Impaired glucose-insulin metabolism in males with obstructive sleep apnoea syndrome.
The aim of this cross-sectional study was to evaluate the frequency of type-2 diabetes and impaired glucose tolerance (IGT) in a large clinic-based male population presenting various degrees of obstructive sleep apnoea syndrome (OSAS) and to analyse the relationship between OSAS and glucose-insulin metabolism. Male patients (n=595) with suspected OSAS underwent both nocturnal polysomnography and a 2-h oral glucose-tolerance test with measurements of fasting and postload blood glucose and plasma insulin. Insulin sensitivity was evaluated by the ratio of fasting glucose to fasting insulin. OSAS was diagnosed in 494 patients, while 101 patients were nonapnoeic snorers. Type-2 diabetes was present in 30.1% of OSAS patients and 13.9% of nonapnoeic snorers. IGT was diagnosed in 20.0% of OSAS patients and 13.9% of nonapnoeic snorers. Fasting and postload blood glucose increased with severity of sleep apnoea. Insulin sensitivity decreased with increasing severity of sleep apnoea. In addition to body mass index and age, the apnoea/hypopnoea index independently influenced postload blood glucose and insulin sensitivity. The authors conclude that in a clinic-based sample of patients, obstructive sleep apnoea syndrome is associated with a high frequency of type-2 diabetes and impaired glucose tolerance. The relationship between sleep-disordered breathing and impaired glucose-insulin metabolism is independent of obesity and age.


Increased circulating progenitor cells in Alzheimer's disease patients with moderate to severe dementia: evidence for vascular repair and tissue regeneration?
Cerebrovascular dysfunction is a common finding in patients with Alzheimer's disease (AD) and may contribute to cognitive decline. Abundant evidence suggests that vascular and neuronal repair mechanisms are mediated by circulating progenitor cells in vivo. Whether CD34+ and, specifically, CD34+/CD133+ progenitor cells are involved in the pathophysiology of AD is poorly understood so far. In the present study, peripheral blood concentrations of circulating CD34+/CD133+ and CD34+ progenitor cells were measured in 45 AD patients and in 30 healthy elderly controls by flow cytometry. The severity of dementia was assessed by Mini-Mental Status Examination and Clinical Dementia Rating scale. AD patients were stratified into two groups showing mild (n=17) and moderate to severe (n= 28) dementia. In the present study, AD patients with moderate to severe dementia, but not those with mild dementia, showed significantly increased circulating CD34+/CD133+ and CD34+ progenitor cells compared to healthy elderly controls independent of cardiovascular risk factors and medication. In addition, the number of circulating CD34+/CD133+ progenitor cells in AD patients was significantly inversely correlated with cognitive function, age, and plasma levels of SDF-1, the most potent chemokine for progenitor cells. Our findings suggest a stage-dependent upregulation of circulating CD34+/CD133+ and CD34+ progenitor cells in AD patients, which could take part in tissue healing processes of the brain in AD.


A full set of iridium(iv) pyridine-alkoxide stereoisomers: highly geometry-dependent redox properties.
We introduce and characterize the complete set of possible isomers of IrIV(pyalk)2Cl2 (pyalk = 2-(pyridin-2-yl)propan-2-oate), providing valuable insights on the properties of Ir(iv) species. The pyridine alkoxide ligand strongly stabilizes high oxidation states, essential to accessing the catalytically relevant Ir(iv) state, and results in robust complexes that can be handled under ambient conditions, even permitting chromatographic separation. The redox properties are isomer-dependent, spanning a 300 mV range, rationalized with ligand-field theory and DFT calculations. The reported complexes exhibit very high kinetic inertness against isomerization, despite highly disparate predicted thermodynamic stabilities, presenting a unique opportunity to study all five possible isomeric complexes with the same ligand set.


Applications of CRISPR/Cas9 in a rice protein expression system via an intron-targeted insertion approach.
The sugar starvation-inducible rice αAmy3 promoter and signal peptide are widely used to produce valuable recombinant proteins in rice suspension culture cells. Conventionally, the recombinant gene expression cassette is inserted into the genome at random locations by Agrobacterium- or particle bombardment-mediated transformation. CRISPR/Cas9 gene editing enables gene insertion at a precise target site in the genome. In this study the CRISPR/Cas9 approach was modified for intron-targeted insertion by adding an artificial 3' splicing site upstream of the recombinant gene. Knock-in transgenic rice cell lines containing the recombinant GFP gene inserted in intron 1 of αAmy3 were generated. The endogenous αAmy3 promoter regulated recombinant gene expression and the αAmy3 signal peptide directed secretion of the recombinant GFP protein into the culture medium. In addition, the recombinant GFP protein was localized in amyloplasts, identical to the subcellular localization of endogenous αAmy3 reported previously. This modified CRISPR/Cas9 knock-in approach is simple and highly efficient, and the recombinant gene insertion frequency attained 12.5%. The approach can be applied in the production of pharmaceutical proteins in rice suspension cell cultures. The high efficiency of the GFP reporter gene knock-in method and the maintenance of target gene behavior also make the strategy applicable to endogenous gene functional studies in rice.


Evaluation of Th17 pathway in the diagnosis of autosomal dominant polycystic kidney disease.
Current assessment tools of autosomal dominant polycystic kidney disease (ADPKD) diagnosis are challenging. This study evaluated the possible application of assessment of interleukin (IL)-17-related cytokines and the circulatory T helper 17 cells in the diagnosis of ADPKD. Enrolling 54 ADPKD patients and 54 healthy individuals, we measured serum and urine levels of IL-6, IL-17, IL-23, and transforming growth factor-β and the peripheral blood frequency of T helper 17 cells through flowcytometry. We computed sensitivity and specificity of each inflammatory marker as well as their different combinations using the receiver operating characteristic curve and discriminant function analysis. The mean serum and urine levels of IL-17 and IL-23 as well as urine levels of IL-6 were higher in ADPKD patients compared to the healthy controls (P < .001). There was no significant difference in the number of T helper 17 cells between the two groups. Among different combinations of the inflammatory markers, the serum IL-17 was the best factor in the diagnosis of ADPKD with a sensitivity as well as specificity of 100%. It is likely that T helper 17 pathway is involved in the pathogenesis of ADPKD; therefore, it may be beneficial if such a pathway be considered in its diagnosis.


[Pontine reversible leucopathy in an AIDS patient associated with highly active antiretroviral therapy (HAART): Report of one case].
Posterior reversible encephalopathy (PRES) is a condition characterized by T2 and FLAIR hyperintensities in magnetic resonance imaging (MRI) studies, localized preferentially in the occipital-parietal white matter regions. Pathological MRI images located in midbrain, pons, medulla and spinal cord, that could be asymptomatic, were recently included in this entity. These images are interpreted as vasogenic edema, which is caused by arterial hypertension or eclampsia, neurotoxicity related to immunosuppressive agents or chemotherapy, among other causes. We report a 25 years old asymptomatic male with AIDS, with normal blood pressure who after initiating highly active antiretroviral therapy (HAART) reported vertigo. The MRI showed a central pontine T2 hyperintensity with diffusion restriction, which was interpreted as a central pontine myelinolysis (CPM), but the lack of motor symptoms made improbable a real demyelination of the pons. The follow-up MRI revealed complete regression of the images. To our knowledge, this case could be the second report of a reversible leucopathy of the pons in a patient with AIDS, were the MRI images also simulated a CPM. This report extends the knowledge around the variability of the pathogenic interpretation of CPM images and their association with HAART.


Do hematopoietic cells exposed to a neurogenic environment mimic properties of endogenous neural precursors?
Hematopoietic progenitors are cells, which under challenging experimental conditions can develop unusual phenotypic properties, rather distant from their original mesodermal origin. As previously reported, cells derived from human umbilical cord blood (HUCB) or human bone marrow (BM) under certain in vivo or in vitro conditions can manifest neural features that resemble features of neural-derived cells, immunocytochemically and in some instances also morphologically. The present study explored how hematopoietic-derived cells would respond to neurogenic signals from the subventricular zone (SVZ) of adult and aged (6 and 16 months old) rats. The mononuclear fraction of HUCB cells was transplanted into the SVZ of immunosuppressed (single cyclosporin or three-drug treatment) animals. The triple-suppression paradigm allowed us to protect transplanted human cells within the brain and to explore further their phenotypic and migratory properties. One week after implantation, many surviving HUCB cells were located within the SVZ and the vertical limb of the rostral migratory stream (RMS). The migration of HUCB cells was restricted exclusively to the pathway leading to the olfactory bulb. In younger animals, grafted cells navigated almost halfway through the vertical limb, whereas, in the older animals, the migration was less pronounced. The overall cell survival was greater in younger animals than in older ones. Immunocytochemistry for surface CD antigen expression showed that many HUCB cells, either cultured or within the brain parenchyma, retained their hematopoietic identity. A few cells, identified by using human-specific antibodies (anti-human nuclei, or mitochondria) expressed nestin and doublecortin, markers of endogenous neural progenitors. Therefore, it is believed that the environment of the neurogenic SVZ, even in aged animals, was able to support survival, "neuralization," and migratory features of HUCB-derived cells.


Prediction of Match Outcomes with Multivariate Statistical Methods for the Group Stage in the UEFA Champions League.
The aim of this study was to analyse the win, draw, and loss outcomes of soccer matches with situational variables and performance indicators. Data from group stage matches spanning the ten years between the 2010/2011 and 2019/2020 seasons in the European Champions League, were used. One-way analysis of variance (ANOVA) and Tukey HSD (honestly significant difference) tests indicated performance indicators which affected the outcome of matches. K-mean clustering, with statistically significant variables, categorized the quality of the opposition into three clusters: weak, balanced, and strong. Multidimensional scaling (MDS) and decision tree analysis were applied to each of these clusters, highlighting that performance indicators of the teams differed according to the quality of their opponent. Furthermore, according to the decision tree analysis, certain performance indicators, including scoring first and shots on target, increased the chances of winning regardless of the quality of the opposition. Finally, particular performance indicators increased the chance of winning, while others decreased this, in accordance with the quality of the opposition. These findings can help coaches develop different strategies, before or during the match, based on the quality of opponents, situational variables, and performance indicators.


Stimulating Neoblast-Like Cell Proliferation in Juvenile Fasciola hepatica Supports Growth and Progression towards the Adult Phenotype In Vitro.
Fascioliasis (or fasciolosis) is a socioeconomically important parasitic disease caused by liver flukes of the genus Fasciola. Flukicide resistance has exposed the need for new drugs and/or a vaccine for liver fluke control. A rapidly improving 'molecular toolbox' for liver fluke encompasses quality genomic/transcriptomic datasets and an RNA interference platform that facilitates functional genomics approaches to drug/vaccine target validation. The exploitation of these resources is undermined by the absence of effective culture/maintenance systems that would support in vitro studies on juvenile fluke development/biology. Here we report markedly improved in vitro maintenance methods for Fasciola hepatica that achieved 65% survival of juvenile fluke after 6 months in standard cell culture medium supplemented with 50% chicken serum. We discovered that this long-term maintenance was dependent upon fluke growth, which was supported by increased proliferation of cells resembling the "neoblast" stem cells described in other flatworms. Growth led to dramatic morphological changes in juveniles, including the development of the digestive tract, reproductive organs and the tegument, towards more adult-like forms. The inhibition of DNA synthesis prevented neoblast-like cell proliferation and inhibited growth/development. Supporting our assertion that we have triggered the development of juveniles towards adult-like fluke, mass spectrometric analyses showed that growing fluke have an excretory/secretory protein profile that is distinct from that of newly-excysted juveniles and more closely resembles that of ex vivo immature and adult fluke. Further, in vitro maintained fluke displayed a transition in their movement from the probing behaviour associated with migrating stage worms to a slower wave-like motility seen in adults. Our ability to stimulate neoblast-like cell proliferation and growth in F. hepatica underpins the first simple platform for their long-term in vitro study, complementing the recent expansion in liver fluke resources and facilitating in vitro target validation studies of the developmental biology of liver fluke.


Single-trial EEG dissociates motivation and conflict processes during decision-making under risk.
In making decisions under risk (i.e., choosing whether to gamble when the outcome probabilities are known), two aspects of decision are of particular concern. The first, if gambling, is how large are potential gains compared to losses? The subjectively larger, the more rewarding to gamble. Thus, this aspect of decision-making, quantified through expected utility (EU), is motivation-related. The second concern is how easy is it to reach the decision? When subjective desirability between gambling and not-gambling is clearly different from each other (regardless of the direction), it is easier to decide. This aspect, quantified through utility distance (UD), is conflict-related. It is unclear how the brain simultaneously processes these two aspects of decision-making. Forty-five participants decided whether to gamble during electroencephalogram (EEG) recording. To compute trial-by-trial variability in EU and UD, we fit participants' choices to models inspired by Expected-Utility and Prospect theories using hierarchical-Bayesian modeling. To examine unique influences of EU and UD, we conducted model-based single-trial EEG analyses with EU and UD as simultaneous regressors. While both EU and UD were positively associated with P3-like activity and delta-band power, the contribution of EU was around 200 ms earlier. Thus, during decision-making under risk, people may allocate their attention to motivation-related aspects before conflict-related aspects. Next, following learning the options and before reporting their decision, higher EU was associated with stronger alpha and beta suppression, while higher UD was associated with a stronger contingent-negativity-variation-like activity. This suggests distinct roles of EU and UD on anticipation-related processes. Overall, we identified time and frequency characteristics of EEG signals that differentially traced motivation-related and conflict-related information during decision-making under risk.


CXCR4, CXCR5 and CD44 May Be Involved in Homing of Lymphoma Cells into the Eye in a Patient Derived Xenograft Homing Mouse Model for Primary Vitreoretinal Lymphoma.
Background: Primary vitreoretinal lymphoma (PVRL), a rare malignancy of the eye, is strongly related to primary central nervous system lymphoma (PCNSL). We hypothesized that lymphoma cells disseminate to the CNS and eye tissue via distinct homing receptors. The objective of this study was to test expression of CXCR4, CXCR5, CXCR7 and CD44 homing receptors on CD20 positive B-lymphoma cells on enucleated eyes using a PCNSL xenograft mouse model. Methods: We used indirect immunofluorescence double staining for CD20/CXCR4, CD20/CXCR5, CD20/CXCR7 and CD20/CD44 on enucleated eyes of a PCNSL xenograft mouse model with PVRL phenotype (PCNSL group) in comparison to a secondary CNS lymphoma xenograft mouse model (SCNSL group). Lymphoma infiltration was evaluated with an immunoreactive score (IRS). Results: 11/13 paired eyes of the PCNSL but none of the SCNSL group were infiltrated by CD20-positive cells. Particularly the choroid and to a lesser extent the retina of the PCNSL group were infiltrated by CD20+/CXCR4+, CD20+/CXCR5+, few CD20+/CD44+ but no CD20+/CXCR7+ cells. Expression of CXCR4 (p = 0.0205), CXCR5 (p = 0.0004) and CD44 (p < 0.0001) was significantly increased in the PCNSL compared to the SCNSL group. Conclusions: CD20+ PCNSL lymphoma cells infiltrating the eye co-express distinct homing receptors such as CXCR4 and CXCR5 in a PVRL homing mouse model. These receptors may be involved in PVRL homing into the eye.


Prescribing habits of Peruvian physicians and factors influencing them.
A survey conducted between September 1991 and August 1992 approached 800 physicians in two marginal areas of the cities of Lima and Chimbote, Peru. Among other things, the survey sought data about information sources influencing the drug prescription practices of Peruvian physicians, about how these practices were modified by experience, and about the rationality of drug treatments prescribed for dealing with selected common ailments. Of the 800 physicians, 184 had already established themselves in private practice, 309 were recent medical school graduates, and 307 did not complete the survey questionnaire. The responses provided suggested that knowledge acquired in medical school had little influence on the prescribing habits of either the established physicians or the recent graduates. Over two-thirds of both groups (69.6% of the physicians in private practice and 79.9% of the recent medical school graduates) indicated that their primary source of drug information was medical literature. Overall, however, data from this and related studies suggest that while the medical school influence was limited, the role of medical literature was less powerful than the survey participants claimed-because advertising materials distributed by pharmaceutical companies appeared to constitute a key source of information, one that tended to promote irrational drug use.


Plasma levels of soluble receptor for advanced glycation end products in patients with acute respiratory distress syndrome.
The acute respiratory distress syndrome (ARDS) is a syndrome of acute respiratory failure associated with severe inflammation and diffuse alveolar damage. Recent studies have demonstrated that the soluble receptor for advanced glycation end products (sRAGE) plays an important role in the pathogenesis of ARDS. The aim of this study was to ascertain whether plasma levels of sRAGE were elevated in ARDS patients compared with appropriate controls. Furthermore, we explored whether plasma levels of sRAGE were related to disease severity, ventilatory parameters and clinical outcome. We prospectively enrolled twenty-two ARDS patients, fourteen ventilated controls and twelve healthy subjects. The Sequential Organ Failure Assessment (SOFA) score was applied to assess illness severity. In addition, ventilator parameters (arterial oxygen tension (PaO2): inspiratory oxygen fraction (FiO2) ratio, arterial carbon dioxide tension (PaCO2), tidal volume and positive end-expiratory pressure (PEEP)) of ARDS patients and ventilated controls were also recorded. Plasma samples were collected within 24 hours and levels of sRAGE were determined using a commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. Possible correlation between plasma sRAGE levels and clinical parameters were explored using a simple linear model. Plasma sRAGE levels were significantly elevated in the plasma samples taken from patients with ARDS (1797 ± 383 pg/ml) when compared with both ventilated (650 ± 192 pg/ml, P < 0.01) and healthy (415 ± 178 pg/ml, P < 0.01) controls. Significant correlations were found between plasma sRAGE levels and PaO2:FiO2 ratio (P < 0.05, r=0.36). There was no significant difference in plasma sRAGE levels between survivors and non-survivors (P=0.34). Our results demonstrate that elevated levels of plasma sRAGE may provide a useful marker for ventilated ARDS patients. Furthermore, the relationship between plasma sRAGE levels and PaO2:FiO2 ratio in the ARDS population provides the hypothesis that ventilatory strategy may influence alveolar epithelial damage in ARDS.


Glycomic and Glycoproteomic Techniques in Neurodegenerative Disorders and Neurotrauma: Towards Personalized Markers.
The proteome represents all the proteins expressed by a genome, a cell, a tissue, or an organism at any given time under defined physiological or pathological circumstances. Proteomic analysis has provided unparalleled opportunities for the discovery of expression patterns of proteins in a biological system, yielding precise and inclusive data about the system. Advances in the proteomics field opened the door to wider knowledge of the mechanisms underlying various post-translational modifications (PTMs) of proteins, including glycosylation. As of yet, the role of most of these PTMs remains unidentified. In this state-of-the-art review, we present a synopsis of glycosylation processes and the pathophysiological conditions that might ensue secondary to glycosylation shortcomings. The dynamics of protein glycosylation, a crucial mechanism that allows gene and pathway regulation, is described. We also explain how-at a biomolecular level-mutations in glycosylation-related genes may lead to neuropsychiatric manifestations and neurodegenerative disorders. We then analyze the shortcomings of glycoproteomic studies, putting into perspective their downfalls and the different advanced enrichment techniques that emanated to overcome some of these challenges. Furthermore, we summarize studies tackling the association between glycosylation and neuropsychiatric disorders and explore glycoproteomic changes in neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington disease, multiple sclerosis, and amyotrophic lateral sclerosis. We finally conclude with the role of glycomics in the area of traumatic brain injury (TBI) and provide perspectives on the clinical application of glycoproteomics as potential diagnostic tools and their application in personalized medicine.


Pediatric Hand Surgery Training in Nicaragua: A Sustainable Model of Surgical Education in a Resource-Poor Environment.
Recent reports have demonstrated that nearly two-thirds of the world's population do not have access to adequate surgical care, a burden that is borne disproportionately by residents of resource-poor countries. Although the reasons for limited access to surgical care are complex and multi-factorial, among the most substantial barriers is the lack of trained surgical providers. This is particularly true in surgical subspecialties that focus on life-improving, rather than life-saving, treatments, such as pediatric hand and upper extremity surgery, which manages such conditions as congenital malformations, trauma and post-traumatic deformities including burns, and neuromuscular conditions (brachial plexus birth palsy, spinal cord injury, and cerebral palsy). Many models of providing surgical care in resource-limited environments have been described and implemented, but few result in sustainable models of health-care delivery. We present our experience developing a pediatric hand and upper extremity surgery training program in Nicaragua, a resource-limited nation, that grew out of a collaboration of American and Nicaraguan orthopedic surgeons. We compare this experience to that of surgeons undergoing subspecialty training in pediatric upper limb surgery in the US, highlighting the similarities and differences of these training programs. Finally, we assess the results of this training program and identify areas for further growth and development.


Ampelopsin suppresses TNF-α-induced migration and invasion of U2OS osteosarcoma cells.
Ampelopsin has been suggested as a novel anticancer agent, however, there is no evidence regarding its direct effect on the migration and invasion of osteosarcoma cells. The aims of the present study were to investigate the influence of ampelopsin on the migration and invasion of osteosarcoma cells and to clarify the underlying mechanisms. Scratch wound healing and Transwell assays were used to measure the migratory and invasive activities of the cells, respectively. The protein and RNA levels of matrix metalloproteinase-2 (MMP-2) were detected with western blot and RT-qPCR, respectively, following stimulation with tumor necrosis factor‑α (TNF-α) and ampelopsin. The expression levels of phospho‑ and total-p38MAPK were detected using western blot analysis. Additionally, SB203580, an inhibitor of p38MAPK, was used to investigate the effect of TNF‑α and ampelopsin. The results demonstrated that TNF‑α upregulated the expression level of MMP‑2 and promoted the migration and invasion of osteosarcoma cells. TNF‑α also activated the p38MAPK pathway, and SB203580 significantly inhibited the effect of TNF‑α on MMP‑2 expression. The application of ampelopsin abolished the effects of TNF‑α on the activation of the p38MAPK pathway and the expression of MMP‑2, and downregulated the migration and invasion of the osteosarcoma cells. These results demonstrated that ampelopsin inhibits the TNF‑α‑induced migration and invasion of osteosarcoma cells, and that the effect of ampelopsin was mediated by p38MAPK/MMP‑2 signaling.


Multimeric structures of HLA-G isoforms function through differential binding to LILRB receptors.
The non-classical Human leukocyte antigen G (HLA-G) differs from classical HLA class I molecules by its low genetic diversity, a tissue-restricted expression, the existence of seven isoforms, and immuno-inhibitory functions. Most of the known functions of HLA-G concern the membrane-bound HLA-G1 and soluble HLA-G5 isoforms, which present the typical structure of classical HLA class I molecule: a heavy chain of three globular domains α1-α2-α3 non-covalently bound to β-2-microglobulin (B2M) and a peptide. Very little is known of the structural features and functions of other HLA-G isoforms or structural conformations other than B2M-associated HLA-G1 and HLA-G5. In the present work, we studied the capability of all isoforms to form homomultimers, and investigated whether they could bind to, and function through, the known HLA-G receptors LILRB1 and LILRB2. We report that all HLA-G isoforms may form homodimers, demonstrating for the first time the existence of HLA-G4 dimers. We also report that the HLA-G α1-α3 structure, which constitutes the extracellular part of HLA-G2 and HLA-G6, binds the LILRB2 receptor but not LILRB1. This is the first report of a receptor for a truncated HLA-G isoform. Following up on this finding, we show that the α1-α3-Fc structure coated on agarose beads is tolerogenic and capable of prolonging the survival of skin allografts in B6-mice and in a LILRB2-transgenic mouse model. This study is the first proof of concept that truncated HLA-G isoforms could be used as therapeutic agents.


Primates highly responsive to dietary cholesterol up-regulate hepatic ACAT2, and less responsive primates do not.
The role of liver acyl-CoA:cholesterol acyltransferase 2 (ACAT2), earlier shown to be the principal ACAT enzyme within primate hepatocytes, as a regulator of the hypercholesterolemia induced by dietary cholesterol was studied. At the end of low and high cholesterol diet periods, liver biopsies were taken from cynomolgus monkeys, a species highly responsive to dietary cholesterol, and less responsive African green monkeys. Liver cholesterol and cholesteryl ester concentrations were highest in cynomolgus monkeys fed cholesterol, despite the fact that in order to induce equivalent hypercholesterolemia, dietary cholesterol levels were 50% lower than was fed to green monkeys. Hepatic cholesteryl oleate secretion rate, measured during liver perfusion as an indicator of ACAT activity, was significantly higher in cynomolgus monkeys. Liver microsomal ACAT activity was 2-3-fold higher in cynomolgus monkeys than in green monkeys. The responses of ACAT2 were compared with those of ACAT1 that is found primarily in Kupffer cells. ACAT2 protein mass was significantly correlated to microsomal total ACAT activity in both species; ACAT1 mass was less well correlated. Dietary cholesterol induced a significant 3-fold increase of ACAT2 protein mass in cynomolgus monkeys, a much greater increase than was found for mRNA abundance; neither ACAT2 mRNA nor protein was diet-responsive in green monkeys. In cynomolgus monkeys but not in green monkeys, liver free cholesterol concentrations were elevated when cholesterol was fed and were correlated with ACAT2 protein levels. The data suggest a mechanism whereby the elevation of hepatic free cholesterol concentrations by dietary cholesterol, seen only in cynomolgus monkeys, resulted in higher ACAT2 protein levels in hepatocytes, either through increased production or stabilization of the protein. Regulation of ACAT2 gene transcription was not a factor.


Hydrodynamic description of elastic or viscoelastic composite materials: Relative strains as macroscopic variables.
One possibility to adjust material properties to a specific need is to embed units of one substance into a matrix of another substance. Even materials that are readily tunable during operation can be generated in this way. In (visco)elastic substances, both the matrix material as well as the inclusions and/or their immediate environment can be dynamically deformed. If the typical dynamic response time of the inclusions and their surroundings approach the macroscopic response time, their deformation processes need to be included into a dynamic macroscopic characterization. Along these lines, we present a hydrodynamic description of (visco)elastic composite materials. For this purpose, additional strain variables reflect the state of the inclusions and their immediate environment. These additional strain variables in general are not set by a coarse-grained macroscopic displacement field. Apart from that, during our derivation, we also include the macroscopic variables of relative translations and relative rotations that were previously introduced in different contexts. As a central point, our approach reveals and classifies the importance of a macroscopic variable termed relative strains. We analyze two simplified minimal example geometries as an illustration.


Readmissions to Intensive Care: A Prospective Multicenter Study in Australia and New Zealand.
To determine factors independently associated with readmission to ICU and the independent association of readmission with subsequent mortality. Prospective multicenter observational study. Forty ICUs in Australia and New Zealand. Consecutive adult patients discharged alive from ICU to hospital wards between September 2009 and February 2010. Measurement of hospital mortality. We studied 10,210 patients and 674 readmissions. The median age was 63 years (interquartile range, 49-74), and 6,224 (61%) were male. The majority of readmissions were unplanned (84.1%) but only deemed preventable in a minority (8.9%) of cases. Time to first readmission was shorter for unplanned than planned readmission (3.2 vs 6.9 d; p < 0.001). Primary diagnosis changed between admission and readmission in the majority of patients (60.2%) irrespective of planned (58.2%) or unplanned (60.6%) status. Using recurrent event analysis incorporating patient frailty, we found no association between readmissions and hospital survival (hazard ratios: first readmission 0.88, second readmission 0.90, third readmission 0.44; p > 0.05). In contrast, age (hazard ratio, 1.03), a medical diagnosis (hazard ratio, 1.43), inotrope use (hazard ratio, 3.47), and treatment limitation order (hazard ratio, 17.8) were all independently associated with outcome. In this large prospective study, readmission to ICU was not an independent risk factor for mortality.


Modulation of dendritic synaptic processing in the lateral superior olive by hyperpolarization-activated currents.
We have previously shown that mice lateral superior olive (LSO) neurons exhibit a large hyperpolarization-activated current (I(h) ), and that hyperpolarization-activated cyclic-nucleotide-gated type 1 channels are present in both the soma and dendrites of these cells. Here we show that the dendritic I(h) in LSO neurons modulates the integration of multiple synaptic inputs. We tested the LSO neuron's ability to integrate synaptic inputs by evoking excitatory post-synaptic potentials (EPSPs) in conjunction with brief depolarizing current pulses (to simulate a second excitatory input) at different time delays. We compared LSO neurons with the native I(h) present in both the soma and dendrites (control) with LSO neurons without I(h) (blocked with ZD7288) and with LSO neurons with I(h) only present peri-somatically (ZD7288+ computer-simulated I(h) using a dynamic clamp). LSO neurons without I(h) had a wider time window for firing in response to inputs with short time separations. Simulated somatic I(h) (dynamic clamp) could not reverse this effect. Blocking I(h) also increased the summation of EPSPs elicited at both proximal and distal dendritic regions, and dramatically altered the integration of EPSPs and inhibitory post-synaptic potentials. The addition of simulated peri-somatic I(h) could not abolish a ZD7288-induced increase of responsiveness to widely separated excitatory inputs. Using a compartmental LSO model, we show that dendritic I(h) can reduce EPSP integration by locally decreasing the input resistance. Our results suggest a significant role for dendritic I(h) in LSO neurons, where the activation/deactivation of I(h) can alter the LSO response to synaptic inputs.


[Use of leukocytic serum in treatment of shin trophic ulcers with protracted healing].
The results of treatment of 85 patients with trophic ulcers of various origin by leukocytic serum were compared with the results of treatment of 46 patients treated by routine method. The best clinical and aesthetic effect of this treatment was revealed in a group of patients with trophic ulcers due to vein varicosity. From 58 patients epithelization was detected in 49 (84,5%). The relapses of trophic ulcers in a period from 6 months to 1,5 years were revealed in 5 patients. The use of leukocytic serum ensures high percent of closure of the ulcers chiefly of venous etiology.


Regulation of the groESL1 transcription by the HrcA repressor and a novel transcription factor Orf7.5 in the cyanobacterium Synechococcus elongatus PCC7942.
The CIRCE/HrcA system is highly conserved in cyanobacterial genomes. We have shown that heat-shock induction of the groESL1 operon in the cyanobacterium Synechocystis sp. PCC6803 is negatively regulated by the CIRCE/HrcA system. In Synechococcus elongatus PCC7942, a novel heat shock protein, Orf7.5, is involved in positive regulation of the groESL1 transcription. However, Orf7.5 is not conserved in some cyanobacteria, including Synechocystis sp. PCC6803. The purpose of this study is to evaluate the functional conservation of the CIRCE/HrcA system in S. elongatus PCC7942 and to understand the interplay between the CIRCE/HrcA system and the Orf7.5 regulatory system. We constructed single and double mutants of S. elongatus orf7.5, hrcA and orf7.5/hrcA and heat induction of the groESL1 transcription in these mutants was analyzed. Unexpectedly, derepression of the groESL1 transcription in an hrcA mutant was not observed. In all these mutants, the transcription was greatly suppressed under both normal and heat stress conditions, indicating that both HrcA and Orf7.5 are involved in regulation of the groESL1 transcription in a positive way. Consistent with the decrease in the groESL1 mRNA level, all the single and double mutants showed a great loss of acquired thermotolerance. Heat induction of the orf7.5 promoter activity was totally diminished in the orf7.5 mutant, indicating that Orf7.5 activates its own transcription. Yeast two hybrid analysis showed that the principle sigma factor RpoD1 interacts with Orf7.5. These results indicate that Orf7.5 enhances the transcription of groESL1 and orf7.5 by interacting with RpoD1.


Patterns of Polydrug Use Classes Among a Subset of Latino Male Seasonal Workers in South Florida: A Latent Class Analysis.
Little is known about polydrug use among Latino seasonal farmworkers. This cross-sectional study with male Latino seasonal workers (LSWs) living in South Florida categorized distinct classes of drug use and then characterized each drug use typology by demographic, structural, and psychological factors. One hundred and twenty-five male LSWs were recruited during community events using convenience sampling between July 2019-March 2020. Latent class analysis was conducted by leveraging measures of self-reported use of nine drugs in the past year (sedatives, cannabis, stimulants, heroin, opioids, cocaine, PCP, hallucinogens, and inhalants). Correlates of latent class membership were examined using 3-step categorical latent variable logistic regression. Analyses were performed using Mplus version 8 and SAS 9.4. Four drug use classes were identified, male LSWs who exhibited: 1) use of illegal opioids only (n = 32); 2) concurrent cannabis and cocaine use (n = 75); 3) concurrent sedative and cannabis use (n = 13); and 4) high concurrent drug use (n = 5). About 84.7% of the sample reported use of at least one drug in the past 12 months. LSWs who identified as White and were married or in a stable relationship were likely to only use illegal opioids. LSWs with less than high school education and self-reported good to excellent health were more likely to use cannabis and cocaine. Men with moderate to severe anxiety and self-reported bad health were classified as engaging in sedative and cannabis co-use. Survivors of physical abuse were more commonly classified as people using high concurrent substances relative to non-abused men among the four classes. This pilot study suggests the presence of heterogeneity in polydrug use classes among LSWs in South Florida.


Effect of dexamethasone on vascular function in RIF-1 tumors.
The present series of experiments was conducted to determine the effect of dexamethasone on vascular function and cell proliferation in s.c. RIF-1 tumors. 125I-BSA, 51Cr-EDTA dilution techniques were used to evaluate dexamethasone induced changes in tumor plasma water, capillary permeability, and extracellular water volumes, while 59Fe and 51Cr labeled erythrocyte techniques were used to assess changes in tumor exchangeable erythrocyte volumes. 86RbCl distribution studies were also conducted to evaluate vascular perfusion in RIF-1 tumors after dexamethasone treatment. In this corticosteroid receptor containing tumor model, dexamethasone had profound effects on all of the measured parameters of vascular function. Reduced tumor cell proliferation after dexamethasone treatments was accompanied by reduced capillary permeability, reduced interstitial water volumes, increased plasma volumes, and reduced vascular perfusion. Serial studies after dexamethasone treatments indicated that increases in vascular perfusion preceded proliferative recovery. Intervals of maximal [3H]thymidine labeling after dexamethasone were characterized by transient increases in capillary permeability, interstitial water volumes, and tumor erythrocyte exchange with the general circulation. At intervals of maximal cell proliferation (36-48 h after dex) 86RbCl distribution in tumors was about 3 times that seen in untreated controls. The results seem to indicate that, as in edematous normal tissues, dexamethasone can have profound effects on vascular function and water compartmentalization in RIF-1 tumors.


The Effect of Breath Pacing on Task Switching and Working Memory.
The cortical and subcortical circuit regulating both cognition and cardiac autonomic interactions are already well established. This circuit has mainly been analyzed from cortex to heart. Thus, the heart rate variability (HRV) is usually considered a reflection of cortical activity. In this paper, we investigate whether HRV changes affect cortical activity. Short-term local autonomic changes were induced by three breathing strategies: spontaneous (Control), normal (NB) and slow paced breathing (SB). We measured the performance in two cognition domains: executive functions and processing speed. Breathing maneuvres produced three clearly differentiated autonomic states, which preconditioned the cognitive tasks. We found that the SB significantly increased the HRV low frequency (LF) power and lowered the power spectral density (PSD) peak to 0.1[Formula: see text]Hz. Meanwhile, executive function was assessed by the working memory test, whose accuracy significantly improved after SB, with no significant changes in the response times. Processing speed was assessed by a multitasking test. Consistently, the proportion of correct answers (success rate) was the only dependent variable affected by short-term and long-term breath pacing. These findings suggest that accuracy, and not timing of these two cognitive domains would benefit from short-term SB in this study population.


Hypoglycemic effects of date seed extract. Possible mechanism of action, and potential therapeutic implications.
To investigate the possible mechanism, by which an extract from date seeds exert its hypoglycemic effect. This study was performed at the Anatomy Department, College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia from May to December 2012. Eighty rats were divided into 4 groups. Group 1 received no treatment. Group 2 received daily ingestions of 10 ml of date seed extract for 8 weeks. Animals of groups 3 and 4 were made diabetic by streptozotocin injection, and were given daily subcutaneous injections of 3 IU/day of insulin for 8 weeks. Group 4 received, in addition, daily ingestions of 10 ml of seed extracts. Rats were sacrificed, and the sera were separated for estimation of serum C-peptide levels. Pancreatic tissues were processed for histological study of the islet cells, immunohistochemical study for insulin secretion and image analysis for insulin quantification. Mean serum C-peptide level was significantly higher in group 4 compared to group 3. Pancreatic islets from rats of group 3 showed weak immunoreactivity for insulin, while those of group 4 showed strong immunoreactivity in some hypertrophied beta cells. Immunopositive cells were detected in the wall of interlobular ducts and in centroacinar cells of pancreas only in group 4. Quantification of insulin immunoreactivity showed a marked reduction in islet size and extent of insulin immunoreactivity in diabetic compared to control groups. Date seed extracts may stimulate endogenous insulin secretion through extra-islet sources.


Dynamic MRI of cerebrospinal fluid flow in endoscopic percutaneous ventriculostomy.
Endoscopic percutaneous ventriculostomy (EPV) is a new technique to restore the flow of the cerebrospinal fluid (CSF) to the basal cistern in patients with non-communicating hydrocephalus (NCH). Cardiac gated MRI techniques have been applied to demonstrate normal and abnormal CSF flow in humans. The aim of this study was to evaluate the ability of a new multislice spin echo dynamic MRI technique and amplitude and phase reconstruction to demonstrate the impairment of CSF flow through the aqueduct preoperatively and to assess the patency of the ventriculostomy after surgery. Thirteen patients with NCH were studied with dynamic MRI before and after EPV using multiple sagittal multislice gated SE acquisitions to demonstrate the CSF flow. Nine patients were clinically improved by EPS, two remained unchanged and two deteriorated. The permeability of the ventriculostomy was confirmed in all patients. We think that MRI flow studies are useful to demonstrate the site of impairment of CSF flow and its aetiology preoperatively, and to assess the permeability of the ventriculostomy after surgery in a non invasive way.


Influence of tube voltage, tube current and newer iterative reconstruction algorithms in CT perfusion imaging in rabbit liver VX2 tumors.
We aimed to explore the influence of tube voltage, current and iterative reconstruction (IR) in computed tomography perfusion imaging (CTPI) and to compare CTPI parameters with microvessel density (MVD). Hepatic CTPI with three CTPI protocols (protocol A, tube voltage/current 80 kV/40 mAs; protocol B, tube voltage/current 80 kV/80 mAs; protocol C: tube voltage/current 100 kV/80 mAs) were performed in 25 rabbit liver VX2 tumor models, and filtered back projection (FBP) and IR were used for reconstruction of raw data. Hepatic arterial perfusion (HAP), hepatic portal perfusion (HPP), total perfusion (TP), hepatic arterial perfusion index (HPI), blood flow (BF) and blood volume (BV) of VX2 tumor and normal hepatic parenchyma were measured. Image noise, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were quantified and radiation dose was recorded. MVD was counted using CD34 stain and compared with CTPI parameters. The highest radiation dose was found in protocol C, followed by protocols B and A. IR lowered image noise and improved SNR and CNR in all three protocols. There was no statistical difference between HAP, HPP, TP, HPI, BF and BV of VX2 tumor and normal hepatic parenchyma among the three protocols (P > 0.05) with FBP or IR reconstruction, and no statistical difference between IR and FBP reconstruction (P > 0.05) in either protocol. MVD had a positive linear correlation with HAP, TP, BF, with best correlation observed with HAP; MVD of VX2 tumor showed no or poor correlation with HPI and BV. CTPI parameters are not affected by tube voltage, current or reconstruction algorithm; HAP can best reflect MVD, but no correlation exists between BV and MVD.


Study of the titer of common antibodies against superficial antigens of Pityrosporum ovale in dermatitis seborrhoides.
Pityrosporum ovale is the yeast form of the dimorphic lipophilic fungus Malassezia furfur which is part of the normal skin microflora in adults. It is suggested that Pityrosporum ovale has a primary role in the pathogenesis of Dermatitis seborrhoides. The aim of the present study was to determine the titer of the common antibodies against superficial antigens of Pityrosporum ovale in the serum of Dermatitis seborrhoides patients and compare the results with the findings of examinations of serum antibodies in healthy subjects and patients with Pityriasis simplex capitis, Pityriasis versicolor, Pityrosporum folliculitis. Indirect immunofluorescent technique was used in the study. The Pityrosporum ovale antigen was obtained using own method. The results show that Dermatitis seborrhoides patients have an antibody titer of 1:640 and above, which is a higher titer than the antibody titers of healthy subjects and patients with other forms of the infection. The study results suggest that Pityrosporum ovale yeast might be implicated in causing a humoral immune response, which is important for the developing inflammatory reactions in Dermatitis seborrhoides. The results help to elucidate the pathogenic mechanisms and supplement the therapy strategy of the disorder. The authors are the first in Bulgaria to study the immune response to Pityrosporum ovale in healthy subjects and patients suffering from different forms of the infection.


Moving From Transactional to Relational: How Funders Can Work in Partnership With Black, Indigenous and People of Color Communities.
The Racial Equity Coalition (REC) formed to address persistent educational disparities. The coalition was composed of 14 Black, Indigenous and People of Color (BIPOC) organizations that provide culturally integrative youth services. REC, with support from United Way of King County, engaged in participatory research to identify commonalities and shared struggles to inform collective action. Participatory research aligns with REC's commitment to equitable participatory processes. This article focuses on REC's experiences with funders. The objective was to understand what creates positive and challenging experiences with funders, and to identify recommendations for funders to become more culturally responsive. A research committee was formed including representatives of nine REC organizations and United Way of King County staff. The committee conducted interviews with each of the 14 REC organizations and conducted thematic analysis of interview transcripts. Through participatory analysis, the committee drafted narratives that were further refined through a series of research retreats attended by all REC organizations. Recommendations were to incentivize collaboration, listen to communities to create culturally responsive definitions of success and measurement strategies, arrive at mutually agreed upon approaches with organizations, honor the connections BIPOC organizations have with their communities, and provide unrestricted funding to allow BIPOC organizations greater agency. A major challenge for BIPOC organizations is navigating White dominant culture that too often shows up in funding requirements. Having to fit dominant culture standards stifles BIPOC organizations' abilities to meet community needs and the responsiveness of their approaches. REC identified recommendations for funders to be more culturally responsive and community centered.


[The surgical anatomy of the sublingual gland].
Because of its position, the sublingual gland is clinically important especially in the events of injuries and infections in the anterior part of the sublingual region. The morphology and relationships of this gland were studied by dissection methods applied on 80 fresh or formaldehyde fixed preparations of the mouth floor and of the tongue, which were partly (31 preparations) taken out together with the mandible. As for the shape of the gland, three main types were found: the cuneiform type which was the most frequent (71%), the pyramidal type which was less frequent (16%) and the fusiform type (13%) which comprised the case of a very elongated gland (up to 65 mm). The space in which the gland lied had four walls. Its internal wall consisted of the mylohyoid muscle and it comprised the hyoglossus muscle as well when the gland was very elongated. The inferior wall consisted of the mylohyoid muscle and sometimes it comprised also a narrow part of the superior surface of the geniohyoglossus muscle. An osseous depression on the internal side of the mandible represented the external wall of the sublingual gland space. The superior wall is clinically the most significant. It consists of the sublingual mucosa and a sublingual fold. This wall represents a main surgical access to the gland. In edentulous mandibles this mucous fold may be at the level of the upper mandibular border which may hinder the use of the lower dental prosthesis.


A preliminary evaluation of the psychometric profiles in Chinese men with chronic prostatitis/chronic pelvic pain syndrome.
As one of the most commonly diagnosed diseases, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is characterized by a variety of complex symptoms. Anxiety and depression are two of the most prevalent clinical manifestations of patients with CP/CPPS, and have adverse effects on the health of the subjects and prognosis of comorbidities. Such psychological disorders, however, have not been deeply and thoroughly studied in China. The aim of this study was to investigate the prevalence and severity of psychological disorders in Chinese adults with CP/CPPS. From April 2008 to June 2009, 80 patients and 40 age-matched healthy men participating in a voluntary health examination were recruited. The majority of the subjects completed the questionnaires on the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) as well as the hospital anxiety and depression scale (HADS). Of all the participants, 77 (96.3%) patients and 37 (92.5%) healthy controls completed the questionnaires. The average NIH-CPSI total score was 21.0 ± 9.5 for the patients and 2.2 ± 1.5 for the controls (P = 0.03). Of the 77 patients with CP/CPPS, 48 (62.3%), 5 (6.5%), and 1 (1.2%) had anxiety symptoms, depression symptoms, or both anxiety and depression symptoms, respectively. For the controls, the average HADS anxiety and depression scores in patients were 14.5 ± 6.8 and 5.2 ± 4.5, which were both significantly higher than in controls. Moreover, the prevalence and the symptom scores of both the HADS anxiety and depression were higher for the younger age group (< 35 years) than for the older age group (< 35 years). This preliminary study revealed that male patients with CP/CPPS had a higher prevalence of psychological disorders than in the control subjects. Moreover, the differences of the prevalence and severity of the psychological symptoms between the two different age groups may imply that psychological disorders related to CP/CPPS may be relieved with increasing age. The present study indicated that psychological evaluation is important in men with CP/CPPS, especially in younger men.


On the relationship between head circumference, brain size, prenatal long-chain PUFA/5-methyltetrahydrofolate supplementation and cognitive abilities during childhood.
Head circumference in infants has been reported to predict brain size, total grey matter volume (GMV) and neurocognitive development. However, it is unknown whether it has predictive value on regional and subcortical brain volumes. We aimed to explore the relationship between several head circumference measurements since birth and distributions of GMV and subcortical volumes at later childhood. We examined seventy-four, Caucasian, singleton, term-born infants born to mothers randomised to receive fish oil and/or 5-methyltetrahydrofolate or placebo prenatal supplementation. We assessed head circumference at birth and at 4 and 10 years of age and cognitive abilities at 7 years of age. We obtained brain MRI at 10 years of age, on which we performed voxel-based morphometry, cortical surface extraction and subcortical segmentation. Analyses were controlled for sex, age, height, weight, family status, laterality and total intracranial volume. Prenatal supplementation did not affect head circumference at any age, cognitive abilities or total brain volumes. Head circumference at 4 years presented the highest correlation with total GMV, white matter volume and brain surface area, and was also strongly associated with GMV of frontal, temporal and occipital areas, as well as with caudate nucleus, globus pallidus, putamen and thalamus volumes. As relationships between brain volumes in childhood and several outcomes extend into adulthood, we have found that ages between 0 and 4 years as the optimal time for brain growth; postnatal factors might have the most relevant impact on structural maturation of certain cortical areas and subcortical nuclei, independent of prenatal supplementation.


[Clinical importance of gut hormones].
The lecture includes materials on gut hormones. Descriptions of the main synthesis places as well as structure and functions of hormones are given. The introduction of radioimmunoassay and immunoenzyme techniques to clinical practice made it possible to reach a success in the field of studying gastrointestinal hormones. Basic gut hormones and their role in the control over functioning digestive system and body as a whole under normal and pathological conditions are given.


Coagulation changes during thoracoabdominal aneurysm repair.
The cause of coagulopathic hemorrhage during thoracoabdominal aneurysm (TAA) repair has not been well defined in human studies. We investigated changes in the coagulation system associated with supraceliac versus infrarenal cross-clamping to address this critical issue. Blood levels of fibrinogen, the prothrombin fragment F1.2, D-dimer, and factors II, V, VII, VIII, IX, X, XI, and XII were analyzed in 19 patients with TAAs and four patients with abdominal aortic aneurysms (AAAs) at: (A) induction; (B) 30 minutes into supraceliac (TAA) or infrarenal (AAA) clamping; (C) 30 minutes after release of supraceliac or infrarenal clamps; and (D) immediately after surgery. Preoperative and intraoperative variables, including but not limited to aneurysm type, pathologic findings, comorbid conditions, clamp times, volume and timing of blood products, and clinical outcome, were prospectively recorded. Significance was determined by analysis of variance, Student's t test, and univariate linear regression. Levels of fibrinogen and factors II, V, VIII, VIII, IX, X, XI, and XII decreased (p < 0.05) at time B versus time A and returned to near baseline by time D. D-dimer and F1.2 increased starting at time B and reached significance (p < 0.05) by time D. Data points were compared for the TAA and AAA groups. Although AAA groups demonstrated a trend to factor activity reduction and increased fibrinolysis, the effect was much less pronounced than in TAA and did not approach significance. No correlation of coagulation change with clamping time was present; however, visceral clamping times were all less than 65 minutes (mean, 44 minutes). Blood and factor replacement was initiated after time B. Univariate regression analysis of factor level versus total blood replacement demonstrated a significant (p < 0.04) correlation between the reduction in the levels of factors II, V, VII, VIII, X, and XII, and the increase in the level of D-dimer at time B and subsequent total blood replacement. Thoracoabdominal aneurysm repair is associated with a reduction in clotting factor activity and an increase in fibrinolytic function, which occurs after placement of the supraceliac clamp. Explanations include visceral ischemia or a greater and longer ischemic tissue burden as the likely cause of coagulation alterations. Total blood replacement during TAA procedures was correlated to the degree of factor reduction and fibrinolysis at the time of visceral cross-clamping. An aggressive approach to early blood component replacement and to coagulation monitoring could lessen blood loss during TAA repair and avoid potentially disastrous bleeding complications.


Sorting of lipids and transmembrane peptides between detergent-soluble bilayers and detergent-resistant rafts.
Specific proteins and lipids sequester to regions of cell membranes called rafts. Due to their high content of sphingomyelin (SM) and cholesterol, raft bilayers are thicker than nonraft bilayers and, at least at 4 degrees C, are resistant to Triton X-100 extraction. It has been postulated that rafts concentrate proteins with long transbilayer domains because of "hydrophobic matching" between the transbilayer domain and the thick bilayer hydrocarbon region. However, because the area compressibility and bending moduli of SM:cholesterol bilayers are larger than that of nonraft bilayers, there should be an energy cost to partition proteins or peptides into rafts. To determine the effects on peptide sorting of raft thickness and mechanical properties, we incorporated two transbilayer peptides (P-23, P-29) into bilayers composed of SM, dioleoylphosphatidylcholine, and cholesterol, separated detergent-soluble membranes (DSMs) from detergent-resistant membranes (DRMs), and measured their peptide and lipid compositions. P-23 and P-29 were designed to have transbilayer domains that matched the hydrocarbon thicknesses of DSMs and DRMs, respectively. At both 4 degrees C and 37 degrees C DSMs were enriched in dioleoylphosphatidylcholine and DRMs were enriched in SM and cholesterol. At both temperatures both P-23 and P-29 preferentially localized to DSMs, demonstrating the importance of bilayer mechanical properties relative to hydrophobic mismatch. However, at 37 degrees C significantly more P-29 than P-23 was located in DRMs, implying that hydrophobic matching played a role in peptide sorting at physiological temperature. These experiments demonstrate that the sorting of peptides as measured by detergent extraction is temperature-dependent and both bilayer mechanical properties and hydrophobic matching impact peptide distribution between DSMs and DRMs.


Safe Sleep and Skin-to-Skin Care in the Neonatal Period for Healthy Term Newborns.
Skin-to-skin care (SSC) and rooming-in have become common practice in the newborn period for healthy newborns with the implementation of maternity care practices that support breastfeeding as delineated in the World Health Organization's "Ten Steps to Successful Breastfeeding." SSC and rooming-in are supported by evidence that indicates that the implementation of these practices increases overall and exclusive breastfeeding, safer and healthier transitions, and improved maternal-infant bonding. In some cases, however, the practice of SSC and rooming-in may pose safety concerns, particularly with regard to sleep. There have been several recent case reports and case series of severe and sudden unexpected postnatal collapse in the neonatal period among otherwise healthy newborns and near fatal or fatal events related to sleep, suffocation, and falls from adult hospital beds. Although these are largely case reports, there are potential dangers of unobserved SSC immediately after birth and throughout the postpartum hospital period as well as with unobserved rooming-in for at-risk situations. Moreover, behaviors that are modeled in the hospital after birth, such as sleep position, are likely to influence sleeping practices after discharge. Hospitals and birthing centers have found it difficult to develop policies that will allow SSC and rooming-in to continue in a safe manner. This clinical report is intended for birthing centers and delivery hospitals caring for healthy newborns to assist in the establishment of appropriate SSC and safe sleep policies.


Estimating cumulative point prevalence of rare diseases: analysis of the Orphanet database.
Rare diseases, an emerging global public health priority, require an evidence-based estimate of the global point prevalence to inform public policy. We used the publicly available epidemiological data in the Orphanet database to calculate such a prevalence estimate. Overall, Orphanet contains information on 6172 unique rare diseases; 71.9% of which are genetic and 69.9% which are exclusively pediatric onset. Global point prevalence was calculated using rare disease prevalence data for predefined geographic regions from the 'Orphanet Epidemiological file' (http://www.orphadata.org/cgi-bin/epidemio.html). Of the 5304 diseases defined by point prevalence, 84.5% of those analysed have a point prevalence of <1/1 000 000. However 77.3-80.7% of the population burden of rare diseases is attributable to the 4.2% (n = 149) diseases in the most common prevalence range (1-5 per 10 000). Consequently national definitions of 'Rare Diseases' (ranging from prevalence of 5 to 80 per 100 000) represent a variable number of rare disease patients despite sharing the majority of rare disease in their scope. Our analysis yields a conservative, evidence-based estimate for the population prevalence of rare diseases of 3.5-5.9%, which equates to 263-446 million persons affected globally at any point in time. This figure is derived from data from 67.6% of the prevalent rare diseases; using the European definition of 5 per 10 000; and excluding rare cancers, infectious diseases, and poisonings. Future registry research and the implementation of rare disease codification in healthcare systems will further refine the estimates.


Estimation methods for marginal and association parameters for longitudinal binary data with nonignorable missing observations.
In longitudinal studies, missing observations occur commonly. It has been well known that biased results could be produced if missingness is not properly handled in the analysis. Authors have developed many methods with the focus on either incomplete response or missing covariate observations, but rarely on both. The complexity of modeling and computational difficulty would be the major challenges in handling missingness in both response and covariate variables. In this paper, we develop methods using the pairwise likelihood formulation to handle longitudinal binary data with missing observations present in both response and covariate variables. We propose a unified framework to accommodate various types of missing data patterns. We evaluate the performance of the methods empirically under a variety of circumstances. In particular, we investigate issues on efficiency and robustness. We analyze longitudinal data from the National Population Health Study with the use of our methods.


Targeting lipid biosynthesis on the basis of conventional treatments for clear cell renal cell carcinoma: A promising therapeutic approach.
A variety of cancer cells exhibit dysregulated lipid metabolism, characterized by excessive intracellular lipid accumulation, and clear cell renal cell carcinoma (ccRCC) is the most typical disease with these characteristics. As the most common malignancy of all renal cell carcinomas (RCCs), ccRCC is typically characterized by a large accumulation of lipids and glycogen in the cytoplasm and a nucleus that is squeezed by the accumulated lipid droplets and localized to the marginal areas within the cytoplasm. This lipid accumulation has been found to be critically involved in the maintenance of malignant features observed in various cancers. Firstly, it maintains the persistent proliferative and metastasis properties of cancer cells. Secondly, it acts as a buffer against lipid peroxidation, preventing lipid peroxidation-induced ferroptosis. Moreover, lipids can diminish the sensitivity of cancer cells to radiotherapy. As ccRCC is a type of cancer with high lipid synthesis, targeting lipid synthesis-related genes in cancer cells may be a promising therapeutic modality for single treatment or in combination with radiotherapy, chemotherapy, and immunotherapy. This may revolutionize the choice of treatment modality for ccRCC patients. In this review, we concentrate on the current status and progress of research on lipid biosynthesis in ccRCC and the potential applications of targeting lipid synthesis to treat ccRCC. At last, we propose perspective and future research directions for targeting inhibition of lipid biosynthesis in combination with conventional therapeutic approaches for the treatment of ccRCC, which will help to evolve the therapeutic model.


[Spondylodiscitis in childhood].
Spondylodiscitis is a frequently unrecognized disease in childhood because of unspecific symptoms and late arising or radiological signs. The heterogeneous symptoms, the value of diagnostic procedures and the outcome of 8 patients suffering from spondylodiscitis in the time period of 1989 to 1995 are demonstrated. Guiding symptoms were back pain and refusal to walk or sit. Furthermore, abdominal pain and psoas abscess were the only symptoms in two cases. The pathogenomonical narrowing of the disc space arose in X-ray films earliest 3 weeks after onset of symptoms. The MRI was the best method for early diagnosis and detection of complications. In contrast to persistent radiological changes the clinical outcome was good in most of the patients.


The influence of a supervised group exercise intervention combined with active lifestyle recommendations on breast cancer survivors' health, physical functioning, and quality of life indices: study protocol for a randomized and controlled trial.
Most cancer patients, under active treatment or not, are sedentary, despite increasing scientific and clinical understanding of the benefits of exercise and physical activity, such as improving quality of life, limiting disease symptoms, decreasing cancer recurrence, and increasing overall survival. Studies have shown that both supervised exercise and unsupervised physical activity programs have low adherence and limited long-term benefits among cancer survivors. Therefore, interventions focused on increasing physical activity levels have clinical and psychological relevance. The present study will examine the feasibility and efficacy of an intervention that combines supervised group exercise with active lifestyle recommendations, analyzing its clinical, psychological, physiological, functional, and immunological effects in breast cancer survivors. Women aged 35-75 years who have completed chemotherapy, radiotherapy, and surgery for breast cancer will be recruited from the Cancer Institute of the State of Sao Paulo (ICESP) and take part in a 16-week, parallel-group, randomized, and controlled trial. They will receive a booklet with recommendations for achieving a physically active lifestyle by increasing overall daily movement and undertaking at least 150 min/week of structured exercise. Then, they will be randomized into two groups: the supervised group will take part in two canoeing group exercise sessions every week, and the unsupervised group will increase their overall physical activity level by any means, such as active commuting, daily activities, or home-based exercise. Primary outcome includes aerobic capacity. Secondary outcomes are physical activity, physical functioning, self-reported quality of life, fatigue, presence of lymphedema, body composition, immune function, adherence to physical activity guidelines, and perceptions of self-image. Results should contribute to advance knowledge on the impact of a supervised group exercise intervention to improve aspects related to health, physical functioning, and quality of life in female breast cancer survivors. Brazilian Registry of Clinical Trials Number: RBR-3fw9xf. Retrospectively Registered on 27 December 2018. Items from the World Health Organization Trial Registration Data Set can be accessed on http://www.ensaiosclinicos.gov.br/rg/RBR-3fw9xf/ .


Environmental novelty activates β2-adrenergic signaling to prevent the impairment of hippocampal LTP by Aβ oligomers.
A central question about human brain aging is whether cognitive enrichment slows the development of Alzheimer changes. Here, we show that prolonged exposure to an enriched environment (EE) facilitated signaling in the hippocampus of wild-type mice that promoted long-term potentiation. A key feature of the EE effect was activation of β2-adrenergic receptors and downstream cAMP/PKA signaling. This EE pathway prevented LTP inhibition by soluble oligomers of amyloid β-protein (Aβ) isolated from AD cortex. Protection by EE occurred in both young and middle-aged wild-type mice. Exposure to novelty afforded greater protection than did aerobic exercise. Mice chronically fed a β-adrenergic agonist without EE were protected from hippocampal impairment by Aβ oligomers. Thus, EE enhances hippocampal synaptic plasticity by activating β-adrenoceptor signaling and mitigating synaptotoxicity of human Aβ oligomers. These mechanistic insights support using prolonged exposure to cognitive novelty and/or oral β-adrenergic agonists to lessen the effects of Aβ accumulation during aging.


[Physical exercise and serum lipids].
The physical activity shows an inverse correlation with Ischaemic Cardiopathy, with evidence that lipids and lipoproteins blood levels are favourably modified by exercise. In this way, this study compared the different degrees of physical activity and the levels of blood lipids/lipoproteins, as well as the anthropometric and physiological variants. One hundred fifty seven non smoking males, aged 15 to 31 years old, average 21 years, were divided in two groups: G1 comprises 88 athletes individuals and G2, 69 non-athletes. The G1 individuals showed less corporal fat and better aerobic capacity than the G2 individuals. The levels of cholesterol, triglycerides, and the VLDL/cholesterol ratio were lower in the G1 individuals, as well as the risk rate 1 and 2, respectively the ratio of cholesterol/HDL cholesterol and LDL cholesterol/HDL cholesterol. There was no difference in both groups regarding the LDL and HDL cholesterol. In the G2 individuals the percentage of corporal fat had a direct correlation to the blood levels of triglycerides and VLDL cholesterol, and an inverse correlation to the HDL cholesterol blood level. Also, in this group there was a significative correlation to the risk rate 1 and 2. However, in G1 individuals the lipidic/lipoprotein levels were more favourable, which suggests a lower risk of developing Ischaemic Cardiopathy. Statistical analysis was obtained through "t"-Student, X2 and Spearman methods, with significance level of 0.05.


Villous adenoma of the renal pelvis and ureter.
Villous adenoma originating in the urinary tract is a rare condition. Mucus-filled kidney (muconephrosis), one of the manifestations of this condition, occurs due to intestinal type of metaplastic changes occurring in the urothelium. This condition is commonly associated with urolithiasis and/or chronic infection. Concomitant adenocarcinomatous changes in the urothelium may be present along with this and unless a careful search is made to identify this, this serious condition may be overlooked leading to an inappropriate follow-up and dire consequences. We are reporting the third case of muconephrosis due to villous adenomatous changes of the renal pelvis and ureter.


Treatment of subtalar calcanean fractures using trans-osseous limited lateral approach.
Calcaneal fractures are the most common fractures of the tarsal bones. The majority of these fractures are produced by axial force like a fall from a height. Controversy still exists on the best line of treatment. This study is to evaluate the results of trans-osseous limited lateral approach as a minimally invasive surgical treatment of the displaced intra-articular calcaneal fractures. The study included forty two patients (46 feet) with displaced intra-articular calcaneal fractures admitted to El-Hadra University Hospital. They were treated by trans-osseous open reduction of subtalar joint and internal fixation by k-wires consuming the trans-osseous limited lateral approach. Out of 42 patients, 36 pateints (85.7%) were males. Using calcaneal fracture scoring system, the mean score was 67.55+17.35. Satisfactory results were found in 26 patients (61.9%), while 16 patients (38.1%) had unsatisfactory results. There was significant relationship between classification of the fracture and the final results (the more the grade of the fracture, the worse the final score) (x 2 =5.914, p=0.05). The value of calcaneal angles were significantly improved after surgery including bohler angle (p=0.0001), gissane angle (p=0.0001), calcaneal pitch angle (p=0.001) and calcaneofibular space (p=0.0021). 1. Trans-osseous limited lateral approach is an effective method for management of intra articular calcaneal fractures. 2. Anatomical reduction for intra articular calcaneal fractures is essential. 3. Functional outcome of intra articular calcaneal fractures depends upon the initial damage of the articular cartilage. 4. There is a need for multi-center prospective randomized study for accurate assessment of the results of operative management of intra articular calcaneal fractures involving pre and post-operative CT for assessment of reduction and using a rational scoring system and a long period of follow up.


[A Trypanosoma cruzi infection without serologic evidence].
Trypanosoma cruzi was isolated from a 20 year old male with no evidence of antibodies against this parasite until 12 months after the isolation and with no electrocardiographic alterations. The isolated sample obtained was characterized as T. cruzi I through PCR mini-exon. It had been reported without serologic reactivity to T. cruzi. It is the first case with lack reactivity reported in Mexico.


Vertical heterophoria and postural control in nonspecific chronic low back pain.
The purpose of this study was to test postural control during quiet standing in nonspecific chronic low back pain (LBP) subjects with vertical heterophoria (VH) before and after cancellation of VH; also to compare with healthy subjects with, and without VH. Fourteen subjects with LBP took part in this study. The postural performance was measured through the center of pressure displacements with a force platform while the subjects fixated on a target placed at either 40 or 200 cm, before and after VH cancellation with an appropriate prism. Their postural performance was compared to that of 14 healthy subjects with VH and 12 without VH (i.e. vertical orthophoria) studied previously in similar conditions. For LBP subjects, cancellation of VH with a prism improved postural performance. With respect to control subjects (with or without VH), the variance of speed of the center of pressure was higher, suggesting more energy was needed to stabilize their posture in quiet upright stance. Similarly to controls, LBP subjects showed higher postural sway when they were looking at a target at a far distance than at a close distance. The most important finding is that LBP subjects with VH can improve their performance after prism-cancellation of their VH. We suggest that VH reflects mild conflict between sensory and motor inputs involved in postural control i.e. a non optimal integration of the various signals. This could affect the performance of postural control and perhaps lead to pain. Nonspecific chronic back pain may results from such prolonged conflict.


Neuroscience highlights: The mirror inside our brain.
Over the second half of the 19th century, numerous theories arose concerning mechanisms involved in understanding of action, imitative learning, language development and theory of mind. These explorations gained new momentum with the discovery of the so called "mirror neurons". Rizzolatti's work inspired large groups of scientists seeking explanation in a new and hitherto unexplored area of how we perceive and understand the actions and intentions of others, how we learn through imitation to help our own survival, and what mechanisms have helped us to develop a unique human trait, language. Numerous studies have addressed these questions over the years, gathering information about mirror neurons themselves, their subtypes, the different brain areas involved in the mirror neuron system, their role in the above mentioned mechanisms, and the varying consequences of their dysfunction in human life. In this short review, we summarize the most important theories and discoveries that argue for the existence of the mirror neuron system, and its essential function in normal human life or some pathological conditions.


Important features of home-based support services for older Australians and their informal carers.
In Australia, newly initiated, publicly subsidised 'Home-Care Packages' designed to assist older people (≥ 65 years of age) living in their own home must now be offered on a 'consumer-directed care' (CDC) basis by service providers. However, CDC models have largely developed in the absence of evidence on users' views and preferences. The aim of this study was to determine what features (attributes) of consumer-directed, home-based support services are important to older people and their informal carers to inform the design of a discrete choice experiment (DCE). Semi-structured, face-to-face interviews were conducted in December 2012-November 2013 with 17 older people receiving home-based support services and 10 informal carers from 5 providers located in South Australia and New South Wales. Salient service characteristics important to participants were determined using thematic and constant comparative analysis and formulated into attributes and attribute levels for presentation within a DCE. Initially, eight broad themes were identified: information and knowledge, choice and control, self-managed continuum, effective co-ordination, effective communication, responsiveness and flexibility, continuity and planning. Attributes were formulated for the DCE by combining overlapping themes such as effective communication and co-ordination, and the self-managed continuum and planning into single attributes. Six salient service features that characterise consumer preferences for the provision of home-based support service models were identified: choice of provider, choice of support worker, flexibility in care activities provided, contact with the service co-ordinator, managing the budget and saving unspent funds. Best practice indicates that qualitative research with individuals who represent the population of interest should guide attribute selection for a DCE and this is the first study to employ such methods in aged care service provision. Further development of services could incorporate methods of consumer engagement such as DCEs which facilitate the identification and quantification of users' views and preferences on alternative models of delivery.


So how do you feel about that? Assessing reflective practice.
Despite a lack of evidence base, reflective practice remains a central feature of education for many professional groups. In addition, current trends in learning, teaching and assessing require a robust alignment between learning outcomes and assessed course work [Active Learning Higher Educat. 2 (2002) 145)]. Varied definitions of what it means to be a 'reflective practitioner' and limited research make it difficult to know how and what to assess [Reflective Practice in Nursing, Blackwell Science]. Assessment of reflective practice frequently requires students to recount narratives about their practice and both formative feedback and assessment criteria make it clear that such narratives must demonstrate the students' application of appropriate and safe professional practice. This paper suggests that only three 'stories' are legitimate and identifies these as 'valedictory' 'condemnatory' and 'redemptive' This conclusion drawn is that the imperative to do well academically discourages students from engaging in honest and open reflection. This being the case, it may be argued that the assessment of reflective practice is a potential barrier to the personal growth and integrity that programmes are trying to nurture.


[Effectiveness of fluoxetine (portal) in atypical depressions].
Efficiency of fluoxetine (one of the selective serotonin reuptake inhibitors) was examined in the course of treatment of 24 patients with atypical depressions that were characterized by prevalence of either negative (12 patients) or positive (12 patients) affectivity. Fluoxetine was more effective in patients with domination of negative affectivity (apathias, angedonias, alexithymias). Total efficiency of fluoxetine was equal to 91% in group with prevalence of negative affectivity and 41% with prevalence of positive affectivity. In the latter group the side-effects were more pronounced that resulted in prescription of corrective therapy.


MicroRNA, miR-501 Regulate the V(D)J Recombination in B Cells.
The stringent regulation of RAGs (Recombination activating genes), the site-specific endonuclease responsible for V(D)J recombination, is important to prevent genomic rearrangements and chromosomal translocations in lymphoid cells. In the present study, we identify a microRNA, miR-501, which can regulate the expression of RAG1 in lymphoid cells. Overexpression of the pre-miRNA construct led to the generation of mature miRNAs and a concomitant reduction of RAG1 expression, whereas inhibition using anti-miRs resulted in its enhanced expression. The direct interaction of the 3'UTR of miR-501 with RAG1 was confirmed by the reporter assay. Importantly, overexpression of miRNAs led to inhibition of V(D)J recombination in B cells, revealing their impact on the physiological function of RAGs. Of interest is the inverse correlation observed for miR-501 with RAG1 in various leukemia patients and lymphoid cell lines, suggesting its possible use in cancer therapy. Thus, our results reveal the regulation of RAG1 by miR-501-3p in B cells and thus V(D)J recombination and its possible implications on immunoglobulin leukemogenesis.


Assessment of outcomes with delayed (18)F-FDG PET-CT response assessment in head and neck squamous cell carcinoma.
To assess the accuracy of a 4-month post-(chemo)radiotherapy 18-fludeoxyglucose ((18)F-FDG) positron emission tomography (PET)-CT for head and neck squamous cell carcinoma (HNSCC). 105 patients who underwent a baseline and response assessment (18)F-FDG PET-CT scan between 2008 and April 2013 were identified. (18)F-FDG PET-CT outcomes were analysed with reference to clinicopathological outcomes. 79 of 105 (75%) (18)F-FDG PET-CT scans demonstrated a complete metabolic response; 19 of 101 (19%) for assessable primary tumours were positive; and 19 of 93 (20%) for patients with nodal disease were equivocal (n = 10) or positive (n = 9). The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for primary and nodal disease were 90%, 89%, 47%, 99% and 91%, 89%, 53% and 99%, respectively. Eight of nine patients with a positive nodal response scan had clinicopathological evidence of residual nodal disease (PPV, 89%). 2 of 10 patients with equivocal nodal responses had clinicopathological evidence of residual nodal disease (PPV, 20%). (18)F-FDG PET-CT 4 months post treatment has a very high NPV. A positive (18)F-FDG PET-CT has a high PPV for residual nodal disease. By contrast, patients who have an equivocal nodal response have a low PPV. Response assessment (18)F-FDG PET-CT is a valuable tool in guiding the selective use of neck dissection following (chemo)radiotherapy for HNSCC. An equivocal lymph node response has a limited predictive value for persistent disease, and optimal management remains a clinical challenge.


Preparation of PP-g-(AA-MAH) Fibers Using Suspension Grafting and Melt-Blown Spinning and its Adsorption for Aniline.
This paper uses polypropylene (PP) as the matrix and acrylic acid (AA) and maleic anhydride (MAH) as functional monomers to prepare PP-g-(AA-MAH) fibers by suspension grafting and melt-blown spinning technology that are easy to industrially scale-up. The fibers can be used to adsorb aniline. Results showed that the grafting ratio reached the maximum of 12.47%. The corresponding optimal conditions were grafting time of 3 h, AA: MAH = 0.75, total monomer content of 55%, benzoyl peroxide 1.4%, xylene concentration of 6 mL/g PP, and deionized water content of 8 mL/g PP. Owing to its good fluidity and thermal stability, the product of suspension grafting can be used for melt-blown spinning. Infrared spectroscopic and nuclear magnetic resonance spectroscopic analyses indicated that AA and MAH were successfully grafted onto PP fibers. After grafting, the hydrophilicity of PP-g-(AA-MAH) fiber increased. Therefore, it had higher absorptivity for aniline and the adsorption capacity could reach 42.2 mg/g at 45 min and pH = 7. Moreover, the PP-g-(AA-MAH) fibers showed good regeneration performance.


The multiple faces of ketamine in anaesthesia and analgesia.
Ketamine is an anaesthetic agent with a unique dissociative profile and pharmacological effects ranging from the induction and maintenance of anaesthesia to analgesia and sedation, depending on the dose. This article provides information for the clinical use of ketamine in anaesthesia, in both conventional and special circumstances. This is a non-systematic review of the literature, through a PubMed search up to February 2021. With a favourable pharmacokinetic profile, ketamine is used in hospital and prehospital settings for emergency situations. It is suitable for patients with many heart conditions and, unlike other anaesthetics, its potential for cardiorespiratory depression is low. Furthermore, it may be used when venous access is difficult as it may be administered through various routes. Ketamine is the anaesthetic of choice for patients with bronchospasm thanks to its bronchodilatory and anti-inflammatory properties. With a favourable pharmacokinetic profile, ketamine is used in hospital and prehospital settings for emergency situations and is suitable for patients with many cardiac and respiratory conditions.


Analytical link bandwidth model based square array reception for non-line-of-sight ultraviolet communication.
An analytical model is presented firstly in this paper to formulate the link bandwidth of non-line-of-sight (NLOS) ultraviolet (UV) channel. The link bandwidth is characterized by three geometrical parameters including transmitter (Tx) elevation angle, receiver (Rx) field of view (FOV), and transceiver separation distance, and further expressed as a closed-form through software-aided numerical fitting. Comparison with the link bandwidth obtained via a Monte Carlo model is done to verify the feasibility of this model. Based on this model, we investigate the diversity reception on the NLOS UV communication from a new perspective. A spatially squared distributed Rx array is customized for the NLOS UV channel. Lower temporal broadening is enabled, leading to a higher link bandwidth. Numerical results suggest that over 100% improvement of the link bandwidth is predicted by the square array reception and the ratio grows rapidly with the narrowing of Tx beam divergence. Therefore, this paper provides a guide for link analysis and receiver design for NLOS UV communication.


Context and the evidence-based paradigm: The potential for participatory research and systems thinking in oral health.
The implementation of research evidence to promote oral health is critical, given the intransigent and emerging challenges for policymakers at a population level. Despite this, little attention has been paid to implementation research within the evidence-based paradigm. This is important as getting research evidence into clinical practice is not a linear path that consists of simple sequential steps. In this article, we argue that we need to consider a broader range of conceptual and methodological approaches to increase the value of information generated. This should be undertaken either in parallel with empirical and experimental designs, or in some cases, instead of. This is important if we are going to understand the complexity and contextual knowledge of the 'system', within which interventions are implemented. Involving key stakeholders alongside empirical and experimental designs is one helpful approach. Examples of these approaches include Patient and Public Involvement and the development of Core Outcome Sets, where the views of those that will be potentially affected by the research, are included. The use of theoretical frameworks and process evaluations alongside trials are also important, if they are fully integrated into the approach taken to address the research question. A more radical approach is using participatory designs and 'systems thinking'. Participatory approaches include subject matter 'experts by experience'. These include patients, their families, carers, healthcare professionals, services managers, policymakers, commissioners and researchers. Participatory approaches raise important questions about who facilitates the process, when it should happen and how the diverse actors become meaningfully engaged so that their involvement is active, democratic and ongoing. We argue that the issues of control, power and language are central to this and represent a paradigmatic shift to conventional approaches. Systems thinking captures the idea that public health problems commonly involve multiple interdependent and interconnected factors, which interact with each other dynamically. This approach challenges the simplicity of the hierarchy of evidence and linear sequential logic, when it does not account for context. In contrast, systems thinking accepts complexity de novo and emphasizes the need to understand the whole system rather than its individual component parts. We conclude with the idea that participatory and systems thinking help to unpack the diverse agents that are often involved in the generation and translation of evidence into clinical dental practice. It moves our conception of research away from a simple exchange between 'knowledge producers' and 'knowledge users' and raises both methodological and epistemological challenges.


Current and future modalities for functional renal replacement.
Approximately 310,000 Americans suffer from end-stage renal disease, with more than 70,000 new cases reported each year. Advances in immunosuppressive therapy for transplanted patients, in addition to the refined care of patients who are dependent on dialysis, have led to an improved survival for patients with renal failure. Structural, molecular, and pharmacologic developments continue to enhance the efficacy and safety of dialysis in the future. In addition, progressive improvements in the past 2 decades in organ transplantation, a greater insight into the immunobiology of graft rejection, and better surgical and medical management have resulted in improved outcomes. Although renal xenotransplantation is still in its early stages of development, additional research is leading this technology forward. Recent successes in harvesting and expanding renal cells in vitro and the development of biologically active synthetic materials allow for the creation of three-dimensional functioning renal units, which, in the future, may be applied ex vivo or in vivo for partial or full replacement of kidney function.


Stereo-, Temporal and Chemical Control through Photoactivation of Living Radical Polymerization: Synthesis of Block and Gradient Copolymers.
Nature has developed efficient polymerization processes, which allow the synthesis of complex macromolecules with a perfect control of tacticity as well as molecular weight, in response to a specific stimulus. In this contribution, we report the synthesis of various stereopolymers by combining a photoactivated living polymerization, named photoinduced electron transfer-reversible addition-fragmentation chain transfer (PET-RAFT) with Lewis acid mediators. We initially investigated the tolerance of two different photoredox catalysts, i.e., Ir(ppy)3 and Ru(bpy)3, in the presence of a Lewis acid, i.e., Y(OTf)3 and Yb(OTf)3, to mediate the polymerization of N,N-dimethyl acrylamide (DMAA). An excellent control of tacticity as well as molecular weight and dispersity was observed when Ir(ppy)3 and Y(OTf)3 were employed in a methanol/toluene mixture, while no polymerization or poor control was observed with Ru(bpy)3. In comparison to a thermal system, a lower amount of Y(OTf)3 was required to achieve good control over the tacticity. Taking advantage of the temporal control inherent in our system, we were able to design complex macromolecular architectures, such as atactic block-isotactic and isotactic-block-atactic polymers in a one-pot polymerization approach. Furthermore, we discovered that we could modulate the degree of tacticity through a chemical stimulus, by varying [DMSO]0/[Y(OTf)3]0 ratio from 0 to 30 during the polymerization. The stereochemical control afforded by the addition of a low amount of DMSO in conjunction with the inherent temporal control enabled the synthesis of stereogradient polymer consisting of five different stereoblocks in one-pot polymerization.


Citrobacter rodentium induces rapid and unique metabolic and inflammatory responses in mice suffering from severe disease.
The mouse pathogen Citrobacter rodentium is used to model infections with enterohaemorrhagic and enteropathogenic Escherichia coli (EHEC and EPEC). Pathogenesis is commonly modelled in mice developing mild disease (e.g., C57BL/6). However, little is known about host responses in mice exhibiting severe colitis (e.g., C3H/HeN), which arguably provide a more clinically relevant model for human paediatric enteric infection. Infection of C3H/HeN mice with C. rodentium results in rapid colonic colonisation, coinciding with induction of key inflammatory signatures and colonic crypt hyperplasia. Infection also induces dramatic changes to bioenergetics in intestinal epithelial cells, with transition from oxidative phosphorylation (OXPHOS) to aerobic glycolysis and higher abundance of SGLT4, LDHA, and MCT4. Concomitantly, mitochondrial proteins involved in the TCA cycle and OXPHOS were in lower abundance. Similar to observations in C57BL/6 mice, we detected simultaneous activation of cholesterol biogenesis, import, and efflux. Distinctly, however, the pattern recognition receptors NLRP3 and ALPK1 were specifically induced in C3H/HeN. Using cell-based assays revealed that C. rodentium activates the ALPK1/TIFA axis, which is dependent on the ADP-heptose biosynthesis pathway but independent of the Type III secretion system. This study reveals for the first time the unfolding intestinal epithelial cells' responses during severe infectious colitis, which resemble EPEC human infections.