Regional variation in immature Ixodes scapularis parasitism on North American songbirds: implications for transmission of the Lyme pathogen, Borrelia burgdorferi.
Borrelia burgdorferi, the etiological agent of Lyme disease, is transmitted among hosts by the black-legged tick, Ixodes scapularis, a species that regularly parasitizes various vertebrate hosts, including birds, in its immature stages. Lyme disease risk in the United States is highest in the Northeast and in the upper Midwest where I. scapularis ticks are most abundant. Because birds might be important to the range expansion of I. scapularis and B. burgdorferi, we explored spatial variation in patterns of I. scapularis parasitism on songbirds, as well as B. burgdorferi infection in bird-derived I. scapularis larvae. We sampled birds at 23 sites in the eastern United States to describe seasonal patterns of I. scapularis occurrence on birds, and we screened a subset of I. scapularis larvae for presence of B. burgdorferi. Timing of immature I. scapularis occurrence on birds is consistent with regional variation in host-seeking activity with a generally earlier peak in larval parasitism on birds in the Midwest. Significantly more I. scapularis larvae occurred on birds that were contemporaneously parasitized by nymphs in the Midwest than the Northeast, and the proportion of birds that yielded B. burgdorferi-infected larvae was also higher in the Midwest. We conclude that regional variation in immature I. scapularis phenology results in different temporal patterns of parasitism on birds, potentially resulting in differential importance of birds to B. burgdorferi transmission dynamics among regions.


Durable response to amivantamab in treatment refractory NSCLC harboring EGFR and complex MET mutations: A case report.
Targeted therapies have revolutionized treatment for metastatic non-small cell lung cancer (NSCLC) with oncogenic driver mutations. However, challenges arise in managing concurrent mutations and overcoming resistance. We present the case of a patient with epidermal growth factor receptor (EGFR) (L747_A750delinsP exon19 deletion) and mesenchymal-epithelial transition factor (MET) mutations (D1228H, D1228N, D1228Y, Y1230H, MET amplification) who achieved a durable response to amivantamab (14 months ongoing) after progression on multiple lines of therapy including platinum-based chemotherapy, EGFR tyrosine kinase inhibitors (TKI) and combination TKI and MET inhibitors. This case highlights the utility of longitudinal next-generation sequencing (NGS) testing to identify acquired resistance and the need for continued research into understanding mechanisms of resistance to help develop future treatment strategies.


Delivery of biotinylated IGF-1 with biotinylated self-assembling peptides combined with bone marrow stem cell transplantation promotes cell therapy for myocardial infarction.
Cell therapy is a promising approach for cardiac repair. The aim of the present study was to determine the feasibility of using biotinylated insulin-like growth factor 1 (IGF-1) with biotinylated self-assembling peptides (tethered IGF-1) combined with bone marrow stem cells (BMSCs) transplantation for the treatment of heart failure. Tethered IGF-1 was synthesized and its effect on H9c2 cells was analyzed. Reverse transcription-quantitative polymerase chain reaction and western blot assays demonstrated that tethered IGF-1 did not significantly affect the expression and phosphorylation of AKT, whereas it significantly increased the expression of cardiac troponin T (P<0.01). A rabbit myocardial infarction model was constructed and rabbits were divided into four groups: Control group (no treatment), group 1 (G1; BMSC transplantation), group 2 (G2; BMSCs + non-biotinylated IGF-1) and group 3 (G3; BMSCs + tethered IGF-1). At 4 weeks after modeling, cardiac tissues were obtained for analysis. In the control group, myocardial fibers were disordered, a large number of inflammatory cells infiltrated the cardiac tissues, and apoptosis occurred in ~50% of cells. However, in G1, G2 and G3, muscle cells were well ordered, and a lesser degree of myocardial degeneration and inflammatory cell infiltration was observed. Compared with the control group, the apoptosis rates of myocardial cells in G1-G3 were significantly decreased (P<0.01). Furthermore, compared with G1 and G2, tissue morphology was improved in G3and the number of apoptotic myocardial cells was significantly decreased (P<0.01). These results suggest that treatment with tethered IGF-1 + BMSCs significantly suppresses cell apoptosis and induces the expression of cardiac maturation proteins. These findings provide a novel insight into how the delivery of tethered IGF-1 with BMSCs could potentially enhance the prognosis of patients with heart failure treatment.


Five-year survival following cryosurgery for oral cancer.
In the years 1964 through 1970, sixty selected patients with oral cancer were treated by freezing in situ with the intent to cure the disease. Early results demonstrated the suitability of the method for high-surgical-risk patients and showed that the technique permitted avoidance of bone-sacrificing operations. Five-year survival statistics show that cryosurgery was most successfully used on small to moderate-sized cancers without cervical lymphadenopathy. The results justify continued use of cryosurgery in carefully selected patients.


Ibero-American Society of Interventionism (SIDI) and the Spanish Society of Vascular and Interventional Radiology (SERVEI) Standard of Practice (SOP) for the Management of Inferior Vena Cava Filters in the Treatment of Acute Venous Thromboembolism.
to present an interventional radiology standard of practice on the use of inferior vena cava filters (IVCFs) in patients with or at risk to develop venous thromboembolism (VTE) from the Iberoamerican Interventional Society (SIDI) and Spanish Vascular and Interventional Radiology Society (SERVEI). a group of twenty-two interventional radiologist experts, from the SIDI and SERVEI societies, attended online meetings to develop a current clinical practice guideline on the proper indication for the placement and retrieval of IVCFs. A broad review was undertaken to determine the participation of interventional radiologists in the current guidelines and a consensus on inferior vena cava filters. Twenty-two experts from both societies worked on a common draft and received a questionnaire where they had to assess, for IVCF placement, the absolute, relative, and prophylactic indications. The experts voted on the different indications and reasoned their decision. a total of two-hundred-thirty-three articles were reviewed. Interventional radiologists participated in the development of just two of the eight guidelines. The threshold for inclusion was 100% agreement. Three absolute and four relative indications for the IVCF placement were identified. No indications for the prophylactic filter placement reached the threshold. interventional radiologists are highly involved in the management of IVCFs but have limited participation in the development of multidisciplinary clinical practice guidelines.


First report of mitochondrial COI in foraminifera and implications for DNA barcoding.
Foraminifera are a species-rich phylum of rhizarian protists that are highly abundant in many marine environments and play a major role in global carbon cycling. Species recognition in Foraminifera is mainly based on morphological characters and nuclear 18S ribosomal RNA barcoding. The 18S rRNA contains variable sequence regions that allow for the identification of most foraminiferal species. Still, some species show limited variability, while others contain high levels of intragenomic polymorphisms, thereby complicating species identification. The use of additional, easily obtainable molecular markers other than 18S rRNA will enable more detailed investigation of evolutionary history, population genetics and speciation in Foraminifera. Here we present the first mitochondrial cytochrome c oxidase subunit 1 (COI) gene sequences ("barcodes") of Foraminifera. We applied shotgun sequencing to single foraminiferal specimens, assembled COI, and developed primers that allow amplification of COI in a wide range of foraminiferal species. We obtained COI sequences of 49 specimens from 17 species from the orders Rotaliida and Miliolida. Phylogenetic analysis showed that the COI tree is largely congruent with previously published 18S rRNA phylogenies. Furthermore, species delimitation with ASAP and ABGD algorithms showed that foraminiferal species can be identified based on COI barcodes.


The dynamic and motile properties of intermediate filaments.
For many years, cytoplasmic intermediate filaments (IFs) were considered to be stable cytoskeletal elements contributing primarily to the maintenance of the structural and mechanical integrity of cells. However, recent studies of living cells have revealed that IFs and their precursors possess a remarkably wide array of dynamic and motile properties. These properties are in large part due to interactions with molecular motors such as conventional kinesin, cytoplasmic dynein, and myosin. The association between IFs and motors appears to account for much of the well-documented molecular cross talk between IFs and the other major cytoskeletal elements, microtubules, and actin-containing microfilaments. Furthermore, the associations with molecular motors are also responsible for the high-speed, targeted delivery of nonfilamentous IF protein cargo to specific regions of the cytoplasm where they polymerize into IFs. This review considers the functional implications of the motile properties of IFs and discusses the potential relationships between malfunctions in these motile activities and human diseases.


Developing services for lesbian and gay adolescents.
The needs of lesbian and gay adolescents for service provision are discussed in this paper. These needs are identified through research investigating milestones in the coming-out process. In addition, the way in which the research results influenced community development initiatives is described. The social context in which the research was conducted is also described.


Alphav integrins mediate adhesion and migration of breast carcinoma cell lines.
Integrins with the alphav subunit are involved in cell adhesion and cellular signaling. Some alphav integrins have been associated with tumor progression and dissemination. The objective of this study was to assess the contribution of alphav integrins to the adhesive and migratory behavior of cells derived from breast carcinoma (BCA). The expression and function of alphav integrins was characterized in three BCA cell lines which exhibit different metastatic potentials. These include MCF-7 cells which metastasize inefficiently, MDA-MB-231 cells, which have a moderate metastatic potential, and MDA-MB-435 cells, which metastasize extensively. Each cell type displays a different repertoire of alphav integrins on the cell surface. The complement of alphav integrins on each cell type influences their ability to adhere and migrate. The most striking difference among these cell lines was the expression of the alphavbeta3 integrin. The highly metastatic MDA-MB-435 cells express substantial levels of this receptor, whereas MDA-MB-231 and MCF-7 cells do not. The MDA-MB-435 cells showed a greater ability to adhere and to migrate and this functional difference can largely be attributed to the expression of alphavbeta3 integrin. This characterization is a first step toward determining the role of alphav integrins in animal models of BCA metastasis, and lends support to the hypothesis that the alphavbeta3 integrin can be a contributing factor in metastatic disease.


Nonlinear regime-switching state-space (RSSS) models.
Nonlinear dynamic factor analysis models extend standard linear dynamic factor analysis models by allowing time series processes to be nonlinear at the latent level (e.g., involving interaction between two latent processes). In practice, it is often of interest to identify the phases--namely, latent "regimes" or classes--during which a system is characterized by distinctly different dynamics. We propose a new class of models, termed nonlinear regime-switching state-space (RSSS) models, which subsumes regime-switching nonlinear dynamic factor analysis models as a special case. In nonlinear RSSS models, the change processes within regimes, represented using a state-space model, are allowed to be nonlinear. An estimation procedure obtained by combining the extended Kalman filter and the Kim filter is proposed as a way to estimate nonlinear RSSS models. We illustrate the utility of nonlinear RSSS models by fitting a nonlinear dynamic factor analysis model with regime-specific cross-regression parameters to a set of experience sampling affect data. The parallels between nonlinear RSSS models and other well-known discrete change models in the literature are discussed briefly.


L1, N-cadherin, and laminin induce distinct distribution patterns of cytoskeletal elements in growth cones.
Growth cones are highly motile extensions of growing neuronal processes that have a well-characterized cytoskeleton, which is necessary for motility and directed growth. In culture, neurons have been observed to extend processes on a variety of substrates made of cell adhesion molecules (CAMs) or extracellular matrix molecules (ECM molecules). We have previously shown that retinal ganglion cell (RGC) growth cones exhibit characteristic morphologies dependent on the substrate on which they are grown (Payne et al., 1992: Cell Motil. Cytoskel. 21:65-73). Upon contact with a sharp border between two substrates, the growth cones display rapid changes in morphology (Burden-Gulley et al., 1995: J. Neurosci. 15:4370-4381) that may result from extensive restructuring of the cytoskeleton. In the present study, immunocytochemical methods were used to examine the distribution of three cytoskeletal elements in RGC growth cones growing on L1, N-cadherin, or laminin as well as on dishes coated with alternating lanes of these substrates. Distinct distribution patterns of f-actin, microtubules (MTs), and neurofilaments (NFs) were observed in growth cones growing on individual substrates. At border regions between two substrates, growth cones with extensive lamellipodial contact with the second substrate were observed to have f-actin and MT distribution patterns appropriate for the new substrate encountered. Contact via filopodia alone did not evoke this change. Redistribution of NFs was observed only after the majority of the growth cone had crossed onto the second substrate. These results suggest that actin and MTs, but probably not NFs, are directly influenced by CAMs and ECM molecules to produce changes in growth cone morphology. The distribution of two members of the protein tyrosine kinase family, pp60arc and p59fyn, and phosphorylated tyrosine residues was also examined. No differences were observed in the distribution patterns of the kinases and phosphorylated tyrosine residues in growth cones on any of the substrate molecules tested. In addition, the distribution patterns were unchanged in growth cones that contacted and crossed borders between two substrates. These results suggest that redistribution of pp60arc or p59fyn is not required to produce alterations in growth cone morphology induced by contact with L1, N-cadherin or laminin.


Development of evidence-based Australian medication-related indicators of potentially preventable hospitalisations: a modified RAND appropriateness method.
Indicators of potentially preventable hospitalisations have been adopted internationally as a measure of health system performance; however, few assess appropriate processes of care around medication use, that if followed may prevent hospitalisation. The aim of this study was to develop and validate evidence-based medication-related indicators of potentially preventable hospitalisations. Australian primary healthcare. Medical specialists, general practitioners and pharmacists. A modified RAND appropriateness method was used for the development of medication-related indicators of potentially preventable hospitalisations, which included a literature review, assessment of the strength of the supporting evidence base, an initial face and content validity by an expert panel, followed by an independent assessment of indicators by an expert clinical panel across various disciplines, using an online survey. Analysis of ratings was performed on the four key elements of preventability; the medication-related problem must be recognisable, the adverse outcomes foreseeable and the causes and outcomes identifiable and controllable. A total of 48 potential indicators across all major disease groupings were developed based on level III evidence or greater, that were independently assessed by 78 expert clinicians (22.1% response rate). The expert panel considered 29 of these (60.4%) sufficiently valid. Of these, 21 (72.4%) were based on level I evidence. This study provides a set of face and content validated indicators of medication-related potentially preventable hospitalisations, linking suboptimal processes of care and medication use with subsequent hospitalisation. Further analysis is required to establish operational validity in a population-based sample, using an administrative health database. Implementation of these indicators within routine monitoring of healthcare systems will highlight those conditions where hospitalisations could potentially be avoided through improved medication management.


Climate change selects for heterozygosity in a declining fur seal population.
Global environmental change is expected to alter selection pressures in many biological systems, but the long-term molecular and life history data required to quantify changes in selection are rare. An unusual opportunity is afforded by three decades of individual-based data collected from a declining population of Antarctic fur seals in the South Atlantic. Here, climate change has reduced prey availability and caused a significant decline in seal birth weight. However, the mean age and size of females recruiting into the breeding population are increasing. We show that such females have significantly higher heterozygosity (a measure of within-individual genetic variation) than their non-recruiting siblings and their own mothers. Thus, breeding female heterozygosity has increased by 8.5% per generation over the last two decades. Nonetheless, as heterozygosity is not inherited from mothers to daughters, substantial heterozygote advantage is not transmitted from one generation to the next and the decreasing viability of homozygous individuals causes the population to decline. Our results provide compelling evidence that selection due to climate change is intensifying, with far-reaching consequences for demography as well as phenotypic and genetic variation.


Acid-base and electrolyte balance in dairy heifers fed forage and concentrate rations: effects of sodium bicarbonate.
Eight Holstein heifers were fed diets of alfalfa hay, corn silage, or finely ground corn grain with or without NaHCO3 in a rotating experimental design. Acid-base status and renal excretion of electrolytes were evaluated during short-term (1 and 5 day) and long-term (24 day) feeding trials. Heifers fed alfalfa hay had a greater metabolic buffering capacity than did heifers fed corn silage. Heifers fed grain had lower blood pH and bicarbonate values than did those fed the forage diets. The most pronounced effects of grain-feeding were aciduria and phosphaturia. Aciduria did not occur when NaHCO3 was added to the grain at 2% of the ration on a dry matter basis. Grain-fed heifers had significantly (P less than 0.05) lower blood and urine pH and bicarbonate values, and excreted significantly more calcium, phosphorus, and magnesium in the urine than did those fed grain plus NaHCO3. Sodium bicarbonate, as a 2% dietary supplement, counteracted many effects of high-grain diets.


In this case report, a 55-year-old man presented with back pain, urinary retention, sensory disturbances, erectile dysfunction, leg paresis and orthostatism. Spinal MRI showed longitudinal extensive myelitis. Lymph node biopsy was compatible with sarcoidosis and a diagnosis of probable neurosarcoidosis (NS) was made. The patient benefited from prednisolone but relapsed during withdrawal. Infliximab resulted in almost complete remission. In conclusion, relapse is often seen when phasing out prednisolone, whereas infliximab appears to have a lasting effect and should be considered in the early stages of severe NS.


Exclusive potassium dependence of the membrane potential in cultured mouse oligodendrocytes.
Membrane potential, conductance, and intracellular potassium concentration were measured in oligodendrocytes in 3- to 10-week-old cultures of embryonic mouse spinal cord. After intracellular recording the cells were first injected with Lucifer Yellow and then stained by immunofluorescence using rhodamine-labeled monoclonal antibody 01 specific for oligodendrocyte cell surfaces. The membrane potential of these identified oligodendrocytes was in mV -66 +/- 4.3 SD; it could be reversibly reduced almost to zero by the addition of ouabain. Changes in external K+ but not Na+, Ca++, or Cl- changed the membrane potential. A 10-fold increase in extracellular potassium concentration ([K+]0) depolarized the cell by about 52 mV. This is less than the 61 mV predicted by the Nernst equation for a K+ electrode assuming a constant intracellular potassium concentration ([K+]i). However, when [K+]i was measured with an ion-selective electrode during the increase in [K+]0 it was found to rise. The Nernst equation for K+ accurately predicts the oligodendrocyte membrane potential when the increase in [K+]i is taken into account. Oligodendrocytes may be described as accurate K+ electrodes with a variable reference solution.


Highly recombinant VGII Cryptococcus gattii population develops clonal outbreak clusters through both sexual macroevolution and asexual microevolution.
An outbreak of the fungal pathogen Cryptococcus gattii began in the Pacific Northwest (PNW) in the late 1990s. This outbreak consists of three clonal subpopulations: VGIIa/major, VGIIb/minor, and VGIIc/novel. Both VGIIa and VGIIc are unique to the PNW and exhibit increased virulence. In this study, we sequenced the genomes of isolates from these three groups, as well as global isolates, and analyzed a total of 53 isolates. We found that VGIIa/b/c populations show evidence of clonal expansion in the PNW. Whole-genome sequencing provided evidence that VGIIb originated in Australia, while VGIIa may have originated in South America, and these were likely independently introduced. Additionally, the VGIIa outbreak lineage may have arisen from a less virulent clade that contained a mutation in the MSH2 ortholog, but this appears to have reverted in the VGIIa outbreak strains, suggesting that a transient mutator phenotype may have contributed to adaptation and evolution of virulence in the PNW outbreak. PNW outbreak isolates share genomic islands, both between the clonal lineages and with global isolates, indicative of sexual recombination. This suggests that VGII C. gattii has undergone sexual reproduction, either bisexual or unisexual, in multiple locales contributing to the production of novel, virulent subtypes. We also found that the genomes of two basal VGII isolates from HIV(+) patients contain an introgression tract spanning three genes. Introgression substantially contributed to intra-VGII polymorphism and likely occurred through sexual reproduction with VGI. More broadly, these findings illustrate how both microevolution and sexual reproduction play central roles in the development of infectious outbreaks from avirulent or less virulent progenitors. Importance: Cryptococcus gattii is the causative agent responsible for ongoing infections in the Pacific Northwest of the United States and western Canada. The incidence of these infections increased dramatically in the 1990s and remains elevated. These infections are attributable to three clonal lineages of C. gattii, VGIIa, VGIIb, and VGIIc, with only VGIIa identified once previously in the Pacific Northwest prior to the start of the outbreak, albeit in a less virulent form. This study addresses the origin and emergence of this outbreak, using whole-genome sequencing and comparison of both outbreak and global isolates. We show that VGIIa arose mitotically from a less virulent clonal group, possibly via the action of a mutator phenotype, while VGIIb was likely introduced from Australia, and VGIIc appears to have emerged in the United States or in an undersampled locale via sexual reproduction. This work shows that multiple processes can contribute to the emergence of an outbreak.


Proteins that interact with bacterial small RNA regulators.
Small regulatory RNAs have been identified in a wide range of organisms, where they modify mRNA stability, translation or protein function. Small RNA regulators (sRNAs) either pair with mRNA targets or modify protein activities. Here we discuss current knowledge of the various proteins that interact with RNA regulators and review the physiologic implications of sRNA-protein complexes in DNA, RNA and protein metabolism, as well as in RNA and protein quality control in prokaryotes. Proteins that interact with the sRNAs can possess catalytic activity, induce conformational changes of the sRNA, or be sequestered by the sRNA to prevent the action of the protein.


Laparoscopic splenectomy for solitary splenic tumors.
Solitary splenic masses are a rare entity. There is a paucity of data in the literature on the evaluation and laparoscopic treatment for splenic masses. To further elucidate the evaluation and laparoscopic management of splenic masses we evaluated our own data. Data was collected retrospectively for all patients who underwent laparoscopic splenectomy (LS) in our institution for the diagnosis of a solid mass. Patients' charts were reviewed. Complementary data was completed when needed by telephone interviews. 28 patients underwent LS for solid splenic masses between 1997 and 2006. Mean age was 54.3 years and 68% were women. Patients' symptoms included abdominal pain (46.5%), anemia (32%), weight loss (21%), and palpable abdominal mass (21%). Fifty-three percent were asymptomatic at diagnosis. Preoperative patients' imaging included computed tomography (92.8%), abdominal ultrasound (71.4%), and positron emission tomography (PET, 32%). Seven patients (25%) had a history of lymphoproliferative disease. The mass size as measured by computed tomography (CT) scan ranged from 4 to 11 cm. Three patients (10.7%) had multiple splenic lesions. Mean operative time was 125 min. Mean estimated blood loss was 200 ml. Five patients (17.9%) had massive splenomegaly. Conversion rate was 14.3%. In three patients (10.7%) the spleen was removed with additional organs' tissue (stomach and pancreas). Two patients (7.1%) were reoperated. There was no postoperative mortality. Mean hospital stay was 4.7 days. Four patients (14.3%) were readmitted due to complications. Pathology revealed eight patients (28%) with benign tumors and the rest (71.4%) with malignant lymphoma. Splenic solid tumor is a rare entity. Most of the cases were eventually diagnosed as malignant tumors. In our series, all malignant tumors were non-Hodgkin lymphoma. The most common benign lesion was inflammatory pseudotumor. This study has demonstrated the feasibility and safety of LS for diagnosis and treatment of both benign and malignant tumors of the spleen.


Neuromodulation and aging: implications of aging neuronal gain control on cognition.
The efficacy of various transmitter systems declines with advancing age. Of particular interest, various pre-synaptic and post-synaptic components of the dopaminergic system change across the human lifespan; impairments in these components play important roles in cognitive deficits commonly observed in the elderly. Here, we review evidence from recent multimodal neuroimaging, pharmacological and genetic studies that have provided new insights for the associations among dopamine functions, aging, functional brain activations and behavioral performance across key cognitive functions, ranging from working memory and episodic memory to goal-directed learning and decision making. Specifically, we discuss these empirical findings in the context of an established neurocomputational theory of aging neuronal gain control. We also highlight gaps in the current understanding of dopamine neuromodulation and aging brain functions and suggest avenues for future research.


Porewater dynamics of silver, lead and copper in coastal sediments and implications for benthic metal fluxes.
To determine the conditions that lead to a diffusive release of dissolved metals from coastal sediments, porewater profiles of Ag, Cu, and Pb have been collected over seven years at two contrasting coastal sites in Massachusetts, USA. The Hingham Bay (HB) site is a contaminated location in Boston Harbor, while the Massachusetts Bay (MB) site is 11 km offshore and less impacted. At both sites, the biogeochemical cycles include scavenging by Fe-oxyhydroxides and release of dissolved metals when Fe-oxyhydroxides are reduced. Important differences in the metal cycles at the two sites, however, result from different redox conditions. Porewater sulfide and seasonal variation in redox zone depth is observed at HB, but not at MB. In summer, as the conditions become more reducing at HB, trace metals are precipitated as sulfides and are no longer associated with Fe-oxyhydroxides. Sulfide precipitation close to the sediment-water interface limits the trace metal flux in summer and autumn at HB, while in winter, oxidation of the sulfide phases drives high benthic fluxes of Cu and Ag, as oxic conditions return. The annual diffusive flux of Cu at HB is found to be significant and contributes to the higher than expected water column Cu concentrations observed in Boston Harbor. At MB, due to the lower sulfide concentrations, the association of trace metals with Fe-oxyhydroxides occurs throughout the year, leading to more stable fluxes. A surface enrichment of solid phase trace metals was found at MB and is attributed to the persistent scavenging by Fe-oxyhydroxides. This process is important, particularly at sites that are less reducing, because it maintains elevated metal concentrations at the surface despite the effects of bioturbation and sediment accumulation, and because it may increase the persistence of metal contamination in surface sediments.


Micronutrient management following bariatric surgery: the role of the dietitian in the postoperative period.
Bariatric surgery is increasingly being utilized to manage obesity and obesity related comorbidities, but may lead to the development of micronutrient deficiencies postoperatively. The anatomical, physiological, nutritional and behavioral reasons for micronutrient vulnerabilities are reviewed, along with recommendations for routine monitoring and replacement following surgery. The role the dietitian and their contribution in the postoperative identification, prevention and management of micronutrient vulnerabilities in bariatric patients is described. Specific considerations such as the nutritional and dietetic management of pregnant and lactating women post-bariatric surgery is also discussed.


Phosphorylation of Cdc20/fizzy negatively regulates the mammalian cyclosome/APC in the mitotic checkpoint.
The cyclosome/anaphase promoting complex (APC) is a multisubunit ubiquitin ligase that targets mitotic regulators for degradation in exit from mitosis. It is activated at the end of mitosis by phosphorylation and association with the WD-40 protein Cdc20/Fizzy and is then kept active in the G1 phase by association with Cdh1/Hct1. The mitotic checkpoint system that keeps cells with defective spindles from leaving mitosis interacts with Cdc20 and prevents its stimulatory action on the cyclosome. The activity of Cdh1 is negatively regulated by phosphorylation, while the abundance of Cdc20 is cell cycle regulated, with a peak in M-phase. Cdc20 is also phosphorylated in G2/M and in mitotically arrested cells, but the role of phosphorylation remained unknown. Here we show that phosphorylation of Cdc20 by Cdk1/cyclin B abrogates its ability to activate cyclosome/APC from mitotic HeLa cells. A nonphosphorylatable derivative of Cdc20 stimulates cyclin-ubiquitin ligation in extracts from nocodazole-arrested cells to a much greater extent than does wild-type Cdc20. It is suggested that inhibitory phosphorylation of Cdc20/Fizzy may have a role in keeping the cyclosome inactive in early mitosis and under conditions of mitotic checkpoint arrest.


FAS and RAS related Apoptosis defects: From autoimmunity to leukemia.
The human adaptive immune system recognizes almost all the pathogens that we encounter and all the tumor antigens that may arise during our lifetime. Primary immunodeficiencies affecting lymphocyte development or function therefore lead to severe infections and tumor susceptibility. Furthermore, the fact that autoimmunity is a frequent feature of primary immunodeficiencies reveals a third function of the adaptive immune system: its self-regulation. Indeed, the generation of a broad repertoire of antigen receptors (via a unique strategy of random somatic rearrangements of gene segments in T cell and B cell receptor loci) inevitably creates receptors with specificity for self-antigens and thus leads to the presence of autoreactive lymphocytes. There are many different mechanisms for controlling the emergence or action of autoreactive lymphocytes, including clonal deletion in the primary lymphoid organs, receptor editing, anergy, suppression of effector lymphocytes by regulatory lymphocytes, and programmed cell death. Here, we review the genetic defects affecting lymphocyte apoptosis and that are associated with lymphoproliferation and autoimmunity, together with the role of somatic mutations and their potential involvement in more common autoimmune diseases.


Nurses' perceptions of their self-confidence and the benefits and risks of family presence during resuscitation.
Debate continues among nurses about the advantages and disadvantages of family presence during resuscitation. Knowledge development about such family presence is constrained by the lack of reliable and valid instruments to measure key variables. To test 2 instruments used to measure nurses' perceptions of family presence during resuscitation, to explore demographic variables and perceptions of nurses' self-confidence and the risks and benefits related to such family presence in a broad sample of nurses from multiple hospital units, and to examine differences in perceptions of nurses who have and who have not invited family presence. Nurses (n = 375) completed the Family Presence Risk-Benefit Scale and the Family Presence Self-confidence Scale. Nurses' perceptions of benefits, risks, and self-confidence were significantly and strongly interrelated. Nurses who invited family presence during resuscitation were significantly more self-confident in managing it and perceived more benefits and fewer risks (P < .001). Perceptions of more benefits and fewer risks were related to membership in professional organizations, professional certification, and working in an emergency department (P < .001). Data supported initial reliability and construct validity for the 2 scales. Nurses' perceptions of the risks and benefits of family presence during resuscitation vary widely and are associated with how often the nurses invite family presence. After further testing, the 2 new scales may be suitable for measuring interventional outcomes, serve as self-assessment tools, and add to conceptual knowledge about family presence.


Transmission of Borrelia afzelii from Apodemus mice and Clethrionomys voles to Ixodes ricinus ticks: differential transmission pattern and overwintering maintenance.
This study deals with the ecology of Lyme borreliosis in Europe. The relationships between Borrelia burgdorferi sensu lato spirochetes, Clethrionomys and Apodemus rodent reservoirs and the Ixodes ricinus tick vector were investigated during 16 consecutive months in an enzootic area in Switzerland. Cultivation of ear skin biopsies was used to isolate spirochetes from C. glareolus, A. sylvaticus, A. flavicollis and Glis glis. Borrelia infection was more frequently observed in Clethrionomys than in Apodemus. Tick xenodiagnosis was used to determine the infectivity of rodents. The infection rate in ticks fed on Clethrionomys was higher than that in ticks fed on Apodemus, but Apodemus yielded more infected ticks than Clethrionomys because of a better tick moulting success. Xenodiagnostic ticks were placed into BSK medium to obtain isolates. Isolates from rodents and rodent-feeding ticks were all identified as B. afzelii. The follow-up of the infectivity status of repeatedly recaptured rodents clearly demonstrated that these hosts remained infective for ticks during winter till the following spring. Comparing C. glareolus and A. sylvaticus, each rodent species showed different host infection, different host infectivity and contributed differently to the moulting success of feeding ticks. These factors influence differentially the pattern of transmission of B. afzelii from Clethrionomys voles and Apodemus mice to I. ricinus ticks.


Immunocytochemical localization of fibronectin to the retinal pigment epithelium of the rat.
Fibronectin is an anionic asialoglycoprotein that is found on a variety of cell types. This study was undertaken in an attempt to localize fibronectin to the rat retinal pigment epithelium with ultrastructural immunocytochemistry. Using Fab-HRP conjugates specific for fibronectin, reaction product was localized on the surface of the apical processes and within the cell to GERL. After treatment of tissue by the biotin-avidin method employing ferritin-avidin, ferritin particles marked the apical processes in a quasi-regular distribution. Tufts of particles were separated by a linear distance of 65-85 nm. Fibronectin was not localized to rod outer segments.


Increasing hygiene productivity.
Dentists have many opportunities to expand the role of dental hygienists and provide patients with better oral health care, while increasing production and profits. But the proper business systems and verbal skills need to be incorporated. You must train hygienists to do all they can do for every patient. Begin with one service and add others, as the hygienists becomes familiar with each one. Set a goal of a 15% increase in production per year for the hygiene department. Clinicians using these strategies have experienced as much as a 100% to 200% increase in hygiene revenue during the first year of incorporating these services. An added benefit is that these dentists often see a substantial increase in dental treatment diagnosis and case acceptance. An effective and efficient hygiene department will often identify and help secure more than 50% of a doctor's production.


Comparative Study of Dry Eye Indices Following Cataract Surgery.
This study aims to assess dry eye indices following cataract surgery. A single center descriptive and comparative study was performed. A total of 100 eyes of 100 cases fulfilling the inclusion criteria from 1st June 2017 to 30th May 2018 were enrolled. Out of 100 eyes, 50 eyes each went through manual small incision cataract surgery (MSICS) and phacoemulsification respectively. For objective analysis : schirmer 1 test(ST-I), tear breakup Time(TBUT) along with lissamine Green Surface Staining(LGSS) was performed on pre-operative day, 1st, 4th and 12th week respectively. Ocular Surface Disease Index (OSDI) was done for subjective analysis on pre-operative day and at 12th week. The mean age of the patient was 53.66 ± 7.839 years with 34 (68%) being female in a small incision cataract surgery group. In the phacoemulsification group, mean age was 54.72 ± 7.985 years and 32 (64%) were female. On analyzing the objective dry eye indices: ST-I,TBUT and LGSS at 12thweek was 18.80 ± 7.393 mm, 11.30 ± 5.456 seconds and 1.62 ± 1.193 in Small incision cataract surgery group and 27.10 ± 6.326 mm, 16.60 ± 4.699 seconds and 0.38 ± 0.602 in Phacoemulsification group respectively which was statistically significant. (p< 0.001). Regardless of the type of cataract surgery, dry eye disease is unavoidable affecting both tear quality and quantity postoperatively. In our study, phacoemulsification had lesser effect in dry eye indices than small incision cataract surgery.


Potential rise in iron deficiency due to future anthropogenic carbon dioxide emissions.
Iron deficiency reduces capacity for physical activity, lowers IQ, and increases maternal and child mortality, impacting roughly a billion people worldwide. Recent studies have shown that certain highly consumed crops-C3 grains (e.g., wheat, rice, and barley), legumes, and maize-have lower iron concentrations of 4-10% when grown under increased atmospheric CO2 concentrations (550 ppm). We examined diets in 152 countries globally (95.5% of the population) to estimate the percentage of lost dietary iron resulting from anthropogenic CO2 emissions between now and 2050, specifically among vulnerable age-sex groups: children (1-5 years) and women of childbearing age (15-49 years), holding diets constant. We also cross-referenced these with the current prevalence of anemia to identify most at-risk countries. We found that 1.4 billion children aged 1-5 and women of childbearing age (59% of global total for these groups) live in high-risk countries, where the prevalence of anemia exceeds 20% and modeled loss in dietary iron would be in the most severe tertile (>3.8%). The countries with the highest anemia prevalence also derive their iron from the fewest number of foods, even after excluding countries consuming large amounts of unaccounted wild-harvest foods. The potential risk of increased iron deficiency adds greater incentive for mitigating anthropogenic CO2 emissions and highlights the need to address anticipated health impacts via improved health delivery systems, dietary behavioral changes, or agricultural innovation. Because these are effects on content rather than yield, it is unlikely that consumers will perceive this health threat and adapt to it without education.


Interactions of homocysteine, nitric oxide, folate and radicals in the progressively damaged endothelium.
The endothelium exerts fundamental control over vascular tone, and injury to the endothelium followed by dysfunction is an early key event preceding manifestation of vessel pathology. Both elevated plasma homocysteine and low folate status have been identified as major and independent risk factors for atherosclerosis and have stirred an enormous and still increasing interest. The damaging effects of hyperhomocysteinemia on endothelial function are, at least in part, reversible through folate supplementation. Because of the inverse relationship between plasma folate and homocysteine levels, however, it is difficult to discriminate between their respective effects. Endothelial dysfunction refers mainly to reduced bioavailability of nitric oxide (NO), which is involved in homocysteinemediated vascular damage. Accumulating evidence further suggests that radical oxygen species are fundamentally involved in hyperhomocysteinemia. NO production is determined by cofactors such as tetrahydrobiopterin, which is oxidized and depleted in conditions of oxidant stress by peroxynitrite. Deficiency of tetrahydrofolate contributes to uncoupling, turning the NO synthase into a superoxide radical-producing enzyme. It appears that progression of vascular disease is likely to determine the multiple interactions between homocysteine, NO, oxygen radicals and folate. Folate has only recently been found to exert direct anti-oxidative effects and contribute to restoration of impaired NO metabolism. Understanding of the complex interactions between homocysteine, radicals, NO and folate offers promising perspectives in the individual treatment of vascular disease. Thus, preventive and therapeutic strategies may require a more distinct approach and better discrimination of target groups for greatest possible efficacy.


The impact of the Covid-19 pandemic on quality of life in skin cancer patients.
With more than 82 million cases worldwide and almost two million deaths, the Covid-19 global pandemic shows little sign of abating. However, its effect on quality of life (QoL) in skin cancer patients has not been systematically evaluated to date. Given that QoL impairments may be associated with increased psychological morbidity, and may interfere with engagement with cancer therapy and follow-up, we prospectively evaluated quality of life in skin cancer patients using the Covid-19 Emotional Impact Survey (C-19EIS) and the EORTC QLQ-C30 questionnaires. 101 patients (48 females and 53 males) completed both questionnaires. The mean C-19EIS score was 3.8 on a scale from 0 (no impact) to 12 (severe impact). Patients undergoing systemic therapy showed significantly impaired physical (p = 0.006) and social functioning (p = 0.003). However, when compared to the published normative EORTC QLQ-C30 data, there was no evidence that the Covid-19 pandemic had significantly impacted upon overall quality of life. Subscales of the EORTC QLQ-C30 were significantly inversely correlated with the C-19EIS, validating its use in skin cancer patients. Despite the Covid-19 pandemic, skin cancer patients in our tertiary referral center were surprisingly resilient. However, given the geographical variations in the rates of Sars-CoV-2 infection it is possible that the low incidence in Northern Germany may have resulted in a lack of general QoL impairments. Multi-center studies are required to further determine the impact of Covid-19 on psychological wellbeing in skin cancer patients in order to develop supportive interventions and to ensure that engagement with cancer care services is maintained in order to enable early detection of cancer progression and/or recurrence.


Cell associated urokinase activity and colonic epithelial cells in health and disease.
It is not known if urokinase-type plasminogen activator (uPA) is associated with normal colonic epithelial cells. The aims of this study were to determine if normal colonic epithelial cells have uPA activity and whether this is concentrated at the cell membrane. In addition, the contribution of colonic epithelial cell associated uPA activity to disease related pertubations of mucosal uPA activity were examined. A highly enriched population of colonic epithelial cells was isolated from resected colon or biopsy specimens by an enzymatic technique. uPA activity was measured in cell homogenates by a specific and sensitive colorimetric method and expressed relative to cellular DNA. In two experiments subcellular fractionation of colonic epithelial cells was performed by nitrogen cavitation followed by ultracentrifugation over a linear sucrose gradient. The fractions collected were analysed for uPA and organelle-specific enzyme activities. Normal colonic epithelial cells have cell associated uPA activity (mean (SEM) 5.6 (1.1) IU/mg, n = 18). This colocalised with fractions enriched for leucine-beta-naphthylamidase and 5'-nucleotidase, markers of plasma membrane. uPA activities in epithelial cells from cancerous colons (9.8 (3.1) n = 7) or from mucosa affected by inflammatory bowel disease (3.8 (0.7) n = 15) were not significantly different from normal (paired t test), while that in epithelial cells from greatly inflamed mucosa was similar to that from autologous normal or mildly inflamed areas (4.4 (1.2) v 5.9 (3.6), n = 9). Thus normal colonic epithelial cells have cell associated uPA activity which is concentrated on the plasma membranes, suggesting the presence of uPA receptors. Increased mucosal levels of uPA previously reported in patients with inflammatory bowel disease are not due to increased colonic epithelial cell associated uPA.


Lessons to be Learned: The Knowledge, Attitudes, and Practices of Turkish People towards the COVID-19 Pandemic.
The world experienced the greatest pandemic of the 21st century with the emergence of a new and readily transmissible the coronavirus disease. Understanding knowledge, attitudes, and practices (KAP) of the public towards the pandemic is an essential part of developing effective preventive strategies. The objective of this study was to investigate the knowledge, attitudes, and practices (KAP) concerning the coronavirus (COVID-19) among population in Istanbul. This is a cross-sectional and multi-stage, stratified random sampling based on multi-center population of Istanbul. A total of 5,414 persons were contacted and 4361 participants (80.5%) gave consent. The data were analyzed using descriptive and multiple regression analyses. There were significant differences between low education and high educational level with respect to age groups, gender, occupation, income, residence, number of rooms and family members (P < 0.001). Responses concerning knowledge of COVID-19 indicated that subjects with high education level were significantly higher regarding knowledge of the signs and symptoms of COVID-19 and methods of detecting COVID-19 respectively. Majority of the participants consider COVID-19 risk is higher than AIDS or Cancer (75.8% of low education vs. 67.2% of high education level (P < 0.001). Multivariate stepwise regression analysis revealed that monthly income status (P < 0.001), appropriate method of detecting COVID-19 (P < 0.001), occupational status (P < 0.001), medical mask prevent against COVID-19 (P < 0.001), eating or contacting wild animals (P < 0.001), isolation and treatment of people reduce risk (P < 0.001), isolation 14 days (P < 0.001), avoid going to crowded places such as train-metro, bus, restaurants and shopping (P = 0.003), COVID-19 spreads via-respiratory droplets (P = 0.004), afraid of travel (P = 0.026) were significantly associated with COVID-19 knowledge. The current study results revealed that the educational level and occupation especially sedentary are correlated positively with knowledge, attitude and practices. This finding is not surprising since higher education levels and professional status are associated with good KAP in most epidemic diseases including COVID-19. Nevertheless, the recent experience with COVID-19 has provided lessons on strategy and policy making.


The effect of field condition and shoe type on lower extremity injuries in American Football.
Considerable improvement has been made in football field surfaces and types of shoe, yet relatively few epidemiological studies have investigated their roles in the risk of football injuries. This study examined the effects of field surface, surface condition and shoe type on the likelihood of lower extremity football injuries. Deidentified data from 188 players from one division I university football team during the 2007-2010 seasons were analysed. Lower extremity injury rate and rate ratio, along with 95% confidence limits, were calculated by football activity, playing surface condition and shoe type. A total of 130 lower extremity injuries were sustained, with an overall lower extremity injury rate of 33.5/10 000 athlete-sessions. The lower extremity injury rate was 2.61 times higher when the surface condition was abnormal compared with when the surface condition was normal. During games, the risk for lower extremity injury was 3.34 times higher (95% CI 1.70 to 6.56) on artificial turf compared with natural grass. However, this trend was not statistically significant in practice sessions. Furthermore, neither the number of shoe cleats nor the height of the shoe top was statistically associated with risk of lower extremity injuries. Football players who played on artificial turf or when the surface condition was abnormal were susceptible to lower extremity injuries. Evidence from this study suggests that further research into playing surfaces and shoe types may provide fruitful opportunities to reduce injuries to collegiate football players.


Response Mechanisms of Invertebrates to Bacillus thuringiensis and Its Pesticidal Proteins.
Extensive use of chemical insecticides adversely affects both environment and human health. One of the most popular biological pest control alternatives is bioinsecticides based on Bacillus thuringiensis This entomopathogenic bacterium produces different protein types which are toxic to several insect, mite, and nematode species. Currently, insecticidal proteins belonging to the Cry and Vip3 groups are widely used to control insect pests both in formulated sprays and in transgenic crops. However, the benefits of B. thuringiensis-based products are threatened by insect resistance evolution. Numerous studies have highlighted that mutations in genes coding for surrogate receptors are responsible for conferring resistance to B. thuringiensis Nevertheless, other mechanisms may also contribute to the reduction of the effectiveness of B. thuringiensis-based products for managing insect pests and even to the acquisition of resistance. Here, we review the relevant literature reporting how invertebrates (mainly insects and Caenorhabditis elegans) respond to exposure to B. thuringiensis as either whole bacteria, spores, and/or its pesticidal proteins.


Perfluorinated compounds in fish and blood of anglers at Lake Möhne, Sauerland area, Germany.
Perfluorinated compounds (PFCs) were measured in fish samples and blood plasma of anglers in a cross-sectional study at Lake Möhne, Sauerland area, Germany. Human plasma and drinking water samples were analyzed by solid phase extraction, high-performance liquid chromatography (HPLC), and tandem mass spectrometry (MS/MS). PFCs in fish fillet were measured by ion pair extraction followed by HPLC and MS/MS. PFOS concentrations in 44 fish samples of Lake Möhne ranged between 4.5 and 150 ng/g. The highest median PFOS concentrations have been observed in perches (median: 96 ng/g) and eels (77 ng/g), followed by pikes (37 ng/g), whitefish (34 ng/g), and roaches (6.1 ng/g). In contrast, in a food surveillance program only 11% of fishes at retail sale contained PFOS at detectable concentrations. One hundred five anglers (99 men, 6 women; 14-88 years old; median 50.6 years) participated in the human biomonitoring study. PFOS concentrations in blood plasma ranged from 1.1 to 650 μg/L (PFOA: 2.1-170 μg/L; PFHxS: 0.4-17 μg/L; LOD: 0.1 μg/L). A distinct dose-dependent relationship between fish consumption and internal exposure to PFOS was observed. PFOS concentrations in blood plasma of anglers consuming fish 2-3 times per month were 7 times higher compared to those without any fish consumption from Lake Möhne. The study results strongly suggest that human internal exposure to PFC is distinctly increased by consumption of fish from PFC-contaminated sites.


Influence of recombinant hematopoietins and of fetal bovine serum on the globin synthetic pattern of human BFUe.
We have studied the effects of recombinant hematopoietic growth factors, granulocyte-macrophage colony-stimulating factor (GM-CSF) and/or interleukin-3 (IL-3) on the globin program of adult human erythroid progenitors (BFUe) stimulated to terminal differentiation by erythropoietin under fetal bovine serum (FBS)-supplemented or FBS-deprived culture conditions. Fetal globin production by BFUe-derived erythroblasts was assessed at the protein and mRNA level and its cellular distribution was evaluated by immunofluorescence. Although hemoglobinization and maturation of BFUe-derived erythroblasts was by and large comparable in FBS-replete versus FBS-deprived cultures, the latter had significantly less (up to 20-fold) gamma-globin and gamma-globin mRNA levels. Reduced gamma-globin in serum-deprived cultures was also reflected by a smaller proportion of erythroblasts with detectable gamma-globin by immunofluorescence. Erythroid bursts induced by either GM-CSF or IL-3 produced similar levels of gamma-globin both in FBS-supplemented and in FBS-deprived cultures. These results, obtained even in cultures of highly enriched BFUe, suggest that GM-CSF and IL-3, although they significantly increase the number and size of erythroid bursts, do not by themselves exert a direct influence on the level of fetal globin synthesis. By contrast, factor(s) present in FBS appear to exert a dominant influence on fetal globin synthesis in vitro. Although FBS-deprived conditions appear to largely abrogate the in vitro activation of fetal hemoglobin (Hb F) in normal samples, they do support increased Hb F production in samples from patients with hereditary persistence of fetal hemoglobin or from cord blood.


Oral azithromycin for treatment of posterior blepharitis.
To evaluate the effects of oral azithromycin in patients with posterior blepharitis. Twenty-six eyes of 13 patients with posterior blepharitis diagnosed by a qualified ophthalmologist were enrolled in this study. Patients were instructed to use oral azithromycin 500 mg per day for 3 days in 3 cycles with 7-day intervals. Subjective clinical outcomes were graded and scored 1 day before and 30 days after the end of the treatment (53 days after initiating the treatment) based on severity scores of: (1) eyelid debris; (2) eyelid telangiectasia; (3) swelling of the eyelid margin; (4) redness of the eyelid margin; and (5) ocular mucus secretion. For the assessment of global efficacy, patients were asked by the investigator to rate the subjective symptoms (eyelid itching, ocular itching, eyelid hyperemia, ocular hyperemia, ocular mucus secretion, photophobia, foreign body sensation, and dry eye sensation) on a scale of 0 (no symptoms) to 5 (severe symptoms). Break-up time, Schirmer I test, corneal fluorescein staining score, and rose bengal staining score were also performed in all patients. All clinical outcomes scoring showed statistically significant improvement after oral azithromycin, except for eyelid swelling. Average subjective symptom grading improved statistically after treatment with oral azithromycin, except for eyelid hyperemia, photophobia, and foreign body sensation. Average tear film break-up time values showed statistically significant improvement after the treatment with oral azithromycin. No statistically significant improvement was observed on average values of Schirmer I test, corneal fluorescein staining score, and rose bengal staining score. The combination of multiple clinical parameters shown in this study supports the clinical efficacy of pulsed oral azithromycin therapy for the management of posterior blepharitis.


The mental health of US adolescents adopted in infancy.
To determine whether adopted adolescents are at excess risk for clinically relevant behavioral and emotional problems. We examined whether adopted and nonadopted adolescents differed on quantitative indicators of mental health and the prevalence of childhood disorders and whether differences exist between internationally and domestically placed adoptees. Assessments occurred at the University of Minnesota from December 11, 1998, to June 4, 2004. Adolescents adopted in infancy were systematically ascertained from records of 3 large Minnesota adoption agencies; nonadopted adolescents were ascertained from Minnesota birth records. The final sample included these adolescents with their rearing parents. Main Exposure The main exposure was adoptive status: nonadopted (n = 540), international adoptive placement (n = 514), or domestic adoptive placement (n = 178). Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) clinical assessments based on child and parent reports of attention-deficit/hyperactivity, oppositional defiant, conduct, major depressive, and separation anxiety disorders; teacher reports of psychological health; and contact with mental health professionals. Adoptees scored only moderately higher than nonadoptees on quantitative measures of mental health. Nevertheless, being adopted approximately doubled the odds of having contact with a mental health professional (odds ratio [OR], 2.05; 95% confidence interval [CI], 1.48-2.84) and of having a disruptive behavior disorder (OR, 2.34; 95% CI, 1.72-3.19). Relative to international adoptees, domestic adoptees had higher odds of having an externalizing disorder (OR, 2.60; 95% CI, 1.67-4.04). Moderate mean differences in quantitative indicators of mental health can lead to substantial differences in disorder prevalence. Although most adopted adolescents are psychologically healthy, they may be at elevated risk for some externalizing disorders, especially among those domestically placed.


Reconsidering access: park facilities and neighborhood disamenities in New York City.
With increasing concern about rising rates of obesity, public health researchers have begun to examine the availability of parks and other spaces for physical activity, particularly in cities, to assess whether access to parks reduces the risk of obesity. Much of the research in this field has shown that proximity to parks may support increased physical activity in urban environments; however, as yet, there has been limited consideration of environmental impediments or disamenities that might influence individuals' perceptions or usage of public recreation opportunities. Prior research suggests that neighborhood disamenities, for instance crime, pedestrian safety, and noxious land uses, might dissuade people from using parks or recreational facilities and vary by neighborhood composition. Motivated by such research, this study estimates the relationship between neighborhood compositional characteristics and measures of park facilities, controlling for variation in neighborhood disamenities, using geographic information systems (GIS) data for New York City parks and employing both kernel density estimation and distance measures. The central finding is that attention to neighborhood disamenities can appreciably alter the relationship between neighborhood composition and spatial access to parks. Policy efforts to enhance the recreational opportunities in urban areas should expand beyond a focus on availability to consider also the hazards and disincentives that may influence park usage.


Robust Performance of Potentially Functional SNPs in Machine Learning Models for the Prediction of Atorvastatin-Induced Myalgia.
Statins can cause muscle symptoms resulting in poor adherence to therapy and increased cardiovascular risk. We hypothesize that combinations of potentially functional SNPs (pfSNPs), rather than individual SNPs, better predict myalgia in patients on atorvastatin. This study assesses the value of potentially functional single nucleotide polymorphisms (pfSNPs) and employs six machine learning algorithms to identify the combination of SNPs that best predict myalgia. Methods: Whole genome sequencing of 183 Chinese, Malay and Indian patients from Singapore was conducted to identify genetic variants associated with atorvastatin induced myalgia. To adjust for confounding factors, demographic and clinical characteristics were also examined for their association with myalgia. The top factor, sex, was then used as a covariate in the whole genome association analyses. Variants that were highly associated with myalgia from this and previous studies were extracted, assessed for potential functionality (pfSNPs) and incorporated into six machine learning models. Predictive performance of a combination of different models and inputs were compared using the average cross validation area under ROC curve (AUC). The minimum combination of SNPs to achieve maximum sensitivity and specificity as determined by AUC, that predict atorvastatin-induced myalgia in most, if not all the six machine learning models was determined. Results: Through whole genome association analyses using sex as a covariate, a larger proportion of pfSNPs compared to non-pf SNPs were found to be highly associated with myalgia. Although none of the individual SNPs achieved genome wide significance in univariate analyses, machine learning models identified a combination of 15 SNPs that predict myalgia with good predictive performance (AUC >0.9). SNPs within genes identified in this study significantly outperformed SNPs within genes previously reported to be associated with myalgia. pfSNPs were found to be more robust in predicting myalgia, outperforming non-pf SNPs in the majority of machine learning models tested. Conclusion: Combinations of pfSNPs that were consistently identified by different machine learning models to have high predictive performance have good potential to be clinically useful for predicting atorvastatin-induced myalgia once validated against an independent cohort of patients.


Effects of the celecoxib on the acute necrotizing pancreatitis in rats.
The investigation of the effects of the celecoxib as a cylooxygenase-2 (COX-2) inhibitor on the course of the acute necrotising pancreatitis (ANP) in rats. ANP was induced in 72 rats by standardized intraductal glycodeoxycholic acid infusion and intravenous cerulein infusion. The rats were divided into four groups (six rats in each group): Sham + saline, sham + celecoxib, ANP + saline, ANP + celecoxib. Six hours later after the ANP induction, celecoxib (10 mg/kg) or saline was given i.p. In the 12th hour, routine cardiorespiratuar, renal parameters were monitored to assess the organ function. The serum amylase, alanine amino transferase (ALT), interleukin 6 (IL-6), lactate dehydrogenase (LDH) in bronchoalveolar lavage (BAL) fluid, the serum concentration of the urea, the tissue activity of myeloperoxidase (MPO) and malondialdehyde (MDA) in pancreas and lungs were measured. The pancreas histology was examined. In the second part of the study, 48 rats were studied in four groups similar to the first part. Survival of all the rats after the induction of ANP was observed for 24 h. The induction of the pancreatitis increased the mortality from 0/12, in the sham groups to 4/12 (30%) in the acute pancreatitis with saline group, 5/12 (42%) in the acute pancreatitis with celecoxib group respectively, heart rate, the serum activities of amylase, ALT, the tissue activities of MPO, MDA in the pancreas and lung, and LDH in BAL fluid, the serum concentration of the urea and IL-6, the degree of the pancreatic damage and decreased the blood pressure, the urine production, pO(2) and the serum concentration of calcium. The use of celecoxib did not alter these changes except the serum IL-6 concentration, urine production and MPO, MDA activities in the tissue of the lungs and pancreas. Serum urea concentration and pancreatic damage in ANP + celecoxib group were insignificantly lesser than ANP + saline group. Whereas treatment with celecoxib improves lung and renal functions, the degree of pancreatic damage partially and the serum IL-6 level completely, it does not improve the cardiovascular and liver functions, the mortality rate and the calcium level. Celecoxib may be useful for the support of some organ functions during ANP in rats.


Monitoring for AF: Identifying the Burden of Atrial Fibrillation and Assessing Post-Ablation.
The management of atrial fibrillation (AF) is among the most challenging aspects of cardiology and uncertainties abound concerning stroke assessment and stroke risk reduction. Currently, AF is viewed as a dichotomous variable (fully present or absent) when it comes to stroke risk; there is no regard to the amount of AF either spontaneously or due to rhythm control strategies. For this reason, monitoring in patients with a known AF history, particularly after ablation, has focused on easily measured outcomes such as time to recurrence. However, emerging data suggest that thresholds exist between stroke risk and AF quantity as measured by either duration or burden. As a result, there is an increasing interest in long-term continuous monitoring following a rhythm control strategy to assess efficacy beyond typical symptom reduction. Insertable cardiac monitors (ICMs) with AF-sensing algorithms and remote data transmission capabilities can be used for this purpose, and wearable devices with similar functions are on the horizon. In addition to their diagnostic potential, these tools are also being used therapeutically with efforts to target anticoagulation therapy only in response to AF episodes.


Impact of donor age on outcome of kidney transplantation from controlled donation after cardiac death.
Previous reports regarding donation after cardiac death (DCD) have called for caution in extending the age of kidney donors beyond 60 years due to the risk of poor graft function. The aim of this study was to determine the impact of donor age on renal transplantation from DCD in one center. All DCD transplants from 2005 to 2009 were included in the study. Immunosuppression and recipient follow-up were as per unit protocol. Donor and recipient details were entered prospectively into a renal database and analyzed for graft outcome. Of the 147 renal transplants, 102 were from donors <60 years old and 45 were from donors ≥60 years old. The incidence of delayed graft function varied significantly according to donor-recipient age groups (P = 0.01). The mean glomerular filtration rate at 12 months was 50.3 mL/min for transplants from young donors compared with 39.3 mL/min for transplants from old donors (P = 0.001). The cumulative graft survival rates at 1 and 5 years were 88% and 79% for young donors, while for old donors these were 78% and 72%, respectively (P = 0.101). By transplanting kidneys from old DCD donors into elderly patients, their survival is improved compared with dialysis, and organs from younger donors are made available for younger recipients.


The Influence of Squat Kinematics and Cam Morphology on Acetabular Stress.
To evaluate the effect of varying degrees of simulated cam morphology on acetabular stress magnitude and location using a finite element model with 1 subject that incorporates population-specific hip/pelvis kinematics during a squat task. A reference model of the hip joint was created from magnetic resonance images obtained from 1 asymptomatic 28-year-old man without femoroacetabular impingement (FAI) morphology or hip dysplasia (alpha angle 41.9°, lateral center edge angle 34.0°, neck-shaft angle 137°, and no visible articular cartilage lesions or bone marrow edema on magnetic resonance). The femoral head/neck geometry was manipulated to mimic different cam morphology severities as reported in a previous study (minimum, moderate, and large). Peak hip and pelvis squat kinematics from healthy individuals (hip flexion 112.6°, abduction 10.5°, internal rotation 14.8°) and persons with FAI (hip flexion 106.3°, abduction 10.5°, internal rotation 8.9°) were applied to the control and cam models. Relative acetabular joint stress values and location of contact were the variables of interest. Average von Mises stress values for control, minimum, moderate, and large cam models were 9.64, 9.27, 11.36, and 28.43 MPa, respectively. Contact in the control and minimum cam models occurred within the acetabular cup. In the moderate and large cam models, contact shifted anterosuperiorly within the acetabular cup and to anterosuperior acetabular rim, respectively. Despite simulating lower degrees of hip flexion and internal rotation, increased stress and a shift in contact location were observed in the simulated models of FAI. This finding suggests that decreased hip internal rotation in this population during functional tasks may be the result of bony abutment. Clinicians should be cautious about prescribing deep squats for persons with cam morphology. Performing squat exercises with neutral or external hip rotation may limit bony abutment at high hip flexion angles.


Interleukin-1 beta potentiates bradykinin-induced macromolecular efflux from hamster oral mucosa.
The purpose of this study was to determine whether interleukin-1 beta (IL-1 beta) elicits macromolecular efflux from the in situ oral mucosa and whether it amplifies that evoked by bradykinin. Using intravital microscopy, we found that suffusion of recombinant human IL-1 beta (50 ng/ml) had no significant effects on leaky site formation and increase in clearance of fluorescein isothiocyanate-labeled dextran (mol mass 70 kDa) from the hamster cheek pouch. However, it significantly potentiated bradykinin-induced macromolecular efflux (P < 0.05). The potentiating effects of IL-1 beta on bradykinin-induced responses were abrogated by a bradykinin B2-receptor antagonist and by a recombinant human IL-1-receptor antagonist. They were not mediated by substance P, prostaglandins, or changes in vasomotor tone. IL-1 beta had no significant effects on adenosine-induced macromolecular efflux. Collectively, these data indicate that IL-1 beta potentiates bradykinin-induced macromolecular efflux from the in situ hamster oral mucosa in a specific fashion. We suggest that this interaction could play a role in the pathogenesis of oral mucosa inflammation.


Atmospheric physics and Earth observations: atmospheric spectral imaging.
An array of imaging spectrometers flown on the Spacelab 1 mission was capable of providing spectra of the atmospheric emissions over a broad wavelength range from 300 to 12,700 angstroms and acquiring each complete spectrum nearly simultaneously. The instrument was used to make observations on the day side and night side of the earth, looking down in the nadir direction, radially away from the earth, and in various limb-scanning modes. Observations were made looking at various angles to the vehicle velocity vector and during thruster firings and water dumps as well as at times when such events were inhibited. As a result of the mission a data base has been acquired that is valuable for studies of both the upper atmosphere and the shuttle-Spacelab vehicle environment.


Attenuation of cerebellar tremor with implantation of an intrathecal baclofen pump: the role of gamma-aminobutyric acidergic pathways. Case report.
The authors present the case of a 49-year-old woman with disabling bilateral upper-extremity cerebellar tremor that resolved unexpectedly after placement of an intrathecal baclofen pump for lower-extremity spasticity. The tremor amplitude decreased nearly linearly with increasing intrathecal baclofen dosage, and disappeared completely at a dose of 250 microg/day. In this report the authors demonstrate the role of the gamma-aminobutyric acidergic system in the pathogenesis of cerebellar tremor, and these findings may lead to a new treatment modality for patients disabled by this manifestation of their disease.


Understanding and Challenges in Taking Tyrosine Kinase Inhibitors among Malaysian Chronic Myeloid Leukemia Patients: A Qualitative Study
Background: In Malaysia, the treatment for chronic myeloid leukemia (CML) has long been delivered under the Malaysian Patient Assistance Program (MYPAP), but research on identifying factors contributing to non-adherence to tyrosine kinase inhibitors (TKIs) is still limited. The current study explored understanding and challenges of Malaysian CML patients in taking imatinib and nilotinib. Methods: Semi-structured, face-to-face interviews were conducted with 13 CML patients receiving treatment at a public tertiary care center, and were analyzed using the content analysis approach. Results: The patients generally demonstrated inadequate knowledge, particularly of the natural history and staging of CML, the function of TKIs, and the methods used for monitoring the effectiveness of treatment. A number of them also had experiences of withholding, skipping or altering the treatment, mainly due to the life-disturbing adverse drug effects (ADRs), forgetfulness, and religious and social issues. Besides, most of them were found having limited skills in managing the ADRs, and not using prompts as reminders to take the medications. Furthermore, even though nilotinib was generally perceived as better tolerated as compared with imatinib, the inconvenience caused by the need to take it twice daily and on an empty stomach was constantly highlighted by the patients. Conclusion: While TKIs are widely used for CML treatment in Malaysia, the findings have revealed a lack of patient education and awareness, which warrants an integrated plan to reinforce medication adherence.


Association of 6-year waist circumference gain and incident hypertension.
The risk of incident hypertension with gain in waist circumference (WC) has not been fully addressed among Chinese adults. A total of 10 265 non-hypertensive participants ≥18 years old who underwent health examinations in rural China were recruited in 2007-2008 and followed up in 2013-2014. Participants were classified by gender according to categories of per cent WC gain at follow-up: ≤-2.5%, -2.5% to 2.5%, 2.5% to 5% and >5%. Relative risk (RR) and 95% CI values for effect of WC gain on the incident hypertension were calculated by using modified Poisson regression models. During 6 years of follow-up, we identified 2027 hypertension cases (1213 women). From baseline to follow-up, the prevalence of abdominal obesity increased from 21.1% to 29.6% for men and 49.8% to 61.9% for women. As compared with participants who were not abdominally obese at both baseline and follow-up, both genders who were abdominally obese at follow-up showed greater risk of hypertension regardless of abdominal obesity status at baseline. Compared with the reference group of -2.5% to 2.5% change in WC, with >5% WC gain, risk of incident hypertension was increased for men (RR=1.34, 95% CI 1.15 to 1.57) and women (RR=1.28, 95% CI 1.10 to 1.50). The hypertension risk decreased for men with WC loss ≥2.5% (RR=0.81, 95% CI 0.67 to 0.98). Abdominal obesity is seriously prevalent in China. The risk of hypertension increased significantly with increasing WC for both genders in a rural Chinese population.


Characterization of Triptolide-Induced Hepatotoxicity by Imaging and Transcriptomics in a Novel Zebrafish Model.
Triptolide is a vine extract used in traditional Chinese medicines and associated with hepatotoxicity. In vitro data suggest that inhibition of RNA synthesis may be the mechanism of toxicity. For studying drug-induced liver injury the zebrafish has experimental, practical and financial advantages compared with rodents. The aim of this study was to explore the mechanism of triptolide toxicity using zebrafish as the model system. The effect of triptolide exposure on zebrafish larvae was determined with regard to mortality, histology, expression of liver specific microRNA-122 and liver volume. Fluorescent microscopy was used to track toxicity in the Tg(-2.8lfabp:GFP)as3 zebrafish line. Informed by microscopy, RNA-sequencing was used to explore the mechanism of toxicity. Triptolide exposure resulted in dose-dependent mortality, a reduction in the number of copies of microRNA-122 per larva, hepatocyte vacuolation, disarray and oncotic necrosis, and a reduction in liver volume. These findings were consistent across replicate experiments. Time-lapse imaging indicated the onset of injury was 6 h after the start of exposure, at which point, RNA-sequencing revealed that 88% of genes were down-regulated. Immune response associated genes were up-regulated in the triptolide-treated larvae including nitric oxide synthase. Inhibition of nitric oxide synthase increased mortality. Triptolide induces hepatotoxicity in zebrafish larvae. This represents a new model of drug-induced liver injury that complements rodents. RNA sequencing, guided by time-lapse microscopy, revealed early down-regulation of genes consistent with previous invitro studies, and facilitated the discovery of mechanistic inflammatory pathways.


Perceptions of healthy eating and physical activity in an ethnically diverse sample of young children and their parents: the DEAL prevention of obesity study.
Ethnicity is a consistent correlate of obesity; however, little is known about the perceptions and beliefs that may influence engagement with obesity prevention programmes among ethnic minority children. Barriers to (and facilitators of) healthy lifestyles were examined in the qualitative arm of the London (UK) DiEt and Active Living (DEAL) study. Children aged 8-13 years and their parents, from diverse ethnic groups, were recruited through schools and through places of worship. Thirteen focus group sessions were held with 70 children (n = 39 girls) and eight focus groups and five interviews with 43 parents (n = 34 mothers). Across ethnic groups, dislike of school meals, lack of knowledge of physical activity guidelines for children and negativity towards physical education at school among girls, potentially hindered healthy living. Issues relating to families' wider neighbourhoods (e.g. fast food outlets; lack of safety) illustrated child and parental concerns that environments could thwart intentions for healthy eating and activity. By contrast, there was general awareness of key dietary messages and an emphasis on dietary variety and balance. For ethnic minorities, places of worship were key focal points for social support. Discourse around the retention of traditional practices, family roles and responsibilities, and religion highlighted both potential facilitators (e.g. the importance of family meals) and barriers (reliance on convenience stores for traditional foods). Socio-economic circumstances intersected with key themes, within and between ethnic groups. Several barriers to (and facilitators of) healthy lifestyles were common across ethnic groups. Diversity of cultural frameworks not only were more nuanced, but also shaped lifestyles for minority children.


Glycan engagement dictates hydrocephalus induction by serotype 1 reovirus.
Receptors expressed on the host cell surface adhere viruses to target cells and serve as determinants of viral tropism. Several viruses bind cell surface glycans to facilitate entry, but the contribution of specific glycan moieties to viral disease is incompletely understood. Reovirus provides a tractable experimental model for studies of viral neuropathogenesis. In newborn mice, serotype 1 (T1) reovirus causes hydrocephalus, whereas serotype 3 (T3) reovirus causes encephalitis. T1 and T3 reoviruses engage distinct glycans, suggesting that glycan-binding capacity contributes to these differences in pathogenesis. Using structure-guided mutagenesis, we engineered a mutant T1 reovirus incapable of binding the T1 reovirus-specific glycan receptor, GM2. The mutant virus induced substantially less hydrocephalus than wild-type virus, an effect phenocopied by wild-type virus infection of GM2-deficient mice. In comparison to wild-type virus, yields of mutant virus were diminished in cultured ependymal cells, the cell type that lines the brain ventricles. These findings suggest that GM2 engagement targets reovirus to ependymal cells in mice and illuminate the function of glycan engagement in reovirus serotype-dependent disease. Receptor utilization strongly influences viral disease, often dictating host range and target cell selection. Different reovirus serotypes bind to different glycans, but a precise function for these molecules in pathogenesis is unknown. We used type 1 (T1) reovirus deficient in binding the GM2 glycan and mice lacking GM2 to pinpoint a role for glycan engagement in hydrocephalus caused by T1 reovirus. This work indicates that engagement of a specific glycan can lead to infection of specific cells in the host and consequent disease at that site. Since reovirus is being developed as a vaccine vector and oncolytic agent, understanding reovirus-glycan interactions may allow manipulation of reovirus glycan-binding properties for therapeutic applications.


Imaging Correlates of Adult Glioma Genotypes.
Primary brain tumors, most commonly gliomas, are histopathologically typed and graded as World Health Organization (WHO) grades I-IV according to increasing degrees of malignancy. These grades provide prognostic information and guidance on treatment such as radiation therapy and chemotherapy after surgery. Despite the confirmed value of the WHO grading system, results of a multitude of studies and prospective interventional trials now indicate that tumors with identical morphologic criteria can have highly different outcomes. Molecular markers can allow subtypes of tumors of the same morphologic type and WHO grade to be distinguished and are, therefore, of great interest in personalization of brain tumor treatment. Recent genomic-wide studies have resulted in a far more comprehensive understanding of the genomic alterations in gliomas and provide suggestions for a new molecularly based classification. Magnetic resonance (MR) imaging phenotypes can serve as noninvasive surrogates for tumor genotypes and can provide important information for diagnosis, prognosis, and, eventually, personalized treatment. The newly emerged field of radiogenomics allows specific MR imaging phenotypes to be linked with gene expression profiles. In this article, the authors review the conventional and advanced imaging features of three tumoral genotypes with prognostic and therapeutic consequences: (a) isocitrate dehydrogenase mutation; (b) the combined loss of the short arm of chromosome 1 and the long arm of chromosome 19, or 1p19q codeletion; and (c) methylguanine methyltransferase promoter methylation. © RSNA, 2017.


In vitro protein digestibility of different soy-based products: effects of microstructure, physico-chemical properties and protein aggregation.
This study investigates the effects of protein structure and food microstructure on the in vitro protein gastrointestinal digestibility of different soy-based products, such as soy drink, reconstituted soy drink powder, firm tofu, and yuba. The results of the chemical cross-linking analysis showed that hydrogen bonds and hydrophobic interactions were the main forces driving protein aggregation in (reconstituted) soy drink powder and firm tofu, whereas disulphide bonds were significantly more important for soy drink and yuba. The β-sheet content of soy drink (36.5%) was lower than that of yuba (43.3%), but significantly higher than those of soy drink powder (23.2%) and firm tofu (29.8%). The in vitro protein digestibility decreased in the order of firm tofu > reconstituted soy drink powder > yuba > soy drink. Principal component analysis showed that protein gastrointestinal digestibility was positively correlated with the surface SH content and soluble protein content released by SDS + urea (SB-SA) but negatively correlated with the disulphide bonds and β-sheet content for the four soybean products.


Different cutoff value of motor evoked potentials for the postoperative outcome in the ossification of the posterior longitudinal ligament surgery in the cervical and thoracic spine.
Transcranial muscle motor evoked potentials (Tc-mMEPs), a key component of intraoperative neurophysiologic monitoring (IONM), effectively reflect the changes in corticospinal tract integrity and are closely related to the occurrence of the postoperative motor deficit (PMD). Most institutions have applied a specified (fixed) alarm criterion for the heterogenous groups in terms of etiologies or lesion location. However, given the high risk of PMD in ossification of the posterior longitudinal ligament (OPLL) surgery, it is essential to determine a tailored cutoff value for IONM. We aimed to establish the intraoperative cutoff value of Tc-mMEPs reduction for predicting PMD in OPLL according to lesion levels. Retrospective analysis using a review of electrical medical records. In this study, we included 126 patients diagnosed with OPLL, who underwent surgery and IONM. The occurrence of PMD immediately and 1-year after operation, as well as the decrement of intraoperative Tc-mMEPs amplitude. We analyzed OPLL surgery outcomes using Tc-mMEPs monitoring. Limbs with acceptable baseline Tc-mMEPs in the tibialis anterior or abductor hallucis were included in the final set. PMD was defined as a ≥ 1 decrease in Medical Research Council score in the legs, and it was evaluated immediately and 1-year after operation. The reduction ratios of Tc-mMEPs amplitude compared to baseline value were calculated at the two-time points: the maximal decrement during surgery and at the end of surgery. Receiver operating characteristic curve analysis was used to determine the cutoff value of Tc-mMEPs amplitude decrement for predicting PMDs. In total, 203 limbs from 102 patients with cervical OPLL and 42 limbs from 24 patients with thoracic OPLL were included. PMD developed more frequently in thoracic lesions than in cervical lesions (immediate, 9.52% vs. 2.46%; 1-year, 4.76% vs. 0.99%). The Tc-mMEPs amplitude cutoff point at the end of surgery for PMD (both immediate and 1-year) was a decrease of 93% in cervical and 50% in thoracic OPLL surgeries. Similarly, the Tc-mMEPs amplitude cutoff point at the maximal decrement during surgery for PMD (both immediate and 1-year) was a reduction of 97% in cervical and 85% in thoracic OPLL surgeries. The thoracic lesion exhibited a lower cutoff value than the cervical lesion for both immediate and long-term persistent PMD in OPLL surgery (Tc-mMEPs at the end of surgery measuring 93% vs 50%; and Tc-mMEPs at the maximal decrement measuring 97% vs 85% for cervical and thoracic lesions, respectively). To enhance the reliability of monitoring, considering the application of tailored alarm criteria for Tc-mMEPs changes based on lesion location in OPLL could be beneficial.


Association study of nicotinic acetylcholine receptor genes identifies a novel lung cancer susceptibility locus near CHRNA1 in African-Americans.
Studies in European and East Asian populations have identified lung cancer susceptibility loci in nicotinic acetylcholine receptor (nAChR) genes on chromosome 15q25.1 which also appear to influence smoking behaviors. We sought to determine if genetic variation in nAChR genes influences lung cancer susceptibly in African-Americans, and evaluated the association of these cancer susceptibility loci with smoking behavior. A total of 1308 African-Americans with lung cancer and 1241 African-American controls from three centers were genotyped for 378 single nucleotide polymorphisms (SNPs) spanning the sixteen human nAChR genes. Associations between SNPs and the risk of lung cancer were estimated using logistic regression, adjusted for relevant covariates. Seven SNPs in three nAChR genes were significantly associated with lung cancer at a strict Bonferroni-corrected level, including a novel association on chromosome 2 near the promoter of CHRNA1 (rs3755486: OR = 1.40, 95% CI = 1.18-1.67, P = 1.0 x 10-4). Association analysis of an additional 305 imputed SNPs on 2q31.1 supported this association. Publicly available expression data demonstrated that the rs3755486 risk allele correlates with increased CHRNA1 gene expression. Additional SNP associations were observed on 15q25.1 in genes previously associated with lung cancer, including a missense variant in CHRNA5 (rs16969968: OR = 1.60, 95% CI = 1.27-2.01, P = 5.9 x 10-5). Risk alleles on 15q25.1 also correlated with an increased number of cigarettes smoked per day among the controls. These findings identify a novel lung cancer risk locus on 2q31.1 which correlates with CHRNA1 expression and replicate previous associations on 15q25.1 in African-Americans.


Primary localized cutaneous nodular amyloidosis and CREST syndrome: a case report and review of the literature.
Primary localized cutaneous nodular amyloidosis (PLCNA) is a form of primary localized cutaneous amyloidosis (PLCA) that presents as yellowish waxy nodules on the extremities, face, trunk, or genitalia. We report the case of a patient with PLCNA and CREST (calcinosis, Raynaud phenomenon, esophageal motility disorders, sclerodactyly, and telangiectasia) syndrome. A diagnosis of her extensive PLCNA was made after biopsy specimens from the bilateral shins stained positive for amyloid extending from the superficial papillary dermis to the subcutis. Results of a workup were negative for paraproteinemia or signs of systemic amyloidosis and have remained so after 8 years of follow-up. We present a review of the literature describing the presentation and histopathology of the varying forms of amyloidosis.


Phytochemical profile and biological activity of Juglans regia.
Juglans regia Linn. (Juglandaceae), popularly known as English or Persian walnut, is a valuable medicinal plant with a potency to cure various diseases in traditional medicine. Since ancient time, different local ethnic groups have used various part of J. regia for a wide array of ailments including helminthiasis, diarrhea, sinusitis, stomach ache, arthritis, asthma, eczema, scrofula, skin disorders, diabetes mellitus, anorexia, thyroid dysfunction, cancer and infectious diseases. Biological activities of J. regia have been reported in several peer review journals and scientific attention is increasing. The present review attempts to provide comprehensive information on plant description, ethnobotanical use, toxicity, phytochemical profile, pharmacology, clinical studies and current research prospective of the J. regia. Currently, there is an immense interest on isolation/identification of active constituents from walnut and screening those active compounds for pharmacological activities. In addition, researchers are performing clinical trials as well as screening various solvent extracts or fractions of J. regia in several animal diseases models to identify promising therapeutic benefits. In the present work, we review the latest information based on published scientific investigations of J. regia.


High intensity, interval exercise improves quality of life of patients with chronic heart failure: a randomized controlled trial.
The aim of this study was to evaluate the effect of high intensity, interval exercise on quality of life (QoL) and depression status, in chronic heart failure (CHF) patients. A randomized controlled trial (phase III). Of the 100 consecutive CHF patients (NYHA classes II-IV, ejection fraction ≤ 50%) that were randomly allocated to exercise intervention (n = 50, high-intensity intermittent endurance training 30 s at 100% of max workload, 30 s at rest, for 45 min/day-by-12 weeks) or no exercise advice (n = 50), 72 (exercise group, n = 33, 63 ± 9 years, 88% men, 70% ischemic CHF and control group, n = 39, 56 ± 11 years, 82% men, 70% ischemic CHF) completed the study. QoL was assessed using the validated and translated Minnesota Living with Heart Failure questionnaire. Depressive symptomatology was evaluated using the validated and translated Zung Depression Rating Scale (ZDRS). Maximal oxygen uptake (VO(2max)) and carbon dioxide production (VCO(2max)) were also measured breath-by-breath. Data analysis demonstrated that in the intervention group MLHFQ score was reduced by 66% (P = 0.003); 6-min-walk distance increased by 13% (P < 0.05), VO(2max) level increased by 31% (P = 0.001), VCO(2max) level increased by 28% (P = 0.001) and peak power output increased by 25% (P = 0.001), as compared with the control group. High intensity, systematic aerobic training, could be strongly encouraged in CHF patients, since it improves QoL, by favorably modifying their fitness level.


Atrial fibrillation and congestive heart failure.
Atrial fibrillation (AF) and congestive heart failure (CHF) are common cardiac conditions that frequently coexist. There is a complex interplay between the two conditions, with each increasing the morbidity and mortality associated with the other. The management of AF in patients with CHF requires special care because of the increased risk of antiarrhythmic drug therapy in the group. This report reviews current treatment options and assesses the role of the newer therapies of biventricular pacing for CHF and radiofrequency ablation for AF. It also discusses results of the AF-CHF study, which were reported in November 2007.


Ferrous sulfate-induced increase in requirement for thyroxine in a patient with primary hypothyroidism.
Recent studies have shown that under experimental conditions ferrous sulfate may reduce the gastrointestinal absorption of orally administered levothyroxine sodium in patients with primary hypothyroidism. We describe a patient who became hypothyroid while taking ferrous sulfate. The hypothyroid status was corrected by increasing the dose of levothyroxine. Subsequently, when ferrous sulfate was discontinued, the patient became hyperthyroid while taking the higher dose of thyroid hormone preparation. Since both hypothyroidism and iron deficiency anemia may coexist, additional thyroid function testing is recommended in patients treated concurrently with ferrous sulfate and L-thyroxine.


Antiretroviral effects on HIV-1 RNA, CD4 cell count and progression to AIDS or death: a meta-regression analysis.
Governments, clinicians and drug-licensing bodies have adopted changes in CD4 cell counts and HIV-1 RNA levels as evidence of effectiveness for new therapeutic interventions. We aimed to determine the strength of the association between the magnitude of the effect of changes in CD4 cell count and HIV-1 RNA and progression to AIDS or death in the highly active antiretroviral therapy (HAART) era. We identified all randomized clinical trials (RCTs) evaluating the effect of HAART on both clinical and surrogate endpoints (1994 to September 2006). We performed a meta-regression and weighted linear regression. We additionally estimated potential RCT sample sizes that would be required to assess the effectiveness of new interventions in terms of clinical endpoints. We included data from 178 RCTs. We were unable to demonstrate a strong relationship at any time-point. Specifically, this was the case when CD4 T-cell change and clinical outcomes were examined at week 24 [coefficient -0.01, 95% confidence interval (CI) -0.03 to 0.001, P=0.54], week 48 (coefficient -0.01, 95% CI -0.02 to 0.001, P=0.83) and week 96 (coefficient 0.00, 95% CI -0.03 to 0.04, P=0.76). This was also the case when viral load was examined as a surrogate marker. Given the small number of clinical events occurring in new interventional RCTs, any RCT aiming to evaluate clinical endpoints within these time-points would require an exceptionally large sample size. Our findings indicate that, within short-term clinical trial settings, it is not possible to estimate the proportion of treatment effect associated with surrogate endpoints.