Crystal-Storing Histiocytosis: Report of a Rare Case Presenting With Pathological Fracture of Femur. Is There More to the Entity?
Crystal-storing histiocytosis (CSH) is a rare histiocytic lesion, most often described in association with lymphoid malignancies, especially plasma cell myeloma or lymphomas associated with monoclonal gammopathy. A few cases have also been described in patients without an underlying lymphoid/plasmacytic neoplasm. The histiocytes are characterized by intralysosomal accumulation of crystals composed of whole or part of the immunoglobulin molecule. The pathobiology is largely unclear. It is a rare phenomenon and the available literature is restricted to case reports and a few case series. We present a case of a 70-year-old gentleman who presented with pathological fracture of left neck of femur secondary to CSH, a presentation so far unreported in the literature. Because of associated clinical features, a plasma cell dyscrasia was suspected and the workup, including bone marrow biopsy, yielded a diagnosis of plasma cell myeloma. Histological examination of the excised femoral head showed near complete replacement of the marrow spaces with sheets of histocytes rich in intracytoplasmic crystals and only occasional plasma cells. The peculiar presentation with pathological fracture of femur in the index case and predominant tumefactive lesions in the cases in the literature might suggest a possible neoplastic origin of this lesion.


Biofilm Formation and Virulence of Shigella flexneri Are Modulated by pH of Gastrointestinal Tract.
Shigella infection remains a public health problem in much of the world. Classic models of Shigella pathogenesis suggest that microfold epithelial cells in the small intestine are the preferred initial site of invasion. However, recent evidence supports an alternative model in which Shigella primarily infects a much wider range of epithelial cells that reside primarily in the colon. Here, we investigated whether the luminal pH difference between the small intestine and the colon could provide evidence in support of either model of Shigella flexneri pathogenesis. Because virulence factors culminating in cellular invasion are linked to biofilms in S. flexneri, we examined the effect of pH on the ability of S. flexneri to form and maintain adherent biofilms induced by deoxycholate. We showed that a basic pH (as expected in the small intestine) inhibited formation of biofilms and dispersed preassembled mature biofilms, while an acidic pH (similar to the colonic environment) did not permit either of these effects. To further elucidate this phenomenon at the molecular level, we probed the transcriptomes of biofilms and S. flexneri grown under different pH conditions. We identified specific amino acid (cysteine and arginine) metabolic pathways that were enriched in the bacteria that formed the biofilms but decreased when the pH increased. We then utilized a type III secretion system reporter strain to show that increasing pH reduced deoxycholate-induced virulence of S. flexneri in a dose-dependent manner. Taken together, these experiments support a model in which Shigella infection is favored in the colon because of the local pH differences in these organs.


Systemic inflammation mediates environmental polycyclic aromatic hydrocarbons to increase chronic obstructive pulmonary disease risk in United States adults: a cross-sectional NHANES study.
This study explored the relationship between environmental polycyclic aromatic hydrocarbons (PAHs) and Chronic obstructive pulmonary disease (COPD), and identified systemic inflammation as a mediator of the increased risk of COPD from PAHs. Data were obtained from 60,936 middle-aged and older Americans recruited in the National Health and Nutrition Examination Survey 2005-2016. Environmental PAHs were measured in terms of urinary concentrations of PAHs metabolites (NAP: 1-hydroxynaphthalene, FLU: 2-hydroxyfluorene, PA: 1-hydroxyphenanthrene, and PYR: 1-hydroxypyrene). We used multifactor logical analysis to figure out the link between PAHs and COPD, and the non-linear relationship was examined using Restricted cubic spline. Spearman correlation analysis was utilized to analyze the connection between PAHs and systemic immune-inflammation index (SII). The results showed that the COPD population had higher NAP (3.550 vs. 3.282, p < 0.001), FLU (2.501 vs. 2.307, p < 0.001), PA (2.155 vs. 2.082, p = 0.005), and PYR (2.013 vs. 1.959, p = 0.008) levels than non-COPD population. In unadjusted logistics analysis, the risk of COPD with log NAP was higher [OR = 1.461, 95% CI (1.258-1.698), p < 0.001]. Upon taking into account, confounders like sex, age, race, and log NAP still increased a possible COPD risk [OR = 1.429, 95% CI (1.224-1.669), p < 0.001]. Similarly, FLU, PA, and PYR significantly increased the risk of COPD (all OR > 1, p < 0.05), both unadjusted and adjusted. Furthermore, Restricted cubic spline demonstrated a strong link between PAHs levels and COPD risk (p < 0.05). Additionally, a Spearman correlation analysis revealed a favorable association between log FLU and log SII (R = 0.43, p = 0.006), while NAP, PA, and PYR levels were not associated with log SII (all p > 0.05). Ultimately, the mediating effect analysis revealed a mediating effect capacity of 5.34% for the SII-mediated association between FLU and COPD. The findings suggest that the risk of COPD is significantly increased when environmental PAHs exposure is at high levels, and that systemic inflammation may be involved in the process.


Use of a design challenge to develop postural support devices for intermediate wheelchair users.
The provision of an appropriate wheelchair, one that provides proper fit and postural support, promotes wheelchair users' physical health and quality of life. Many wheelchair users have postural difficulties, requiring supplemental postural support devices for added trunk support. However, in many low- and middle-income settings, postural support devices are inaccessible, inappropriate or unaffordable. This article describes the use of the design challenge model, informed by a design thinking approach, to catalyse the development of an affordable, simple and robust postural support device for low- and middle-income countries. The article also illustrates how not-for-profit organisations can utilise design thinking and, in particular, the design challenge model to successfully support the development of innovative solutions to product or process challenges.


Specificity of dye-ligand interaction with the polynucleotide binding domain of 1,25-dihydroxyvitamin D3-receptor complexes of chicken intestinal cytosol.
The binding of 1,25-dihydroxyvitamin D3-receptor complexes from chick intestinal cytosol to DNA-cellulose and isolated intestinal nuclei is inhibited by several dye-ligands in a dose-dependent manner. Concentrations of Cibacron blue F3GA, blue dextran, Procion red HE3B, and Green A dye causing 50% competition for receptor binding to DNA-cellulose ranged from 2.8 to 3.6 microM. A structural analogue of the anthraquinone moiety of Cibacron blue F3GA, bromaminic acid, was 111-fold less potent in inhibiting DNA-cellulose binding. Moreover, the inhibitory effects of these dye-ligands is not due to a simple electrostatic effect, since two other polyanions, heparin and poly-L-glutamate, are much less effective. Whereas dye-ligands can cause the release of receptors bound to DNA-cellulose, they do not alter the dissociation of 1,25-dihydroxyvitamin D3 from its receptor nor do they affect the apparent equilibrium binding constant of the receptor or the concentration of available sterol-binding sites. The inhibition of binding by dye-ligands is competitive with respect to DNA-cellulose binding, indicating that the effect of these dyes is at a domain common to polynucleotides.


Severe lactic acidosis after an iatrogenic propylene glycol overdose.
Propylene glycol is a diluent found in many intravenous and oral drugs, including phenytoin, diazepam, and lorazepam. Propylene glycol is eliminated from the body by oxidation through alcohol dehydrogenase to form lactic acid. Under normal conditions, the body converts lactate to pyruvate and metabolizes pyruvate through the Krebs cycle. Lactic acidosis has occurred in patients, often those with renal dysfunction, who were receiving prolonged infusions of drugs that contain propylene glycol as a diluent. We describe a 50-year-old man who experienced severe lactic acidosis after receiving an accidental overdose of lorazepam, which contains propylene glycol. The patient was acutely intoxicated, with a serum ethanol concentration of 406 mg/dl. He had choked on a large piece of meat and subsequently experienced pulseless electrical activity with ventricular fibrillation cardiac arrest. He was brought to the emergency department; within 2 hours, he was admitted to the intensive care unit for initiation of the hypothermia protocol. The patient began to experience generalized tonic-clonic seizures 12 hours later, which resolved after several boluses of lorazepam. A lorazepam infusion was started; however, it was inadvertently administered at a rate of 2 mg/minute instead of the standard rate of 2 mg/hour. Ten hours later, the administration error was recognized and the infusion stopped. The patient's peak propylene glycol level was 659 mg/dl, pH 6.9, serum bicarbonate level 5 mEq/L, and lactate level 18.6 mmol/L. Fomepizole was started the next day and was continued until hospital day 3. Continuous renal replacement therapy was started and then replaced with continuous venovenous hemofiltration (CVVH) for the remainder of the hospital stay. The patient's acidosis resolved by day 3, when his propylene glycol level had decreased to 45 mg/dl. Fomepizole was discontinued, but the patient's prognosis was poor (anoxic brain injury); thus care was withdrawn and the patient died. Although the patient's outcome was death, his lactic acidosis was treated successfully with fomepizole and CVVH. Clinicians should be aware that an iatrogenic overdose of lorazepam may result in severe propylene glycol toxicity, which may be treated with fomepizole and CVVH.


Thiopurine methyltransferase activity in Spain: a study of 14,545 patients.
We sought to assess the activity of thiopurine methyltransferase (TPMT) in 14,545 Spanish patients with different diseases amenable to treatment with azathioprine/6-mercaptopurine (6-MP), and to evaluate the proportion of patients with low TPMT activity and therefore a higher risk of myelotoxicity with these drugs. TPMT activity in red blood cells (RBCs) was measured by a radiochemical method. The association between several clinical variables and TPMT activity was assessed by multiple linear regression. We included 14,545 patients: autoimmune hepatitis (n=359 patients), inflammatory bowel disease (n=7,046), multiple sclerosis (n = 814), myasthenia gravis (n=344), pemphigus (n=133), and other diseases (n=5,849). Mean TPMT activity was 20.1 +/- 6 U/mL, but differed depending on the disease (P<.001). TPMT distribution was low (<5) in 0.5%; intermediate (5.0-13.7) in 11.9%; or high (>or=13.8) in 87.6%. Only when TPMT activity was considered separately in each disease did it reveal a normal distribution. In the multivariate analysis, gender, hematocrit, and treatment with 5-aminosalicylates/steroids/azathioprine/6-MP statistically influenced TPMT activity, although, probably, in a clinically irrelevant manner. This study shows, in a large sample of 14,545 patients, that 0.5% had low TPMT activity, indicating a higher risk of myelotoxicity with azathioprine/6-MP, a figure similar or slightly higher than that reported in other areas. Nevertheless, the trimodal distribution of TPMT activity varied depending on disease, and the proportion of patients with low activity values ranged from 0-0.8%. The drugs prescribed for the treatment of autoimmune diseases, including azathioprine/6-MP, modified TPMT activity, but the magnitude of this effect was very small and the differences found are probably irrelevant from the clinical point of view.


Reducing operating costs for struvite formation with a carbon dioxide stripper.
One of the major operational costs of phosphorus recovery as struvite is the cost of caustic chemical that is added to maintain a desired level of operative pH. A study was conducted at the Lulu Island Wastewater Treatment Plant (LIWWTP), Richmond, BC, using a struvite crystallizer and a cascade stripper designed at the University of British Columbia (UBC). The stripper was tested under different operating conditions to determine the effectiveness of CO(2) stripping in increasing the pH of the water matrix and thereby reducing caustic chemical use. This reduction is expected to reduce the operational costs of struvite production. Throughout the project, a high percentage (90%) of phosphorus removal was achieved under each condition. The cascade stripper was very effective in saving caustic usage, ranging from 35% to 86%, depending on the operating conditions. However, the stripper showed relatively poor performance regarding ammonia stripping.


Altered Endoplasmic Reticulum Calcium Pump Expression during Breast Tumorigenesis.
Endoplasmic reticulum calcium homeostasis is involved in several essential cell functions including cell proliferation, protein synthesis, stress responses or secretion. Calcium uptake into the endoplasmic reticulum is performed by Sarco/Endoplasmic Reticulum Calcium ATPases (SERCA enzymes). In order to study endoplasmic reticulum calcium homeostasis in situ in mammary tissue, in this work SERCA3 expression was investigated in normal breast and in its benign and malignant lesions in function of the cell type, degree of malignancy, and histological and molecular parameters of the tumors. Our data indicate, that although normal breast acinar epithelial cells express SERCA3 abundantly, its expression is strongly decreased already in very early non-malignant epithelial lesions such as adenosis, and remains low in lobular carcinomas. Whereas normal duct epithelium expresses significant amounts of SERCA3, its expression is decreased in several benign ductal lesions, as well as in ductal adenocarcinoma. The loss of SERCA3 expression is correlated with Elston-Ellis grade, negative hormone receptor expression or triple negative status in ductal carcinomas. The concordance between decreased SERCA3 expression and several histological, as well as molecular markers of ductal carcinogenesis indicates that endoplasmic reticulum calcium homeostasis is remodeled during tumorigenesis in the breast epithelium.


The Use of Mobile Applications Among Adults with Type 1 and Type 2 Diabetes: Results from the Second MILES-Australia (MILES-2) Study.
While the number of diabetes-specific mobile applications (apps) continues to grow, there is a lack of knowledge about their actual use. The second MILES (Management and Impact for Long-term Empowerment and Success)-Australia study was a national cross-sectional survey of the psychological, behavioral, and social aspects of diabetes for adults with type 1 diabetes (T1D) and type 2 diabetes (T2D). Associations between diabetes-specific app usage and demographic, clinical, and psychosocial variables were examined. Of the 1589 respondents responding to the diabetes-specific app questions, 795 had T1D (mean ± standard deviation age 43 ± 14 years; 61% women; diabetes duration 19 ± 14 years) and 794 had T2D (age 60 ± 9 years; 40% women; diabetes duration 11 ± 7 years). Among adults with T1D, 24% (n = 188) reported using apps, with carbohydrate counting (74%; n = 139) as the most common cited purpose. App usage was significantly associated with shorter diabetes duration, more frequent glucose monitoring, and lower self-reported HbA1c. Among adults with T2D, 8% (n = 64) reported using apps, with glucose monitoring (62%; n = 39) as the most common purpose. For all respondents, the most commonly reported reason for not using apps was a belief that they could not help with diabetes self-management. A minority of adults with T1D and T2D use apps to support their self-management. App use among adults with T1D is associated with a more recent T1D diagnosis, more frequent glucose monitoring, and lower self-reported HbA1c. Future efforts should focus on this association and determine the mechanisms by which app use is related to better clinical outcomes.


An overview of mild traumatic brain injuries and emerging therapeutic targets.
The majority of traumatic brain injuries (TBIs), approximately 90%, are classified as mild (mTBIs). Globally, an estimated 4 million injuries occur each year from concussions or mTBIs, highlighting their significance as a public health crisis. TBIs can lead to substantial long-term health consequences, including an increased risk of developing Alzheimer's Disease, Parkinson's Disease (PD), chronic traumatic encephalopathy (CTE), and nearly doubling one's risk of suicide. However, the current management of mTBIs in clinical practice and the available treatment options are limited. There exists an unmet need for effective therapy. This review addresses various aspects of mTBIs based on the most up-to-date literature review, with the goal of stimulating translational research to identify new therapeutic targets and improve our understanding of pathogenic mechanisms. First, we provide a summary of mTBI symptomatology and current diagnostic parameters such as the Glasgow Coma Scale (GCS) for classifying mTBIs or concussions, as well as the utility of alternative diagnostic parameters, including imaging techniques like MRI with diffusion tensor imaging (DTI) and serum biomarkers such as S100B, NSE, GFAP, UCH-L1, NFL, and t-tau. Our review highlights several pre-clinical concussion models employed in the study of mTBIs and the underlying cellular mechanisms involved in mTBI-related pathogenesis, including axonal damage, demyelination, inflammation, and oxidative stress. Finally, we examine a selection of new therapeutic targets currently under investigation in pre-clinical models. These targets may hold promise for clinical translation and address the pressing need for more effective treatments for mTBIs.


Attitudes toward opioids for refractory dyspnea in COPD among Dutch chest physicians.
Dyspnea is the most frequently reported symptom of outpatients with advanced chronic obstructive pulmonary disease (COPD). Opioids are an effective treatment for dyspnea. Nevertheless, the prescription of opioids to patients with advanced COPD seems limited. The aims of this study are to explore the attitudes of Dutch chest physicians toward prescription of opioids for refractory dyspnea to outpatients with advanced COPD and to investigate the barriers experienced by chest physicians toward opioid prescription in these patients. All chest physicians (n = 492) and residents in respiratory medicine (n = 158) in the Netherlands were invited by e-mail to complete an online survey. A total of 146 physicians (response rate 22.5%) completed the online survey. Fifty percent of the physicians reported to prescribe opioids for refractory dyspnea in 20% or less of their outpatients with advanced COPD and 18.5% reported never to prescribe opioids in these patients. The most frequently reported barriers toward prescription of opioids were resistance of the patient, fear of possible adverse effects, and fear of respiratory depression. To conclude, Dutch chest physicians and residents in respiratory medicine rarely prescribe opioids for refractory dyspnea to outpatients with advanced COPD. This reluctance is caused by perceived resistance of the patient and fear of adverse effects, including respiratory adverse effects.


Postoperative intra-abdominal pressure and renal function after liver transplantation.
Intra-abdominal hypertension frequently threatens renal function early after orthotopic liver transplantation (OLT). A prospective study of consecutive patients who underwent OLT. The intensive care unit of a National Health Service teaching hospital. The intra-abdominal pressure (IAP) of 108 consecutive patients who underwent OLT was postoperatively measured 3 times a day for 72 hours using the urinary bladder technique. Intra-abdominal hypertension was defined as an IAP of 25 mm Hg or higher. Thirty-four patients (31%) had a high IAP. Acute renal failure developed in 17 recipients (16%), 11 (65%) of whom had intra-abdominal hypertension (P<.01), with a mean +/- SD IAP of 27.9 +/- 9.9 mm Hg vs 18.6 +/- 5.2 mm Hg in those without acute renal failure (P<.001). The subjects with a high IAP were more frequently administered loop diuretics to maintain adequate diuresis (P<.001) and had a low mean arterial pressure on the day of surgery (P<.01), despite the fact that they were given more intravenous fluids (P<.01) and did not differ in the need for inotropic drugs. Logistic regression analysis showed that intraoperative transfusions of more than 15 U, respiratory failure, and intra-abdominal hypertension (P<.01) were independent risk factors for renal failure. The length of intensive care unit stay was similar in the patients with a normal and a high IAP, but mortality was higher among the latter (P =.02). Intra-abdominal hypertension is common after OLT and is significantly associated with renal failure, reduced urinary output, and intensive care unit mortality. It is, therefore, worth monitoring IAP in those undergoing OLT.


Fascin 1 is an actin filament-bundling protein that regulates ectoplasmic specialization dynamics in the rat testis.
In the testis, spermatids are polarized cells, with their heads pointing toward the basement membrane during maturation. This polarity is crucial to pack the maximal number of spermatids in the seminiferous epithelium so that millions of sperms can be produced daily. A loss of spermatid polarity is detected after rodents are exposed to toxicants (e.g., cadmium) or nonhormonal male contraceptives (e.g., adjudin), which is associated with a disruption on the expression and/or localization of polarity proteins. In the rat testis, fascin 1, an actin-bundling protein found in mammalian cells, was expressed by Sertoli and germ cells. Fascin 1 was a component of the ectoplasmic specialization (ES), a testis-specific anchoring junction known to confer spermatid adhesion and polarity. Its expression in the seminiferous epithelium was stage specific. Fascin 1 was localized to the basal ES at the Sertoli cell-cell interface of the blood-testis barrier in all stages of the epithelial cycle, except it diminished considerably at late stage VIII. Fascin 1 was highly expressed at the apical ES at stage VII-early stage VIII and restricted to the step 19 spermatids. Its knockdown by RNAi that silenced fascin 1 by ~70% in Sertoli cells cultured in vitro was found to perturb the tight junction-permeability barrier via a disruption of F-actin organization. Knockdown of fascin 1 in vivo by ~60-70% induced defects in spermatid polarity, which was mediated by a mislocalization and/or downregulation of actin-bundling proteins Eps8 and palladin, thereby impeding F-actin organization and disrupting spermatid polarity. In summary, these findings provide insightful information on spermatid polarity regulation.


Whole genomic comparative analysis of Streptococcus pneumoniae serotype 1 isolates causing invasive and non-invasive infections among children under 5 years in Casablanca, Morocco.
Streptococcus pneumoniae serotype 1 remains a leading cause of invasive pneumococcal diseases, even in countries with PCV-10/PCV-13 vaccine implementation. The main objective of this study, which is part of the Pneumococcal African Genome project (PAGe), was to determine the phylogenetic relationships of serotype 1 isolates recovered from children patients in Casablanca (Morocco), compared to these from other African countries; and to investigate the contribution of accessory genes and recombination events to the genetic diversity of this serotype. The genome average size of the six-pneumococcus serotype 1 from Casablanca was 2,227,119 bp, and the average content of coding sequences was 2113, ranging from 2041 to 2161. Pangenome analysis of the 80 genomes used in this study revealed 1685 core genes and 1805 accessory genes. The phylogenetic tree based on core genes and the hierarchical bayesian clustering analysis revealed five sublineages with a phylogeographic structure by country. The Moroccan strains cluster in two different lineages, the five invasive strains clusters altogether in a divergent clade distantly related to the non-invasive strain, that cluster with all the serotype 1 genomes from Africa. The whole genome sequencing provides increased resolution analysis of the highly virulent serotype 1 in Casablanca, Morocco. Our results are concordant with previous works, showing that the phylogeography of S. pneumoniae serotype 1 is structured by country, and despite the small size (six isolates) of the Moroccan sample, our analysis shows the genetic cohesion of the Moroccan invasive isolates.


"Living an Obstacle Course": A Qualitative Study Examining the Experiences of Caregivers of Children with Rett Syndrome.
Background: Rett syndrome has considerable effects on the quality of life of affected children, impairing everyday activities and potentially impacting the life of both the caregivers and the family. Our aim was to explore the experiences of a group of caregivers of children with Rett syndrome with regards to living and caring for their children. Methods: We conducted a qualitative case study to examine how 31 caregivers of children with Rett syndrome perceived living with their children. Data were collected through in-depth interviews, focus groups, researchers' field notes and caregivers' personal documents. A thematic analysis was performed following the Consolidated Criteria for Reporting Qualitative Research (COREQ) guideline. Results: The experience of being a caregiver of a child with Rett syndrome was expressed as being akin to an "obstacle course", and was described via three main themes: (a) looking for answers, with two subthemes identified, namely 'the first symptoms', and 'the need for a diagnosis'; (b) managing day to day life, with the subthemes 'applying treatments', and 'learning to care'; and (c) money matters. Conclusions: Rett syndrome has a considerable impact on the lives of the caregivers involved. The health-care process and the management of economic resources are some of the aspects highlighted by caregivers. These findings have important implications for the planning of support services, health systems and health policies.


[Diagnosis of the composition of urinary calculi based on ions study in blood and urine].
Description of a diagnostic procedure by presumption of urinary calculi composition, based on the comparative statistical study of a group of blood and urine ions which have allowed identification of such composition, with little margin of error, in 264 renal calculi prior to complete fragmentation by extracorporeal lithotrity with pressure waves, and for which it was possible to choose the most suitable cycle and intensity.


Predicting the functional motions of p97 using symmetric normal modes.
p97 is a protein complex of the AAA+ family. Although functions of p97 are well understood, the mechanism by which p97 performs its unfolding activities remains unclear. In this work, we present a novel way of applying normal mode analysis to study this six-fold symmetric molecular machine. By selecting normal modes that are axial symmetric and give the largest movements at D1 or D2 pore residues, we are able to predict the functional motions of p97, which are then validated by experimentally observed conformational changes. Our results shed light and provide new understandings on several key steps of the p97 functional process that were previously unclear or controversial, and thus are able to reconcile multiple previous findings. Specifically, our results reveal that (i) a venous valve-like mechanism is used at D2 pore to ensure a one-way exit-only traffic of substrates; (ii) D1 pore remains shut during the functional process; (iii) the "swing-up" motion of the N domain is closely coupled with the vertical motion of the D1 pore along the pore axis; (iv) because of the shut D1 pore and the one-way traffic at D2 pore, it is highly likely that substrates enter the chamber through the gaps at the D1/D2 interface. The limited chamber volume inside p97 suggests that a substrate may be pulling out from D2 while at the same time being pulling in at the interface; (v) lastly, p97 uses a series of actions that alternate between twisting and pulling to remove the substrate. Proteins 2016; 84:1823-1835. © 2016 Wiley Periodicals, Inc.


The Disconnect Between Extracorporeal Circulation and the Microcirculation: A Review.
Extracorporeal circulation (ECC) procedures, such as cardiopulmonary bypass (CPB) and extracorporeal membrane oxygenation (ECMO), take over the function of one or more organs, providing clinicians time to treat underlying pathophysiological conditions. ECMO and CPB carry significant mortality rates for patients, despite prior decades of research focused on the resulting failure of critical organs. Since the focus of these procedures is to support blood flow and provide oxygen-rich blood to tissues, a shift in research toward the effects of ECMO and CPB on the microcirculation is warranted. Along with provoking systemic responses, both procedures disrupt the integrity of red blood cells, causing release of hemoglobin (Hb) from excessive foreign surface contact and mechanical stresses. The effects of hemolysis are especially pronounced in the microcirculation, where plasma Hb leads to nitric oxide scavenging, oxidization, formation of reactive oxygen species, and inflammatory responses. A limited number of studies have investigated the implications of ECMO in the microcirculation, but more work is needed to minimize ECMO-induced reduction of microcirculatory perfusion and consequently oxygenation. The following review presents existing information on the implications of ECMO and CPB on microvascular function and proposes future studies to understand and leverage key mechanisms to improve patient outcomes.


Type and location of venous thromboembolism in carriers of Factor V Leiden or prothrombin G20210A mutation versus patients with no mutation.
Factor V Leiden (FVLeiden) and prothrombin G20210A are the most common genetic causes of thrombophilia and established risk factors for different clinical manifestations of venous thromboembolism (VTE). This study investigated whether the clinical manifestation of VTE, the extension of deep vein thrombosis (DVT) and the presence of transient risk factors at the time of the first VTE, differed among patients with mutations (97 with FVLeiden; 33 with prothrombin G20210A) and in 109 patients without thrombophilia. Isolated pulmonary embolism (PE) was less prevalent in patients with FVLeiden (6%) and no thrombophilia (6%) than in those with prothrombin G20210A (15%). No difference was found in the incidence of distal DVT. Regarding the extension of proximal DVT, the lowest incidence for isolated popliteal vein and the highest for iliofemoral vein were observed in patients with prothrombin G20210A. No difference was observed between groups of patients with or without thrombophilia by unprovoked VTE. The pregnancy/puerperium was the most prevalent risk factor in carriers of prothrombin G20210A. Among FVLeiden carriers, the most prevalent risk factor was surgery, and in patients without thrombophilia, it was trauma (P < .05). Thrombosis of the upper limb was more frequent in a group without thrombophilia than in patients with mutations (P < .01). Transverse sinus venous thrombosis was present only in patients with prothrombin G20210A. Carriers of prothrombin G20210A have an increased risk of developing isolated PE and more severe clinical manifestations than those with FVLeiden or without thrombophilia.


Intraglomerular localization of platelet related antigens, platelet factor 4 and beta-thromboglobulin in glomerulonephritis.
We examined renal biopsies from 121 patients with various forms of glomerulonephritis, using antisera against platelet membrane antigens, platelet factor 4, beta-thromboglobulin and fibrinogen using the indirect immunofluorescent technique. Eight biopsies were also studied by electron microscopy for recognizable platelets. Thirty-six of sixty-four (56%) biopsies from patients with severe forms of glomerulonephritis showed some intraglomerular platelet antigen, extensive fluorescence in seventeen (25%). Of forty-six patient with milder, usually non-progressive forms of nephritis, twenty (44%) were positive, but only four (9%) showed extensive fluorescence. Platelets were identified by electron microscopy within the capillary lumina equally in those with positive and negative results for platelet-related antigens. There was no correlation between the presence of fibrin and platelet-related material in the glomeruli, nor between the presence or extent of intraglomerular platelet antigen and simultaneous measurements of intraplatelet serotonin in circulating platelets. However, there was a strong correlation between presence, extent and distribution of platelet-related antigen and platelet factor 4 fluorescence. These studies provide further evidence for the involvement of platelets in some forms of glomerular disease.


Holistic processing of Chinese characters in college students with dyslexia.
Expert face recognition has long been marked by holistic processing. Hence, due to the many visual properties shared between face perception and Chinese characters, it has been suggested that Chinese character recognition may induce stronger holistic processing in expert readers than in novices. However, there have been different viewpoints presented about Chinese character recognition, one of which suggests that expertise in this skill involved reduced holistic processing which may be modulated by writing experiences/performances. In this study we examined holistic processing in Chinese character recognition in adults with and without dyslexia, using the complete composite paradigm. Our results showed that the adults with dyslexia recognized Chinese characters with a stronger holistic processing effect than the typical controls. It seems that those with dyslexia relied overly on the visual spatial information of characters and showed deficits in attending selectively to their components when processing Chinese characters, which hindered the development of expert reading and writing skills. This effect was in contrast to previous perceptual expertise studies in which reduced holistic processing marked deficits in face/visual object recognition. This study is also the first to show that Chinese adults with dyslexia had persistent below average performances in Chinese literacy.


Great potential of renal progenitor cells in kidney: From the development to clinic.
The mammalian renal organ represents a pinnacle of complexity, housing functional filtering units known as nephrons. During embryogenesis, the depletion of niches containing renal progenitor cells (RPCs) and the subsequent incapacity of adult kidneys to generate new nephrons have prompted the formulation of protocols aimed at isolating residual RPCs from mature kidneys and inducing their generation from diverse cell sources, notably pluripotent stem cells. Recent strides in the realm of regenerative medicine and the repair of tissues using stem cells have unveiled critical signaling pathways essential for the maintenance and generation of human RPCs in vitro. These findings have ushered in a new era for exploring novel strategies for renal protection. The present investigation delves into potential transcription factors and signaling cascades implicated in the realm of renal progenitor cells, focusing on their protection and differentiation. The discourse herein elucidates contemporary research endeavors dedicated to the acquisition of progenitor cells, offering crucial insights into the developmental mechanisms of these cells within the renal milieu and paving the way for the formulation of innovative treatment modalities.


Reversible male sterility in transgenic tobacco carrying a dominant-negative mutated glutamine synthetase gene under the control of microspore-specific promoter.
Metabolic engineering was used to disrupt glutamine metabolism in microspores in order to block pollen development. We used a dominant-negative mutant (DNM) approach of cytosolic glutamine synthetase (GS1) gene under the microspore-specific promoter NTM19 to block glutamine synthesis in developing pollen grains. We observed partial male sterility in primary transgenic plants by using light microscopy, FDA, DAPI and in vitro pollen germination test. Microspores started to die in the early unicellular microspore stage, pollen viability in all primary transgenic lines ranged from 40-50%. All primary transgenics produced seeds like control plants, hence the inserted gene did not affect the sporophyte and was inherited through the female germline. We regenerated plants by in vitro microspore embryogenesis from 4 individual lines, pollen viability of progeny ranged from 12 to 20%, but some of them also showed 100% male sterility. After foliage spray with glutamine, 100% male-sterile plants were produced viable pollen and seed set was also observed. These results suggested that mutated GS1 activity on microspores had a significant effect on normal pollen development. Back-cross progenies (T2) of DH 100% male-sterile plants showed normal seed set like primary transgenics and control plants.


Reproductive outcomes after multiagent chemotherapy for high-risk gestational trophoblastic neoplasia.
To analyze the reproductive outcomes of women with high-risk gestational trophoblastic neoplasia (GTN) treated with multiagent EMA-CO chemotherapy. Of 212 patients treated with chemotherapy for GTN between 1986 and 2012, 65 (31%) could be contacted by telephone or mail and consented to participate in a questionnaire designed to assess their menstrual and reproduction outcomes. Twenty-four high-risk (HR) and 41 low-risk (LR) patients consented to the study. Fifteen (63%) HR and 34 (83%) LR women had not undergone hysterectomy (p = 0.08). Of the 12 HR and 33 LR women who could recall their menstrual history, all 12 (100%) HR and 32 (97%) LR women resumed menses after chemotherapy. Both groups also had a similar age of menopause (HR, 43.8 years; LR, 48.5 years) (p = 0.19). Although fewer women in the HR group desired to become pregnant after chemotherapy (HR 5/15 [33%] vs. LR 25/34 [74%]) (p = 0.01), 8 HR women (53%) and 29 LR women (85%) eventually became pregnant (p = 0.03), with equivalent live birth rates of 74% and 76%, respectively. Multiagent EMA-CO chemotherapy did not significantly alter menstrual or reproductive outcomes compared to single-agent methotrexate chemotherapy for GTN.


Direct detection of 8-oxodeoxyguanosine and 8-oxoguanine by avidin and its analogues.
8-Oxodeoxyguanosine is present in DNA from many tissues. The direct demonstration of 8-oxodeoxyguanosine as a potential biomarker of oxidative DNA damage has implications for the study of mutagenesis, carcinogenesis, and free radical toxicity. Avidin is shown here to bind with high specificity to this potentially mutagenic oxidized nucleoside, 8-oxodeoxyguanosine, and to the oxidatively modified base, 8-oxoguanine. The serendipitous finding that avidin bound to the nuclei of UVA-irradiated cells has led to the development of a technique which allows detection of the damage product in a manner analogous to that of immunological techniques. The technique has been shown to be applicable to isolated DNA and to DNA in fixed cellular material and postmortem tissue. Statistically different levels of damage can be demonstrated in both isolated DNA and cultured cells exposed to free radical generating systems using a 96-well plate-based methodology. The sensitivity of this method allows the detection of 10(-19) mol of 8-oxodeoxyguanosine. This novel usage of avidin conjugates applies also to its bacterial analogue, streptavidin, and to a lesser extent to the monoclonal antibody to biotin (the ligand bound by the parent compound). This finding has tremendous potential as a simple method analogous to immunotechniques for the direct detection of 8-oxodeoxyguanosine. From structural considerations we speculate that avidin would also bind to 8-oxodeoxyadenosine.


Familial aggregation of blood pressure in a paediatric population.
Familial aggregation of blood pressure in childhood and the difference between males and females were studied in a random sample of a nursery and school-age population in Milan. Age, sex, height, weight, skinfold thicknesses and heart rate were obtained. Blood pressure was measured in accordance with the recommendations of the Task Force of Blood Pressure Control in Children. After adjusting for age, significant correlation coefficients were found between mother and son (r = 0.17 and r = 0.11), mother and daughter (r = 0.11 and r = 0.15), and father and son (r = 0.16 and r = 0.17) for systolic and diastolic pressure, respectively; the father-daughter correlations were not statistically different (r = 0.08 and r = 0.03). Multiple regression analysis underlined the difference between males and females; height was an important determinant in the males and body weight in the females. In conclusion, anthropometric measurements should be considered in evaluations of blood pressure status. Our results suggest important differences between males and females. The BP pattern of the parents also seems more important for sons, and there seems to be a lower correlation between fathers and daughters.


A novel chemokine biomarker to distinguish active tuberculosis from latent tuberculosis: a cohort study.
Interferon-γ release assays (IGRAs), which are widely used to diagnose tuberculosis (TB), cannot effectively discriminate latent TB infection (LTBI) from active TB (ATB). This study aimed to identify potential antigen-specific biomarkers for differentiating LTBI cases from ATB cases. Ongoing recruitment was conducted of individuals meeting study inclusion criteria at Beijing Chest Hospital from May 2020-April 2022; 208 participants were enrolled and assigned to three groups: HC (60 healthy controls), LTBI (52 subjects with LTBI) and ATB (96 active TB patients). After participants were assigned to the discovery cohort (20 or 21 subjects/group), all others were assigned to the verification cohort. Discovery cohort blood levels of 40 chemokines were measured using Luminex assays to identify chemokines that could be used to discriminate LTBI cases from ATB cases; candidate biomarkers were verified using enzyme-linked immunosorbent assay-based testing of validation cohort samples. Luminex results revealed highest ATB group levels of numerous cytokines, growth factors and chemokines. Receiving operating characteristic curve-based analysis of 40 biomarkers revealed CCL8 (AUC=0.890) and CXCL9 (AUC=0.883) effectively discriminated between LTBI and TB cases; greatest diagnostic efficiency was obtained using both markers together (AUC=0.929). Interpretation of CCL8 and CXCL9 levels for validation cohort IGRA-positive subjects (based on a 0.658-ng/ml cutoff) revealed ATB group CCL8-based sensitivity and specificity rates approaching 90.79% and 100.00%, respectively. TB-specific chemokines hold promise as ATB diagnostic biomarkers. Additional laboratory confirmation is needed to establish whether CCL8-based assays can differentiate between ATB and LTBI cases, especially for bacteriologically unconfirmed TB cases.


Bone Immune Response to Materials, Part I: Titanium, PEEK and Copper in Comparison to Sham at 10 Days in Rabbit Tibia.
Bone anchored biomaterials have become an indispensable solution for the restoration of lost dental elements and for skeletal joint replacements. However, a thorough understanding is still lacking in terms of the biological mechanisms leading to osseointegration and its contrast, unwanted peri-implant bone loss. We have previously hypothesized on the participation of immune mechanisms in such processes, and later demonstrated enhanced bone immune activation up to 4 weeks around titanium implants. The current experimental study explored and compared in a rabbit tibia model after 10 days of healing time, the bone inflammation/immunological reaction at mRNA level towards titanium, polyether ether ketone (PEEK) and copper compared to a Sham control. Samples from the test and control sites were, after a healing period, processed for gene expression analysis (polymerase chain reaction, (qPCR)) and decalcified histology tissue analysis. All materials displayed immune activation and suppression of bone resorption, when compared to sham. The M1 (inflammatory)/M2 (reparative) -macrophage phenotype balance was correlated to the proximity and volume of bone growth at the implant vicinity, with titanium demonstrating a M2-phenotype at 10 days, whereas copper and PEEK were still dealing with a mixed M1- and M2-phenotype environment. Titanium was the only material showing adequate bone growth and proximity inside the implant threads. There was a consistent upregulation of (T-cell surface glycoprotein CD4) CD4 and downregulation of (T-cell transmembrane glycoprotein CD8) CD8, indicating a CD4-lymphocyte phenotype driven reaction around all materials at 10 days.


[Effect of reclamation on the vertical distribution of SOC and retention of DOC].
Contents and density of soil organic carbon (SOC) in soil profiles and dissolved organic carbon (DOC) of soil solution in different soil depths in wetland, soybean and paddy field reclaimed from the wetland around Xingkai Lake were determined to investigate how reclamation of wetland for soybean and rice farming impacts vertical distribution of SOC and retention of DOC. SOC contents in 0-40 cm soil layers were significantly influenced. SOC contents in 0-10, 10-20, 20-30 and 30-40 cm soil layers in soybean and paddy field were 79.07% and 82.01%, 79.01% and 82.28%, 79.86% and 92.90%, 37.49% and 78.05% respectively lower than those in wetland. Before and after reclamation, SOC contents in soil layers deeper than 40 cm were not significantly different. SOC densities in soybean and paddy field were 25.50% and 47.35% respectively lower than those in wetland. However, either in wetland or farm land, most of the SOC storage in 0-100 cm soil layer was stored in 0-50 cm soil layer. The relationships between SOC content and soil depth in wetland and two farm lands all could be described by exponential functions; cultivation did not change the variation of SOC content with soil depth. The retention of DOC was more obvious for soybean farming than wetland and rice farming, and that was roughly the same for wetland as rice farming.


Laparoscopic management of giant type III hiatal hernia and short esophagus. Objective follow-up at three years.
We wished to evaluate the long-term effectiveness of the laparoscopic Hill repair in the treatment of type III hiatal hernia. Fifty-two patients underwent laparoscopic repair of a type III hiatal hernia. No esophageal lengthening procedures were performed. Short esophagus was determined from the operative record. Late symptomatic follow-up and a satisfaction questionnaire were completed in 71% (37/52) of patients at a mean of 39 months (range 6 to 84 months). Esophagrams were completed in 65% (34/52) of patients at a mean of 37 months (range to 84 months) after repair. Eighty-one percent were without any adverse symptoms, and 86% rated outcome as excellent or good at 39 months. Symptoms requiring treatment were present in 19% (7/37). Esophagrams revealed a recurrent hernia in 32% (11/34) of patients of whom 36% (4/11) were asymptomatic. Six patients with short esophagus underwent esophagram with one recurrence identified (17%). This was compared with 28 patients without short esophagus, of whom 10 had a recurrence (35%) (P = 0.70). The laparoscopic Hill repair provides long-term satisfaction and relief of symptoms. The incidence of anatomic recurrence on video esophagram is high and does not always correlate with symptoms. The presence of short esophagus does not play a role in recurrence when the Hill repair is used.


Dental anxiety: a comparison of students of dentistry, biology, and psychology.
Dental anxiety is an important challenge for many patients and clinicians. It is thus of importance to know more about dental students' own experiences with dental anxiety and their understanding of dental anxiety. The aim was to investigate differences in dental anxiety levels between dental students, psychology students, and biology students at a Norwegian university. A total of 510 students of dentistry, psychology, and biology at the University of Tromsø received a questionnaire consisting of the Modified Dental Anxiety Scale, demographic questions, and questions relating to their last visit to the dentist/dental hygienist; 169 students gave complete responses. Nonparametric tests were used to investigate differences between the student groups. The respondents were 78% female and 22% male; their mean age was 24 years. The dental students showed a significantly lower degree of dental anxiety than the psychology (P<0.001) and biology students (P<0.001). A significant decrease in dental anxiety levels was found between novice and experienced dentistry students (P<0.001). The dental students had less dental anxiety compared to psychology students and biology students. Experienced dental students also had less dental anxiety than novice dental students. This could indicate that the dentistry program structure at the university may influence dental anxiety levels. Dental anxiety seemed to be less frequent in dentistry students compared to students of biology or clinical psychology. The practice-oriented dentistry education at the university might contribute to the differences in anxiety levels between new and experienced dentistry students.


Applying the lessons of high risk industries to health care.
High risk industries such as commercial aviation and the oil and gas industry have achieved exemplary safety performance. This paper reviews how they have managed to do that. The primary reasons are the positive attitudes towards safety and the operation of effective formal safety management systems. The safety culture provides an important explanation of why such organisations perform well. An evolutionary model of safety culture is provided in which there is a range of cultures from the pathological through the reactive to the calculative. Later, the proactive culture can evolve towards the generative organisation, an alternative description of the high reliability organisation. The current status of health care is reviewed, arguing that it has a much higher level of accidents and has a reactive culture, lagging behind both high risk industries studied in both attitude and systematic management of patient risks.


Oxidation-derived anticancer potential of sumanene-ferrocene conjugates.
An effective synthetic protocol towards the oxidation of sumanene-ferrocene conjugates bearing one to four ferrocene moieties has been established. The oxidation protocol was based on the transformation of FeII from ferrocene to FeIII-containing ferrocenium cations by means of the treatment of the title organometallic buckybowls with a mild oxidant. Successful isolation of these ferrocenium-tethered sumanene derivatives 5-7 gave rise to the biological evaluation of the first, buckybowl-based anticancer agents, as elucidated by in vitro assays with human breast adenocarcinoma cells (MDA-MB-231) and embryotoxicity trials in zebrafish embryos supported with in silico toxicology studies. The designed ferrocenium-tethered sumanene derivatives featured attractive properties in terms of their use in cancer treatments in humans. The tetra-ferrocenium sumanene derivative 7 featured especially beneficial biological features, elucidated by low (<40% for 10 μM) viabilities of MDA-MB-231 cancer cells together with a 1.4-1.7-fold higher viability of normal cells (human mammary fibroblasts, HMF) for respective concentrations. Compound 7 featured significant cytotoxicity against cancer cells thanks to the presence of sumanene and ferrocenium moieties; the latter motif also provided the selectivity of anticancer action. The biological properties of 7 were also improved in comparison with those of native building blocks, which suggested the effects of the presence of the sumanene skeleton towards the anticancer action of this molecule. Ferrocenium-tethered sumanene derivatives exhibited potential towards the generation of reactive oxygen species (ROS), responsible for biological damage to the cancer cells, with the most efficient generation of the tetra-ferrocenium sumanene derivative 7. Derivative 7 also did not show any embryotoxicity in zebrafish embryos at the tested concentrations, which supports its potential as an effective and cancer-specific anticancer agent. In silico computational analysis also showed no chromosomal aberrations and no mutation with AMES tests for the compound 7 tested with and without microsomal rat liver fractions, which supports its further use as a potent drug candidate in detailed anticancer studies.


Survival benefit of liver transplantation and the effect of underlying liver disease.
The benefit of liver transplantation relative to initial degree of underlying liver disease and time on the waiting list remains poorly defined. We sought to examine the survival benefit attributable to liver transplantation across a wide range of Model for End-Stage Liver Disease (MELD) scores. The study population included patients with end-stage liver disease enlisted in Rio Grande do Sul, Brazil, between 2001 and 2005. Survival and hazard function for enlisted and transplanted patients were estimated using parametric and nonparametric methods. MELD score was utilized to account for underlying liver disease. Of 1,130 eligible patients, 520 (46.0%) were transplanted, 266 (23.5%) died on the waiting list, 141 (12.5%) were excluded from the waiting list, and 203 (18.0%) remained enlisted and were awaiting transplantation at the time of last observation. At 1 year after transplantation, a MELD score of 15 represented a transition point in terms of overall survival benefit (MELD 10, 90% vs 83%; MELD 15, 81% vs 80%; MELD 20, 63% vs 78%; MELD 25, 42% vs 74%; MELD 30, 21% vs71%; enlisted vs transplant patients, respectively). MELD scores at which transplantation seemed to be beneficial relative to the amount of follow-up time was MELD 23, 17, 15, and 12 at 6 months, and 1, 2, and 5 years, respectively, from time of transplantation/enlistment. Although patients with greater MELD scores enjoy a pronounced and early benefit from transplantation, patients with lesser MELD scores do gain from transplantation, although a greater period of time is needed to realize the survival benefit.


Recurrent gliomas: comparison of computed tomography (CT)-guided 125I seed implantation therapy and traditional radiochemotherapy.
Primary brain tumors have always been associated with high morbidity and mortality. Glioma is the most common type of malignant brain tumors,with a high probability of recurrence after surgical excision and with poor prognosis.The purpose of this study was to compare the therapeutic efficacy of computed tomography (CT)-guided interstitial (125)I seed implantation with traditional radiochemotherapy for treatment of recurrent gliomas. The response rate at 1, 3, 6 and 12 months after (125)I seed implantation was 68.6, 74.3, 77.1 and 62.8% respectively, which was significantly higher than the group treated with the conventional chemoradiation protocol (p < 0.05). Patients exposed to (125)I seed implantation had a median survival of 29.0 months, whereas the median survival of those treated with traditional radiochemotherapy was 19.0 months. The difference observed between the two groups was significant. There were no severe complications or mortality associated with either treatment, except for one case of intracerebral hemorrhage around the tumor area in the (125)I seed implants group. From November 2002 to May 2010, 73 consecutive patients with recurrent gliomas were treated with CT-guided (125)I seed implantation (35 cases) or traditional radiochemotherapy (38 cases). Patients were followed up after treatment and the therapeutic effect was evaluated by comparing the response and survival rates of the two groups. In particular, patients treated with (125)I seed implantation were monitored for adverse side effects. CT-guided (125)I seed implantation is safe and well-tolerated and more importantly, shows superior efficacy compared with conventional radiochemotherapy. This suggests that CT-guided (125)I seed implantation could be an alternative approach for recurrent gliomas.


Changes in left atrial size in patients with persistent atrial fibrillation: a prospective echocardiographic study with a 5-year follow-up period.
Atrial fibrillation (AF) is a common arrhythmia, occurring in 0.4% of the general population. AF has been shown to be associated with left atrial enlargement, which is considered both a cause and a consequence of the arrhythmia. The aim of the study was to determine the influence of AF on changes in echocardiographically determined left atrial (LA) size, during 5 year follow-up period, in a population with well-controlled hypertension, free from structural heart disease, except mild left ventricle thickening, and with an absence of other potential causes of atrial enlargement. The study group, comprised of 81 patients with persistent AF, with underlying hypertensive heart disease, consecutively referred for elective direct current cardioversion. The mean age of the study population was 59.3+/-8.4 years (ranged from 43 to 80), a mean AF duration was 8.8+/-8.7 months (ranged from 1 to 30 months). The patients underwent two-dimensional echocardiography to determine left atrial size, before and 5 years after cardioversion. Twenty out of eighty-one cardioverted patients maintained sinus rhythm 5 years after cardioversion (25%). In this group anteroposterior LA dimension and LA volume decreased from a mean (+/-S.D.) 49.7+/-4.5 to 46.8+/-4.8 mm (-6%, p < 0.05) and from 103.6+/-28.8 to 91.1+/-18.3 cm2 (-9.2%, p < 0.05), respectively. Left ventricle ejection fraction increased from 52.8+/-6.3% to 60.0+/-4.0% (p < 0.05) and clinical stage improved in patients who maintained sinus rhythm through 5 years. In contrast, in the AF group, anteroposterior LA dimension and LA volume increased from 46.6+/-4.3 to 48.1+/-5.6 mm, and from 91.3+/-20 to 103+/-34 cm2 (by an average 3.3% and 14.3%, respectively), at the end of study. When divided into two groups: Imid R:II and III NYHA class, in AF patients LA volume increased by an 21.4% in the III NYHA class and 7.3% in the Imid R:II NYHA class. Left ventricular ejection fraction did not change between the two echocardiographic studies in the AF group (44.9+/-14.3% vs. 44.6+/-12.9%, Ns). In conclusion, it has been proved that AF occurring in patients with hypertensive heart disease causes a slow and progressive increase in LA size especially in patients in functional III NYHA class, and that the maintenance of sinus rhythm partially reverts the process of LA enlargement in patients with well-controlled hypertension, a history of AF and successfully treated for AF.


Stop treating waste pickers like garbage: An autoethnography on informal waste picking in Brazil.
There are almost 8 billion people on the planet with every single one of them producing some type of waste. The cost of recycling and money made by selling recyclable products has created a strong foundation for informal waste picking to exist. Waste pickers sort through garbage to find recyclable material; it is estimated that there are around 20 million waste pickers worldwide. In 2022, I went to experience life as a waste picker in Brasilia, Brazil for a day to understand issues that may continue to exist in this informal industry. I worked in a triage center and used this experience to inform my autoethnography; even though I have worked in waste picker research for almost a decade, this experience led to a different conclusion. The most interesting issue that I found while working as a waste picker was the lack of uniformity in waste picking, which led to people working on the streets or in co-op triage centers. This population is vulnerable which is worsened from exposure to hazards by nature of the informal environment; this situation contributes to ongoing poor working conditions through lack of governmental oversight, policy development, and change. Ultimately, informality needs to be addressed.


Investigating the Effects of Peripheral Electrical Stimulation on Corticomuscular Functional Connectivity Stroke Survivors.
Electrical stimulation (ES) in the periphery can induce brain plasticity and has been used clinically to promote motor recovery in patients with central nervous system lesion. Electroencephalogram (EEG) and electromyogram (EMG) are readily applicable in clinical settings and can detect real-time functional connectivity between motor cortex and muscles with EEG-EMG (corticomuscular) coherence. The purpose of this study was to determine whether EEG-EMG coherence can detect changes in corticomuscular control induced by peripheral ES. Fifteen healthy young adults and 15 stroke survivors received 40-min electrical stimulation session on median nerve. The stimulation (1-ms rectangular pulse, 100 Hz) was delivered with a 20-s on-20-s off cycle, and the intensity was set at the subjects' highest tolerable level without muscle contraction or pain. Both before and after the stimulation session, subjects performed a 20-s steady-hold thumb flexion at 50% maximal voluntary contraction (MVC) while EEG and EMG were collected. Our results demonstrated that after ES, EEG-EMG coherence in gamma band increased significantly for 22.1 and 48.6% in healthy adults and stroke survivors, respectively. In addition, after ES, force steadiness was also improved in both groups, as indicated by the decrease in force fluctuation during steady-hold contraction (-1.7% MVC and -3.9%MVC for healthy and stroke individuals, respectively). Our results demonstrated that EEG-EMG coherence can detect ES-induced changes in the neuromuscular system. Also, because gamma coherence is linked to afferent inputs encoding, improvement in motor performance is likely related to ES-elicited strong sensory input and enhanced sensorimotor integration.


Representation of tone in fluctuating maskers in the ascending auditory system.
Humans and animals detect low-level tones masked by slowly fluctuating noise very efficiently. A possible neuronal correlate of this phenomenon is the ability of low-level tones to suppress neuronal locking to the envelope of the fluctuating noise ("locking suppression"). Using in vivo intracellular and extracellular recordings in cats, we studied neuronal responses to combinations of fluctuating noise and tones in three successive auditory stations: inferior colliculus (IC), medial geniculate body (MGB), and primary auditory cortex (A1). We found that although the most sensitive responses in the IC were approximately isomorphic to the physical structure of the sounds, with only a small perturbation in the responses to the fluctuating noise after the addition of low-level tones, some neurons in the MGB and all A1 neurons displayed striking suppressive effects. These neurons were hypersensitive, showing suppression already with tone levels lower than the threshold of the neurons in silence. The hypersensitive locking suppression in A1 and MGB had a special timing structure, starting >75 ms after tone onset. Our findings show a qualitative change in the representation of tone in fluctuating noise along the IC-MGB-A1 axis, suggesting the gradual segregation of signal from noise and the representation of the signal as a separate perceptual object in A1.


Mechanism and Stereoselectivity Control of Terminal Alkyne Dimerization Activated by a Zr/Co Heterobimetallic Complex: A DFT Study.
Heterobimetallic complexes have recently garnered considerable attention in organic synthesis owing to their high activity and selectivity, which surpass those of monometallic complexes. In this study, the detailed mechanisms of terminal alkyne dimerization activated by the heterobimetallic Zr/Co complex, as well as the different stereoselectivities of Me3SiC≡CH and PhC≡CH dimerization, were investigated and elucidated by using density functional theory calculations. After excluding the three-molecule reaction and outer-sphere mechanisms, the inner-sphere mechanism was determined as the most optimal process. The inner-sphere mechanism involves four processes: THF dissociation and coordination of the first alkyne; ligand migration and C-H activation; N2 dissociation and insertion of the second alkyne; and reductive elimination. The stereoselectivity between the E-/Z- and gem-isomers is determined by the C-C coupling mode of the two alkynes and that of the E- and Z-isomers is determined by the sequence of the C-C coupling and hydrogen migration in the reductive elimination process. Me3SiC≡CH dimerization yields only an E-isomer owing to the large differences in the distortion and interaction energies, whereas PhC≡CH dimerization produces an E-, Z-, and gem-isomers owing to the reduced interaction energy differences.


Social perceptions of individuals missing upper front teeth.
Although it is assumed that there are negative social consequences for individuals missing visible front teeth, no study of the way in which edentulous individuals were perceived in a social context and the potential social repercussions could be located. This initial study concerned college students' perceptions of individuals missing visible upper front teeth. 200 volunteers, 19 to 50 years of age (M = 20.6, SD = 4.4), rated five photographs depicting tooth presence or absence, from a full dentition to missing as many as four upper front teeth, on social traits including attractiveness, health status, educational attainment, satisfaction with life, active social life, aggressiveness, intelligence, trustworthiness, amount of caring, friendship, dating, and likelihood to live as a neighbor. Analysis suggested a person missing visible teeth was more negatively perceived on all social traits than a person with full dentition. Results were strongest when students were proposed to be linked to the edentulous individual in a personal way, i.e., dating or living as neighbor. Men and women agreed on perceptions of social traits and dentition condition. These results suggest the presence of strong Western cultural values, whereby those who are missing teeth may experience significant barriers to personal and social success.


Curcumin inhibits hypoxia-induced proliferation and invasion of MG-63 osteosarcoma cells via downregulating Notch1.
Curcumin is a biologically active ingredient abundantly present in the ground rhizomes of Curcuma longa with a wide range of bioactive properties, including antitumor effects. Hypoxia is a common characteristic of solid tumors, including osteosarcoma. However, whether curcumin has antitumor effects on osteosarcoma under hypoxic conditions, and its underlying molecular mechanisms, remain unclear. The present study demonstrated that the MG‑63 osteosarcoma cell line exhibited increased proliferation and enhanced invasiveness upon exposure to hypoxic conditions. However, these effects were prevented by curcumin treatment. Further investigation revealed that curcumin may inhibit Notch1 upregulation induced by hypoxia. Overexpression of Notch1 via Notch1 cDNA transfection ameliorated curcumin‑inhibited MG‑63 cell growth under hypoxic conditions. Taken together, these data revealed that curcumin may suppress the growth of osteosarcoma cells in hypoxia via inhibiting Notch1 signaling.


A 3D in vitro bone organ model using human progenitor cells.
Three-dimensional (3D) organotypic culture models based on human cells may reduce the use of complex and costly animal models, while gaining clinical relevance. This study aimed at developing a 3D osteoblastic-osteoclastic-endothelial cell co-culture system, as an in vitro model to mimic the process of bone turnover. Osteoprogenitor and endothelial lineage cells were isolated from the stromal vascular fraction (SVF) of human adipose tissue, whereas CD14+ osteoclast progenitors were derived from human peripheral blood. Cells were co-cultured within 3D porous ceramic scaffolds using a perfusion-based bioreactor device, in the presence of typical osteoclastogenic factors. After 3 weeks, the scaffolds contained cells with endothelial (2.0±0.3%), pre/osteoclastic (14.0±1.4%) and mesenchymal/osteoblastic (44.0±8.4%) phenotypes, along with tartrate-resistant acid phosphatase-positive (TRAP+) osteoclastic cells in contact with deposited bone-like matrix. Supernatant analysis demonstrated sustained matrix deposition (by C-terminus procollagen-I propeptides), resorption (by N-terminus collagen-I telopeptides and phosphate levels) and osteoclastic activity (by TRAP-5b) only when SVF and CD14+ cells were co-cultured. Scanning electron microscopy and magnetic resonance imaging confirmed the pattern of matrix deposition and resorption. The effectiveness of Vitamin D in replacing osteoclastogenic factors indicated a functional osteoblast-osteoclast coupling in the system. The formation of human-origin bone-like tissue, blood vessels and osteoclasts upon ectopic implantation validated the functionality of the developed cell types. The 3D co-culture system and the associated non-invasive analytical tools can be used as an advanced model to capture some aspects of the functional coupling of bone-like matrix deposition and resorption and could be exploited toward the engineering of multi-functional bone substitute implants.


Supramolecular assembly of designed α-helical polypeptide-based nanostructures and luminescent conjugated polyelectrolytes.
Designed polypeptides with controllable folding properties are utilized as supramolecular templates for fabrication of ordered nanoscale molecular and fibrous assemblies of LCPs. The properties of the LCPs as well as the three dimensional conformation of the polypeptide-scaffold determine how the polymers are arranged in the supramolecular construct, which highly affects the properties of the hybrid material. The ability to control the polypeptide conformation and assembly into fibers provides a promising route for tuning the optical properties of LCPs and for fabrication of complex functional supramolecules with well defined structural properties.


Analysis of 100 cases of free-muscle transplantation for facial paralysis.
Free-muscle transplantation is the treatment of choice for long-standing facial paralysis. It enables the reconstructive surgeon to restore facial movement and some emotional animation. Despite all technical innovations and 20 years of experience with free-muscle transplantation, the aesthetic and functional outcomes of the surgery are still unpredictable. The present report reviews 100 free-muscle transplantations to the face by a single surgeon and analyzes various preoperative, intraoperative, and postoperative factors in relation to the functional recovery of the muscle transplants. These factors were demographic variables such as age, gender, and etiology as well as intraoperative variables such as choice of muscles, number of nerve coaptations, and ischemia time of the muscle. Additionally, four independent raters not involved in the care of these patients rated standardized preoperative and postoperative videos and judged the functional and aesthetic outcomes. From 1981 to 1993, 93 patients with facial paralysis underwent free-muscle transplantation. A total of 100 muscles were transplanted, since 7 patients received two muscle transplants. There were 33 male and 60 female patients ranging in age from 3 to 57 years, with an average of 22.2 +/- 14.9 years. The gracilis muscle was used in 63 cases of free-muscle transplantation, while the pectoralis minor was used in 34 cases. In 2 patients a segment of the rectus abdominis was transferred, and in 1 patient a small segment of the latissimus dorsi was transferred. In 89 patients the onset of muscle function was reported. The range was from 6 to 48 weeks postoperatively. The average was 21.6 +/- 9.14 weeks after muscle transplantation. The correlations showed a trend to earlier onset of function and higher aesthetic rating in young female patients. The intraoperative ischemia of the free muscle did not correlate with the onset of muscle function. Using a five-step scale of judgments, a higher postoperative rating was seen in 94 percent of the patients, and 80 percent of all patients achieved a moderate or better result.


Hormonal stimulation of cyclic AMP accumulation and glycogen phosphorylase activity in calcium-depleted hepatocytes from euthyroid and hypothyroid rats.
Activation of glycogen phosphorylase by hormones was examined in hepatocytes isolated from euthyroid and hypothyroid female rats and incubated by Ca2+-free buffer containing 1 mM-EGTA. Basal glycogen phosphorylase activity was decreased in Ca2+-free buffer. However, the activation of hepatocyte glycogen phosphorylase, in the absence of extracellular Ca2+, in response to adrenaline, glucagon or phenylephrine was slightly lower, whereas that by vasopressin was abolished. The activation of glycogen phosphorylase by phenylephrine, adrenaline or isoproterenol (isoprenaline) in hepatocytes from euthyroid rats incubated in the absence of Ca2+ was not accompanied by any detectable increase in total cyclic AMP. The log-dose/response curves for activation of phosphorylase by phenylephrine or low concentrations of adrenaline were the same in hepatocytes from hypothyroid as compared wit euthyroid rats, whereas the response to isoproterenol was greater in hepatocytes from hypothyroid rats. However, the increases in total cyclic AMP accumulation caused by adrenaline or isoproterenol were greater in hepatocytes from hypothyroid rats than in hepatocytes from euthyroid rats. The increases in cyclic AMP accumulation caused by adrenaline or isoproterenol in Ca2+-depleted hepatocytes from hypothyroid rats were blocked by propranolol, a beta-adrenergic antagonist. In contrast, propranolol was only partially effective asan inhibitor of the activation of glycogen phosphorylase by phenylephrine or adrenaline in hepatocytes from hypothyroid rats and ineffective on phosphorylase activation in cells from euthyroid rats. These data indicate that the alpha-adrenergic activation of glycogen phosphorylase is not affected by the absence of extracellular Ca2+, and the extent to which total cyclic AMP was increased by adrenergic amines did not correlate with glycogen phosphorylase activation.


T-Cell Cytokine Response in Salmonella Typhimurium-Vaccinated versus Infected Pigs.
Vaccination with the live attenuated vaccine Salmoporc is an effective measure to control Salmonella Typhimurium (STM) in affected swine populations. However, the cellular immune response evoked by the Salmoporc vaccine including differences in vaccinated pigs versus non-vaccinated pigs upon STM infection have not been characterized yet. To investigate this, tissue-derived porcine lymphocytes from different treatment groups (vaccination-only, vaccination and infection, infection-only, untreated controls) were stimulated in vitro with heat-inactivated STM and abundances of IFN-γ, TNF-α and/or IL-17A-producing T-cell subsets were compared across organs and treatment groups. Overall, our results show the induction of a strong CD4+ T-cell response after STM infection, both locally and systemically. Low-level induction of STM-specific cytokine-producing CD4+ T cells, notably for the IFN-γ/TNF-α co-producing phenotype, was detected after vaccination-only. Numerous significant contrasts in cytokine-producing T-cell phenotypes were observed after infection in vaccinated and infected versus infected-only animals. These results suggest that vaccine-induced STM-specific cytokine-producing CD4+ T cells contribute to local immunity in the gut and may limit the spread of STM to lymph nodes and systemic organs. Hence, our study provides insights into the underlying immune mechanisms that account for the efficacy of the Salmoporc vaccine.


Spinal control of motor outputs by intrinsic and externally induced electric field potentials.
Despite numerous studies on spinal neuronal systems, several issues regarding their role in motor behavior remain unresolved. One of these issues is how electric fields associated with the activity of spinal neurons influence the operation of spinal neuronal networks and how effects of these field potentials are combined with other means of modulating neuronal activity. Another closely related issue is how external electric field potentials affect spinal neurons and how they can be used for therapeutic purposes such as pain relief or recovery of motor functions by transspinal direct current stimulation. Nevertheless, progress in our understanding of the spinal effects of electric fields and their mechanisms has been made over the last years, and the aim of the present review is to summarize the recent findings in this field.


Health-related quality of life and psychosocial status in breast cancer prognosis: analysis of multiple variables.
Evidence that psychosocial status and health-related quality of life (HRQOL) are associated with breast cancer (BC) outcomes is weak and inconsistent. We examined prognostic effects of these factors in a prospective cohort study. Three hundred ninety-seven women with surgically resected T1 to T3, N0/N1, M0 BC completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (Core 30 items), Profile of Mood States, Psychosocial Adjustment to Illness Scale, Impact of Events Scale, Mental Adjustment to Cancer Scale, and the Courtauld Emotional Control Scale 2 months after diagnosis and 1 year later. Data on tumor-related factors, treatment, and outcomes were obtained prospectively from medical records, and Cox survival analyses were performed. Mean age was 52.0 +/- 9.9 years. Two hundred twenty-five women had T1, 136 women had T2, 16 women had T3, and 20 women had TX tumors; 127 were N1. One hundred thirteen women received adjuvant chemotherapy, 130 received hormone therapy, 45 received both, and 109 received neither. We investigated 140 prognostic associations; four were found to be statistically significant at a P value of </= .05 (three fewer than expected by chance). Two were in the hypothesized direction of effect, and two were in the opposite direction. All arose from measurements 1 year after diagnosis, which were most susceptible to confounding by treatment. There was no evidence of consistency of associations across outcomes or questionnaires. These results are in keeping with chance as the explanation for our statistically significant findings. HRQOL and psychosocial status at diagnosis and 1 year later are not associated with medical outcome in women with early-stage BC.


Excrement from Heron colonies for environmental assessment of toxic elements.
Excrement cast from Great Blue Heron nests was collected during the nesting period of 1978 from four colonies in Washington and Idaho. Cheesecloth strips placed on the ground beneath the nests served as excrement collecting devices. Chemical analysis for lead, mercury and cadmium were performed on dried samples. Lead was the most abundant trace metal found in heron debris. The Idaho colony at Lake Chatcolet had an average concentration of 46 ppm in the beneath-nest samples and 6 ppm in control samples. A heron colony near Tacoma, Washington had beneath-nest samples averaging 28 ppm and control samples averaging 20 ppm. Two colonies located in the interior region of Washington had substantially lower concentrations of lead. The difference observed between colonies was attributed to their associations with a polluted watershed (Chatcolet colony) an interstate highway (Tacoma colony) and an unpopulated largely agricultural area (inland Washington).


Antibacterial Activity of Thymus vulgaris L. Essential Oil Vapours and Their GC/MS Analysis Using Solid-Phase Microextraction and Syringe Headspace Sampling Techniques.
While the inhalation of Thymus vulgaris L. essential oil (EO) is commonly approved for the treatment of mild respiratory infections, there is still a lack of data regarding the antimicrobial activity and chemical composition of its vapours. The antibacterial activity of the three T. vulgaris EOs against respiratory pathogens, including Haemophilus influenzae, Staphylococcus aureus, and Streptococcus pyogenes, was assessed in both liquid and vapour phases using the broth microdilution volatilisation (BMV) method. With the aim of optimising a protocol for the characterisation of EO vapours, their chemical profiles were determined using two headspace sampling techniques coupled with GC/MS: solid-phase microextraction (HS-SPME) and syringe headspace sampling technique (HS-GTS). All EO sample vapours exhibited antibacterial activity with minimum inhibitory concentrations (MIC) ranging from 512 to 1024 μg/mL. According to the sampling technique used, results showed a different distribution of volatile compounds. Notably, thymol was found in lower amounts in the headspace-peak percentage areas below 5.27% (HS-SPME) and 0.60% (HS-GTS)-than in EOs (max. 48.65%), suggesting that its antimicrobial effect is higher in vapour. Furthermore, both headspace sampling techniques were proved to be complementary for the analysis of EO vapours, whereas HS-SPME yielded more accurate qualitative results and HS-GTS proved a better technique for quantitative analysis.


[Psychology and nutrition in the ontogenetic development in the infant-adolescence years].
The relationship between the psychic development and the nutritional condition from the fetal stage up to the teenage years is the innermost objective of this study. The importance of eating and having an adequate diet during the pregnancy period, the training of the future mother to breast feed in the first months of the baby's life and the subsequent application of the ablactación process and its relation with psychomotor development and the personality progression in the different stages of the psychological, physiological and social development of the infant-adolescent period. The results shown were obtained from various studies carried out in the Nutritional Clinical Service. They are related to the reinduction of breast feeding in children less than 4 months of age with protein energetic malnutrition, as well as other stages of the infant-juvenile obese and other chronic and genetic diseases related to the nourishment and nutrition (diabetes, fenilcetonuria, hiperamonemia, homocistinuria y fibrosis quística), in which the close relationship betweeen the Psychology, and the Nutrition stands, all through the Psychotherapeutic and educational treatments and based on the application of the clinic psychology in the prevention, promotion and treatment of the nutritional alterations and other chronic and genetic diseases related to nourishment and malnutrition. Aspects related to the psychological and social characterizations as well as the personality evolution of these patients and their relatives environment are established.


Infrared spectroscopy of wafer-scale graphene.
We report spectroscopy results from the mid- to far-infrared on wafer-scale graphene, grown either epitaxially on silicon carbide or by chemical vapor deposition. The free carrier absorption (Drude peak) is simultaneously obtained with the universal optical conductivity (due to interband transitions) and the wavelength at which Pauli blocking occurs due to band filling. From these, the graphene layer number, doping level, sheet resistivity, carrier mobility, and scattering rate can be inferred. The mid-IR absorption of epitaxial two-layer graphene shows a less pronounced peak at 0.37 ± 0.02 eV compared to that in exfoliated bilayer graphene. In heavily chemically doped single-layer graphene, a record high transmission reduction due to free carriers approaching 40% at 250 μm (40 cm(-1)) is measured in this atomically thin material, supporting the great potential of graphene in far-infrared and terahertz optoelectronics.


Greenlandic sheep farming controlled by vegetation response today and at the end of the 21st century.
The spatial heterogeneity of vegetation greenness and potential aboveground biomass production for sheep farming has been assessed for Southwest Greenland. A Multi-Criteria Evaluation (MCE) model was set up to identify biophysical constraints on the present spatial distribution of farms and fields based on all existing sheep farms in a detailed study area. Time-integrated NDVI (TI-NDVI) from MODIS and observed temperatures (2000-2012) have been combined with a downscaled regional climate model (HIRHAM5) in order to establish a spatio-temporal model for future TI-NDVI, thus forecasting the dry biomass production available for sheep farming in steps of decades for the next 85 years. The model has been validated against observed biomass production and the present distribution of fields. Future biomass production is used to discuss the expansion of current farms and to identify new suitable areas for sheep farming. Interestingly, new suitable areas are located where sheep farms were situated during the Norse era more than 1000 years ago; areas which have been abandoned for the past 500 years. The study highlights the potential of establishing new areas for sheep farming in Arctic Greenland, where current and future climate changes are markedly amplified compared to global trends. However, for the study area the MCE model clearly indicates that the potential of expansion relies on contemporary infrastructural development.


Safety and efficacy of a feed additive consisting of endo-1,4-β-xylanase produced by Bacillus subtilisLMG S-27588 (Beltherm MP/ML) for laying hens, minor poultry species and all avian species (Puratos NV).
Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of an endo-1,4-β-xylanase (Beltherm MP/ML), produced by a genetically-modified Bacillus subtilis strain, as a zootechnical additive for laying hens, minor poultry species and all avian species. The additive is authorised for use in feed for poultry species for fattening or reared for laying/breeding, weaned piglets, pigs for fattening and minor porcine species for fattening. The safety and efficacy of the additive for those species have been evaluated previously by the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP Panel). The current application is for an extension of use of the additive. No viable cells were detected in the additive, but the data provided to support the absence of DNA in the additive was not sufficient to conclude on the absence of recombinant DNA in the additive. However, the Panel concluded that no safety concerns would arise from the presence of DNA from the production strain in the additive. In the current assessment, the FEEDAP Panel concluded that the additive is safe for all avian species at the recommended level of 100 ADXU/kg feed. Similarly, the FEEDAP Panel concluded that Beltherm MP/ML is safe for the consumer and the environment. Concerning the user safety, the FEEDAP Panel concluded that the additive is not toxic by inhalation or irritant for skin or eyes, but it is considered a potential dermal and a respiratory sensitiser. In a previous opinion, the efficacy of the additive in poultry species for fattening was shown. However, owing to the insufficient data submitted in previous and current assessments, the Panel could not conclude on the efficacy of the product for the target species for which the application was made.


Genetic basis of HDL variation in 129/SvImJ and C57BL/6J mice: importance of testing candidate genes in targeted mutant mice.
To evaluate the effect of genetic background on high-density lipoprotein cholesterol (HDL) levels in Soat1(-/-) mice, we backcrossed sterol O-acyltransferase 1 (Soat1)(-/-) mice, originally reported to have elevated HDL levels, to C57BL/6 mice and constructed a congenic strain with only a small region (3.3Mb) of 129 alleles, specifically excluding the nearby apolipoprotein A-II (Apoa2) gene from 129. HDL levels in these Soat1(-/-) mice were no different from C57BL/6, indicating that the passenger gene Apoa2 caused the previously reported elevation of HDL in these Soat1(-/-) mice. Because many knockouts are made in strain 129 and then subsequently backcrossed into C57BL/6, it is important to identify quantitative trait loci (QTL) that differ between 129 and C57BL/6 so that one can guard against effects ascribed to a knockout but really caused by a passenger gene from 129. To provide such data, we generated 528 F(2) progeny from an intercross of 129S1/SvImJ and C57BL/6 and measured HDL concentrations in F(2) animals first fed chow and then atherogenic diet. A genome wide scan using 508 single-nucleotide polymorphisms (SNPs) identified 19 QTL, 2 of which were male specific and 2 were female specific. Using comparative genomics and haplotype analysis, we narrowed QTL on chromosomes 3, 5, 8, 17, and 18 to 0.5, 6.3, 2.6, 1.1, and 0.6 Mb, respectively. These data will serve as a reference for any effort to test the impact of candidate genes on HDL using a knockout strategy.


Changes in arm tissue composition with slowly progressive weight-lifting among women with breast cancer-related lymphedema.
Studies in breast cancer-related lymphedema (BRCL) have exclusively examined total arm volume, but not the specific tissue composition that contributes to total volume. We evaluated baseline differences in arm tissue composition [fat mass, lean mass, bone mineral content (BMC), and bone mineral density (BMD)] between the affected and unaffected arms in women with BRCL. We compared changes in arm tissue composition and self-reported lymphedema symptoms after 1 year of weight-lifting versus control. We utilized data from physical activity and lymphedema trial that included 141 women with BRCL. Arm tissue composition was quantified using dual-energy X-ray absorptiometry. The severity of lymphedema was quantified using self-report survey. Weight-lifting was performed at community fitness facilities. At baseline, the affected arm had more fat (∆ = 89.7 g; P < 0.001) and lean mass (∆ = 149.1 g; P < 0.001), but less BMC (∆ = -3.2 g; P < 0.001) and less BMD (∆ = -5.5 mg/cm2; P = 0.04) than the unaffected arm. After 12 months of weight-lifting, composition of the affected arm was improved: lean mass (71.2 g; P = 0.01) and BMD (14.0 mg/cm2; P = 0.02) increased, arm fat percentage decreased (-1.5%; P = 0.003). Composition of the unaffected arm was only improved in lean mass (65.2 g; P = 0·04). Increases in lean mass were associated with less severe BCRL symptoms. Among women with BRCL, slowly progressive weight-lifting could improve arm tissue composition. Changes in arm tissue composition predict changes in symptom burden. Investigating the combined effects of exercise and weight loss on arm tissue composition and BCRL symptoms may provide additional insight into the benefits of lifestyle modification on lymphedema biology.


IL-22 Plays a Critical Role in Maintaining Epithelial Integrity During Pulmonary Infection.
Pulmonary infection is a leading cause of hospitalization in world. Lung damage due to infection and host mediated pathology can have life threatening consequences. Factors that limit lung injury and/or promote epithelial barrier function and repair are highly desirable as immunomodulatory therapeutics. Over the last decade, interleukin-22 has been shown to have pulmonary epithelial protective functions at the mucosal immune interface with bacterial and viral pathogens. This article summarizes recent findings in this area and provides perspective regarding the role of IL-22 in mucosal host defense.


[Treadmill versus field trial. Movement analysis and pressure distribution in the athletic shoe].
Our current knowledge on interactions between runner and runningshoe is mainly based on treadmill measurements. In order to reveal stress load and adaptation on playing surfaces it was necessary to develop a combined measuring device out of 3-D video motion analysis and portable pressure measurement system. By means of a motor driven cart moving parallel to the subject with comparable position of cameras to the treadmill test it was possible to set up an identical trial for track and field. 12 subjects (male, age 24-32, size 9) were tested at a speed of 2.8 m/s. The varying conditions were treadmill and grass and two different constructed running shoes. 200 cycles and over 1000 steps were analyzed. The quantitative analysis of 37 parameters describing the contact phase was performed using the wilcoxon test for paired samples.-A qualitative comparison of running styles was introduced by using angle-angle-diagrams (knee and ankle by 3-D data) similar to those first described for 2-D by P.R. Cavanagh in 1973. It showed a huge interindividual variability under same conditions. Comparing the angle-angle-diagrams for the four different running conditions it was possible to classify them into three characteristic groups: non-adaptors, surface-adaptors and shoe-adaptors. Comparing track and field to treadmill measurements significant differences were found for the knee at impact: On treadmill the initial knee angle was 4.6 degrees more extended at a 13% higher angle velocity and a 30% higher angle deceleration (sig. p less than 0.05). A 7.3% higher impulse was found on grass at a 5.9% higher step length. No difference in maximum pressure was found. These results show that adaptation is performed mainly by the knee. Changing the motion pattern the knee seems to be capable of homogenizing the different stress loads to the foot. Comparing the running shoes significant differences were found in the motion of the ankle: a controversial behaviour was found to be on treadmill and grass. The pressure data revealed significant differences for the treadmill test to be in the heel area, for grass in the arch area. This points to an--up to now--unknown importance of the arch on unplain surfaces that are obviously influenced by the construction of the shoe and are not accessible by treadmill tests. The described different behaviour of shoes in treadmill and track and field tests points out the reduced validity of single treadmill tests.(ABSTRACT TRUNCATED AT 400 WORDS)


Efficient microalgae harvesting using a thermal flotation method with response surface methodology.
Thermal pre-flocculation to enable dispersed air flotation is an economical and ecofriendly technology for harvesting microalgae from water. However, the underlying mechanism and optimal conditions for this method remain unclear. In this study, Chlorella vulgaris (C. vulgaris) and Scenedesmus obliquus (S. obliquus) were harvested using a thermal flotation process. The surface structure and characteristics (morphology, electricity, and hydrophobicity) of the microalgae were analyzed using FT-IR (Fourier transform infrared spectroscopy), SEM (scanning electron microscopy), zeta potential, and a hydrophobic test. Further, response surface methodology (RSM) was used to optimize the flotation process. The hydrophobicity of S. obliquus exceeded that of C. vulgaris; as such, under the thermal pre-flocculation, S. obliquus (88.16%) was harvested more efficiently than C. vulgaris (47.16%). Thermal pre-flocculation denatured the lipids, carbohydrate, and proteins of microalgal cell surfaces. This resulted in a decrease in the electrostatic repulsion between the cells and air bubbles. The highest harvesting efficiency was 91.96% at 70 °C, 1,412 rpm, and 13.36 min. The results of this study demonstrate the potential for economic and ecofriendly harvesting of microalgae for biofuels and other bioproducts industries.


The time for reflection: a luxury of the past.
We have examined the in vitro effect of glucocorticoid and nonglucocorticoid steroids on the transport of [3-(14)C]alpha aminoisobutyric acid (AIB) in lymphocytes from patients with chronic lymphocytic leukemia (CLL), and myeloblasts from patients with acute granulocytic leukemia (AGL). AIB uptake by CLL lymphocytes was markedly inhibited at 1.0 muM (52+/-2.1%) and slightly inhibited at 0.1 muM (17+/-3.0%) cortisol. A similar degree of inhibition developed at 50-fold lower concentrations of dexamethasone, indicating that the effect of these steroids on AIB accumulation parallels their glucocorticoid activity in vivo. In contrast, minimal or no inhibition was observed with steroids devoid of glucocorticoid activity (progesterone, testosterone, cortisone). 11-deoxycortisol, a nonglucocorticoid known to impede the binding of cortisol to cellular receptors in animal lymphocytes, failed to inhibit AIB uptake by CLL lymphocytes appreciably, but reduced the effect of cortisol to a statistically significant degree. Hence, cortisol-induced inhibition of AIB transport in CLL lymphocytes is related to its glucocorticoid activity and appears to require initial interaction with glucocorticoid-specific cellular receptors. In contrast, 1.0 muM cortisol enhanced the accumulation of AIB in AGL myeloblasts from each of five patients studied (mean = 19%, range 7-43%). Neither cortisone nor 11-deoxycortisol stimulated AIB uptake, and cortisol-mediated stimulation was not seen during simultaneous treatment with 11-deoxycortisol, suggesting that this effect of cortisol also represents a specific glucocorticoid effect. The divergent effects of cortisol on amino acid transport in CLL lymphocytes and AGL myeloblasts may explain, in part, the contrasting clinical effects of glucocorticoids administered to patients with these lymphoid and granulocytic hematopoietic malignancies.


[Automatic data processing in the studies of the electric activity of the heart].
A generalized analysis of the work going on at the Kaunas Medical Institute in automation of instrumental investigations is reported. The aim, destination and the field of application for the systems of automated analysis of electrocardiograms and rhythmograms, whose construction is based on the use of LIBM-22 and BECM-6 computers, are described. Fundamental prinicples laid at the root of the systems (data file, algorhythms employed, structure of response), mathematical and technical provisions, analysis of basic errors and possibilities of their elimination are presented.