All-atom crystal simulations of DNA and RNA duplexes.
Molecular dynamics simulations can complement experimental measures of structure and dynamics of biomolecules. The quality of such simulations can be tested by comparisons to models refined against experimental crystallographic data. We report simulations of DNA and RNA duplexes in their crystalline environment. The calculations mimic the conditions for PDB entries 1D23 [d(CGATCGATCG)2] and 1RNA [(UUAUAUAUAUAUAA)2], and contain 8 unit cells, each with 4 copies of the Watson-Crick duplex; this yields in aggregate 64μs of duplex sampling for DNA and 16μs for RNA. The duplex structures conform much more closely to the average structure seen in the crystal than do structures extracted from a solution simulation with the same force field. Sequence-dependent variations in helical parameters, and in groove widths, are largely maintained in the crystal structure, but are smoothed out in solution. However, the integrity of the crystal lattice is slowly degraded in both simulations, with the result that the interfaces between chains become heterogeneous. This problem is more severe for the DNA crystal, which has fewer inter-chain hydrogen bond contacts than does the RNA crystal. Crystal simulations using current force fields reproduce many features of observed crystal structures, but suffer from a gradual degradation of the integrity of the crystal lattice. The results offer insights into force-field simulations that test their ability to preserve weak interactions between chains, which will be of importance also in non-crystalline applications that involve binding and recognition. This article is part of a Special Issue entitled Recent developments of molecular dynamics.


[Neuroleukemia in mice with leukemia L1210 treated with methotrexate].
Histological investigations were conducted in 33 methotrexate-treated mice with leukemia L1210. It has been found that in nonsuppressed systemic leukemia process the development and progressing of initial morphologic signs of neuroleukemia takes place as a result of perivascular growth of leukemic infiltrates from the bone marrow of the cranial and vertebral bones into the adjacent structures of the central nervous system.


Endoscopic third ventriculostomy for hydrocephalus due to tectal glioma.
Tectal gliomas commonly present with hydrocephalus from obstruction of the aqueduct of Sylvius. The creation of a ventriculostomy in the floor of the third ventricle (ETV) has been previously reported to by-pass aqueduct obstruction. The goal of this study was to determine the safety and efficacy of ETV in the presence of an obstructing tectal glioma. We retrospectively reviewed the clinical presentation, management, and clinical outcome after ETV in patients diagnosed with tectal glioma and obstructive hydrocephalus in our institution over a period of 15 years. Shunt freedom at follow-up was the main outcome variable. Long-term clinical outcome was assessed at the most recent clinic visit. Clinical outcome was ranked as excellent, good, or poor according to resolution of symptoms and patient functional status. The median age at presentation was 16.5 years (range: 6.4 to 59 years) and the most common presenting symptom was headache. Eleven patients had ETV as a primary procedure and three patients underwent ETV as a substitute for shunt revision at the time of shunt failure. At follow-up (median 3.9 years, range: 2.2 to 7 years) 13 of 14 patients remain shunt independent with excellent (n=9) or good outcomes (n=5). In patients with tectal glioma causing obstructive hydrocephalus, ETV can be performed safely in the primary setting or as a substitute for shunt revision. A high rate of shunt freedom (78%-100%) at prolonged follow-up can be expected in this patient population.


EST-SSR development from 5 Lactuca species and their use in studying genetic diversity among L. serriola biotypes.
Prickly lettuce (Lactuca serriola L.) is a problematic weed of Pacific Northwest and recently developed resistance to the auxinic herbicide 2,4-D. There are no publically available simple sequence repeat (SSR) markers to tag 2,4-D resistance genes in L. serriola. Therefore, a study was conducted to develop SSR markers from expressed sequence tags (ESTs) of 5 Lactuca species. A total of 15,970 SSRs were identified among 57,126 EST assemblies belonging to 5 Lactuca species. SSR-containing ESTs (SSR-ESTs) ranged from 6.23% to 7.87%, and SSR densities ranged from 1.28 to 2.51 kb(-1) among the ESTs of 5 Lactuca species. Trinucleotide repeats were the most abundant SSRs detected during the study. As a representative sample, 45 ESTs carrying class I SSRs (≥ 20 nucleotides) were selected for designing primers and were also searched against the dbEST entries for L. sativa and Helianthus annuus (≤ 10(-50); score ≥ 100). In silico analysis of 45 SSR-ESTs showed 82% conservation across species and 68% conservation across genera. Primer pairs synthesized for the above 45 EST-SSRs were used to study genetic diversity among a collection of 22 L. serriola biotypes. Comparison of the resultant dendrogram to that developed using phenotypic evaluation of the same subset of lines showed limited correspondence. Taken together, this study reported a collection of useful SSR markers for L. serriola, confirmed transferability of these markers within and across genera, and demonstrated their usefulness in studying genetic diversity.


In vivo efficacy of 81.723 hfu, a new pleuromutilin derivative against experimentally induced airsacculitis in chicks and turkey poults.
The efficacy of the pleuromutilin derivative 81.723 hfu was tested in chicks and turkey poults by experimentally infecting them with Mycoplasma gallisepticum. The data were treated to obtain the mean effective doses, and these were compared to those obtained with tylosin tartrate. The compounds were administered either by ingluvial catheter or via the drinking water. Therapy was started on the day of inoculation or 7 days thereafter, respectively. The experiments showed that the compound 81.723 hfu was significantly more active in chickens than tylosin tartrate by both methods of administration of drinking water. In turkey poults the pleuromutilin derivative and tylosin tartrate had comparable activity.


The use of mobile apps to improve nutrition outcomes: A systematic literature review.
We conducted a systematic review to determine if the use of nutrition apps resulted in improved outcomes, including knowledge and behavior, among healthy adults. Using app(s), cellular phone, iPads, mobile phone, mobile telephone, smart phone, mobile and mHealth as search terms with diet, food and nutrition as qualifiers we searched PubMed, CINAHL (January 2008-October 2013) and Web of Science (January 2008-January 2014). Inclusion criteria were peer-reviewed randomized controlled trials, non-controlled trials, and cohort studies published in English that used apps to increase nutrition knowledge or improve behavior related to nutrition. Studies that were descriptive, did not include apps, focused on app development, app satisfaction app feasibility, text messaging, or digital photography were excluded. We evaluated article quality using the Academy of Nutrition and Dietetics Evidence Analysis Manual. Data was extracted for knowledge, behavior and weight change. Our initial search identified 12,010 titles from PubMed, 260 from CINAHL and 4762 from Web of Science; of these, only four articles met all search criteria. Positive quality ratings were given to three articles; only one reported knowledge outcomes (non-significant). All four articles evaluated weight loss and suggested an advantage to using nutrition apps. Behavioral changes in reviewed studies included increased adherence to diet monitoring (p < 0.001) and decreased effort to continue diet without app (p = 0.024). Few studies, however, have explored the use of nutrition apps as supportive educational interventions. Most apps focus on weight loss with inconsistent outcomes. We conclude that using apps for education needs additional research which includes behavior theory within the app and improved study design.


[Ultrastructural characteristics of the salivary glands of of the tick Ixodes persulcatus. II. Type III alveoli of the sucking female].
Electron microscope observations were conducted to study changes in the cellular structure of IIId type alveoli of feeding females of I. persulcatus. Within the first 1-2 days of feeding granulosecreting glandular cells "d" and "e" get free of secretory inclusions. After that cells "d" degenerate completely and cells "e" undergo morphological transformations and start to fulfil osmoregulatory functions. From the third day of feeding cytoplasm of cells "e" and basal intersticial cells form a complex labyrinth from a system of branching processes limiting intercellular space from the basal to apical surfaces of alveolar wall. Cells "e" of I. persulcatus in their structure and functional activity closely resemble the earlier described cells "f" in alveoli III of the tick Rhipicephalus appendiculatus.


Exploration of the lysis mechanisms of leukaemic blasts by chimaeric T-cells.
Adoptive transfer of specific cytotoxic T lymphocytes (CTL) and Cytokine Induced Killer Cells (CIK) following genetic engineering of T-cell receptor zeta hold promising perspective in immunotherapy. In the present work we focused on the mechanisms of anti-tumor action of effectors transduced with an anti-CD19 chimaeric receptor in the context of B-lineage acute lymphoblastic leukemia (B-ALL). Primary B-ALL blasts were efficiently killed by both z-CD19 CTL and z-CD19 CIK effectors. The use of death receptor mediated apoptosis of target cells was excluded since agonists molecules of Fas and TRAIL-receptors failed to induce cell death. Perforin/granzyme pathway was found to be the mechanism of chimaeric effectors mediated killing. Indeed, cytolytic effector molecules perforin as well as granzymes were highly expressed by CTL and CIK. CD19 specific stimulation of transduced effectors was associated with degranulation as attested by CD107 membrane expression and high IFN-gamma and TNF-alpha release. Moreover inhibitors of the perforin-based cytotoxic pathway, Ca(2+)-chelating agent EGTA and Concanamycin A, almost completely abrogated B-ALL blast killing. In conclusion we show that the cytolysis response of z-CD19 chimaeric effectors is predominantly mediated via perforin/granzyme pathway and is independent of death receptors signaling in primary B-ALL.


Functional diversity of microboring Ostreobium algae isolated from corals.
The filamentous chlorophyte Ostreobium sp. dominates shallow marine carbonate microboring communities, and is one of the major agents of reef bioerosion. While its large genetic diversity has emerged, its physiology remains little known, with unexplored relationship between genotypes and phenotypes (endolithic versus free-living growth forms). Here, we isolated nine strains affiliated to two lineages of Ostreobium (>8% sequence divergence of the plastid gene rbcL), one of which was assigned to the family Odoaceae, from the fast-growing coral host Pocillopora acuta Lamarck 1816. Free-living isolates maintained their bioerosive potential, colonizing pre-bleached coral carbonate skeletons. We compared phenotypes, highlighting shifts in pigment and fatty acid compositions, carbon to nitrogen ratios and stable isotope compositions (δ13 C and δ15 N). Our data show a pattern of higher chlorophyll b and lower arachidonic acid (20:4ω6) content in endolithic versus free-living Ostreobium. Photosynthetic carbon fixation and nitrate uptake, quantified via 8 h pulse-labeling with 13 C-bicarbonate and 15 N-nitrate, showed lower isotopic enrichment in endolithic compared to free-living filaments. Our results highlight the functional plasticity of Ostreobium phenotypes. The isotope tracer approach opens the way to further study the biogeochemical cycling and trophic ecology of these cryptic algae at coral holobiont and reef scales.


Ethanol ingestion inhibits cell-mediated immune responses of unprimed T-cell receptor transgenic mice.
This paper introduces a transgenic (Tg) mouse in which the majority of the CD4-bearing T cells have T-cell receptors that react with ovalbumin (OVA) as a model for ethanol research. Although these Tg animals were bred onto the BALB/c genetic background, a strain generally considered to be nonpreferring in ethanol consumption, we determined that BALB/c mice would consume an ethanol-containing liquid diet, without significant mortality, and assessed alteration of specific immune responses. BALB/c, C57BL/6 (B6), or (BALB/c x C57BL/6)F-1 hybrid (CB6F1) mice were fed LED containing 35, 30, 25, or 20% ethanol-derived calories. Significant mortality (> 40%) was seen only in BALB/c and pronounced weight loss was seen in BALB/c, B6, CB6F1 mice when they were fed the diet containing the greatest ethanol concentration (LED35). Diets containing lesser amounts of ethanol did not cause mortality. Liquid diets containing > or = 30% ethanol-derived calories significantly impaired the chicken gamma-globulin-specific delayed hypersensitivity responses in BALB/c, B6, and CB6F1mice without significantly affecting the humoral immune response to sheep red blood cells. We show that immunization of the Tg mice is not required for the development of a vigorous "delayed hypersensitivity" response to OVA or the I-Ad-restricted peptide OVA323-339 in mice fed standard solid lab chow or liquid control diet. In marked contrast, OVA Tg mice fed ethanol show a profound inhibition of this immune response, indicating that ethanol-induced inhibition of cell-mediated immunity occurs independently of antigen priming.


CHIVA method for the treatment of chronic venous insufficiency.
Many surgical approaches are available to treat varicose veins secondary to chronic venous insufficiency. One of the least invasive techniques is the ambulatory conservative hemodynamic correction of venous insufficiency method (cure conservatrice et hémodynamique de l'insuffisance veineuse en ambulatoire (CHIVA)), an approach based on venous hemodynamics with deliberate preservation of the superficial venous system. To compare the efficacy and safety of the CHIVA method with alternative therapeutic techniques to treat varicose veins. The Trials Search Co-ordinator of the Cochrane Peripheral Vascular Diseases Group searched the Specialised Register (November 2012), CENTRAL (2012, Issue 10) and clinical trials databases. The review authors searched PubMed and EMBASE (December 2012). There was no language restriction. We contacted study authors to obtain more information when necessary. We included randomized controlled trials (RCTs) that compared the CHIVA method versus any other treatments. Two review authors independently selected and evaluated the studies. One review author extracted data and performed the quantitative analysis. Two independent review authors extracted data from the selected papers. We calculated the risk ratio (RR), mean difference (MD), the number of people needed to treat for an additional beneficial outcome (NNTB), and the number of people needed to treat for an additional harmful outcome (NNTH), with 95% confidence intervals (CI) using Review Manager 5. We included four RCTs with 796 participants (70.5% women) from the 434 publications identified by the search strategy. Three RCTs compared the CHIVA method with vein stripping, and one RCT compared the CHIVA method with compression dressings in people with venous ulcers. We judged the methodological quality of the included studies as low to moderate. The overall risk of bias across studies was high because neither participants nor outcome assessors were blinded to the interventions. The primary endpoint, clinical recurrence, pooled between studies over a follow-up of 3 to 10 years, showed more favorable results for the CHIVA method than for vein stripping (721 people; RR 0.63; 95% CI 0.51 to 0.78; I(2) = 0%, NNTB 6; 95% CI 4 to 10) or compression dressings (47 people; RR 0.23; 95% CI 0.06 to 0.96; NNTB 3; 95% CI 2 to 17). Only one study reported data on quality of life and these results presented graphically significantly favored the CHIVA method.The vein stripping group had a higher risk of side effects than the CHIVA group; specifically, the RR for bruising was 0.63 (95% CI 0.53 to 0.76; NNTH 4; 95% CI 3 to 6) and the RR for nerve damage was 0.05 (95% CI 0.01 to 0.38; I(2) = 0%; NNTH 12; 95% CI 9 to 20). There were no statistically significant differences between groups regarding the incidence of limb infection and superficial vein thrombosis. The CHIVA method reduces recurrence of varicose veins and produces fewer side effects than vein stripping. However, we based these conclusions on a small number of trials with a high risk of bias as the effects of surgery could not be concealed. New RCTs are needed to confirm these results and to compare CHIVA with approaches other than open surgery.


Prevalence of multiple micronutrient deficiencies amongst pregnant women in a rural area of Haryana.
Deficiencies of micronutrients (zinc, iron, folic acid and iodine) during pregnancy are known causes of Low Birth Weight (LBW). Studies have documented status of one or two micronutrients amongst pregnant women (PW). However, no attempt has been made to concurrently assess the prevalence of multiple micronutrient deficiencies and the factors associated with them amongst PW. The present study was undertaken to assess the prevalence of multiple micronutrient deficiencies amongst PW in a rural area. A community based cross sectional survey was conducted in six villages of a rural area of district Faridabad in Haryana state, India during November 2000 and October 2001. All PW aged 18 years or more, with pregnancy duration of more than 28 weeks were enrolled. Data were collected on socio-economic status and other demographic parameters. Serum zinc, copper and magnesium levels were estimated by utilizing the Atomic absorption spectrophotometry (AAS); serum ferritin and folate was estimated by Enzyme Linked Immuno Sorbent Assay (ELISA) method and the Radio-Immuno Assay (RIA) method, respectively and serum thyroid stimulating hormone (TSH) level was estimated by the Abbot AxSYM System. Serum zinc, copper, magnesium, ferritin, and folate levels less than 70.0 microg/dl, 80.0 microg/dl, 1.80 mg/dl, 15 ng/ml, and 3 ng/ml, respectively were considered as indicative of deficiency for respective micronutrients. The TSH levels of 4.670 and more indicated iodine deficiency status. Dietary intake of micronutrients was assessed utilizing 1-day 24-hour dietary recall methodology. Food consumption pattern was assessed utilizing the food frequency questionnaire methodology. Nearly 73.5, 2.7, 43.6, 73.4, 26.3, and 6.4 percent PW were deficient in zinc, copper, magnesium, iron, folic acid and iodine, respectively. The highest concurrent prevalence of two, three, four and five micronutrient deficiency was of zinc and iron (54.9%); zinc, magnesium and iron (25.6%); zinc, magnesium, iron and folic acid (9.3%) and zinc, magnesium, iron, folic acid and iodine (0.8%), respectively. No pregnant woman was found to have concomitant deficiencies of all the six micronutrients. Dietary intake data revealed an inadequate nutrient intake. Over 19% PW were consuming less than 50% of the recommended calories. Similarly, 99, 86.2, 75.4, 23.6, 3.9 percent of the PW were consuming less than 50% of the recommended folic acid, zinc, iron, copper, and magnesium. The consumption of food groups rich in micronutrients (pulses, vegetables, fruits, nuts and oil seeds, animal foods) was infrequent. Univariate and Multivariate logistic regression analysis revealed that low dietary intake of nutrients, low frequency of consumption of food groups rich in micronutrients and increased reproductive cycles with short interpregnancy intervals were important factors leading to micronutrient deficiencies. There was a high prevalence of micronutrient deficiencies amongst the PW of the area, possibly due to the poor dietary intake of food and low frequency of consumption of food groups rich in micronutrients. The concurrent prevalence of two, three, four and five micronutrient deficiencies were common.


Highly stable, edible cellulose films incorporating chitosan nanoparticles.
The need for biodegradable polymers for packaging has fostered the development of novel, biodegradable polymeric materials from natural sources, as an alternative to reduce amount of waste and environmental impacts. The present investigation involves the synthesis of chitosan nanoparticles-carboxymethylcellulose films, in view of their increasing areas of application in packaging industry. The entire process consists of 2-steps including chitosan nanoparticles preparation and their incorporation in carboxymethylcellulose films. Uniform and stable particles were obtained with 3 different chitosan concentrations. The morphology of chitosan nanoparticles was tested by transmission electron microscopy, revealing the nanoparticles size in the range of 80 to 110 nm. The developed film chitosan nanoparticles-carboxymethylcellulose films were characterized by Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis, solubility tests, and mechanical analysis. Improvement of thermal and mechanical properties were observed in films containing nanoparticles, with the best results occurring upon addition of nanoparticles with 110 nm size in carboxymethylcellulose films. Carboxymethylcellulose films containing chitosan nanoparticles synthesized and characterized in this article could be a potential material for food and beverage packaging applications products due to the increase mechanical properties and high stability. The potential application of the nanocomposites prepared would be in packaging industry to extend the shelf life of products.


Prognostic value of left atrial reverse remodelling in heart failure with preserved ejection fraction.
Left atrial reverse remodelling (LARR) reflects an improvement in the function or structure. However, it is unclear whether the presence of LARR is associated with better outcomes in patients with heart failure with preserved ejection fraction (HFpEF). The study was a monocentric retrospective cohort one. Consecutive HFpEF patients admitted to the hospital between 1 January 2018 and 30 June 2020 were included. This cohort was divided into LARR and non-LARR groups based on the recovery of the left atrium. The primary endpoints were all-cause mortality, rehospitalization for heart failure, and the composite of death or readmission. Significant predictors of LARR were examined. A total of 409 patients were enrolled, including 90 cases in the LARR group and 319 in the non-LARR group. Kaplan-Meier analysis showed that compared with the non-LARR group, the LARR group had a lower incidence of rehospitalization for heart failure and the composite of death or readmission but not all-cause mortality. Similar results were observed in a subgroup analysis of patients with and without atrial fibrillation. Cox regression analysis demonstrated that the non-LARR group experienced higher risks of heart failure-related readmission [hazard ratio: 1.785, 95% confidence interval (CI) 1.236-3.215, P = 0.037] and the composite outcome (hazard ratio: 1.684, 95% CI 1.254-2.865, P = 0.044), but not all-cause mortality (hazard ratio: 1.475, 95% CI: 0.481-3.527, P = 0.577) compared with the LARR group after adjusting for significant confounders. Logistic regression analysis showed that mild mitral regurgitation and the use of loop diuretics were two positive predictors of LARR in patients with HFpEF. LARR is an effective echocardiographic index that can be used to predict heart failure-related readmission in HFpEF. Therefore, regular assessment of left atrial size can provide a useful marker for risk stratification of heart failure.


Pericytes and their potential in regenerative medicine across species.
The discovery that pericytes are in vivo counterparts of Mesenchymal Stem/Stromal Cells (MSCs) has placed these perivascular cells in the research spotlight, bringing up hope for a well-characterized cell source for clinical applications, alternative to poorly defined, heterogeneous MSCs preparations currently in use. Native pericytes express typical MSC markers and, after isolation by fluorescence-activated cell sorting, display an MSC phenotype in culture. These features have been demonstrated in different species, including humans and horses, the main targets of regenerative treatments. Significant clinical potential of pericytes has been shown by transplantation of human cells into rodent models of tissue injury, and it is hoped that future studies will demonstrate clinical potential in veterinary species. Here, we provide an overview of the current knowledge on pericytes across different species including humans, companion and large animal models, in relation to their identification in different body tissues, methodology for prospective isolation, characterization, and potential for tissue regeneration. © 2017 International Society for Advancement of Cytometry.


Effects of glucose infusion on hepatic and muscle glycogenolysis in exercising dogs.
Hepatic glucose production (Ra) and the rate of utilization of nonglucose sources (essentially muscle glycogen) were measured in dogs running on a treadmill (15%, 133 m/min) with indwelling catheters in the jugular vein and carotid artery. A mixture of [3-3H]glucose and [U-14C]glucose was used as tracer according to the principles of the primed constant-rate infusion techniques. Glucose was infused intravenously at a rate (12 mg.kg-1.min-1) about 20% higher than the endogenous glucose Ra in exercising dogs. Glucose infusion started either at the beginning of the run or midexercise. Plasma insulin (IRI), glucagon (IRG), and cAMP levels were measured. Exogenous glucose prevented the usual decline of both plasma glucose and IRI without causing hyperglycemia. Exercise increased the molar ratio of IRG/IRI from 0.7 to 1.4, and glucose infusion lowered it to the resting value. The rise of plasma cAMP was slowed significantly. Both the hepatic glucose Ra and intramuscular glycogenolysis were strongly inhibited and the metabolic clearance rate of glucose was increased by 60-100%. The ratio of the specific activities of [14C]lactate to [14C]glucose indicated that 75-95% of the lactate turnover arose from plasma glucose. The corresponding value in the control group was 40-50%. It is concluded that in prolonged exercise the decline of both plasma glucose and insulin play a major role in preserving glucose homeostasis, by limiting the glucose uptake of the working muscle and by helping to achieve an approximately equal contribution of the liver and the muscle glycogen for the elevated glycolysis.


Clinical efficacy of the SmartPlug™ in the treatment of primary Sjogren's syndrome with keratoconjunctivitis sicca: one-year follow-up study.
To evaluate the efficacy of a thermo-sensitive punctum plug, (SmartPlug™) in Primary Sjogren's Syndrome (pSS) patients with dry eyes, whose symptoms persist despite preservative-free artificial tear treatment. In this study, 22 Primary Sjögren's Syndrome (pSS), as defined by American-European Consensus Group Classification Criteria. All patients being followed up by Ege University Departments of Rheumatology and Ophthalmology. The patients had positive Schirmer test results (<5 mm without anesthesia). SmartPlug™ (Medennium, Irvine, California, USA) was inserted into the inferior lacrimal canaliculi of both eyes. Visual acuity measurements, Schirmer I test measurements, lissamine green staining scores, and tear-film breakup times (BUT) were noted before plug insertion and at the 1st, 6th, and 12th months following the procedure. Minimum follow-up period was 6 months for 19 patients and 12 months for 16 patients. Significant improvements were seen in the Schirmer I test scores (before insertion: 1.98 ± 2.67; 1st month: 5.68 ± 6.69; 6th month: 5.35 ± 5.38; 12th month 6.43 ± 5.14 P = 0.006), tear-film BUT in seconds (before insertion: 4.64 ± 3.7; 1st month: 5.80 ± 2.36; 6th month: 7.53 ± 2.92; 12th month 7.50 ± 2.52, P < 0.0001), respectively. Thermodynamic punctum plug insertion only in inferior canaliculus is a simple, effective, and comfortable option for treatment of severe aqueous tear deficiency that cannot be controlled using preservative-free tears.


A Longitudinal Examination of the Moderating Effects of Symptoms on the Relationship between Functional Competence and Real World Functional Performance in Schizophrenia.
Many individuals with schizophrenia experience remission of prominent positive symptoms but continue to experience impairments in real world functioning. Residual negative and depressive symptoms may have a direct impact on functioning and impair patients' ability to use the cognitive and functional skills that they possess (competence) in the real world (functional performance). 136 individuals (100 men, 36 women) with schizophrenia were classified as having primarily positive symptoms, primarily negative symptoms, primarily depressive symptoms, or undifferentiated symptom profiles. Performance based measures of cognition and adaptive and interpersonal functional competence were used, along with ratings of real world behavior by high contact clinicians. Assessments were performed at baseline and at an 18-month follow-up. The relationships between neurocognition and capacity / performance were not moderated by symptom group ps > .091; neurocognition predicted capacity and performance for all groups ps < .001. The relationship between adaptive competence and adaptive performance was moderated by symptom group, ps < .01, such that baseline competence only predicted future performance ratings for participants with primarily positive or undifferentiated symptoms, and not for individuals with primarily negative or depressive symptoms. This same moderation effect was found on the relationship between interpersonal competence and interpersonal performance, ps < .002. Residual negative and depressive symptoms are distinct constructs that impede the use of functional skills in the real world. Depressive symptoms are often overlooked in schizophrenia but appear to be an important factor that limits the use of functional ability in real world environments.


Influence of heat treatment and oxygen doping on the mechanical properties and biocompatibility of titanium-niobium binary alloys.
The most commonly used titanium (Ti)-based alloy for biological applications is Ti-6Al-4V, but some studies associate the vanadium (V) with the cytotoxic effects and adverse reactions in tissues, while aluminum (Al) has been associated with neurological disorders. Ti-Nb alloys belong to a new class of Ti-based alloys with no presence of Al and V and with elasticity modulus values that are very attractive for use as a biomaterial. It is well known that the presence of interstitial elements (such as oxygen, for example) changes the mechanical properties of alloys significantly, particularly the elastic properties, the same way that heat treatments can change the microstructure of these alloys. This article presents the effect of heat treatment and oxygen doping in some mechanical properties and the biocompatibility of three alloys of the Ti-Nb system, characterized by density measurements, X-ray diffraction, optical microscopy, Vickers microhardness, in vitro cytotoxicity, and mechanical spectroscopy.


How the causes, consequences and solutions for problem gambling are reported in Australian newspapers: a qualitative content analysis.
To inform public health approaches to problem gambling by examining how the news media covers problem gambling, with a particular focus on the causes, consequences and solutions to problem gambling, and the 'actors' and sources who influence media coverage. A qualitative content analysis guided by framing theory analysed coverage of problem gambling in Australian newspapers in the period 1 July 2011 to 30 June 2012. Solutions to problem gambling were more frequently discussed than causes and consequences. A focus on the responsibility of individuals was preferred to reporting that focused on broader social, ecological, and industry determinants of problem gambling. Reporting was highly politicised, with politicians frequently quoted and political issues frequently discussed. In contrast, the community sector, health professionals and problem gamblers were rarely quoted. This analysis has revealed the need for a more proactive, coordinated approach to the media by both public health researchers and health groups. The establishment of a gambling-specific coalition to push for evidence-based reform is recommended.


Bifunctional atrial natriuretic peptide receptor (type A) exists as a disulfide-linked tetramer in plasma membranes of bovine adrenal cortex.
Type A atrial natriuretic peptide (ANP) receptor was demonstrated to be present as a tetramer in the bovine adrenal cortex. Type A ANP receptor is composed of two functional domains, namely extracellular ANP-binding and cytoplasmic guanylate cyclase domains, and generally considered to be present as a single polypeptide chain of about 140 kDa based on its primary structure deduced from the cDNA sequence and its SDS/PAGE profile under reducing conditions. Characterization of the type A receptor or receptor/cyclase under non-reducing conditions led to the discovery stated in the title. The type A ANP receptor was partially purified from bovine adrenal cortex membranes by Blue-Sepharose and GTP-agarose chromatography. SDS-PAGE analysis of the receptor preparation revealed that although under reducing conditions it migrated as a 140-kDa band, the mobility of the receptor was greatly retarded in the absence of reducing agents, suggesting that the type A ANP receptor is present as a disulfide-linked oligomer in its native state. Further analysis using SDS-polyacrylamide-agarose gels suitable for determining the sizes of high-molecular-weight proteins revealed that the oligomer has an Mr of 500,000-550,000. This result clearly indicates that the native form of the type A receptor is a tetramer composed of four 140-kDa disulfide-linked receptor/cyclase molecules.


Can ornamental potted plants remove volatile organic compounds from indoor air? A review.
Volatile organic compounds (VOCs) are found in indoor air, and many of these can affect human health (e.g. formaldehyde and benzene are carcinogenic). Plants affect the levels of VOCs in indoor environments, thus they represent a potential green solution for improving indoor air quality that at the same time can improve human health. This article reviews scientific studies of plants' ability to remove VOCs from indoor air. The focus of the review is on pathways of VOC removal by the plants and factors affecting the efficiency and rate of VOC removal by plants. Laboratory based studies indicate that plant induced removal of VOCs is a combination of direct (e.g. absorption) and indirect (e.g. biotransformation by microorganisms) mechanisms. They also demonstrate that plants' rate of reducing the level of VOCs is influenced by a number of factors such as plant species, light intensity and VOC concentration. For instance, an increase in light intensity has in some studies been shown to lead to an increase in removal of a pollutant. Studies conducted in real-life settings such as offices and homes are few and show mixed results.


The effect of light level, CO2 flow rate, and anesthesia on the stress response of mice during CO2 euthanasia.
Euthanasia protocols are designed to mitigate the stress experienced by animals, and an environment that induces minimal stress helps achieve that goal. A protocol that is efficient and practical in a typical animal research facility is also important. Light intensity, isoflurane, and CO2 flow rate were studied for their impact on the stress response of mice during CO2 euthanasia. Behavior was observed and scored during euthanasia and serum corticosterone was measured immediately after death. Unsurprisingly, animals euthanized with a high-flow rate of CO2 became unconscious in the least amount of time, while animals euthanized with a low-flow rate required the most time to reach unconsciousness. There was a significant increase in anxious behaviors in animals in the isoflurane group (F1,12 = 6.67, P = 0.024), the high-flow rate CO2 group (F1,12 = 10.24, P = 0.007), and bright chamber group (F1,12 = 7.27, P = 0.019). Serum corticosterone was highest in the isoflurane group (124.72 ± 83.98 ng/ml), however there was no significant difference in corticosterone levels observed for the other study variables of light and flow-rate. A darkened chamber and low CO2 flow rates help to decrease stress experienced during CO2 euthanasia, while the use of isoflurane was observed to increase the stress response during euthanasia.


Standardized Bacopa monnieri Extract Ameliorates Learning and Memory Impairments through Synaptic Protein, Neurogranin, Pro-and Mature BDNF Signaling, and HPA Axis in Prenatally Stressed Rat Offspring.
Prenatal stress (PNS) influences offspring neurodevelopment, inducing anxiety-like behavior and memory deficits. We investigated whether pretreatment of Bacopa monnieri extract (CDRI-08/BME) ameliorates PNS-induced changes in signaling molecules, and changes in the behavior of Wistar rat offspring. Pregnant rats were randomly assigned into control (CON)/prenatal stress (PNS)/PNS and exposed to BME treatment (PNS + BME). Dams were exposed to stress by placing them in a social defeat cage, where they observed social defeat from gestational day (GD)-16-18. Pregnant rats in the PNS + BME group were given BME treatment from GD-10 to their offspring's postnatal day (PND)-23, and to their offspring from PND-15 to -30. PNS led to anxiety-like behavior; impaired memory; increased the level of corticosterone (CORT), adrenocorticotropic hormone, glucocorticoid receptor, pro-apoptotic Casepase-3, and 5-HT2C receptor; decreased anti-apoptotic Bcl-2, synaptic proteins (synaptophysin, synaptotagmin-1), 5-HT1A, receptor, phosphorylation of calmodulin-dependent protein kinase II/neurogranin, N-methyl-D-aspartate receptors (2A,2B), postsynaptic density protein 95; and conversion of pro and mature brain derived neurotropic factor in their offspring. The antioxidant property of BME possibly inhibiting the PNS-induced changes in observed molecules, anxiety-like behavior, and memory deficits. The observed results suggest that pretreatment of BME could be an effective coping strategy to prevent PNS-induced behavioral impairments in their offspring.


Magnetic metamaterial superlens for increased range wireless power transfer.
The ability to wirelessly power electrical devices is becoming of greater urgency as a component of energy conservation and sustainability efforts. Due to health and safety concerns, most wireless power transfer (WPT) schemes utilize very low frequency, quasi-static, magnetic fields; power transfer occurs via magneto-inductive (MI) coupling between conducting loops serving as transmitter and receiver. At the "long range" regime - referring to distances larger than the diameter of the largest loop - WPT efficiency in free space falls off as (1/d)(6); power loss quickly approaches 100% and limits practical implementations of WPT to relatively tight distances between power source and device. A "superlens", however, can concentrate the magnetic near fields of a source. Here, we demonstrate the impact of a magnetic metamaterial (MM) superlens on long-range near-field WPT, quantitatively confirming in simulation and measurement at 13-16 MHz the conditions under which the superlens can enhance power transfer efficiency compared to the lens-less free-space system.


Expression of xenotropic-like env RNA sequences in normal DBA/2 and NZB mouse tissues.
Using a DNA probe prepared from cloned env gene sequences of Friend spleen focus-forming viruses, we detected the differential expression of multiple RNA species in uninfected DBA/2 fibroblasts and in various tissues from adult DBA/2 and NZB mice. The size of the major RNA species detected was estimated to be 24S . The 24S RNA species was enriched in polyadenylate-selected preparations and thus may represent a message for endogenous viral envelope glycoproteins. The viral origin of the 24S RNA was further characterized by its hybridization to DNA probes containing the long terminal repeats of Harvey murine sarcoma virus, mouse mammary tumor virus, or the U3 region of an endogenous xenotropic virus. Although the env-related 24S RNA failed to react with either Harvey murine sarcoma virus or mouse mammary tumor virus long terminal repeat probes, it hybridized well with the xenotropic virus long terminal repeat probe. Therefore, it is likely that the RNA detected with the Friend spleen focus-forming virus env probe reflects transcription of xenotropic envelope sequences in uninfected tissues. Our finding that the level of 24S RNA varied in different organs indicated some tissue specificity in the expression of these xenotropic-like env proteins.


Lipid assessment, metabolic syndrome and coronary heart disease risk.
Although the total to high-density lipoprotein cholesterol ratio (TC/HDL-C) has been used for decades to identify individuals at risk for coronary heart disease (CHD), apolipoprotein-based (apolipoprotein B/apolipoprotein A-I [apoB/apoA-I]) and nuclear magnetic resonance spectroscopy (NMR)-based lipoprotein concentrations (low-density lipoprotein(NMR) /high-density lipoprotein(NMR) [LDL(NMR) /HDL(NMR)]) may also be useful for CHD risk stratification. In a case-control study conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk study population, 870 individuals who developed CHD during a 6-year follow-up were matched to 1659 controls on the basis of gender, age and enrollment time. LDL(NMR) and HDL(NMR) were measured by proton NMR spectroscopy. After adjusting for traditional CHD risk factors, men in the top quintile of the various lipoprotein ratios proved to be at increased CHD risk (OR = 2·59 [95% IC, 1·76-3·83] for TC/HDL-C ratio, 2·59 [1·75-3·83] for apoB/apoA-I ratio and 2·78 [1·86-4·17] for LDL(NMR) /HDL(NMR) ratio) compared with men in the bottom quintile. Similar associations were observed in women (OR = 2·86 [1·71-4·80] for TC/HDL-C ratio, 2·94 [1·74-4·97] for apoB/apoA-I ratio and 2·03 [1·21-3·43] for LDL(NMR)/HDL(NMR) ratio). Compared with participants with only one component of the metabolic syndrome, those who had five had an increased TC/HDL-C ratio (73·0% and 80·4% in men and women respectively), apoB/apoA-I ratio (58·0% and 62·9% in men and women respectively) and for LDL(NMR)/HDL(NMR) ratio (52·6% and 54·1% in men and women respectively). In this European study population, the TC/HDL-C, apoB/apoA-I and LDL(NMR) /HDL(NMR) ratios were similarly associated with components of the metabolic syndrome and CHD risk.


Proliferative effect of ammodytin L from the venom of Vipera ammodytes on 208F rat fibroblasts in culture.
Ammodytin L, purified from the venom of Vipera ammodytes, triggers a rapid and dramatic lytic process in myotubes in vitro, as well as in differentiated muscle cells in vivo, through a mechanism that is not well understood. Despite its great sequence similarity to phospholipase A2, it is devoid of any enzyme activity. Data on artificial membranes demonstrating a direct interaction between this toxin and the hydrophobic core of the lipid bilayer suggest that the toxin also acts on the lipid microenvironment in cell membranes. Recent experiments on living cells do not confirm this hypothesis, and a more intricate mechanism is proposed. In vitro, ammodytin L has necrotic effects only in well-differentiated myogenic cells, whereas other cell types such as platelets, red blood cells and lymphocytes show neither morphological nor functional alterations. In this work we demonstrate that rat 208F fibroblasts in culture after ammodytin L challenge increase [3H]thymidine incorporation, indicating that this toxin has a myogenic effect. Moreover, ammodytin L increases intracellular Ca2+ by acting on intracellular stores probably by activating a phosphatidylinositol-specific phospholipase C. Preincubation of the cells with ammodytin L did not prevent the massive Ca2+ release evoked by bradykinin, a phenomenon observed when fibroblasts were incubated with both thapsigargin and ionomycin. Heparin, an agent that inhibits the necrotic effect of the myotoxin in myotubes, also reduces the effect of ammodytin L on DNA synthesis. Heparin inhibits only the late sustained increase in intracellular Ca2+ induced by the toxin.


Suicide, guns, and buyback programs: An epidemiologic analysis of firearm-related deaths in Connecticut.
Gun buyback programs aim to remove unwanted firearms from the community with the goal of preventing firearm injury and death. Buyback programs are held in many communities, but evidence demonstrating their effectiveness is lacking. The purpose of this study is to compare firearms collected at buyback events to crime guns and firearms used in homicides and suicides. Detailed firearm and case data were obtained from the Hartford Police Department and the Office of the Chief Medical Examiner from January through December of 2015. Information was reviewed for guns collected at buyback events, crime guns confiscated by police, and for weapons associated with firearm fatalities. Detailed firearm data included type, manufacturer, model, and caliber (small, ≤ 0.32 caliber; medium, 0.357 caliber to 9 mm; large, ≥ 0.40 caliber). χ analyses were used for comparisons between groups. In 2015, 224 crime guns were seized by the Hartford Police, 169 guns were collected at four community buyback events, and there were 187 firearm-related deaths statewide (105 suicides, 81 homicides, 1 legal intervention). Comparisons between buyback, crime, and fatality-related firearms are shown in the table below. Medium caliber handguns account for the majority of crime guns and fatalities, and buyback programs collected smaller caliber handguns. The demographics of individuals who turn in guns at buyback events and commit suicide are similar: age (buyback, 63 ± 11; suicide, 52 ± 18; homicide, 34 ± 12 years), sex (buyback, 81%; suicide, 91%; homicide, 84% men), and race (buyback, 80%; suicide, 97%; homicide, 47% white). Handguns account for the majority of crime guns and firearm-related fatalities in Connecticut. Buyback programs are both an opportunity to remove unwanted handguns from the community and to remove firearms from the homes of individuals at increased risk of suicide. Epidemiologic/therapeutic study, level IV.


[Immunohistochemistry of biomolecular markers of early thyroid cancer].
Surgery material from 28 cases was studied. Thyroid adenoma differs from thyroid carcinoma by a lower level of expression of Ki-67 and bcl-2, while the mutated p53 expression is lacking. These indices may be used for early and differential diagnosis of thyroid carcinoma. Medullary carcinoma is a tumor with the highest malignant potential and p53 and bcl-2 may serve as markers of a higher degree of malignancy. Ki-67 may serve a marker of proliferative activity of tumors belonging to the same histological type. Thus, its high expression in follicular carcinoma is an index of a high proliferative activity of its cells, correlates with its rapid growth and should be taken into consideration in therapy and prognosis. Expression of bcl-2 clearly correlates with neuroendocrine differentiation of carcinoma and its highest expression was found in the medullary carcinoma as well as in the chromogranin positive cells of the papillary thyroid carcinoma. APUD amyloid deposits in medullary carcinoma and high levels of c-myc in adenomas indicate some genetic restructurizations in malignant and benign thyroid tumors.


Isolation of amino acids from natural samples using sublimation.
Amino acids have appreciable vapor pressures above 150 degrees C and will sublime under partial vacuum at elevated temperatures without any racemization or decomposition. The recoveries of several amino acids including aspartic acid, serine, glycine, alanine, alpha-aminoisobutyric acid, and valine were optimized by varying the temperature and duration of sublimation. Sublimation has been shown to be a rapid and effective technique for the isolation of amino acids from natural samples for enantiomeric analyses and a good substitute for conventional cation-exchange desalting techniques.


Bacterial and fungal aerosols in indoor environment in Central and Eastern European countries.
Studies of indoor bioaerosols conducted in Central and Eastern European countries, as a result of the scarcity of funding, mostly do not attain the level presented by similar studies in Northern America and Western Europe. For socio-economic reasons, most of the intense studies on indoor bioaerosols in Central and Eastern European countries were carried out in industrial facilities and have contributed significantly to occupational health science. In contrast, until recently, insufficient of studies have been conducted on bioaerosols of residential and communal premises (dwellings, offices, schools, etc.) and no network for monitoring the microbiological quality of air in such premises exists. In Poland, in the mid-1990s complex bioaerosol investigations were carried out by the Bioaerosol Group at the Institute of Occupational Medicine and Environmental Health in Sosnowiec. The concentrations of airborne bacteria and fungi in dwellings without mold problems were between 88-4297 cfu/m(3) and 0-1997 cfu/m(3), while in moldy homes they were 178-4751 cfu/m(3) and 49-16,968 cfu/m(3), respectively. As many as 167 microbial species were isolated from the air of examined dwellings. Most frequently occurred Gram-positive cocci (Micrococcus/ Kocuria spp., Staphylococcus spp.), endospore-forming bacilli (Bacillus spp.), Gram-negative bacteria (Pseudomonadaceae, Aeromonas spp.), filamentous fungi (Penicillium spp., Aspergillus spp.), and yeasts. Notable studies of indoor bioaerosols have also been performed in the other Central and Eastern European countries: Lithuania, Latvia, Estonia, Russian Federation, Ukraine, Czech Republic, Slovakia, Bulgaria and Hungary, are reviewed in this article. The lack of reference limit values for bioaerosols seriously hinders interpretation of results obtained in various countries. The following residential limit values (RLV) for dwellings and communal premises are proposed for the concentration of airborne bacteria, fungi and bacterial endotoxin: 5 x 10(3) cfu/m(3), 5 x 10(3) cfu/m(3) and 5 ng/m(3) (50 EU), respectively. The proposed values of occupational exposure limit (OEL) for industrial settings contaminated by organic dust are 100 x (3) cfu/m(3), 50 x (3) cfu/m(3) and 200 ng/m(3) (2000 EU), respectively. It is also proposed that the presence in indoor air of microorganisms from risk groups 3 and 4 of European Community Directive 2000/54/EC (e.g., Mycobacterium tuberculosis, Bacillus anthracis, Coxiella burnetii), independently of the concentration, should always be inadmissible and result in preventive actions.


Rituximab: an insider's historical perspective.
Rituximab (Rituxan; Genentech, Inc, South San Francisco, CA and IDEC Pharmaceutical Corporation, San Diego, CA) is a unique monoclonal antibody for the treatment of non-Hodgkin's lymphoma. This chimeric mouse/human antibody was discovered in 1991 at IDEC Pharmaceuticals' laboratories, where the antibody was genetically engineered and produced utilizing high-yield expression systems. It is a human IgG1 kappa antibody with mouse variable regions isolated from a murine anti-CD20 antibody, IDEC-2B8, that binds with high affinity to cells expressing the CD20 antigen found on the surface of malignant and normal B cells, but not on other normal tissues. It mediates complement-dependent cell lysis in the presence of human complement, and antibody-dependent cellular cytotoxicity with human effector cells. Also, it has been shown to induce apoptosis and to sensitize chemoresistant human lymphoma cell lines in vitro. Clinical development was expedited (3 years) with the first patient entered in phase I trials in March 1993 and the last patient entered in the phase III study in March 1996. IDEC Pharmaceuticals began a collaboration with Genentech, Inc in March 1995 and with F. Hoffman-LaRoche (Nutley, NJ) shortly thereafter. Marketing approval was granted by the US Food and Drug Administration on November 26, 1997 (and by the European Union on June 2, 1998) for the indication of relapsed or refractory, CD20-positive, B-cell, low-grade or follicular non-Hodgkin's lymphoma. Rituximab is the first therapeutic monoclonal antibody approved for the treatment of cancer and the first single agent approved specifically for therapy for a lymphoma. Substantial research has been performed over the past 8 years to further the understanding of this novel therapeutic. Nevertheless, much remains to be accomplished in key areas such as mechanism of action and resistance, combinations with chemotherapy, biologics and radiotherapy/radioimmunotherapy, role within multimodality regimens, and nonmalignant applications. Research conducted in the coming years should be targeted toward resolving these important issues.


Skin homing of Treponema pallidum in early syphilis: an immunohistochemical study.
The incidence of syphilis is increasing in most parts of the world including some major European cities. The lesions developing during secondary syphilis may be difficult to diagnose clinically. Similarly, the histopathologic changes do not always fulfill the typical diagnostic criteria. The objective of this study was to assess the contribution of immunohistochemistry for the identification and localization of Treponema pallidum on the skin. We retrieved from our files 12 paraffin-embedded biopsies of skin lesions, which had posed diagnostic problems in the past. Only a serologic test had proven that the patients had syphilis. Controls consisted of lichenoid dermatoses unrelated to syphilis and borreliosis. Immunohistochemistry using an antispirochete (T. pallidum and Borrelia) antibody was performed retrospectively. In all samples from primary and secondary syphilis, T. pallidum was highlighted, but none of the control lesions unrelated to syphilis showed positivity. Interestingly enough, T. pallidum present in the lower mid-part of the epidermis often outnumbered that in the dermis. This difference was more striking in secondary syphilis compared with primary syphilis. Immunohistochemistry for T. pallidum considerably increased the sensitivity and the specificity of the histologic diagnosis. The strong epidermal homing of T. pallidum is highlighted in early syphilis.


Parental experiences of the impacts of Covid-19 on the care of young children; qualitative interview findings from the Nairobi Early Childcare in Slums (NECS) project.
The Covid-19 pandemic, and societal attempts to control it, have touched almost every aspect of people's lives around the world, albeit in unequal ways. In particular, there is considerable concern about the way that stringent 'lockdowns', as implemented in Kenya and many other countries, affected young children, especially those living in informal settlements. However, to date, there has been little research attempting to unpack and understand how the pandemic has impacted on the care of young children. In-depth telephone interviews were conducted with 21 parents/carers of children aged under five years living in three Nairobi slums between May and September 2021 exploring the ways in which Covid-19, and policies to control the pandemic, impacted on their household and the care of their child/children. The impacts of Covid-19 control measures on the care of children have been widely felt, deep and multiple. The impact of economic hardship has been significant, reportedly undermining food security and access to services including healthcare and childcare. Respondents reported an associated increase in domestic and community violence. Many people relied on help from others; this was most commonly reported to be in the form of variable levels of flexibility from landlords and help from other community members. No direct harms from Covid-19 disease were reported by respondents. The impacts of Covid-19 control measures on the care of young children in informal settlements have been indirect but dramatic. Given the breadth and depth of these reported impacts, and the particular vulnerability of young children, deeper consideration ought to inform decisions about approaches to implementation of stringent disease control measures in future. In addition, these findings imply a need for both short- and long-term policy responses to ameliorate the impacts described.


Mastoid and epitympanic bony obliteration in pediatric cholesteatoma.
The primary goal of cholesteatoma surgery is complete eradication of the disease. To lower the recurrence rate in the pediatric population in canal wall up techniques and to avoid the disadvantages of canal wall down techniques, the bony obliteration technique with epitympanic and mastoid obliteration has been developed. The objective of this study was to evaluate the long-term surgical outcome and recurrence rate of this technique in children. Retrospective case review. : Tertiary referral center. Fifty-two children (<16 yr) were operated on in 90.4% (n = 47) for a primary or recurrent cholesteatoma and in 9.6% (n = 5) for an unstable cavity. In all cases, we closed the tympanoattical barrier and the posterior tympanotomy with sculpted cortical bone and then completed obliteration of the epitympanum and mastoid with bone pâté. A reconstruction of the middle ear was performed by means of an allograft tympanic membrane including the malleus handle and a sculpted allograft malleus or incus for columellar reconstruction. Recurrent rate; residual rate; functional outcome; hygienic status of the ear; long-term safety issues. The mean follow-up time was 49.5 months (range, 12-101.3 mo). Recurrent cholesteatoma occurred in 1.9% (n = 1). Residual cholesteatoma was detected in 15.4% (n = 8) of the cases. Postoperative hearing results revealed a median gain on pure-tone averages of 14.3 dB and a median postoperative air-bone gap of 25.6 dB. The mastoid and epitympanic BOT is an effective technique to lower the recurrence rate of cholesteatoma in the pediatric population. Follow-up by magnetic resonance imaging provides a safe, noninvasive method for postoperative detection of residual cholesteatoma.


Virtual planning for corrections of hemifacial microsomia.
This article describes the many anomalies within and outside the head and neck of hemifacial microsomia (HFM). The OMENS+ classification system is described with particular reference to the mandibular features classified by Pruzansky and modified by Kaban. The application of virtual surgical planning (VSP) to HFM, largely in children, is described and taken through to aspects indicated in maturity. VSP is demonstrated with clinical cases examples in HFM patients for (1) grafts and flaps replacing missing parts of the zygomatic bone, temporo-mandibular joint and mandible, (2) distraction osteogenesis for lengthening of the mandibular ramus, advancement of the mandibular body, widening of the face and simultaneous mid-face and mandibular rotation, (3) implants and correction of microtia for bone anchored ear prostheses, (4) correction of microtia by autogenous ear construction, and (5) end stage rotational bimaxillary osteotomies. 3D virtual and physical planning is a valuable adjunct to the treatment of this complex condition.


Effects of Radix Puerariae flavones on liver lipid metabolism in ovariectomized rats.
To study the effects of Radix Puerariae flavones (RPF) on liver lipid metabolism in ovariectomized (OVX) rats. Forty adult female Wistar rats were randomly divided into four groups: OVX group; sham-OVX group; OVX+estrogen group and OVX+RPF group. One week after operation rats of the first two groups were treated with physiological saline, rats of OVX+estrogen group with estrogen (1 mg/kg.b.w.) and rats of OVX+RPF group with RPF (100 mg/kg.b.w.), respectively for 5 weeks. After the rats were killed, their body weight, the weight of the abdominal fat and uterus were measured, and the levels of total cholesterol (TC) and triglyceride (TG) in liver homogenate were determined. Compared with the sham-OVX group, the body mass of the rats in OVX group was found increased significantly; more abdominal fat in store; TC and TG in liver increased and uterine became further atrophy. As a result, the RPF was found to have an inhibitive action on those changes of various degrees. RPF has estrogen-like effect on lipid metabolism in liver and adipose tissue.


The associations between a polygenic score, reproductive and menstrual risk factors and breast cancer risk.
We evaluated whether 13 single nucleotide polymorphisms (SNPs) identified in genome-wide association studies interact with one another and with reproductive and menstrual risk factors in association with breast cancer risk. DNA samples and information on parity, breastfeeding, age at menarche, age at first birth, and age at menopause were collected through structured interviews from 1,484 breast cancer cases and 1,307 controls who participated in a population-based case-control study conducted in three US states. A polygenic score was created as the sum of risk allele copies multiplied by the corresponding log odds estimate. Logistic regression was used to test the associations between SNPs, the score, reproductive and menstrual factors, and breast cancer risk. Nonlinearity of the score was assessed by the inclusion of a quadratic term for polygenic score. Interactions between the aforementioned variables were tested by including a cross-product term in models. We confirmed associations between rs13387042 (2q35), rs4973768 (SLC4A7), rs10941679 (5p12), rs2981582 (FGFR2), rs3817198 (LSP1), rs3803662 (TOX3), and rs6504950 (STXBP4) with breast cancer. Women in the score's highest quintile had 2.2-fold increased risk when compared to women in the lowest quintile (95 % confidence interval: 1.67-2.88). The quadratic polygenic score term was not significant in the model (p = 0.85), suggesting that the established breast cancer loci are not associated with increased risk more than the sum of risk alleles. Modifications of menstrual and reproductive risk factors associations with breast cancer risk by polygenic score were not observed. Our results suggest that the interactions between breast cancer susceptibility loci and reproductive factors are not strong contributors to breast cancer risk.


Can we predict peritoneal adhesions formation after cesarean delivery?
To examine demographic and obstetrical factors that are associated with adhesion formation following cesarean delivery. We conducted a population-based study that included all women over 18 years og age who underwent two cesarean deliveries between the years 1988 and 2016 in a large tertiary medical center. We excluded women with adhesions already diagnosed during the first cesarean delivery, history of other abdominal or pelvic surgery, history of pelvic infection or pelvic inflammatory disease, history of endometriosis and history of uterine Müllerian anomalies. In addition, women with a classical or T-shaped uterine incision, non-singleton pregnancies, and fetal chromosomal or structural abnormalities were excluded. During the study period, 32.6% (n = 2283) of women were diagnosed with peritoneal adhesions during the second cesarean delivery. Factors found to be significantly associated with peritoneal adhesions were maternal age 35 years or older at the first cesarean delivery, Bedouin Arab ethnicity, composite of intrapartum and postpartum infectious morbidity, and cesarean deliveries that were performed after the onset of labor. In contrast, having a previous vaginal birth was found to be protective. Our results suggest that a woman's characteristics at her first cesarean delivery and her obstetrical history may be predictive of the likelihood of adhesion formation.


Isolated Flailed P3 Scallop of the Mitral Valve Leaflet in the Setting of Newly Diagnosed Heart Failure With Preserved Ejection Fraction.
Mitral valve prolapse (MVP) is characterized by typical fibromyxomatous changes in the mitral leaflet tissue with superior displacement of one or both leaflets into the left atrium. An echocardiogram is a fundamental study required for the diagnosis of MVP with a flail leaflet and grading of mitral regurgitation (MR) severity. Most patients with MVP have a risk of cardiovascular morbidity and mortality similar to that of the general population, though moderate to severe MR and left ventricular (LV) ejection fraction less than 50% have been postulated to increase the risk of adverse cardiac events. In this case report, we present an isolated flailed P3 scallop of the mitral valve leaflet leading to severe MR and acute congestive heart failure. A 54-year-old African-American male with a medical history of hypertension, hyperlipidemia, and transient ischemic attack, presented to the emergency department (ED) for evaluation of dyspnea on exertion. The patient reported that his dyspnea started one week prior to ED visit and was associated with intermittent chest pain. He also endorsed mild orthopnea and lightheadedness, though he denied any syncopal event. Vital signs were found within normal limits on arrival. He clinically appeared to be volume overloaded which improved quickly with IV furosemide. Transesophageal echocardiogram (TEE) with 3D image acquisition showed significant for hyper-dynamic LV function and evidence of isolated flailed P3 scallop of the mitral valve (MV) leaflet resulting in a severe eccentric, anteriorly directed MR jet. The MV leaflets did not appear thickened, and there was no evidence of mitral or aortic stenosis. Cardiac catheterization showed multivessel disease for which the patient underwent coronary artery bypass grafting and MV repair. This patient presented with new-onset congestive heart failure secondary to severe MR associated with undiagnosed MVP. Commonly, the middle scallop (P2) of the posterior leaflet is more prone to prolapse due to its redundancy and variable thickness with the impact of greater systolic pressure. However, in this case of acute severe MR, we identified an isolated flail of the P3 segment. We believe that this rare TEE finding was associated with a torn chordae or ruptured papillary muscle secondary to ischemic disease as the posteromedial papillary muscle has a single blood supply and is particularly prompted to injury from myocardial infarction.


Survival of bone marrow mesenchymal stem cells labelled with red fluorescent protein in an ovine model of collagenase-induced tendinitis.
The aim of this study was to track the survival and efficacy of allogeneic bone marrow mesenchymal stem cells (BM-MSC) marked with red fluorescent protein (BM-MSCRFP) in an ovine model of collagenase-induced tendinopathy. Bone marrow was harvested from one donor sheep and BM-MSC were isolated, cultivated and transfected with red fluorescent protein (BM-MSCRFP). Collagenase was injected into both Achilles tendons in the remaining nine sheep. After two weeks the left tendon was injected with a solution of 6 x 10⁶ BM-MSCRFP and fibrin glue, while only fibrin glue was administered to the contra-lateral tendon in each sheep. After three, four and six weeks the tendons were harvested and evaluated for morphology, collagen I deposition, presence of CD34+ cells, and fluorescent labelled BM-MSC. We demonstrated that delivery of BM-MSC into tendon lesions had positive effects on the injured tendons. The BM-MSCRFP survived at three, four and six weeks after treatment, leading to better quality healing of tendons as compared to the controls, where no labelled cells were detected. Interestingly, we demonstrated high expression of CD34+ cells in tendons that had been treated with BM-MSCRFP. Mesenchymal stem cell allografts have a positive effect on tendon healing and local injection of BM-MSC directly into the tendon allows the homing of BM-MSC for good efficiency of engraftment.


[Chronic obstructive lung diseases associated with systemic arterial hypertension].
A total of 203 patients with chronic obstructive pulmonary diseases (COPD) with normal blood pressure (BP) as well as with systemic arterial hypertension of different character (labile and stable pulmonogenic essential hypertension) were examined. It was established that if COPD is associated with labile pulmonogenic hypertension and essential hypertension, the underlying disease runs a more benign course. In patients with COPD associated with normal BP or with labile pulmonogenic hypertension, use can be made of broncholytic drugs of different adrenoreceptor action. In associated COPD and stable pulmonogenic hypertension or essential hypertension it is desirable to administer selective stimulants of beta-2-adrenoreceptors, e.g. salbutamol.


Cardiac involvement and treatment-related mortality after non-myeloablative haemopoietic stem-cell transplantation with unselected autologous peripheral blood for patients with systemic sclerosis: a retrospective analysis.
Autologous haemopoietic stem-cell transplantation (HSCT) benefits patients with systemic sclerosis but has been associated with significant treatment-related mortality and failure to improve diffusion capacity of carbon monoxide (DLCO). We aimed to assess efficacy of HSCT and use of rigorous cardiac screening in this group. We assessed patients with diffuse systemic sclerosis or limited systemic sclerosis and interstitial lung disease who were treated with HSCT as part of a study or on a compassionate basis at Northwestern University (Chicago, IL, USA) or the University of São Paulo (Ribeirão Preto, Brazil). Unselected peripheral blood stem cells were harvested with cyclophosphamide (2 g/m(2)) and filgrastim. The transplant regimen was a non-myeloablative regimen of cyclophosphamide (200 mg/kg) and rabbit anti-thymocyte globulin (rATG; 4·5-6·5 mg/kg). We followed patients up to 5 years for overall survival, relapse-free survival, modified Rodnan skin score, and pulmonary function tests. Five (6%) of 90 patients died from treatment-related causes. Despite standard guidelines that recommend echocardiogram for screening before transplantation, four treatment-related deaths occurred because of cardiovascular complications (one constrictive pericarditis, two right heart failures without underlying infection, and one heart failure during mobilisation), and one death was secondary to sepsis without documented underlying heart disease. Kaplan-Meier analysis showed survival was 78% at 5 years (after eight relapse-related deaths) and relapse-free survival was 70% at 5 years. Compared with baseline, we noted improvements after HSCT in modified Rodnan skin scores at 1 year (58 patients; p<0·0001), 2 years (42 patients; p<0·0001), and 3 years (27 patients; p<0·0001) and forced vital capacity at 1 year (58 patients; p=0·009), 2 years (40 patients; p=0·02), and 3 years (28 patients; p=0·004), but total lung capacity and DLCO were not improved significantly after HSCT. Overall mean DLCO was significantly improved in patients with normal baseline echocardiograms (p=0·005) or electrocardiographs (p=0·05). Autologous HSCT with a non-myeloablative regimen of cyclophosphamide and rATG with a non-selected autograft results in sustained improvement in skin thickness and forced vital capacity. DLCO is affected by baseline cardiac function. Guidelines for cardiac screening of patients with systemic sclerosis to assess treatment-related risk from pulmonary artery hypertension, primary cardiac involvement, or pericardial disease should be reconsidered and updated. None.


Using measured 30-150 kVp polychromatic tungsten x-ray spectra to determine ion chamber calibration factors, Nx (Gy C(-1)).
Two methods for determining ion chamber calibration factors (Nx) are presented for polychromatic tungsten x-ray beams whose spectra differ from beams with known Nx. Both methods take advantage of known x-ray fluence and kerma spectral distributions. In the first method, the x-ray tube potential is unchanged and spectra of differing filtration are measured. A primary standard ion chamber with known Nx for one beam is used to calculate the x-ray fluence spectrum of a second beam. Accurate air energy absorption coefficients are applied to the x-ray fluence spectra of the second beam to calculate actual air kerma and Nx. In the second method, two beams of differing tube potential and filtration with known Nx are used to bracket a beam of unknown Nx. A heuristically derived Nx interpolation scheme based on spectral characteristics of all three beams is described. Both methods are validated. Both methods improve accuracy over the current half value layer Nx estimating technique.


Ultrasound-Assisted Marination: Role of Frequencies and Treatment Time on the Quality of Sodium-Reduced Poultry Meat.
The objective of this study was to evaluate the influence of high-power ultrasound (US) to accelerate marination of chicken breast; the effect of ultrasonic frequencies and marination times were investigated on samples containing full sodium levels (FS) or 25% sodium reduction, either by reducing NaCl (R50) or by its partial substitution with KCl (SR). Chicken breasts were marinated in plastic bags immersed in an ultrasonic bath operating with a frequency of 25, 45 or 130 kHz for 1, 3 or 6 h at a temperature of 2.5 ± 0.5 °C. Chicken marinated using US had a significantly higher uptake (p < 0.05) of sodium compared to control samples (no US) marinated for the same amount of time. No significant changes were observed in the quality parameters of sonicated chicken samples compared to controls. However, significant decreases (p < 0.05) in lipid oxidation were observed in SR samples when treated by US. These results suggest the use of ultrasound in the meat processing industry as a novel technology for enhancing marination processes and formulation of reduced sodium meat products.


Effect of an Aquatic Balance-Training Program in Patients with Chronic Stroke: A Single-Group Experimental Pilot Study.
Background and Objectives: Stroke survivors face severe problems affecting their mobility, such as balance impairments and an increased risk of falls. The principal aim of this study was to quantify the effects of 12 sessions of Halliwick aquatic therapy for the treatment of balance in patients with chronic stroke. Materials and Methods: Twenty-nine people with stroke participated in this single-group experimental pilot study. Sessions were performed three times a week for a total of 12 sessions. A stabilometric assessment was conducted using a computerized platform. The evaluations were performed at baseline, at four weeks, and one month after completing the aquatic program. Results: The results obtained revealed significant differences for postural stability values (p < 0.001) and single-leg stabilometry. However, in the case of values within the limits of stability, such as forward (F = 0.339, p = 0.676), backward (F = 0.449, p = 0.644), forward right oscillations (F = 1.637, p = 0.21), and the anterior/posterior instability index (F = 0.614, p = 0.55), no significant differences were found. Conclusions: These findings suggest that Halliwick therapy may potentially improve stroke balance impairments. The main limitations of the study were the sample size, the lack of a control group, and the study not being blind.


Cochlear Implantation in Cases of Unilateral Hearing Loss: Initial Localization Abilities.
The present study evaluated early auditory localization abilities of cochlear implant (CI) recipients with normal or near-normal hearing (NH) in the contralateral ear. The goal of the study was to better understand the effect of CI listening experience on localization in this population. Twenty participants with unilateral hearing loss enrolled in a prospective clinical trial assessing outcomes of cochlear implantation (ClinicalTrials.gov Identifier: NCT02203305). All participants received the MED-EL Standard electrode array, were fit with an ear-level audio processor, and listened with the FS4 coding strategy. Localization was assessed in the sound field using an 11-speaker array with speakers uniformly positioned on a horizontal, semicircular frame. Stimuli were 200-msec speech-shaped noise bursts. The intensity level (52, 62, and 72 dB SPL) and sound source were randomly interleaved across trials. Participants were tested preoperatively, and 1, 3, and 6 months after activation of the audio processor. Performance was evaluated in two conditions at each interval: (1) unaided (NH ear alone [NH-alone] condition), and (2) aided, with either a bone conduction hearing aid (preoperative interval; bone conduction hearing aid + NH condition) or a CI (postoperative intervals; CI + NH condition). Performance was evaluated by comparing root-mean-squared (RMS) error between listening conditions and between measurement intervals. Mean RMS error for the soft, medium, and loud levels were 66°, 64°, and 69° in the NH-alone condition and 72°, 66°, and 70° in the bone conduction hearing aid + NH condition. Participants experienced a significant improvement in localization in the CI + NH condition at the 1-month interval (38°, 35°, and 38°) as compared with the preoperative NH-alone condition. Localization in the CI + NH condition continued to improve through the 6-month interval. Mean RMS errors were 28°, 25°, and 28° in the CI + NH condition at the 6-month interval. Adult CI recipients with normal or near-normal hearing in the contralateral ear experienced significant improvement in localization after 1 month of device use, and continued to improve through the 6-month interval. The present results show that binaural acclimatization in CI users with unilateral hearing loss can progress rapidly, with marked improvements in performance observed after only 1 month of listening experience.


Diamide exposure, thermal resistance, and synthesis of stress (heat shock) proteins.
Chinese hamster ovary (CHO) cells were treated with the thiol oxidant diamide for 1 hr at 37 degrees, incubated in diamide-free medium for 4 hr at 37 degrees, and then exposed to hyperthermic treatment (43 degrees) or assayed for the presence of 110, 90 and 66 kilodalton (kD) stress (heat shock) proteins. Cellular inactivation produced by the hyperthermic treatment was measured using colony formation as the end point. Low concentrations of diamide, which did not result in depletion of intracellular GSH, induced a moderate degree of protection against thermal toxicity but did not affect the pattern of protein synthesis. Exposure to 0.4 mM diamide, which reduced intracellular GSH concentrations by 50-60%, significantly reduced the rate of hyperthermic cellular inactivation. This occurred coincidentally with the synthesis of stress proteins of approximate molecular weights of 110, 90 and 66 kD. Furthermore, this concentration of diamide protected cells from thermal inhibition of protein synthesis. These results indicate that thiol oxidation by diamide can induce both the development of thermal resistance to cellular inactivation and the synthesis of stress proteins.


Neighborhood socioeconomic status, depression, and health status in the Look AHEAD (Action for Health in Diabetes) study.
Depression and diminished health status are common in adults with diabetes, but few studies have investigated associations with socio-economic environment. The objective of this manuscript was to evaluate the relationship between neighborhood-level SES and health status and depression. Individual-level data on 1010 participants at baseline in Look AHEAD (Action for Health in Diabetes), a trial of long-term weight loss among adults with type 2 diabetes, were linked to neighborhood-level SES (% living below poverty) from the 2000 US Census (tracts). Dependent variables included depression (Beck Inventory), and health status (Medical Outcomes Study (SF-36) scale). Multi-level regression models were used to account simultaneously for individual-level age, sex, race, education, personal yearly income and neighborhood-level SES. Overall, the % living in poverty in the participants' neighborhoods varied, mean =11% (range 0-67%). Compared to their counterparts in the lowest tertile of neighborhood poverty (least poverty), those in the highest tertile (most poverty) had significantly lower scores on the role-limitations(physical), role limitations(emotional), physical functioning, social functioning, mental health, and vitality sub-scales of the SF-36 scale. When evaluating SF-36 composite scores, those living in neighborhoods with more poverty had significantly lower scores on the physical health (beta-coefficient [beta]= -1.90 units, 95% CI: -3.40,-0.039), mental health (beta= -2.92 units, -4.31,-1.53) and global health (beta= -2.77 units, -4.21,-1.33) composite scores. In this selected group of weight loss trial participants, lower neighborhood SES was significantly associated with poorer health status. Whether these associations might influence response to the Look AHEAD weight loss intervention requires further investigation.


Prevalence and sociodemographic characteristics of women with induced abortion in a population sample of São Paulo, Brazil.
This study aims at estimating the prevalence of women with induced abortion among women of childbearing age (15-49 years) who had any previous pregnancy, in the city of Sao Paulo, Brazil, in the last quarter of 2008, and identifying the Sociodemographic Characteristics (SC) associated with it. A cross-sectional survey was carried out. The dependent variable was dichotomized as: no abortion and induced abortion. The independent variables were: age, paid work/activity, familial monthly income, schooling, marital status, contraceptive use and number of live births. Statistical analysis was performed using log-binomial regression models with approximation of Poisson to estimate the Prevalance Ratios (PR). Of all women with any previous pregnancy (n = 683), 4.5% (n = 31) reported induced abortion. The final multivariate model showed that having now between 40 and 44 years (PR = 2.76, p = 0.0043), being single (PR = 2.79, p = 0.0159), having 5 or more live births (PR = 3.97, p = 0.0013), current oral contraception or IUD use (PR = 2.70, p = 0.454) and using a "non effective" (or of low efficacy) contraceptive method (PR = 4.18, p = 0.0009) were sociodemographic characteristics associated with induced abortion in this population. Induced abortion seems to be used to limit fertility, more precisely after having reached the desired number of children. The inadequate use or non-use of effective contraceptive methods, and / or the use of contraceptives " non effective", exposed also the women to the risk of unintended pregnancies and, therefore, induced abortions. In addition, when faced with a pregnancy, single women were more likely to have an abortion than married women.


Combined Race and Gender Trend Disparities in Depressive Symptoms among U.S. High School Students: 1999-2019.
In 2019, over 3.2 million adolescents in the U.S. reported depressive symptoms-a number that continues to increase annually. Not only can depression negatively impact an adolescent's academic performance, social development, and cognitive function, but it is also the most common condition associated with suicide. Previous studies have reported prevalence rates and statistical trends by either gender or race. We conducted an in-depth analysis of the current racial and gender trend disparities in adolescent depressive symptoms by examining linear and quadratic trends from the Youth Behavior Risk Survey (N = 158,601) over two decades (1999-2019), stratified by gender and race subgroups, both separately and combined. This novel quantitative method allows for a more nuanced approach when exploring social and cultural influences on adolescent depressive symptoms. We found a significant difference in the prevalence of depressive symptoms between males and females among Black, Hispanic, and multiracial adolescents in each separate year of pooled data. However, an increased prevalence trend over the 20-year period was only seen among the females of these three racial categories. White and Asian female adolescents also exhibited a statistical increase in prevalence of depressive symptoms over time. The only group of males with a significant trend increase over time were White adolescents. Understanding the intersection of gender and race in adolescent depressive symptoms trends enhances evidence for nurses and other healthcare professionals when developing and implementing targeted, effective prevention and intervention measures.


Optimizing amino acid groupings for GPCR classification.
There is much interest in reducing the complexity inherent in the representation of the 20 standard amino acids within bioinformatics algorithms by developing a so-called reduced alphabet. Although there is no universally applicable residue grouping, there are numerous physiochemical criteria upon which one can base groupings. Local descriptors are a form of alignment-free analysis, the efficiency of which is dependent upon the correct selection of amino acid groupings. Within the context of G-protein coupled receptor (GPCR) classification, an optimization algorithm was developed, which was able to identify the most efficient grouping when used to generate local descriptors. The algorithm was inspired by the relatively new computational intelligence paradigm of artificial immune systems. A number of amino acid groupings produced by this algorithm were evaluated with respect to their ability to generate local descriptors capable of providing an accurate classification algorithm for GPCRs.


Erythropoietin mediates brain-vascular-kidney crosstalk and may be a treatment target for pulmonary and resistant essential hypertension.
Organ crosstalk pathways represent the next frontier for target-mining in molecular medicine for existing syndromes. Pulmonary hypertension and resistant essential hypertension are syndromes that have been proven elusive in etiology, and frequently refractory to first-line management. Underlying crosstalk mechanisms, not yet considered in these treatments, may hinder outcomes or unlock novel treatments. This review focuses systematically on erythropoietin, a synthesizable molecule, as a mediator of brain-kidney crosstalk. Insights gained from this review will be applied to cardiovascular diseases in a clinician-directed fashion.


Essential tremor.
Essential tremor, including the juvenile and senile variations, may be a result of a disorder of the servomechanism that controls physiologic tremor. Hands and arms are affected most commonly, and the tremor can vary in amplitude as well as frequency. Long-term treatment with propranolol has been helpful for some patients, although older patients are less likely to benefit. Other drugs and behaviour modification therapy have been less successful. Surgical treatment is effective but should probably be reserved for severe cases. An effective instrument for measuring the subjective and objective aspects of the tremor is still needed, as is an effective long-term method of treatment.


Ethical considerations in caring for women with substance use disorders.
People living with addiction endure many hardships, and this may be especially true for women who face distinct clinical and significant psychologic and socioeconomic repercussions of addictive disorders and their companion stresses. Clinicians who work with women with addictions are confronted by many challenges, particularly in the care of pregnant and parenting women. The dilemmas faced by patients with addictions and their providers often arise directly from tensions among core ethical principles, from inconsistencies in the way these principles are applied, and from the pervasive effects of stigma. Although difficult issues are to be expected in the arena of substance abuse treatment, consideration of principles of voluntarism, beneficence, respect for persons and justice, confidentiality and truth-telling, and informed consent are invaluable in shaping clinical ethical decision making. Furthermore, proactive steps can be taken to enhance the ethical caliber of care. These steps involve policy-level and systemic actions, such as the development and expansion of programs serving women's unique needs, empiric research into the most effective treatments for women with various disorders, and reexamination of legal and societal stances toward pregnant and parenting women who have addictions. In addition, local and individual steps are needed, including addressing gaps or inherent biases in programs, training counselors and clinicians in effective strategies or counseling styles, and developing awareness of one's own attitudes when dealing with difficult patients and challenging disorders. Such efforts will help ensure that women who have addictions will be cared for in a manner that is respectful, beneficent, compassionate, honest, and just.


Concentrating ability of lymphatic vessels.
The fluid from implanted capsules was analyzed for plasma proteins and compared with fluid sampled from small lymphatics which drained the region of the implanted capsules. The plasma protein concentration of capsular and lymphatic fluids were not found to be statistically different, for capsules implanted for greater than one month. Capsules implanted for less than one month demonstrate a much higher total protein than lymphatic fluid. This difference is thought to be due to several factors: (1) length of time that capsule has been implanted, (2) inflammation surrounding capsule, (3) time lag between sampling of lymphatic and tissue fluids. If capsules were used that had been implanted for greater than 1-1/2 months, then capsular and lymphatic fluids are not statistically different. A model is presented which predicts that the small initial lymphatics could or could not concentrate plasma proteins depending on the fate of the leaked fluid. The concentrating ability of the initial lymphatics will depend on whether or not the fluid leaked from the initial lymphatic is large relative to the surrounding volume, the time course of protein diffusion to the vicinity of the lymphatic and the rate of fluid removal from the space immediately surrounding the lymphatic. While there is a distinct possibility, since the forces exist, for a concentrating mechanism in larger lymphatic vessels, the data from implanted capsules indicate that we can assume that lymphatic vessels, especially in the subcutaneous region, contain plasma protein concentrations that are fairly representative of the tissue fluids of that region.


Is more frequent hemodialysis beneficial and what is the evidence?
The HEMO study results have shown that increasing dialysis dose in conventional thrice weekly hemodialysis does not improve patient outcomes. Interest has therefore turned to more frequent (daily) hemodialysis treatments. This review covers the rationale for such an approach together with a current review of the published study data. Recent studies have suggested improvements in a number of intermediate patient outcomes such as cardiovascular (blood pressure control, left ventricular hypertrophy), anemia, phosphate control, nutritional status and quality of life. Some of these outcomes are associated with increased survival in the dialysis population. The inference from these studies is that more frequent hemodialysis will indeed reduce mortality and morbidity. To date, however, the studies have all been small and underpowered to detect such primary outcomes. No randomized controlled trials are yet reported. The US National Institutes of Health have sponsored larger scale North American based studies and an International Registry of Daily Dialysis patients has been created to attain further information of the possible benefits of such therapy. In spite of the paucity of hard evidence the studies to date have been enough to convince some jurisdictions to recognize and fund daily hemodialysis treatments.


Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis.
Advances in cardiac imaging have resulted in greater recognition of cardiac amyloidosis in everyday clinical practice, but the diagnosis continues to be made in patients with late-stage disease, suggesting that more needs to be done to improve awareness of its clinical manifestations and the potential of therapeutic intervention to improve prognosis. Light chain cardiac amyloidosis, in particular, if recognized early and treated with targeted plasma cell therapy, can be managed very effectively. For patients with transthyretin amyloidosis, there are numerous therapies that are currently in late-phase clinical trials. In this review, we address common questions encountered in clinical practice regarding etiology, clinical presentation, diagnosis, and management of cardiac amyloidosis, focusing on recent important developments in cardiac imaging and biochemical diagnosis. The aim is to show how a systematic approach to the evaluation of suspected cardiac amyloidosis can impact the prognosis of patients in the modern era.


Application of a lumped-process mathematical model to dissolution of non-uniformly distributed immiscible liquid in heterogeneous porous media.
The use of a lumped-process mathematical model to simulate the complete dissolution of immiscible liquid non-uniformly distributed in physically heterogeneous porous-media systems was investigated. The study focused specifically on systems wherein immiscible liquid was poorly accessible to flowing water. Two representative, idealized scenarios were examined, one wherein immiscible liquid at residual saturation exists within a lower-permeability unit residing in a higher-permeability matrix, and one wherein immiscible liquid at higher saturation (a pool) exists within a higher-permeability unit adjacent to a lower-permeability unit. As expected, effluent concentrations were significantly less than aqueous solubility due to dilution and by-pass flow effects. The measured data were simulated with two mathematical models, one based on a simple description of the system and one based on a more complex description. The permeability field and the distribution of the immiscible-liquid zones were represented explicitly in the more complex, distributed-process model. The dissolution rate coefficient in this case represents only the impact of local-scale (and smaller) processes on dissolution, and the parameter values were accordingly obtained from the results of experiments conducted with one-dimensional, homogeneously-packed columns. In contrast, the system was conceptualized as a pseudo-homogeneous medium with immiscible liquid uniformly distributed throughout the system for the simpler, lumped-process model. With this approach, all factors that influence immiscible-liquid dissolution are incorporated into the calibrated dissolution rate coefficient, which in such cases serves as a composite or lumped term. The calibrated dissolution rate coefficients obtained from the simulations conducted with the lumped-process model were approximately two to three orders-of-magnitude smaller than the independently-determined values used for the simulations conducted with the distributed-process model. This disparity reflects the difference in implicit versus explicit consideration of the larger-scale factors influencing immiscible-liquid dissolution in the systems.


Naegleria gruberi de novo basal body assembly occurs via stepwise incorporation of conserved proteins.
Centrioles and basal bodies are discrete structures composed of a cylinder of nine microtubule triplets and associated proteins. Metazoan centrioles can be found at mitotic spindle poles and are called basal bodies when used to organize microtubules to form the core structure of flagella. Naegleria gruberi, a unicellular eukaryote, grows as an amoeba that lacks a cytoplasmic microtubule cytoskeleton. When stressed, Naegleria rapidly (and synchronously) differentiates into a flagellate, forming a complete cytoplasmic cytoskeleton de novo, including two basal bodies and flagella. Here, we show that Naegleria has genes encoding conserved centriole proteins. Using novel antibodies, we describe the localization of three centrosomal protein homologs (SAS-6, gamma-tubulin, and centrin-1) during the assembly of the flagellate microtubule cytoskeleton. We also used these antibodies to show that Naegleria expresses the proteins in the same order as their incorporation into basal bodies, with SAS-6 localizing first, followed by centrin and finally gamma-tubulin. The similarities between basal body assembly in Naegleria and centriole assembly in animals indicate that mechanisms of assembly, as well as structure, have been conserved throughout eukaryotic evolution.


Fast, label-free force spectroscopy of histone-DNA interactions in individual nucleosomes using nanopores.
Herein we report a novel approach for fast, label-free probing of DNA-histone interactions in individual nucleosomes. We use solid-state nanopores to unravel individual DNA/histone complexes for the first time and find that the unraveling time depends on the applied electrophoretic force, and our results are in line with previous studies that employ optical tweezers. Our approach for studying nucleosomal interactions can greatly accelerate the understanding of fundamental mechanisms by which transcription, replication, and repair processes in a cell are modulated through DNA-histone interactions, as well as in diagnosis of diseases with abnormal patterns of DNA and histone modifications.