/hyperactive classes had significantly earlier onsets of drinking, drunkenness, and marijuana use than the healthy class. Illicit drug use was also significantly increased in the comorbid, aggressive, and inattentive/hyperactive classes compared to the healthy class. Three levels of behavioral risk of substance abuse exist, the highest having trajectories of increased aggressive and inattentive/hyperactive problems throughout childhood, the next involving only an increased inattentive/hyperactive behavioral trajectory, and the lowest involving those with neither type of problem. Children with both inattention/hyperactivity and aggression have the greatest need for childhood intervention to prevent substance abuse in adolescence.


Blood Volume Status in ME/CFS Correlates With the Presence or Absence of Orthostatic Symptoms: Preliminary Results.
Introduction: Conflicting data have been published on the reduction of circulating blood volume in adults with Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). The aim of the present study was to compare blood volumes based on the presence or absence of orthostatic symptoms. Methods and results: Twenty consecutive adults with ME/CFS participated in the study. All underwent dual isotope blood volume measurement and were evaluated for a clinical suspicion of orthostatic intolerance (OI). The mean age was 34 (10) years, and median duration of disease was 7.5 (6-10) years. The mean (SD) absolute blood volume was 59 (8) ml/kg, a value -11 (7) ml/kg below the reference blood volume. Of the 12 patients, 4 had no OI and 8 had a clinical suspicion of OI. In 8 patients with OI, absolute blood volumes were significantly lower than for the 4 without OI (56 [2] vs. 66 [5]; p < 0.05) as were the differences between the measured and the reference blood volume (-14 [2]; vs. -4 [3]; p < 0.02). Conclusions: Adults with ME/CFS had a significantly lower blood volume if they had a clinical suspicion of OI compared to those without a clinical suspicion of OI, as well as a significantly lower blood volume compared to the expected value. The data suggest that accounting for symptoms of OI could enhance the detection of the subset with reduced blood volume.


Synthesis of multivalent host and guest molecules for the construction of multithreaded diamide pseudorotaxanes.
A series of di-, tri- and tetravalent axles and wheels for the synthesis of pseudorotaxanes bearing the tetralactam macrocycle/diamide axle binding motif was prepared. Starting from iodinated monovalent precursors, Sonogashira cross-coupling reactions were utilized to couple the binding sites to appropriate spacer groups. Through this "Lego" or "toolbox" approach, the convergent synthesis of host and guests with a well-defined number of the binding sites is possible. In addition, the spatial arrangement of the binding sites can be controlled through the quite rigid connections between linker and binding sites. Although a quantitative assessment of binding strengths was not possible by NMR titration experiments, typical and significant shifts of the signals of the diamide moiety indicate qualitatively the formation of pseudorotaxanes from the axle and wheel precursors.


Finding a needle in the haystack: computational modeling of Mg2+ binding in the active site of protein farnesyltransferase.
Studies aimed at elucidating the unknown Mg2+ binding site in protein farnesyltransferase (FTase) are reported. FTase catalyzes the transfer of a farnesyl group to a conserved cysteine residue (Cys1p) on a target protein, an important step for proteins in the signal transduction pathways (e.g., Ras). Mg2+ ions accelerate the protein farnesylation reaction by up to 700-fold. The exact function of Mg2+ in catalysis and the structural characteristics of its binding remain unresolved to date. Molecular dynamics (MD) simulations addressing the role of magnesium ions in FTase are presented, and relevant octahedral binding motifs for Mg2+ in wild-type (WT) FTase and the Dβ352A mutant are explored. Our simulations suggest that the addition of Mg2+ ions causes a conformational change to occur in the FTase active site, breaking interactions known to keep FPP in its inactive conformation. Two relevant Mg2+ ion binding motifs were determined in WT FTase. In the first binding motif, WT1, the Mg2+ ion is coordinated to D352β, zinc-bound D297β, two water molecules, and one oxygen atom from the α- and β-phosphates of farnesyl diphosphate (FPP). The second binding motif, WT2, is identical with the exception of the zinc-bound D297β being replaced by a water molecule in the Mg2+ coordination complex. In the Dβ352A mutant Mg2+ binding motif, D297β, three water molecules, and one oxygen atom from the α- and β-phosphates of FPP complete the octahedral coordination sphere of Mg2+. Simulations of WT FTase, in which Mg2+ was replaced by water in the active site, recreated the salt bridges and hydrogen-bonding patterns around FPP, validating these simulations. In all Mg2+ binding motifs, a key hydrogen bond was identified between a magnesium-bound water and Cys1p, bridging the two metallic binding sites and, thereby, reducing the equilibrium distance between the reacting atoms of FPP Cys1p. The free energy profiles calculated for these systems provide a qualitative understanding of experimental results. They demonstrate that the two reactive atoms approach each other more readily in the presence of Mg2+ in WT FTase and mutant. The flexible WT2 model was found to possess the lowest barrier toward the conformational change, suggesting it is the preferred Mg2+ binding motif in WT FTase. In the mutant, the absence of D352β makes the transition toward a conformational change harder. Our calculations find support for the proposal that D352β performs a critical role in Mg2+ binding and Mg2+ plays an important role in the conformational transition step.


Models and analyses to understand threats to polio eradication.
To achieve complete polio eradication, the live oral poliovirus vaccine (OPV) currently used must be phased out after the end of wild poliovirus transmission. However, poorly understood threats may arise when OPV use is stopped. To counter these threats, better models than those currently available are needed. Two articles recently published in BMC Medicine address these issues. Mercer et al. (BMC Med 15:180, 2017) developed a statistical model analysis of polio case data and characteristics of cases occurring in several districts in Pakistan to inform resource allocation decisions. Nevertheless, despite having the potential to accelerate the elimination of polio cases, their analyses are unlikely to advance our understanding OPV cessation threats. McCarthy et al. (BMC Med 15:175, 2017) explored one such threat, namely the emergence and transmission of serotype 2 circulating vaccine derived poliovirus (cVDPV2) after OPV2 cessation, and found that the risk of persistent spread of cVDPV2 to new areas increases rapidly 1-5 years after OPV2 cessation. Thus, recently developed models and analysis methods have the potential to guide the required steps to surpass these threats. 'Big data' scientists could help with this; however, datasets covering all eradication efforts should be made readily available.Please see related articles: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0937-y and https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-017-0941-2 .


Analysis of Clinical Factors Associated with Retinal Morphological Changes in Patients with Primary Sjögren's Syndrome.
To investigate clinical factors associated with abnormal retinal morphologies in patients with primary Sjögren's syndrome (pSS). One-hundred-thirty patients with pSS who underwent immunoserological tests, minor salivary gland biopsies, and optical coherence tomography examinations were retrospectively analyzed. Risk factors for abnormally reduced peripapillary retinal nerve fiber layer (pRNFL) and macular ganglion cell-inner plexiform layer (mGCIPL) thicknesses were evaluated, as well as the correlation between clinical factors and pRNFL and mGCIPL thicknesses. Anti-Sjögren's syndrome type B (SSB) antibody positivity (P = 0.048) was identified as a risk factor associated with abnormally reduced pRNFL thickness, and anti-SSB positivity (P = 0.005) and erythrocyte sedimentation rate (ESR) level (P = 0.031) were identified as risk factors associated with an abnormally reduced mGCIPL thickness as revealed by multivariate logistic regression analysis. There was a significant negative correlation between anti-SSB antibody levels and the thickness of pRNFL and mGCIPL. The thicknesses of pRNFL and mGCIPL were significantly reduced in anti-SSB-positive eyes when compared to anti-SSB-negative eyes (P < 0.05). However, histopathologic grading was not associated with the pRNFL and mGCIPL thicknesses. Anti-SSB antibody positivity and ESR levels may be useful for predicting an abnormally reduced pRNFL or mGCIPL thickness in patients with pSS. Our results may provide clinical evidence to substantiate the association between aberrant autoimmunity and inner retinal changes in patients with pSS.


Serum Uric Acid and Progression of Kidney Disease: A Longitudinal Analysis and Mini-Review.
Increasing evidence supports the association between hyperuricemia and incident chronic kidney disease (CKD); however, there are conflicting data regarding the role of hyperuricemia in the progression of CKD. This study retrospectively assessed the longitudinal association between uric acid (UA) level and CKD progression in a Chinese population lived in Taiwan. Patients with physician diagnosis of hyperuricemia or receiving urate-lowering therapy between 2003 and 2005 were identified in the electronic medical records (EMR) of a tertiary medical center and were followed up until December 31, 2011. Patients were divided into four UA categories at the cut-off 6, 8, and 10 mg/dL. CKD progression was estimated by the change of estimated glomerular filtration rate (eGFR) in the linear mixed models. Kidney failure was defined as an eGFR less than 15 mL/min/1.73 m2 or requiring renal replacement therapy. A total of 739 patients were analyzed. In the full-adjusted model, patients with a baseline UA level ≥6 mg/dL had greater decline in eGFR ((β = -9.6, 95% CI -16.1, -3.1), comparing to those with a UA level less than 6 mg/dL. When stratifying patients into four UA categories, all three hyperuricemia categories (UA6-8, 8-10, ≥10 mg/dL) associated with a greater decline in eGFR over the follow-up period with an increasing dose-response, comparing to the lowest UA category. The risk of progression to renal failure increased 7% (hazard ratio 1.07, 95% CI 1.00, 1.14) for each 1mg/dL increase in baseline UA level. The influences of hyperuricemia on eGFR decline and the risk of kidney failure were more prominent in patients without proteinuria than those with proteinuria. Our study showed a higher uric acid level is associated with a significant rapid decline in eGFR and a higher risk of kidney failure, particularly in patients without proteinuria. Our findings suggest hyperuricemia is a potential modifiable factor of CKD progression.


Optimization of the field of view of a Brillouin-enhanced four-wave-mixing phase conjugator.
A Brillouin-enhanced four-wave mixing phase conjugator featuring a field of view that varies by approximately an order of magnitude, i.e., from 2 to 20 mrad, is described. We control this variable field of view by utilizing a slightly noncollinear pumping geometry and by adjusting the pump-pump frequency difference to optimize the phase mismatch for the overall process. A model that describes the interplay between frequency and geometry to the Brillouin-enhanced four-wave-mixing phase mismatch is found to predict the expandable field of view.


The impact of ignoring multiple membership data structures in multilevel models.
This study compared the use of the conventional multilevel model (MM) with that of the multiple membership multilevel model (MMMM) for handling multiple membership data structures. Multiple membership data structures are commonly encountered in longitudinal educational data sets in which, for example, mobile students are members of more than one higher-level unit (e.g., school). While the conventional MM requires the user either to delete mobile students' data or to ignore prior schools attended, MMMM permits inclusion of mobile students' data and models the effect of all schools attended on student outcomes. The simulation study identified underestimation of the school-level predictor coefficient, as well as underestimation of the level-two variance component with corresponding overestimation of the level-one variance when multiple membership data structures were ignored. Results are discussed along with limitations and ideas for future MMMM methodological research as well as implications for applied researchers.


The relationship between the presence of anti-cyclic citrullinated peptide antibodies and clinical phenotype in very early rheumatoid arthritis.
Anti-cyclic citrullinated peptide (anti-CCP) antibodies are highly specific for RA, but are not detectable in all RA patients. The aim of this study was to establish whether the clinical phenotypes of anti-CCP positive and negative disease are distinct at the earliest clinically apparent phase of disease. Patients were recruited from the Birmingham early inflammatory arthritis clinic. Participants were included in the current study if they presented within 3 months of symptom onset and fulfilled 1987 ACR criteria for RA at some point during an 18 month follow-up. Data were collected on demographic variables, joint symptoms and tender (n = 68) and swollen (n = 66) joint counts. CRP, ESR, rheumatoid factor and anti-CCP2 status were measured. 92 patients were included (48 anti-CCP positive). The anti-CCP positive and negative groups were comparable in terms of demographic variables, inflammatory markers, joint counts and 1987 ACR classification criteria, except that more anti-CCP positive patients were rheumatoid factor positive (83.3% vs. 11.4%, p < 0.01). There was no significant difference in the pattern of joint involvement, except for an increased prevalence of knee joint swelling in anti-CCP positive patients (42.9% vs. 22.2%, p = 0.03). Patients with and without anti-CCP antibodies present in a similar way, even within three months of clinically apparent disease that eventually develops into RA.


Changes in reflectin protein phosphorylation are associated with dynamic iridescence in squid.
Many cephalopods exhibit remarkable dermal iridescence, a component of their complex, dynamic camouflage and communication. In the species Euprymna scolopes, the light-organ iridescence is static and is due to reflectin protein-based platelets assembled into lamellar thin-film reflectors called iridosomes, contained within iridescent cells called iridocytes. Squid in the family Loliginidae appear to be unique in which the dermis possesses a dynamic iridescent component with reflective, coloured structures that are assembled and disassembled under the control of the muscarinic cholinergic system and the associated neurotransmitter acetylcholine (ACh). Here we present the sequences and characterization of three new members of the reflectin family associated with the dynamically changeable iridescence in Loligo and not found in static Euprymna iridophores. In addition, we show that application of genistein, a protein tyrosine kinase inhibitor, suppresses ACh- and calcium-induced iridescence in Loligo. We further demonstrate that two of these novel reflectins are extensively phosphorylated in concert with the activation of iridescence by exogenous ACh. This phosphorylation and the correlated iridescence can be blocked with genistein. Our results suggest that tyrosine phosphorylation of reflectin proteins is involved in the regulation of dynamic iridescence in Loligo.


Acute mental health care according to recent mental health legislation. Part III. Structuring space for acute mental health care.
This is the third of three reports on the follow-up review of mental health care at Helen Joseph Hospital (HJH). The study reviewed existing South African standards for mental health care facilities. Architectural principles and implications for the use of space were deducted from recent legislation. Objectives were to evaluate the use of space in the existing physical facilities, to identify appropriate architectural solutions considering identified human rights requirements and to provide provisional cost estimates to align the unit towards its designated functions. Personal interviews were conducted. An on-site assessment and survey was made of existing and potential new spaces. Spatial requirements for implementing the Mental Health Act, No. 17 of 2002 (MHCA) were explored. Principles for spatial design of acute facilities include that: - spaces should communicate clear individual identity; - space should be segregated into zones according to user functionality and privacy; - communal leisure spaces should open into safe contained outdoor spaces; - circulation routes should preferably be circular; - sufficient visual connection should exist between circulation space and group activities; and - open lines of sight should be provided to all access points. The potential options for extension included: - an extensive unused single storey structural shell for a potential office wing on the same floor; - a huge vacant double volume space which could be accessed across the existing flat roof for potential occupational therapy activities; and - the existing roof area could be altered and secured to become an adequate outside leisure and garden area. A proposed concept design in two phases - based on these principles - was submitted to hospital and provincial management. To implement the MHCA without violating the human rights of mental health care users at HJH will require specific adjustment and extension of the current use of space at HJH.


Conserved elements within open reading frames of mammalian Hox genes.
A recent study in BMC Evolutionary Biology shows that many of the open reading frames in mammalian Hox genes are more conserved than expected on the basis of their protein sequence. The presence of highly conserved DNA elements is thus not confined to the noncoding DNA in neighboring regions but clearly overlaps with coding sequences. These findings support an emerging view that gene regulatory and coding sequences are likely to be more intermingled than once believed.


Self-Reorientation Following Colorectal Cancer Treatment - A Grounded Theory Study.
After colorectal cancer (CRC) treatment, people reorganize life in ways that are consistent with their understanding of the illness and their expectations for recovery. Incapacities and abilities that have been lost can initiate a need to reorient the self. To the best of our knowledge, no studies have explicitly focused on the concept of self-reorientation after CRC treatment. The aim of the present study was therefore to explore self-reorientation in the early recovery phase after CRC surgery. Grounded theory analysis was undertaken, using the method presented by Charmaz. The present results explained self-reorientation as the individual attempting to achieve congruence in self-perception. A congruent self-perception meant bringing together the perceived self and the self that was mirrored in the near environs. The results showed that societal beliefs and personal explanations are essential elements of self-reorientation, and that it is therefore important to make them visible.


Familial back shape in adolescent scoliosis. A photogrammetric population study.
A stereophotogrammetric technique (ISIS scanning) was used to assess the back shape of children with adolescent idiopathic scoliosis (index cases), their unaffected relatives, normal adults and children, and children with small idiopathic scoliotic curves (Cobb's angle less than 30 degrees) to detect any familial trends that may predispose to scoliosis. The analysis revealed a characteristic three-dimensional scoliotic back shape; no differences in unaffected relatives as regards sex or a positive family history of scoliosis; similar back shapes in unaffected parents and normal adults, both of whom differ from index cases and children with small curves. Unaffected siblings had a sagittal profile between those of normal children and children with small curves. This may represent an inherited tendency to scoliosis.


Inhibitory effects of Zingiber officinale Roscoe derived components on aldose reductase activity in vitro and in vivo.
Ginger (Zingiber officinale Roscoe) continues to be used as an important cooking spice and herbal medicine around the world. Scientific research has gradually verified the antidiabetic effects of ginger. Especially gingerols, which are the major components of ginger, are known to improve diabetes including the effect of enhancement against insulin-sensitivity. Aldose reductase inhibitors have considerable potential for the treatment of diabetes, without increased risk of hypoglycemia. The assay for aldose reductase inhibitors in ginger led to the isolation of five active compounds including 2-(4-hydroxy-3-methoxyphenyl)ethanol (2) and 2-(4-hydroxy-3-methoxyphenyl)ethanoic acid (3). Compounds 2 and 3 were good inhibitors of recombinant human aldose reductase, with IC50 values of 19.2 +/- 1.9 and 18.5 +/- 1.1 microM, respectively. Furthermore, these compounds significantly suppressed not only sorbitol accumulation in human erythrocytes but also lens galactitol accumulation in 30% of galactose-fed cataract rat model. A structure-activity relationship study revealed that the applicable side alkyl chain length and the presence of a C3 OCH3 group in the aromatic ring are essential features for enzyme recognition and binding. These results suggested that it would contribute to the protection against or improvement of diabetic complications for a dietary supplement of ginger or its extract containing aldose reductase inhibitors.


Studying Cellular Signal Transduction with OMIC Technologies.
In the gulf between genotype and phenotype exists proteins and, in particular, protein signal transduction systems. These systems use a relatively limited parts list to respond to a much longer list of extracellular, environmental, and/or mechanical cues with rapidity and specificity. Most signaling networks function in a highly non-linear and often contextual manner. Furthermore, these processes occur dynamically across space and time. Because of these complexities, systems and "OMIC" approaches are essential for the study of signal transduction. One challenge in using OMIC-scale approaches to study signaling is that the "signal" can take different forms in different situations. Signals are encoded in diverse ways such as protein-protein interactions, enzyme activities, localizations, or post-translational modifications to proteins. Furthermore, in some cases, signals may be encoded only in the dynamics, duration, or rates of change of these features. Accordingly, systems-level analyses of signaling may need to integrate multiple experimental and/or computational approaches. As the field has progressed, the non-triviality of integrating experimental and computational analyses has become apparent. Successful use of OMIC methods to study signaling will require the "right" experiments and the "right" modeling approaches, and it is critical to consider both in the design phase of the project. In this review, we discuss common OMIC and modeling approaches for studying signaling, emphasizing the philosophical and practical considerations for effectively merging these two types of approaches to maximize the probability of obtaining reliable and novel insights into signaling biology.


Conditional linkage disequilibrium analysis of a complex disease superlocus, IDDM1 in the HLA region, reveals the presence of independent modifying gene effects influencing the type 1 diabetes risk encoded by the major HLA-DQB1, -DRB1 disease loci.
Type 1 diabetes mellitus is a common disease with a complex mode of inheritance. Its aetiology is underpinned by a major locus, insulin-dependent diabetes mellitus 1 (IDDM1) in the human leukocyte antigen (HLA) region of chromosome 6p21, and an unknown number of loci of lesser individual effect. In linkage analyses IDDM1 is a single peak, but it is evident that the linkage is caused by allelic variation of three adjacent genes in a 75 kb region, namely the class II genes, HLA-DRB1, -DQA1 and -DQB1. However, even these three genes may not explain all of the HLA association. We investigated, in the founder population of Sardinia, whether non-DQ/DR polymorphic markers within a 9.452 Mb region encompassing the whole HLA complex further influence the disease risk, after taking into account linkage disequilibrium with the disease loci HLA-DQB1, -DQA1 and -DRB1. We generalized the conditional association test, the haplotype method, to detect marker associations that are independent of the main DR/DQ disease associations. Three regions were identified as risk modifiers. These associations were not only independent of the polymorphic exon 2 sequences of HLA-DQB1, -DQA1 and -DRB1, but also independent of each other. The individual contributions of these risk modifiers were relatively modest but their combined impact was highly significant. Together, alleles of single nucleotide polymorphisms at the DMB and DOB genes, and the microsatellite locus TNFc, identified approximately 40% of Sardinian DR3 haplotypes as non-predisposing. This conditional analysis approach can be applied to any chromosome region involved in the predisposition to complex traits.


LacdiNAc-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.
Although Gal beta 1-4GlcNAc (LacNAc) moieties are the most common constituents of N-linked glycans on vertebrate proteins, GalNAc beta 1-4GlcNAc (LacdiNAc, LDN)-containing glycans are widespread in invertebrates, such as helminths. We postulated that LDN might be a molecular pattern for recognition of helminth parasites by the immune system. Using LDN-based affinity chromatography and mass spectrometry, we have identified galectin-3 as the major LDN-binding protein in macrophages. By contrast, LDN binding was not observed with galectin-1. Surface plasmon resonance (SPR) analysis and a solid phase binding assay demonstrated that galectin-3 binds directly to neoglycoconjugates carrying LDN glycans. In addition, galectin-3 bound to Schistosoma mansoni soluble egg Ags and a mAb against the LDN glycan inhibited this binding, suggesting that LDN glycans within S. mansoni soluble egg Ags contribute to galectin-3 binding. Immunocytochemistry demonstrated high levels of galectin-3 in liver granulomas of S. mansoni-infected hamsters, and a colocalization of galectin-3 and LDN glycans was observed on the parasite eggshells. Finally, we demonstrate that galectin-3 can mediate recognition and phagocytosis of LDN-coated particles by macrophages. These findings provide evidence that LDN-glycans constitute a parasite pattern for galectin-3-mediated immune recognition.


Membrane isolation on polylysine-coated beads. Plasma membrane from HeLa cells.
HeLa cell plasma membranes have been purified after binding cells to polylysine-coated polyacrylamide beads. Cell attachment to beads and membrane recovery were maximal in a sucrose-acetate buffer, pH 5.0, at 25 degrees C. Measurements of ouabain-sensitive NaK-adenosine triphosphatase, membrane-bound 125I-wheat germ agglutinin, and chemical analyses showed that membranes on beads were of comparable or greater purity than membranes isolated by conventional methods. Because the isolation procedure is rapid (approximately 2.5 h), and produces membranes whose protoplasmic surfaces are fully exposed, it should be a useful supplement to standard isolation techniques.


Whole Genome Analysis of a Single Scottish Deerhound Dog Family Provides Independent Corroboration That a SGK3 Coding Variant Leads to Hairlessness.
The breeds of domestic dog, Canis lupus familiaris, display a range of coat types with variation in color, texture, length, curl, and growth pattern. One trait of interest is that of partial or full hairlessness, which is found in a small number of breeds. While the standard for some breeds, such as the Xoloitzcuintli, requires sparse hair on their extremities, others are entirely bald, including the American Hairless Terrier. We identified a small, rare family of Scottish Deerhounds in which coated parents produced a mixed litter of coated and hairless offspring. To identify the underlying variant, we performed whole genome sequencing of the dam and five offspring, comparing single nucleotide polymorphisms and small insertions/deletions against an established catalog of 91 million canine variants. Of 325 homozygous alternative alleles found in both hairless dogs, 56 displayed the expected pattern of segregation and only a single, high impact variant within a coding region was observed: a single base pair insertion in exon two of SGK3 leading to a potential frameshift, thus verifying recently published findings. In addition, we observed that gene expression levels between coated and hairless dogs are similar, suggesting a mechanism other than non-sense mediated decay is responsible for the phenotype.


Sex-related differences in hemato-biochemical indices of adult Vanaraja chickens during summer and winter seasons.
The objective of this study was to evaluate the changes in hemato-biochemical indices in male and female Vanaraja chickens under tropical environment during summer and winter season. A total of 120 day-old sexed Vanaraja chicks were selected as experimental chickens and distributed equally in two groups having 60 female and 60 male chickens in each group, respectively. The experiment was continued for 8 weeks (56 days) and both male and female chickens were slaughtered by cervical dislocation method. All parameters were estimated at the end of the experiment in both seasons. Male had higher blood glucose, Ca and P level. Blood glucose level significantly (p<0.05) reduced in summer. Female had higher total protein, albumin, globulin, and albumin/globulin ratio. Alanine aminotransferase and aspartate aminotransferase enzyme concentration were significantly (p<0.05) higher in summer. Total erythrocyte count, total leukocyte count, hemoglobin (Hb), Hb/lymphocyte ratio, and packed cell volume were significantly (p<0.05) higher in males. Mean corpuscular volume and mean corpuscular Hb were significantly (p<0.05) higher in females. Sex of chickens had a significant (p<0.05) effect on different parameters whereas season had nonsignificant (p>0.05) effect in most of the observed parameters. Hence, Vanaraja chickens are adaptable to local tropical climate and can be reared efficiently as backyard poultry.


Does Internal Fixation for Unstable Osteochondritis Dissecans of the Skeletally Mature Knee Work? A Systematic Review.
To report the rate of radiographic union, patient-reported outcomes, complications, and reoperations after internal fixation of unstable osteochondritis dissecans (OCD) in the skeletally mature knee. A literature search was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Patients were included if they were skeletally mature and underwent internal fixation of an unstable OCD lesion of the knee. Risk of bias assessment was performed using the Methodological Index for Non-randomized Studies scoring system. Surgical technique, rate of union, patient-reported outcomes, complications, and reoperations were collected. Thirteen studies resulted in 148 patients (150 knees) for inclusion. Patient age ranged from 14 to 45 years. Numerous fixation procedures were used, including biodegradable devices (rods, pins, nails, and screws), metal screws, Kirschner wire, and autologous bone sticks. Overall, reported outcome measures were heterogeneous in nature. The rate of radiographic healing ranged from 67% to 100% across 6 studies. Improved subjective results and Hughston criteria on final follow-up ranged from 83% to 100% across 4 studies each. Mean postoperative Lysholm scores ranged from 42 to 98 in studies that reported them. Both complication and reoperation rates ranged from 0% to 44%. The most commonly performed reoperations were loose body excision and cartilage resurfacing procedures. A variety of surgical techniques are available for treatment of unstable OCD lesions in the skeletally mature knee. In this systematic review, internal fixation of the native fragment showed acceptable rates of radiographic union and improved patient-reported outcomes relative to other techniques. Level IV, systematic review of level III-IV studies.


Impact of JIA on parents' work absences.
Children with JIA have long-term morbidity and require extensive parental assistance. This study aimed to evaluate the impact of having a child with JIA on parents' missed work time, which can lead to decreased work productivity. The Truven Health MarketScan Commercial Database (2000-9) was accessed to identify a cohort of parents having a child with newly diagnosed JIA. For comparison, a cohort of parents having no children with JIA was identified and matched with the preceding cohort. Parents' work absences were analysed using descriptive statistics and multivariable regression. Estimates were weighted to be generalizable to the US employer-sponsored insurance population. The study identified 108 parents having a child with newly diagnosed JIA (mean age 42.5 years), representing an estimated 3335 (weighted) parents nationally. Most of them were from the South (45%), male (71%) and employed in the transportation and utilities industry (58%). The demographic characteristics of the control cohort of parents were generally similar. Children with JIA (mean age 10.6 years) represented an estimated 3528 cases nationally. The mean number of reported missed work-time hours was 281.81 (s.e. 40.50) in a 9 year period for parents having a child with JIA compared with other parents 183.36 (28.55). Work-time loss was significantly related to having a child with JIA, sex and geographical region of residence. Parents having a child with JIA were 2.78 times more likely to report work-time loss [odds ratio (OR) 2.78 (95% CI 1.47, 5.26)] than those having no children with JIA. Parents having a child with JIA report significant work-time loss compared with parents with no children having JIA, particularly during the year following the child's diagnosis.