Pleurotus giganteus (Berk.) Karunarathna & K.D. Hyde: Nutritional value and in vitro neurite outgrowth activity in rat pheochromocytoma cells.
Drugs dedicated to alleviate neurodegenerative diseases like Parkinson's and Alzheimer's have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal. The fruiting bodies P. giganteus were analysed for its nutritional values. Cytotoxicity of the mushroom's aqueous and ethanolic extracts towards PC12, a rat pheochromocytoma cell line was assessed by using 3-[4,5-dimethythiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Neurite outgrowth stimulation assay was carried out with nerve growth factor (NGF) as control. To elucidate signaling mechanisms involved by mushroom extract-induced neurite outgrowth, treatment of specific inhibitor for MEK/ERK and PI3K signalling pathway was carried out. The fruiting bodies of P. giganteus were found to have high carbohydrate, dietary fibre, potassium, phenolic compounds and triterpenoids. Both aqueous and ethanolic extracts induced neurite outgrowth of PC12 cells in a dose- and time-dependant manner with no detectable cytotoxic effect. At day 3, 25 μg/ml of aqueous extract and 15 μg/ml of ethanolic extract showed the highest percentage of neurite-bearing cells, i.e. 31.7 ± 1.1% and 33.3 ± 0.9%; respectively. Inhibition treatment results suggested that MEK/ERK and PI3K/Akt are responsible for neurite outgrowth of PC12 cells stimulated by P. giganteus extract. The high potassium content (1345.7 mg/100 g) may be responsible for promoting neurite extension, too. P. giganteus contains bioactive compounds that mimic NGF and are responsible for neurite stimulation. Hence, this mushroom may be developed as a nutraceutical for the mitigation of neurodegenerative diseases.


New developments in the management of congenital Factor XIII deficiency.
Congenital Factor XIII (FXIII) deficiency is a rare, inherited, autosomal recessive coagulation disorder. Most mutations of this condition are found in the A-subunit with almost half these being missense mutations. Globally, approximately one in three million people suffer from this deficiency. Factor XIII deficiency is associated with severe life threatening bleeding, intracranial hemorrhage, impaired wound healing, and recurrent pregnancy losses. FXIII is known to have a potential role in mediating inflammatory processes, insulin resistance, bone metabolism, neoplasia, and angiogenesis. The algorithm provided for FXIII diagnosis and classification will enable prompt identification and early intervention for controlling potential life threatening complications. Prophylactic replacement therapy using blood products containing FXIII such as fresh frozen plasma, cryoprecipitate, or using FXIII concentrate remains the mainstay for the management of FXIII deficiency. In most parts of the world, cryoprecipitate and plasma transfusions are the only treatments available. Management developments have revealed the effectiveness and safety of recombinant FXIII concentrate for prophylaxis and treatment. The aim of this review is to provide an overview of advancements made in the management of FXIII deficiency from the time it was first detected, highlighting novel developments made in recent years. Greater research is warranted in identifying novel approaches to manage FXIII deficiency in light of its underlying pathophysiology.


Bcl-2 expression and apoptosis in the regulation of hematopoietic stem cells.
Apoptosis or programmed cell death plays a pivotal role in regulating tissue homeostasis in the adult and in tissue remodeling during embryogenesis. As in other tissues, apoptosis plays an important role within the hematopoietic system in removing aged and non-functional cells. It plays a particularly important role in regulating the cells of the immune system. The signals and molecules regulating apoptosis in these immune cells have been intensely investigated over the years, providing great insight into the mechanisms involved. In contrast, much less is known about the regulation and role of apoptosis in the cells that produce differentiated hematopoietic cells, namely the hematopoietic stem cells (HSCs). It is appreciated that HSCs are under tight regulatory control, as either excessive proliferation or apoptosis will result in too many or too few hematopoietic cells (for example, leukemia or anemia). Apoptosis thus plays an essential role in maintaining the appropriate balance of HSC and mature blood cells and in protecting the HSC pool for life-long hematopoiesis. This review summarizes the current knowledge concerning apoptosis and its role in the physiology of the hematopoietic system, especially within the HSC compartment.


Five hundred patients with Merkel cell carcinoma evaluated at a single institution.
To identify factors associated with survival in Merkel cell carcinoma (MCC). Merkel cell carcinoma is a rare cutaneous neoplasm. Staging and treatment are based on studies, which incompletely characterize the disease. Review of a prospective database was performed. Overall survival (OS) was estimated by the Kaplan-Meier method. Disease-specific death (DSD) was analyzed by the competing risks method. Factors associated with OS and DSD were determined by the log-rank test and Gray's test, respectively. A total of 500 patients with MCC treated at our institution from 1969 to 2010 were identified. Eighty-eight patients presented older than 6 months after diagnosis and were excluded from further analysis. Of the remaining 412 patients, the median age at diagnosis was 71 years. Median follow-up was 3 years. Fifty percent of patients died during follow-up: 25% died of disease, 24% died of other causes. Five-year OS and DSD were 56% and 30%, respectively. Pathologic stage and lymphovascular invasion were independent predictors of DSD. Patients with metastatic disease (stage 4) or clinically positive lymph nodes (stage 3b) had increased DSD compared with patients with microscopically positive (stage 3a) or negative lymph nodes (stage 1 and 2). There was no difference in DSD between stage 3a or 2 compared with stage 1. Importantly, only 1 of 132 patients without lymphovascular invasion died of MCC. OS is a poor measure of the influence of MCC on life expectancy. The presence of lymphovascular invasion and clinically, but not microscopically, positive lymph nodes were associated with increased DSD. These factors should be incorporated into MCC staging and treatment recommendations.


The digital TV filter and nonlinear denoising.
Motivated by the classical TV (total variation) restoration model, we propose a new nonlinear filter-the digital TV filter for denoising and enhancing digital images, or more generally, data living on graphs. The digital TV filter is a data dependent lowpass filter, capable of denoising data without blurring jumps or edges. In iterations, it solves a global total variational (or L(1)) optimization problem, which differs from most statistical filters. Applications are given in the denoising of one dimensional (1-D) signals, two-dimensional (2-D) data with irregular structures, gray scale and color images, and nonflat image features such as chromaticity.


A Fluorescent Sensor for Quantitative Super-Resolution Imaging of Amyloid Fibril Assembly.
Many soluble proteins can self-assemble into macromolecular structures called amyloids, a subset of which are implicated in a range of neurodegenerative disorders. The nanoscale size and structural heterogeneity of prefibrillar and early aggregates, as well as mature amyloid fibrils, pose significant challenges for the quantification of amyloid morphologies. We report a fluorescent amyloid sensor AmyBlink-1 and its application in super-resolution imaging of amyloid structures. AmyBlink-1 exhibits a 5-fold increase in ratio of the green (thioflavin T) to red (Alexa Fluor 647) emission intensities upon interaction with amyloid fibrils. Using AmyBlink-1, we performed nanoscale imaging of four different types of amyloid fibrils, achieving a resolution of ≈30 nm. AmyBlink-1 enables nanoscale visualization and subsequent quantification of morphological features, such as the length and skew of individual amyloid aggregates formed at different times along the amyloid assembly pathway.


Spectrum of Spinal Cord, Spinal Root, and Brain MRI Abnormalities in Congenital Zika Syndrome with and without Arthrogryposis.
Arthrogryposis is among the malformations of congenital Zika syndrome. Similar to the brain, there might exist a spectrum of spinal cord abnormalities. The purpose of this study was to explore and describe in detail the MR imaging features found in the spinal cords, nerve roots, and brains of children with congenital Zika syndrome with and without arthrogryposis. Twelve infants with congenital Zika syndrome (4 with arthrogryposis and 8 without) who had undergone brain and spinal cord MR imaging were retrospectively selected. Qualitative and quantitative analyses were performed and compared between groups. At visual inspection, both groups showed reduced thoracic spinal cord thickness: 75% (6/8) of the group without arthrogryposis and 100% (4/4) of the arthrogryposis group. However, the latter had the entire spinal cord reduced and more severely reduced conus medullaris anterior roots (respectively, P = .002 and .007). Quantitative differences were found for conus medullaris base and cervical and lumbar intumescences diameters (respectively, P = .008, .048, .008), with more prominent reduction in arthrogryposis. Periventricular calcifications were more frequent in infants with arthrogryposis (P = .018). Most infants had some degree of spinal cord thickness reduction, predominant in the thoracic segment (without arthrogryposis) or in the entire spinal cord (with arthrogryposis). The conus medullaris anterior roots were reduced in both groups (thinner in arthrogryposis). A prominent anterior median fissure of the spinal cord was absent in infants without arthrogryposis. Brain stem hypoplasia was present in all infants with arthrogryposis, periventricular calcifications, in the majority, and polymicrogyria was absent.


Stable DNA replication: interplay between DNA replication, homologous recombination, and transcription.
Chromosome replication in Escherichia coli is normally initiated at oriC, the origin of chromosome replication. E. coli cells possess at least three additional initiation systems for chromosome replication that are normally repressed but can be activated under certain specific conditions. These are termed the stable DNA replication systems. Inducible stable DNA replication (iSDR), which is activated by SOS induction, is proposed to be initiated from a D-loop, an early intermediate in homologous recombination. Thus, iSDR is a form of recombination-dependent DNA replication (RDR). Analysis of iSDR and RDR has led to the proposal that homologous recombination and double-strand break repair involve extensive semiconservative DNA replication. RDR is proposed to play crucial roles in homologous recombination, double-strand break repair, restoration of collapsed replication forks, and adaptive mutation. Constitutive stable DNA replication (cSDR) is activated in mhA mutants deficient in RNase HI or in recG mutants deficient in RecG helicase. cSDR is proposed to be initiated from an R-loop that can be formed by the invasion of duplex DNA by an RNA transcript, which most probably is catalyzed by RecA protein. The third form of SDR is nSDR, which can be transiently activated in wild-type cells when rapidly growing cells enter the stationary phase. This article describes the characteristics of these alternative DNA replication forms and reviews evidence that has led to the formulation of the proposed models for SDR initiation mechanisms. The possible interplay between DNA replication, homologous recombination, DNA repair, and transcription is explored.


Pharmaceuticals as a market for "lemons": Theory and practice.
Drawing on economic theory and institutional analysis, this paper reframes Akerlof's theory of how a market for lemons operates and argues that each of the many markets for lemons must be studied empirically to document how different stakeholders cope with the problems of information asymmetry, secrecy, and power. Such markets are a new field for sociological analysis. To illustrate, the paper characterizes pharmaceuticals as a multi-tier market of information asymmetry in which actors in each tier have substantial control over how much they disclose about hidden risks of harm. Such a market rewards the production and sale of "lemons." Current incentives and institutional practices reward developing a large number of barely therapeutically innovative drugs and ignoring their often hidden or understated harmful side effects. They reward designing and executing substandard, biased trials that mislead the FDA and regulators abroad to approve new drugs without clear evidence of their degree of harm. Approved drugs are likely to be "lemons" but promoted as "safe and effective." The result is substantial hospitalizations and deaths from adverse drug reactions. A "risk proliferation syndrome" of institutional practices maximizes sales, profits, and exposure to toxic side effects. An "inverse benefit law" of marketing operates as companies try to maximize sales. The probability of benefits decreases but the chances of lemons adverse events do not. The details presented here deepen understanding of how markets for lemons thrive on information asymmetry, secrecy, and power. Lessons can be applied to other markets.


Phosphate-induced mineralization of tracheal smooth muscle and cartilage cells.
During aging or various diseases, pathologic mineralization may occur in joints or in the vascular wall. This is due to the deposition of phosphate (Pi)-containing crystals into the extracellular matrix of articular chondrocytes or vascular smooth muscle cells. The mineralization ability of chondrocytes and smooth muscle cells of other tissue has not been investigated. In this context, our work seeks to study the response induced by Pi on cartilage and smooth muscle cells from tracheal origin. We have established a dissection procedure to harvest and isolate chondrocyte and smooth muscle cells from adult mouse trachea. Both cell types were then exposed to different concentrations of Pi (1, 3 or 5 mM) up to 14 days. Mineralization was evaluated by alizarin red staining, which identifies calcium deposition. The expression of genes characterizing the phenotypic identity of the cells and involved in the mineralization process was assessed by RT-qPCR. Treatment of tracheal chondrocytes and smooth muscle cells with increasing concentrations of Pi (3 and 5 mM) induced mineralization as revealed by positive alizarin red staining as early as 7 days of culture. Moreover, gene expression analysis revealed profound phenotypic changes in both cell types and suggested they mineralize through TNAP-independent or -dependent mechanisms, respectively. Our data indicate that, comparably to articular chondrocytes or vascular smooth muscles, chondrocyte and smooth muscle cells from the trachea are prone to mineralize under high-phosphate conditions.


Implications of extending the ADHD age-of-onset criterion to age 12: results from a prospectively studied birth cohort.
To evaluate whether including children with onset of symptoms between ages 7 and 12 years in the ADHD diagnostic category would: (a) increase the prevalence of the disorder at age 12, and (b) change the clinical and cognitive features, impairment profile, and risk factors for ADHD compared with findings in the literature based on the DSM-IV definition of the disorder. A birth cohort of 2,232 British children was prospectively evaluated at ages 7 and 12 years for ADHD using information from mothers and teachers. The prevalence of diagnosed ADHD at age 12 was evaluated with and without the inclusion of individuals who met DSM-IV age-of-onset criterion through mothers' or teachers' reports of symptoms at age 7. Children with onset of ADHD symptoms before versus after age 7 were compared on their clinical and cognitive features, impairment profile, and risk factors for ADHD. Extending the age-of-onset criterion to age 12 resulted in a negligible increase in ADHD prevalence by age 12 years of 0.1%. Children who first manifested ADHD symptoms between ages 7 and 12 did not present correlates or risk factors that were significantly different from children who manifested symptoms before age 7. Results from this prospective birth cohort might suggest that adults who are able to report symptom onset by age 12 also had symptoms by age 7, even if they are not able to report them. The data suggest that the prevalence estimate, correlates and risk factors of ADHD will not be affected if the new diagnostic scheme extends the age-of-onset criterion to age 12.


Crucial role of CGI-58/alpha/beta hydrolase domain-containing protein 5 in lipid metabolism.
The surfaces of lipid droplets (LDs) constitute major sites of regulated accumulation and degradation of lipid in cells, and hence play important roles in lipid homeostasis of the whole body. CGI-58 (also called alpha/beta hydrolase domain-containing protein 5 (ABHD5)) is a member of the alpha/beta-hydrolase family of proteins and is a product of the causal gene of Chanarin-Dorfman syndrome (CDS), which is characterized by excessive storage of triacylglycerol (TG) in various tissues. CGI-58 is distributed predominantly on the surface of LDs and plays a crucial role in TG degradation in cells. In the process of lipolysis, CGI-58 coordinates with several proteins, including perilipin, a member of the PAT family of proteins, and adipose triglyceride lipase (ATGL), a putative rate-limiting enzyme for TG degradation in adipocytes. Besides its role in adipocytes, CGI-58 is involved in lipid degradation in various tissues, including those of skin and liver. This review focuses on the functions and protein interactions of CGI-58 on the surface of LDs in the regulation of fat mobilization in cells.


Caffeic Acid Phenethyl Ester (CAPE) derived from propolis, a honeybee product, inhibits growth of breast cancer stem cells.
Cancer stem cells (CSC) are chemoresistant and implicated in tumor recurrence, metastasis and high patient mortality; thus substances impairing CSC activity, could be invaluable as novel cancer therapeutics. We previously showed that CAPE (caffeic acid phenethyl ester), a component of propolis, a honeybee product, inhibits growth of MDA-MB-231 (MDA-231) cells, mdr gene expression, NF-κB, EGFR, and VEGF. We hypothesized that CAPE also acts by interfering with CSC-mediated effects. We isolated breast CSC (bCSC) from MDA-231 cells, a model of human triple-negative breast cancer, and mouse xenografts. bCSC grow as mammospheres (MMS) and when dissociated into single cells, form MMS again, a sign of self-renewal. bCSC exhibited the characteristic CD44(+)/CD24(-/low) phenotype and generated progenitors in the presence of serum, a CSC trait responsible for regenerating tumor mass. CAPE caused dose-dependent bCSC self-renewal inhibition and progenitor formation. Clonal growth on soft agar was inhibited dose-dependently, but apoptosis was not induced as determined by Annexin-V/PI assay. Instead, bCSC were noted to significantly progress from a quiescent cell cycle state in G0/G1 (82%), S phase (12%) to a cycling state with an increase in S phase (41%) and subsequent decrease in G0/G1 (54%). Treatment of bCSC with CAPE (4.5-days) decreased CD44 levels by 95%, while another cell population containing 10-100-fold lower CD44 content concurrently increased. Results suggest that CAPE causes pronounced changes in bCSC characteristics manifested by inhibition of self renewal, progenitor formation, clonal growth in soft agar, and concurrent significant decrease in CD44 content, all signs of decreased malignancy potential.


The joint role of impulsivity and distorted cognitions in recreational and problem gambling: A cluster analytic approach.
The Pathways Model (Blaszczynski & Nower, 2002) posits that problem gambling is a heterogeneous disorder with distinct subgroups (behaviorally conditioned gamblers, emotionally vulnerable gamblers, and antisocial-impulsivist gamblers). Impulsivity traits and gambling-related cognitions are recognized as two key psychological factors in the onset and maintenance of problem gambling. To date, these constructs have been explored separately, and their joint role in determining problem gambling subtypes has received little attention. The goal of our study was to identify subgroups of gamblers based on impulsivity traits and gambling-related cognitions, and to determine whether this approach is consistent with the Pathways model. Gamblers from the community (N = 709) and treatment-seeking pathological gamblers (N = 122) completed questionnaires measuring gambling habits, disordered gambling symptoms, gambling-related cognitions, and impulsivity traits. Cluster analyses revealed that three clusters globally aligned with the pathways proposed by Blaszczynski & Nower (2002). Two other clusters emerged: (1) impulsive gamblers without cognitive-related cognitions; and (2) gamblers without impulsivity or gambling-related cognitions. Gamblers with both heightened impulsive traits and gambling-related cognitions had more severe problem gambling symptoms. We successfully identified, based on an a priori theoretical framework, different subtypes of gamblers that varied in terms of problem gambling symptoms and clinical status. The diversity of the cluster profiles supports the development of personalized prevention strategies and psychological interventions.


Red Yeast Rice (RYR) supplementation in patients treated with second-generation antipsychotics.
Second-generation antipsychotics (SGAs) have a negative impact on metabolic syndrome (MetS) risk factors for their effects on body weight and on metabolic parameters. Statins are widely used in the treatment of dyslipidemia; less is known on the ability of statins to treat SGAs-induced dyslipidemia, and nutraceutical approaches may represent promising strategies in SGAs-treated patients. Red Yeast Rice (RYR), the fermented product of the Aspergillaceae mold Monascus purpureus (red yeast) grown on white rice, has been shown to have a cholesterol-lowering effect which can be ascribed to monacolin K, although other active compounds may play a role management of hyperlipidemia. The present study was aimed to explore the efficacy and safety of RYR treatment on clinical and metabolic parameters in a sample of subjects receiving SGAs. Fifteen outpatients treated with SGAs assumed RYR at the oral daily dose of 200 mg/day (total monacolin K = 11.88 mg) for 30 days. Fasting levels of triglycerides, total cholesterol, high density lipoprotein cholesterol, low density lipoprotein cholesterol and glucose were determined. RYR administration resulted in a statistically significant reduction of LDL (p = 0.029), corresponding to 11.0% decrease from baseline mean value. No significant differences in clinical and in other and metabolic parameters were observed. Our findings suggest that RYR, at the daily dose of 200 mg for 30 days, could be a promising agent to prevent and/or treat SGAs-induced hyperlipidemia. However, future adequately-powered and well-designed studies with long-term follow-up should evaluate RYR effectiveness, as an alternative option to statins, on the SGAs-induced metabolic side effects.


Pregnancy specific glycoprotein 18 induces IL-10 expression in murine macrophages.
Pregnancy specific glycoproteins (PSG) are secreted into the maternal circulation and may function to regulate the immune system to ensure survival of the fetal allograft. In this study, we have cloned and determined by in situ hybridization the placental sites of expression of Psg18, a murine member of the PSG family that belongs to the Ig superfamily. Recombinant PSG18 and a truncated form containing only the N-terminal domain (PSG18N) were used to treat peritoneal elicited macrophages and RAW 264.7 cells. PSG18 and PSG18N induced IL-10 mRNA expression in the presence and absence of lipopolysaccharide (LPS). IL-10 protein was also detected in the supernatant of macrophages and RAW 264.7 cells following PSG18N treatment, albeit higher concentrations were required in the absence of LPS. In contrast, treatment of these cells with PSG18N resulted in no change in the expression of IL-1/beta, TNF-alpha, inducible NO synthase, IL-12p40 and TGF-beta mRNA. Taken together, these results suggest that PSG18 selectively up-regulates IL-10 production by macrophages, providing a possible mechanism by which this protein helps promote successful pregnancy.


Lipoprotein hydrolysis and fat accumulation in chicken adipose tissues are reduced by chronic administration of lipoprotein lipase monoclonal antibodies.
The lipoprotein lipase (LPL) catalyzed hydrolysis of plasma lipoproteins is a rate-limiting step in the lipid transport into peripheral tissues. The aim of the present study was to isolate monoclonal antibodies against chicken adipose LPL and to investigate whether chronic infusion of the LPL monoclonal antibodies inhibits adipose LPL activity and consequently reduces fat accumulation in broiler chickens. The LPL catalyzed very low density lipoprotein (VLDL) hydrolysis was completely inhibited by the addition of 100 microg/mL of monoclonal antibodies (CLP10, CLP14, CLP16) in the in vitro incubation with plasma VLDL and LPL. A single injection of CLP10 and CLP16 into chickens fed or starved for 24 h elevated plasma triacylglycerol concentrations for 24 h, whereas that of CLP14 was ineffective. Intravenous injection every other day and continuous infusion by osmotic minipump with CLP16 maintained higher plasma triacylglycerol concentration for 5 d than that of the control group and extensively reduced LPL activity in adipose tissues and abdominal fat pad weight. Lipoprotein lipase mRNA and protein levels in adipose tissue were not modified by chronic administration of anti-LPL antibody. The results indicate that chronic administration of anti-LPL antibodies is effective in retarding fatness in broiler chickens, and the antibodies are a proper subject for studies of lipoprotein metabolism.


Effect of modified atmosphere packaging on the persistence and expression of virulence factors of Escherichia coli O157:H7 on shredded iceberg lettuce.
Fresh-cut leafy greens contaminated with Escherichia coli O157:H7 have caused foodborne outbreaks. Packaging conditions, coupled with abusive storage temperatures of contaminated lettuce, were evaluated for their effect on the potential virulence of E. coli O157:H7. Shredded lettuce was inoculated with 5.58 and 3.98 log CFU E. coli O157:H7 per g and stored at 4 and 15°C, respectively, for up to 10 days. Lettuce was packaged under treatment A (modified atmosphere packaging conditions used for commercial fresh-cut produce, in gas-permeable film with N(2)), treatment B (near-ambient air atmospheric conditions in a gas-permeable film with microperforations), and treatment C (high-CO(2) and low-O(2) conditions in a gas-impermeable film). E. coli O157:H7 populations from each treatment were determined by enumeration of numbers on MacConkey agar containing nalidixic acid. RNA was extracted from packaged lettuce for analysis of expression of virulence factor genes stx(2), eae, ehxA, iha, and rfbE. E. coli O157:H7 populations on lettuce at 4°C under all treatments decreased, but most considerably so under treatment B over 10 days. At 15°C, E. coli O157:H7 populations increased by at least 2.76 log CFU/g under all treatments. At 15°C, expression of eae and iha was significantly greater under treatment B than it was under treatments A and C on day 3. Similarly, treatment B promoted significantly higher expression of stx(2), eae, ehxA, and rfbE genes on day 10, compared with treatments A and C at 15°C. Results indicate that storage under near-ambient air atmospheric conditions can promote higher expression levels of O157 virulence factors on lettuce, and could affect the severity of E. coli O157:H7 infections associated with leafy greens.


Schistosomiasis japonica in field rats in Leyte, Philippines.
Approximately 73% of wild caught field rats were found infected with schistosomiasis japonica as revealed by the finding of eggs in liver sections; 49% of rats showed eggs in histological sections of the large intestine and about 13% showed eggs in their stools. Male rats appear to have higher schistosomiasis infection rate then female rats and that rats caught from endemic areas with smooth or normal looking livers do not necessarily mean that they are not infected with schistosomiasis. Examination for miracidia using only 2-3 pellets of field rat's stool by Faust-Meleney egg hatching technique revealed that 58% of them were positive with a mean of 5 miracidia per rat. A slightly lower hatchability rate was observed among laboratory infected white rats. Our figures on hatchability of Schistosoma ova are higher than those obtained by Pesigan and his co-workers probably because we used freshly collected rat faeces.


Coping, anxiety and quality of life after coronary artery bypass graft surgery.
This paper is a report of a study to explore the relationship between ways of coping, anxiety level and quality of life for patients after coronary artery bypass grafting. Coronary artery bypass grafting requires appropriate coping strategies to achieve successful adaptation. In Taiwan, the incidence of this surgery is increasing, but research on adaptation following surgery is limited, with no research examining outcomes for women, who often have poorer adaptation outcomes than men. An integrated research design, based on Lazarus and Folkman's transaction coping theory, was used. The research employed convenience sampling with four instruments: the Revised Ways of Coping Checklist, State-Trait Anxiety Inventory, Short Form 36-Health Survey, and a demographic questionnaire, sent to 50 men and 50 women who were recruited from a medical centre in Taiwan. Additionally, qualitative data from interviews with three men and three women, who had completed the instruments, were analysed. Better quality of life was associated with lower anxiety level, greater use of problem-focused coping strategies and those who had more gender role responsibility. Women scored lower on the physical dimensions of quality of life, used more self-blaming coping strategies and experienced slightly higher levels of anxiety compared to men. The qualitative analysis supported the conclusions of the quantitative analysis. The results will help nurses design specific interventions intended to lower anxiety levels, promote the use of problem-focused strategies and identify patients' values, necessary to achieve optimal quality of life.


Effect of aging on risk for hepatocellular carcinoma in chronic hepatitis C virus infection.
An increase in the aging population is an impending problem. A large cohort study was carried out to determine the influence of aging and other factors on hepatocarcinogenesis in patients treated with interferon. Biopsy-proven 2547 chronic hepatitis C patients registered at our referral center since 1992 were included. Of these, 2166 were treated with interferon-based therapy. Incidences of hepatocellular carcinoma (HCC) associated with interferon were analyzed by Kaplan-Meier and person-years methods for an average follow-up of 7.5 years. Factors associated with HCC risk were determined by Cox proportional hazard analysis. HCC developed in 177 interferon-treated patients. The risk for HCC depended on age at primary biopsy and increased more than 15-fold after 65 years of age. Even when stratified by stage of fibrosis, the cumulative and annual incidences of HCC were significantly higher in older patients than in younger patients (P < 0.001) at the same stage of fibrosis, except for cirrhosis. Progression of fibrosis over time was significantly accelerated in older patients. The impact of viral eradication on HCC prevention was less significant in older patients than in younger patients. Multivariate analysis confirmed that age, gender, liver fibrosis, liver steatosis, total cholesterol level, fasting blood sugar level, baseline and postinterferon alpha-fetoprotein level, and virological response to interferon were independent risk factors associated with HCC. Aging was the strongest risk factor for a nonvirological response to interferon-based antiviral therapy. Elderly patients are at a higher risk for HCC. Hepatitis C viral eradication had a smaller effect on hepatocarcinogenesis in older patients. Patients should therefore be identified at an earlier age and treatment should be initiated.


Abnormal cerebral cortex structure in children with ADHD.
Examination of cerebral cortical structure in children with Attention-Deficit/Hyperactivity Disorder (ADHD) has thus far been principally limited to volume measures. In the current study, an automated surface-based analysis technique was used to examine the ADHD-associated differences in additional morphologic features of cerebral cortical gray matter structure, including surface area, thickness, and cortical folding. MPRAGE images were acquired from 21 children with ADHD (9 girls) and 35 typically developing controls (15 girls), aged 8-12 years. Statistical difference maps were used to compare mean cortical thickness between groups along the cortical surface. Cortical volume, surface area, mean thickness, and cortical folding were measured within regions of interest, including the right/left hemispheres, frontal, temporal, parietal, and occipital lobes within each hemisphere, and sub-lobar regions. Children with ADHD showed a decrease in total cerebral volume and total cortical volume of over 7 and 8%, respectively; volume reduction was observed throughout the cortex, with significant reduction in all four lobes bilaterally. The ADHD group also showed a decrease in surface area of over 7% bilaterally, and a significant decrease in cortical folding bilaterally. No significant differences in cortical thickness were detected. Results from the present study reveal that ADHD is associated with decreased cortical volume, surface area, and folding throughout the cerebral cortex. The findings suggest that decreased cortical folding is a key morphologic feature associated with ADHD. This would be consistent with onset early in neural development and could help to identify neurodevelopmental mechanisms that contribute to ADHD.


RNA in unexpected places: long non-coding RNA functions in diverse cellular contexts.
The increased application of transcriptome-wide profiling approaches has led to an explosion in the number of documented long non-coding RNAs (lncRNAs). While these new and enigmatic players in the complex transcriptional milieu are encoded by a significant proportion of the genome, their functions are mostly unknown. Early discoveries support a paradigm in which lncRNAs regulate transcription via chromatin modulation, but new functions are steadily emerging. Given the biochemical versatility of RNA, lncRNAs may be used for various tasks, including post-transcriptional regulation, organization of protein complexes, cell-cell signalling and allosteric regulation of proteins.


Interaction network of the 14-3-3 protein in the ancient protozoan parasite Giardia duodenalis.
14-3-3s are phosphoserine/phosphotreonine binding proteins that play pivotal roles as regulators of multiple cellular processes in eukaryotes. The flagellated protozoan parasite Giardia duodenalis, the causing agent of giardiasis, is a valuable simplified eukaryotic model. A single 14-3-3 isoform (g14-3-3) is expressed in Giardia, and it is directly involved in the differentiation of the parasite into cyst. To define the overall functions of g14-3-3, the protein interactome has been investigated. A transgenic G. duodenalis strain was engineered to express a FLAG-tagged g14-3-3 under its own promoter. Affinity chromatography coupled with tandem mass spectrometry analysis have been used to purify and identify FLAG-g14-3-3-associated proteins from trophozoites and encysting parasites. A total of 314 putative g14-3-3 interaction partners were identified, including proteins involved in several pathways. Some interactions seemed to be peculiar of one specific stage, while others were shared among the different stages. Furthermore, the interaction of g14-3-3 with the giardial homologue of the CDC7 protein kinase (gCDC7) was characterized, leading to the identification of a multiprotein complex containing not only g14-3-3 and gCDC7 but also a newly identified and highly divergent homologue of DBF4, the putative regulatory subunit of gCDC7. The relevance of g14-3-3 interactions in G. duodenalis biology was discussed.


Protecting the social body: use of the organism metaphor in fighting the "menace of the feebleminded".
Although persons with developmental disabilities living in the United States have been treated in a pejorative manner at various times throughout the nation's history, the eugenics era (1900-1930) stands out as a time when such individuals-then referred to as "feebleminded"--were subject to particularly extreme indignities. Numerous methods of dehumanizing such persons were employed during this era. Of special significance was the use of the organism metaphor, whereby the "unfit" members of society were compared to a parasite, cancer, virus, or plague infecting the social body. The use of rhetoric advancing the organism metaphor in eugenic writing is described in this paper as is the effect that such rhetoric had on the societal response to such persons.


The localization of sensory nerve fibers and receptor binding sites for sensory neuropeptides in canine mesenteric lymph nodes.
Previous work has established that the central nervous system can modulate the immune response. Direct routes through which this regulation may occur are the sympathetic and sensory innervation of lymphoid organs. We investigated the innervation of canine mesenteric lymph nodes using immunohistochemistry and the expression of binding sites for sensory neuropeptides using quantitative receptor autoradiography. The sympathetic innervation of lymph nodes was examined by immunohistochemical methods using an antiserum directed against tyrosine hydroxylase (TOH), the rate limiting enzyme in catecholamine synthesis. TOH-containing fibers were associated with 90% of the blood vessels (arteries, veins, arterioles and venules) in the hilus, medullary and internodular regions of lymph nodes and in trabeculae with no obvious relationship to blood vessels. The sensory innervation of lymph nodes was investigated using antisera directed against the putative sensory neurotransmitters calcitonin gene-related peptide (CGRP) and substance P (SP). CGRP- and SP-containing fibers were detected in the hilus, the medullary region, and the internodular region of lymph nodes usually in association with arterioles and venules. About 50% of the arterioles and venules exhibited a CGRP innervation and a smaller fraction (5-10%) were innervated by SP-containing fibers. Few if any TOH, CGRP, and SP nerve fibers were detected in the germinal centers of lymph nodes. Using quantitative receptor autoradiography we studied the distribution of receptor binding sites for the sensory neuropeptides CGRP, SP, substance K (SK), vasoactive intestinal peptide (VIP), somatostatin (SOM), and bombesin. Specific CGRP binding sites were expressed throughout lymph nodes by trabeculae, arterioles, venules and 25% of the germinal centers. SP receptor binding sites were localized to arterioles and venules in the T cell regions and 25-30% of the germinal centers. VIP binding sites were localized to the internodular and T cell regions, to medullary cords, and to 10-20% of germinal centers. SK, SOM, and bombesin binding sites were not detected in the lymph nodes, although receptor binding sites for these peptides were detected with high specific/nonspecific binding ratios in other canine peripheral tissues. Taken together with previous results these findings suggest that the sympathetic and sensory innervation of mesenteric lymph nodes appears to be involved with the regulation of their blood and lymph flow. The neuropeptide receptor binding sites in lymph node germinal centers may be expressed by lymphocytes upon activation by antigens.(ABSTRACT TRUNCATED AT 400 WORDS)


Metal-based anion receptors: an application of second-sphere coordination.
This tutorial review describes metal-based anion receptors in the context of first- and second-sphere coordination. Selected examples (case studies) are used to show how metal ions can be used to (1) organise hydrogen-bond donor sites on ligands in order to bind anions, (2) influence the conformation of ligands to enhance anion binding, (3) alter the binding conformation of a receptor depending on the solvent and (4) develop a receptor to target a specific anion (sulfate) for sequestration.


[Formal thought disorders and speech disorders in schizophrenia--new findings from empirical studies?].
The investigation of formal thought and speech disorders in schizophrenia is hampered by the missing differentiation of speech and thought. Empirical investigations paying attention to this differentiation do not argue for specific schizophrenic speech or thought disorders but for a clinically relevant continuum of these disorders within the group of endogenous psychoses.


Clinical Utility of Fedratinib in Myelofibrosis.
Myelofibrosis (MF) is a clonal hematologic malignancy characterized by bone marrow fibrosis, extramedullary hematopoiesis, splenomegaly, and constitutional symptoms with a propensity towards leukemic transformation. Constitutive activation of the JAK/STAT pathway is a well-described pathogenic feature of MF. Allogeneic stem cell transplant is the only curative therapy, but due to high morbidity and mortality this option is not available for most patients. There are two approved targeted therapy options for MF, ruxolitinib and fedratinib. In this review, we discuss the clinical utility of fedratinib in the myelofibrosis treatment paradigm. Fedratinib has shown impressive pre-clinical and clinical efficacy in patients with untreated MF as well as in those with ruxolitinib intolerance and those with relapsed/refractory MF. Here, we review the pre-clinical and clinical trials that led to the approval of fedratinib, and the ongoing late-phase trials. We highlight several areas regarding the clinical utility of fedratinib that remain unanswered. We discuss the limitations of fedratinib and address areas that are understudied and require further clinical evaluation and research. The approval of fedratinib has provided a significant expansion to the very limited treatment armamentarium available to patients with MF.


A new scale measuring adaptive perceived control for people with Parkinson's: Initial construction and further validation.
Perceived control is an important concept in understanding adjustment to chronic conditions such as Parkinson's. While generic measures have been used to measure the construct in Parkinson's, no Parkinson's-specific scale currently exists. This study outlines the initial development and further validation of a free-to-use scale, the Parkinson's UK Scale of Perceived Control (PUKSoPC). Focus groups were used to create items for the new scale. Potential items were then subject to screening for readability and coherence by people affected by the condition. This left 49 items that were then completed, along with other measures, by 231 people with Parkinson's. Exploratory factor analysis then created a 15-item scale with five distinct subscales. This initial structure was then further tested using confirmatory factor analysis with 2032 people with Parkinson's. Structural equation modelling confirmed the acceptability of the total scale and subscale structures. The final scale is concluded to be a psychometrically robust measure of perceived control. It has good face validity, evidence of convergent and criterion (concurrent and divergent) validity, good test-retest reliability and is internally coherent, with a demonstrably solid factor structure. While further testing would be useful to assess the scale's predictive ability, it is currently considered robust enough for more widespread use. The PUKSoPC is an appropriate scale to provide a more comprehensive measure of perceived control. It is preferable to single item, non-validated measures and can provide evidence of perceptions of control across a number of domains important in the measurement of the construct.


Characterization of the activation of rat liver beta-glucosidase by sialosylgangliotetraosylceramide.
We show that sialosylgangliotetraosylceramide (GM1) is a potent activator of delipidated (sodium cholate- and 1-butanol-extracted) lysosomal rat liver glucocerebroside:beta-glucosidase. Stimulation of 4-methylumbelliferyl-beta-D-glucopyranoside hydrolysis by the beta-glucosidase was markedly dependent upon the concentration of GM1 in the assay medium. Estimations of critical micellar concentration (CMC) performed fluorometrically using the dye N-phenylnaphthylamine revealed two CMC values of GM1 above 18 degrees C; the CMC of the primary micelles (3.32 microM) was temperature-independent whereas that of the secondary micelles decreased with decreasing temperature (17.2 and 10.8 microM at 37 and 20 degrees C, respectively). In the temperature range of 18-39 degrees C, beta-glucosidase activity increased sharply when the GM1 concentration was above the CMC of the secondary micelles. Although a heat-stable factor, purified from the spleen of a patient with Gaucher's disease, had a profound effect on the activation of beta-glucosidase by GM1, it decreased the CMC only slightly (14.8 versus 17.2 microM at 37 degrees C). The heat-stable factor (8 micrograms/ml) changed the shape of the activation curve from sigmoidal to hyperbolic, suggesting that the heat-stable factor permits beta-glucosidase to be activated by primary micelles or monomers. The results of gel filtration chromatography and sucrose gradient centrifugation in H2O and D2O revealed that the activation of beta-glucosidase by GM1 was associated with an increase in the size of the enzyme from 45,800 to 178,500 daltons and an increase in the partial specific volume from 0.697 to 0.740 ml/g. The active, reconstituted beta-glucosidase appears to consist of 50% protein and 50% ganglioside (56 molecules/178,500 g). Concentrations of GM1 below the CMC of secondary micelles increased the rate of inactivation of the enzyme by the irreversible inhibitor conduritol B epoxide at 37 degrees C, indicating that GM1 monomers or primary micelles do interact with the enzyme, even though they do not increase the rate of hydrolysis of 4-methylumbelliferyl-beta-D-glucopyranoside by the enzyme.


Factors associated with obesity: a case-control study of young adult Singaporean males.
A case-control study among Singapore Armed Forces' newly enlisted Servicemen was conducted to examine factors associated with male obesity. Four hundred and fifty-nine individuals from the Obese Basic Military Training program were selected as "cases" (average age: 19.5, body mass index: 30.4) and another 340 individuals were selected from the Normal Basic Military Training program as "controls" (average age: 19.3, body mass index: 21.4). Information such as family background, socioeconomic factors, and lifestyle practices were captured using facilitator-led questionnaires. Several variables were significantly associated with obesity after adjustments for possible confounders. These include childhood obesity (odds ratio [OR] = 2.06), less than an hour of exercise per day (OR = 2.97), Indian ethnicity (OR = 2.22), specific education backgrounds (especially that of Institute of Technical Education-OR = 2.75), father's employment at nonmanagerial/professional jobs (OR = 1.52), mother's employment at managerial/professional jobs (OR = 2.02), regular smoking (OR = 1.73) and alcohol consumption (OR = 2.26), 6 hours or less of sleep (OR = 3.73), obesity among family members (OR = 1.86 for mother; OR = 2.98 for siblings), parental history of diabetes mellitus (OR = 2.22 for father; OR = 2.70 for mother), and eating at inexpensive local food stalls (OR = 1.82). Our study found that a number of factors, ranging from personal and family backgrounds to lifestyle choices, were significantly associated with obesity among male youths.


A lateral cephalometric x-ray study of selected vertical dimensions in children with atypical deglutition.
Atypical deglutition (tongue thrust swallowing) has been thought by some to be an etiological factor related to dental malocclusion, especially changes related to excessive increase in vertical facial growth. The purpose of this study was to investigate this possible relationship between atypical deglutition and vertical facial growth by documenting the lower, middle and upper facial areas of children with atypical deglutition. 55 lateral cephalometric radiographs were analyzed and measured in each of two groups of subjects according to standardized facial plane angles between the (I) palatal plane and mandibular plane, (II) palatal plane and occlusal plane, (III) mandibular plane and occlusal plane, (IV) skull base and Frankfurt plane, and (V) mandibular angle. The experimental group was comprised of 55 subjects with atypical deglutition, while 55 subjects with normal swallowing were used as a control group. The linear/angular measurements were subjected to Mann-Whitney statistical test with a significance level of 5%. The average angle of the variables I, II, III and IV are, respectively: 29, 14, 14 and 9 degrees in both groups. There were no significant differences in the variables studied in the normal and atypical swallowing groups. However, for variable V there were 3 degrees of difference between the groups, which was statistically significant. The results of this study suggest that the problem of atypical swallowing may be of functional origin and not associated with anatomical changes seen in vertical growth patterns.


T-cell-rich B-cell lymphoma.
We analyzed 23 cases of T-cell-rich B-cell lymphomas (BCL) to determine if the clinical features are characteristic of a discrete entity. Cases encoded as T-cell-rich BCL in the hematopathology archives of the University of Texas M.D. Anderson Cancer Center between 1988 and 1991 formed the basis of this study. At least 50% of the total population of cells were required to be of T-cell phenotype. Actually, all but one patient had more than 70% T cells in the total population. Sixty-five percent of all cases were referred with other diagnosis such as Hodgkin's mixed cellularity, peripheral T-cell lymphoma (PTCL), or diffuse mixed lymphoma, and had received therapy accordingly. With the exception of splenomegaly, which occurred in 35% of cases, the other clinical characteristics and the response to therapy did not indicate that this entity represents a distinct type of lymphoma. Ann Arbor stage I-II presentations were seen in 10 of 23 (43%) T-cell-rich BCLs. Serum lactate dehydrogenase (LDH) was elevated in eight of 19 patients. Age, sex, and beta 2-microglobulin were not significantly different from classical B-cell large cell lymphoma. The clinical presentation and clinical outcome of T-cell-rich BCL did not differ from that of common B-cell large cell lymphoma, except for the higher proportion of splenomegaly seen in patients with T-cell-rich BCL. The presence of the T-cell-rich infiltrate varied: it frequently was not seen at relapse or at other sites of disease at presentation. It was thus considered an unstable parameter. The major importance of identifying this entity is to distinguish it pathologically from other disorders such as Hodgkin's disease and PTCL, which would be treated in a different manner.


[Analysis of BCRP expression in breast cancer patients].
Breast cancer resistance protein (BCRP, ABCG2) is a xenobiotic half-transporter protein. It is a member of the ATP-binding cassette protein family and functions as an energy-dependent efflux pump. BCRP is involved in multidrug resistance. The study aimed at examining BCRP expression in breast cancers and at defining a relationship between activity of this protein and clinical course of the cancer. We analyzed the expression of BCRP in 101 stage II breast cancer patients. All the patients were diagnosed and treated at the Lower Silesia Oncology Centre (LSOC) between January 1993 and June 1994. After the treatment the patients remained under constant control at LSOC. Mean duration of the observation was 14.2 years (ranging between 9.1 and 16.5 years). Data related to relapse of the disease and deaths were obtained from medical documentation stored in LSOC. The immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against BCRP. The intensity of immunohistochemical reactions with BCRP antibody was evaluated using the semi-quantitative IRS (ImmunoReactive Score) scale, which took into account the intensity of the colour reaction and percentage of positive cells. Results of the immunohistochemical reactions, pathological and of clinical observations were subjected to statistical analysis. Correlations between these factors and BCRP were analyzed using Spearman and Chi2 tests. In order to estimate the survival rate, we used Kaplan Meier statistics, log-rank tests and Cox proportional hazard regression. In our analysis we observed a positive correlation between the expression of the BCRP protein and grade of tumour advancement (r = 0.2 p = 0.03). We found also a negative correlation between the expression of BCRP and the estrogen (r = 0.24 p = 0.02) and progesteron (r = 0.28 p = 0.02) receptors. In a univariate analysis a significantly shorter disease free survival (DFS) and disease specific survival (DSS) was noted in patients with metastases to the lymph nodes (p = 0.003 and p = 0.0006), over the age of 50 years old ((p = 0.02 and p = 0.04) and clearly statistically significant in patients with a high expression of BCRP (p = 0.00044 and p = 0.00005). Overall survival (OS) was shorter in patients over the age of 50 (p = 0.01), with higher stage of the disease - IIB (p = 0.025), with metastases to the lymph nodes (p = 0.003) and also clearly statistically significant in patients with a high expression of BCRP (p = 0.00004). A multivariate analysis allowed to reveal that only higher expression of BCRP and metastases to lymph nodes were typical for cases of DFS (p = 0.,028 and p = 0.00015), DSS (p = 0.00052 and 0.000017) and OS (p = 0.0018 and p = 0.000007) time. We demonstrated that high BCRP expression level is associated with poor survival in early stage breast cancer patients.


Fairness, health, and access.
During the past two years, much of my work at The Hastings Center has explored the implementation of health reform in the United States and its implications for poor and vulnerable groups. These projects include a study of access to care for undocumented patients and one that examines state-level decisions about health reform, including Medicaid expansion and the creation of health insurance "marketplaces." Both raise issues central to bioethics, including fairness, justice, and the stewardship of society's resources. Our nation spent about 2.7 trillion dollars on health care in 2012, and its major public health insurance programs represent over 20 percent of the federal budget. Despite these investments, there are troubling differences in life expectancy, infant mortality, and premature death depending on factors like income, race, ethnicity, gender, and where people live.


On the application of multilevel modeling in environmental and ecological studies.
This paper illustrates the advantages of a multilevel/hierarchical approach for predictive modeling, including flexibility of model formulation, explicitly accounting for hierarchical structure in the data, and the ability to predict the outcome of new cases. As a generalization of the classical approach, the multilevel modeling approach explicitly models the hierarchical structure in the data by considering both the within- and between-group variances leading to a partial pooling of data across all levels in the hierarchy. The modeling framework provides means for incorporating variables at different spatiotemporal scales. The examples used in this paper illustrate the iterative process of model fitting and evaluation, a process that can lead to improved understanding of the system being studied.


Structure and function of the temporomandibular joint disc: implications for tissue engineering.
The temporomandibular joint (TMJ) disc is a little understood structure that, unfortunately, exhibits a plethora of pathologic disorders. Tissue engineering approaches may be warranted to address TMJ disc pathophysiology, but first a clear understanding of structure-function relationships needs to be developed, especially as they relate to the regenerative potential of the tissue. In this review, we correlate the biochemical content of the TMJ disc to its mechanical behavior and discuss what this correlation infers for tissue engineering studies of the TMJ disc. The disc of the TMJ exhibits a somewhat biconcave shape, being thicker in the anterior and posterior bands and thinner in the intermediate zone. The disc, which is certainly an anisotropic and nonhomogeneous tissue, consists almost entirely of type I collagen with trace amounts of type II and other types. In general, collagen fibers in the intermediate zone appear to run primarily in an anteroposterior direction and in a ringlike fashion around the periphery. Collagen orientation is reflected in higher tensile stiffness and strength in the center anteroposteriorly than mediolaterally and in the anterior and posterior bands than the intermediate zone mediolaterally. Tensile tests have shown the disc is stiffer and stronger in the direction of the collagen fibers. Elastin fibers in general appear along the collagen fibers and most likely function in restoring and retaining disc form after loading. The 2 primary glycosaminoglycans of the disc by far are chondroitin sulfate and dermatan sulfate, although their distribution is not clear. Compression studies are conflicting, but evidence suggests the disc is compressively stiffest in the center. Only a few tissue engineering studies of the TMJ disc have been performed to date. Tissue engineering studies must take advantage of existing information for experimental design and construct validation, and more research is necessary to characterize the disc to create a clearer picture of our goals in tissue engineering the TMJ disc.


Language of interview, self-rated health, and the other Latino health puzzle.
We investigated whether the conventional Spanish translation of the self-rated health survey question helps explain why Latinos' self-rated health is worse than Whites' despite more objective health measures showing them to be as healthy as or healthier than are Whites. We analyzed the relationship between language of interview and self-rated health in the Chicago Community Adult Health Study (2001-2003) and the 2003 Behavioral Risk Factor Surveillance System. Being interviewed in Spanish was associated with significantly higher odds of rating health as fair or poor in both data sets. Moreover, adjusting for language of interview substantially reduced the gap between Whites and Latinos. Spanish-language interviewees were more likely to rate their health as fair (regular in Spanish) than as any other choice, and this preference was strongest when compared with categories representing better health (good, very good, and excellent). Our findings suggest that translation of the English word "fair" to regular induces Spanish-language respondents to report poorer health than they would in English. Self-rated health should be interpreted with caution, especially in racial/ethnic comparisons, and research should explore alternative translations.


Budesonide nasal irrigations in the postoperative management of chronic rhinosinusitis.
Nasal steroids play an important role in the postoperative management of patients with chronic rhinosinusitis (CRS). However, commercially available nasal steroid sprays may not deliver adequate amounts of medication to the entire postoperative sinus cavity. The off-label use of budesonide nasal irrigation (BNI) theoretically solves this problem by delivering concentrated steroid solution through a high-pressure, high-volume system. Several studies have attested to the safety of BNI, but there are very few reports of its efficacy. This is a retrospective review of prospectively-collected data. We identified 60 patients who were prescribed BNI postoperatively, but had a lapse in therapy for 1 month or longer. The 20-item Sinonasal Outcomes Test (SNOT-20) and Lund-Kennedy endoscopy scores while the patients were using BNI were compared with scores from the same patients while they were not using BNI. Student paired t test was used for statistical analysis. Thirty patients had eosinophilic chronic rhinosinusitis (eCRS) with polyps (eCRSwNP), 13 had allergic fungal sinusitis (AFS), 13 had Samter's triad (ST), and 4 had eosinophilic chronic rhinosinusitis without polyps (eCRSsNP). Mean follow-up time was 25 months (range, 2-89 months). Overall, SNOT-20 scores were significantly lower with BNI (p < 0.05). On subgroup analysis, SNOT-20 scores were significantly improved with BNI for patients with eCRS and Samter's triad (p = 0.04, 0.03). Endoscopy scores were significantly improved only in the eCRS group (p = 0.02). The addition of BNI is beneficial in the postoperative management of patients with CRS.


The relationship between malnutrition risk and clinical outcomes in a cohort of frail older hospital patients.
Malnutrition has an adverse effect on clinical outcomes and frail older people may be at greater risk of malnutrition. The purpose and aims of this study was to investigate the relationship between markers of malnutrition risk and clinical outcomes in a cohort of frail older hospital patients. 78 frail older hospital patients had the following measurements recorded; length of stay (LOS), time to medical fitness for discharge (TMFFD), body mass index (BMI), malnutrition universal screening tool (MUST) and mini-nutritional assessment short-form (MNA-SF) scores, blood urea, C-reactive protein (CRP), albumin, CRP-albumin ratio; and bioelectrical impedance assessment (BIA) measurements (n = 66). Patients were grouped by mortality status 12 months post hospital admission. Grouping by albumin classification was performed (n = 66) whereby, <30 g/l indicated severe malnutrition, 30-34.9, moderate and >35, low. Receiver-operating characteristic (ROC) curve analysis was performed on variables as potential predictors of mortality. After 12 months, 31% (n = 24) of patients died. LOS was significantly greater in this group (25.0 ± 22.9 vs 15.4 ± 12.7d, P < 0.05). BMI (23.8 ± 4.9 vs 26.4 ± 5.5 kg/m2); fat mass (FM) (17.2 ± 9.9 vs 25.5 ± 10.5 kg), fat mass index (FMI) (9.3 ± 4.1 vs 17.9 ± 2.4 kg/m2); and MNA-SF score (6.6 ± 2.4 vs 8.6 ± 2.7) were significantly lower (P < 0.05), and urea significantly higher (11.4 ± 8.7 vs 8.8 ± 4.4 mmol/l, P = 0.05). Albumin was typically low across the entire group (30.5 ± 5.9 g/l) and a potential relationship was identified between albumin and MNA-SF score. MNA-SF, FM, and FMI were significant predictors of mortality outcome by ROC curve analysis, whereas MUST was a poor predictor. This study highlights a potential relationship between indicators of malnutrition risk and clinical outcomes in frail older hospital patients which should be studied in larger cohorts with an aim to improve patient care.


Immunity to non-dengue flaviviruses impacts dengue virus IgG ELISA specificity in Cambodia.
Seroprevalence studies are the gold standard for disease surveillance, and serology was used to determine eligibility for the first licensed dengue vaccine. However, expanding flavivirus endemicity, co-circulation, and vaccination complicate serology results. Among 713 healthy Cambodian children, a commonly used indirect dengue virus IgG ELISA (PanBio) had a lower specificity than previously reported (94% vs. 100%). Of those with false positive PanBio results, 46% had detectable neutralizing antibodies against other flaviviruses, with the highest frequency against West Nile virus (WNV). Immunity to non-dengue flaviviruses can impact dengue surveillance and potentially pre-vaccine screening efforts.


An automated bayesian framework for integrative gene expression analysis and predictive medicine.
This work constructs a closed loop Bayesian Network framework for predictive medicine via integrative analysis of publicly available gene expression findings pertaining to various diseases. An automated pipeline was successfully constructed. Integrative models were made based on gene expression data obtained from GEO experiments relating to four different diseases using Bayesian statistical methods. Many of these models demonstrated a high level of accuracy and predictive ability. The approach described in this paper can be applied to any complex disorder and can include any number and type of genome-scale studies.


Moderate-to-severe atopic dermatitis in adolescents treated with dupilumab: A multicentre Italian real-world experience.
Moderate-to-severe atopic dermatitis (AD) in the adolescence is a high burden disease, and its treatment can be very challenging due to paucity of approved systemic drugs for this age and their side-effects. Dupilumab was recently approved for treatment of adolescent AD. A multicentre, prospective, real-world study on the effectiveness and safety of dupilumab in adolescents (aged from ≥12 to <18 years) with moderate-to-severe AD was conducted. The main AD clinical phenotypes were also examined. Data of adolescents with moderate-to-severe AD treated with dupilumab at label dosage for 16 weeks were collected. Treatment outcome was assessed by EASI, NRS itch, NRS sleep loss and CDLQI scores at baseline and after 16 weeks of treatment. The clinical scores were also evaluated according to clinical phenotypes. One hundred and thirty-nine adolescents were enrolled in the study. Flexural eczema and head and neck eczema were the most frequent clinical phenotypes, followed by hand eczema and portrait-like dermatitis. Coexistence of more than 1 phenotype was documented in 126/139 (88.5%) adolescents. Three patients (2.1%) contracted asymptomatic SARS-CoV-2 infection and 1 of the discontinued dupilumab treatment before the target treatment period. A significant improvement in EASI, NRS itch, NRS sleep loss and CDLQI was observed after 16 weeks of treatment with dupilumab. This outcome was better than that observed in clinical trials. Dupilumab resulted effective in all AD phenotypes, especially in diffuse eczema. Twenty-eight (20.1%) patients reported adverse events, conjunctivitis and flushing being the most frequent. None of patients discontinued dupilumab due to adverse event. Dupilumab in adolescent AD showed excellent effectiveness at week 16 with consistent improvement of all clinical scores. Moreover, dupilumab showed a good safety profile also in this COVID-19 pandemic era.


Isolation of an algal morphogenesis inducer from a marine bacterium.
Ulva and Enteromorpha are cosmopolitan and familiar marine algal genera. It is well known that these green macroalgae lose their natural morphology during short-term cultivation under aseptic conditions and during long-term cultivation in nutrient-added seawater and adopt an unusual form instead. These phenomena led to the belief that undefined morphogenetic factors that were indispensable to the foliaceous morphology of macroalgae exist throughout the oceans. We characterize a causative factor, named thallusin, isolated from an epiphytic marine bacterium. Thallusin induces normal germination and morphogenesis of green macroalgae.


Conformation and dynamics of soluble repetitive domain elucidates the initial β-sheet formation of spider silk.
The β-sheet is the key structure underlying the excellent mechanical properties of spider silk. However, the comprehensive mechanism underlying β-sheet formation from soluble silk proteins during the transition into insoluble stable fibers has not been elucidated. Notably, the assembly of repetitive domains that dominate the length of the protein chains and structural features within the spun fibers has not been clarified. Here we determine the conformation and dynamics of the soluble precursor of the repetitive domain of spider silk using solution-state NMR, far-UV circular dichroism and vibrational circular dichroism. The soluble repetitive domain contains two major populations: ~65% random coil and ~24% polyproline type II helix (PPII helix). The PPII helix conformation in the glycine-rich region is proposed as a soluble prefibrillar region that subsequently undergoes intramolecular interactions. These findings unravel the mechanism underlying the initial step of β-sheet formation, which is an extremely rapid process during spider silk assembly.


Anti-calculus and whitening toothpastes.
In terms of novel formulations, there seems to have been a shift in emphasis from anti-caries/anti-gingivitis to anti-calculus/whitening toothpastes in recent years. The anti-calculus and whitening effects of toothpastes are to some extent based on the same active ingredients: compounds of high affinity for tooth mineral. Due to this affinity, crystal growth may be hindered (anti-calculus) and chromophores be displaced (whitening). Besides these common ingredients, both types of toothpaste may contain agents specifically aimed at each condition. Clinical studies have shown that these active ingredients can be successfully formulated in fluoride toothpastes to give significant reductions in supragingival calculus and stain formation and facilitate their removal. Some of the ingredients are formulated in toothpastes that additionally contain anti-plaque and anti-gingivitis ingredients, making these toothpastes (together with the fluoride) truly multi-functional. The development of these products is not straightforward because of interaction between formulation components and because the active ingredients must maintain their beneficial characteristics during the shelf life of the paste. Neither a therapeutic benefit (in terms of less gingivitis or less caries) nor a societal benefit (in terms of less treatment demand) has been demonstrated as a result of the anti-calculus and whitening effects of toothpastes.


Pregnane X receptor is associated with unfavorable survival and induces chemotherapeutic resistance by transcriptional activating multidrug resistance-related protein 3 in colorectal cancer.
Although chemotherapy represents a predominant anti-cancer therapeutic modality, drug treatment efficacy is often limited due to the development of resistant tumor cells. The pregnane X receptor (PXR) affects chemotherapeutic effects by regulating targets involved in drug metabolism and transportation, but the regulatory mechanism is poorly understood. Oxaliplatin (L-OHP) content in tumor cells was analyzed by mass cytometry. The roles of PXR on cancer cell proliferation, apoptosis and tumor growth with L-OHP-treated were investigated by MTS, colony formation, flow cytometry and xenograft tumor assays. Luciferase reporter, Chromatin-immunoprecipitation and Site-directed mutagenesis were evaluated the mechanisms. The PXR and multidrug resistance-related protein 3 (MRP3) expressions were examined by western blot, RT-PCR or immunohistochemistry of TMA. Kaplan-Meier and Cox regression were adopted to analyze the prognostic value of PXR in colorectal cancer (CRC). PXR over-expression significantly increased oxaliplatin (L-OHP) transport capacity with a reduction of its content and repressed the effects of L-OHP on tumour cell proliferation and apoptosis. Conversely, PXR knockdown augments L-OHP-mediated cellular proliferation and apoptosis. Moreover, PXR significantly reduced the therapeutic effects of L-OHP on tumor growth in nude mice. Further studies indicated a positive correlation between PXR and MRP3 expression and this finding was confirmed in two independent cohorts. Significantly increased MRP3 expression was also found in PXR over-expressing cell lines. Mechanistically, PXR could directly bind to the MRP3 promoter, activating its transcription. The PXR binding sites were determined to be at -796 to -782bp (CTGAAGCAGAGGGAA) and the key binding sites were the "AGGGA" (-787 to -783bp) on the MRP3 promoter. Accordingly, blockade of MRP3 diminishes the effects on drug resistance of PXR. In addition, PXR expression is significantly associated with poor overall survival and represents an unfavorable and independent factor for male or stage I + II CRC patient prognosis. PXR is a potential biomarker for predicting outcome and activates MRP3 transcription by directly binding to its promoter resulting in an increased L-OHP efflux capacity, and resistance to L-OHP or platinum drugs in CRC. Our work reveals a novel and unique mechanism of drug resistance in CRC.


Quorum quenching bacteria can be used to inhibit the biofouling of reverse osmosis membranes.
Over the last few decades, significant efforts have concentrated on mitigating biofouling in reverse osmosis (RO) systems, with a focus on non-toxic and sustainable strategies. Here, we explored the potential of applying quorum quenching (QQ) bacteria to control biofouling in a laboratory-scale RO system. For these experiments, Pantoea stewartii was used as a model biofilm forming organism because it was previously shown to be a relevant wastewater isolate that also forms biofilms in a quorum sensing (QS) dependent fashion. A recombinant Escherichia coli strain, which can produce a QQ enzyme, was first tested in batch biofilm assays and significantly reduced biofilm formation by P. stewartii. Subsequently, RO membranes were fouled with P. stewartii and the QQ bacterium was introduced into the RO system using two different strategies, direct injection and immobilization within a cartridge microfilter. When the QQ bacterial cells were directly injected into the system, N-acylhomoserine lactone signals were degraded, resulting in the reduction of biofouling. Similarly, the QQ bacteria controlled biofouling when immobilized within a microfilter placed downstream of the RO module to remove QS signals circulating in the system. These results demonstrate the proof-of-principle that QQ can be applied to control biofouling of RO membranes and may be applicable for use in full-scale plants.


The relationships between Ixodes ricinus and small mammal species at the woodland-pasture interface.
Ixodes ricinus, as vector, and small mammals, as reservoirs, are implicated in pathogen transmission between wild fauna, domestic animals and humans at the woodland-pasture interface. The ecological relationship between ticks and small mammals was monitored in 2005 on four bocage (enclosed pastureland) sites in central France, where questing ticks were collected by dragging and small mammals were trapped. Questing I. ricinus tick and small mammal locations in the environment were assessed through correspondence analysis. I. ricinus larval burden on small mammals was modeled using a negative binomial law. The correspondence analyses underlined three landscape features: grassland, hedgerow, and woodland. Seven small mammal species were trapped, while questing ticks were all I. ricinus, with the highest abundance in woodland and the lowest in pasture. The small mammals were overall more abundant in hedgerow, less present in woodland and sparse in grassland. They carried mainly I. ricinus, and secondarily I. acuminatus and I. trianguliceps. The most likely profile for a tick-infested small mammal corresponded to a male wood mouse (Apodemus sylvaticus) in woodland or hedgerow during a dry day. A. sylvaticus, which was the only species captured in grassland, but was also present in hedgerow and woodland, may be a primary means of transfer of I. ricinus larvae from woodland to pasture.


A high-power linear ultrasonic motor using longitudinal vibration transducers with single foot.
A high-power linear ultrasonic motor using longitudinal vibration transducers with single foot was proposed in this paper. The stator of proposed motor contains a horizontal transducer and a vertical transducer. Longitudinal vibrations are superimposed in the stator and generate an elliptical trajectory at the driving foot. The sensitivity analysis of structural parameters to the resonance frequencies of two working modes of the stator was performed using the finite element method. The resonance frequencies of two working modes were degenerated by adjusting the structural parameters. The vibration characteristics of stator were studied and discussed. A prototype motor was fabricated and measured. Typical output of the prototype is a no-load speed of 1160 mm/s and maximum thrust force of 20 N at a voltage of 200 V(rms).


Multiparameter extrapolation of biodistribution data between species.
Values of an inaccessible biological parameter in man may be predicted from values measured in animals by correlating with a parameter accessible in both species, such as body weight, energy production, excretion rate, etc. Predicting toxic effects, from environmental chemicals, of therapeutic doses for drug administration and of radiation absorbed dose from medical and environmental radioactivity depends on the rationalization of relationships between concentration and time when scaling to humans from animal data. For example, the retention of 99mTc, injected intravenously as pertechnetate, reaches 10% in the mouse at about 1 d, but this level occurs in humans at about 7 d. Making a simultaneous transformation between two species for the concentration and time variables by using a method of least-squares fitting, we have derived a series of transformation factors for several species. When correlated with a biological parameter such as body weight, these factors can be used to yield predicted values that are in good agreement with measured values. This system may be used with any related variables, making it useful for predicting other types of biological data.


[Normal killer function in CBA mice as affected by long-term intake of tritium oxide].
A study was made of the cytotoxic function of normal killers of CBA mice during long-term administration of tritium oxide in potable water (a cumulative absorbed dose of 8.7 Gy, dose-rate, 4.5 Gy/day) and at different times after termination of the radionuclide injection. A mean decrease of 20-30% in the lytic effect of the effectors from spleen of the experimental mice on cell-targets of K-562 human erythroleukosis was demonstrated by a 17-19-hour test with 51Cr. At later times after termination of action of tritium oxide, the cytotoxic effect of normal killers increased by 1.8 times as compared to intact controls of the same age.


Involvement of multiple functionally distinct cerebellar regions in visual discrimination: a human functional imaging study.
We investigated the contribution of the human cerebellum to cerebral function during visual discrimination using PET and fMRI. The cognitive task was a successive discrimination of shades of brown with a parametric variation of the stimulus presentation rate and a constant task difficulty. The successive color discrimination task was contrasted to a dimming detection control task, with identical retinal input but with double the number of motor responses. Three sets of activated cerebellar and cerebral regions were observed: rate-dependent and rate-independent color discrimination networks and a motor-and-detection network. The rate-dependent color discrimination network included both an anterior and a posterior activation site in lobule-VI of the two lateral cerebellar hemispheres, whereas the rate-independent network involved a bilateral activation site in lateral Crus-I. Cerebellar sites of the motor-and-detection network were located in medial lobule-V bilaterally, in the vermis, and in posterior left Crus-I and right Crus-II. An additional fMRI study was performed to control for differences in motor output and response timing between the tasks. In this control study, the cerebellar activation sites of the rate-dependent and rate-independent color discrimination networks remained unaltered. The motor-and-detection network included cerebellar activations in posterior left Crus-I and right Crus-II, but none in lobule-V or the vermis. Thus, cerebellar activation sites of the motor-and-detection network could be subdivided into those related to a motor network and those belonging to a dimming detection network. We conclude that successive color discrimination activates multiple, functionally distinct cerebellar regions.


The direction after-effect is a global motion phenomenon.
Prior experience influences visual perception. For example, extended viewing of a moving stimulus results in the misperception of a subsequent stimulus's motion direction-the direction after-effect (DAE). There has been an ongoing debate regarding the locus of the neural mechanisms underlying the DAE. We know the mechanisms are cortical, but there is uncertainty about where in the visual cortex they are located-at relatively early local motion processing stages, or at later global motion stages. We used a unikinetic plaid as an adapting stimulus, then measured the DAE experienced with a drifting random dot test stimulus. A unikinetic plaid comprises a static grating superimposed on a drifting grating of a different orientation. Observers cannot see the true motion direction of the moving component; instead they see pattern motion running parallel to the static component. The pattern motion of unikinetic plaids is encoded at the global processing level-specifically, in cortical areas MT and MST-and the local motion component is encoded earlier. We measured the direction after-effect as a function of the plaid's local and pattern motion directions. The DAE was induced by the plaid's pattern motion, but not by its component motion. This points to the neural mechanisms underlying the DAE being located at the global motion processing level, and no earlier than area MT.


Demonstration of co-resistance of Haemonchus contortus to ivermectin and moxidectin.
Studies were conducted to determine whether organisms which are resistant to ivermectin are also resistant to moxidectin. The mechanisms of action of moxidectin and ivermectin were compared by measuring the changes in membrane conductance they induced in leg muscle fibres of the common shore crab (Pachygrapsus crassipes) by using standard micro-electrode techniques. Meriones unguiculatus (jirds) were infected with ivermectin-resistant or -susceptible strains of Haemonchus contortus, treated with moxidectin or ivermectin at a dose which routinely clears more than 98 per cent of the susceptible strain, and examined for parasite clearance. The results showed that moxidectin induced a rapid loss of membrane resistance in the muscle preparation, and that the effect was almost 50 per cent reversible with the chloride channel-blocker picrotoxinin; this pattern of activity is qualitatively similar to that of ivermectin. In the jird model, moxidectin achieved a clearance of only < or = 47.2 per cent against ivermectin-resistant H contortus at a dose which invariably clears > or = 98 per cent of an ivermectin-susceptible strain. These results indicate that moxidectin and ivermectin share a common mechanism of action, and that organisms that are resistant to ivermectin are also likely to be resistant to moxidectin.


Prevention of pulmonary emboli in a respiratory intensive care unit: efficacy of low-dose heparin.
Ninety-eight patients admitted to our respiratory intensive care unit during a one-year period were compared retrospectively with 99 well-matched patients admitted during a second one-year period. The use of prophylactic low-dose heparin in the second year was associated with a significant decrease in pulmonary emboli documented by ventilation-perfusion scan, pulmonary angiography, and autopsy. No specific bleeding complications could be directly attributed to the use of low-dose heparin. The frequency and severity of gastrointestinal hemorrhage as determined by hemoglobin fall and transfusion requirements were not significantly affected by the prophylactic use of low-dose heparin. Low-dose heparin appears to be effective and safe in respiratory intensive care unit patients in the prevention of pulmonary emboli.


[Differentiation of Mycobacteria].
The lipase, phosphatase, and aryl sulfatase activities of 387 mycobacterial cultures of various species of 4 groups according to Ragnion were studied with the aim of differentiation of these bacteria. Phosphatase activity was shown by M. fortuitum, M. phlei, M. marinum, M. bovis, M. tuberculosis, M. avium, M. intracellulare, and Group III nonphotochromogenic Mycobacteria (according to Ragnion); M. smegmatis and M. thamnopheos negatively reacted to phosphatase; and the cultures of Group II Mycobacteria showed heterogeneous phosphatase activity. M. phlei, M. smegmatis, M. fortuitum, M. scrofulaceum and M. gordonae showed marked lipase activities; M. bovis, M. marinum, M. thamnopheo, M. avium, M. intracellulare, nonphotochromogenous Mycobacteria of Group III, M. terrae and M. gastri were negative. In the rest mycobacterial cultures the lipase activity varied. Only M. fortuitum and some cultures of M. scrofulaceum, M. marinum, M. avium, M. intracellulare and Group II Mycobacteria showed aryl sulfatase activity.


Albinism in the domestic cat (Felis catus) is associated with a tyrosinase (TYR) mutation.
Albino phenotypes are documented in a variety of species including the domestic cat. As albino phenotypes in other species are associated with tyrosinase (TYR) mutations, TYR was proposed as a candidate gene for albinism in cats. An Oriental and Colourpoint Shorthair cat pedigree segregating for albinism was analysed for association with TYR by linkage and sequence analyses. Microsatellite FCA931, which is closely linked to TYR and TYR sequence variants were tested for segregation with the albinism phenotype. Sequence analysis of genomic DNA from wild-type and albino cats identified a cytosine deletion in TYR at position 975 in exon 2, which causes a frame shift resulting in a premature stop codon nine residues downstream from the mutation. The deletion mutation in TYR and an allele of FCA931 segregated concordantly with the albino phenotype. Taken together, our results suggest that the TYR gene corresponds to the colour locus in cats and its alleles, from dominant to recessive, are as follows: C (full colour) > c(b) (burmese) > or = c(s) (siamese) > c (albino).


Antinuclear antibody and HLA-B27 positive uveitis: combination of two diseases?
Anterior uveitis associated with juvenile chronic arthritis concerns two different clinical entities: firstly, antinuclear antibody (ANA) positive patients who have a chronic anterior uveitis with severe complications and often a poor visual prognosis; secondly, usually HLA-B27 positive children, predominantly boys, with unilateral recurrent anterior uveitis. Three patients are described who had a combination of clinical and laboratory features of both diseases. Retrospective clinical and laboratory analysis of three patients. Ocular features in the three patients combined the clinical picture of ANA positive chronic anterior uveitis during early childhood with the clinical features of HLA-B27 unilateral acute anterior uveitis during adolescence. The patients fulfilled the diagnostic criteria of juvenile chronic arthritis, and they had no ankylosing spondylitis. All three patients had the HLA-B*2705 subtype. Whether the association of ANA positive chronic anterior uveitis and HLA-B27 unilateral acute anterior uveitis is a coincidence or represents a distinct clinical entity is not yet clear.


Why is the force-velocity relationship in leg press tasks quasi-linear rather than hyperbolic?
Force-velocity relationships reported in the literature for functional tasks involving a combination of joint rotations tend to be quasi-linear. The purpose of this study was to explain why they are not hyperbolic, like Hill's relationship. For this purpose, a leg press task was simulated with a musculoskeletal model of the human leg, which had stimulation of knee extensor muscles as only independent input. In the task the ankles moved linearly, away from the hips, against an imposed external force that was reduced over contractions from 95 to 5% of the maximum isometric value. Contractions started at 70% of leg length, and force and velocity values were extracted when 80% of leg length was reached. It was shown that the relationship between leg extension velocity and external force was quasi-linear, while the relationship between leg extension velocity and muscle force was hyperbolic. The discrepancy was explained by the fact that segmental dynamics canceled more and more of the muscle force as the external force was further reduced and velocity became higher. External power output peaked when the imposed external force was ∼50% of maximum, while muscle power output peaked when the imposed force was only ∼15% of maximum; in the latter case ∼70% of muscle power was buffered by the leg segments. According to the results of this study, there is no need to appeal to neural mechanisms to explain why, in leg press tasks, the force-velocity relationship is quasi-linear rather than hyperbolic.


Computed tomographic evaluation of Finnhorse cadaver forefeet with radiographically problematic findings on the flexor aspect of the navicular bone.
Computed tomography (CT) was performed on 12 Finnhorse cadaver forefeet with known radiographic changes in the navicular bone (poor corticomedullary junction, irregular appearance of the flexor central eminence, uneven or unequal thickness of the flexor cortex, and/or irregular outline of the proximal or distal flexor margin). The purpose was to confirm the radiographic findings and to investigate if further information of the flexor aspect of the bone could be gained with CT. In CT, the midsagittal outline as well as the internal structure of the bones varied greatly. Different combinations of trabecular and compact bone were seen within the flexor central eminence. Lucencies within the compact bone were commonly present in the proximal half of the eminence, but in five bones lucencies were also identified in the distal half. Due to partial overlapping of the bone and varying bony composition of the eminence, accurate radiographic evaluation of the shape and internal structure of the flexor central eminence was often found to be difficult. The flexor cortex usually appeared to be thinner in CT than in conventional radiographs. Medullary sclerosis and poor flexor corticomedullary junction were commonly overinterpreted radiographically. New bone formation on the proximal flexor margin of the navicular bone was generally visualized in radiographs, but CT allowed also the evaluation of the internal structure of the bone. In one navicular bone, an avulsion fragment on the distal flexor margin was seen in CT images; radiographically this fragment could not be visualized. It was concluded that the flexor aspect of the navicular bone may be difficult to assess reliably with conventional radiography.


Sex differences in the immune response to acute COVID-19 respiratory tract infection.
Sex differences in COVID-19 are increasingly recognized globally. Although infection rates are similar between the sexes, men have more severe illness. The mechanism underlying these sex differences is unknown, but a differential immune response to COVID-19 has been implicated in several recent studies. However, how sex differences shape the immune response to COVID-19 remains understudied. We collected demographics and blood samples from over 600 hospitalized patients diagnosed with COVID-19 from May 24th 2020 to April 28th, 2021. These patients were divided into two cohorts: Cohort 1 was further classified into three groups based on the severity of the disease (mild, moderate and severe); Cohort 2 patients were longitudinally followed at three time points from hospital admission (1 day, 7 days, and 14 days). MultiPlex and conventional ELISA were used to examine inflammatory mediator levels in the plasma in both cohorts. Flow cytometry was conducted to examine leukocyte responses in Cohort 2. There were more COVID+ males in the total cohort, and the mortality rate was higher in males vs. females. More male patients were seen in most age groups (in 10-year increments), and in most ethnic groups. Males with severe disease had significantly higher levels of pro-inflammatory cytokines (IL-6, IL-8, MCP-1) than females; levels of IL-8, GRO, sCD40L, MIP-1β, MCP-1 were also significantly higher in severe vs. mild or control patients in males but not in females. Females had significantly higher anti-inflammatory cytokine IL-10 levels at 14 days compared to males, and the level of IL-10 significantly increased in moderate vs. the control group in females but not in males. At 7 days and 14 days, males had significantly more circulating neutrophils and monocytes than females; however, B cell numbers were significantly higher in females vs. males. Sex differences exist in hospitalized patients with acute COVID-19 respiratory tract infection. Exacerbated inflammatory responses were seen in male vs. female patients, even when matched for disease severity. Males appear to have a more robust innate immune response, and females mount a stronger adaptive immune response to COVID-19 respiratory tract infection.


Halterman Corroles and Their Use as a Probe of the Conformational Dynamics of the Inherently Chiral Copper Corrole Chromophore.
Halterman corroles have been synthesized for the first time from pyrrole and Halterman's aldehyde via Gryko's "water-methanol method". These were derivatized to the corresponding copper complexes and subsequently to the β-octabromo complexes. Electronic circular dichroism spectra were recorded for the enantiopure copper complexes, affording the first such measurements for the inherently chiral Cu corrole chromophore. Interestingly, for a given configuration of the Halterman substituents, X-ray crystallographic studies revealed both P and M conformations of the Cu-corrole core, proving that the substituents, even in conjunction with β-octabromination, are unable to lock the Cu-corrole core into a given chirality. The overall body of evidence strongly indicates a dynamic equilibrium between the P and M conformations. Such an interconversion, which presumably proceeds via saddling inversion, provides a rationale for our failure so far to resolve sterically hindered Cu corroles into their constituent enantiomers by means of chiral HPLC.


Ocular straylight in albinism.
Albinism is an inherited disorder that affects the melanin biosynthesis pathway, which results in reduced or absent pigment formation. This may lead to increased light transmission through the iris and more reflected light from the fundus. Both these effects contribute to the occurrence of ocular straylight. One aim of this study is to determine whether and how increased iris transmission and fundus reflection in subjects with albinism contributes to the occurrence of ocular straylight. The other aim is to determine the effect that an iris print-contact lens (CL) could have in terms of reducing the occurrence of ocular straylight. Ocular straylight was quantified by means of the straylight parameter s and measured as a function of angle and wavelength in 17 subjects with different types of albinism, none of whom wore an iris print-CL. The measurements were then repeated with the subjects wearing an iris print-CL to reduce the iris transmission component and thus the occurrence of ocular straylight. The contributions of transmission and reflectance components were estimated for each individual. Straylight level increase varied from normal (s ≈9) to severe (8x). In 15 cases, the reflectance component contributed s >3 to up to s = 17. In eight cases, the transmission component contributed s >3 to up to s = 101. A significant reduction in straylight was observed using an iris print-CL in six subjects with elevated straylight values. In the other 11 subjects with albinism, the iris print-CL had no significant effect on straylight because of the low values of the transmission component. This study gives insight into the effects of transmission and reflectance on the total measured straylight occurrence in subjects with albinism. Subjects experiencing increased ocular straylight values may benefit significantly from wearing iris print-CLs because transmission of light through the natural iris may cause a significant increase in straylight.