Dual γ rhythm generators control interlaminar synchrony in auditory cortex.
Rhythmic activity in populations of cortical neurons accompanies, and may underlie, many aspects of primary sensory processing and short-term memory. Activity in the gamma band (30 Hz up to >100 Hz) is associated with such cognitive tasks and is thought to provide a substrate for temporal coupling of spatially separate regions of the brain. However, such coupling requires close matching of frequencies in co-active areas, and because the nominal gamma band is so spectrally broad, it may not constitute a single underlying process. Here we show that, for inhibition-based gamma rhythms in vitro in rat neocortical slices, mechanistically distinct local circuit generators exist in different laminae of rat primary auditory cortex. A persistent, 30-45 Hz, gap-junction-dependent gamma rhythm dominates rhythmic activity in supragranular layers 2/3, whereas a tonic depolarization-dependent, 50-80 Hz, pyramidal/interneuron gamma rhythm is expressed in granular layer 4 with strong glutamatergic excitation. As a consequence, altering the degree of excitation of the auditory cortex causes bifurcation in the gamma frequency spectrum and can effectively switch temporal control of layer 5 from supragranular to granular layers. Computational modeling predicts the pattern of interlaminar connections may help to stabilize this bifurcation. The data suggest that different strategies are used by primary auditory cortex to represent weak and strong inputs, with principal cell firing rate becoming increasingly important as excitation strength increases.


Women's collective constructions of embodied practices through memory work: Cartesian dualism in memories of sweating and pain.
The research presented in this paper uses memory work as a method to explore six women's collective constructions of two embodied practices, sweating and pain. The paper identifies limitations in the ways in which social constructionist research has theorized the relationship between discourse and materiality, and it proposes an approach to the study of embodiment which enjoins, rather than bridges, the discursive and the non-discursive. The paper presents an analysis of 25 memories of sweating and pain which suggests that Cartesian dualism is central to the women's accounts of their experiences. However, such dualism does not operate as a stable organizing principle. Rather, it offers two strategies for the performance of a split between mind and body. The paper traces the ways in which dualism can be both functional and restrictive, and explores the tensions between these two forms. The paper concludes by identifiying opportunities and limitations associated with memory work as a method for studying embodiment.


Impact of Age, Frailty, and Dementia on Prescribing for Type 2 Diabetes at Hospital Discharge 2012-2016.
The risks of intensive blood glucose lowering may outweigh the benefits in vulnerable older people. Our primary aim was to determine whether age, frailty, or dementia predict discharge treatment types for patients with type 2 diabetes (T2D) and related complications. Secondly, we aimed to determine the association between prior hypoglycemia and discharge treatment types. We conducted a cohort study involving 3,067 patients aged 65-99 years with T2D and related complications, discharged from Melbourne's Eastern Health Hospital Network between 2012 and 2016. Multinomial logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CI) for the association between age, frailty, dementia and hypoglycemia, and being prescribed insulin-only, non-insulin glucose-lowering drugs (GLDs) or combined insulin and non-insulin GLDs compared to no GLD. International Classification of Diseases-10 codes were used to identify dementia status and prior hypoglycemia; frailty was quantified using the Hospital Frailty Risk Score. Insulin-only, non-insulin GLDs, combined insulin and non-insulin GLDs, and no GLDs were prescribed to 19%, 39%, 20%, and 23% of patients, respectively. Patients >80 years were less likely than patients aged 65-80 to be prescribed any of the GLD therapies, (eg. non-insulin GLDs [OR 0.67; 95%CI 0.55-0.82]), compared to no GLD. Similarly, high vs. low frailty scores were associated with not being prescribed any of the three GLD therapies, (eg. non-insulin GLDs [OR 0.63; 95%CI 0.45-0.87]). However, dementia was not associated with discharge prescribing of GLD therapies. Patients with a hypoglycemia-related admission were more likely than those not hospitalized with hypoglycemia to receive insulin-only (OR 4.28; 95%CI 2.89-6.31). Clinicians consider age and frailty when tailoring diabetes treatment regimens for patients discharged from hospital with T2D and related complications. There is scope to optimize prescribing for patients with dementia and for those admitted with hypoglycemia.


Allometric engineering: a causal analysis of natural selection on offspring size.
Techniques of offspring size manipulation, "allometric engineering," were used in combination with studies of natural selection to elucidate the causal relation between egg size and offspring survival of lizards. The results experimentally validate premises underlying theories of optimal egg size: fecundity selection favoring the production of large clutches of small eggs was balanced by survival selection favoring large offspring. However, large hatchlings did not always have the highest survival, contrary to most theoretical expectations. Optimizing selection on offspring size per se was the most common pattern. Moreover, matches between average and optimal egg size were qualitative, not quantitative, perhaps reflecting known functional constraints on the production of large eggs.


The Use of Generic and Individual Speed Thresholds for Assessing the Competitive Demands of Field Hockey.
The current study compared the running demands of professional field hockey players using individualized speed zones and generic default settings of the GPS manufacturer. In addition, the differences in slow, moderate and fast players were studied. Sixteen male players from the same club participated in the study (age: 25.5 ± 2.9 years; body mass: 74.6 ± 5.5 kg; stature 1.77 ± 0.05 m). The peak speed of each participant was established at the end of the data collection period by analyzing all training and playing data throughout the season. Using players peak speed achieved for each participant during the season, individualized speed zones were retrospectively applied to all match-play data. Peak speed was used to categorize players into three groups, slow (5 players: 29.2-30.2 km·h-1), moderate (6 players: 30.7-31.5 km·h-1) and fast (5 players: 32.2-33.7 km·h-1). Significant differences were observed between generic and individual thresholds for the distance covered in moderate, high, and very high-speed running in all positions (p = 0.01). Our findings show that the distances covered at high-speeds in midfielders and forwards were overestimated, while the very high-speed running and sprinting in backs were underestimated. Generic speed thresholds should be used if comparisons between positions is of importance. However, based on the different capacities of field hockey players, individual speed thresholds may be more suitable when addressing the relative stress on individual athletes.


Viral myocarditis.
The article traces the pathways leading from viral infection of the heart by coxsackievirus B3 to autoimmune myocarditis in its various manifestations. Myocarditis can be induced by a number of different infectious agents and represents a significant cause of death especially in young individuals. Following infection, patients may develop lymphocytic, eosinophilic, or giant cell/granulomatous myocardial inflammation. It can lead to infectious dilated cardiomyopathy, a disease frequently requiring cardiac transplantation. Although acute viral myocarditis is frequently subclinical and recovery may be spontaneous, treatment of chronic myocarditis is currently unsatisfactory. Ongoing disease may be because of persistent virus in the heart or to immunopathic attack. Depending on the cause, treatment may be antiviral or immunosuppressive. Endomyocardial biopsy is proving of value in determining cause and deciding future therapy. A great deal of information about the pathogenesis of myocarditis has been gained from experimental models in rodents using heart disease induced by infection using coxsackievirus B3 or by immunization with cardiac myosin. Treatment of myocarditis is still problematic and may depend on etiologic diagnosis to distinguish infectious from immune-mediated disease. Both pathogenic mechanisms may co-occur in individual patients. In the future, treatment may depend upon endomyocardial biopsy, immunohistologic testing, improved imaging, and molecular genetic analysis for providing more precise diagnoses.


Spermine. A regulator of mitochondrial calcium cycling.
Steady-state free Ca2+ concentrations have been measured with a Ca2+ electrode using suspensions of isolated rat liver mitochondria or saponin-treated hepatocytes. Mitochondria, when incubated in the presence of Mg2+ and MgATP2-, maintain a steady-state pCa2+ (-log [Ca2+]) of approximately 6.1 (0.8 microM). Addition of spermine lowered this value to a pCa2+ of 6.6 (0.25 microM). Spermine was the most effective polyamine, giving half-maximal effects at 170 microM and maximal effects at 400 microM. With saponin-permeabilized hepatocytes, spermine addition similarly showed that the mitochondria buffered the steady-state medium-free Ca2+ at a level approximating the cytosolic free Ca2+ concentration of intact hepatocytes. The initial rate of Ca2+ uptake by the mitochondrial Ca2+ uniporter was investigated using Ca2+-depleted mitochondria incubated in the presence of succinate and 0.3 mM free Mg2+. Under control conditions, Ca2+ uptake was not observed at free Ca2+ concentrations below 0.5 microM. Spermine (350 microM) increased the rate of Ca2+ uptake at all Ca2+ concentrations below 4.5 microM, but at higher Ca2+ concentrations, it was inhibitory. Spermine also affected mitochondrial Ca2+ efflux by decreasing the apparent Km from 16 to 3.8 nmol of Ca2+/mg of mitochondrial protein with no change of Vmax. Experiments with 45Ca2+ confirmed that spermine increased mitochondrial Ca2+ cycling at 0.2 microM free Ca2+. Hepatic spermine contents are reported to be about 1 mumol/g, wet weight, suggesting that this polyamine may have an important physiological role in intracellular calcium homeostasis.


Ricci flow for 3D shape analysis.
Ricci flow is a powerful curvature flow method, which is invariant to rigid motion, scaling, isometric, and conformal deformations. We present the first application of surface Ricci flow in computer vision. Previous methods based on conformal geometry, which only handle 3D shapes with simple topology, are subsumed by the Ricci flow-based method, which handles surfaces with arbitrary topology. We present a general framework for the computation of Ricci flow, which can design any Riemannian metric by user-defined curvature. The solution to Ricci flow is unique and robust to noise. We provide implementation details for Ricci flow on discrete surfaces of either euclidean or hyperbolic background geometry. Our Ricci flow-based method can convert all 3D problems into 2D domains and offers a general framework for 3D shape analysis. We demonstrate the applicability of this intrinsic shape representation through standard shape analysis problems, such as 3D shape matching and registration, and shape indexing. Surfaces with large nonrigid anisotropic deformations can be registered using Ricci flow with constraints of feature points and curves. We show how conformal equivalence can be used to index shapes in a 3D surface shape space with the use of Teichmüller space coordinates. Experimental results are shown on 3D face data sets with large expression deformations and on dynamic heart data.


[Detection of human bocavirus DNA by polymerase chain reaction in children and adults with acute respiratory tract infections].
Human bocavirus (HBoV) which was described in 2005 by molecular techniques, is a member of Parvoviridae. The role of HBoV is being questioned in acute respiratory diseases (ARD) in many recent studies. The aim of this study was to determine the presence of HBoV DNA in the respiratory specimens of patients with ARD. A total of 155 throat swab and/or washing specimens from 76 children and 79 adults with ARD were examined. HBoV DNA was investigated by single step in-house polymerase chain reaction (PCR) using NS1 primers (5-'TATGGCCAAGGCAATCGTCCAAG-3', 5'-GCC GCGTGAACATGAGAAA-CAG-3') which amplify the 290 base pair region of NS1 gene located between nucleotides 1545-1835 of prototype HBoV st1 strain. HBoV DNA was detected in 5 (6.5%) of 76 children and 2 (2.5%) of 79 adults. Three sequenced samples showed 100% homology with the reference sequences. This study in which HBoV DNA was detected in children and adults with ARD, is the first HBoV prevalence study in Turkey. Larger scale prospective clinical and molecular studies are required to explain the association between HBoV and respiratory disease.


The relationship between metacognitive beliefs, auditory hallucinations, and hallucination-related distress in clinical and non-clinical voice-hearers.
To test the hypothesis that metacognitive beliefs are implicated in the development of distress associated with auditory verbal hallucinations (AVHs) rather than in their aetiology. A cross sectional questionnaire design was used. Three groups of participants were recruited (n= 20 in each group); clinical voice-hearers diagnosed with psychiatric disorders; non-clinical voice-hearers with no psychiatric history; and non-clinical participants with no history of voices or psychiatric disorder. All participants were screened for psychiatric symptomatology and completed a self-report measure of their metacognitive beliefs (MCQ-30). In addition, the two groups of voice-hearers were interviewed about dimensions of their voices (i.e., content, frequency, distress, and disruption). The clinical group scored significantly higher than the two non-clinical groups on two subscales of the MCQ-30 (negative beliefs about worry concerning controllability and danger and negative beliefs about thoughts concerning need for control). There were no significant differences between the two non-clinical groups on MCQ-30 scores. Regression analyses revealed that the negative beliefs about need for control subscale of the MCQ-30 was the only significant predictor of voice-related distress, although this effect was no longer significant after controlling for the effect of group. These results are consistent with previous findings suggesting that metacognitive beliefs are not directly implicated in the aetiology of AVHs, but may be associated with psychological distress. Further research is however needed to determine whether metacognitive style may directly impact upon voice-related distress.


Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate.
Anabolic responsiveness to teriparatide can be blunted or delayed in patients previously treated with alendronate. The extent of this effect is different for other antiresorptives. This study evaluated the early anabolic effects of teriparatide in postmenopausal women with osteoporosis previously treated with alendronate or risedronate. Patients treated for at least 24 months with alendronate or risedronate discontinued their bisphosphonate and received teriparatide for 12 months. The primary endpoint was a comparison of changes from baseline in N-terminal propeptide of type 1 collagen after 3 months between prior bisphosphonate groups. We also examined changes in other bone turnover markers, bone mineral density (BMD), and relationships between early changes in bone turnover markers and 12-month areal and volumetric BMD. In the prior risedronate group, the N-terminal propeptide of type 1 collagen increase was significantly greater after 3 months of teriparatide than in the prior alendronate group (mean +/- se, 86.0 +/- 5.6 vs. 61.2 +/- 5.3 ng/ml, respectively; P < 0.001). Findings were similar for the other bone turnover markers. The changes in areal BMD and trabecular spine volumetric BMD were also greater in the prior risedronate group (P < 0.05). Early changes in bone turnover markers correlated with changes in trabecular spine volumetric BMD at 12 months (Spearman r = 0.45). Teriparatide was well tolerated. This nonrandomized but prospective study suggests that there may be differences in anabolic responsiveness to teriparatide as a function of the type of prior bisphosphonate exposure.


Renal cell apoptosis in human lupus nephritis: a histological study.
Nuclear autoantigens from apoptotic cells are believed to drive the immunological response in systemic lupus erythematosus (SLE). Conflicting data exist as to the possible renal origin of apoptotic cells in SLE patients with nephritis. We assessed the level of renal cell apoptosis in kidney biopsies from 35 patients with lupus nephritis by means of terminal deoxynucleotidyl-transferase (TdT)-mediated deoxyuridine triphosphate (dUTP)-digoxigenin nick end labeling (TUNEL). Five samples of normal kidney tissue served as control specimens. We did not observe apoptotic glomerular cells in any of the control or nephritis biopsies. Scarce apoptotic tubular cells were seen in 13 of 35 (37%) of the nephritis specimens and in two of five (40%) of the control sections. Within the SLE cohort, patients with TUNEL-positive tubular cells in their renal biopsies had significantly higher activity index scores for tubulointerstitial mononuclear cell infiltration than patients without apoptotic tubular cells in their biopsies (P = 0.01). Furthermore, the level of tubular cell apoptosis displayed a statistically significant, positive correlation with the activity index score for mononuclear cell infiltration (r(s) = 0.472, P = 0.004) but not with scores for other activity or chronicity index components. These observations indicate that the degree of tubular cell apoptosis correlates with the severity of tubulointerstitial inflammation in SLE-associated nephritis. However, our findings do not suggest that apoptotic renal cells constitute a quantitatively important source of auto-antibody-inducing nuclear auto-antigens in human lupus nephritis.


Effects of age on balance assessment using voluntary and involuntary step tasks.
Taking a step while standing and modifying a step while walking are two strategies often used to maintain balance when balance disturbances are encountered during activities of daily living. This study investigated whether performance on an involuntary step task, which is assumed to be a surrogate for fall recovery abilities, was comparable to performance on a voluntary step task. The performance of a voluntary and an involuntary step task was measured in healthy young adult (mean age 21 years) and healthy elderly adult (mean age 68 years) female subjects. Subjects stepped as fast as possible in the direction of a minimally destabilizing lateral waist pull (voluntary step task), or they responded naturally to a large destabilizing lateral waist pull (involuntary step task). The effects of age, task, and their interaction on the primary outcome variables of step foot liftoff time, landing time, step length, and step height were examined. In the voluntary step task, the older adults, compared to the young, required significantly more time to lift their foot (Young: 307 msec; Elderly: 424 msec). In the involuntary step task, the elderly were as quick as the young in lifting their foot (Young: 322 msec; Elderly: 335 msec). The young lifted their foot at about the same time for the two tasks. The elders, on the other hand, lifted their foot significantly earlier in the involuntary step task, compared to the voluntary step task (Vol: 424 msec; Invol: 335 msec). A voluntary step task underestimates the ability of healthy elderly adults to respond quickly when large destabilizing balance disturbances are encountered.


Braving difficult choices alone: children's and adolescents' medical decision making.
What role should minors play in making medical decisions? The authors examined children's and adolescents' desire to be involved in serious medical decisions and the emotional consequences associated with them. Sixty-three children and 76 adolescents were presented with a cover story about a difficult medical choice. Participants were tested in one of four conditions: (1) own informed choice; (2) informed parents' choice to amputate; (3) informed parents' choice to continue a treatment; and (4) uninformed parents' choice to amputate. In a questionnaire, participants were asked about their choices, preference for autonomy, confidence, and emotional reactions when faced with a difficult hypothetical medical choice. Children and adolescents made different choices and participants, especially adolescents, preferred to make the difficult choice themselves, rather than having a parent make it. Children expressed fewer negative emotions than adolescents. Providing information about the alternatives did not affect participants' responses. Minors, especially adolescents, want to be responsible for their own medical decisions, even when the choice is a difficult one. For the adolescents, results suggest that the decision to be made, instead of the agent making the decision, is the main element influencing their emotional responses and decision confidence. For children, results suggest that they might be less able than adolescents to project how they would feel. The results, overall, draw attention to the need to further investigate how we can better involve minors in the medical decision-making process.


A functional methylome map of ulcerative colitis.
The etiology of inflammatory bowel diseases is only partially explained by the current genetic risk map. It is hypothesized that environmental factors modulate the epigenetic landscape and thus contribute to disease susceptibility, manifestation, and progression. To test this, we analyzed DNA methylation (DNAm), a fundamental mechanism of epigenetic long-term modulation of gene expression. We report a three-layer epigenome-wide association study (EWAS) using intestinal biopsies from 10 monozygotic twin pairs (n = 20 individuals) discordant for manifestation of ulcerative colitis (UC). Genome-wide expression scans were generated using Affymetrix UG 133 Plus 2.0 arrays (layer 1). Genome-wide DNAm scans were carried out using Illumina 27k Infinium Bead Arrays to identify methylation variable positions (MVPs, layer 2), and MeDIP-chip on Nimblegen custom 385k Tiling Arrays to identify differentially methylated regions (DMRs, layer 3). Identified MVPs and DMRs were validated in two independent patient populations by quantitative real-time PCR and bisulfite-pyrosequencing (n = 185). The EWAS identified 61 disease-associated loci harboring differential DNAm in cis of a differentially expressed transcript. All constitute novel candidate risk loci for UC not previously identified by GWAS. Among them are several that have been functionally implicated in inflammatory processes, e.g., complement factor CFI, the serine protease inhibitor SPINK4, and the adhesion molecule THY1 (also known as CD90). Our study design excludes nondisease inflammation as a cause of the identified changes in DNAm. This study represents the first replicated EWAS of UC integrated with transcriptional signatures in the affected tissue and demonstrates the power of EWAS to uncover unexplained disease risk and molecular events of disease manifestation.


Craniovertebral junction abnormalities with hindbrain herniation and syringomyelia: regression of syringomyelia after removal of ventral craniovertebral junction compression.
Hindbrain herniation syndrome, or Chiari malformation Type I (CM-I), occurs frequently with craniovertebral junction (CVJ) abnormalities when there is reduction in the posterior fossa volume. Syringomyelia is often present. Posterior fossa dorsal decompression (PFDD) is typically performed but has adverse results when ventral bone abnormality exists. This paper presents the results of a prospective study on CVJ abnormalities in patients with CM-I and syringomyelia. Between 1984 and 2008 (the MR imaging era), 298 patients with CVJ abnormalities and CM-I underwent ventral cervicomedullary decompression. Eighty-four patients had associated syringomyelia (15 with secondary invagination and 69 with primary basilar invagination, os odontoideum, or malunion of fractures). Of these 84 patients with CVJ abnormalities, CM-I, and syringomyelia, 46 had previously undergone PFDD, and 28 had previously undergone PFDD combined with fusion procedures or shunt placements. Of the 84 patients, a cervicothoracic syrinx was observed in 57, thoracic syrinx in 14, and holocord syrinx in 13. Studies included CT, MR imaging, and cine flow studies. All 298 patients who underwent ventral CVJ decompression had irreducible or partially reducible pathology. All 84 with syringomyelia showed brainstem dysfunction, lower cranial nerve symptoms, or myelopathy. Brainstem signs improved in 66 of the 84 patients, myelopathy improved in 58, and syringomyelia regressed in 64. Neurological improvement and syringomyelia resolution can occur using only ventral cervicomedullary junction decompression in patients with basilar invagination and basilar impression. This is likely due to the relief of neural encroachment and reestablishment of CSF pathways.


Effects of branched-chain amino acids (BCAAs) on the progression of advanced liver disease: A Korean nationwide, multicenter, retrospective, observational, cohort study.
Evidence of the potential benefits of long-term oral branched-chain amino acid (BCAA) supplementation in reducing the severity of liver disease is limited.Patients who were diagnosed with liver cirrhosis with a Child-Pugh (CP) score of 8-10 were included. The BCAA group consumed BCAAs daily for at least 6 months, and the control group consumed a diet without BCAA. We analyzed the improvements based on the model for end-stage liver disease (MELD) score, CP score, incidence of cirrhosis-related complications, and event-free survival over 2 years. Among the 867 recruited patients, 307 (166 in the BCAA group and 141 in the control group) were analyzed. The BCAA group was divided into 3 subgroups, whose patients consumed 4.15 g, 8.3 g, or 12.45 g of BCAAs daily for the analysis. There were significant differences in the CP score, albumin, and hepatic encephalopathy between the 2 groups at baseline. After matching the propensity scores, we analyzed patients in the BCAA-12.45 g group (12.45 g of BCAAs daily, n = 41) and matched control group (n = 41). The MELD score significantly improved in the BCCA-12.45 g group compared to the matched control group (P = .004). The changes in the serum bilirubin level (P = .014) and CP score (P = .033) over time also differed significantly between the 2 groups. The incidence rates of cirrhosis-related complications (P = .973) and development of hepatocellular carcinoma (2 cases each) did not differ significantly between the 2 groups.Long-term oral BCAA supplementation has beneficial effects in patients with advanced liver cirrhosis. A further large-scale prospective study is needed to delineate these beneficial effects.


Mortality and host response aberrations associated with transient and persistent acute kidney injury in critically ill patients with sepsis: a prospective cohort study.
Sepsis is the most frequent cause of acute kidney injury (AKI). The "Acute Disease Quality Initiative Workgroup" recently proposed new definitions for AKI, classifying it as transient or persistent. We investigated the incidence, mortality, and host response aberrations associated with transient and persistent AKI in sepsis patients. A total of 1545 patients admitted with sepsis to 2 intensive care units in the Netherlands were stratified according to the presence (defined by any urine or creatinine RIFLE criterion within the first 48 h) and evolution of AKI (with persistent defined as remaining > 48 h). We determined 30-day mortality by logistic regression adjusting for confounding variables and analyzed 16 plasma biomarkers reflecting pathways involved in sepsis pathogenesis (n = 866) and blood leukocyte transcriptomes (n = 392). AKI occurred in 37.7% of patients, of which 18.4% was transient and 81.6% persistent. On admission, patients with persistent AKI had higher disease severity scores and more frequently had severe (injury or failure) RIFLE AKI stages than transient AKI patients. Persistent AKI, but not transient AKI, was associated with increased mortality by day 30 and up to 1 year. Persistent AKI was associated with enhanced and sustained inflammatory and procoagulant responses during the first 4 days, and a more severe loss of vascular integrity compared with transient AKI. Baseline blood gene expression showed minimal differences with respect to the presence or evolution of AKI. Persistent AKI is independently associated with sepsis mortality, as well as with sustained inflammatory and procoagulant responses, and loss of vascular integrity as compared with transient AKI.


Downregulation of endotoxin-induced uveitis by intravitreal injection of vasoactive intestinal Peptide encapsulated in liposomes.
To reestablish the immunosuppressive microenvironment of the eye, disrupted by ocular inflammation during endotoxin-induced uveitis (EIU), by means of intravitreal injection of vasoactive intestinal peptide (VIP) in saline or encapsulated in liposomes, to increase its bioavailability and efficiency. EIU was induced in Lewis rats by subcutaneous injection of lipopolysaccharide (LPS). Simultaneously, animals were intravitreally injected with saline, saline/VIP, VIP-loaded liposomes (VIP-Lip), or unloaded liposomes. EIU severity and cellular infiltration were assessed by clinical examination and specific immunostaining. VIP concentration was determined in ocular fluids by ELISA. Ocular expression of inflammatory cytokine and chemokine mRNAs was detected by semiquantitative RT-PCR. Biodistribution of rhodamine-conjugated liposomes (Rh-Lip) was analyzed by immunohistochemistry in eyes and regional cervical lymph nodes (LNs). Twenty-four hours after intravitreal injection of VIP-Lip, VIP concentration in ocular fluids was 15 times higher than after saline/VIP injection. At that time, EIU clinical severity, ocular infiltrating polymorphonuclear leukocytes (PMNs), and, to a lesser extent, ED1(+) macrophages, as well as inflammatory cytokine and chemokine mRNA expression, were significantly reduced in VIP-Lip-injected rats compared with rats injected with saline/VIP, unloaded liposomes, or saline. Rh-Lip was distributed in vitreous, ciliary body, conjunctiva, retina, and sclera. It was internalized by macrophages and PMNs, and VIP colocalized with liposomes at least up to 14 days after injection. In cervical LNs, resident macrophages internalized VIP-Rh-Lip, and some adjacent lymphocytes showed VIP expression. VIP was efficient at reducing EIU only when formulated in liposomes, which enhanced its immunosuppressive effect and controlled its delivery to all tissues affected by or involved in ocular inflammation.


The Longue Durée of genetic ancestry: multiple genetic marker systems and Celtic origins on the Atlantic facade of Europe.
Celtic languages are now spoken only on the Atlantic facade of Europe, mainly in Britain and Ireland, but were spoken more widely in western and central Europe until the collapse of the Roman Empire in the first millennium a.d. It has been common to couple archaeological evidence for the expansion of Iron Age elites in central Europe with the dispersal of these languages and of Celtic ethnicity and to posit a central European "homeland" for the Celtic peoples. More recently, however, archaeologists have questioned this "migrationist" view of Celtic ethnogenesis. The proposition of a central European ancestry should be testable by examining the distribution of genetic markers; however, although Y-chromosome patterns in Atlantic Europe show little evidence of central European influence, there has hitherto been insufficient data to confirm this by use of mitochondrial DNA (mtDNA). Here, we present both new mtDNA data from Ireland and a novel analysis of a greatly enlarged European mtDNA database. We show that mtDNA lineages, when analyzed in sufficiently large numbers, display patterns significantly similar to a large fraction of both Y-chromosome and autosomal variation. These multiple genetic marker systems indicate a shared ancestry throughout the Atlantic zone, from northern Iberia to western Scandinavia, that dates back to the end of the last Ice Age.


Client perceptions of the value of veterinary anesthesiologist involvement with anesthesia and pain management, benefits of a preanesthetic consultation, and quality of care for dogs undergoing elective orthopedic surgery.
To compare perceptions related to veterinary anesthesiologist involvement with anesthesia and pain management, benefits of a preanesthetic consultation (PAC) with an anesthesiologist, and quality of patient care between clients who did and did not participate in a PAC prior to their dogs' elective orthopedic surgery. 80 dog owners. Owners of dogs undergoing elective stifle joint surgery participated in the study. Participants were randomly assigned to PAC and control groups (n = 40 participants/group). The PAC group participated in a PAC with an anesthesiologist and completed a written survey (12 items with Likert-type response options). The control group completed a similar survey (identical except for 2 statements related to the PAC experience) without participating in a PAC. Results were compared between groups by statistical methods. The proportion of clients in the PAC group who strongly agreed with the statements that a PAC was beneficial, their questions about the pet's anesthesia and pain management plan were answered, they knew who would perform anesthesia and what safeguards were in place, veterinary specialty hospitals should have an anesthesiologist on staff, they were willing to pay more to have an anesthesiologist supervise the anesthesia and pain management, and a PAC with an anesthesiologist should be standard of care in veterinary medicine was greater than that for control group clients. Responses to quality-of-care items did not differ between groups. Participating in a PAC was associated with more positive perceptions of anesthesiologists and knowledge about the anesthesia plan. Further research with a validated survey instrument is needed to confirm these findings.


Cryptosporidiosis and other intestinal protozoan infections in children less than one year of age in Mexico City.
Parasitic diseases are very important in Mexico because of their economic impact and adverse effects on normal growth in children. Cryptosporidiosis has been associated with acute diarrhea in immune competent and incompetent human hosts, fecal contamination of drinking water sources, and handling of animals. Due to the lack of reports on cryptosporidiosis in Mexico, we conducted a parasitologic study in children with diarrhea and other clinical symptoms. The main objectives were 1) to determine the prevalence of cryptosporidiosis in children less than one year of age in Mexico City, and 2) to correlate Cryptosporidium infection with gastrointestinal symptoms. Two hundred fecal samples from children seen at the Gabriel Mancera Familiar Medicine Unit of the Instituto Mexicano del Seguro Social were studied. Children were divided into two groups. Group A was composed of sick children with 6-8 watery diarrheic episodes every 24 hours attended at the emergency service. Group B was composed of healthy babies getting routine check ups. Only children in group A were found to be infected with intestinal protozoa (50% with Giardia lamblia, 41% with Cryptosporidium spp., and 4% with Entamoeba histolytica). The results suggested a high incidence of Cyrptosporidium infections in children in Mexico City, which make these observations useful for future studies.


Language profiles and literacy outcomes of children with resolving, emerging, or persisting language impairments.
Children with language impairment (LI) show heterogeneity in development. We tracked children from pre-school to middle childhood to characterize three developmental trajectories: resolving, persisting and emerging LI. We analyzed data from children identified as having preschool LI, or being at family risk of dyslexia, together with typically developing controls at three time points: t1 (age 3;09), t3 (5;08) and t5 (8;01). Language measures are reported at t1, t3 and t5, and literacy abilities at t3 and t5. A research diagnosis of LI (irrespective of recruitment group) was validated at t1 by a composite language score derived from measures of receptive and expressive grammar and vocabulary; a score falling 1SD below the mean of the typical language group on comparable measures at t3 and t5 was used to determine whether a child had LI at later time points and then to classify LIs as resolving, persisting or emerging. Persisting preschool LIs were more severe and pervasive than resolving LIs. Language and literacy outcomes were relatively poor for those with persisting LI, and relatively good for those with resolving LI. A significant proportion of children with average language abilities in preschool had LIs that emerged in middle childhood - a high proportion of these children were at family risk of dyslexia. There were more boys in the persisting and resolving LI groups. Children with early LIs which resolved by the start of formal literacy instruction tended to have good literacy outcomes; children with late-emerging difficulties that persisted developed reading difficulties. Children with late-emerging LI are relatively common and are hard to detect in the preschool years. Our findings show that children whose LIs persist to the point of formal literacy instruction frequently experience reading difficulties.


The Impact of Aerobic Exercise on Quality of Life in Women with Breast Cancer: A Randomized Controlled Trial.
The women with breast cancer experience high rates of morbidity due to different treatments. The objective of this study was to evaluate the role of aerobic exercise in the quality of life (QoL) among women suffering from breast cancer in Hamadan, western Iran. Participants who had consummated the eligibility criteria were randomly assigned in exercise group (n=30) and control group (n=30). Written informed consent was obtained from all participants. The mean age was 42.70 ±9.6 and 43.50 ±8.60 yr old in exercise and control groups, respectively. The quality of life was assessed by two widely used standard questionnaires (EORTC QLQ-C30 and EORTC QLQ-BR23). The exercise group received supervised exercise 2 days per week for 10 weeks. Through two stages (before and after intervention) these groups were evaluated. Analyzing the data was performed by SPSS/20.0, using t-test, chi-squared and ANCOVA. P<0.05 was regarded as significant level. The global health status QoL, based on EORTC QLQ-C30, developed significantly in the exercise group (48.76±24.96 vs. 81.79±16.34) in comparison with the controls (47.75 ±15.73 vs. 52.88 ±14.51) (P<0.001). The exercise intervention was associated with substantial development in total score of functions and symptoms of QoL using EORTC QLQ-BR23 (P<0.001). The statistically and clinically crucial developments were indicated in functions and symptoms of QoL in response to exercise in breast cancer women.


Phenolic compounds as cultivar- and variety-distinguishing factors in some plant products.
The aim of the study was to determine whether phenolic compounds in some varieties of buckwheat, winter and spring barley and peas can be used as factors which distinguish selected cultivars and varieties of plant material. It was observed that the content of total phenolics might be useful as a cultivar-distinguishing factor for all the plant materials analyzed, but it was a distinguishing factor for only some varieties. Individual cultivars and varieties were best distinguished by the content of syringic acid. The levels of syringic and vanillic acids were in reverse proportion to the total amount of phenolics soluble in methanol and a positive correlation between syringic and ferulic acid was observed. Moreover, the protein content of plant material was analyzed and a significant (p ≤ 0.05) correlation between this component and ferulic and vanillic acids was noted.


Preoperative and intraoperative predictors of postoperative acute respiratory distress syndrome in a general surgical population.
Acute respiratory distress syndrome (ARDS) is a devastating condition with an estimated mortality exceeding 30%. There are data suggesting risk factors for ARDS development in high-risk populations, but few data are available in lower incidence populations. Using risk-matched analysis and a combination of clinical and research data sets, we determined the incidence and risk factors for the development of ARDS in this general surgical population. We conducted a review of common adult surgical procedures completed between June 1, 2004 and May 31, 2009 using an anesthesia information system. This data set was merged with an ARDS registry and an institutional death registry. Preoperative variables were subjected to multivariate analysis. Matching and multivariate regression was used to determine intraoperative factors associated with ARDS development. In total, 50,367 separate patient admissions were identified, and 93 (0.2%) of these patients developed ARDS. Preoperative risk factors for ARDS development included American Society of Anesthesiologist status 3-5 (odds ratio [OR] 18.96), emergent surgery (OR 9.34), renal failure (OR 2.19), chronic obstructive pulmonary disease (OR 2.16), number of anesthetics during the admission (OR 1.37), and male sex (OR 1.65). After matching, intraoperative risk factors included drive pressure (OR 1.17), fraction inspired oxygen (OR 1.02), crystalloid administration in liters (1.43), and erythrocyte transfusion (OR 5.36). ARDS is a rare condition postoperatively in the general surgical population and is exceptionally uncommon in low American Society of Anesthesiologists status patients undergoing scheduled surgery. Analysis after matching suggests that ARDS development is associated with median drive pressure, fraction inspired oxygen, crystalloid volume, and transfusion.


Embolization of patent foramen ovale closure devices: incidence, role of imaging in identification, potential causes, and management.
Transcatheter patent foramen ovale (PFO) closure is an alternative to antiplatelet or anticoagulative therapy in patients with cryptogenic stroke, and it is associated with a small incidence of periprocedural sequelae. Because embolization of PFO closure devices is a very rare procedural complication, data on its frequency, causes, and management are sparse. We sought to review the medical literature and the cases of PFO closure-device embolization at our institution with the aim of identifying likely problems and reporting potential solutions. Out of 310 adult patients who underwent transcatheter PFO closure from June 2002 through April 2011, there were 2 cases (0.6%) of PFO closure-device embolization. In both patients, hypermobile septum primum and thick septum secundum were present. In one patient, failure to use a sizing balloon might have resulted in an underestimation of the PFO's size. In both patients, device embolization was identified in a timely fashion, the embolized device was safely retrieved, and the PFO was percutaneously closed with success. The incidence of PFO closure-device embolization is very low. The cases described here underscore the importance of imaging in the identification of morphologic predispositions to closure-device malpositioning, in the recognition of impending embolization, and in the timely management of embolization.


Homeostasis and function of regulatory T cells (Tregs) in vivo: lessons from TCR-transgenic Tregs.
The identification of CD25 and subsequently Forkhead box protein 3 (Foxp3) as markers for regulatory T cells (Tregs) has revolutionized our ability to explore this population experimentally. In a similar vein, our understanding of antigen-specific Treg responses in vivo owes much to the fortuitous generation of T-cell receptor (TCR)-transgenic Tregs. This has permitted tracking of Tregs with a defined specificity in vivo, facilitating analysis of how encounter with cognate antigen shapes Treg homeostasis and function. Here, we review the key lessons learned from a decade of analysis of TCR-transgenic Tregs and set this in the broader context of general progress in the field. Use of TCR-transgenic Tregs has led to an appreciation that Tregs are a highly dynamic proliferative population in vivo, rather than an anergic population as they were initially portrayed. It is now clear that Treg homeostasis is positively regulated by encounter with self-antigen expressed on peripheral tissues, which is likely to be relevant to the phenomenon of peripheral repertoire reshaping that has been described for Tregs and the observation that the Treg TCR specificities vary by anatomical location. Substantial evidence has also accumulated to support the role of CD28 costimulation and interleukin-2 in Treg homeostasis. The availability of TCR-transgenic Tregs has enabled analysis of Treg populations that are sufficient or deficient in particular genes, without the comparison being confounded by repertoire alterations. This approach has yielded insights into genes required for Treg function in vivo, with particular progress being made on the role of ctla-4 in this context. As the prospect of manipulating Treg populations in the clinic becomes reality, a full appreciation of the rules governing their homeostasis will prove increasingly important.


Natural history of tuberculosis: duration and fatality of untreated pulmonary tuberculosis in HIV negative patients: a systematic review.
The prognosis, specifically the case fatality and duration, of untreated tuberculosis is important as many patients are not correctly diagnosed and therefore receive inadequate or no treatment. Furthermore, duration and case fatality of tuberculosis are key parameters in interpreting epidemiological data. To estimate the duration and case fatality of untreated pulmonary tuberculosis in HIV negative patients we reviewed studies from the pre-chemotherapy era. Untreated smear-positive tuberculosis among HIV negative individuals has a 10-year case fatality variously reported between 53% and 86%, with a weighted mean of 70%. Ten-year case fatality of culture-positive smear-negative tuberculosis was nowhere reported directly but can be indirectly estimated to be approximately 20%. The duration of tuberculosis from onset to cure or death is approximately 3 years and appears to be similar for smear-positive and smear-negative tuberculosis. Current models of untreated tuberculosis that assume a total duration of 2 years until self-cure or death underestimate the duration of disease by about one year, but their case fatality estimates of 70% for smear-positive and 20% for culture-positive smear-negative tuberculosis appear to be satisfactory.


Payers' experiences with confidential pharmaceutical price discounts: A survey of public and statutory health systems in North America, Europe, and Australasia.
Institutional payers for pharmaceuticals worldwide appear to be increasingly negotiating confidential discounts off of the official list price of pharmaceuticals purchased in the community setting. We conducted an anonymous survey about experiences with and attitudes toward confidential discounts on patented pharmaceuticals in a sample of high-income countries. Confidential price discounts are now common among the ten health systems that participated in our study, though some had only recently begun to use these pricing arrangements on a routine basis. Several health systems had used a wide variety of discounting schemes in the past two years. The most frequent discount received by participating health systems was between 20% and 29% of official list prices; however, six participants reported their health system received one or more discount over the past two years that was valued at 60% or more of the list prices. On average, participants reported that confidential discounts were more common, complex, and significant for specialty pharmaceuticals than for primary care pharmaceuticals. Participants had a more favorable view of the impact of confidential discount schemes on their health systems than on the global marketplace. Overall, the frequency, complexity, and scale of confidential discounts being routinely negotiated suggest that the list prices for medicines bear limited resemblance to what many institutional payers actually pay.


Recent trends in breast surgery in the United States and United Kingdom.
Data on breast surgery from national samples of patients discharged from hospital in the United States and in England and Wales were reviewed for the years 1970-80. In the United States the rate of breast surgery increased dramatically in 1974 and 1975, but in Britain it remained constant and well below the level in the United States. In both countries the proportion of radical mastectomies declined and the proportion of less extensive procedures rose. The increase in mastectomy rates in the United States probably resulted from increased public concern about breast cancer and from the promotion of breast screening in the mid-1970s. The costs, morbidity, and early mortality associated with a higher rate of mastectomy are substantial and the advantages unclear.


Vascular permeability--the essentials.
The vasculature, composed of vessels of different morphology and function, distributes blood to all tissues and maintains physiological tissue homeostasis. In pathologies, the vasculature is often affected by, and engaged in, the disease process. This may result in excessive formation of new, unstable, and hyperpermeable vessels with poor blood flow, which further promotes hypoxia and disease propagation. Chronic vessel permeability may also facilitate metastatic spread of cancer. Thus, there is a strong incentive to learn more about an important aspect of vessel biology in health and disease: the regulation of vessel permeability. The current review aims to summarize current insights into different mechanisms of vascular permeability, its regulatory factors, and the consequences for disease.


Dual-Reporter Drift Correction To Enhance the Performance of Electrochemical Aptamer-Based Sensors in Whole Blood.
The continuous, real-time monitoring of specific molecular targets in unprocessed clinical samples would enable many transformative medical applications. Electrochemical aptamer-based (E-AB) sensors appear to be a promising approach to this end because of their selectivity (performance in complex samples, such as serum) and reversible, single-step operation. E-AB sensors suffer, however, from often-severe baseline drift when challenged in undiluted whole blood. In response we report here a dual-reporter approach to performing E-AB baseline drift correction. The approach incorporates two redox reporters on the aptamer, one of which serves as the target-responsive sensor and the other, which reports at a distinct, nonoverlapping redox potential, serving as a drift-correcting reference. Taking the difference in their relative signals largely eliminates the drift observed for these sensors in flowing, undiluted whole blood, reducing drift of up to 50% to less than 2% over many hours of continuous operation under these challenging conditions.


Multiple pathways of T-T interaction in the generation of cytotoxic T lymphocytes to alloantigens.
The interaction of T helper (Th) cells with syngeneic and allogeneic cytotoxic T lymphocyte precursors (CTL.P) has been investigated. Unprimed and mixed lymphocyte culture-primed peripheral T cells were used as a source of Th. Thymocytes, which depend upon exogenous Th cells for activation, were used as a source of cytotoxic precursors. Data is presented that demonstrates that at least two pathways of T-T interaction can lead to the activation of cytotoxic lymphocytes. The first is an allogeneic effect, in which Th cells recognize and respond to alloantigens expressed on CTL.P. The second is the interaction of Th cells with syngeneic CTL.P, in which both cell types are thought to respond to alloantigens on stimulator cells. The latter interaction can be shown to be restricted by H-2-linked determinants when primed Th cells are used and allogeneic effects against thymocytes are minimized. Restricted interactions between unprimed Th cells and thymocyte CTL.P have never been observed. Mechanisms that may explain the difference between the interaction of unprimed and primed Th cells with CTL.P are discussed.


The health of adolescents in detention: a global scoping review.
Adolescents detained within the criminal justice system are affected by complex health problems, health-risk behaviours, and high rates of premature death. We did a global synthesis of the evidence regarding the health of this population. We searched Embase, PsycINFO, Education Resources Information Center, PubMed, Web of Science, CINCH, Global Health, the Cochrane Database of Systematic Reviews, the Campbell Library, the National Criminal Justice Reference System Abstract Database, and Google Scholar for peer-reviewed journal articles, including reviews, that reported the prevalence of at least one health outcome (physical, mental, sexual, infectious, and neurocognitive) in adolescents (aged <20 years) in detention, and were published between Jan 1, 1980, and June 30, 2018. The reference lists of published review articles were scrutinised for additional relevant publications. Two reviewers independently screened titles and abstracts, and three reviewed full texts of relevant articles. The protocol for this Review was registered with PROSPERO (CRD42016041392). 245 articles (204 primary research articles and 41 reviews) were included, with most primary research (183 [90%]) done in high-income countries. A high lifetime prevalence of health problems, risks, and conditions was reported in detained adolescents, including mental disorders (0-95%), substance use disorders (22-96%), self-harm (12-65%), neurodevelopmental disabilities (2-47%), infectious diseases (0-34%), and sexual and reproductive conditions (pregnant by age 19 years 20-37%; abnormal cervical screening test result 16%). Various physical and mental health problems and health-risk behaviours are more common among adolescents in detention than among their peers who have not been detained. As the social and structural drivers of poor health overlap somewhat with factors associated with exposure to the criminal justice system, strategies to address these factors could help to reduce both rates of adolescent detention and adolescent health inequalities. Improving the detection of mental and physical disorders, providing appropriate interventions during detention, and optimising transitional health care after release from detention could improve the health outcomes of these vulnerable young people.


Fast estimation of adsorption isotherm parameters in gradient elution preparative liquid chromatography II: the competitive case.
Experimental competitive adsorption isotherms were successfully determined directly from overloaded elution profiles in gradient elution mode using an extended inverse method. This approach differs from the existing methods in one important aspect - no isocratic experiments are necessary which makes it possible to study adsorption of substances whose retention factors vary strongly with the mobile-phase composition. The approach was verified with simulated binary data and with experimental data from gradient separations of a cyclohexanone/cycloheptanone mixture. For the synthetic data, the original adsorption isotherm parameters were found using a two-step estimation procedure. In the first step analytical peaks were used to estimate the "analytical" part of the Langmuir equation and in the second step the association equilibrium parameters were estimated from two simulated overloaded elution profiles. For the experimental data, a three-step approach was used. The two first steps were used to reduce the calculation time so that parameter estimation could be performed on an ordinary computer. In the first step, analytical peaks were used to estimate the "analytical" part of the bi-Langmuir equation. In the second step, initial guesses for all other parameters were determined separately for each solute using the faster Rouchon algorithm. In the final and third step, the more accurate orthogonal collocation on finite elements algorithm, was used to fine-tune the isotherm parameters. The model could accurately predict the shape of overloaded elution profiles. The shape of the adsorption isotherms agreed well with those determined with the standard isocratic method, although the numerical values were not the same. The extended inverse method is well suited for process optimization where few experiments and accurate predictions are important.


The impact of intra-DRG severity of illness on hospital profitability: implications for payment reform.
We examined the relationship between variations in intra-DRG severity of illness classifications and hospital profitability. Unlike in previous studies, we created a direct hospital-level measure of severity, formed from MedisGroup severity scores. We estimated separate regression equations for total margin, operating margin, net revenue per admission, and expense per admission. We examined data for 201 Pennsylvania hospitals and found that hospital profits were inversely related to the severity of illness index. Expense per admission was positively related to severity; however the relationship between severity and net revenue per admission was not significant. The results suggest that hospitals with a more severe case mix may not recover the full costs of providing services. Thus payment reform should include adjustments for severity of illness.


Of predators, parasites, and fickle friends.
When we think about food undoubtedly we are the protagonists, the eaters. However, within the broader biological context our own bodies are also living meals for a myriad of parasites. It is often through the very food we eat that we animals become unsuspecting hosts to a variety of parasites, and thus links within the wider food chain. As unappetizing as they are, these trophic connections are as significant as they are profound. Indeed, much of what biologists have come to know about the complex ecology and evolution of life on the planet over the last 4.5 billion years is premised on the dynamics of eating and being eaten. Whether a relationship is symbiotic or in fact parasitic between species can be a very fuzzy line and is often a matter of looking at the remarkable gustatory details. With an ecological perspective on the wider world of eating, our notions of "food" take on new meaning.


Abnormal high-frequency burst firing of cerebellar neurons in rapid-onset dystonia-parkinsonism.
Loss-of-function mutations in the α3 isoform of the Na(+)/K(+) ATPase (sodium pump) are responsible for rapid-onset dystonia parkinsonism (DYT12). Recently, a pharmacological model of DYT12 was generated implicating both the cerebellum and basal ganglia in the disorder. Notably, partially blocking sodium pumps in the cerebellum was necessary and sufficient for induction of dystonia. Thus, a key question that remains is how partially blocking sodium pumps in the cerebellum induces dystonia. In vivo recordings from dystonic mice revealed abnormal high-frequency bursting activity in neurons of the deep cerebellar nuclei (DCN), which comprise the bulk of cerebellar output. In the same mice, Purkinje cells, which provide strong inhibitory drive to DCN cells, also fired in a similarly erratic manner. In vitro studies demonstrated that Purkinje cells are highly sensitive to sodium pump dysfunction that alters the intrinsic pacemaking of these neurons, resulting in erratic burst firing similar to that identified in vivo. This abnormal firing abates when sodium pump function is restored and dystonia caused by partial block of sodium pumps can be similarly alleviated. These findings suggest that persistent high-frequency burst firing of cerebellar neurons caused by sodium pump dysfunction underlies dystonia in this model of DYT12.


Flexoelectricity in atomic monolayers from first principles.
We study the flexoelectric effect in fifty-four select atomic monolayers using ab initio Density Functional Theory (DFT). Specifically, considering representative materials from each of the Group III monochalcogenides, transition metal dichalcogenides (TMDs), Groups IV, III-V, and V monolayers, Group IV dichalcogenides, Group IV monochalcogenides, transition metal trichalcogenides (TMTs), and Group V chalcogenides, we perform symmetry-adapted DFT simulations to calculate transversal flexoelectric coefficients along the principal directions at practically relevant bending curvatures. We find that the materials demonstrate linear behavior and have similar coefficients along both principal directions, with values for TMTs being up to a factor of five larger than those of graphene. In addition, we find electronic origins for the flexoelectric effect, which increases with monolayer thickness, elastic modulus along the bending direction, and sum of polarizability of constituent atoms.


Venomous snakebite in eastern Ecuador.
Treatment outcome of 294 hospitalized victims of snakebite injuries in Eastern Ecuador are reported, documenting high rates of morbidity and mortality. One or more major complications occurred in 25% of patients. Complications included blood loss severe enough to require transfusion (29 patients), abscess (26 patients), intracranial hemorrhage (15 patients) and major tissue loss (10 patients). Sixteen patients died, yielding a mortality rate of 5.4%. Death resulted from intracranial hemorrhage in 12 patients and from sequelae of hypovolemic shock in 4 patients.


Studying receptor-ligand interactions using encoded amino acid scanning.
A novel technique is described that allows the synthesis, functional analysis, and quantitative readout of defined arrays of polypeptide analogues in aqueous solution. Key to this approach is the use of a simple encoding-decoding system in which a unique Fmoc-amino acid tag is covalently attached to the C terminus of each member of a molecular array through a selectively cleavable bond. These tags can be cleanly removed from the molecules they encode, allowing single-step characterization and quantification of the entire mixture by HPLC. The utility of this technique is illustrated through the preparation of an array of proline-rich sequences based on the exchange factor C3G, one of the natural ligands of the N-terminal SH3 domain from the proto-oncogene, c-Crk. The array was designed to systematically modify those residues within the C3G peptide ligand thought to make key interactions with the c-Crk SH3 domain. Using competition binding experiments, it was possible to determine the relative ED50 values for the entire array of molecules simultaneously. These studies revealed that in order to maintain optimal binding to the SH3 domain, the P-3 side chain of the ligand must be positively charged and the P-0 side chain must be hydrophobic and extend beyond the gamma-carbon. The excellent correlation between these relative ED50 values and a series of relative Kd values determined from individual peptides suggests that this approach may be useful in determining, in a parallel fashion, the relative biological activities of arrays of polypeptides.


Intracranial aneurysm segmentation in 3D CT angiography: method and quantitative validation with and without prior noise filtering.
Intracranial aneurysm volume and shape are important factors for predicting rupture risk, for pre-surgical planning and for follow-up studies. To obtain these parameters, manual segmentation can be employed; however, this is a tedious procedure, which is prone to inter- and intra-observer variability. Therefore there is a need for an automated method, which is accurate, reproducible and reliable. This study aims to develop and validate an automated method for segmenting intracranial aneurysms in Computed Tomography Angiography (CTA) data. Also, it is investigated whether prior smoothing improves segmentation robustness and accuracy. The proposed segmentation method is implemented in the level set framework, more specifically Geodesic Active Surfaces, in which a surface is evolved to capture the aneurysmal wall via an energy minimization approach. The energy term is composed of three different image features, namely; intensity, gradient magnitude and intensity variance. The method requires minimal user interaction, i.e. a single seed point inside the aneurysm needs to be placed, based on which image intensity statistics of the aneurysm are derived and used in defining the energy term. The method has been evaluated on 15 aneurysms in 11 CTA data sets by comparing the results to manual segmentations performed by two expert radiologists. Evaluation measures were Similarity Index, Average Surface Distance and Volume Difference. The results show that the automated aneurysm segmentation method is reproducible, and performs in the range of inter-observer variability in terms of accuracy. Smoothing by nonlinear diffusion with appropriate parameter settings prior to segmentation, slightly improves segmentation accuracy.


Kinetics of the thermal degradation of patulin in the presence of ascorbic acid.
Degradation of the mycotoxin patulin between 25 and 85 °C without and with added ascorbic acid was studied, and the effectiveness of linear and nonlinear models for predicting reaction rates was compared. In agreement with previous reports, ascorbic acid significantly increased (P ≤ 0.05) the rate of patulin degradation at all temperatures studied. The data for patulin degradation in the absence of ascorbic acid were adequately modeled using a zero-order linear kinetic model. However, the predictive abilities of zero and higher-order linear models were not adequate to describe the more complex reactions that likely occurred when ascorbic acid was added. In contrast, the nonlinear Weibull model adequately described the patulin-ascorbic acid reaction throughout the temperature range studied. Zero-order rate constants and Weibull scale values for each of the respective reactions followed the Arrhenius law. Activation energies of 58.7 ± 3.9 and 29.6 ± 1.9 kJ mol⁻¹ for the reaction without and with ascorbic acid, respectively, confirmed decreased patulin stability in the presence of ascorbic acid and suggested that the mechanisms for the 2 degradation reactions were different.


Duration of thyroid dysfunction correlates with all-cause mortality. the OPENTHYRO Register Cohort.
The association between thyroid dysfunction and mortality is controversial. Moreover, the impact of duration of thyroid dysfunction is unclarified. Our aim was to investigate the correlation between biochemically assessed thyroid function as well as dysfunction duration and mortality. Register-based follow-up study of 239,768 individuals with a serum TSH measurement from hospitals and/or general practice in Funen, Denmark. Measurements were performed at a single laboratory from January 1st 1995 to January 1st 2011. Cox regression was used for mortality analyses and Charlson Comorbidity Index (CCI) was used as comorbidity score. Hazard ratios (HR) with 95% confidence intervals (CI) for mortality with decreased (<0.3 mIU/L) or elevated (>4.0 mIU/L) levels of TSH were 2.22; 2.14-2.30; P<0.0001 and 1.28; 1.22-1.35; P<0.0001, respectively. Adjusting for age, gender, CCI and diagnostic setting attenuated the risk estimates (HR 1.23; 95% CI: 1.19-1.28; P<0.0001, mean follow-up time 7.7 years, and HR 1.07; 95% CI: 1.02-1.13; P = 0.004, mean follow-up time 7.2 years) for decreased and elevated values of TSH, respectively. Mortality risk increased by a factor 1.09; 95% CI: 1.08-1.10; P<0.0001 or by a factor 1.03; 95% CI: 1.02-1.04; P<0.0001 for each six months a patient suffered from decreased or elevated TSH, respectively. Subdividing according to degree of thyroid dysfunction, overt hyperthyroidism (HRovert 1.12; 95% CI: 1.06-1.19; P<0.0001), subclinical hyperthyroidism (HRsubclinical 1.09; 95% CI: 1.02-1.17; P = 0.02) and overt hypothyroidism (HRovert 1.57; 95% CI: 1.34-1.83; P<0.0001), but not subclinical hypothyroidism (HRsubclinical 1.03; 95% CI: 0.97-1.09; P = 0.4) were associated with increased mortality. In a large-scale, population-based cohort with long-term follow-up (median 7.4 years), overt and subclinical hyperthyroidism and overt but not subclinical hypothyroidism were associated with increased mortality. Excess mortality with increasing duration of decreased or elevated serum TSH suggests the importance of timely intervention in individuals with thyroid dysfunction.


Excessive infant crying doubles the risk of mood and behavioral problems at age 5: evidence for mediation by maternal characteristics.
The onset of behavioral problems starts in early life. This study examined whether excessive infant crying (maternal ratings) is a determinant of emotional and behavioral problems at age 5-6 years. In the Amsterdam Born Children and their Development (ABCD) study, a large prospective, observational, population-based multiethnic birth cohort, excessive infant crying (crying for three or more hours per 24 h day over the past week) during the 13th week after birth (range 11-25 weeks, SD 2 weeks), maternal burden of infant care and maternal aggressive behavior (either angry speaking, or physical aggression) was assessed using a questionnaire. Children's behavioral and emotional problems at the age of 5-6 were assessed by Goodman's Strengths and Difficulties Questionnaire (SDQ), by the subscale of generalized anxiety of the preschool anxiety scale (PAS), and by the Short Mood and Feelings Questionnaire (SMFQ). Inclusion criterion was singleton birth. Exclusion criteria were preterm born babies or congenital disorders. Among 3389 children, excessive infant crying (n = 102) was associated with a twofold increased risk of the overall problem behavior, conduct problems, hyperactivity, and mood problems at the age of 5-6 [ORs between 1.75 (95 % CI 1.09-2.81) and 2.12 (95 % CI 1.30-3.46)]. This association was mediated by maternal burden of infant care (change in odds' ratio 1-17 %) and maternal aggressive behavior (change in odds' ratio 4-10 %). There was no effect modification by the child's gender or maternal parity. Excessive infant crying was not associated with general anxiety problems. Excessive infant crying doubles the risk of behavioral, hyperactivity, and mood problems at the age of 5-6, as reported by their mother. Maternal burden of infant care partially mediates the association between excessive crying and behavioral and mood problems. Special care for mothers with a high burden of care for their excessive crying infant, notwithstanding their own good health, can be a feasible strategy for possible prevention of mood and behavioral problems in their children later in life.


Assignment of a form of congenital muscular dystrophy with secondary merosin deficiency to chromosome 1q42.
We have previously reported an autosomal recessive form of congenital muscular dystrophy, characterized by proximal girdle weakness, generalized muscle hypertrophy, rigidity of the spine, and contractures of the tendo Achilles, in a consanguineous family from the United Arab Emirates. Early respiratory failure resulting from severe diaphragmatic involvement was present. Intellect and the results of brain imaging were normal. Serum creatine kinase levels were grossly elevated, and muscle-biopsy samples showed dystrophic changes. The expression of the laminin-alpha2 chain of merosin was reduced on several fibers, but linkage analysis excluded the LAMA2 locus on chromosome 6q22-23. Here, we report the results of genomewide linkage analysis of this family, by use of homozygosity mapping. In all four affected children, an identical homozygous region was identified on chromosome 1q42, spanning 6-15 cM between flanking markers D1S2860 and D1S2800. We have identified a second German family with two affected children having similar clinical and histopathological features; they are consistent with linkage to the same locus. The cumulative LOD score was 3.57 (straight theta=.00) at marker D1S213. This represents a novel locus for congenital muscular dystrophy. We suggest calling this disorder "CMD1B." The expression of three functional candidate genes in the CMD1B critical region was investigated, and no detectable changes in their level of expression were observed. The secondary reduction in laminin-alpha2 chain in these families suggests that the primary genetic defect resides in a gene coding for a protein involved in basal lamina assembly.


Forest stand structure, productivity, and age mediate climatic effects on aspen decline.
Because forest stand structure, age, and productivity can mediate the impacts of climate on quaking aspen (Populus tremuloides) mortality, ignoring stand-scale factors limits inference on the drivers of recent sudden aspen decline. Using the proportion of aspen trees that were dead as an index of recent mortality at 841 forest inventory plots, we examined the relationship of this mortality index to forest structure and climate in the Rocky Mountains and Intermountain Western United States. We found that forest structure explained most of the patterns in mortality indices, but that variation in growing-season vapor pressure deficit and winter precipitation over the last 20 years was important. Mortality index sensitivity to precipitation was highest in forests where aspen exhibited high densities, relative basal areas, quadratic mean diameters, and productivities, whereas sensitivity to vapor pressure deficit was highest in young forest stands. These results indicate that the effects of drought on mortality may be mediated by forest stand development, competition with encroaching conifers, and physiological vulnerabilities of large trees to drought. By examining mortality index responses to both forest structure and climate, we show that forest succession cannot be ignored in studies attempting to understand the causes and consequences of sudden aspen decline.


Economic consequences of postinfarction prophylaxis with beta blockers: cost effectiveness of metoprolol.
Treatment with certain beta adrenoceptor blocking agents after myocardial infarction reduces mortality and the incidence of reinfarction. Data from a randomised placebo controlled study of the beta 1 selective blocker metoprolol given as secondary prophylaxis were therefore analysed for the possible cost effectiveness of extending this treatment to the general population of patients with myocardial infarction. Metoprolol 100 mg twice daily and matching placebo were given to 154 and 147 patients, respectively, for three years. During this period drug costs for the beta blocker, digitalis, and diuretics were analysed as well as costs of readmission for cardiac problems and indirect costs arising from sick leave or early retirement. Active treatment with metoprolol significantly reduced costs of readmission as well as indirect costs. The net effect per patient over the three years was a reduction of roughly kr 19,000 (1930 pounds). These results suggest that beta blocker treatment given as secondary prophylaxis after myocardial infarction is highly cost effective.


Using self-reported health measures to predict high-need cases among Medicaid-eligible adults.
To assess the ability of different self-reported health (SRH) measures to prospectively identify individuals with high future health care needs among adults eligible for Medicaid. The 1997-2008 rounds of the National Health Interview Survey linked to the 1998-2009 rounds of the Medical Expenditure Panel Survey (n = 6,725). Multivariate logistic regression models are fitted for the following outcomes: having an inpatient visit; membership in the top decile of emergency room utilization; and membership in the top cost decile. We examine the incremental predictive ability of six different SRH domains (health conditions, mental health, access to care, health behaviors, health-related quality of life [HRQOL], and prior utilization) over a baseline model with sociodemographic characteristics. Models are evaluated using the c-statistic, integrated discrimination improvement, sensitivity, specificity, and predictive values. Self-reports of prior utilization provide the greatest predictive improvement, followed by information on health conditions and HRQOL. Models including these three domains meet the standard threshold of acceptability (c-statistics range from 0.703 to 0.751). SRH measures provide a promising way to prospectively profile Medicaid-eligible adults by likely health care needs.


NSAID prescribing precautions.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used, but have risks associated with their use, including significant upper gastrointestinal tract bleeding. Older persons, persons taking anticoagulants, and persons with a history of upper gastrointestinal tract bleeding associated with NSAIDs are at especially high risk. Although aspirin is cardioprotective, other NSAIDs can worsen congestive heart failure, can increase blood pressure, and are related to adverse cardiovascular events, such as myocardial infarction and ischemia. Cyclooxygenase-2 inhibitors have been associated with increased risk of myocardial infarction; however, the only cyclooxygenase-2 inhibitor still available in the United States, celecoxib, seems to be safer in this regard. Hepatic damage from NSAIDs is rare, but these medications should not be used in persons with cirrhotic liver diseases because bleeding problems and renal failure are more likely. Care should be used when prescribing NSAIDs in persons taking anticoagulants and in those with platelet dysfunction, as well as immediately before surgery. Potential central nervous system effects include aseptic meningitis, psychosis, and tinnitus. Asthma may be induced or exacerbated by NSAIDs. Although most NSAIDs are likely safe in pregnancy, they should be avoided in the last six to eight weeks of pregnancy to prevent prolonged gestation from inhibition of prostaglandin synthesis, premature closure of the ductus arteriosus, and maternal and fetal complications from antiplatelet activity. Ibuprofen, indomethacin, and naproxen are safe in breastfeeding women. Care should be taken to prevent accidental NSAID overdose in children by educating parents about correct dosing and storage in childproof containers.


Children with severe early childhood caries: pilot study examining mutans streptococci genotypic strains after full-mouth caries restorative therapy.
Genotypic strains of mutans streptococci (MS) may vary in important virulence properties and be differentially affected by specific components of full-mouth caries restorative therapy. The purpose of this pilot study was to identify mutans streptococci strains that predominate following caries restorative therapy. Plaque from 7 children with severe early childhood caries was collected before and following therapy. MS isolates (N=828) were subjected to polymerase chain reaction (PCR) and arbitrarily primed-PCR (AP-PCR) for assignment within MS strains. Determining the longitudinal changes in MS strain distribution over time within each patient required the isolation of larger numbers of isolates per patient, but from fewer patients. Up to 39 genotypic strains of Streptococcus mutans and Streptococcus sobrinus, and 7 genotypic strains of non-MS streptococci were identified by AP-PCR and 16S ribosomal rRNA gene sequencing. The number of MS strains isolated from each patient were 3 to 7 prior to treatment, diminishing to 1 to 2 dominant MS strains in most patients 6 months following therapy. Caries restorative therapy resulted in shifts of specific mutans streptococcus and non-mutans streptococcus strains. The implications are that caries restorative therapy affects the distribution of MS strains, and that well-accepted practices for caries prevention should be more closely examined for efficacy.


LAR protein tyrosine phosphatase receptor associates with TrkB and modulates neurotrophic signaling pathways.
The identities of receptor protein tyrosine phosphatases (PTPs) that associate with Trk protein tyrosine kinase (PTK) receptors and modulate neurotrophic signaling are unknown. The leukocyte common antigen-related (LAR) receptor PTP is present in neurons expressing TrkB, and like TrkB is associated with caveolae and regulates survival and neurite outgrowth. We tested the hypothesis that LAR associates with TrkB and regulates neurotrophic signaling in embryonic hippocampal neurons. Coimmunoprecipitation and coimmunostaining demonstrated LAR interaction with TrkB that is increased by BDNF exposure. BDNF neurotrophic activity was reduced in LAR-/- and LAR siRNA-treated LAR+/+ neurons and was augmented in LAR-transfected neurons. In LAR-/- neurons, BDNF-induced activation of TrkB, Shc, AKT, ERK, and CREB was significantly decreased; while in LAR-transfected neurons, BDNF-induced CREB activation was augmented. Similarly, LAR+/+ neurons treated with LAR siRNA demonstrated decreased activation of Trk and AKT. LAR is known to activate the Src PTK by dephosphorylation of its negative regulatory domain and Src transactivates Trk. In LAR-/- neurons, or neurons treated with LAR siRNA, phosphorylation of the Src regulatory domain was increased (indicating Src inactivation), consistent with a role for Src in mediating LAR's ability to up-regulate neurotrophic signaling. Interactions between LAR, TrkB, and Src were further confirmed by the findings that Src coimmunoprecipitated with LAR, that the Src inhibitor PP2 blocked the ability of LAR to augment TrkB signaling, and that siRNA-induced depletion of Src decreased LAR interaction with TrkB. These studies demonstrate that receptor PTPs can associate with Trk complexes and promote neurotrophic signaling and point to receptor PTP-based strategies as a novel approach for modulating neurotrophin function.


Creating a specialist protein resource network: a meeting report for the protein bioinformatics and community resources retreat.
During 11-12 August 2014, a Protein Bioinformatics and Community Resources Retreat was held at the Wellcome Trust Genome Campus in Hinxton, UK. This meeting brought together the principal investigators of several specialized protein resources (such as CAZy, TCDB and MEROPS) as well as those from protein databases from the large Bioinformatics centres (including UniProt and RefSeq). The retreat was divided into five sessions: (1) key challenges, (2) the databases represented, (3) best practices for maintenance and curation, (4) information flow to and from large data centers and (5) communication and funding. An important outcome of this meeting was the creation of a Specialist Protein Resource Network that we believe will improve coordination of the activities of its member resources. We invite further protein database resources to join the network and continue the dialogue.


Palliative radiotherapy for painful bone metastases: short-course or long-course?
For patients of bony metastases, the survival time becomes much longer as the anti-tumor strategies developed. External beam radiotherapy is effective for pain-relieving. The appropriate fractionation scheme for the most effective regimen of palliative radiotherapy to treat bone metastases is still in debate. This article reviews the prospective randomized trials comparing short-course or long-course regimens of palliative radiotherapy for painful bone metastases.


A Collaborative Platform for Management of Chronic Diseases via Guideline-Driven Individualized Care Plans.
Older age is associated with an increased accumulation of multiple chronic conditions. The clinical management of patients suffering from multiple chronic conditions is very complex, disconnected and time-consuming with the traditional care settings. Integrated care is a means to address the growing demand for improved patient experience and health outcomes of multimorbid and long-term care patients. Care planning is a prevalent approach of integrated care, where the aim is to deliver more personalized and targeted care creating shared care plans by clearly articulating the role of each provider and patient in the care process. In this paper, we present a method and corresponding implementation of a semi-automatic care plan management tool, integrated with clinical decision support services which can seamlessly access and assess the electronic health records (EHRs) of the patient in comparison with evidence based clinical guidelines to suggest personalized recommendations for goals and interventions to be added to the individualized care plans. We also report the results of usability studies carried out in four pilot sites by patients and clinicians.


Thyroid autoantibodies in women with and without thyroid disorders in an iodine-replete area.
To compare the prevalence of positive autoantibodies in patients with thyroid disorders and healthy subjects in an iodine-replete area of the Islamic Republic of Iran, we studied 930 women in a clinic-based study: 698 patients (286 hypothyroid, 140 hyperthyroid, 272 with simple goitre) and 232 healthy women. Serum thyroxine (T4), triiodothyronine (T3), thyroid stimulating hormone, and anti-thyroid antibodies were measured. Positive autoantibodies were detected in 75.5% of patients with hypothyroidism, 73.6% of those with hyperthyroidism, 48.9% of those with simple goitre and 35.8% of the control group (P < 0.001). Autoimmunity may have a role in the genesis of common thyroid disorders.


Films loaded with insulin-coated nanoparticles (ICNP) as potential platforms for peptide buccal delivery.
The goal of this investigation was to develop films containing insulin-coated nanoparticles and evaluate their performance in vitro as potential peptide delivery systems. To incorporate insulin into the films, a new antisolvent co-precipitation fabrication process was adapted to obtain insulin-coated nanoparticles (ICNPs). The ICNPs were embedded in polymeric films containing a cationic polymethacrylate derivative (ERL) or a combination of ERL with hydroxypropyl methylcellulose (HPMC). ICNP-loaded films were characterized for morphology, mucoadhesion, and insulin release. Furthermore, in vitro insulin permeation was evaluated using a cultured tridimensional human buccal mucosa model. The antisolvent co-precipitation method was successfully adapted to obtain ICNPs with 40% (w/w) insulin load, achieving 323±8nm particles with a high zeta potential of 32.4±0.8mV, indicating good stability. High yields were obtained after manufacture and the insulin content did not decrease after one month storage. ICNP-embedded films using ERL as the polymer matrix presented excellent mucoadhesive and insulin release properties. A high permeation enhancement effect was observed for ICNP-loaded ERL films in comparison with ICNP-loaded ERL-HPMC films and a control insulin solution. ICNP-loaded ERL formulations were found to be more effective in terms of film performance and insulin permeation through the human buccal mucosa model, and thus are a promising delivery system for buccal administration of a peptide such as insulin.


Review of AlloDerm Acellular Human Dermis Regenerative Tissue Matrix in Multiple Types of Oculofacial Plastic and Reconstructive Surgery.
AlloDerm acellular human dermis is used for repair or replacement of damaged or inadequate skin tissue. It has been used successfully in multiple types of surgeries, including abdominal wall reconstruction, breast reconstruction, and head and neck reconstruction. Its application to ophthalmic plastic and reconstructive surgery is less well described. This study seeks to evaluate the efficacy and factors influencing surgical outcomes using Alloderm in multiple types of oculofacial plastic surgery. Institutional Review Board-approved retrospective review of 84 patients who underwent surgical procedures using Alloderm. Preoperative demographic data, comorbidities, smoking, clinical etiology, surgical methods, Alloderm type, and outcome (cosmetic and functional) were evaluated. This study included 84 patients, accounting for a total of 98 procedures. Mean age was 52.5 years (3-93 years). Etiologies necessitating surgery included malignancy in 26 patients (31.0%), trauma in 19 patients (22.6%), congenital lesions in 15 patients (17.9%), and senile change in 11 patients (13.1%). Surgical procedures included lower eyelid posterior lamella elongation, socket and fornix reconstruction, scar repair, patch grafts, and filler. Mean duration of follow up was 530 days. Overall, 92.8% of patients had favorable outcomes. Factors associated with significantly worse outcomes included smoking, congenital anomaly etiologies, and previous graft/flaps in the same area (p = 0.03, p = 0.029, and p = 0.007, respectively). This study suggests that Alloderm acellular human dermis can be used safely and effectively in multiple types of oculofacial procedures. Smoking, congenital anomaly etiologies, and previous graft/flap were associated with poor cosmetic and functional outcomes.


COVID -19 Complicated By Acute Respiratory Distress Syndrome, Myocarditis, and Pulmonary Embolism. a Case Report.
A 49-year-old female Qatari woman, with no past medical history, presented at a hospital complaining of a history of cough and shortness of breath. The patient tested positive for severe acute respiratory syndrome (ARDS) and COVID-19. Subsequently, her course of treatment was complicated by severe acute respiratory distress syndrome, pulmonary embolism and severe myocarditis requiring treatment with venous-arterial extracorporeal membrane oxygenation as a bridge to complete recovery.


Improved layout of phylogenetic networks.
Split networks are increasingly being used in phylogenetic analysis. Usually, a simple equal angle algorithm is used to draw such networks, producing layouts that leave much room for improvement. Addressing the problem of producing better layouts of split networks, this paper presents an algorithm for maximizing the area covered by the network, describes an extension of the equal-daylight algorithm to networks, looks into using a spring embedder and discusses how to construct rooted split networks.


Bisphenol A modified DNA: A possible immunogenic stimulus for anti-DNA autoantibodies in systemic lupus erythematosus.
Anti-DNA antibodies are now considered as a universal diagnostic feature for the patients with systemic lupus erythematosus (SLE) but the mechanism(s) involved in the generation of these autoantibodies remains to be investigated. Bisphenol A (BPA) is a synthetic phenol extensively used in the manufacturing of polycarbonated plastics. Upon mixing in the diet, it causes several health hazards. This study was undertaken to investigate the contribution of BPA induced DNA damage in SLE patients. Human DNA was modified by BPA in-vitro and the binding characteristics of SLE circulating immunoglobulin Gs (SLE-IgGs) with BPA damaged DNA (BPA-DNA) were screened and compared with the IgGs from normal healthy humans (NH-IgGs). Immunogenicity of BPA-DNA was determined by immunisation in rabbits. DNA from SLE patients (SLE-DNA) or healthy humans (NH-DNA) were isolated and their binding specificity with rabbit anti-BPA-DNA-IgGs was studied. Treatment of human DNA with BPA caused extensive damaged. Circulating SLE-IgGs showed strong recognition of BPA-DNA. BPA-DNA induced high titre antibodies in rabbits. Rabbit anti-BPA-DNA-IgGs showed strong cross reaction with isolated DNA from SLE patients. In short, we concluded that the structural alterations in DNA by BPA, generate neo-epitopes that may be a factor responsible for the induction of anti-DNA autoantibodies in SLE.


Facile Mixing of Phospholipids Promotes Self-Assembly of Low-Molecular-Weight Biodegradable Block Co-Polymers into Functional Vesicular Architectures.
In this work, we have used low-molecular-weight (PEG12-b-PCL6, PEG12-b-PCL9 or PEG16-b-PLA38; MW, 1.25-3.45 kDa) biodegradable block co-polymers to construct nano- and micron-scaled hybrid (polymer/lipid) vesicles, by solvent dispersion and electroformation methods, respectively. The hybrid vesicles exhibit physical properties (size, bilayer thickness and small molecule encapsulation) of a vesicular boundary, confirmed by cryogenic transmission electron microscopy, calcein leakage assay and dynamic light scattering. Importantly, we find that these low MW polymers, on their own, do not self-assemble into polymersomes at nano and micron scales. Using giant unilamellar vesicles (GUVs) model, their surface topographies are homogeneous, independent of cholesterol, suggesting more energetically favorable mixing of lipid and polymer. Despite this mixed topography with a bilayer thickness similar to that of a lipid bilayer, variation in surface topology is demonstrated using the interfacial sensitive phospholipase A2 (sPLA2). The biodegradable hybrid vesicles are less sensitive to the phospholipase digestion, reminiscent of PEGylated vesicles, and the degree of sensitivity is polymer-dependent, implying that the nano-scale surface topology can further be tuned by its chemical composition. Our results reveal and emphasize the role of phospholipids in promoting low MW polymers for spontaneous vesicular self-assembly, generating a functional hybrid lipid-polymer interface.


Endocoprid activity of Aphodius fossor (Coleoptera: Scarabaeidae) related to bovine dung decomposition in a mixed grass prairie.
Aphodius fossor (L.) (Coleoptera: Scarabaeidae), a common endocoprid dung beetle in southeastern Wyoming, may have a survival strategy to maintain dung pad integrity and moisture crucial to larval survival in an arid climate (annual precipitation <30 cm). Typically, A. fossor seems to contribute little to dung pad decomposition, because inhabited dung pads seem to be intact and weigh approximately the same as uninhabited pads, even after 1 yr on pasture. To assess the role of A. fossor in dung pad decomposition and nutrient recycling, artificially formed bovine dung pads were inoculated with five pairs of adult A. fossor. After 40 d, A. fossor activity had no measurable effect on external surface area or moisture retention within the dung pad cores. Pads inhabited by A. fossor weighed significantly more than did control pads on most weigh dates of the experiment, possibly because of incorporation of soil particles at the dung/soil interface. Externally, A. fossor-inhabited dung pads seemed intact; however extensive tunneling was evident throughout the core of the pad leaving an intact, protective crust. A. fossor activity increased microbial biomass carbon in the soil beneath the dung pad. Levels of total nitrogen (N) and carbon (C) decreased in the pads but increased in soil beneath the pads. Dung in the core and in the crust of pads with A. fossor had significantly less total N than pads with no beetles and total C was significantly lower in the crust.


Endometriosis - morphology, clinical presentations and molecular pathology.
Endometriosis is found predominantly in women of childbearing age. The prevalence of endometriosis is difficult to determine accurately. Laparoscopy or surgery is required for the definitive diagnosis. The most common symptoms are dysmenorrhea, dyspareunia, and low back pain that worsen during menses. Endometriosis occurring shortly after menarche has been frequently reported. Endometriosis has been described in a few cases at the umbilicus, even without prior history of abdominal surgery. It has been described in various atypical sites such as the fallopian tubes, bowel, liver, thorax, and even in the extremities. The most commonly affected areas in decreasing order of frequency in the gastrointestinal tract are the recto-sigmoid colon, appendix, cecum, and distal ileum. The prevalence of appendiceal endometriosis is 2.8%. Malignant transformation is a well-described, although rare (<1% of cases), complication of endometriosis. Approximately 75% of these tumors arise from endometriosis of the ovary. Other less common sites include the rectovaginal septum, rectum, and sigmoid colon. Unopposed estrogens therapy may play a role in the development of such tumors. A more recent survey of 27 malignancies associated with endometriosis found that 17 (62%) were in the ovary, 3 (11%) in the vagina, 2 (7%) each in the fallopian tube or mesosalpinx, pelvic sidewall, and colon, and 1 (4%) in the parametrium. Two cases of cerebral endometriosis and a case of endometriosis presenting as a cystic mass in the cerebellar vermis has been described. Treatment for endometriosis can be expectant, medical, or surgical depending on the severity of symptoms and the patient's desire to maintain or restore fertility.