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Using in-depth face-to-face interviews, this study explored 34 homeless shelter workers' perceptions of homelessness and working with the homeless. We asked the following questions: 1) What were the barriers that homeless shelter residents faced in combating homelessness, from the perspective of the homeless shelter workers? 2) What were the challenges that homeless shelter workers encountered in working with this at-risk population? Our findings shared the realities that the homeless population faced from the lens of shelter workers with different job responsibilities (ranging from customer service workers to case managers, program directors/coordinators, and shelter administrators). Overall, we found that working with the homeless community could present a challenge for shelter workers given the limited availability of funding, discrepancies in agreement of solutions, the lack of qualified helping professionals, the limits of service coordination, preconceived judgment/prejudice from the public, and a series of obstacles that the homeless population faces including barriers to accessing services, employability, personal hardship, and social stigma. [ABSTRACT FROM AUTHOR]

The objective of this study was to identify common communication issues that arise during the electronic resource lifecycle and identify communication strategies academic libraries are using effectively to manage electronic resources. A survey of academic librarians and staff received 240 responses and included 5-point Likert scale ratings on communication surrounding acquisitions, access, administration, support, evaluation, and renewal​ at their institutions. The study found that the acquisitions, evaluation, and renewal stages of the lifecycle experienced the most issues in communication, while support had the most positive responses. This article provides further discussion on the communication mechanisms used by academic institutions across the electronic resources lifecycle. [ABSTRACT FROM AUTHOR]

The article examines the housing policy failure, alternatives to low income housing and a new model homeownership in the U.S. Topics discussed include the relationship between housing, health care access, job opportunities and personal safety, among others, benefit of using the therapeutic jurisprudence interdisciplinary approach to affordable housing law, and the components of the Village homeownership model such as land trust and communal spaces.

Objective: To systematically review the literature on the psychometric properties of the Clinical Dementia Rating (CDR) scale among Hispanic-Latinx communities. Data Selection: We searched multiple cross-disciplinary databases from January 1970 until April 2023 for relevant papers written in English and Spanish. We used the following terms: (1) Clinical Dementia Rating, (2) validity, (3) reliability, (4) psychometric, (5) Hispanic, (6) Latinos or Latinx, (7) outcome measures, (8) Spanish language, and (9) Alzheimer's disease. Data Synthesis: We found 609 studies with 56 eligible studies. Only 5 studies examined psychometric properties of the CDR in Hispanic-Latinx communities. Each study implemented divergent study designs. Of the 5 selected studies, one study evaluated the validity of the CDR Sum of Boxes among 1073 Mexican Americans. A second study evaluated the CDR's test–retest reliability and internal consistency among 94 Spanish speaking participants from the United States. The third study examined the validity of the CDR Sum of Boxes among 343 Brazilians living in Brazil. A fourth study assessed the CDR Sum of Boxes sensitivity and specificity among 407 Brazilians living in Brazil, whereas a fifth study evaluated the validity of a Portuguese CDR version on 424 Brazilians living in Brazil. Conclusions: Our systematic review revealed limited studies examining the validation of the CDR in the Hispanic-Latinx communities. The limited number of studies raises concerns about versions of the CDR scale implemented in ad clinical trials, and its implications to study results, interpretation, and generalizability of findings. [ABSTRACT FROM AUTHOR]

The paper describes the design of a methodology in infrastructure solutions applicable to technological implementation projects. For the development, the documentary chain method was used, which consists of three stages: collection, treatment and diffusion. In the collection step relevant information is collected from the methodological processes used in degree thesis developed in the Computing Major of the Escuela Superior Politécnica Agropecuaria de Manabí Manuel Félix López, until 2015. In the treatment step, a descriptive case study of the methodologies used in the technological infrastructure research subline was carried out. In the diffusion step, the proposal was socialized. The research shows that the methodological processes used for the execution of technological infrastructure projects are acceptable in only 20%. This demonstrates that the proposed methodology presents clarity and precision. [ABSTRACT FROM AUTHOR]

This study compared the past-year prevalence rates of nonsuicidal self-injury produced by a behavioral checklist assessment and a single-item measure. In order to extend previous research on differences in prevalence rates across research samples, we employed both assessment types within a single sample of young adults (N = 433). Moreover, as an indicator of convergent validity, those rates were analyzed in association with participants' depression and anxiety scores, bindings indicated that the checklist assessment, relative to the single-item measure, produced a substantially higher prevalence rate, thereby providing greater evidence for the validity of its outcomes on the basis of convergence. [ABSTRACT FROM AUTHOR]

Introduction: Impulse oscillometry is a test that evaluates the respiratory mechanics by the application of small pulses of pressure, which produce flow oscillations to a certain frequency. Its main application is in the study of the illnesses of the small airline. The integrated software of the test equipment generates predictive values for each of the oscillometric parameters, based on German population data. Objective: To standardize the impulse oscillometry test in order to design pilot equations for reference values in our population. Material and methods: We performed a pilot, experimental, analytical, longitudinal study with healthy volunteer subjects. Spirometry and impulse oscillometry tests were performed, both basal impedances, resistances, and reactances of the respiratory system to and after bronchodilator application; we measured and registered the 5, 10, 15, and 20 Hz. The results were analyzed by sex, age, height, and weight. The analysis was performed using a model of multiple linear retrogression. Results: A total of 127 healthy participants were recruited, 51.5% men (68) and 48.5% (64) women, with an average age of 39.65 ± 15.26 years; their height was an average of 1.63 ± 0.09 m. It was proved that the gender infl uences the oscillometry values of tidal volume (VT), the impedance, the resistances and reactance area (p < 0.05), but not the reactances (XRs) (p > 0.05); this parameter is mainly associated with the size (r = 0.727, r2 = 0.528). The age infl uences the oscillometry values since the resistances (Rrs) are lower in the youngest groups; the BMI and the weight had no infl uence on the values of IOS. Conclusions: This study provides pilot reference equations for the common indexes of impulse oscillometry in Mexican subjects, in order to integrate this test of pulmonary function to facilitate the detection of functional alterations in the small airline. We suggest more studies should be done on Mexican population, and especially on people of advanced age, to confi rm our results and to provide a more solid base for the equations of reference to IOS, with clinical and epidemiologic purposes. [ABSTRACT FROM AUTHOR]

• Criteria were established to define key foods and critical nutrients in Costa Rica. • Our country has a limited installed capacity to generate food composition data. • A lack of accredited methods was identified in the laboratories consulted. • It is necessary to promote alliances between entities to produce this data. Analyze the methodological components and available resources for generation of food composition data (FCD) in Costa Rica (CR). Laboratories that perform food composition analysis in CR were consulted in order to characterize them and evaluate which complied with the standards established by international authorities for the generation of FCD. Finally, the applicability of the technical criteria determined by the international authorities for food and nutrient analysis was evaluated with experts in CR. We found that several entities have the capacity of both in infrastructure and human resources to generate FCD, however their work is disjointed, they have a very limited budget and there is no national FCD system. One of the limitations that we identified is that public laboratories don't offer analysis of water-soluble vitamins, which limits obtaining complete data on food samples. In addition, there is no consensus in the country regarding which foods and nutrients should be included in the food composition databases (FCDB). Costa Rica need to improve the generation of our own data in the country for some specific foods. Promote alliances between entities that have the capacity to produce data and work towards achieving an integrated FCD system in the country. [ABSTRACT FROM AUTHOR]

The tomato budworm, Tuta absoluta, is considered main pest of tomato crops. Control of this pest is performed with hemicals, although, there are other strategies such as biological and ethological control. In Colombia there is not precedent that combines both strategies: ethological control with sexual pheromone and biological control with Apanteles gelechiidivoris, for the control of this pest in tomato crops. In this work four different treatments under greenhouse conditions were evaluated including biological control with A. gelechiidivoris, ethological control with sexual pheromone traps, combined action of both controls and traditional control (Chemicals). The experiments aimed to developing a control strategy to reduce populations of T. absoluta. This was done sampling a plant every to 2 meters. From each plant a sample composed by one leaf by stratum was taken and the variables number of total larvae of third instar and parasited and number of captured adults for trap. The maximum parasitism in the population of susceptible larvae was 86.38 % and for total population of larvae was 68.75 %. The combined action of pheromone traps and A gelechiidivoris presented a greater efficiency and permanence on the control of larvae of T. absoluta. [ABSTRACT FROM AUTHOR]

Chondrocytes are the only cells in cartilage, and their death by apoptosis contributes to cartilage loss in inflammatory joint diseases, such as rheumatoid arthritis (RA). A putative therapeutic intervention for RA is the inhibition of apoptosis-mediated cartilage degradation. The hormone prolactin (PRL) frequently increases in the circulation of patients with RA, but the role of hyperprolactinemia in disease activity is unclear. Here, we demonstrate that PRL inhibits the apoptosis of cultured chondrocytes in response to a mixture of proinflammatory cytokines (TNF-α, IL-1β, and IFN-γ) by preventing the induction of p53 and decreasing the BAX/BCL-2 ratio through a NO-independent, JAK2/STAT3-dependent pathway. Local treatment with PRL or increasing PRL circulating levels also prevented chondrocyte apoptosis evoked by injecting cytokines into the knee joints of rats, whereas the proapoptotic effect of cytokines was enhanced in PRL receptor-null (Prlr-/-) mice. Moreover, eliciting hyperprolactinemia in rats before or after inducing the adjuvant model of inflammatory arthritis reduced chondrocyte apoptosis, proinflammatory cytokine expression, pannus formation, bone erosion, joint swelling, and pain. These results reveal the protective effect of PRL against inflammation-induced chondrocyte apoptosis and the therapeutic potential of hyperprolactinemia to reduce permanent joint damage and inflammation in RA. [ABSTRACT FROM AUTHOR]

Background: In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls. Methods: Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with Tissue Factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received Tissue Factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair. Results: All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue. Conclusions: Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. [ABSTRACT FROM AUTHOR]

Chitosan is a biocompatible polysaccharide composed of glucosamine and N-acetylglucosamine. The polymer has a unique behavior of fluctuating between soluble chains at pH 6 and insoluble microparticles at pH 7. The purpose of this study was to test the hypothesis that chitosan structure, solubility state, and serum influence the rate of cell uptake. Chitosans with 80% and 95% degree of deacetylation (medium and low viscosity) were tagged with rhodamine and analyzed for particle size, media solubility, and uptake by HEK293 epithelial cells using live confocal microscopy and flow cytometry. In media pH 7.4 with or without 10% serum, chitosans fully precipitated into 0.5 to 1.4 μm diameter microparticles with a slight negative charge. During 24 h of culture in serum-free medium, chitosan particles remained extracellular. In cultures with serum, particles were taken up into intracellular vesicles in a serum dose-dependent manner. Opsonization of chitosan with serum, or replacement of serum by epidermal growth factor (EGF) failed to mediate serum-free chitosan particle uptake. Serum stimulated cells to acidify the media, partly by lactate generation. Media acidified to pH 6.5 by 7 mM lactate maintained 50% of chitosan in the soluble fraction, and led to minor uniform serum-free uptake in small vesicles. Conclusion: Media acidification mediates minor in vitro uptake of non-biofouled soluble chitosan chains, while serum-biofouled insoluble chitosan microparticles require sustained serum exposure to generate energy required for macropinocytosis. [ABSTRACT FROM AUTHOR]

Hypertension is prevalent in patients with systemic lupus erythematosus (SLE). The goal of the current study is to track the pathogenesis of hypertension and renal injury in SLE, identify contributory mechanisms, and highlight differences in disease development among sexes. Mean arterial pressure was measured in conscious male and female SLE (NZBWF1) and control (NZW) mice at 34–35 wk of age using indwelling arterial catheters. Measures of renal injury, renal inflammation, and renal hemodynamics were used to monitor the potential contributors to latent sex differences. Both male and female SLE mice were hypertensive at 35 wk of age, and the hypertension was linked to renal injury in females, but not in males. A known contributor of renal pathology in SLE, Toll-like receptor (TLR)-7, and its downstream effector, the proinflammatory cytokine tumor necrosis factor (TNF)-α, were lower in male SLE mice than in females. Male SLE mice also had higher glomerular filtration rate (GFR) and lower renal vascular resistance (RVR) than females. Our data suggest that although hypertension in female SLE mice is associated with renal mechanisms, hypertension in male SLE mice may develop independent of renal changes. Future studies will continue to dissect sex-specific factors that should be considered when treating patients with hypertension with underlying chronic inflammation and/or autoimmunity. NEW & NOTEWORTHY There is a high prevalence of hypertension in male and female SLE; however, male SLE mice are hypertensive without renal involvement. The development of hypertension in female SLE mice is renocentric and strongly associated with injurious renal mechanisms like the TLR-7→TNF-α pathway. This clear difference in the pathogenesis among the sexes could have a significant impact on how we treat patients with hypertension with underlying chronic autoimmune/inflammatory diseases. [ABSTRACT FROM AUTHOR]

Abstract: Alternatively activated macrophages have been implicated in the therapeutic activity of biodegradable chitosan on wound healing, however, the mechanisms of phenotypic differentiation are still unclear. In vitro, macrophages stimulated with high doses of chitosan (⩾500μg/mL) were reported to produce low-level markers associated with alternative activation (arginase-1) as well as classical activation (nitric oxide), and to undergo apoptosis. In this study, we tested the hypothesis that 40kDa biodegradable chitosan (5–500μg/mL) is sufficient to polarize mouse bone marrow-derived macrophages (BMDM) in vitro to an alternatively activated phenotype. Control cultures were stimulated with IL-4 (alternative activation), IFN-γ/LPS (classical activation), 1μm diameter latex beads (phagocytosis), or left untreated. After 48h of in vitro exposure, BMDM phagocytosed fluorescent chitosan particles or latex beads, and remained viable and metabolically active, although some cells detached with increasing chitosan and latex bead dosage. Arginase-1 was over 100-fold more strongly induced by IL-4 than by chitosan, which induced only sporadic and weak arginase-1 activity over untreated BMDM, and no nitric oxide. IFN-γ/LPS stimulated nitric oxide production and arginase-1 activity and high concentrations of inflammatory cytokines (IL-6, IL-1β, TNF-α, MIP-1α/MIP-1β), while latex beads stimulated nitric oxide and not arginase-1 activity. Chitosan or latex bead exposure, but not IL-4, tended to promote the release of several chemokines (MIP-1α/β, GM-CSF, RANTES, IL-1β), while all treatments promoted MCP-1 release. These data show that chitosan phagocytosis is not sufficient to polarize BMDM to the alternative or the classical pathway, suggesting that biodegradable chitosan elicits alternatively activated macrophages in vivo through indirect mechanisms. [Copyright &y& Elsevier]

Introduction: Type 2 diabetes (DM 2) is one of the first ten causes of mortality in Colombia. Pre-diabetes is a state of hyperglycemia that associated with other risk factors appears 5-10 years before this disease. It has been reported that controlling the diet and exercise decreases the probability of suffering DM 2 by 60%. This intervention requires establishing the risk in pre-diabetic patients. Objectives: To detect patients with pre-diabetes who are members of a private health care provider (EPS for its name in Spanish) in Cali and to describe the clinical and epidemiological characteristics related to the risk of developing DM 2. Materials and methods: This is a cross-sectional descriptive study in patients with altered glucemias (Impaired fasting glucose: 100-125 mg/dl and impaired glucose tolerance: 140-199 mg/dl). Clinical histories were reviewed and surveys on risk factors, habits and perception of knowledge were conducted. We determined: fasting glucose, vital signs, and anthropometric measures. Results: 111 patients were included (64% women) whose most common occupation was home duties (39.6%). The descriptive analysis reported high risk; the results were: noticeable presence of associate pathological antecedents as follows: Diabetes in the family (64%), obesity (54.1%), dyslipidemia (72.1%), and hypertension (66.7%) in a population with a mean age at 51 years and 10.8% were under 40 years of age. This great proportion of overweight or obesity (86.5%), according to BMI, influenced the determination of the high cardio-metabolic risk (81%, agreeing with the WHO). When evaluating diet with consumption frequency, we still found the intake of simple carbohydrates and animal fats; when reviewing physical activity, 53.2% of the patients reported activity in the last 7 days according to the International Physical Activity Questionnaire (IPAQ). Conclusions: 66% of pre-diabetics did not have diagnosis of some disorder of the metabolism of carbohydrates. More than 70% of the patients have high risk of DM 2 with pathological antecedents, inadequate health habits, and low perception of disease complications. [ABSTRACT FROM AUTHOR]

Introduction: Type 2 diabetes (DM 2) is one of the first ten causes of mortality in Colombia. Pre-diabetes is a state of hyperglycemia that associated with other risk factors appears 5-10 years before this disease. It has been reported that controlling the diet and exercise decreases the probability of suffering DM 2 by 60%. This intervention requires establishing the risk in pre-diabetic patients. Objectives: To detect patients with pre-diabetes who are members of a private health care provider (EPS for its name in Spanish) in Cali and to describe the clinical and epidemiological characteristics related to the risk of developing DM 2. Materials and methods: This is a cross-sectional descriptive study in patients with altered glucemias (Impaired fasting glucose: 100-125 mg/dl and impaired glucose tolerance: 140-199 mg/dl). Clinical histories were reviewed and surveys on risk factors, habits and perception of knowledge were conducted. We determined: fasting glucose, vital signs, and anthropometric measures. Results: 111 patients were included (64% women) whose most common occupation was home duties (39.6%). The descriptive analysis reported high risk; the results were: noticeable presence of associate pathological antecedents as follows: Diabetes in the family (64%), obesity (54.1%), dyslipidemia (72.1%), and hypertension (66.7%) in a population with a mean age at 51 years and 10.8% were under 40 years of age. This great proportion of overweight or obesity (86.5%), according to BMI, influenced the determination of the high cardio-metabolic risk (81%, agreeing with the WHO). When evaluating diet with consumption frequency, we still found the intake of simple carbohydrates and animal fats; when reviewing physical activity, 53.2% of the patients reported activity in the last 7 days according to the International Physical Activity Questionnaire (IPAQ). Conclusions: 66% of pre-diabetics did not have diagnosis of some disorder of the metabolism of carbohydrates. More than 70% of the patients have high risk of DM 2 with pathological antecedents, inadequate health habits, and low perception of disease complications. [ABSTRACT FROM AUTHOR]

The distributions of Fe in mitochondria isolated from respiring, respiro-fermenting, and fermenting yeast cells were determined with an integrative biophysical approach involving Mössbauer and electronic absorption spectroscopies, electron paramagnetic resonance, and inductively coupled plasma emission mass spectrometry. Approximately 40% of the Fe in mitochondria from respiring cells was present in respiration-related proteins. The concentration and distribution of Fe in respiro-fermenting mitochondria, where both respiration and fermentation occur concurrently, were similar to those of respiring mitochondria. The concentration of Fe in fermenting mitochondria was also similar, but the distribution differed dramatically. Here, levels of respiration-related Fe-containing proteins were diminished ∼3-fold, while non-heme HS FeII species, non-heme mononuclear HS FeIII, and FeIII nanoparticles dominated. These changes were rationalized by a model in which the pool of non-heme HS FeII ions serves as feedstock for Fe-S cluster and heme biosynthesis. The integrative approach enabled us to estimate the concentration of respiration-related proteins. [ABSTRACT FROM AUTHOR]

Abstract: Chitosan is a polysaccharide scaffold used to enhance cartilage repair during treatments involving bone marrow stimulation, and it is reported to increase angiogenesis and osteogenesis in vivo. Here, we tested the hypotheses that addition of chitosan particles to the media of human bone marrow stromal cell (BMSC) cultures stimulates osteogenesis by promoting osteoblastic differentiation and by favoring the release of angiogenic factors in vitro. Confluent BMSCs were cultured for 3 weeks with 16% fetal bovine serum, ascorbate-2-phosphate and disodium β-glycerol phosphate, in the absence or presence of dexamethasone, an anti-inflammatory glucocorticoid commonly used as an inducer of BMSC osteoblast differentiation in vitro. As expected, dexamethasone slowed cell division, stimulated alkaline phosphatase activity and enhanced matrix mineralization. Added chitosan particles accumulated intra- and extracellularly and, while not affecting most osteogenic features, they inhibited osteocalcin release to the media at day 14 and interfered with mineralized matrix deposition. Interestingly, dexamethasone promoted cell attachment and suppressed the release and activation of matrix metalloprotease-2 (MMP-2). While chitosan particles had no effect on the release of angiogenic factors, dexamethasone significantly inhibited (p <0.05 to p <0.0001) the release of vascular endothelial growth factor (VEGF), granulocyte-macrophage colony stimulating factor (GM-CSF), tumor necrosis factor-alpha (TNF-α), interleukins 1β, 4, 6, and 10 (IL-1β, IL-4, IL-6, IL-10), and a host of other inflammatory factors that were constitutively secreted by BMSCs. These results demonstrate that chitosan particles alone are not sufficient to promote osteoblast differentiation of BMSCs in vitro, and suggest that chitosan promotes osteogenesis in vivo through indirect mechanisms. Our data further show that continuous addition of dexamethasone promotes osteoblastic differentiation in vitro partly by inhibiting gelatinase activity and by suppressing inflammatory cytokines which result in increased cell attachment and cell cycle exit. [Copyright &y& Elsevier]

R4691 --> Chronic inflammation contributes to the morbidity and mortality in advanced systemic lupus erythematosus (SLE). Endogenous neuroimmune mechanisms like the cholinergic anti‐inflammatory pathway can be targeted to modulate inflammation, but the ability to manipulate such pathways and reduce inflammation and end organ damage has not been fully explored in SLE. Positive allosteric modulators (PAM) are pharmacological agents that inhibit desensitization of the nicotinic acetylcholine receptor (α7‐nAChR), the main anti‐inflammatory feature within the cholinergic anti‐inflammatory pathway, and may augment α7‐dependent cholinergic tone to generate therapeutic benefits in SLE. In the current study, we hypothesized that activating the cholinergic anti‐inflammatory pathway at the level of the α7‐nAChR with systemic administration of a partial agonist, GTS‐21 or a PAM, PNU‐120596, would reduce inflammation, eliminating the associated end organ damage in a mouse model of SLE with advanced disease. Further, we hypothesized that these α7 ligands will have central effects and improve behavioral deficits in SLE mice. Female control (NZW) and SLE mice (NZBWF1) were administered GTS‐21 (15 mg/kg/day), PNU‐120596 (10 mg/kg/day), or vehicle (DMSO) subcutaneously via minipumps for two weeks starting at 33 weeks of age. A subgroup of these mice were subjected to randomized, blinded behavioral tests for sensorimotor and emotional deficits (i.e., open‐field, light‐dark box and tail suspension tests) pre‐ and post‐drug administration. SLE mice had higher plasma dsDNA autoantibodies, a hallmark of SLE and marker of disease severity, than control mice (9.2e5 ± 1.1e5 vs. 1.6e5 ± 3.9e4 U/mL; p < 0.001), but this increase was not altered by GTS‐21 (1.1e6 ± 2.2e5) or PNU‐120596 (1.1e6 ± 2.1e5) in SLE mice. The cholinergic anti‐inflammatory pathway directly alters splenic inflammation and indirectly alters renal inflammation, so we measured TNF‐α in the spleen and renal cortex of control and SLE mice. Splenic and renal TNF‐α was 2‐ and 4‐times higher in SLE mice compared to controls (235.0 ± 28.2 and 417.2 ± 122.7; % difference from controls), but neither was altered by GTS‐21 (262.5 ± 33.4 and 320.8 ± 91.4) or PNU‐120596 (306.1 ± 34.4 and 343.9 ± 97.7) in SLE mice. The anxiety‐like behavior (i.e., decrease in locomotion, increase in sleeping, and decrease distance traveled during open‐field test in SLE mice compared to controls (all p<0.001)) presented by SLE mice was also not improved by GTS‐21 or PNU‐120596. Although no significant beneficial effects of α7 ligands were observed in SLE mice at this advanced stage, we predict that potentiating acetylcholine and targeting this receptor earlier in the pathogenesis of SLE may prove to be efficacious and should be addressed in future studies. [ABSTRACT FROM AUTHOR]

A new bivariate beta distribution based on the Humbert's confluent hypergeometric function of the second kind is introduced. Various representations are derived for its product moments, marginal densities, marginal moments, conditional densities and entropies. [ABSTRACT FROM AUTHOR]

Background: In this study we evaluated a novel approach to guide the bone marrow-driven articular cartilage repair response in skeletally aged rabbits. We hypothesized that dispersed chitosan particles implanted close to the bone marrow degrade in situ in a molecular mass-dependent manner, and attract more stromal cells to the site in aged rabbits compared to the blood clot in untreated controls.Methods: Three microdrill hole defects, 1.4 mm diameter and 2 mm deep, were created in both knee trochlea of 30 month-old New Zealand White rabbits. Each of 3 isotonic chitosan solutions (150, 40, 10 kDa, 80% degree of deaceylation, with fluorescent chitosan tracer) was mixed with autologous rabbit whole blood, clotted with tissue factor to form cylindrical implants, and press-fit in drill holes in the left knee while contralateral holes received tissue factor or no treatment. At day 1 or day 21 post-operative, defects were analyzed by micro-computed tomography, histomorphometry and stereology for bone and soft tissue repair.Results: All 3 implants filled the top of defects at day 1 and were partly degraded in situ at 21 days post-operative. All implants attracted neutrophils, osteoclasts and abundant bone marrow-derived stromal cells, stimulated bone resorption followed by new woven bone repair (bone remodeling) and promoted repair tissue-bone integration. 150 kDa chitosan implant was less degraded, and elicited more apoptotic neutrophils and bone resorption than 10 kDa chitosan implant. Drilled controls elicited a poorly integrated fibrous or fibrocartilaginous tissue.Conclusions: Pre-solidified implants elicit stromal cells and vigorous bone plate remodeling through a phase involving neutrophil chemotaxis. Pre-solidified chitosan implants are tunable by molecular mass, and could be beneficial for augmented marrow stimulation therapy if the recruited stromal cells can progress to bone and cartilage repair. [ABSTRACT FROM AUTHOR]

R2320 --> 856.11 --> Background: Systemic lupus erythematosus (SLE) is an autoimmune disorder associated with exaggerated immune activation, autoantibody production, and immune complex formation. SLE patients are predominantly women of reproductive age that often present with end organ damage, specifically in the kidneys, and hypertension. This detrimental sequelae is likely due to deposition of the immune complexes and the resulting inflammation, but the exact mechanisms are unknown. It is known however that immune complexes activate toll like receptors (TLRs) on immune cells and TLR7 particularly is known to promote the development and acceleration of the pathogenesis of SLE. Therefore, we hypothesized that renal TLR7 drives the renal injury and hypertension in female SLE mice. Methods: Double‐stranded DNA (dsDNA) autoantibodies, a hallmark of SLE, and albuminuria, a marker of renal injury, were monitored at 30 and 35 weeks of age in female and male SLE (NZBWF1) and control (NZW) mice. Glomerular filtration rate (GFR) was measured by sinistrin clearance and renal TLR7 and tumor necrosis factor (TNF)‐α expression were measured via Western blot to assess renal function and renal inflammation at the end of 35 weeks. Mean arterial pressure was also measured in conscious mice at 35 weeks of age using indwelling arterial catheters. Results: At 30 weeks, female SLE mice had elevated plasma dsDNA autoantibodies compared to female controls (4.6e5 ± 1.3e5 vs 8.9e4 ± 3.3e4; n=3‐5; all p<0.05), male SLE mice (6.3e4 ± 2.7e4 U/mL), and male controls (4.8e4 ± 9.3e3). At 30 weeks, 32% (7 out of 22) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 20) of male SLE, and no male controls. At 35 weeks, 63% (10 out of 16) of female SLE mice had albuminuria versus 5% (1 out of 22) of female controls, 5% (1 out of 19) of male SLE, and no male controls. GFR was lower in female SLE mice compared to males at this same time point (865 ± 77 vs. 1066 ±60 μL/min/100 g body weight; p=0.029). Female SLE mice expressed a significantly higher renal cortical expression of TLR7 (3.9e5 ± 8.0e4 intensity units) than both female control (7.5e4 ± 2.6e3 intensity units; p < 0.001) and male SLE mice (7.0e4 ± 1.5e4 intensity units; p < 0.001). Renal cortical expression of TNF‐α, a downstream effector of TLR7, was increased in female SLE mice (1.3e6 ± 3.7e5 intensity units) when compared to both female control mice (1.2e5 ± 3.4e4 intensity units; p < 0.001) and male SLE mice (5.1e5 ± 1.6e5 intensity units; p < 0.001). Both female and male SLE mice were hypertensive at 35 weeks: blood pressure was higher in female SLE than female controls (152 ± 5 vs. 126 ± 3 mmHg; n=6‐8; p=0.003) and in male SLE compared to male controls (152 ± 4 vs. 136 ± 4 mmHg; n=6‐11; p=0.041). Conclusion: These data indicate that increased expression of renal TLR7 and TNF‐α is associated with renal injury and hypertension in female SLE mice. In addition, these data suggest a potential sex difference in the pathogenesis of SLE in males. Therapeutic strategies targeting the TLR7 molecular pathway should be further investigated in both female and male lupus nephritis. [ABSTRACT FROM AUTHOR]

Mössbauer spectroscopy was used to detect pools of Fe in mitochondria from fermenting yeast cells, including those consisting of nonheme high-spin (HS) FeII species, FeIII nanoparticles, and mononuclear HS FeIII species. At issue was whether these species were located within mitochondria or on their exterior. None could be removed by washing mitochondria extensively with ethylene glycol tetraacetic acid or bathophenanthroline sulfonate (BPS), FeII chelators that do not appear to penetrate mitochondrial membranes. However, when mitochondrial samples were sonicated, BPS coordinated the FeII species, forming a low-spin FeII complex. This treatment also diminished the levels of both FeIII species, suggesting that all of these Fe species are encapsulated by mitochondrial membranes and are protected from chelation until membranes are disrupted. 1,10-Phenanthroline is chemically similar to BPS but is membrane soluble; it coordinated nonheme HS FeII in unsonicated mitochondria. Further, the HS FeIII species and nanoparticles were not reduced by dithionite until the detergent deoxycholate was added to disrupt membranes. There was no correlation between the percentage of nonheme HS FeII species in mitochondrial samples and the level of contaminating proteins. These results collectively indicate that the observed Fe species are contained within mitochondria. Mössbauer spectra of whole cells were dominated by HS FeIII features; the remainder displayed spectral features typical of isolated mitochondria, suggesting that the Fe in fermenting yeast cells can be coarsely divided into two categories: mitochondrial Fe and (mostly) HS FeIII ions in one or more non-mitochondrial locations. [ABSTRACT FROM AUTHOR]

ABSTRACT: Yah ip, an [Fe2S2]-containing ferredoxin located in the matrix of Saccharomyces cerevisiae mitochondria, functions in the synthesis of Fe/S clusters and heme a prosthetic groups. EPR, Mössbauer spectroscopy, and electron microscopy were used to characterize the Fe that accumulates in Yahip- depleted isolated intact mitochondria. Gal-YAH1 cells were grown in standard rich media (YPD and YPGa1) under O2 or argon atmospheres. Mitochondria were isolated anaerobically, then prepared in the as-isolated redox state, the dithionite-treated state, and the O2-treated state. The absence of strong EPR signals from Fe/S clusters when Yahip was depleted confirms that Yahip is required in Fe/S cluster assembly. Yahip- depleted mitochondria, grown with O2 bubbling through the media, accumulated excess Fe (up to 10 mM) that was present as 2-4 nm diameter ferric nanoparticles, similar to those observed in mitochondria from yfh1Δ cells. These particles yielded a broad isotropic EPR signal centered around g = 2, characteristic of superparamagnetic relaxation. Treatment with dithionite caused Fe3+ ions of the nanoparticles to become reduced and largely exported from the mitochondria. Fe did not accumulate in mitochondria isolated from cells grown under Ar; a significant portion of the Fe in these organelles was in the high-spin Fe2+ state. This suggests that the O2 used during growth of Gal-YAH1 cells is responsible, either directly or indirectly, for Fe accumulation and for oxidizing Fe2+→Fe3+ prior to aggregation. Models are proposed in which the accumulation of ferric nanoparticles is caused either by the absence of a ligand that prevents such precipitation in wild-type mitochondria or by a more oxidizing environment within the mitochondria of Yahip-depleted cells exposed to O2. The efficacy of reducing accumulated Fe along with chelating it should be considered as a strategy for its removal in diseases involving such accumulations. [ABSTRACT FROM AUTHOR]

Objective  This work aimed to evaluate the factors associated with Streptococcus pneumoniae nasopharyngeal colonization and antimicrobial susceptibility among pediatric outpatients in southwestern Colombia, 2019. Methods  A cross-sectional study was performed using survey-based interviews and the collection of nasopharyngeal-swab specimens for microbiological characterization and antimicrobial susceptibility testing. Logistic regression analyses were performed for factors associated with nasopharyngeal carriage. Results  A total of 452 children under the age of 5 years were examined in which 41.8% carried S. pneumoniae. Higher pneumococcal carriage frequencies were observed among participants aged <2 years and in individuals belonging to indigenous communities, which were lacking established pneumococcal-conjugated vaccine-10 immunization schemes. Additionally, children attending childcare institutions were also highly colonized by pneumococci. S. pneumoniae showed 57.7% nonsusceptibility to benzyl-penicillin (meningitis-cut); 45.5% intermediate-sensitivity to benzyl-penicillin (oral-cut) and 21.7% to cefotaxime; and resistance to erythromycin (40.7%), tetracycline (36.0%), trimethoprim/sulfamethoxazole (24.9%), clindamycin (24.3%), and ceftriaxone (27.0%). Conclusion  The 41.8% of participants carrying S. pneumoniae show a scenario with the presence of multidrug and extensively drug-resistant strains, which constitutes important reservoirs of bacterial transmission by children aged <5 years in Colombia, leading to an onset of pneumococcal diseases. Hence, there is an urgent need to expand conjugate pneumococcal immunization in the community and ensure compliance with established immunization schedules. [ABSTRACT FROM AUTHOR]

The 16 kDa N-terminal fragment of prolactin (16K-prolactin) is a potent antiangiogenic factor. Here, we demonstrate that matrix metalloproteases (MMPs) produced and secreted by chondrocytes generate biologically functional 16K-prolactin from full-length prolactin. When incubated with human prolactin at neutral pH, chondrocyte extracts and conditioned medium, as well as chondrocytes in culture, cleaved the Ser155-Leu156 peptide bond in prolactin, yielding - upon reduction of intramolecular disulfide bonds - a 16 kDa N-terminal fragment. This 16K-prolactin inhibited basic fibroblast growth factor (FGF)-induced endothelial cell proliferation in vitro. The Ser155-Leu156 site is highly conserved, and both human and rat prolactin were cleaved at this site by chondrocytes from either species. Conversion of prolactin to 16K-prolactin by chondrocyte lysates was completely abolished by the MMP inhibitors EDTA, GM6001 or 1,10-phenanthroline. Purified MMP-1, MMP-2, MMP-3, MMP-8, MMP-9 and MMP-13 cleaved human prolactin at Gln157, one residue downstream from the chondrocyte protease cleavage site, with the following relative potency: MMP-8>MMP-13 >MMP-3>MMP-1=MMP-2>MMP-9. Finally, chondrocytes expressed prolactin mRNA (as revealed by RT-PCR) and they contained and released antiangiogenic N-terminal 16 kDa prolactin (detected by western blot and endothelial cell proliferation). These results suggest that several matrix metalloproteases in cartilage generate antiangiogenic 16K-prolactin from systemically derived or locally produced prolactin. [ABSTRACT FROM AUTHOR]

Background: Variants in the 5-lipoxygenase-activating protein (ALOX5AP) and phosphodiesterase 4D (PDE4D) genes have first been associated with ischemic stroke (IS) through whole-genome linkage screens. However, association studies obtained conflicting results. We aimed to investigate the contribution of selected single nucleotide polymorphisms (SNPs) in these genes for the first time in a large Iberian population. Methods: A case-control design was used to analyze one SNP in ALOX5AP and five SNPs in PDE4D in a total of 1,092 IS patients and 781 healthy controls of two different subsets from Spain and Portugal. The analysis was adjusted for confounding variables and the results were integrated in a meta-analysis of all case-control studies. In addition, ALOX5AP gene expression levels were determined in controls and IS cases. Results: A first meta-analysis of both subsets showed that the T allele of the SG13S114 SNP in ALOX5AP was a risk factor for IS after Bonferroni correction [OR = 1.22 (1.06–1.40); p = 0.006]. A second meta-analysis of white populations confirmed these results [OR = 1.18 (1.07–1.31); p = 0.001]. ALOX5AP gene expression analysis in a subset of controls and cases revealed that the SG13S114 genotypes modulate mRNA levels of ALOX5AP (p = 0.001) and mRNA levels were higher in IS cases (2.8 ± 2.4%) than in controls (1.4 ± 1.3%; p = 0.003). No association of the variants in PDE4D with IS was observed in our study. Conclusions: The ALOX5AP SG13S114 variant is an independent risk factor for IS in the Iberian population and is associated with ALOX5AP expression levels. The role of this gene in stroke merits further investigation. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: Genetic factors contribute to the development of ischemic stroke (IS). In order to identify susceptibility variants, we analyzed single nucleotide polymorphisms (SNPs) that had been previously linked to stroke in a genome-wide association study. Methods: We analyzed 12 SNPs in a White population comprising IS patients and healthy controls. The analysis was adjusted for confounding variables and stratified by stroke etiology. Functional studies were then performed to elucidate the role of these variants in IS. Results: In a preliminary analysis of 268 controls and 531 IS cases, the rs10947803 SNP of KCNK17 (p =0.012) and the rs7506045 of IMPA2 (p =0.040) were associated with IS, although only the KCNK17 gene was an independent risk factor for IS. In a second phase, analysis of 271 new IS cases revealed that the A allele of rs10947803 was associated with stroke after correction for Bonferroni (OR=1.48; 95% CI, 1.14–1.91, p =0.003). Gene expression analysis revealed that KCNK17 mRNA levels were higher in the IS cases in the acute phase than in controls (14±78% vs. 91±41, p =0.002) but not in the chronic phase (56±57%; p =0.230). Moreover, RNA levels depended on the alleles of the rs10947803 SNP in the control group (p =0.021) and in the chronic phase (p =0.033). Conclusions: The A allele of the rs10947803 variant of KCNK17 was associated with increased risk of IS and increased levels of KCNK17 gene expression. The role of this potassium channel gene in IS opens diagnostic and therapeutic expectations and merits further investigation. [Copyright &y& Elsevier]

Triggering receptor expressed on myeloid cells-like (TREM-like) transcript-1 (TLT-1), a type 1 single Ig domain orphan receptor specific to platelet and megakaryocyte alpha-granules, relocates to the platelet surface upon platelet stimulation. We found here that patients diagnosed with sepsis, in contrast to healthy individuals, had substantial levels of soluble TLT-1 (sTLT-1) in their plasma that correlated with the presence of disseminated intravascular coagulation. sTLT-1 bound to fibrinogen and augmented platelet aggregation in vitro. Furthermore, the cytoplasmic domain of TLT-1 could also bind ezrin/radixin/moesin family proteins, suggesting its ability to link fibrinogen to the platelet cytoskeleton. Accordingly, platelets of Treml1-/- mice failed to aggregate efficiently, extending tail-bleeding times. Lipopolysaccharide-treated Treml1-/- mice developed higher plasma levels of TNF and D-dimers than wild-type mice and were more likely to succumb during challenge. Finally, Treml1-/- mice were predisposed to hemorrhage associated with localized inflammatory lesions. Taken together, our findings suggest that TLT-1 plays a protective role during inflammation by dampening the inflammatory response and facilitating platelet aggregation at sites of vascular injury. Therefore, therapeutic modulation of TLT-1-mediated effects may provide clinical benefit to patients with hypercoagulatory conditions, including those associated with inflammation. [ABSTRACT FROM AUTHOR]