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Study design Prospective observational studyObjective The population of patients with advanced stages of cancer, including metastatic spinal disease, is growing because of better treatment options allowing for longer control of disease. The main goal of treatment for these patients is to improve or maintain their health-related quality of life (HRQOL). A spine oncology-specific outcome measure has been developed by the Spine Oncology Study Group and validated through international studies. We proposed to translate and validate the questionnaire in Italian language.Methods The cross-cultural adaptation of the questionnaire has been performed according to guidelines previously proposed. After this process, an observational prospective study has been conducted to validate the efficacy of SOSGOQ in Italian language. SOSGOQ has been compared to SF-36 (Short Form Health Survey-36), a generic validated questionnaire to assess HRQOL. Starting from January 2020, SOSGOQ and SF-36 questionnaires were auto-administered to 150 patients affected by spinal metastases who provided written informed consent for study participation.Results The confirmatory factor analysis on the 4 domains examined showed a good model fit (comparative fit index, .95; RMSEA .07 (90% CI, .05-.09) and SRMR, .05), endorsing construct validity. The analysis of concurrent validity demonstrated strong correlation for physical function, pain and mental health domains with the corresponding domain scores of SF-36. The reliability across item was high with a Cronbach’s alpha coefficient of .91.Conclusions The statistical analysis of the results will allow to accept the Italian version of SOSGOQ as a specific and efficient tool to measure HRQOL in Italian-speaking patients affected by spinal metastases.

Backed by decades of empirical research, there has been increasing acknowledgment in policy, practice and research of the importance of neighborhood opportunity in shaping well-being. This has led to the proliferation of opportunity maps in cities throughout the United States with the purpose of identifying low opportunity neighborhoods in need of investment and intervention and high opportunity neighborhoods that can offer access to resources and amenities to disadvantaged population groups. By explicitly linking investment to the identification of neighborhoods that are high or low in opportunity, opportunity indices have the potential to help transform local and regional landscapes of spatial inequality. Despite this common goal, indices rely on varying theoretical conceptualizations, data, variables, and statistical approaches. How much these opportunity definitions overlap has yet to be fully examined. In this study, we compared five approaches to measuring neighborhood opportunity in California. We found low to moderate overlap across the indices, with disagreement higher for low opportunity designations. As with any quantitative analysis, opportunity mapping is not a purely technical exercise and requires a series of subjective decisions. The only way to validate these decisions is for opportunity measures to be constructed transparently and vetted by the research community. This study is a first step in this process.

Otitis externa is a common problem in both primary care and referral practice. A wide range of factors contribute to the successful management of disease. A logical approach and investigation are important and should always include an appreciation of underlying primary causes, predisposing and perpetuating factors, and secondary infection. Cytology is essential to help choose appropriate therapy and represents an opportunity to use the expertise of the nurses within the veterinary team. COVID-19 has forced many veterinary professionals to use remote consultation techniques to provide care for patients and it may be that some of the lessons we have learned during lockdown can be applied to our working practices to improve the level of veterinary care in the future. The selection of appropriate topical anti-microbial and anti-inflammatory drugs is, of course, important but without good levels of owner compliance even the best therapy is ineffective. This article presents the outcome of a workshop in which a group of experts discussed many of these topics.

Individuals with severe psychiatric disorders have a reduced life expectancy compared to the general population. At the biological level, patients with these disorders present features that suggest the involvement of accelerated aging, such as increased circulating inflammatory markers and shorter telomere length (TL). To date, the role of the interplay between inflammation and telomere dynamics in the pathophysiology of severe psychiatric disorders has been scarcely investigated. In this study we measured T-lymphocytes TL with quantitative fluorescent in situ hybridization (Q-FISH) and plasma levels of inflammatory markers in a cohort comprised of 40 patients with bipolar disorder (BD), 41 with schizophrenia (SZ), 37 with major depressive disorder (MDD), and 36 non-psychiatric controls (NPC). TL was shorter in SZ and in MDD compared to NPC, while it was longer in BD (model F6, 137= 20.128, p= 8.73 × 10−17, effect of diagnosis, F3= 31.870; p= 1.08 × 10−15). There was no effect of the different classes of psychotropic medications, while duration of treatment with mood stabilizers was associated with longer TL (Partial correlation controlled for age and BMI: correlation coefficient = 0.451; p= 0.001). Levels of high-sensitivity C-Reactive Protein (hsCRP) were higher in SZ compared to NPC (adjusted p = 0.027), and inversely correlated with TL in the whole sample (r= −0.180; p= 0.042). Compared to NPC, patients with treatment resistant (TR) SZ had shorter TL (p= 0.001), while patients with TR MDD had higher levels of tumor necrosis factor-α (TNFα) compared to NPC (p= 0.028) and to non-TR (p= 0.039). Comorbidity with cardio-metabolic disorders did not influence the observed differences in TL, hsCRP, and TNFα among the diagnostic groups. Our study suggests that patients with severe psychiatric disorders present reduced TL and increased inflammation.

We studied the role of galectin-3 (Gal-3) in the expression of alternative activation markers (M2) on macrophage, cytokines, and fibrosis through the temporal evolution of healing, ventricular remodeling, and function after myocardial infarction (MI). C57BL/6J and Gal-3 knockout mice (Lgals3-/-) were subjected to permanent coronary ligation or sham. We studied i) mortality, ii) macrophage infiltration and expression of markers of alternative activation, iii) cytokine, iv) matrix metalloproteinase-2 activity, v) fibrosis, and vi) cardiac function and remodeling. At 1 week post-MI, lack of Gal-3 markedly attenuated F4/80+ macrophage infiltration and significantly increased the expression of Mrc1and Chil1, markers of M2 macrophages at the MI zone. Levels of IL-10, IL-6, and matrix metalloproteinase-2 were significantly increased, whereas tumor necrosis factor-α, transforming growth factor-β, and fibrosis were remarkably attenuated at the infarct zone. In Gal-3 knockout mice, scar thinning ratio, expansion, and cardiac remodeling and function were severely affected from the onset of MI. At 4 weeks post-MI, the natural evolution of fibrosis in Gal-3 knockout mice was also affected. Our results suggest that Gal-3 is essential for wound healing because it regulates the dynamics of macrophage infiltration, proinflammatory and anti-inflammatory cytokine expression, and fibrosis along the temporal evolution of MI in mice. The deficit of Gal-3 affected the dynamics of wound healing, thus aggravating the evolution of remodeling and function.

Aim:To assess the role of lithium treatment in the relationship between bipolar disorder (BD) and leukocyte telomere length (LTL). Materials & methods:We compared LTL between 131 patients with BD, with or without a history of lithium treatment, and 336 controls. We tested the association between genetically determined LTL and BD in two large genome-wide association datasets. Results:Patients with BD with a history lithium treatment showed longer LTL compared with never-treated patients (p = 0.015), and similar LTL compared with controls. Patients never treated with lithium showed shorter LTL compared with controls (p = 0.029). Mendelian randomization analysis showed no association between BD and genetically determined LTL. Conclusion:Our data support previous findings showing that long-term lithium treatment might protect against telomere shortening.

Thyroid hormones are regarded as the major controllers of metabolic rate and oxygen consumption in mammals. Although it has been demonstrated that thyroid hormone supplementation improves bovine embryo development in vitro, the cellular mechanisms underlying these effects are so far unknown. In this study, we investigated the role of thyroid hormone in development of human preimplantation embryos. Embryos were cultured in the presence or absence of 10−7M triiodothyronine (T3) till blastocyst stage. Inner cell mass (ICM) and trophectoderm (TE) were separated mechanically and subjected to RNAseq or quantification of mitochondrial DNA copy number. Analyses were performed using DESeq (v1.16.0 on R v3.1.3), MeV4.9 and MitoMiner 4.0v2018 JUNplatforms. We found that the exposure of human preimplantation embryos to T3 had a profound impact on nuclear gene transcription only in the cells of ICM (1178 regulated genes—10.5% of 11 196 expressed genes) and almost no effect on cells of TE (38 regulated genes—0.3% of expressed genes). The analyses suggest that T3 induces in ICM a shift in ribosome and oxidative phosphorylation activity, as the upregulated genes are contributing to the composition and organization of the respiratory chain and associated cofactors involved in mitoribosome assembly and stability. Furthermore, a number of genes affecting the citric acid cycle energy production have reduced expression. Our findings might explain why thyroid disorders in women have been associated with reduced fertility and adverse pregnancy outcome. Our data also raise a possibility that supplementation of culture media with T3 may improve outcomes for women undergoing in vitro fertilization. Embryos cultured in the presence or absence of triiodothyronine (T3) till blastocyst stage upregulate genes contributing to the composition and organization of the respiratory chain and associated cofactors involved in mitoribosome assembly and stability. Furthermore, a number of genes affecting the citric acid cycle energy production have reduced expression.

Background: Diabetic foot ulcers (DFUs) constitute a complication that occurs in 19% to 34% of patients with diabetes mellitus (DM). The aim of this study is to describe median days to healing, average velocity of wound closure, and percentage of wound surface closed at 3, 6, and 12 weeks through the use of homogenized and lyophilized amniotic membrane (hAMpe) dressings for the treatment of DFUs in ambulatory patients.Methods: An observational, descriptive, longitudinal study was performed. Patients presenting with granulation-based DFU, after proper debridement, were included from August 19, 2021, until July 14, 2023. hAMpe dressings placed every 3 days were used for the treatment of these ulcers.Results: Sixteen patients were included with a mean age of 52.38 (8.07) years. The analyzed lesions were postsurgical ulcers in 15 of the 16 included patients. Median ulcer size was 19.5 cm2(6.12-36). The median ABI was 1.10 (1-1.14). The median days to healing was 96 (71-170). The median percentage closure of the wound at 3 weeks was 41% (28.9%-55.3%), at 6 weeks it was 68.2% (48.6%-74.2%), and at 12 weeks it was 100% (81%-100%). The average velocity closure was 1.04% per day (95% CI 0.71%-1.31%). It was higher during the closure of the first 50% of the ulcer, 2.12% per day (95% CI 0.16%-4.09%), and decreased from 50% to 25% of the ulcer size to 0.67% per day (95% CI 0.23%-1.10%) and from 25% to closure to 0.47% per day (95% CI 0.14%-0.80%), P< .001.Conclusion: These results are difficult to compare to other studies given the higher surface area of the ulcers included in our sample. The development of hAMpe dressings enables patients to apply them without requiring assistance from health care teams and was not associated with any recognized complications.Level of Evidence: Level IV, case series.

ABSTRACTThere is ongoing interest on the outcomes of residential mobility during the young adulthood. In this paper, we examine movement in and out of disadvantaged and advantaged neighborhoods as individuals move out of the family home and experience significant life course events. Using longitudinal data on young adults in the United States from the National Longitudinal Study of Adolescent to Adult Health, we find that while the point-in-time measure of the neighborhood poverty gap (the difference between the most and least advantaged neighborhoods) remained nearly identical from adolescence to young adulthood. But the neighborhood poverty gap between individuals starting out in the least and most disadvantaged residential settings decreased by 18.2 percentage points. In other words, cross sectional estimates of the poverty gap do not capture the dynamism of changes in poverty with young adult transitions. Partner formation, home ownership, and educational attainment are important life course transitions associated with significant moves up and down the neighborhood poverty distribution.

The success of environmental justice (EJ) struggles is dependent on community-based action. However, grassroots environmentalism is most successful when groups act during periods of increased political opportunity. Considering President Trump's promise to roll back environmental protections, tolerance of racism, and anti-immigrant stance, EJ scholars and advocates question how local communities can promote EJ under the Trump administration. This article explores the advocacy campaign to ban chlorpyrifos, a hazardous insecticide, and traces the administration's impact on advocates' tactics and outcomes. Advocates frame efforts to ban chlorpyrifos as an EJ struggle because exposure risk disproportionately impacts children and Latinx, immigrant farmworker communities. During the Obama administration, in response to advocacy groups' petition to ban chlorpyrifos use, the Environmental Protection Agency (EPA) proposed to revoke all food tolerances and to cancel all registrations for chlorpyrifos. However, this proposed ruling was reversed after President Trump took office and nominated Scott Pruitt, an opponent of environmental regulations, as Administrator of the EPA. Furthermore, the EPA appealed the ensuing court decision ordering the agency to revoke all tolerances for chlorpyrifos. Nonetheless, advocates successfully pressured California and Hawaii to strengthen chlorpyrifos regulation. While changes to environmental policymaking under the Trump administration constrained the campaign's success at the federal level, opportunities for restricting chlorpyrifos expanded at the state level. [ABSTRACT FROM AUTHOR]

Quality of life (QoL) is defined as “the degree to which an individual enjoys his or her life.” In canine dermatology, 2 research groups have developed and validated questionnaires for QoL assessment in dogs with dermatologic conditions, the first being limited to canine atopic dermatitis, and the second one applicable to all skin conditions. A third group is working on the validation of a different QoL questionnaire coupled with a treatment success assessment tool. In general, there is an inverse correlation between QoL and pruritus.

Mitochondrial DNA (mtDNA) mutations cause inherited diseases and are implicated in the pathogenesis of common late-onset disorders, but how they arise is not clear1,2. Here we show that mtDNA mutations are present in primordial germ cells (PGCs) within healthy female human embryos. Isolated PGCs have a profound reduction in mtDNA content, with discrete mitochondria containing ~5 mtDNA molecules. Single-cell deep mtDNA sequencing of in vivo human female PGCs showed rare variants reaching higher heteroplasmy levels in late PGCs, consistent with the observed genetic bottleneck. We also saw the signature of selection against non-synonymous protein-coding, tRNA gene and D-loop variants, concomitant with a progressive upregulation of genes involving mtDNA replication and transcription, and linked to a transition from glycolytic to oxidative metabolism. The associated metabolic shift would expose deleterious mutations to selection during early germ cell development, preventing the relentless accumulation of mtDNA mutations in the human population predicted by Muller’s ratchet. Mutations escaping this mechanism will show shifts in heteroplasmy levels within one human generation, explaining the extreme phenotypic variation seen in human pedigrees with inherited mtDNA disorders.

The foundations of mammalian development lie in a cluster of embryonic epiblast stem cells. In response to extracellular matrix signalling, these cells undergo epithelialization and create an apical surface in contact with a cavity, a fundamental event for all subsequent development. Concomitantly, epiblast cells transit through distinct pluripotent states, before lineage commitment at gastrulation. These pluripotent states have been characterized at the molecular level, but their biological importance remains unclear. Here we show that exit from an unrestricted naive pluripotent state is required for epiblast epithelialization and generation of the pro-amniotic cavity in mouse embryos. Embryonic stem cells locked in the naive state are able to initiate polarization but fail to undergo lumenogenesis. Mechanistically, exit from naive pluripotency activates an Oct4-governed transcriptional program that results in expression of glycosylated sialomucin proteins and the vesicle tethering and fusion events of lumenogenesis. Similarly, exit of epiblasts from naive pluripotency in cultured human post-implantation embryos triggers amniotic cavity formation and developmental progression. Our results add tissue-level architecture as a new criterion for the characterization of different pluripotent states, and show the relevance of transitions between these states during development of the mammalian embryo.

The microbiome is the defined as the microbial communities of bacteria, archaea, viruses, fungi, protists and arthropods that live in and on our body. New methods, called next-generation sequencing technologies, have allowed the identification of thousands of microbial species, the majority of which it is impossible to culture with traditional methods. Sophisticated bioinformatic tools are used for basic sequence processing, taxonomic assignment, diversity analyses and community comparisons. The first studies on cutaneous microbiome in veterinary medicine have been published and dysbiosis has been recognized in association with canine atopic dermatitis. This review summarizes the main findings on human and veterinary cutaneous microbiome.

Oil refineries release harmful pollutants affecting the neighboring communities. Τhe environmental impact of the continuous operation of an oil refinery was explored in soils and vegetables in northern Greece. The investigation focused on the presence of radionuclides and heavy metals in the surrounding area of the oil refinery. The determination of the activity concentrations of uranium, radium and thorium was performed by gamma and alpha spectrometry while the concentrations of heavy metals and trace elements (As, Pb, Cu, Mn, Zn, Ni, Fe) were determined by X-ray fluorescence (EDXRF) and inductively coupled plasma spectroscopy (ICP-OES). The results obtained from a two-years survey, in cold and warm periods, showed slight temporal variation and the concentrations of the dispersed metals do not exceed literature values. Determination of pollution indexes, as contamination factor and degree (CF and Cd), as well as enrichment (EF) and transfer factor (TF) from soil to plants and hazard quotient (HQ) led to a better assessment of the environmental status so that measures can be taken to limit the pollution and the effects on human health.

In this study, for the first time ZnO nanoparticles and diatomite-supported ZnO nanocomposite have been utilized as adsorbent for the removal of Th(IV) ions from aqueous solutions under different experimental conditions. The Langmuir, Freundlich, Temkin and Dubinin– Radushkevich (D–R) isotherms were used to analyze the equilibrium data. The sorption equilibrium data were fitted well to the Langmuir isotherm with maximum sorption capacities values was found to be 1.105 mmol/g and 0.320 mmol/g for ZnO nanoparticles and diatomite supported ZnO nanocomposite, respectively. Pseudo-first and pseudo-second order equations, Intraparticle diffusion and Bangham’s models were considered to evaluate the rate parameters and sorption mechanism. Sorption kinetics were better reproduced by the pseudo-second order model (R2> 0.999), with an activation energy (Ea) of +99.74 kJ/mol and +62.95 kJ/mol for ZnO nanoparticles and diatomite-supported ZnO nanocomposite, respectively. In order to specify the type of sorption reaction, thermodynamic parameters were also determined. The evaluated ΔG*and ΔH*indicate the non-spontaneous and endothermic nature of the reactions. The results of this work suggest that both of the used materials are fast and effective adsorbents for removing Th(IV) from aqueous solutions and chemical sorption plays a role in controlling the sorption rate.

Bruton’s tyrosine kinase (BTK) is essential for B-cell proliferation/differentiation and it is generally believed that its expression and function are limited to bone marrow-derived cells. Here, we report the identification and characterization of p65BTK, a novel isoform abundantly expressed in colon carcinoma cell lines and tumour tissue samples. p65BTK protein is expressed, through heterogeneous nuclear ribonucleoprotein K (hnRNPK)-dependent and internal ribosome entry site-driven translation, from a transcript containing an alternative first exon in the 5′-untranslated region, and is post-transcriptionally regulated, via hnRNPK, by the mitogen-activated protein kinase (MAPK) pathway. p65BTK is endowed with strong transforming activity that depends on active signal-regulated protein kinases-1/2 (ERK1/2) and its inhibition abolishes RAS transforming activity. Accordingly, p65BTK overexpression in colon cancer tissues correlates with ERK1/2 activation. Moreover, p65BTK inhibition affects growth and survival of colon cancer cells. Our data reveal that BTK, via p65BTK expression, is a novel and powerful oncogene acting downstream of the RAS/MAPK pathway and suggest that its targeting may be a promising therapeutic approach.

Background/Context A long line of research has empirically examined the effects of social context on child and adolescent well-being. Scholars have paid particular attention to two specific levels of social context: the school and neighborhood. Although youths occupy these social contexts simultaneously, empirical research on schools and neighborhoods has largely been conducted independently of one another.Purpose/Objective/Research Question/Focus of Study This study reviews neighborhood and school effects studies conducted between 2005 and 2013 to determine the degree to which these research domains have exclusively examined a single context. The study then uses nationally representative data to compare estimates of school and neighborhood effects across a variety of youth outcomes. The comparison reveals how much estimates of school and neighborhood effects change after accounting for both levels of context.Research Design Cross-classified random effects models are used to estimate the effects of school and neighborhood disadvantage on a variety of youth outcomes. For each youth outcome, I compare the effects of concentrated disadvantage and the percent of variation explained at the school and neighborhood levels across two models: a single context effects model that includes only the school or neighborhood and a model including characteristics of both contexts.Findings/Results Of the 238 school and neighborhood effects studies examined in the review, only 46, or 21%, account for both neighborhoods and schools in the analysis. The multivariate regression results indicate that excluding a level of context has greater consequences on the estimates of neighborhood effects than on school effects. However, ignoring the neighborhood obscures its independent effects on key adolescent outcomes.Conclusions/Recommendations An empirical analysis of context effects on youth well-being should account for both neighborhoods and schools in order to minimize bias in parameter estimates. Furthermore, simultaneously analyzing schools and neighborhoods will move the study of school and neighborhood effects forward by illuminating policies and strategies in which neighborhoods and schools can work together to increase the overall well-being of children and adolescents.

The muographic imaging of volcanoes relies on the measured transmittance of the atmospheric muon flux through the target. An important bias affecting the result comes from background contamination mimicking a higher transmittance. The MU‐RAY and TOMUVOL collaborations measured independently in 2013 the atmospheric muon flux transmitted through the Puy de Dôme volcano using their early prototype detectors, based on plastic scintillators and on Glass Resistive Plate Chambers, respectively. These detectors had three (MU‐RAY) or four (TOMUVOL) detection layers of 1 m2each, tens (MU‐RAY) or hundreds (TOMUVOL) of nanosecond time resolution, a few millimeter position resolution, an energy threshold of few hundreds MeV, and no particle identification capabilities. The prototypes were deployed about 1.3 km away from the summit, where they measured, behind rock depths larger than 1000 m, remnant fluxes of 1.83±0.50(syst)±0.07(stat) m−2d−1deg−2(MU‐RAY) and 1.95±0.16(syst)±0.05(stat) m−2d−1deg−2(TOMUVOL), that roughly correspond to the expected flux of high‐energy atmospheric muons crossing 600 meters water equivalent (mwe) at 18° elevation. This implies that imaging depths larger than 500 mwe from 1 km away using such prototype detectors suffer from an overwhelming background. These measurements confirm that a new generation of detectors with higher momentum threshold, time‐of‐flight measurement, and/or particle identification is needed. The MU‐RAY and TOMUVOL collaborations expect shortly to operate improved detectors, suitable for a robust muographic imaging of kilometer‐scale volcanoes. The feasibility of muon imaging of km thick volcanoes was checked using two different detectors

Aim. We present three patients with epilepsy of infancy with migrating focal seizures treated with the ketogenic diet. Methods. Between February 1, 2012 and January 31, 2014, three patients who met the diagnostic criteria for migrating focal seizures in infancy at our department were placed on the ketogenic diet and followed for a minimum of seven months. Results. Two of the three children responded well to the ketogenic diet. One of these patients became seizure‐free and his neuropsychological performance also significantly improved. The other child had a seizure reduction of 75% to 99% with only weekly seizures and moderate psychomotor improvement. For these two patients who responded well to the ketogenic diet, hospital admission was not required. The remaining patient had a seizure reduction of less than 50%. Tolerability of the diet was good in all three patients. Conclusion. Early treatment with the ketogenic diet should be considered for epilepsy of infancy with migrating focal seizures to control seizures and status epilepticus, and avoid progressive cognitive impairment.

Biological processes require close cooperation of multiple transcription factors that integrate different signals. Thyroid hormone receptors (TRs) induce Krüppel‐like factor 9 (KLF9) to regulate neurogenesis. Here, we show that triiodothyronine (T3) also works through TR to induce KLF9 in HepG2 liver cells, mouse liver, and mouse and human primary hepatocytes and sought to understand TR/KLF9 network function in the hepatocyte lineage and stem cells. Knockdown experiments reveal that KLF9 regulates hundreds of HepG2 target genes and modulates T3 response. Together, T3 and KLF9 target genes influence pathways implicated in stem cell self‐renewal and differentiation, including Notch signaling, and we verify that T3 and KLF9 cooperate to regulate key Notch pathway genes and work independently to regulate others. T3 also induces KLF9 in human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSC) and this effect persists during differentiation to definitive endoderm and hiPSC‐derived hepatocytes. Microarray analysis reveals that T3 regulates hundreds of hESC and hiPSC target genes that cluster into many of the same pathways implicated in TR and KLF9 regulation in HepG2 cells. KLF9 knockdown confirms that TR and KLF9 cooperate to regulate Notch pathway genes in hESC and hiPSC, albeit in a partly cell‐specific manner. Broader analysis of T3 responsive hESC/hiPSC genes suggests that TRs regulate multiple early steps in ESC differentiation. We propose that TRs cooperate with KLF9 to regulate hepatocyte proliferation and differentiation and early stages of organogenesis and that TRs exert widespread and important influences on ESC biology. StemCells2015;33:416–428