Single-shot noninvasive imaging through scattering medium under white-light illumination.
We experimentally investigate image reconstruction through a scattering medium under white-light illumination. To solve the inverse problem of noninvasive scattering imaging, a modified iterative algorithm is employed with an interpretable constraint on the optical transfer function (OTF). As a result, a sparse and real object can be retrieved whether it is illuminated with a narrowband or broadband light. Compared with the well-known speckle correlation technique (SCT), the proposed method requires no restrictions on the speckle autocorrelation and shows a potential advantage in scattering imaging.


Does Limiting Allowable Rating Variation in the Small Group Health Insurance Market Affect Employer Self-Insurance?
The Affordable Care Act (ACA) imposes adjusted community rating in the small group market, which employers can avoid by self-insuring, raising concerns about adverse selection. We evaluate the impact of limiting allowable rating variation on employer self-insurance across industries with varied health risk, using cross-state variation in pre-ACA rating regulations, the nationally-representative 2008-2013 KFF/HRET Employer Health Benefits survey, and a triple-difference regression approach. We find that lower-risk employers subject to laws limiting allowable premium rating variation have a predicted probability of self-insurance that is about 18 percentage points higher than otherwise-similar higher-risk employers, suggesting that these selection concerns are warranted.


The protein burden of lac operon products.
A new approach to measuring the slowing of growth due to the manufacture of proteins not needed by a bacterium is presented. An entire single colony of Escherichia coli was used to start a chemostat culture that was then given a selective pressure by the addition of phenylgalactoside (phi-gal). This enriched the population for constitutive mutants that produced beta-galactosidase without induction and could split phi-gal, consume the galactose, and grow faster. When the phi-gal was removed, the constitutives grew slower than the parental strain and were gradually lost. This procedure allows competition experiments to be carried out with minimum effects due to genetic drift. Experiments with both strains having wild-type and mutant permease genes were conducted. With the former the selective disadvantage was initially much greater than expected from the simplest hypothesis that extra unused proteins would slow growth in proportion to their fraction of the total protein synthesis. This phase was followed by a second phase where the selective disadvantage was smaller than predicted by this simple hypothesis. With a very slowly reverting permease negative strain the selective disadvantage, and therefore the protein burden, was found to be much smaller and not statistically different from zero. Thus, while one would expect under carbon and energy limitation in the chemostat the protein burden to be larger than under unlimited conditions, it is so small that even the refined technique used here could not measure it accurately. It is certainly less than the fraction of 'waste' protein synthesis; but it could be between zero and the fraction of the cells' energy and carbon budget spent on manufacture of the proteins of the lac operon.


SEROLOGICAL GROUPING OF THE PATHOGENIC CLOSTRIDIA.
Ellner, Paul D. (University of Vermont, Burlington), and Stanley S. Green. Serological grouping of the pathogenic clostridia. J. Bacteriol. 86:1098-1100. 1963.-By use of the soluble antigens of ten species of pathogenic clostridia and specific globulins, it has been possible to divide these organisms into a number of groups based upon the presence or absence of precipitin lines in agar gel. A scheme for such a grouping is presented, and the utility of this method is discussed.


Complicated infantile hemangioma of the lip: outcomes of early versus late resection.
Lip hemangiomas have traditionally been approached with expectant management. However, intervention is warranted for associated complications, including facial disfigurement, feeding difficulties, speech impairment, and psychosocial manifestations. The authors evaluated outcomes of complicated lip hemangiomas resected during the proliferative as compared with the involutional phase. A retrospective review of patients with complicated lip hemangiomas managed with resection in the proliferative or involutional phase from 2005 to 2011 was performed. A transverse elliptical vermilion-mucosal resection technique was used. Review parameters included demographics, lesion size and location, growth phase, hemangioma-related complications, and preoperative management (corticosteroid or pulsed dye laser). Evaluated outcomes included surgical complications, recurrence, and patient- and surgeon-reported aesthetics. Twenty-one patients underwent surgical resection of a lip hemangioma (10 proliferative and 11 involutional), with a mean follow-up of 21.4 and 23.3 months, respectively. The two groups were comparable with respect to lesion size and location. Patients in the involutional group experienced higher rates of hemangioma-related complications (bleeding, 45 percent versus 10 percent; speech impairment, 82 percent versus 0 percent; feeding difficulties, 82 percent versus 20 percent; and psychosocial issues, 100 percent versus 80 percent). There were no postoperative aesthetic concerns. One recurrence in the proliferative group was treated with reresection. Speech therapy was required for 82 percent of patients in the involutional group. Surgical resection is efficacious treatment for hemangiomas of the lip and yields acceptable aesthetic results during both the proliferative and involutional phases. Resection in the proliferative phase should be considered to prevent complications associated with delayed treatment.


Regulation of substrate oxidation in isolated myocardial cells by beta-hydroxybutyrate.
The role of ketone bodies in myocardial substrate oxidation was examined using freshly isolated Ca2+-tolerant heart myocytes, beta-hydroxybutyrate (beta OHB) inhibited lactate oxidation by the myocytes by 30-60%, and the inhibition was concentration dependent. Palmitate oxidation was also markedly decreased, whereas octanoate oxidation was only minimally affected by the presence of beta OHB. Lactate, octanoate, or palmitate had little, if any, effect on beta OHB oxidation. beta OHB oxidation was reduced by 22-28% in myocytes isolated from chronically diabetic rats, whereas the oxidation of palmitate remained similar to the controls. However, beta OHB still inhibited palmitate oxidation to the same extent as in the control cells. Our data support the role of beta OHB as a physiologic regulator of myocardial substrate metabolism.


Potential health impact of strong tobacco control policies in 11 South Eastern WHO European Region countries.
While some WHO European Region countries are global tobacco control leaders, the South Eastern region of Europe has the highest tobacco smoking prevalence globally and a relatively low level of overall implementation of the WHO Framework Convention on Tobacco Control (WHO FCTC). An abridged version of SimSmoke has been developed to project the health impact of implementing tobacco control policies in line with the WHO FCTC. Data on population size, smoking prevalence, policy-specific effect sizes and formulas were applied in 11 South Eastern WHO European Region countries [Albania, Bosnia and Herzegovina (the Federation of Bosnia and Herzegovina and the Republika Srpska), Bulgaria, Croatia, Israel, Montenegro, Republic of Moldova, Romania, Serbia, Slovenia and the former Yugoslav Republic of Macedonia] to project the relative reduction in smoking prevalence, number of smokers and number of smoking-attributable deaths resulting from implementing individual and/or combined six WHO FCTC measures. For all countries, an increase in excise cigarette taxes to 75% of price yields the largest relative reduction in smoking prevalence (range 8-28%). The projections show that within 15 years smoking prevalence can be reduced by at least 30% in all countries when all six tobacco control measures are fully implemented in line with the WHO FCTC. The projections show that large health effects can be achieved and the results can be used as an advocacy tool towards acceleration of the enforcement of tobacco control laws in WHO European Region countries.


Aberrant Forkhead box O1 function is associated with impaired hepatic metabolism.
FoxO1 plays an important role in mediating the effect of insulin on hepatic metabolism. Increased FoxO1 activity is associated with reduced ability of insulin to regulate hepatic glucose production. However, the underlying mechanism and physiology remain unknown. We studied the effect of FoxO1 on the ability of insulin to regulate hepatic metabolism in normal vs. insulin-resistant liver under fed and fasting conditions. FoxO1 gain of function, as a result of adenovirus-mediated or transgenic expression, augmented hepatic gluconeogenesis, accompanied by decreased glycogen content and increased fat deposition in liver. Mice with excessive FoxO1 activity exhibited impaired glucose tolerance. Conversely, FoxO1 loss of function, caused by hepatic production of its dominant-negative variant, suppressed hepatic gluconeogenesis, resulting in enhanced glucose disposal and improved insulin sensitivity in db/db mice. FoxO1 expression becomes deregulated, culminating in increased nuclear localization and accounting for its increased transcription activity in livers of both high fat-induced obese mice and diabetic db/db mice. Increased FoxO1 activity resulted in up-regulation of hepatic peroxisome proliferator-activated receptor-gamma coactivator-1beta, fatty acid synthase, and acetyl CoA carboxylase expression, accounting for increased hepatic fat infiltration. These data indicate that hepatic FoxO1 deregulation impairs the ability of insulin to regulate hepatic metabolism, contributing to the development of hepatic steatosis and abnormal metabolism in diabetes.


The use of Ocimum americanum essential oil against the pathogens Aeromonas hydrophila and Gyrodactylus sp. in silver catfish (Rhamdia quelen).
The bactericidal activity (minimum inhibitory concentration (MIC)-test) of Ocimum americanum (inflorescences) essential oil (OAEO) against Aeromonas hydrophila was determined in this study. Also investigated was the potential of OAEO and the main compound found in the oil (linalool) at subinhibitory concentrations to be inhibitors of haemolysis caused by Aer. hydrophila in fish erythrocytes. An in vivo experiment was conducted to evaluate the survival of fish (Rhamdia quelen) experimentally infected with Aer. hydrophila and exposed to OAEO. A second experiment was conducted to evaluate the in vitro and in vivo activity of OAEO (mix from inflorescences and leaves) against the parasite Gyrodactylus sp. The OAEO showed weak in vitro activity against Aer. hydrophila (6400 μg ml(-1) ). Subinhibitory concentrations of OAEO (100 μg ml(-1) ) inhibited haemolysis (90%) caused by Aer. hydrophila in fish erythrocytes, however, linalool did not inhibit haemolysis activity. At the low concentrations (10 and 20 mg l(-1) ) added to the water, OAEO promoted the survival of fish experimentally infected with Aer. hydrophila. Lastly, the OAEO mix (50 mg l(-1) ) was effective against Gyrodactylus sp., significantly reducing (60%) the number of parasites in the fish. Phytochemicals, such as essential oils (EOs) are a great source of new molecules and have shown potential to be used in aquaculture systems. However, additional studies focused on the in vivo efficacy, mode of action and identification of the active compounds are needed. This study determined the potential of Ocimum americanum EO for use against two important fish pathogens, Aeromonas hydrophila and Gyrodactylus sp., as well as providing preliminary information about the role of the main EO compound (linalool) against Aer. hydrophila virulence.


Association of serum Gasdermin D with anti-N-methyl-D-aspartate receptor encephalitis.
Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is an autoimmune disease of the central nervous system. Gasdermin D (GSDMD) is associated with autoimmune disorders and neuroinflammatory disorders, but its role in anti-NMDAR encephalitis is unclear. In this study, we measured serum levels of GSDMD in 42 patients with anti-NMDAR encephalitis and 25 healthy controls. Of the 42 patients, 17 had follow-up evaluation of GSDMD levels and modified Rankin scale (mRS) scores at 3 months. Association of GSDMD with anti-NMDAR encephalitis and its clinical parameters were evaluated. Serum GSDMD levels were significantly higher in patients with anti-NMDAR encephalitis than in healthy controls (p = 0.002, padjusted = 0.009), especially in males (p = 0.001, padjusted = 0.022). This was also evident in patients with severe impairment (mRS >3 vs mRS ≤3; p < 0.001). Serum GSDMD was associated with mRS before and after adjustment for age and gender (r = 0.440 and 0.430, p = 0.004 and 0.006, respectively) as well as serum CH50 (r = -0.419 and -0.426, p = 0.011 and 0.012, respectively). Furthermore, 3-month follow-up evaluation revealed that after treatment, anti-NMDAR encephalitis patients had significantly decreased serum GSDMD levels (p = 0.007) and significantly decreased mRS scores (p = 0.002) compared with before treatment. Furthermore, the changes in mRS scores were negatively associated with changes in GSDMD levels, although the associations were not significant (r = -0.222, p = 0.393). Our findings show that serum GSDMD levels are elevated in anti-NMDAR encephalitis and are associated with disease prognosis.


Tricuspid Regurgitation in Congestive Heart Failure: Management Strategies and Analysis of Outcomes.
Tricuspid regurgitation is a notable aspect of congestive heart failure and is linked with worse outcomes if untreated. Functional tricuspid regurgitation commonly is seen in patients with heart failure, particularly in patients presenting for surgical management, such as those for mechanical cardiac assist device implantation. This review aims to study the published data related to the surgical management of tricuspid regurgitation in the cardiac surgical population comprehensively.


A non-parametric model: free analysis of actigraphic recordings of acute insomnia patients.
Both parametric and non-parametric approaches to time-series analysis have advantages and drawbacks. Parametric methods, although powerful and widely used, can yield inconsistent results due to the oversimplification of the observed phenomena. They require the setting of arbitrary constants for their creation and refinement, and, although these constants relate to assumptions about the observed systems, it can lead to erroneous results when treating a very complex problem with a sizable list of unknowns. Their non-parametric counterparts, instead, are more widely applicable but present a higher detrimental sensitivity to noise and low density in the data. For the case of approximately periodic phenomena, such as human actigraphic time series, parametric methods are widely used and concepts such as acrophase are key in chronobiology, especially when studying healthy and diseased human populations. In this work, we present a non-parametric method of analysis of actigraphic time series from insomniac patients and healthy age-matched controls. The method is fully data-driven, reproduces previous results in the context of activity offset delay and, crucially, extends the concept of acrophase not only to circadian but also for ultradian spectral components.


Selective surgical localization of axillary lymph nodes containing metastases in patients with breast cancer: a prospective feasibility trial.
Nodal ultrasonography with needle biopsy of abnormal lymph nodes helps to define the extent of breast cancer before neoadjuvant chemotherapy. A clip can be placed to designate lymph nodes with documented metastases. Targeted axillary dissection or selective removal of lymph nodes known to contain metastases (clip-containing nodes) as well as sentinel lymph nodes (SLNs) may provide more accurate assessment of the pathologic response after neoadjuvant chemotherapy. To determine the feasibility of image-guided localization and resection of lymph nodes containing known metastases. This prospective feasibility trial performed at MD Anderson Cancer Center, Houston, Texas, included 12 patients with axillary nodal metastases confirmed by results of fine-needle aspiration biopsy who had a clip placed in the lymph node targeted for biopsy from December 1, 2012, through November 30, 2013. Preoperative targeting of the clip-containing lymph node under ultrasonographic guidance consisting of wire localization in 2 patients and placement of radioactive iodine I 125 (125I)-labeled seeds in 10 patients. Surgeons removed the localized lymph node before completion axillary lymph node dissection and used radiography of the specimen to confirm removal of the clip-containing lymph node and seed. Confirmation of the removal of the clip-containing lymph node. Image-guided localization and selective removal were successful in all 12 patients. Five patients underwent SLN dissection in addition to removal of the clip-containing lymph node. Placement of 125I seeds did not interfere with lymphoscintigraphy or intraoperative identification of SLNs. In 4 of the 5 patients (80%), the clip-containing lymph node was one of the SLNs. Ten patients completed neoadjuvant chemotherapy before surgery. Of the 9 patients who underwent lymph node dissection, 4 (44%) had residual nodal disease after chemotherapy; all had disease identified in the clip-containing lymph node. Axillary lymph nodes marked with a clip can be localized and selectively removed to accomplish targeted axillary dissection, which is technically possible after chemotherapy and is easily performed with other axillary surgery, such as SLN dissection. The ability to add selective removal of the clip-containing lymph nodes to SLN dissection may identify patients for limited nodal surgery after chemotherapy with increased accuracy for determining residual disease compared with SLN identification alone.


Molecular Networking-Driven Discovery of Antibacterial Perinadines, New Tetracyclic Alkaloids from the Marine Sponge-Derived Fungus Aspergillus sp.
Two rare tetracyclic skeleton alkaloids named perinadines B and C (1 and 2) were isolated as mixtures of epimers from the marine-derived Aspergillus sp. LS116 driven by molecular networking. The planar structures of 1 and 2 were characterized by comprehensive spectroscopic data. Additionally, compounds 1 and 2 showed moderate in vitro antibacterial activity against Bacillus subtilis with minimum inhibitory concentration values of 32 and 64 μg/mL, respectively. Besides, both of the compounds were evaluated for anti-inflammatory activities in an in vivo zebra fish model.


Assessing the educational value and content of YouTube videos for ultrasound-guided subclavian vein catheterization.
The European Society of Anaesthesiology (ESA) published a guideline regarding continuous ultrasound guidance for central venous catheters in 2020. YouTube has been a popular educational platform since its inception. The purpose of the present study was to evaluate the adequacy of videos on ultrasound-guided subclavian vein catheterization posted on YouTube based on this guideline. YouTube was scanned using the keywords associated with ultrasound-guided subclavian vein catheterization and 46 of the 106 most-watched videos were included in the study. The videos were divided into three groups, as individual, manufacturer, and academic according to their sources, and were evaluated as poor, satisfactory, and good in terms of the overall content. The videos were then evaluated based on ESA's six-title guide for more specific informational content. A total of 46 videos were reviewed and 52.2% (n = 24) were found to be prepared by individuals. Among the videos, the rate of videos describing only venipuncture (poor) was 23.9% (n = 11), 73.9% (n = 34) of videos described the verification of the guidewire location with venipuncture, and 2.2% of videos described all the recommendations suggested by the guide (n = 1). At the end of the catheterization procedure, 4.3% (n = 2) stated that the catheter location should be confirmed by using ultrasound, 15.2% (n = 7) recommended chest-X-ray, and 80.4% (n = 37) did not suggest any. Manufacturer and academic videos can be watched due to their high-quality scores, but it may be practical to prepare training videos with guidelines both for educators and students to have global access to the renewed guideline information.


The RASSF1A tumor suppressor.
RASSF1A (Ras association domain family 1 isoform A) is a recently discovered tumor suppressor whose inactivation is implicated in the development of many human cancers. Although it can be inactivated by gene deletion or point mutations, the most common contributor to loss or reduction of RASSF1A function is transcriptional silencing of the gene by inappropriate promoter methylation. This epigenetic mechanism can inactivate numerous tumor suppressors and is now recognized as a major contributor to the development of cancer. RASSF1A lacks apparent enzymatic activity but contains a Ras association (RA) domain and is potentially an effector of the Ras oncoprotein. RASSF1A modulates multiple apoptotic and cell cycle checkpoint pathways. Current evidence supports the hypothesis that it serves as a scaffold for the assembly of multiple tumor suppressor complexes and may relay pro-apoptotic signaling by K-Ras.


Zebrafish orthopedia (otp) is required for isotocin cell development.
Several behavioral and physiological processes such as social, sexual, and maternal behaviors, learning and memory, and parturition are influenced by the neurohypophysial peptide oxytocin. Studies in knockout mice have identified four transcriptional regulatory genes that are required for oxytocin neuronal development in the hypothalamus. These are the basic helix-loop-helix PAS genes Single-minded 1 (Sim1) and Arylhydrocarbon receptor nuclear translocator 2 (Arnt2), the POU homeobox gene Pou3f2, and the paired homeobox gene Orthopedia (Otp). Overall, however, the molecular control of oxytocin cell development is poorly understood. Studies in zebrafish provide a complementary view to mouse knockout experiments and facilitate understanding of neuroendocrine cell development. Isotocin, which is orthologous to oxytocin, is expressed early in the developing zebrafish brain. In this paper we show that zebrafish otp mRNA expression in the embryonic forebrain is dynamic and complex, and that it overlaps with isotocin expression in the dorsal preoptic area. Additionally, these studies demonstrate that otp is required for isotocin cell development. Evidence is also provided that otp and sim1 function in parallel to direct the differentiation of isotocin cells, and that otp is unlikely to affect brain patterning. Overall, these studies support the hypothesis that the role of otp in zebrafish neuroendocrine cell development is evolutionarily conserved with that of mammals.


Bile acids and their signaling pathways: eclectic regulators of diverse cellular functions.
The field of bile acids has witnessed an impulse in the last two decades. This has been the result of cloning the genes encoding enzymes of bile acid synthesis and their transporters. There is no doubt that the identification of Farnesoid X Receptor (FXR, NR1H4) as the bile acid receptor has contributed substantially to attract the interest of scientists in this area. When FXR was cloned by Forman et al. [1], farnesol metabolites were initially considered the physiological ligands. After identifying FXR and other nuclear receptors as bile acid sensors [2-4], it has become clear that bile acids are involved in the regulation of lipid and glucose metabolism and that these molecules are eclectic regulators of diverse cellular functions. In this review, we will summarize the current knowledge of the functions regulated by bile acids and how their physiological receptors mediate the signaling underlying numerous cellular responses.


TNFAIP3 F127C Coding Variation in Greek Primary Sjogren's Syndrome Patients.
Tumor necrosis factor, alpha-induced protein 3 (TNFAIP3) gene encodes the A20 protein, an important negative feedback regulator of the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) pathway. A coding TNFAIP3 variant, namely rs2230926, has been previously linked to B cell non-Hodgkin's lymphoma (NHL) development in patients with Sjogren's syndrome (SS) of French and UK origin. Herein, we aimed to determine the prevalence of rs2230926 in a Greek primary SS cohort and explore possible associations with disease characteristics. The rs2230926 gene variant was genotyped in 327 primary Greek SS patients (ninety-one complicated by NHL (SS-lymphoma)) and 448 Greek healthy controls (HC) of similar age and sex distribution. Clinical and laboratory characteristics were also recorded and gene expression of relevant genes of the NF-κB pathway was quantitated by real-time PCR in available whole peripheral blood (PB) from 165 primary SS patients. Increased prevalence of the rs2230926 mutant variant was detected in both SS-lymphoma and SS-nonlymphoma subgroups compared to HC (8.8% vs. 7.6% vs. 3.6%, p values: 0.04 and 0.03, respectively) in association with higher IgM, LDH serum levels, and PB Bcl-XL transcripts but lower leucocyte and neutrophil counts. Of interest, approximately one-fifth of SS-lymphoma cases with age at disease onset ≤ 40 years carried the rs2230926 variant (18.2% vs. 3.6%, OR 95% (CI): 6.0 (1.8-19.8), p value: 0.01). We postulate that deregulation of the NF-κB pathway as a result of the TNFAIP3 rs2230926 aberration increases SS and SS lymphoma susceptibility particularly in patients with early disease onset.


Effects of dietary curcumin supplementation on seminal quality indices and fertility rate in broiler breeder roosters.
1. Decreased semen quality is an underlying contributor to age-related subfertility in broiler breeder roosters. This study investigated the effects of dietary curcumin (derived from turmeric) supplementation as an antioxidant source on semen quality and fertility in broiler breeder roosters. 2. Twenty-eight Ross 308 roosters were randomly allotted to four groups with seven birds in each and were fed a standard diet supplemented with different levels of curcumin at 0 (C0), 10 (C10), 20 (C20) and 30 (C30) mg/bird per day from 48 through to 61 weeks of age. Body weight and semen quality traits were evaluated on a weekly basis and seminal concentrations of malondialdehyde (MDA) as a measure of antioxidation status were quantified at one-week intervals during the first 11 weeks of the trial (48-59 weeks of age). Semen samples from last 2 weeks (60 and 61 weeks of age) were used to artificially inseminate to assess the sperm-egg penetration (SP) in perivitelline membrane and fertility rates. 3. Except for body weight and ejaculate volume, other characteristics, including semen concentration, total sperm production, progressive motility and plasma membrane integrity were linearly improved by the increasing levels of curcumin supplementation (P < 0.01). However, dietary curcumin levels were linearly and quadratically associated with decreased seminal concentration of MDA (P < 0.01 and P < 0.03), percentage of abnormal sperm (P < 0.01 and P < 0.07) and increased plasma membrane functionality (P < 0.01 and P < 0.04), respectively. The SP holes in perivitelline membrane were increased in a linear and quadratic manner in response to increasing levels of curcumin (P < 0.01). Moreover, fertility rate was linearly improved (P < 0.01) as the dosage of curcumin increased, and resulted in 8, 12 and 14% improvements in the birds fed C10, C20 and C30, compared to C0, respectively. 4. In conclusion, the results showed that increasing levels of dietary supplementation of curcumin was associated with beneficial effects on semen quality indices and fertility rate in aged broiler breeder roosters.


Software development, nomenclature schemes, and mapping strategies for an international pediatric cardiac surgery database system.
The field of congenital heart surgery has the opportunity to create the first comprehensive international database for a medical subspecialty. An understanding of the demographics of congenital heart disease and the rapid growth of computer technology leads to the realization that creating a comprehensive international database for pediatric cardiac surgery represents an important and achievable goal. The evolution of computer-based data analysis creates an opportunity to develop software to manage an international congenital heart surgery database and eventually become an electronic medical record. The same database data set for congenital heart surgery is now being used in Europe and North America. Additional work is under way to involve Africa, Asia, Australia, and South America. The almost simultaneous publication of the European Association for Cardio-thoracic Surgery/Society of Thoracic Surgeons coding system and the Association for European Paediatric Cardiology coding system resulted in the potential for multiple coding. Representatives of the Association for European Paediatric Cardiology, Society of Thoracic Surgeons, European Association for Cardio-thoracic Surgery, and European Congenital Heart Surgeons Foundation agree that these hierarchical systems are complementary and not competitive. An international committee will map the two systems. The ideal coding system will permit a diagnosis or procedure to be coded only one time with mapping allowing this code to be used for patient care, billing, practice management, teaching, research, and reporting to governmental agencies. The benefits of international data gathering and sharing are global, with the long-term goal of the continued upgrade in the quality of congenital heart surgery worldwide.


An in situ tensile tester for studying electrochemical repassivation behavior: fabrication and challenges.
An in situ tensile rig is proposed, which allows performing electrochemical (repassivation) experiments during dynamic mechanical testing of wires. Utilizing the basic components of a conventional tensile tester, a custom-made minitensile rig was designed and fabricated. The maximal force that can be measured by the force sensor is 80 N, with a sensitivity of 0.5 mV/V. The maximum travel range of the crosshead induced by the motor is 10 mm with a minimum step size of 0.5 nm. The functionality of the tensile test rig was validated by investigating Cu and shape memory NiTi wires. Wires of lengths between 40 and 50 mm with varying gauge lengths can be tested. An interface between wire and electrochemical setup (noncontact) with a smart arrangement of electrodes facilitated the electrochemical measurements during tensile loading. Preliminary results on the repassivation behavior of Al wire are reported.


Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference. October 14-17, 2010, Cascais, Portugal.
The Mechanisms of Cell Death and Disease: Advances in Therapeutic Intervention and Drug Discovery--ESH's Eighth International Conference, held in Cascais, Portugal, included topics covering new therapeutic developments in the field of cell death and cancer. This conference report highlights selected presentations on inhibiting the inhibitor of apoptosis (IAP) proteins, activating death receptors (DRs), and targeting ubiquitins and the Bcl-2 family. Investigational drugs discussed include LCL-161 (Novartis) and navitoclax (Abbott Laboratories/Genentech).


Gray matter asymmetries in chimpanzees as revealed by voxel-based morphometry.
Determination of whether nonhuman primates exhibit neuroanatomical asymmetries would inform our understanding of the evolution of traits in humans that show functional hemispheric dominance, including language and handedness. Here we report the first evidence of population-level asymmetries in the chimpanzee neocortex using voxel-based morphometry (VBM). MRI scans of the brain were collected in a sample of 31 chimpanzees including 9 males and 22 females, and the resulting images were segmented into gray matter, white matter and CSF. Gray matter images were then co-registered to a template and these normally oriented volumes were flipped on the left-right axis to create mirror volumes. In total, significant asymmetries were found in 13 regions including several that have been described previously in great apes using traditional region-of-interest approaches. The results from this VBM analysis support previous reports of hemispheric lateralization in chimpanzees and reinforce the view that asymmetries in the central nervous system are not uniquely human.


The Associations between Body Mass Index of Seven- and Eight-Year-Old Children, Dietary Behaviour and Nutrition-Related Parenting Practices.
Background and objective: Body mass index (BMI) is one of the key indicators used to measure the growth of children. It could be affected by the children's nutrition, which is essential for the proper development of the child. Nutrition of children could be affected by many environmental factors, for example, the socioeconomic environment of the family. The aim of this study was to identify the associations between the BMI of seven- and eight-year-old children, dietary behaviour and nutrition-related parenting practices. Materials and Methods: The study was carried out as part of the World Health Organization European Childhood Obesity Surveillance Initiative (WHO COSI). Data were collected using two instruments: objective anthropometric measurements and a questionnaire. The target participant group was 3969 Lithuanian first-formers. Factor analysis was used to summarise questions from the family form. Linear regression analysis was used to identify the associations between various factors and the BMI value of the children. The association between two groups of factors was analysed using Spearman correlation. Results: Factors of dietary behaviour like unhealthy food and proteins were significantly positively associated with BMI in children, while consumption of plant-based, dairy and confectionery items was significantly negatively associated with BMI. Factors of nutrition-related parenting practices like control of unhealthy food, food as a reward or punishment, and mealtime were significantly positively associated with BMI, while encouragement, pressure to eat, and liberal attitude were significantly negatively associated with BMI. The strongest associations were between control of unhealthy food and unhealthy food; cost of and preferences for food and plant-based food; variety of food and proteins; variety of food and plant-based food compared to other associations. Conclusions: The dietary behaviour and nutrition-related parenting practices were associated with BMI in children.


An interdisciplinary approach to mobility and safety education for caregivers and stroke patients.
A cerebrovascular accident (CVA), or stroke, often results not only in hemiplegia, but also in cognitive and perceptual impairments as well. The hemiplegia causes obvious problems with mobility, while cognitive and perceptual impairments might interfere with and delay progress in therapy. Physiotherapists and occupational therapists have extensive knowledge and training regarding the intricacies of movement and mobility. Unfortunately, little emphasis is given to these areas in most nursing programs; yet nurses spend the most time with hospitalized clients, providing 24-hour care. As stroke patients tend to learn by repetition, a consistent rehabilitation program is essential, especially with respect to mobility and safety education. It is important for the rehabilitation nurse to be knowledgeable regarding mobility techniques to prevent back injury to the caregiver and to reduce the degree of risk of injury to the patient.


Surgical management of chronic hyperplastic candidiasis refractory to systemic antifungal treatment.
Chronic hyperplastic candidiasis (CHC), earlier known as candidal leukoplakia, is a variant of oral candidiasis that classically presents as a white patch on the commissures of the oral mucosa and it is mostly caused by Candida albicans. Clinically, the lesions are usually asymptomatic and regress after appropriate antifungal therapy and correction of the underlying cause. If the lesions are untreated, a small portion may develop dysplasia and later progress into carcinoma. The purpose of this article is to report a case of CHC in a 57-year-old male patient with a significant smoking habit, who presented with a thick, nonscrapable, brownish-white coating on the dorsum of the tongue for 9 years. This case is of particular importance and concern because of the high risk for malignant transformation in CHC. The role of biopsy and histopathology is also stressed through this case report in arriving at a definitive diagnosis and treatment planning. Further, this case is interesting because it was refractory to local and systemic antifungal treatment and so, surgery was chosen as an alternative treatment modality considering the side effects of the prolonged use of antifungal drugs.


Analyzing individual status and change with hierarchical linear models: illustration with depression in college students.
A recently developed class of multilevel or hierarchical linear models (HLM) provides an intuitive and efficient way to estimate individual growth or change curves. The approach also models the between-subjects variation of the individual change curves with treatment factors and individual attributes. Unlike other repeated measures analysis methods common in the behavioral sciences, HLM allows the fit of data with unequal numbers of repeated observations for each subject, variable timing of observations, and missing data, features which are often characteristic of data from field studies. The application of HLM for the analysis of repeated psychological measures is discussed and illustrated here with depression data for college students. Strengths and limitations of the approach are discussed.


[Applications of verbal dichotic listening in neurological and neuropsychiatric clinical practice].
To review the most recent data regarding clinical applications of the dichotic listening technique in neurology and neuropsychiatry. The technique is described, in addition to the two main cognitive abilities we can measure with it. First, language lateralization, following Kimura's model as an anatomical explanation of the right ear advantage effect. Second, the attentional function, including Kinsbourne's model and the forced attention paradigm from Hugdahl as a valuable working tool to evaluate selective attention and executive functions. In subsequent sections, a review is offered respecting both types of cognitive processes for schizophrenia, depression, dyslexia and Multiple Sclerosis, along with data from our laboratory regarding the last illness. The dichotic listening is a useful technique to evaluate the integrity of the temporal and frontal lobes, as well as the interhemispheric communication across the corpus callosum. Application to the clinical practice pretends to incorporate it to the diagnostic, to the description of the pathologies profiles and also to the prediction of illness course, resulting promising in some cases although with reasonable limits while looking for additional research.


A culturally-competent approach to emergency management: What lessons can we learn from the COVID-19?
The COVID-19 pandemic, like other disasters, is exposing and exacerbating social, economic, and health care inequalities. Although the ethical and clinical imperative of providing culturally-competent health care has long been recognized, the influence of culturally-competent interventions within emergency management has not been systematically examined. This paper discusses several culturally-competent strategies that were taken by the Israeli national and local authorities in high-risk areas and communities during the COVID-19 outbreak. In addition to controlling the pandemic outbreak, such an approach has the potential to reduce social disparities in health care, promote community resilience, and facilitate social cohesion. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Follicular T Cells from smB- Common Variable Immunodeficiency Patients Are Skewed Toward a Th1 Phenotype.
Germinal center follicular T helper (GCTfh) cells are essential players in the differentiation of B cells. Circulating follicular T helper (cTfh) cells share phenotypic and functional properties with GCTfh cells. Distinct subpopulations of cTfh with different helper capabilities toward B cells can be identified: cTfh1 (CXCR3+CCR6-), cTfh2 (CXCR3-CCR6-), and cTfh17 (CXCR3-CCR6+). Alterations in cTfh function and/or distribution have been associated with autoimmunity, infectious diseases, and more recently, with several monogenic immunodeficiencies. Common variable immunodeficiency (CVID) disease is the commonest symptomatic primary immunodeficiency with a genetic cause identified in only 2-10% of patients. Although a heterogeneous disease, most patients show a characteristic defective B cell differentiation into memory B cells or antibody-secreting cells. We investigated if alterations in CVID cTfh cells frequency or distribution into cTfh1, cTfh2, and cTfh17 subpopulations and regulatory follicular T (Tfr) cells could be related to defects in CVID B cells. We found increased percentages of cTfh exhibiting higher programmed death-1 expression and altered subpopulations distribution in smB- CVID patients. In contrast to smB+ patients and controls, cTfh from smB- CVID patients show increased cTfh1 and decreased cTfh17 subpopulation percentages and increased CXCR3+CCR6+ cTfh, a population analogous to the recently described pathogenic Th17.1. Moreover, Tfr cells are remarkably decreased only in smB- CVID patients. In conclusion, increased cTfh17.1 and cTfh1/cTfh17 ratio in CVID patients could influence B cell fate in smB- CVID patients, with a more compromised B cell compartment, and the decrease in Tfr cells may lead to high risk of autoimmune conditions in CVID patients.


Achieving the end game: employing "vaccine diplomacy" to eradicate polio in Pakistan.
On April 28, 2014, the World Health Organization (WHO) declared polio a "Public Health Emergency of International Concern" (PHIC) under the authority of the International Health Regulations. Although polio has been eradicated from nearly every nation on earth, Pakistan is one of three countries where wild polio and vaccine-derived polio strains remain, thwarting global eradication efforts. Polio eradication progress is complicated by security and conflict issues at the border area between Pakistan and Afghanistan. In addition to security issues, other critical challenges, such as maintaining cold supply chain for vaccines, active and sentinel surveillance, false beliefs about vaccines, distrust of healthcare workers, and accessibility to conflict areas due to terrorist activities, all play a role in the continued persistence of Polio. In response to these challenges, we assess the local and international policy environment and its impact on polio eradication in Pakistan. Based on our analysis of existing barriers and challenges associated with polio eradication in Pakistan, this study discusses why employing "vaccine diplomacy" represents a key policy and advocacy strategic approach to achieve the overall end game of polio eradication. Specifically, we identify a set of concrete public health, international development, and diplomatic and policy recommendations that can act synergistically under the umbrella of health and vaccine diplomacy to finally put an end to polio.


Chemical and antibacterial studies of two Helichrysum species of Greek origin.
The chemical composition of the essential oils obtained from the aerial parts of Helichrysum stoechas ssp. barrelieri and H. taenari was analysed by GC and GC/MS. From the thirty-nine identified constituents representing the 73.87% and 87.41% of the two oils, respectively, beta-elemene, beta-caryophyllene, geraniol, and camphene were the major components. Furthermore, it was found that the oils exhibited significant antibacterial activity against six Gram (+/-) bacteria.


Electrical stimulation of inner retinal neurons in wild-type and retinally degenerate (rd/rd) mice.
Electrical stimulation of the retina following photoreceptor degeneration in diseases such as retinitis pigmentosa and age-related macular degeneration has become a promising therapeutic strategy for the restoration of vision. Many retinal neurons remain functional following photoreceptor degeneration; however, the responses of the different classes of cells to electrical stimuli have not been fully investigated. Using whole-cell patch clamp electrophysiology in retinal slices we investigated the response to electrical stimulation of cells of the inner nuclear layer (INL), pre-synaptic to retinal ganglion cells, in wild-type and retinally degenerate (rd/rd) mice. The responses of these cells to electrical stimulation were extremely varied, with both extrinsic and intrinsic evoked responses observed. Further examination of the intrinsically evoked responses revealed direct activation of both voltage-gated Na(+) channels and K(+) channels. The expression of these channels, which is particularly varied between INL cells, and the stimulus intensity, appears to dictate the polarity of the eventual response. Retinally degenerate animals showed similar responses to electrical stimulation of the retina to those of the wild-type, but the relative representation of each response type differed. The most striking difference between genotypes was the existence of a large amplitude oscillation in the majority of INL cells in rd/rd mice (as previously reported) that impacted on the signal to noise ratio following electrical stimulation. This confounding oscillation may significantly reduce the efficacy of electrical stimulation of the degenerate retina, and a greater understanding of its origin will potentially enable it to be dampened or eliminated.


[Case of hepatopulmonary syndrome with no vascular dilation in chest CT].
A 69-year-old man afflicted with alcoholic liver cirrhosis complained of dyspnea on effort. His chest CT shows moderate emphysema, and no vascular dilation. An intrapulmonary shunt study using 99mTc-MAA revealed 43% shunt to whole body. Hepatopulmonary syndrome was diagnozed, and he was treated with home oxygen therapy. There is a possibility that the chest CT of patient with hepatopulmonary syndrome complicating emphysema shows no vascular dilation.


Association between early peak temperature and mortality in neutropenic sepsis.
Fever is often the first sign of neutropenic infection, but its prognostic impact has not been established. We aimed to determine whether early peak temperature is associated with mortality in patients with neutropenic sepsis admitted to intensive care units (ICUs). We used a database of admissions to 157 ICUs in Australia and New Zealand between 2005 and 2013 to seek an association between peak temperature within the first 24 h in ICU and in-hospital mortality in neutropenic and non-neutropenic sepsis. Odds ratios for in-hospital death were calculated for four temperature bands, adjusting for illness severity. Two patient cohorts were identified: neutropenic sepsis (N = 4027) and non-neutropenic sepsis (N = 114,040). In-hospital mortality was higher in neutropenic sepsis than non-neutropenic sepsis. In both cohorts, early peak temperature below 36.5 °C was associated with significantly increased mortality compared to normothermia. Among non-neutropenic patients, an early peak temperature of 37.5 °C or higher was associated with reduced mortality compared to normothermia. In contrast, in patients with neutropenic sepsis, fever was not associated with reduced mortality compared to normothermia. Similar findings were seen in a subgroup of the neutropenic sepsis cohort with a documented haematological malignancy. In neutropenic sepsis patients admitted to ICU, a temperature below 36.5 °C is associated with increased mortality compared with normothermia. In contrast to non-neutropenic sepsis, fever was not associated with a significant reduction in mortality in neutropenic patients. Interventional studies are needed to determine whether physical or pharmacological measures to reduce fever influence outcomes during neutropenic infections.


Traditional serrated adenomas of the upper digestive tract.
For many years, it was generally accepted that the vast majority of the colorectal carcinomas (CRCs) evolved from conventional adenomas, via the adenoma-carcinoma sequence. More recently, serrated colorectal polyps (hyperplastic polyps, sessile serrated polyps and traditional serrated adenomas (TSAs)) have emerged as an alternative pathway of colorectal carcinogenesis. It has been estimated that about 30% of the CRC progress via the serrated pathway. Recently, TSAs were also detected in the upper digestive tract. In this work, we review the literature on TSA in the oesophagus, the stomach, the duodenum, the pancreatic main duct and the gallbladder. The review indicated that 53.4% (n=39) out of the 73 TSA of the upper digestive tract now in record showed a simultaneously growing invasive carcinoma. As a corollary, TSAs of the upper digestive tract are aggressive adenomas that should be radically excised, either endoscopically or surgically, to rule out the possibility of a synchronously growing invasive adenocarcinoma or to prevent cancer progression. The present findings substantiate a TSA pathway of carcinogenesis in the upper digestive tract.


In-vitro fertilization and intracytoplasmic sperm injection in the treatment of infertility after testicular cancer.
Treatment of testicular cancer (TC) may cause infertility due to reduced sperm quality with or without an ejaculation problem. In cases of anejaculation or retrograde ejaculation, spermatozoa can be obtained by transrectal electroejaculation (TE) or testicular sperm extraction (TESE) and used for in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI). In this study, 15 out of 17 couples evaluated for infertility after TC, underwent a total of 21 treatment cycles, resulting in 18 embryo transfers. Spermatozoa were obtained by TE in 16 cycles, by masturbation in three cycles and by TESE in one. In one cycle no spermatozoa were found using TESE. Fertilization and cleavage was achieved by IVF in seven cycles and ICSI in 11 cycles; average fertilization rates of 57 and 55% respectively were observed. Twelve clinical pregnancies occurred, of which 11 have been delivered or are ongoing. The ongoing pregnancy rate was 57% per cycle. These results show that infertility after testicular cancer can be treated effectively with IVF and that ICSI even permits treatment of patients who have severe oligozoospermia.


Thionine-Feulgen-Congo red staining of cervical smears for the BioPEPR image-analysis system.
A staining method developed for use with BioPEPR (Biological Precision Encoding and Pattern Recognition), an automated image-analysis system for cervical smears, is described. The stain is a combination of the Feulgen procedure, with thionine-SO2 as the Schiff reagent, and Congo red, which is used as a counterstain. The stain resulted in smears suitable both for microscopic diagnosis and for BioPEPR measurements made on photonegatives at a single wavelength 545 nm. A high level of reproducibility and accuracy of nuclear and cytoplasmic area measurements was obtained. Nuclear integrated optical density could be well measured and was shown to be useful in discriminating between normal and abnormal cells. Using a combination of morphologic features, a high level of cell classification accuracy was reached. The possibility of using the stain for more detailed studies is discussed.


Effect of the butyric short-chain fatty acid on the intracranial pressure and EEG of rabbits.
In the present study we followed the changes in the intracranial pressure and EEG activity of rabbits caused by the butyric short-chain fatty acid infused as an 0.2 M solution at the rate of 12 ml/h. Changes in the rabbit's normal EEG of paroxysmal nature were initially observed, followed by a rise of intracranial pressure as a result of the edema that developed in the brain. Pretreatment of the animals with an inhibitor of the prostaglandin (PG) synthesis (indomethacin, i.v. 10 mg/kg b.w.) prevented the appearance of paroxysms. The intracranial pressure increased in the presence of indomethacin, but there was a tendency towards reduction of the maximal value reached in the control animals. We conclude that the PG system participates to a varying degree in the genesis of the butyrate-induced changes in the bioelectric cerebral activity and intracranial pressure.


Peroxisome proliferator-activated receptor γ agonism attenuates endotoxaemia-induced muscle protein loss and lactate accumulation in rats.
The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5 ± 0.1 mg·kg-1·day-1) for 2 weeks before and during 24 h continuous intravenous infusion of LPS (15 μg·kg-1·h-1) or saline. Rosi blunted LPS-induced increases in muscle tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) mRNA by 70% (P<0.05) and 64% (P<0.01) respectively. Furthermore, Rosi suppressed the LPS-induced reduction in phosphorylated AKT and phosphorylated Forkhead box O (FOXO) 1 protein, as well as the up-regulation of muscle RING finger 1 (MuRF1; P<0.01) mRNA and the LPS-induced increase in 20S proteasome activity (P<0.05). Accordingly, LPS reduced the muscle protein:DNA ratio (∼30%, P<0.001), which Rosi offset. Increased muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA (P<0.001) and muscle lactate accumulation (P<0.001) during endotoxaemia were suppressed by Rosi. Thus, pre-treatment with Rosi reduced muscle cytokine accumulation and blunted muscle protein loss and lactate accumulation during endotoxaemia, and at least in part by reducing activation of molecular events known to increase muscle protein breakdown and mitochondrial pyruvate use.


Experience of low-dose dexamethasone use in the respiratory management of ichthyosis prematurity syndrome.
Ichthyosis prematurity syndrome (IPS) is a rare disorder of autosomal recessive inheritance. The cardinal features include prematurity, vernix like hyperkeratosis, eosinophilia and neonatal asphyxiation. This case report discusses the presentation and management of IPS. We aim to characterise the common features, the spectrum of disease within a single family and discuss a potential role for low-dose dexamethasone in the management of ventilator-dependent patients with IPS.


Chiral and achiral crystals, charge-assisted hydrogen-bond patterns and self-organization of selected solid diaminium thiosulfates.
A series of diaminium thiosulfates, derivatives of diamines: NH2CH2CH(CH3)NH2 (1) and NH2(CH2)nNH2, n = 3-6 [(2)-(5)] and thiosulfuric acid were prepared and their structures determined by single-crystal X-ray diffraction analysis. Compounds (1), (2) and (4) turned out to be hydrates. The crystal structure of 1,2-propylenediaminium thiosulfate is chiral and exhibits spontaneous resolution. Crystals for both enantiomers [(1a) and (1b)] were obtained with high enantiometric excess and examined. An extended network of strong, charge-assisted hydrogen bonding of the +N-H...O- type (also O-H...O and O-H...S for hydrates) is most likely the main factor defining crystal packing and the variable conformation of the cations. The formation of chiral hydrogen-bond motifs - distorted cubans - seems to induce the formation of chiral solid-state structure from achiral components in the case of (4). Diaminium thiosulfates with an odd number of C atoms in the alkyl chain [compounds (1), (2) and (4)] form three-dimensional supramolecular networks, while in the case of diaminium salts with an even number of C atoms [(3) and (5)], two-dimensional layers of hydrogen-bond domains are observed. The aminium thiosulfates were also characterized by elemental analysis, NMR and Fourier transform (FT)-IR spectroscopy. The conformations of α,ω-alkyldiaminium cations in the solid state are discussed and rationalized by DFT calculations.


Seropositivity of toxoplasmosis in patients with schizophrenia.
Recent studies indicate that infectious agents may contribute to some cases of schizophrenia. In animals, infections with Toxoplasma gondii can alter behavior and neurotransmitter function. In humans, acute infection can produce psychotic symptoms similar to those displayed by persons with schizophrenia. In the present study, an enzyme immunoassay (EIA) was employed to measure the level of Toxoplasma IgG antibodies in serum samples from 75 patients of schizophrenia and 85 matched controls. Percentage of positive sera for Toxoplasma IgG antibodies was significantly higher in schizophrenic cases than controls (80% vs. 52.9% respectively). Infection increased with age in both groups and no significant association was found with sex. No association was found with duration of illness or presence of family history of schizophrenia. Circumstantial evidence indicates that infection with Toxoplasma gondii may lead to some cases of schizophrenia.


Exercise for cancer cachexia in adults.
Cancer cachexia is a multi-factorial syndrome characterised by an ongoing loss of skeletal muscle mass, with or without a loss of fat mass, which leads to progressive functional impairment. Physical exercise may attenuate the effects of cancer cachexia via several mechanisms, including the modulation of muscle metabolism, insulin sensitivity and levels of inflammation. The primary objective was to determine the effects of exercise, compared to usual care or no treatment, on lean body mass, the main biomarker of cachexia, in adults with cancer. Secondary objectives, subject to the availability of data, were to examine the acceptability and safety of exercise in this setting and to compare effects according to the characteristics of the exercise intervention or patient population. We searched the databases CENTRAL (Issue 6, 2014) , MEDLINE (1946 to June 2014), EMBASE (1974 to June 2014), DARE and HTA (Issue 6, 2014), ISI Web of Science (1900 to June 2014), LILACS (1985 to 28 June 2014), PEDro (inception to 28 June 2014), SciVerse SCOPUS (inception to 28 June 2014), Biosis Previews PreMEDLINE (1969 to June 2014) and Open Grey (inception to 28 June 2014). We also searched for ongoing studies, checked reference lists and contacted experts to seek potentially relevant research. We included randomised controlled trials (RCTs) in adults meeting the clinical criteria for cancer cachexia comparing a programme of exercise as a sole or adjunct intervention to no treatment or an active control. We imposed no language restriction. Two review authors independently assessed titles and abstracts of articles for relevance and extracted data on study design, participants, interventions and outcomes from potentially relevant articles. We screened 3154 individual references, of which we removed 3138 after title screening and read 16 in full. We found no trials that met the inclusion criteria. There is insufficient evidence to determine the safety and effectiveness of exercise for patients with cancer cachexia. Randomised controlled trials (i.e., preferably parallel-group or cluster-randomised trials) are required to test the effectiveness of exercise in this group. There are ongoing studies on the topic, so we will update this review to incorporate the findings.


Albumin and its application in drug delivery.
Rapid clearance of drugs from the body results in short therapeutic half-life and is an integral property of many protein and peptide-based drugs. To maintain the desired therapeutic effect patients are required to administer higher doses more frequently, which is inconvenient and risks undesirable side effects. Drug delivery technologies aim to minimise the number of administrations and dose-related toxicity while maximising therapeutic efficacy. This review describes albumin's inherent biochemical and biophysical properties, which make it an attractive drug delivery platform and the developmental status of drugs that are associated, conjugated or genetically fused with albumin. Albumin interacts with a number of cell surface receptors including gp18, gp30, gp60, FcRn, cubilin and megalin. The importance of albumin's interaction with the FcRn receptor, the basis for albumin's long circulatory half-life, is described, as are engineered albumins with improved pharmacokinetics. Albumin naturally accumulates at tumours and sites of inflammation, a characteristic which can be augmented by the addition of targeting ligands. The development of albumin drug conjugates which reply upon this property is described. Albumin's inherent biochemical and biophysical properties make it an ideal drug delivery platform. Recent advances in our understanding of albumin physiology and the improvement in albumin-based therapies strongly suggest that albumin-based therapies have a significant advantage over alternative technologies in terms of half-life, stability, versatility, safety and ease of manufacture. Given the importance of the albumin:FcRn interaction, the interpretation of the pharmacokinetic and pharmacodynamic profiles of albumin-based therapeutics with disturbed albumin:FcRn interaction may have to be reassessed. The FcRn receptor has additional functionality, especially in relation to immunology, antigen presentation and delivery of proteins across mucosal membranes, consequently albumin-based fusions and conjugates may have a future role in oral and pulmonary-based vaccines and drug delivery.


Assigning temperatures to eigenstates.
In the study of thermalization in finite isolated quantum systems, an inescapable issue is the definition of temperature. We examine and compare different possible ways of assigning temperatures to energies or equivalently to eigenstates in such systems. A commonly used assignment of temperature in the context of thermalization is based on the canonical energy-temperature relationship, which depends only on energy eigenvalues and not on the structure of eigenstates. For eigenstates, we consider defining temperature by minimizing the distance between (full or reduced) eigenstate density matrices and canonical density matrices. We show that for full eigenstates, the minimizing temperature depends on the distance measure chosen and matches the canonical temperature for the trace distance; however, the two matrices are not close. With reduced density matrices, the minimizing temperature has fluctuations that scale with subsystem and system size but appears to be independent of distance measure. In particular limits, the two matrices become equivalent while the temperature tends to the canonical temperature.


Talk to Patients About: Meningococcal B.
Meningococcal B (MenB) vaccine is the new kid on the block for children and adolescents, having won Food and Drug Administration approval in 2014. This presents a problem for physicians: Because there is an older vaccine for the other types of meningococcal bacteria, many patients who've had that vaccine wrongly believe they're also protected against MenB.


The landscape of Y chromosome polymorphisms in Russia.
The pattern of diversity for the Y chromosome provides a view of male-driven processes of dispersal and settlement. By virtue of the broad geographic continuity, the genetic signature of movements from Asia to Europe can be detected in populations of north-eastern Europe. To directly test previous hypotheses on the peopling of Russia, by considering a broader spectrum of potential diversity. A total of 636 unrelated males (24 samples) from geographically and ethnically defined populations of Russia, Belarus, Azerbaijan and Georgia were analysed for 16 Y-STR loci. Some of the populations represent more or less distinct isolates. Microsatellites alone can have the power of detecting Asian contributions to the gene pool of populations now residing in Europe. Within Europe, a greater heterogeneity among populations sharing the same language than between populations sharing the same ethnic affiliation was found. There was low diversity and marked population differentiation in some Altaic speakers. Sympatry eroded inter-ethnic differentiation. No regular decline in genetic similarity with geography was seen. Two layers of overall diversity represent a main feature of the genetic landscape of the population of the European portion of Russia.


Characterizing the Undergraduate Neuroscience Major in the U.S.: An Examination of Course Requirements and Institution-Program Associations.
Neuroscience is a rapidly expanding field, and many colleges and universities throughout the country are implementing new neuroscience degree programs. Despite the field's growth and popularity, little data exists on the structural character of current undergraduate neuroscience programs. We collected and examined comprehensive data on existing undergraduate neuroscience programs, including academic major requirements and institution characteristics such as size, financial resources, and research opportunities. Thirty-one variables covering information about course requirements, department characteristics, financial resources, and institution characteristics were collected from 118 colleges and universities in the United States that offer a major titled "neuroscience" or "neural sciences." Data was collected from publicly available sources (online databases, institutions' neuroscience program websites) and then analyzed to define the average curriculum and identify associations between institution and program characteristics. Our results suggest that the average undergraduate neuroscience major requires 3 chemistry, 3 biology, 3 laboratory, 2-3 neuroscience, 1 physics, 1 math, and 2 psychology courses, suggesting that most neuroscience programs emphasize the natural sciences over the social sciences. Additionally, while 98% of institutions in our database offer research opportunities, only 31% required majors to perform research. Of note, 70% of institutions offering a neuroscience major do not have a neuroscience department, suggesting that most institutions offer neuroscience as an interdisciplinary major spanning several departments. Finally, smaller liberal arts colleges account for the majority of institutions offering a neuroscience major. Overall, these findings may be useful for informing groups interested in undergraduate neuroscience training, including institutions looking to improve or establish programs, students wanting to major in neuroscience and employers hiring neuroscience graduates.


Colloidally prepared La-doped BaSnO3 electrodes for efficient, photostable perovskite solar cells.
Perovskite solar cells (PSCs) exceeding a power conversion efficiency (PCE) of 20% have mainly been demonstrated by using mesoporous titanium dioxide (mp-TiO2) as an electron-transporting layer. However, TiO2 can reduce the stability of PSCs under illumination (including ultraviolet light). Lanthanum (La)-doped BaSnO3 (LBSO) perovskite would be an ideal replacement given its electron mobility and electronic structure, but LBSO cannot be synthesized as well-dispersible fine particles or crystallized below 500°C. We report a superoxide colloidal solution route for preparing a LBSO electrode under very mild conditions (below 300°C). The PSCs fabricated with LBSO and methylammonium lead iodide (MAPbI3) show a steady-state power conversion efficiency of 21.2%, versus 19.7% for a mp-TiO2 device. The LBSO-based PSCs could retain 93% of their initial performance after 1000 hours of full-Sun illumination.


Intramuscular pain modulatory substances before and after exercise in women with chronic neck pain.
In peripheral tissue, several substances influence pain and pain modulation. Exercise has been found to decrease pain and improve function for chronic pain conditions, but how and why exercise produces beneficial effects remains unclear. This study investigates whether aspects of pain and concentrations of substances with algesic, analgesic and metabolic functions differ between women with chronic neck shoulder pain (CNSP) and healthy women (CON) and whether changes are found after an exercise intervention for CNSP. Forty-one women with CNSP and 24 CON subjects were included. The participants attended two microdialysis sessions with 4-6 months between the experiments. During this period, the CNSP subjects underwent an exercise intervention. Expression levels of substance P, beta-endorphin, cortisol, glutamate, lactate and pyruvate as well as pain intensity and pressure pain thresholds were analysed. At baseline, higher concentrations of glutamate and beta-endorphin and lower concentrations of cortisol in CNSP than CON were found. After exercise, decreased levels of substance P and possibly of glutamate, increased levels of beta-endorphin and cortisol as well as decreased pain intensity and increased pain pressure thresholds were found for CNSP. The findings at baseline indicated algesic and analgesic alterations in the painful trapezius muscles. The findings for CNSP after the exercise intervention, with changes in peripheral substances and decreased pain intensity and sensitivity, could reflect a long-term physiological effect of the exercise.


Excess mortality from mental, neurological and substance use disorders in the Global Burden of Disease Study 2010.
Mortality-associated burden of disease estimates from the Global Burden of Disease 2010 (GBD 2010) may erroneously lead to the interpretation that premature death in people with mental, neurological and substance use disorders (MNSDs) is inconsequential when evidence shows that people with MNSDs experience a significant reduction in life expectancy. We explore differences between cause-specific and excess mortality of MNSDs estimated by GBD 2010. GBD 2010 cause-specific death estimates were produced using the International Classification of Diseases death-coding system. Excess mortality (all-cause) was estimated using natural history models. Additional mortality attributed to MNSDs as underlying causes but not captured through GBD 2010 methodology is quantified in the comparative risk assessments. In GBD 2010, MNSDs were estimated to be directly responsible for 840 000 deaths compared with more than 13 million excess deaths using natural history models. Numbers of excess deaths and attributable deaths clearly demonstrate the high degree of mortality associated with these disorders. There is substantial evidence pointing to potential causal pathways for this premature mortality with evidence-based interventions available to address this mortality. The life expectancy gap between persons with MNSDs and the general population is high and should be a focus for health systems reform.


Complication following intramedullary fixation with a Fixion nail in a patient with osteogenesis imperfecta: a case report.
Osteogenesis imperfecta (O.I.) is a genetic disorder with increased bone fragility and low bone mass. We report the history of a 17-year-old male patient with O.I. who presented a fracture of his left femoral shaft. He had osteogenesis imperfecta type I A according to Silence. He had presented two years previously an ipsilateral cervical fracture of the femur which had healed. Intramedullary fixation with a Fixion intramedullary nail was elected. While the Fixion nail was being inflated to 70 bars with saline, a longitudinal fracture occurred in the femoral shaft. A conventional intramedullary nail and cerclage wire were applied for fixation. The fracture healed without complication in 10 weeks. Based on this observation, we do not recommend using the Fixion IM nail for fracture fixation in patients who have abnormal bone fragility such as in osteogenesis imperfecta.


Hepatocytes of Zones 1 and 3 conjugate sulfobromophthalein with glutathione.
The capacity of hepatocytes of Zones 1 and 3 of the liver acinus to conjugate sulfobromophthalein (BSP) with glutathione and to secrete the conjugate into bile was studied. BSP was infused into the in situ perfused rat liver in concentrations of 0.01 and 0.05 mM. Perfusions were performed either in the portal to hepatic vein direction (forward perfusion) or in the hepatic vein to portal vein direction (retrograde perfusion). Hepatocytes contributing to the uptake, metabolism and biliary secretion of BSP were directly assessed qualitatively by light microscopy, and also semiquantitatively by microspectrophotometry. BSP was taken up predominantly by hepatocytes of Zone 1 during forward perfusion and by those of Zone 3 during the retrograde perfusion of BSP. The biliary products of BSP metabolism by each acinar zone were subsequently assessed. Hepatocytes of both Zones 1 and 3 of the acinus secreted BSP into bile in the form of BSP-glutathione, and BSP-glutathione conjugate represented about 78% of the total BSP secreted into bile by each zone. The rate of BSP biliary secretion by both zones was similar at a concentration of 0.01 mM BSP, while a slight decrease (15%) in BSP secretory rate by hepatocytes of zone 3 was observed at concentrations of BSP near biliary Tm. Liver perfusion with exogenous BSP-glutathione provided results similar to those obtained with BSP. In contrast, the perfusion of 3,6- dibromosulphthalein , a compound which is not conjugated by hepatocytes, resulted in similar biliary secretory rates regardless of the direction of perfusion. These results indicate that: (a) the capacity for glutathione conjugation of BSP is distributed among hepatocytes of all acinar zones; (b) near biliary Tm, the biliary secretory rate of BSP by hepatocytes of Zone 3 is slower than that of hepatocytes of zone 1, and (c) in vivo, all hepatocytes likely contribute to the uptake, metabolism and biliary secretion of BSP.


Expression of sucrase-isomaltase and dipeptidylpeptidase IV in human small intestine and colon.
One monoclonal antibody (8A9) against the human sucrase-isomaltase complex and one (4H3) against the human dipeptidylpeptidase IV were produced in the rat and used to immunolabel thin frozen sections of human small intestine and colon. Both enzymes were found to be expressed in the poorly differentiated crypt cells of the small intestine as well as in the mature villous cells, and very low levels were found to be expressed in the colon. Homogeneous immunolabeling of the whole colonic epithelium with the monoclonal antibody 4H3 was often observed, whereas labeling with the monoclonal antibody 8A9, if any, was either restricted to a few crypts and plateaus. The two antibodies were used to perform specific immunoprecipitation of the corresponding antigen, the N-terminal sequence of which was determined after sodium dodecyl sulfate-polyacrylamide gel electrophoresis purification and electroblotting, and were compared with those of other species. In secretor blood group A humans, both the sucrase-isomaltase and the dipeptidylpeptidase IV have type 3 blood group A determinants.


Jejunal fibroplasia in a rat.
A jejunal nodular mass was identified in an aging rat. Histologically, the boundaries between the lesion and surrounding normal tissue as well as between the inner circular muscle and outer longitudinal muscle were indistinct. The lesion consisted of abundant eosinophilic matrix and cells with a large round to oval nucleus and indistinct cytoplasm. There was no characteristic proliferating pattern, nuclear polymorphism and a low mitotic figure count. Masson's trichrome stain revealed that the intestinal smooth muscles were replaced by the abundant collagen fiber. Immunohistochemistry revealed that the cells with a large round to oval nucleus were labeled with anti-vimentin antibody and not with anti-α smooth muscle actin antibody, suggesting that these cells were fibroblasts. The mass was diagnosed as jejunal fibroplasia.


Short-Term effects of neuromuscular electrical stimulation on muscle architecture of the tibialis anterior and gastrocnemius in children with cerebral palsy: preliminary results of a prospective controlled study.
The aim of this study was to explore the short-term effects of neuromuscular electrical stimulation application on tibialis anterior (stimulated muscle) and gastrocnemius (antagonist) muscles' size and architecture in children with cerebral palsy by using ultrasound. This prospective, controlled study included 28 children diagnosed with spastic diplegic cerebral palsy. Participants were treated either with neuromuscular electrical stimulation application and conventional physiotherapy (group A) or with conventional physiotherapy alone (group B). Outcome was evaluated by clinical (gross motor function, selective motor control, range of motion, spasticity) and ultrasonographic (cross-sectional area, pennation angle, fascicle length of tibialis anterior and gastrocnemius muscles) measurements before and after treatment in both groups. Cross-sectional area values of tibialis anterior (238.7 ± 61.5 vs. 282.0 ± 67.1 mm) and gastrocnemius (207.9 ± 48.0 vs. 229.5 ± 52.4 mm) (P < 0.001 and P = 0.008, respectively) muscles were increased after treatment in group A. Cross-sectional area values of tibialis anterior muscle were decreased (257.3 ± 64.7 vs. 239.7 ± 60.0 mm) after treatment in group B (P < 0.001), and the rest of the measurements were found not to have changed significantly in either group. These results have shown that cross-sectional area of both the agonist and antagonist muscles increased after 20 sessions of neuromuscular electrical stimulation treatment. Future studies with larger samples and longer follow-up are definitely awaited for better evaluation of neuromuscular electrical stimulation application on muscle architecture and its possible correlates in clinical/functional outcome.


Aberrant expression of the K-ras proto-oncogene in B-cell malignancies.
The proto-oncogenes have the capacity for conversion to an oncogene that is capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in the neoplastic transformation of B-cell malignancies, we have analyzed their expression in 18 fresh samples obtained from the peripheral blood of patients with a variety of B-cell malignancies. A high-molecular weight c-k-ras transcript (5.2 kb) was detected in all samples including normal lymphocytes. In contrast, a low-molecular weight c-k-ras transcript (1.2 kb) was not detected in our control normal lymphocytes, but was found in 9 fresh samples. The 1.2 kb c-k-ras transcript was expressed 2-3-fold higher than the 5.2 kb c-k-ras transcript. C-h-ras (2.9 kb, 1.4 kb) was expressed at a low level in 4 and 13 samples, but not in normal lymphocytes. C-myc (2.3 kb) and c-raf (3.8 kb) were expressed in all samples including normal lymphocytes without significant variation in the level of expression. C-fos (2.2 kb) was expressed in 15 samples and normal lymphocytes with a wide range in the level of expression. C-myb (3.7 kb) and c-fes (2.7 kb) were expressed at a low level in 6 and 10 samples, respectively, including normal lymphocytes. C-sis (4.0 kb) was not detected in any sample including normal lymphocytes.


Low temperature rate coefficients for reactions of the butadiynyl radical, C4H, with various hydrocarbons. Part I: reactions with alkanes (CH4, C2H6, C3H8, C4H10).
The kinetics of the reactions of the linear butadiynyl radical, C4H (CCCCH), with methane, ethane, propane and butane have been studied over the temperature range of 39-300 K using a CRESU (Cinétique de Réaction en Ecoulement Supersonique Uniforme or Reaction Kinetics in Uniform Supersonic Flow) apparatus combined with the pulsed laser photolysis-laser induced fluorescence technique. The rate coefficients, except for the reaction with methane, show a negative temperature dependence and can be fitted with the following expressions over the temperature range of this study: k(C2H6) = 0.289 x 10(-10) (T/298 K)(-1.23) exp(-24.8 K/T) cm3 molecule(-1) s(-1); k(C3H8) = 1.06 x 10(-10) (T/298 K)(-1.36) exp(-56.9 K/T) cm3 molecule(-1) s(-1); k(C4H10) = 2.93 x 10(-10) (T/298 K)(-1.30) exp(-90.1 K/T) cm3 molecule(-1) s(-1). The rate coefficients for the reaction with methane were measured only at 200 K and 300 K yielding a positive temperature dependence: k(CH4) = 1.63 x 10(-11) exp(-610 K/T) cm3 molecule(-1) s(-1). Possible reaction mechanisms and product channels are discussed in detail for each of these reactions. Potential implications of these results for models of low temperature chemical environments, in particular cold interstellar clouds and planetary atmospheres such as that of Titan, are considered.


Financial Strain, Negative Interactions, and Mastery: Pathways to Mental Health Among Older African Americans.
This study examines the impact of financial strain, social support, and negative interactions on depressive symptoms among African Americans and the role of mastery as a mediator in these relationships. Structural equation modeling and baseline data from the Americans' Changing Lives Study were used to test these relationships among a sample of African Americans aged 50 to 96 years (N = 583). Findings illustrate the mechanistic pathways whereby financial strain is associated with depressive symptoms. Moreover, the study findings give further credence to the notion that positive and negative aspects of social relationships are distinctive with respect to social status factors, financial strain, and their relationship to depressive symptoms. This research suggests that mastery is an important mechanism linking negative interaction to mental health. The collection of findings provide a number of provocative departures from research conducted primarily using White samples and identifies important areas of intervention with older African Americans.


Covariate selection in multivariate spatial analysis of ovine parasitic infection.
Gastrointestinal (GI) strongyle and fluke infections remain one of the main constraints on health and productivity in sheep dairy production. A cross-sectional survey was conducted in 2004-2005 on ovine farms in the Campania region of southern Italy in order to evaluate the prevalence of Haemonchus contortus, Fasciola hepatica, Dicrocoelium dendriticum and Calicophoron daubneyi from among other parasitic infections. In the present work, we focused on the role of the ecological characteristics of the pasture environment while accounting for the underlying long range geographical risk pattern. Bayesian multivariate spatial statistical analysis was used. A systematic grid (10 km×10 km) sampling approach was used. Laboratory procedures were based on the FLOTAC technique to detect and count eggs of helminths. A Geographical Information System (GIS) was constructed by using environmental data layers. Data on each of these layers were then extracted for pasturing areas that were previously digitalized aerial images of the ovine farms. Bayesian multivariate statistical analyses, including improper multivariate conditional autoregressive models, were used to select covariates on a multivariate spatially structured risk surface. Out of the 121 tested farms, 109 were positive for H. contortus, 81 for D. dendriticum, 17 for C. daubneyi and 15 for F. hepatica. The statistical analysis highlighted a north-south long range spatially structured pattern. This geographical pattern is treated here as a confounder, because the main interest was in the causal role of ecological covariates at the level of each pasturing area. A high percentage of pasture and impermeable soil were strong predictors of F. hepatica risk and a high percentage of wood was a strong predictor of C. daubneyi. A high percentage of wood, rocks and arable soil with sparse trees explained the spatial distribution of D. dendriticum. Sparse vegetation, river, mixed soil and permeable soil explained the spatial distribution of the H. contortus. Bayesian multivariate spatial analysis of parasitic infections with covariates from remote sensing at a very small geographical level allowed us to identify relevant risk predictors. All the covariates selected are consistent with the life cycles of the helminths investigated. This research showed the utility of appropriate GIS-driven surveillance systems. Moreover, spatial features can be used to tailor sampling design where the sampling fraction can be a function of remote sensing covariables.


[Simultaneous determination of nine microcystins in surface water by solid phase extraction and ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry].
A method has been developed for the simultaneous determination of nine microcystins (MCs) in surface water by solid phase extraction-ultra performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (SPE-UPLC-ESI-MS/MS). The samples were enriched and purified by an HLB solid phase extraction column. The separation was performed on an ACQUITY UPLC system with a BEH C18 column with the gradient elution of acidified acetonitrile and water (both containing 0.1% (v/v) formic acid). The nine MCs were determined in the modes of electrospray positive ionization (ESI+) and multiple reaction monitoring (MRM). Good linearities were observed in the ranges of 0.1-50 microg/L for MC-RR and 0.5-100 microg/L for the others with correlation coefficients over 0. 999 0 and the limits of detection for the nine MCs were in the range of 0.1-0.5 ng/L. The recoveries were in the range of 75.8%-109% in the three spiked levels of 1.0, 10 and 50 microg/L with the relative standard deviations of 0.49%-10.0%. The method is characterized by high sensitivity and precision, extensive analytical range and quick analytical rate. This method was used in the analysis of water samples from two reservoirs situated in Hangzhou, and the 3 and 8 microcystins were detected individually.


Cardiac complications during use of etomidate.
Two patients are described who exhibited cardiac complications during administration of etomidate. One patient showed myocardial ischaemia and the other developed cardiac asystole.


The diagnostic value of chest X-ray in coronavirus disease 2019: A comparative study of X-ray and CT.
As the coronavirus disease 2019 (COVID-19) epidemic spreads around the world, the demand for imaging examinations increases accordingly. The value of conventional chest radiography (CCR) remains unclear. In this study, we aimed to investigate the diagnostic value of CCR in the detection of COVID-19 through a comparative analysis of CCR and CT. This study included 49 patients with 52 CT images and chest radiographs of pathogen-confirmed COVID-19 cases and COVID-19-suspected cases that were found to be negative (non-COVID-19). The performance of CCR in detecting COVID-19 was compared to CT imaging. The major signatures that allowed for differentiation between COVID-19 and non-COVID-19 cases were also evaluated. Approximately 75% (39/52) of images had positive findings on the chest x-ray examinations, while 80.7% (42/52) had positive chest CT scans. The COVID-19 group accounted for 88.4% (23/26) of positive chest X-ray examinations and 96.1% (25/26) of positive chest CT scans. The sensitivity, specificity, and accuracy of CCR for abnormal shadows were 88%, 80%, and 87%, respectively, for all patients. For the COVID-19 group, the accuracy of CCR was 92%. The primary signature on CCR was flocculent shadows in both groups. The shadows were primarily in the bi-pulmonary, which was significantly different from non-COVID-19 patients (p = 0.008). The major CT finding of COVID-19 patients was ground-glass opacities in both lungs, while in non-COVID-19 patients, consolidations combined with ground-glass opacities were more common in one lung than both lungs (p = 0.0001). CCR showed excellent performance in detecting abnormal shadows in patients with confirmed COVID-19. However, it has limited value in differentiating COVID-19 patients from non-COVID-19 patients. Through the typical epidemiological history, laboratory examinations, and clinical symptoms, combined with the distributive characteristics of shadows, CCR may be useful to identify patients with possible COVID-19. This will allow for the rapid identification and quarantine of patients.


Defined chromosomal assignment of CLN5 demonstrates that at least four genetic loci are involved in the pathogenesis of human ceroid lipofuscinoses.
We demonstrate here that at least four genetically separate loci are involved in the pathogenesis of human neuronal ceroid lipofuscinoses (NCLs), fatal brain disorders of children. Earlier the assignments of the infantile and juvenile subtypes of NCL to 1p32 and 16p12 had revealed two loci; and here a variant subtype of the late-infantile form of NCL is mapped to a well-defined region on 13q21.1-q32, whereas the clinically similar, classical form of late-infantile NCL was found to represent the fourth, yet-unidentified NCL locus. The linkage disequilibrium was crucial for locus assignment in our highly limited family material, and the data exemplify the significance of this phenomenon in the random mapping of rare human diseases.


A delicate web: household changes in health behaviour enabled by microcredit in Burkina Faso.
Providing microcredit to women in developing countries has long been highlighted as a simple and effective strategy for poverty reduction and health improvement. However, little is known about how microcredit enables changes in health behaviour. This knowledge is critical to further strengthen microcredit initiatives. This qualitative study, conducted in Burkina Faso, shows how microcredit can not only facilitate savings and investment strategies, but also lead to changes in household decision-making, enabling women to initiate health prevention, seek health treatment and manage health emergencies. Some changes led to increased household burdens for women that impeded health gains, such as administrative loan delays by the microcredit institution and reduced household contributions by the husband. Furthermore, the study highlighted the fragile nature of health gains, which may be eroded due to economic shocks on a household, such as crop failure, drought or illness.


[The efficacy of the multidisciplinary approach in colorectal cancer surgery in elderly patients].
Publications of the last few years indicate a steady rise of colorectal cancer in the world. Colorectal cancer is on the second place in the structure of oncological mortality in developed countries, including Russia. The majority of colorectal cancer deaths (up to 50%) occur in elderly. The octogenarians are more likely to have comorbidities and age-specific deteriorating organ function, which could make their tolerance of surgery. To determine the short- and long-term outcomes of the multidisciplinary approach in elective colorectal surgery in patients ≥75 years of age. A review 70 octogerians who underwent colorectal cancer surgery between April 2006 and November 2010 was performed from prospectively collected database. The median age was 79 (75-95) years. Every patient was examined by multidisciplinary team before surgery. Conservative therapy was prescribed or corrected if any organ failure detected. After the period of treatment decision on their suitability for surgery was made. Comorbidities were quantified using the weighted Charlson Comorbidity Index and ASA classification. CR-POSSUM scores and the predicted mortality rates were calculated. Outcome measures were morbidity rates and 30-day mortality rates. The mean index of comorbidity was 7.3 (6-11) and 81% of patients were classified ASA III and above. The mean predicted mortality rate based on CR-POSSUM scoring model was 14.8%. All patients with comorbidities were treated conservatively during mean period of 12.2 days, nine patients (13%) required implantations of pacemakers to control heart rate in perioperative period. In 64 (91%) cases surgical resection of the colon or rectum with primary anastomosis were performed, in 6 (9%) - abdominoperineal resection of the rectum and in two cases - Hartmann's operation. Postoperative complications were noticed in 40 (57%) cases. Postoperative mortality rate (death within 30 days of surgery) was 5.7%, the 2- and 3-year overall survival rate according to Kaplan and Meier was 78.3±5.6% and 74.9±6.3% respectively. Using the multidisciplinary approach in the management of elderly allows reaching the acceptable mortality level (5.7% in comparison with predicted 14.8%) and high 2- and 3-year survival rates. This means that chronological age alone should not be contraindication to the elective curative surgery of colorectal cancer in elderly if overall assessment of the perioperative risk is possible. The study aimed to asses the intermediate and long-term results of the multidisciplinathe colorectal cancer in elderly patients. 70 patients, aged 75-95 years, were prospectively chosen to participate the study. The comorbidity Charlson index and ASA scale were used to measure the perioperative risks. The CR-POSSUM scale was used for postoperative lethality rating. The use of the above listed scales and measurements in combination with multidisciplinary conservative preaparation of patients before the operation allowed to achieve the satisfactory lethality rate of 5.7% and higher long-term survival rates after the colorectal surgery.


Experimental pineocytoma of the Syrian hamster induced by a human papovavirus (JC). A light and electron microscopic study.
The gross, light and electron microscopic features of a pineocytoma of the Syrian hamster (mesocricetus auratus) which had been induced by a human oncogenic virus (JC papovavirus) have been defined. For comparison, adult hamster pineal tissue was studied, and the literature was consulted in regard to other pineal parenchymal tumors, and to pineal cell differentiation during ontogeny and phylogeny. Many differentiated tumor cells contained organelles, such as vesicle-crowned lamellae (synaptic ribbons) and microtubular sheaves, as consistent with adult hamster pineocytes. Some cells showed rudimentary photoreceptor-like differentiation as consistent with fetal hamster pineocytes and with cells seen in the pineal systems of some lower vertebrate species. Such tumor cells had lumen-directed specialized cytoplasmic extensions which, by their richness in mitochondria and presence of centrioles and striated rootlets, resembled inner segments. Extending 9+0 cilia were accompanied by occasional lamellar whorls. Oncogenesis seems to have simulated different stages of hamster pineal ontogeny. This observation would support the theory that the secretory mammalian pineocyte derived phylogenetically from the true photoreceptor cell of the pineal system of fishes and amphibians. The possible influences of host and of virus in the accomplishment of tumor morphology were discussed. This tumor differed considerably in pattern and cell detail from the only other pineocytoma studied previously by electron microscopy. It is the first experimentally induced pineocytoma.


Fast repair of the poly G hydroxyl radical adduct by two phenylpropanoid glycosides.
The repair activities and the reaction mechanisms of two phenylpropanoid glycosides (PPGs), isolated from a herb used in Chinese folk medicine, towards the oxidizing hydroxyl radical adduct of poly G were studied with a pulse radiolytic technique. On pulse irradiation of a nitrous oxide saturated 4 mM aqueous solution of poly G containing one of the tested compounds, the transient absorption spectrum of the hydroxyl radical adduct of poly G decays with the formation of that of the phenoxyl radical of the tested compound within several tens microseconds after the electron pulse irradiation. The results indicated that there was a repair reaction between the hydroxyl radical adduct of poly G and the compounds tested. The rate constants for the repair reactions of poly G hydroxyl radical adducts by verbasicoside and cistanoside C were determined to be 1.4 and 1.0 x 10(9) M(-1) x s(-1), respectively.


Abundant expression of ponsin, a focal adhesion protein, in lens and downregulation of its expression by impaired cytoskeletal signaling.
This study was undertaken to improve understanding of the defective lens developmental changes induced by the transgenic overexpression of the Rho GDP dissociation inhibitor RhoGDIalpha. The study was focused on a single differentially expressed gene encoding ponsin, a cell adhesion interacting signaling adaptor protein. Total RNA extracted from the P7 lenses of Rho GDIalpha transgenic mice was subjected to cDNA microarray analysis. Ponsin distribution in the mouse lenses was determined by immunofluorescence and immunoblot analyses. Interactions among ponsin, actin, and Rho GTPase signaling pathways were explored in lens epithelial cells. The RhoGDIalpha transgenic mouse lenses revealed a marked downregulation of expression of multiple splice variants of ponsin. Expression of one of the ponsins (U58883) was found to be abundant in normal mouse lenses. Although ponsin was localized predominantly to the focal adhesions in lens epithelial cells, it was distributed to both the epithelium and fibers, with some isoforms being enriched primarily in the Triton X-100-insoluble fraction in lens tissue. Further, whereas constitutively active RhoA induced ponsin clustering at the leading edges, inhibition of Rho kinase and latrunculin treatment were noted to lead to decreases in ponsin protein levels in lens epithelial cells. Abundant expression of ponsin, a focal adhesion protein in the lens tissue indicates a potential role for this protein in lens fiber cell migration and adhesion. Ponsin expression appears to be closely dependent on Rho GTPase-regulated integrity of actin cytoskeletal organization.