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  • Synthetic transcription factors have great promise as tools to help elucidate relationships between gene expression and phenotype by allowing tunable alterations of gene expression without genomic alterations of the loci being studied. However, the years-long timescales, high cost, and technical skill associated with plant transformation have limited their use. In this work we developed a technology called VipariNama (ViN) in which vectors based on the Tobacco Rattle Virus (TRV) are used to rapidly deploy Cas9-based synthetic transcription factors and reprogram gene expression in planta. We demonstrate that ViN vectors can implement activation or repression of multiple genes systemically and persistently over several weeks in Nicotiana benthamiana, Arabidopsis (Arabidopsis thaliana), and tomato (Solanum lycopersicum). By exploring strategies including RNA scaffolding, viral vector ensembles, and viral engineering, we describe how the flexibility and efficacy of regulation can be improved. We also show how this transcriptional reprogramming can create predictable changes to metabolic phenotypes, such as gibberellin biosynthesis in N. benthamiana and anthocyanin accumulation in Arabidopsis, as well as developmental phenotypes, such as plant size in N. benthamiana, Arabidopsis, and tomato. https://www.selleckchem.com/products/sodium-cholate.html These results demonstrate how ViN vector-based reprogramming of different aspects of gibberellin signaling can be used to engineer plant size in a range of plant species in a matter of weeks. In summary, VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.Shoot branching and complex leaf development rely on the establishment of boundaries that precedes the formation of axillary meristems and leaflets. The tomato (Solanum lycopersicum) super determinant mutant is compromised in both processes, due to a mutation in Sde1A. Sde1A encodes a protein with a RAWUL domain, which is also present in Polycomb Group Repressive Complex 1 (PRC1) RING finger proteins and WD Repeat Domain 48 proteins. Genetic analysis revealed that Sde1A and Bmi1A cooperate, whereas Bmi1C antagonizes both activities, indicating the existence of functionally opposing PRC1 complexes that interact with Sde1A. Sde1A is expressed at early stages of boundary development in a small group of cells in the center of the leaf-axil boundary, but its activity is required for meristem formation at later stages. This suggests that Sde1A and Bmi1A promote axillary meristem formation and complex leaf development by safeguarding a pool of cells in the developing boundary zones. Genetic and protein interaction analyses showed that Sde1A and Lateral suppressor (Ls) are components of the same genetic pathway. In contrast to ls, sde1a mutants are not compromised in inflorescence branching, suggesting that Sde1A is a potential target for breeding tomato cultivars with reduced side-shoot formation during vegetative development.
    The goal of this systematic review was to evaluate practice-based, real-world research of individualized complementary and integrative health (CIH) therapies for pain as provided in CIH outpatient clinics.

    A systematic review was conducted using PubMed, Ovid, Cochrane, Web of Science, Scopus and Embase through Dec 2020. The study was listed in the PROSPERO database (CRD42020159193). Major categories of variables extracted included study details and demographics; interventions; and outcomes.

    The literature search yielded 3,316 records with 264 assessed for full text review. Of those, 23 studies (including ∼8,464 patients) were specific to pain conditions as a main outcome. Studies included chiropractic, acupuncture, multimodal individualized intervention/programs, physiotherapy, and anthroposophic medicine therapy. Retention rates ranged from 53% to 91%, with studies offering monetary incentives showing the highest retention. The 0-10 numerical rating scale was the most common pain questionnaire (n = 10,r overall understanding of CIH as provided in clinical settings. Accordingly, we present numerous recommendations to improve publication reporting and guide future research. Our call to action is future, practice-based CIH research is needed, but should be more expansive and in association with a CIH scientific society with academic and healthcare members.Flower development is an important determinant of grain yield in crops. In wheat (Triticum spp.), natural variation for the size of spikelet and floral organs is particularly evident in Triticum turgidum ssp. polonicum (also termed Triticum polonicum), a tetraploid subspecies of wheat with long glumes, lemmas, and grains. Using map-based cloning, we identified VEGETATIVE TO REPRODUCTIVE TRANSITION 2 (VRT2), which encodes a MADS-box transcription factor belonging to the SHORT VEGETATIVE PHASE family, as the gene underlying the T. polonicum long-glume (P1) locus. The causal P1 mutation is a sequence rearrangement in intron-1 that results in ectopic expression of the T. polonicum VRT-A2 allele. Based on allelic variation studies, we propose that the intron-1 mutation in VRT-A2 is the unique T. polonicum subspecies-defining polymorphism, which was later introduced into hexaploid wheat via natural hybridizations. Near-isogenic lines differing for the P1 locus revealed a gradient effect of P1 across spikelets and within florets. Transgenic lines of hexaploid wheat carrying the T. polonicum VRT-A2 allele show that expression levels of VRT-A2 are highly correlated with spike, glume, grain, and floral organ length. These results highlight how changes in expression profiles, through variation in cis-regulation, can affect agronomic traits in a dosage-dependent manner in polyploid crops.MicroRNAs (miRNAs) are small non-coding, endogenous RNAs containing 20-24 nucleotides that regulate the expression of target genes involved in various plant processes. A total 1429 conserved miRNA belonging to 95 conserved miRNA families and 12 novel miRNAs were identified from B. monnieri using small RNA sequencing. The Bm-miRNA target transcripts related to the secondary metabolism were further selected for validation. The Bm-miRNA expression in shoot and root tissues were negatively correlated with their target transcripts. The Bm-miRNA cleavage sites were mapped within the coding or untranslated (UTR) region as depicted by the modified RLM-RACE. In the present study, we validate three miRNA targets, including Asparagine synthetase, Cycloartenol synthase, and Ferulate 5 hydroxylase and elucidate the regulatory role of Bm-miR172c-5p, which cleaves the F5H gene involved in the lignin biosynthesis. Overexpression of Bm-miR172c-5p precursor in B. monnieri suppress F5H gene, leading to reduced lignification and secondary xylem thickness under control and drought stress.
    Synthetic transcription factors have great promise as tools to help elucidate relationships between gene expression and phenotype by allowing tunable alterations of gene expression without genomic alterations of the loci being studied. However, the years-long timescales, high cost, and technical skill associated with plant transformation have limited their use. In this work we developed a technology called VipariNama (ViN) in which vectors based on the Tobacco Rattle Virus (TRV) are used to rapidly deploy Cas9-based synthetic transcription factors and reprogram gene expression in planta. We demonstrate that ViN vectors can implement activation or repression of multiple genes systemically and persistently over several weeks in Nicotiana benthamiana, Arabidopsis (Arabidopsis thaliana), and tomato (Solanum lycopersicum). By exploring strategies including RNA scaffolding, viral vector ensembles, and viral engineering, we describe how the flexibility and efficacy of regulation can be improved. We also show how this transcriptional reprogramming can create predictable changes to metabolic phenotypes, such as gibberellin biosynthesis in N. benthamiana and anthocyanin accumulation in Arabidopsis, as well as developmental phenotypes, such as plant size in N. benthamiana, Arabidopsis, and tomato. https://www.selleckchem.com/products/sodium-cholate.html These results demonstrate how ViN vector-based reprogramming of different aspects of gibberellin signaling can be used to engineer plant size in a range of plant species in a matter of weeks. In summary, VipariNama accelerates the timeline for generating phenotypes from over a year to just a few weeks, providing an attractive alternative to transgenesis for synthetic transcription factor-enabled hypothesis testing and crop engineering.Shoot branching and complex leaf development rely on the establishment of boundaries that precedes the formation of axillary meristems and leaflets. The tomato (Solanum lycopersicum) super determinant mutant is compromised in both processes, due to a mutation in Sde1A. Sde1A encodes a protein with a RAWUL domain, which is also present in Polycomb Group Repressive Complex 1 (PRC1) RING finger proteins and WD Repeat Domain 48 proteins. Genetic analysis revealed that Sde1A and Bmi1A cooperate, whereas Bmi1C antagonizes both activities, indicating the existence of functionally opposing PRC1 complexes that interact with Sde1A. Sde1A is expressed at early stages of boundary development in a small group of cells in the center of the leaf-axil boundary, but its activity is required for meristem formation at later stages. This suggests that Sde1A and Bmi1A promote axillary meristem formation and complex leaf development by safeguarding a pool of cells in the developing boundary zones. Genetic and protein interaction analyses showed that Sde1A and Lateral suppressor (Ls) are components of the same genetic pathway. In contrast to ls, sde1a mutants are not compromised in inflorescence branching, suggesting that Sde1A is a potential target for breeding tomato cultivars with reduced side-shoot formation during vegetative development. The goal of this systematic review was to evaluate practice-based, real-world research of individualized complementary and integrative health (CIH) therapies for pain as provided in CIH outpatient clinics. A systematic review was conducted using PubMed, Ovid, Cochrane, Web of Science, Scopus and Embase through Dec 2020. The study was listed in the PROSPERO database (CRD42020159193). Major categories of variables extracted included study details and demographics; interventions; and outcomes. The literature search yielded 3,316 records with 264 assessed for full text review. Of those, 23 studies (including ∼8,464 patients) were specific to pain conditions as a main outcome. Studies included chiropractic, acupuncture, multimodal individualized intervention/programs, physiotherapy, and anthroposophic medicine therapy. Retention rates ranged from 53% to 91%, with studies offering monetary incentives showing the highest retention. The 0-10 numerical rating scale was the most common pain questionnaire (n = 10,r overall understanding of CIH as provided in clinical settings. Accordingly, we present numerous recommendations to improve publication reporting and guide future research. Our call to action is future, practice-based CIH research is needed, but should be more expansive and in association with a CIH scientific society with academic and healthcare members.Flower development is an important determinant of grain yield in crops. In wheat (Triticum spp.), natural variation for the size of spikelet and floral organs is particularly evident in Triticum turgidum ssp. polonicum (also termed Triticum polonicum), a tetraploid subspecies of wheat with long glumes, lemmas, and grains. Using map-based cloning, we identified VEGETATIVE TO REPRODUCTIVE TRANSITION 2 (VRT2), which encodes a MADS-box transcription factor belonging to the SHORT VEGETATIVE PHASE family, as the gene underlying the T. polonicum long-glume (P1) locus. The causal P1 mutation is a sequence rearrangement in intron-1 that results in ectopic expression of the T. polonicum VRT-A2 allele. Based on allelic variation studies, we propose that the intron-1 mutation in VRT-A2 is the unique T. polonicum subspecies-defining polymorphism, which was later introduced into hexaploid wheat via natural hybridizations. Near-isogenic lines differing for the P1 locus revealed a gradient effect of P1 across spikelets and within florets. Transgenic lines of hexaploid wheat carrying the T. polonicum VRT-A2 allele show that expression levels of VRT-A2 are highly correlated with spike, glume, grain, and floral organ length. These results highlight how changes in expression profiles, through variation in cis-regulation, can affect agronomic traits in a dosage-dependent manner in polyploid crops.MicroRNAs (miRNAs) are small non-coding, endogenous RNAs containing 20-24 nucleotides that regulate the expression of target genes involved in various plant processes. A total 1429 conserved miRNA belonging to 95 conserved miRNA families and 12 novel miRNAs were identified from B. monnieri using small RNA sequencing. The Bm-miRNA target transcripts related to the secondary metabolism were further selected for validation. The Bm-miRNA expression in shoot and root tissues were negatively correlated with their target transcripts. The Bm-miRNA cleavage sites were mapped within the coding or untranslated (UTR) region as depicted by the modified RLM-RACE. In the present study, we validate three miRNA targets, including Asparagine synthetase, Cycloartenol synthase, and Ferulate 5 hydroxylase and elucidate the regulatory role of Bm-miR172c-5p, which cleaves the F5H gene involved in the lignin biosynthesis. Overexpression of Bm-miR172c-5p precursor in B. monnieri suppress F5H gene, leading to reduced lignification and secondary xylem thickness under control and drought stress.
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  • ese findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but rather likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischemia. Further studies are needed to define whether these pathologies, if present in patients who survive COVID-19, might contribute to chronic neurological problems.Acute kidney injury (AKI) is a complex syndrome with an abrupt decrease of kidney function, which is associated with high morbidity and mortality. Sepsis is the common cause of AKI. Mounting evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of sepsis-induced AKI. In this study, we aimed to illustrate the function and mechanism of lncRNA SNHG14 in lipopolysaccharide (LPS)-induced AKI. We found that SNHG14 was highly expressed in the plasma of sepsis patients with AKI. SNHG14 inhibited cell proliferation and autophagy and promoted cell apoptosis and inflammatory cytokine production in LPS-stimulated HK-2 cells. Functionally, SNHG14 acted as a competing endogenous RNA (ceRNA) to negatively regulate miR-495-3p expression in HK-2 cells. Furthermore, we identified that HIPK1 is a direct target of miR-495-3p in HK-2 cells. We also revealed that the SNHG14/miR-495-3p/HIPK1 interaction network regulated HK-2 cell proliferation, apoptosis, autophagy, and inflammatory cytokine production upon LPS stimulation. In addition, we demonstrated that the SNHG14/miR-495-3p/HIPK1 interaction network regulated the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) via modulating NF-κB/p65 signaling in LPS-challenged HK-2 cells. In conclusion, our findings suggested a novel therapeutic axis of SNHG14/miR-495-3p/HIPK1 to treat sepsis-induced AKI.Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P  less then  5.30x10-7); including a novel signal near TOMM40/APOE. Joint analysis of TOMM40/APOE variants revealed the TOMM40 signal was attributed to APOE rs429358-T; APOE rs7412 was not associated with liver attenuation. Moreover, rs429358-T was associated with higher serum alanine aminotransferase, liver steatosis, cirrhosis, triglycerides and obesity; as well as, lower cholesterol and decreased risk of myocardial infarction (MI) and Alzheimer's disease (ad) in phenome-wide association analyses in the Michigan Genomics Initiative, United Kingdom Biobank and/or public datasets. These results implicate APOE in imaging-based identification of NAFLD. This association may or may not translate to non-alcoholic steatohepatitis (NASH); however, these results indicate a significant association with advanced liver disease and hepatic cirrhosis. These findings highlight allelic heterogeneity at the APOE locus and demonstrate an inverse link between NAFLD and ad at the exome level in the largest analysis to date.Over the last decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumors. It has become evident that pediatric high-grade gliomas (pHGGs) differ from adult HGGs with respect to multiple defining aspects including DNA copy number, gene expression profiles, tumor locations within the central nervous system, and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with glioma have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumor progression has considerably expanded, little is known concerning the dynamic tumor immune microenvironment (TIME) in pHGGs. https://www.selleckchem.com/products/ms-275.html In this review, we explore the genetic and epigenetic landscape of pHGGs and how this drives the creation of specific tumor sub-groups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the pHGG TIME and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumors.Genes are expressed to proteins for a wide variety of fundamental biological processes at the cellular and organismal levels. However, a protein rarely functions alone, but rather acts through interactions with other proteins to maintain normal cellular and organismal functions. Therefore, it is important to analyze the protein-protein interactions to determine functional mechanisms of proteins, which can also guide to develop therapeutic targets for treatment of diseases caused by altered protein-protein interactions leading to cellular/organismal dysfunctions. There is a large number of methodologies to study protein interactions in vitro, in vivo and in silico, which led to the development of many protein interaction databases, and thus, have enriched our knowledge about protein-protein interactions and functions. However, many of these interactions were identified in vitro, but need to be verified/validated in living cells. Furthermore, it is unclear whether these interactions are direct or mediated via other proteins.
    ese findings suggest that microglial activation, microglial nodules and neuronophagia, observed in the majority of brains, do not result from direct viral infection of brain parenchyma, but rather likely from systemic inflammation, perhaps with synergistic contribution from hypoxia/ischemia. Further studies are needed to define whether these pathologies, if present in patients who survive COVID-19, might contribute to chronic neurological problems.Acute kidney injury (AKI) is a complex syndrome with an abrupt decrease of kidney function, which is associated with high morbidity and mortality. Sepsis is the common cause of AKI. Mounting evidence has demonstrated that long non-coding RNAs (lncRNAs) play critical roles in the development and progression of sepsis-induced AKI. In this study, we aimed to illustrate the function and mechanism of lncRNA SNHG14 in lipopolysaccharide (LPS)-induced AKI. We found that SNHG14 was highly expressed in the plasma of sepsis patients with AKI. SNHG14 inhibited cell proliferation and autophagy and promoted cell apoptosis and inflammatory cytokine production in LPS-stimulated HK-2 cells. Functionally, SNHG14 acted as a competing endogenous RNA (ceRNA) to negatively regulate miR-495-3p expression in HK-2 cells. Furthermore, we identified that HIPK1 is a direct target of miR-495-3p in HK-2 cells. We also revealed that the SNHG14/miR-495-3p/HIPK1 interaction network regulated HK-2 cell proliferation, apoptosis, autophagy, and inflammatory cytokine production upon LPS stimulation. In addition, we demonstrated that the SNHG14/miR-495-3p/HIPK1 interaction network regulated the production of inflammatory cytokines (TNF-α, IL-6, and IL-1β) via modulating NF-κB/p65 signaling in LPS-challenged HK-2 cells. In conclusion, our findings suggested a novel therapeutic axis of SNHG14/miR-495-3p/HIPK1 to treat sepsis-induced AKI.Parkinson's disease is a common neurodegenerative disease in which gastrointestinal symptoms may appear prior to motor symptoms. The gut microbiota of patients with Parkinson's disease shows unique changes, which may be used as early biomarkers of disease. Alteration in gut microbiota composition may be related to the cause or effect of motor or non-motor symptoms, but the specific pathogenic mechanisms are unclear. The gut microbiota and its metabolites have been suggested to be involved in the pathogenesis of Parkinson's disease by regulating neuroinflammation, barrier function and neurotransmitter activity. There is bidirectional communication between the enteric nervous system and the central nervous system, and the microbiota-gut-brain axis may provide a pathway for the transmission of α-synuclein. We highlight recent discoveries and alterations of the gut microbiota in Parkinson's disease, and highlight current mechanistic insights on the microbiota-gut-brain axis in disease pathophysiology. We discuss the interactions between production and transmission of α-synuclein and gut inflammation and neuroinflammation. In addition, we also draw attention to diet modification, use of probiotics and prebiotics and fecal microbiota transplantation as potential therapeutic approaches that may lead to a new treatment paradigm for Parkinson's disease.Non-alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease and is highly correlated with metabolic disease. NAFLD results from environmental exposures acting on a susceptible polygenic background. This study performed the largest multiethnic investigation of exonic variation associated with NAFLD and correlated metabolic traits and diseases. An exome array meta-analysis was carried out among eight multiethnic population-based cohorts (n = 16 492) with computed tomography (CT) measured hepatic steatosis. A fixed effects meta-analysis identified five exome-wide significant loci (P  less then  5.30x10-7); including a novel signal near TOMM40/APOE. Joint analysis of TOMM40/APOE variants revealed the TOMM40 signal was attributed to APOE rs429358-T; APOE rs7412 was not associated with liver attenuation. Moreover, rs429358-T was associated with higher serum alanine aminotransferase, liver steatosis, cirrhosis, triglycerides and obesity; as well as, lower cholesterol and decreased risk of myocardial infarction (MI) and Alzheimer's disease (ad) in phenome-wide association analyses in the Michigan Genomics Initiative, United Kingdom Biobank and/or public datasets. These results implicate APOE in imaging-based identification of NAFLD. This association may or may not translate to non-alcoholic steatohepatitis (NASH); however, these results indicate a significant association with advanced liver disease and hepatic cirrhosis. These findings highlight allelic heterogeneity at the APOE locus and demonstrate an inverse link between NAFLD and ad at the exome level in the largest analysis to date.Over the last decade, remarkable progress has been made towards elucidating the origin and genomic landscape of childhood high-grade brain tumors. It has become evident that pediatric high-grade gliomas (pHGGs) differ from adult HGGs with respect to multiple defining aspects including DNA copy number, gene expression profiles, tumor locations within the central nervous system, and genetic alterations such as somatic histone mutations. Despite these advances, clinical trials for children with glioma have historically been based on ineffective adult regimens that fail to take into consideration the fundamental biological differences between the two. Additionally, although our knowledge of the intrinsic cellular mechanisms driving tumor progression has considerably expanded, little is known concerning the dynamic tumor immune microenvironment (TIME) in pHGGs. https://www.selleckchem.com/products/ms-275.html In this review, we explore the genetic and epigenetic landscape of pHGGs and how this drives the creation of specific tumor sub-groups with meaningful survival outcomes. Further, we provide a comprehensive analysis of the pHGG TIME and discuss emerging therapeutic efforts aimed at exploiting the immune functions of these tumors.Genes are expressed to proteins for a wide variety of fundamental biological processes at the cellular and organismal levels. However, a protein rarely functions alone, but rather acts through interactions with other proteins to maintain normal cellular and organismal functions. Therefore, it is important to analyze the protein-protein interactions to determine functional mechanisms of proteins, which can also guide to develop therapeutic targets for treatment of diseases caused by altered protein-protein interactions leading to cellular/organismal dysfunctions. There is a large number of methodologies to study protein interactions in vitro, in vivo and in silico, which led to the development of many protein interaction databases, and thus, have enriched our knowledge about protein-protein interactions and functions. However, many of these interactions were identified in vitro, but need to be verified/validated in living cells. Furthermore, it is unclear whether these interactions are direct or mediated via other proteins.
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  • Eight medications met our inclusion criteria, which fell into three treatment groups drugs used in substance use disorders; drugs that affect the cholinergic system; and drugs used for the management of cardiovascular-related conditions.

    This study was not designed to confirm a causal association nor inform current clinical practice. Instead, this research and the methods employed intended to be hypothesis generating and help uncover potential treatment pathways that could warrant further investigation.

    Several potential drug targets that could aid further research and discovery into novel treatments for depressive and bipolar disorders were identified.
    Several potential drug targets that could aid further research and discovery into novel treatments for depressive and bipolar disorders were identified.
    Memory control (**) ability is critical for people's mental and physical health. Previous research had conceptually demonstrated that ** ability has close relationship with reappraisal. However, experimental evidence supporting the relationship was limited. Thus, in the present study, we investigated how ** and reappraisal are linked, both in behavior and in the brain.

    The habitual use of reappraisal was assessed by Emotion Regulation Questionnaire, and memory control ability was measured through directed forgetting task. Resting-state functional magnetic resonance imaging was used to test the seed-based functional connectivity in 181 healthy subjects.

    Behavioral results revealed that more frequent reappraisal was associated with an enhanced ability to control negative memories. Resting-state seed-based functional connectivity showed that habitual use of reappraisal was positively related to the strength of functional connectivity between the right ventrolateral prefrontal cortex (VLPFC) and right insula. Most importantly, this functional connectivity mediated the effect of habitual use of reappraisal on control over negative memories.

    Present results mainly showed the habitual use of reappraisal was related with ** ability in negative items. Future study could further explore the relationship between ** ability of different categories of negative emotional memories and other kinds of ER strategies.

    Our results support the notion that reappraisal provides opportunities for individuals to practice and enhance inhibitory control-a relationship underpinned by connectivity between the right VLPFC and right insula.
    Our results support the notion that reappraisal provides opportunities for individuals to practice and enhance inhibitory control-a relationship underpinned by connectivity between the right VLPFC and right insula.
    Intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) has shown promise in open-label trials of depression.

    In this randomized, double-blind, sham controlled trial we evaluate iTBS over the DMPFC for anhedonia, avolition, and blunted affect in patients with schizophrenia or depression. Active iTBS was delivered over the DMPFC with 1200 pulses per session, twice daily over ten weekdays at target intensity with an angled figure-of eight coil. Sham condition comprised the magnetically shielded side of the coil and simultaneous transcutaneous electrical nerve stimulation. https://www.selleckchem.com/products/Cyclopamine.html Primary outcome was change on the Clinical Assessment Interview for Negative Symptoms (CAINS).

    Twenty-eight patients were randomized to active iTBS and 28 to sham. Mean (standard deviation) change in CAINS score from baseline to the day after last treatment was -5.3 (8.1) in active iTBS and -2.1 (7.1) in sham. A linear model showed no significant effect of treatment, accounting for baseline scores p=.088. Sub analyses per diagnostic group showed a significant effect in patients with depression, p=.038, but not in the schizophrenia group, p=.850. However, overall depressive symptoms did not change significantly in patients with depression. There were three serious adverse events, all in the sham group.

    Possibly too short treatment course and few patients with schizophrenia.

    In this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression.
    In this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression.
    Older adults have high suicide rates. We investigated potential time trends in the prevalence of passive and active suicidal ideation in 85-year-olds. Further, we examined factors associated with such ideation in this age group.

    Population-based samples of 85-year-olds were interviewed in 1986 (N=347), 2008 (N=426) and 2015 (N=320). Past-month passive/active suicidal ideation was evaluated with the Paykel questions.

    Reporting any type of passive or active suicidal ideation was less common in 2008 (7.3%, p<0.001) and 2015 (7.2%, p<0.001) compared to 1986 (16.4%). The change was driven by decreases in passive ideation. Passive/active suicidal ideation was associated with higher MADRS score (OR 1.2, 95% CI 1.1-1.2, p<0.001), institution residence (OR 3.9, 95% CI 1.7-8.9, p=0.001) and feelings of loneliness (OR 2.7, 95% CI 1.4-5.2, p=0.003). When stratified by sex, it was associated with institution residence (OR 3.7, 95% CI 1.4-9.9, p=0.008) and feelings of loneliness (OR 3.0, 95% CI 1.4-6.3, p=0.005) in women. In men, we observed a tenfold higher risk in those without partners (OR 9.8, 95% CI 2.9-33.5, p<0.001).

    While differential three-year mortality was not observed in 1986, mortality was higher among non-participants in 2008 and 2015. This might have inflated cohort differences in passive/active suicidal ideation.

    An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners.
    An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners.
    Eight medications met our inclusion criteria, which fell into three treatment groups drugs used in substance use disorders; drugs that affect the cholinergic system; and drugs used for the management of cardiovascular-related conditions. This study was not designed to confirm a causal association nor inform current clinical practice. Instead, this research and the methods employed intended to be hypothesis generating and help uncover potential treatment pathways that could warrant further investigation. Several potential drug targets that could aid further research and discovery into novel treatments for depressive and bipolar disorders were identified. Several potential drug targets that could aid further research and discovery into novel treatments for depressive and bipolar disorders were identified. Memory control (MC) ability is critical for people's mental and physical health. Previous research had conceptually demonstrated that MC ability has close relationship with reappraisal. However, experimental evidence supporting the relationship was limited. Thus, in the present study, we investigated how MC and reappraisal are linked, both in behavior and in the brain. The habitual use of reappraisal was assessed by Emotion Regulation Questionnaire, and memory control ability was measured through directed forgetting task. Resting-state functional magnetic resonance imaging was used to test the seed-based functional connectivity in 181 healthy subjects. Behavioral results revealed that more frequent reappraisal was associated with an enhanced ability to control negative memories. Resting-state seed-based functional connectivity showed that habitual use of reappraisal was positively related to the strength of functional connectivity between the right ventrolateral prefrontal cortex (VLPFC) and right insula. Most importantly, this functional connectivity mediated the effect of habitual use of reappraisal on control over negative memories. Present results mainly showed the habitual use of reappraisal was related with MC ability in negative items. Future study could further explore the relationship between MC ability of different categories of negative emotional memories and other kinds of ER strategies. Our results support the notion that reappraisal provides opportunities for individuals to practice and enhance inhibitory control-a relationship underpinned by connectivity between the right VLPFC and right insula. Our results support the notion that reappraisal provides opportunities for individuals to practice and enhance inhibitory control-a relationship underpinned by connectivity between the right VLPFC and right insula. Intermittent theta burst stimulation (iTBS) over the dorsomedial prefrontal cortex (DMPFC) has shown promise in open-label trials of depression. In this randomized, double-blind, sham controlled trial we evaluate iTBS over the DMPFC for anhedonia, avolition, and blunted affect in patients with schizophrenia or depression. Active iTBS was delivered over the DMPFC with 1200 pulses per session, twice daily over ten weekdays at target intensity with an angled figure-of eight coil. Sham condition comprised the magnetically shielded side of the coil and simultaneous transcutaneous electrical nerve stimulation. https://www.selleckchem.com/products/Cyclopamine.html Primary outcome was change on the Clinical Assessment Interview for Negative Symptoms (CAINS). Twenty-eight patients were randomized to active iTBS and 28 to sham. Mean (standard deviation) change in CAINS score from baseline to the day after last treatment was -5.3 (8.1) in active iTBS and -2.1 (7.1) in sham. A linear model showed no significant effect of treatment, accounting for baseline scores p=.088. Sub analyses per diagnostic group showed a significant effect in patients with depression, p=.038, but not in the schizophrenia group, p=.850. However, overall depressive symptoms did not change significantly in patients with depression. There were three serious adverse events, all in the sham group. Possibly too short treatment course and few patients with schizophrenia. In this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression. In this first transdiagnostic randomized controlled trial of iTBS over DMPFC for anhedonia, avolition, and blunted affect it can be concluded that it was generally tolerable and safe but only more effective than sham in the subgroup of patients with depression. Older adults have high suicide rates. We investigated potential time trends in the prevalence of passive and active suicidal ideation in 85-year-olds. Further, we examined factors associated with such ideation in this age group. Population-based samples of 85-year-olds were interviewed in 1986 (N=347), 2008 (N=426) and 2015 (N=320). Past-month passive/active suicidal ideation was evaluated with the Paykel questions. Reporting any type of passive or active suicidal ideation was less common in 2008 (7.3%, p<0.001) and 2015 (7.2%, p<0.001) compared to 1986 (16.4%). The change was driven by decreases in passive ideation. Passive/active suicidal ideation was associated with higher MADRS score (OR 1.2, 95% CI 1.1-1.2, p<0.001), institution residence (OR 3.9, 95% CI 1.7-8.9, p=0.001) and feelings of loneliness (OR 2.7, 95% CI 1.4-5.2, p=0.003). When stratified by sex, it was associated with institution residence (OR 3.7, 95% CI 1.4-9.9, p=0.008) and feelings of loneliness (OR 3.0, 95% CI 1.4-6.3, p=0.005) in women. In men, we observed a tenfold higher risk in those without partners (OR 9.8, 95% CI 2.9-33.5, p<0.001). While differential three-year mortality was not observed in 1986, mortality was higher among non-participants in 2008 and 2015. This might have inflated cohort differences in passive/active suicidal ideation. An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners. An initial decrease in the prevalence of passive/active suicidal ideation in 85-year-olds was observed but this positive trend did not persist. Results underline that preventive strategies targeting loneliness and focusing on institutional settings are needed, as are interventions for men without partners.
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  • This study determined electrocochleography (ECochG) parameter settings to obtain cochlear microphonics (CM) with less invasive flexible extra-tympanic membrane electrodes. In 24 adult normal-hearing subjects, CMs were elicited by presenting click stimuli at 100 dBnHL, tone bursts (2 kHz) and broadband (BB) CE-chirps® LS (Interacoustics, Middelfart, Denmark), both at 80 dBnHL. Different high-pass filters (HPFs) (3.3 Hz and 100 Hz, respectively) were used to investigate response quality of the CM. CMs were successfully obtained in 92-100% with click-, 75-83% with 2 kHz tone burst- and 58-63% with CE-chirp®-LS stimuli. Click stimuli elicited significantly larger CM amplitudes compared to 2 kHz tone bursts and BB CE-chirp® LS (Interacoustics, Middelfart, Denmark). No significant differences were found between the two different high-pass filter (HPF) settings. The present study shows that it is possible to obtain clear CMs with the flexible extra-tympanic membrane electrodes using click stimuli. In contrast to 2 kHz tone bursts and CE-chirp® (Interacoustics, Middelfart, Denmark) LS, clicks show a significantly higher success rate and are the preferred stimuli to confirm the presence or absence of CMs.Mesenchymal stem cells (****) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. **** possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, **** produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between **** and immune cells in tissue repair and regeneration.The coronavirus disease 2019 (COVID-19) pandemic has a significant impact on both physical and mental health. The aim of this cross-sectional study was to (1) evaluate depression, anxiety, and stress levels among students from Polish universities during the first weeks of the COVID-19 pandemic and (2) assess the risk factors of the higher intensity of emotional distress. We conducted an online survey using the Depression, Anxiety, and Stress Scale-21 (DASS-21) to assess well-being. The study included 2172 respondents (73% female, 27% male) with a mean age of 22.1 ± 2.2. Moderate to extremely severe scores of depression, anxiety, and stress were reported by 43.4%, 27.3%, and 41.0% of the respondents, respectively. Higher scores of DASS-21 were related to female sex (odds ratio (OR) = 3.01), studying sciences (OR = 2.04), co-residence with the roommates (OR = 1.25), suffering from a mental disorder (OR = 5.88), loneliness (OR = 293.30), the usage of psychiatric support before pandemic (OR = 8.06), poor economic situation (OR = 13.49), and the lower scores were found for being currently employed (OR = 0.4). This study highlights an urgent need for (1) crisis-oriented psychological and psychiatric support for students during the outbreak of the COVID-19 pandemic and (2) preparing appropriate psychological interventions to improve the mental health of students for a possible similar situation in the future.
    Body-mass index (BMI) is a popular method implemented to define weight status. However, describing obesity by BMI may result in inaccurate assessment of adiposity. The Body Adiposity Index (BAI) is intended to be a directly validated method of estimating body fat percentage. We set out to compare body weight status assessment by BMI and BAI in a cohort of elderly patients with stable coronary artery disease (***).

    A total of 169 patients with stable *** were enrolled in an out-patient cardiology clinic. The National Research Council (US) Committee on Diet and Health classification was used for individuals older than 65 years as underweight BMI < 24 kg/m
    , normal weight BMI 24-29 kg/m
    , overweight BMI 29-35 kg/m
    , and obesity BMI > 35 kg/m
    . In case of BAI, we used sex- and age-specific classification of weight status. In addition, body fat was estimated by bioelectrical impedance analysis (BImpA).

    Only 72 out of 169 patients (42.6%) had concordant classification of weight status by both BMI anractice as the boundary between health and disease in malnutrition is crucial to accurately define criteria for intervention. Perhaps BMI cut-offs for classifying weight status in the elderly should be revisited.
    There is substantial rate of misclassification of weight status between BMI and BAI. These findings have significant implications for clinical practice as the boundary between health and disease in malnutrition is crucial to accurately define criteria for intervention. Perhaps BMI cut-offs for classifying weight status in the elderly should be revisited.Emotion recognition based on electroencephalograms has become an active research area. Yet, identifying emotions using only brainwaves is still very challenging, especially the subject-independent task. Numerous studies have tried to propose methods to recognize emotions, including machine learning techniques like convolutional neural network (CNN). Since CNN has shown its potential in generalization to unseen subjects, manipulating CNN hyperparameters like the window size and electrode order might be beneficial. To our knowledge, this is the first work that extensively observed the parameter selection effect on the CNN. The temporal information in distinct window sizes was found to significantly affect the recognition performance, and CNN was found to be more responsive to changing window sizes than the support vector machine. https://www.selleckchem.com/products/E7080.html Classifying the arousal achieved the best performance with a window size of ten seconds, obtaining 56.85% accuracy and a Matthews correlation coefficient (MCC) of 0.1369. Valence recognition had the best performance with a window length of eight seconds at 73.34% accuracy and an ****value of 0.4669. Spatial information from varying the electrode orders had a small effect on the classification. Overall, valence results had a **** more superior performance than arousal results, which were, perhaps, influenced by features related to brain activity asymmetry between the left and right hemispheres.
    This study determined electrocochleography (ECochG) parameter settings to obtain cochlear microphonics (CM) with less invasive flexible extra-tympanic membrane electrodes. In 24 adult normal-hearing subjects, CMs were elicited by presenting click stimuli at 100 dBnHL, tone bursts (2 kHz) and broadband (BB) CE-chirps® LS (Interacoustics, Middelfart, Denmark), both at 80 dBnHL. Different high-pass filters (HPFs) (3.3 Hz and 100 Hz, respectively) were used to investigate response quality of the CM. CMs were successfully obtained in 92-100% with click-, 75-83% with 2 kHz tone burst- and 58-63% with CE-chirp®-LS stimuli. Click stimuli elicited significantly larger CM amplitudes compared to 2 kHz tone bursts and BB CE-chirp® LS (Interacoustics, Middelfart, Denmark). No significant differences were found between the two different high-pass filter (HPF) settings. The present study shows that it is possible to obtain clear CMs with the flexible extra-tympanic membrane electrodes using click stimuli. In contrast to 2 kHz tone bursts and CE-chirp® (Interacoustics, Middelfart, Denmark) LS, clicks show a significantly higher success rate and are the preferred stimuli to confirm the presence or absence of CMs.Mesenchymal stem cells (MSCs) are self-renewable, rapidly proliferating, multipotent stem cells which reside in almost all post-natal tissues. MSCs possess potent immunoregulatory properties and, in juxtacrine and paracrine manner, modulate phenotype and function of all immune cells that participate in tissue repair and regeneration. Additionally, MSCs produce various pro-angiogenic factors and promote neo-vascularization in healing tissues, contributing to their enhanced repair and regeneration. In this review article, we summarized current knowledge about molecular mechanisms that regulate the crosstalk between MSCs and immune cells in tissue repair and regeneration.The coronavirus disease 2019 (COVID-19) pandemic has a significant impact on both physical and mental health. The aim of this cross-sectional study was to (1) evaluate depression, anxiety, and stress levels among students from Polish universities during the first weeks of the COVID-19 pandemic and (2) assess the risk factors of the higher intensity of emotional distress. We conducted an online survey using the Depression, Anxiety, and Stress Scale-21 (DASS-21) to assess well-being. The study included 2172 respondents (73% female, 27% male) with a mean age of 22.1 ± 2.2. Moderate to extremely severe scores of depression, anxiety, and stress were reported by 43.4%, 27.3%, and 41.0% of the respondents, respectively. Higher scores of DASS-21 were related to female sex (odds ratio (OR) = 3.01), studying sciences (OR = 2.04), co-residence with the roommates (OR = 1.25), suffering from a mental disorder (OR = 5.88), loneliness (OR = 293.30), the usage of psychiatric support before pandemic (OR = 8.06), poor economic situation (OR = 13.49), and the lower scores were found for being currently employed (OR = 0.4). This study highlights an urgent need for (1) crisis-oriented psychological and psychiatric support for students during the outbreak of the COVID-19 pandemic and (2) preparing appropriate psychological interventions to improve the mental health of students for a possible similar situation in the future. Body-mass index (BMI) is a popular method implemented to define weight status. However, describing obesity by BMI may result in inaccurate assessment of adiposity. The Body Adiposity Index (BAI) is intended to be a directly validated method of estimating body fat percentage. We set out to compare body weight status assessment by BMI and BAI in a cohort of elderly patients with stable coronary artery disease (CAD). A total of 169 patients with stable CAD were enrolled in an out-patient cardiology clinic. The National Research Council (US) Committee on Diet and Health classification was used for individuals older than 65 years as underweight BMI < 24 kg/m , normal weight BMI 24-29 kg/m , overweight BMI 29-35 kg/m , and obesity BMI > 35 kg/m . In case of BAI, we used sex- and age-specific classification of weight status. In addition, body fat was estimated by bioelectrical impedance analysis (BImpA). Only 72 out of 169 patients (42.6%) had concordant classification of weight status by both BMI anractice as the boundary between health and disease in malnutrition is crucial to accurately define criteria for intervention. Perhaps BMI cut-offs for classifying weight status in the elderly should be revisited. There is substantial rate of misclassification of weight status between BMI and BAI. These findings have significant implications for clinical practice as the boundary between health and disease in malnutrition is crucial to accurately define criteria for intervention. Perhaps BMI cut-offs for classifying weight status in the elderly should be revisited.Emotion recognition based on electroencephalograms has become an active research area. Yet, identifying emotions using only brainwaves is still very challenging, especially the subject-independent task. Numerous studies have tried to propose methods to recognize emotions, including machine learning techniques like convolutional neural network (CNN). Since CNN has shown its potential in generalization to unseen subjects, manipulating CNN hyperparameters like the window size and electrode order might be beneficial. To our knowledge, this is the first work that extensively observed the parameter selection effect on the CNN. The temporal information in distinct window sizes was found to significantly affect the recognition performance, and CNN was found to be more responsive to changing window sizes than the support vector machine. https://www.selleckchem.com/products/E7080.html Classifying the arousal achieved the best performance with a window size of ten seconds, obtaining 56.85% accuracy and a Matthews correlation coefficient (MCC) of 0.1369. Valence recognition had the best performance with a window length of eight seconds at 73.34% accuracy and an MCC value of 0.4669. Spatial information from varying the electrode orders had a small effect on the classification. Overall, valence results had a much more superior performance than arousal results, which were, perhaps, influenced by features related to brain activity asymmetry between the left and right hemispheres.
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  • miRNAs hold promise for uncovering new layers in the pathogenesis of PPDs, in order to improve diagnosis and also to develop potential therapeutic options. In the current article, we provide an overview regarding current knowledge of miRNAs in terms of complex pathogenesis of PPDs, and, also, their potential role as biomarkers, predictive factors and therapeutic targets.
    To reassess the diagnostic approach to a patient with a monoarticular disease in light of the up-to-date medical literature and to examine the practical utility of traditional and newer imaging tools in the setting of monoarthritis.

    The monoarticular disease can represent a medical emergency on the one hand and be a diagnostic conundrum on the other. The management rules of patients with monoarthritis have been established long ago, but various pitfalls still lead physicians off the right diagnosis at times. Septic, pseudoseptic arthritis and hemarthrosis are the most common diagnoses made in patients with an acute presentation, and a decision not to perform a diagnostic arthrocentesis is the most prevalent cause of misdiagnosis in this setting. Many rheumatic and infectious diseases can present with more indolent monoarthritis; careful history and physical examination frequently provide clues to the straightforward diagnosis in some cases, but the extensive investigation is needed in others. Imaging methods become indispensable in individuals with the non-inflammatory monoarticular disease, with magnetic resonance imaging being the gold standard for diagnosing pigmented villonodular synovitis, lipoma arborescence, avascular necrosis, or neuropathic arthropathy.

    A great variety of medical disorders can present as a monoarticular disease. The disease presentation dictates different diagnostic behavior, while knowing the available imaging methods' diagnostic potential should further shorten the diagnostic process.
    A great variety of medical disorders can present as a monoarticular disease. The disease presentation dictates different diagnostic behavior, while knowing the available imaging methods' diagnostic potential should further shorten the diagnostic process.Since the start of the "modern era", characterized by the increase in urbanization, a progressive attention to hygiene and autoimmune conditions has considerably grown. https://www.selleckchem.com/products/LBH-589.html Although these diseases are often multifactorial, it was demonstrated that environment factors such as pollution, diet and lifestyles may play a crucial role together with genetic signature. Our research, based on the newest and most significant literature of this topic, highlights that the progressive depletion of microbes and parasites due to increased socioeconomic improvement, may lead to a derangement of immunoregulatory mechanisms. Moreover, special attention was given to the complex interplay between microbial agents, as gut microbiome, diet and vitamin D supplementation with the aim of identifying promising future therapeutic options. In conclusion, autoimmunity cannot be limited to hygiene-hypothesis, but from the point of view of precision medicine, this theory represents a fundamental element together with the study of genomics, the microbiome and proteomics, in order to understand the complex functioning of the immune system.
    Scleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to review studies reporting muscle biopsies from SSc patients with myositis and to identify unique histopathological features of SM.

    A scoping review was conducted and included all studies reporting histopathological findings in SSc patients with myositis searching the following databases PubMed, MEDLINE, EMBASE, CINAHL and EBM-Reviews. Clinical, serological, and histopathological data were extracted using a standardized protocol.

    Out of 371 citations, 77 studies that included 559 muscle biopsies were extracted. Fifty-seven percent (n=227/400) had inflammatory infiltrates, predominantly T cells, which were endomysial (49%), perimysial (42%) and perivascular (41%). Few studies (18%, n=8/44) evaluated the presence of B-cells. Myofiber atrophy was present in 48% (n=104/218d with anti-Ku (85%) and anti-U1RNP (73%), while anti-Ku was also associated with neurogenic features and rimmed vacuoles in 57% and 25% of cases, respectively.

    Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets.
    Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets.
    Coronary sinus (CS) ostial atresia/abnormalities prevent access to the CS from the right atrium (RA) for left ventricular (LV) lead implantation. Some patients with CS ostial abnormalities also have a small persistent left superior vena cava (sPLSVC).

    The purpose of this study was to describe CS ostial abnormalities and sPLSVC as an opportunity for LV lead implantation and unrecognized source of stroke.

    Twenty patients with CS ostial abnormalities and sPLSVC were identified. Clinical information, imaging methods, LV lead implantation techniques, and complications were summarized.

    Forty percent had at least 1 previously unsuccessful LV lead placement. In 70%, sPLSVC was identified by catheter manipulation and contrast injection in the left brachiocephalic vein, and in 30% by levophase CS venography. In 30%, sPLSVC was associated with drainage from the CS into the left atrium (LA). When associated with CS ostial abnormalities, the sPLSVC diameter averaged 5.6 ± 3 mm. sPLSVC was used for successful LV lead implantation in 90% of cases.
    miRNAs hold promise for uncovering new layers in the pathogenesis of PPDs, in order to improve diagnosis and also to develop potential therapeutic options. In the current article, we provide an overview regarding current knowledge of miRNAs in terms of complex pathogenesis of PPDs, and, also, their potential role as biomarkers, predictive factors and therapeutic targets. To reassess the diagnostic approach to a patient with a monoarticular disease in light of the up-to-date medical literature and to examine the practical utility of traditional and newer imaging tools in the setting of monoarthritis. The monoarticular disease can represent a medical emergency on the one hand and be a diagnostic conundrum on the other. The management rules of patients with monoarthritis have been established long ago, but various pitfalls still lead physicians off the right diagnosis at times. Septic, pseudoseptic arthritis and hemarthrosis are the most common diagnoses made in patients with an acute presentation, and a decision not to perform a diagnostic arthrocentesis is the most prevalent cause of misdiagnosis in this setting. Many rheumatic and infectious diseases can present with more indolent monoarthritis; careful history and physical examination frequently provide clues to the straightforward diagnosis in some cases, but the extensive investigation is needed in others. Imaging methods become indispensable in individuals with the non-inflammatory monoarticular disease, with magnetic resonance imaging being the gold standard for diagnosing pigmented villonodular synovitis, lipoma arborescence, avascular necrosis, or neuropathic arthropathy. A great variety of medical disorders can present as a monoarticular disease. The disease presentation dictates different diagnostic behavior, while knowing the available imaging methods' diagnostic potential should further shorten the diagnostic process. A great variety of medical disorders can present as a monoarticular disease. The disease presentation dictates different diagnostic behavior, while knowing the available imaging methods' diagnostic potential should further shorten the diagnostic process.Since the start of the "modern era", characterized by the increase in urbanization, a progressive attention to hygiene and autoimmune conditions has considerably grown. https://www.selleckchem.com/products/LBH-589.html Although these diseases are often multifactorial, it was demonstrated that environment factors such as pollution, diet and lifestyles may play a crucial role together with genetic signature. Our research, based on the newest and most significant literature of this topic, highlights that the progressive depletion of microbes and parasites due to increased socioeconomic improvement, may lead to a derangement of immunoregulatory mechanisms. Moreover, special attention was given to the complex interplay between microbial agents, as gut microbiome, diet and vitamin D supplementation with the aim of identifying promising future therapeutic options. In conclusion, autoimmunity cannot be limited to hygiene-hypothesis, but from the point of view of precision medicine, this theory represents a fundamental element together with the study of genomics, the microbiome and proteomics, in order to understand the complex functioning of the immune system. Scleromyositis (SM) is an emerging subset of myositis associated with features of systemic sclerosis (SSc) but it is currently not recognized as a distinct histopathological subset by the European NeuroMuscular Center (ENMC). Our aim was to review studies reporting muscle biopsies from SSc patients with myositis and to identify unique histopathological features of SM. A scoping review was conducted and included all studies reporting histopathological findings in SSc patients with myositis searching the following databases PubMed, MEDLINE, EMBASE, CINAHL and EBM-Reviews. Clinical, serological, and histopathological data were extracted using a standardized protocol. Out of 371 citations, 77 studies that included 559 muscle biopsies were extracted. Fifty-seven percent (n=227/400) had inflammatory infiltrates, predominantly T cells, which were endomysial (49%), perimysial (42%) and perivascular (41%). Few studies (18%, n=8/44) evaluated the presence of B-cells. Myofiber atrophy was present in 48% (n=104/218d with anti-Ku (85%) and anti-U1RNP (73%), while anti-Ku was also associated with neurogenic features and rimmed vacuoles in 57% and 25% of cases, respectively. Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets. Our review suggests that SM is characterized by heterogeneous pathological features using definitions included in current histopathological criteria. Whether a distinct histopathological signature exists in SM remains to be determined. SSc-specific and SSc-associated autoantibodies may help define more homogeneous histopathological subsets. Coronary sinus (CS) ostial atresia/abnormalities prevent access to the CS from the right atrium (RA) for left ventricular (LV) lead implantation. Some patients with CS ostial abnormalities also have a small persistent left superior vena cava (sPLSVC). The purpose of this study was to describe CS ostial abnormalities and sPLSVC as an opportunity for LV lead implantation and unrecognized source of stroke. Twenty patients with CS ostial abnormalities and sPLSVC were identified. Clinical information, imaging methods, LV lead implantation techniques, and complications were summarized. Forty percent had at least 1 previously unsuccessful LV lead placement. In 70%, sPLSVC was identified by catheter manipulation and contrast injection in the left brachiocephalic vein, and in 30% by levophase CS venography. In 30%, sPLSVC was associated with drainage from the CS into the left atrium (LA). When associated with CS ostial abnormalities, the sPLSVC diameter averaged 5.6 ± 3 mm. sPLSVC was used for successful LV lead implantation in 90% of cases.
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  • To develop consensus recommendations about good clinical practice rules for caring end-of-life patients.

    A steering committee of 12 Spanish and Portuguese experts proposed 37 recommendations. A two rounds Delphi method was performed, with participation of 105 panelists including internists, other clinicians, nurses, patients, lawyers, bioethicians, health managers, politicians and journalists. We sent a questionnaire with 5 Likert-type answers for each recommendation. Strong consensus was defined when >95% answers were completely agree or >90% were agree or completely agree; and weak consensus when >90% answers were completely agree or >80% were agree or completely agree.

    The panel addressed 7 specific areas for 37 recommendations spanning identification of patients; knowledge of the disease, values and preferences of the patient; information; patient's needs; support and care; palliative sedation, and after death care.

    The panel formulated and provided the rationale for recommendations on good clinical practice rules for caring end-of-life patients.
    The panel formulated and provided the rationale for recommendations on good clinical practice rules for caring end-of-life patients.
    To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC).

    A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals.

    A total of 106 patients (61 [57.5%] women, mean age 52.3 ±â€¯14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ±â€¯14.2 years vs 54.5 ±â€¯13.9 years, p < .001). Familial PCCs were more frequently associated with MEN2A (n = 8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3 cm (3-6 cm); 27.7% of the patients had tumors ≥6 cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4 cm [2.4-5.0 cm] vs 5.6 cm [4.0-7.0 cm], p < .001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. https://www.selleckchem.com/products/epz-6438.html Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%).

    PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.
    PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low.
    To describe the frequency, clinical characteristics and outcomes of patients with acute heart failure (AHF) transferred directly from emergency departments to home hospitalisation (HH) and to compare them with those hospitalised in internal medicine (IM) or short-stay units (SSU).

    We included patients with AHF transferred to HH by hospitals that considered this option during the Epidemiology of Acute Heart Failure in Spanish Emergency Departments (EAHFE) 4-5-6 Registries and compared them with patients admitted to IM or SSU in these centres. We compared the adjusted all-cause mortality at 1 year and adverse events 30 days after discharge.

    The study included 1473 patients (HH/IM/SSU68/979/384). The HH rate was 4.7% (95% CI 3.8-6.0%). The patients in HH had few differences compared with those hospitalised in IM and SSUs. The HH mortality was 1.5%, and the HH median stay was 7.5 days (IQR, 4.5-12), similar to that of IM (median stay, 8 days; IQR, 5-13; p = .106) and longer than that of SSU (median stay, 4 days; IQR, 3-7; p < .001). The all-cause mortality at 1 year for HH did not differ from that of IM (HR, 0.91; 95% CI 0.73-1.14) or SSU (HR, 0.77; 95% CI 0.46-1.27); however, the emergency department readmission rate during the 30 days postdischarge was lower than that of IM (HR, 0.50; 95% CI 0.25-0.97) and SSU (HR, 0.37; 95% CI 0.19-0.74). There were no differences in the need for new hospitalisations or in the 30-day mortality rate.

    Direct transfer from the emergency department to HH is infrequent despite being a safe option for a certain patient profile with AHF.
    Direct transfer from the emergency department to HH is infrequent despite being a safe option for a certain patient profile with AHF.Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity; and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis (SEA, for its initials in Spanish), the Spanish Diabetes Society (SED, for its initials in Spanish), and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).
    To develop consensus recommendations about good clinical practice rules for caring end-of-life patients. A steering committee of 12 Spanish and Portuguese experts proposed 37 recommendations. A two rounds Delphi method was performed, with participation of 105 panelists including internists, other clinicians, nurses, patients, lawyers, bioethicians, health managers, politicians and journalists. We sent a questionnaire with 5 Likert-type answers for each recommendation. Strong consensus was defined when >95% answers were completely agree or >90% were agree or completely agree; and weak consensus when >90% answers were completely agree or >80% were agree or completely agree. The panel addressed 7 specific areas for 37 recommendations spanning identification of patients; knowledge of the disease, values and preferences of the patient; information; patient's needs; support and care; palliative sedation, and after death care. The panel formulated and provided the rationale for recommendations on good clinical practice rules for caring end-of-life patients. The panel formulated and provided the rationale for recommendations on good clinical practice rules for caring end-of-life patients. To analyze the clinical and analytical features, diagnostic tests, therapies, and outcomes of pheochromocytoma (PCC). A multicenter retrospective study in surgically treated patients with PCC followed in 3 Spanish tertiary referral hospitals. A total of 106 patients (61 [57.5%] women, mean age 52.3 ±â€¯14.8 years) were evaluated. At diagnosis, PCC was symptomatic in 62% and sporadic in 83%. Patients with familial PCC were significantly younger than those with sporadic disease (40.8 ±â€¯14.2 years vs 54.5 ±â€¯13.9 years, p < .001). Familial PCCs were more frequently associated with MEN2A (n = 8). Levels of 24-h urinary fractionated metanephrines were positively related to tumor size. The maximum tumor diameter was 4.3 cm (3-6 cm); 27.7% of the patients had tumors ≥6 cm. Incidental PCCs were significantly smaller than symptomatic PCCs (3.4 cm [2.4-5.0 cm] vs 5.6 cm [4.0-7.0 cm], p < .001). Scintigraphy by ¹²³I-metaiodobenzylguanidine showed a high sensitivity (81.9%). Preoperative alpha blockade with phenoxybenzamine was used in 93.6% and doxazosin in the rest. https://www.selleckchem.com/products/epz-6438.html Laparoscopic surgery was used in 2/3 of the patients, with a low conversion (1.9%) to open surgery. Perioperative complications appeared in approximately 20% of patients, mainly hypertensive crisis (9.4%). Recurrent disease appeared in 10%, and malignant PCC was uncommon (6.3%). PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low. PCCs surgically treated in Spain are usually large, symptomatic, and sporadic tumors diagnosed around the sixth decade of life. Hereditary PCC is usually associated with MEN2A. The main type of surgical technique used is laparoscopic surgery, and the prevalence of metastatic PCC is low. To describe the frequency, clinical characteristics and outcomes of patients with acute heart failure (AHF) transferred directly from emergency departments to home hospitalisation (HH) and to compare them with those hospitalised in internal medicine (IM) or short-stay units (SSU). We included patients with AHF transferred to HH by hospitals that considered this option during the Epidemiology of Acute Heart Failure in Spanish Emergency Departments (EAHFE) 4-5-6 Registries and compared them with patients admitted to IM or SSU in these centres. We compared the adjusted all-cause mortality at 1 year and adverse events 30 days after discharge. The study included 1473 patients (HH/IM/SSU68/979/384). The HH rate was 4.7% (95% CI 3.8-6.0%). The patients in HH had few differences compared with those hospitalised in IM and SSUs. The HH mortality was 1.5%, and the HH median stay was 7.5 days (IQR, 4.5-12), similar to that of IM (median stay, 8 days; IQR, 5-13; p = .106) and longer than that of SSU (median stay, 4 days; IQR, 3-7; p < .001). The all-cause mortality at 1 year for HH did not differ from that of IM (HR, 0.91; 95% CI 0.73-1.14) or SSU (HR, 0.77; 95% CI 0.46-1.27); however, the emergency department readmission rate during the 30 days postdischarge was lower than that of IM (HR, 0.50; 95% CI 0.25-0.97) and SSU (HR, 0.37; 95% CI 0.19-0.74). There were no differences in the need for new hospitalisations or in the 30-day mortality rate. Direct transfer from the emergency department to HH is infrequent despite being a safe option for a certain patient profile with AHF. Direct transfer from the emergency department to HH is infrequent despite being a safe option for a certain patient profile with AHF.Adequate lifestyle changes significantly reduce the cardiovascular risk factors associated with prediabetes and type 2 diabetes mellitus. Therefore, healthy eating habits, regular physical activity, abstaining from using tobacco, and good sleep hygiene are recommended for managing these conditions. There is solid evidence that diets that are plant-based; low in saturated fatty acids, cholesterol, and sodium; and high in fiber, potassium, and unsaturated fatty acids are beneficial and reduce the expression of cardiovascular risk factors in these subjects. In view of the foregoing, the Mediterranean diet, the DASH diet, a low-carbohydrate diet, and a vegan-vegetarian diet are of note. Additionally, the relationship between nutrition and these metabolic pathologies is fundamental in targeting efforts to prevent weight gain, reducing excess weight in the case of individuals with overweight or obesity; and personalizing treatment to promote patient empowerment. This document is the executive summary of an updated review that includes the main recommendations for improving dietary nutritional quality in people with prediabetes or type 2 diabetes mellitus. The full review is available on the webpages of the Spanish Society of Arteriosclerosis (SEA, for its initials in Spanish), the Spanish Diabetes Society (SED, for its initials in Spanish), and the Spanish Society of Internal Medicine (SEMI, for its initials in Spanish).
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  • ivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE.
    Pre- and post-antivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE.Celiac disease (CeD) is a common autoimmune disorder caused by an abnormal immune response to dietary gluten proteins. The disease has high heritability. HLA is the major susceptibility factor, and the HLA effect is mediated via presentation of deamidated gluten peptides by disease-associated HLA-DQ variants to CD4+ T cells. In addition to gluten-specific CD4+ T cells the patients have antibodies to transglutaminase 2 (autoantigen) and deamidated gluten peptides. These disease-specific antibodies recognize defined epitopes and they display common usage of specific heavy and light chains across patients. Interactions between T cells and B cells are likely central in the pathogenesis, but how the repertoires of naïve T and B cells relate to the pathogenic effector cells is unexplored. To this end, we applied machine learning classification models to naïve B cell receptor (BCR) repertoires from CeD patients and healthy controls. Strikingly, we obtained a promising classification performance with an F1 score of 85%. Clusters of heavy and light chain sequences were inferred and used as features for the model, and signatures associated with the disease were then characterized. These signatures included amino acid (AA) 3-mers with distinct bio-physiochemical characteristics and enriched V and J genes. We found that CeD-associated clusters can be identified and that common motifs can be characterized from naïve BCR repertoires. The results may indicate a genetic influence by BCR encoding genes in CeD. Analysis of naïve BCRs as presented here may become an important part of assessing the risk of individuals to develop CeD. Our model demonstrates the potential of using BCR repertoires and in particular, naïve BCR repertoires, as disease susceptibility markers.Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ+ TNFα+ double positive CD8+ T-cells. https://www.selleckchem.com/products/crenolanib-cp-868596.html In this study, we compared single DNA vs. multiple DNA prime immunizations, and short vs. long time intervals between the DNA prime and the rAd5 boost to evaluate the impact of these different prime-boost strategies on vaccine-induced humoral and cellular responses in non-human primates. We demonstrated that DNA/rAd5 prime-boost strategies can be tailored to induce either CD4+ T-cell or CD8+ T-cell dominant responses while maintaining a high magnitude antibody response. Additionally, a single DNA prime immunization generated a stable memory response that could be boosted by rAd5 3 years later. These results suggest DNA/rAd5 prime-boost provides a flexible platform that can be fine-tuned to generate desirable T-cell memory responses.The expression of Triggering Receptor Expressed on Myeloid cells (TREM)-1 has been described as a predictive marker for anti-Tumor Necrosis Factor (TNF)-α monoclonal antibody (mAb) therapy responsiveness in patients with inflammatory bowel disease (IBD). Here we investigated expression of TREM-1 specifically in CD14+ monocytes in relation to anti-TNF response. The pretreatment TREM-1 expression levels of CD14+ monocytes of Crohn's disease (CD) patients were predictive of outcome to anti-TNF mAb therapy, with low TREM-1 expression associated with response to anti-TNF. FACSorting of CD14+ monocytes with different TREM-1 levels showed that differentiation towards regulatory CD206+ M2 type macrophages by anti-TNF was suppressed in CD14+ monocytes with high TREM-1 expression. Activity of the Fcγ-Receptor and autophagy pathway, both necessary for M2 type differentiation and the response to anti-TNF, were decreased in CD14+ monocytes with high expression of TREM-1. We confirmed that the activity of the Fcγ-Receptor pathway was decreased in the CD patients that did not respond to anti-TNF therapy and that it was negatively correlated with TREM-1 expression levels in the CD patient cohort. In conclusion, our results indicate that TREM-1 expression levels in CD14+ monocytes associate with decreased autophagy and FcγR activity resulting in decreased differentiation to M2 type regulatory macrophages upon anti-TNF mAb treatment, which may explain anti-TNF non-response in IBD patients with high expression levels of TREM-1.It is increasingly clear that an extraordinarily diverse range of clinically important conditions-including infections, vaccinations, autoimmune diseases, transplants, transfusion reactions, aging, and cancers-leave telltale signatures in the millions of V(D)J-rearranged antibody and T cell receptor [TR per the Human Genome Organization (HUGO) nomenclature but more commonly known as TCR] genes collectively expressed by a person's B cells (antibodies) and T cells. We refer to these as the immunome. Because of its diversity and complexity, the immunome provides singular opportunities for advancing personalized medicine by serving as the substrate for a highly multiplexed, near-universal blood test. Here we discuss some of these opportunities, the current state of immunome-based diagnostics, and highlight some of the challenges involved. We conclude with a call to clinicians, researchers, and others to join efforts with the Adaptive Immune Receptor Repertoire Community (AIRR-C) to realize the diagnostic potential of the immunome.Melatonin reportedly alleviates sepsis-induced multi-organ injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1-7). However, whether melatonin attenuates small-intestine injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of **** and ameliorated multiple-organ injury (lung/liver/kidney/small intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1.
    ivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE. Pre- and post-antivenom networks of cytokines and clinical features were associated with functional recovery measured by the PSFS AUPC over 28 days. With additional data, we can identify prognostic models using immunologic and clinical variables to predict recovery from SBE.Celiac disease (CeD) is a common autoimmune disorder caused by an abnormal immune response to dietary gluten proteins. The disease has high heritability. HLA is the major susceptibility factor, and the HLA effect is mediated via presentation of deamidated gluten peptides by disease-associated HLA-DQ variants to CD4+ T cells. In addition to gluten-specific CD4+ T cells the patients have antibodies to transglutaminase 2 (autoantigen) and deamidated gluten peptides. These disease-specific antibodies recognize defined epitopes and they display common usage of specific heavy and light chains across patients. Interactions between T cells and B cells are likely central in the pathogenesis, but how the repertoires of naïve T and B cells relate to the pathogenic effector cells is unexplored. To this end, we applied machine learning classification models to naïve B cell receptor (BCR) repertoires from CeD patients and healthy controls. Strikingly, we obtained a promising classification performance with an F1 score of 85%. Clusters of heavy and light chain sequences were inferred and used as features for the model, and signatures associated with the disease were then characterized. These signatures included amino acid (AA) 3-mers with distinct bio-physiochemical characteristics and enriched V and J genes. We found that CeD-associated clusters can be identified and that common motifs can be characterized from naïve BCR repertoires. The results may indicate a genetic influence by BCR encoding genes in CeD. Analysis of naïve BCRs as presented here may become an important part of assessing the risk of individuals to develop CeD. Our model demonstrates the potential of using BCR repertoires and in particular, naïve BCR repertoires, as disease susceptibility markers.Heterologous prime-boost immunization regimens are a common strategy for many vaccines. DNA prime rAd5-GP boost immunization has been demonstrated to protect non-human primates against a lethal challenge of Ebola virus, a pathogen that causes fatal hemorrhagic disease in humans. This protection correlates with antibody responses and is also associated with IFNγ+ TNFα+ double positive CD8+ T-cells. https://www.selleckchem.com/products/crenolanib-cp-868596.html In this study, we compared single DNA vs. multiple DNA prime immunizations, and short vs. long time intervals between the DNA prime and the rAd5 boost to evaluate the impact of these different prime-boost strategies on vaccine-induced humoral and cellular responses in non-human primates. We demonstrated that DNA/rAd5 prime-boost strategies can be tailored to induce either CD4+ T-cell or CD8+ T-cell dominant responses while maintaining a high magnitude antibody response. Additionally, a single DNA prime immunization generated a stable memory response that could be boosted by rAd5 3 years later. These results suggest DNA/rAd5 prime-boost provides a flexible platform that can be fine-tuned to generate desirable T-cell memory responses.The expression of Triggering Receptor Expressed on Myeloid cells (TREM)-1 has been described as a predictive marker for anti-Tumor Necrosis Factor (TNF)-α monoclonal antibody (mAb) therapy responsiveness in patients with inflammatory bowel disease (IBD). Here we investigated expression of TREM-1 specifically in CD14+ monocytes in relation to anti-TNF response. The pretreatment TREM-1 expression levels of CD14+ monocytes of Crohn's disease (CD) patients were predictive of outcome to anti-TNF mAb therapy, with low TREM-1 expression associated with response to anti-TNF. FACSorting of CD14+ monocytes with different TREM-1 levels showed that differentiation towards regulatory CD206+ M2 type macrophages by anti-TNF was suppressed in CD14+ monocytes with high TREM-1 expression. Activity of the Fcγ-Receptor and autophagy pathway, both necessary for M2 type differentiation and the response to anti-TNF, were decreased in CD14+ monocytes with high expression of TREM-1. We confirmed that the activity of the Fcγ-Receptor pathway was decreased in the CD patients that did not respond to anti-TNF therapy and that it was negatively correlated with TREM-1 expression levels in the CD patient cohort. In conclusion, our results indicate that TREM-1 expression levels in CD14+ monocytes associate with decreased autophagy and FcγR activity resulting in decreased differentiation to M2 type regulatory macrophages upon anti-TNF mAb treatment, which may explain anti-TNF non-response in IBD patients with high expression levels of TREM-1.It is increasingly clear that an extraordinarily diverse range of clinically important conditions-including infections, vaccinations, autoimmune diseases, transplants, transfusion reactions, aging, and cancers-leave telltale signatures in the millions of V(D)J-rearranged antibody and T cell receptor [TR per the Human Genome Organization (HUGO) nomenclature but more commonly known as TCR] genes collectively expressed by a person's B cells (antibodies) and T cells. We refer to these as the immunome. Because of its diversity and complexity, the immunome provides singular opportunities for advancing personalized medicine by serving as the substrate for a highly multiplexed, near-universal blood test. Here we discuss some of these opportunities, the current state of immunome-based diagnostics, and highlight some of the challenges involved. We conclude with a call to clinicians, researchers, and others to join efforts with the Adaptive Immune Receptor Repertoire Community (AIRR-C) to realize the diagnostic potential of the immunome.Melatonin reportedly alleviates sepsis-induced multi-organ injury by inducing autophagy and activating class III deacetylase Sirtuin family members (SIRT1-7). However, whether melatonin attenuates small-intestine injury along with the precise underlying mechanism remain to be elucidated. To investigate this, we employed cecal ligation and puncture (CLP)- or endotoxemia-induced sepsis mouse models and confirmed that melatonin treatment significantly prolonged the survival time of mice and ameliorated multiple-organ injury (lung/liver/kidney/small intestine) following sepsis. Melatonin partially protected the intestinal barrier function and restored SIRT1 and SIRT3 activity/protein expression in the small intestine. Mechanistically, melatonin treatment enhanced NF-κB deacetylation and subsequently reduced the inflammatory response and decreased the TNF-α, IL-6, and IL-10 serum levels; these effects were abolished by SIRT1 inhibition with the selective blocker, Ex527. Correspondingly, melatonin treatment triggered SOD2 deacetylation and increased SOD2 activity and subsequently reduced oxidative stress; this amelioration of oxidative stress by melatonin was blocked by the SIRT3-selective inhibitor, 3-TYP, and was independent of SIRT1.
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  • The COVID-19 pandemic caused dramatic interruptions and shifts to medical education, but students at schools nationwide responded by volunteering to support their physician educators on the frontlines. Relationships between student leaders, school administrators, and hospital administrators were key to the successful creation and organization of volunteer responses. This perspective piece from medical students, as well as hospital and medical school leadership, explores the evolving relationships in the creation of Rutgers New Jersey Medical School's Student COVID Team. https://www.selleckchem.com/GSK-3.html By reflecting on choices made by each group in parallel points in time, the piece highlights where interests and actions aligned and diverged.The purpose of this scoping review is to fill the gap in understanding the current status of intervention-based studies regarding leadership training in undergraduate medical education. As of late, there is an increased focus on the role of physicians as leaders in their fields, and communities. In order to evaluate these studies, both the PubMed and ERIC databases were searched, and an ultimate total of 35 articles methodologies were evaluated for their general methodology, curricular content, specific teaching methods, and evaluation methodologies. There were a number of trends identified, as well as remaining gaps.
    The online version contains supplementary material available at 10.1007/s40670-021-01308-9.
    The online version contains supplementary material available at 10.1007/s40670-021-01308-9.Medical students are taught to include the patient demographics of age and gender in the oral presentation; the inclusion of race is controversial. Epidemiology demonstrates that race, as a social determinant of health, can be a risk factor for disease. However, race, as a social construct, is not a biological cause for disease. In the USA, the relationship between race and health is stained by a long history of scientific racism, and the misuse of science does not rest in our past. Given the complexity and persistence of scientific racism, race should not be included in the oral presentation.During COVID-19, the anatomy faculty and students at Schulich School of Medicine and Dentistry observed strengths and weaknesses in their transition to online learning. A "four-prong" approach to teaching anatomy was developed. Asynchronous content modules were tailored to specific learning objectives, virtual labs were implemented to work through case-based applications, "live from the lab" review sessions provided the opportunity for interaction and integration, and finally, limited face-to-face laboratory sessions provided an opportunity for supervised consolidation with cadaveric specimens. Our approach may be used by other institutions to enhance anatomical education and student engagement.Lignocellulosic wastes, rice straw, sugarcane bagasse, rice bran and sawdust, and pure commercial carboxymethyl cellulose (CMC) and xylan were used as substrates to cultivate cellulolytic fungus, Aspergillus flavus KUB2, in submerged fermentation at 30°C. Of all the substrates, sugarcane bagasse was a good source for the production of cellulolytic and also hemicellulolytic enzymes. The maximum activities of endoglucanase (CMCase), total cellulase (FPase) and xylanase using sugarcane bagasse as substrate were 8%, 75% and 165%, respectively, higher than those of the commercial substrates. The time course determination of enzyme production revealed that the highest CMCase (1.27 U/ml), FPase (0.72 U/ml) and xylanase (376.81 U/ml) activities were observed at 14 days of fermentation. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) analyses confirmed the efficient structural alteration of sugarcane bagasse caused by enzymatic actions during A. flavus KUB2 cultivation. Based on the results of the hydrolytic enzyme activities, FTIR and SEM, A. flavus KUB2 is suggested as an efficient hydrolytic enzymes producer and an effective lignocellulose degrader, while sugarcane bagasse can be applied as a low-cost carbon source for the economical production of lignocellulose hydrolytic enzymes by A. flavus KUB2.Beauveria pseudobassiana formed three-dimensional aggregates of cells (CAs) in liquid culture. CAs were formed mainly by blastospores and conidia, distinct from microsclerotia formed through adhesion of hyphae. The formation, germination and sporulation of CAs were studied, as well as the pathogenicity of conidia produced from them against adults of black beetle. After 4 days of culture, CAs were formed, becoming compact and melanised after 10 days of incubation. Electron microscopy showed three-dimensional CAs averaging 431.65 µm in length with irregular shapes and rough surfaces, where cells were trapped within an extracellular matrix. CAs germinated after 2 days of incubation on agar-plates producing hyphae and forming phialides and conidia after 4 days. Produced conidia caused 45% mortality of black beetle adults. CAs germination and sporulation on soil were directly correlated with soil moisture, reaching 80% and 100% germination on the surface of soil with 17% and 30% moisture, respectively. CAs maintained 100% germination after 2 years of storage under refrigeration. These CAs could have a similar function as microsclerotia in nature, acting as resistant structures able to protect internal cells and their ability to sporulate producing infective conidia, suggesting their potential to be used as bioinsecticides to control soil-dwelling insects.The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the correlations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing (LOWESS) method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization.
    The COVID-19 pandemic caused dramatic interruptions and shifts to medical education, but students at schools nationwide responded by volunteering to support their physician educators on the frontlines. Relationships between student leaders, school administrators, and hospital administrators were key to the successful creation and organization of volunteer responses. This perspective piece from medical students, as well as hospital and medical school leadership, explores the evolving relationships in the creation of Rutgers New Jersey Medical School's Student COVID Team. https://www.selleckchem.com/GSK-3.html By reflecting on choices made by each group in parallel points in time, the piece highlights where interests and actions aligned and diverged.The purpose of this scoping review is to fill the gap in understanding the current status of intervention-based studies regarding leadership training in undergraduate medical education. As of late, there is an increased focus on the role of physicians as leaders in their fields, and communities. In order to evaluate these studies, both the PubMed and ERIC databases were searched, and an ultimate total of 35 articles methodologies were evaluated for their general methodology, curricular content, specific teaching methods, and evaluation methodologies. There were a number of trends identified, as well as remaining gaps. The online version contains supplementary material available at 10.1007/s40670-021-01308-9. The online version contains supplementary material available at 10.1007/s40670-021-01308-9.Medical students are taught to include the patient demographics of age and gender in the oral presentation; the inclusion of race is controversial. Epidemiology demonstrates that race, as a social determinant of health, can be a risk factor for disease. However, race, as a social construct, is not a biological cause for disease. In the USA, the relationship between race and health is stained by a long history of scientific racism, and the misuse of science does not rest in our past. Given the complexity and persistence of scientific racism, race should not be included in the oral presentation.During COVID-19, the anatomy faculty and students at Schulich School of Medicine and Dentistry observed strengths and weaknesses in their transition to online learning. A "four-prong" approach to teaching anatomy was developed. Asynchronous content modules were tailored to specific learning objectives, virtual labs were implemented to work through case-based applications, "live from the lab" review sessions provided the opportunity for interaction and integration, and finally, limited face-to-face laboratory sessions provided an opportunity for supervised consolidation with cadaveric specimens. Our approach may be used by other institutions to enhance anatomical education and student engagement.Lignocellulosic wastes, rice straw, sugarcane bagasse, rice bran and sawdust, and pure commercial carboxymethyl cellulose (CMC) and xylan were used as substrates to cultivate cellulolytic fungus, Aspergillus flavus KUB2, in submerged fermentation at 30°C. Of all the substrates, sugarcane bagasse was a good source for the production of cellulolytic and also hemicellulolytic enzymes. The maximum activities of endoglucanase (CMCase), total cellulase (FPase) and xylanase using sugarcane bagasse as substrate were 8%, 75% and 165%, respectively, higher than those of the commercial substrates. The time course determination of enzyme production revealed that the highest CMCase (1.27 U/ml), FPase (0.72 U/ml) and xylanase (376.81 U/ml) activities were observed at 14 days of fermentation. Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM) analyses confirmed the efficient structural alteration of sugarcane bagasse caused by enzymatic actions during A. flavus KUB2 cultivation. Based on the results of the hydrolytic enzyme activities, FTIR and SEM, A. flavus KUB2 is suggested as an efficient hydrolytic enzymes producer and an effective lignocellulose degrader, while sugarcane bagasse can be applied as a low-cost carbon source for the economical production of lignocellulose hydrolytic enzymes by A. flavus KUB2.Beauveria pseudobassiana formed three-dimensional aggregates of cells (CAs) in liquid culture. CAs were formed mainly by blastospores and conidia, distinct from microsclerotia formed through adhesion of hyphae. The formation, germination and sporulation of CAs were studied, as well as the pathogenicity of conidia produced from them against adults of black beetle. After 4 days of culture, CAs were formed, becoming compact and melanised after 10 days of incubation. Electron microscopy showed three-dimensional CAs averaging 431.65 µm in length with irregular shapes and rough surfaces, where cells were trapped within an extracellular matrix. CAs germinated after 2 days of incubation on agar-plates producing hyphae and forming phialides and conidia after 4 days. Produced conidia caused 45% mortality of black beetle adults. CAs germination and sporulation on soil were directly correlated with soil moisture, reaching 80% and 100% germination on the surface of soil with 17% and 30% moisture, respectively. CAs maintained 100% germination after 2 years of storage under refrigeration. These CAs could have a similar function as microsclerotia in nature, acting as resistant structures able to protect internal cells and their ability to sporulate producing infective conidia, suggesting their potential to be used as bioinsecticides to control soil-dwelling insects.The longitudinal immunologic status of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected patients and its association with the clinical outcome are barely known. Thus, we sought to analyze the temporal profiles of specific antibodies, as well as the correlations between the antibodies, proinflammatory cytokines, and survival of patients with coronavirus disease 2019 (COVID-19). A total of 1830 laboratory-confirmed COVID-19 cases were recruited. The temporal profiles of the virus, antibodies, and cytokines of the patients until 12 weeks since illness onset were fitted by the locally weighted scatter plot smoothing (LOWESS) method. The mediation effect of cytokines on the associations between antibody responses and survival were explored by mediation analysis. Of the 1830 patients, 1435 were detectable for SARS-CoV-2, while 395 were positive in specific antibodies only. Of the 1435 patients, 2.4% presented seroconversion for neither immunoglobulin G (IgG) nor immunoglobulin M (IgM) during hospitalization.
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  • Additive Manufacturing (AM) or rapid prototyping technologies are presented as one of the best options to produce customized prostheses and implants with high-level requirements in terms of complex geometries, mechanical properties, and short production times. The AM method that has been more investigated to obtain metallic implants for medical and biomedical use is Electron Beam Melting (EBM), which is based on the powder bed fusion technique. One of the most common metals employed to manufacture medical implants is titanium. Although discovered in 1790, titanium and its alloys only started to be used as engineering materials for biomedical prostheses after the 1950s. In the biomedical field, these materials have been mainly employed to facilitate bone adhesion and fixation, as well as for joint replacement surgeries, thanks to their good chemical, mechanical, and biocompatibility properties. Therefore, this study aims to collect relevant and up-to-date information from an exhaustive literature review on EBM and its applications in the medical and biomedical fields. This AM method has become increasingly popular in the manufacturing sector due to its great versatility and geometry control.Fipronil -a broad spectrum phenylpyrazole insecticide has high level of toxicity towards environment. Therefore, an easy and reliable analytical method was developed for residue estimation of fipronil to ensure food and environmental safety. A modified QuEChERS technique was followed for estimation of fipronil (5% SC) in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS. The initial residues (0.168-0.794 μg g-1) of total fipronil i.e., sum of fipronil and its metabolites (viz., desulfinyl and sulfone) in leaf and soil were dissipated following first order kinetics. About 92-96% of fipronil residues were degraded after 15 days with half-life of 3.4-4.1 days and pre-harvest interval of 19.4-25.7 days in plant. Residues were below level of quantification ( 1) for soil ecological health.Healthful tasty high protein, vegetable, gluten-free snacks are needed for all as well as those sensitive to gluten for in between meals and for after school events. Peanut meal a low value farm by-product was used to increase protein content and to add value for growers. Bile acid binding okra with cholesterol lowering potential and jalapeno, turmeric and ****** with healthy phytonutrients were included to increase vegetable consumption. The objective was to have healthy tasty snacks with ≥24% protein content. Gluten-free, whole grain, high protein, Sorghum-Peanut meal-Okra (SPO) and SPO-Jalapeno, SPO-Turmeric root and SPO-****** root snacks were sensory evaluated by 73 volunteers. Physical testing of the snacks included water activity, true and bulk density, texture and proximate analyses. Taste and Odor of the SPO and SPO-Jalapeno snacks were similar and significantly (p ≤ 0.05) higher than SPO-Turmeric root and SPO-****** root. Acceptability of SPO and SPO-Jalapeno snacks were both 88%; this value is quite desirable. Acceptability of SPO-Turmeric and SPO-****** were only 56 and 51% respectively. Turmeric and ****** have been reported with many health benefits; however these snacks were not preferred by the tasters. Water activity (Aw) of the snacks tested was SPO (0.42) less then SPO-Turmeric (0.52) less then SPO-Jalapeno (0.54) less then SPO-****** (0.62). Water activity indicates that all the snacks were crispy and had longer shelf life. Expansion of these snacks was SPO-****** root 84%, SPO-Turmeric root 76%, SPO-Jalapeno 42% and SPO only 14%. Data suggest snacks containing spices were fluffy and would give good presentation in packaging. The objective of attaining protein level was clearly attained, as values ranged 24-26%. These snacks are easy to make in house kitchens or by food companies. These healthy snacks offer a gluten-free, high protein, tasty choice for all, including vegetarians and individuals hypersensitive to gluten.Congenital myasthenia syndrome (CMS) is a group of heterogeneous diseases affecting the neuromuscular endplate. CMS has a considerably different phenotypic presentations, with the onset time ranging from early infancy to late adulthood. Here, we report a case of a CMS due to a new DOK7 mutation in a 28-year-old man and two of his sisters, who have a pure limb-girdle weakness. DOK7 CMS has a varying presentation. Typically, the onset occurs in childhood with ptosis, bulbar symptoms, difficulty walking, weakness, and gait abnormality. https://www.selleckchem.com/MEK.html This case sheds light on a novel DOK7 gene mutation with a unique presentation of CMS and provides insight into its unique phenotypic presentation.The purpose of this work has been to analyze, from a structural and functional approach, the families at risk or unprotected by the Family Treatment Teams, inserted in the Public System of Social Services. For this purpose, qualitative research methods and techniques have been used on 26 interdisciplinary reports generated in the most representative cases of family intervention. Significant results have been obtained describing family structures, life-cycle adaptation, pattern repetition across generations, life events and family functioning, and linked patterns. The data reveal that these are families with common problems related mainly to the behaviour of minors and the coverage of basic needs. Negligence is the central element in this type of families as well as the maladjustment to the life cycle of the family system. All this from patterns of repetition linking dysfunctional.This article presents socio-economic, energetic and CO2 emissions' impact by considering a large-scale integrated plant to treat Municipal Solid Waste (MSW) in the Metropolitan Region of São Paulo (MRSP); the most important Brazilian macro-region. As an alternative to landfills, this plant offers a source of renewable energy and a good assessment of benefits the circular economy provides. Based on the most recent interregional economic transactions data, the proposed Input-Output model has shown reductions in the local energy demand (-0.31%), carbon emissions (-3.40%). On the other hand, it has suggested gains in the GDP (+0.21%) and formal job positions (+0.08% or 10.6k) when recyclables are introduced massively in the economy.
    Additive Manufacturing (AM) or rapid prototyping technologies are presented as one of the best options to produce customized prostheses and implants with high-level requirements in terms of complex geometries, mechanical properties, and short production times. The AM method that has been more investigated to obtain metallic implants for medical and biomedical use is Electron Beam Melting (EBM), which is based on the powder bed fusion technique. One of the most common metals employed to manufacture medical implants is titanium. Although discovered in 1790, titanium and its alloys only started to be used as engineering materials for biomedical prostheses after the 1950s. In the biomedical field, these materials have been mainly employed to facilitate bone adhesion and fixation, as well as for joint replacement surgeries, thanks to their good chemical, mechanical, and biocompatibility properties. Therefore, this study aims to collect relevant and up-to-date information from an exhaustive literature review on EBM and its applications in the medical and biomedical fields. This AM method has become increasingly popular in the manufacturing sector due to its great versatility and geometry control.Fipronil -a broad spectrum phenylpyrazole insecticide has high level of toxicity towards environment. Therefore, an easy and reliable analytical method was developed for residue estimation of fipronil to ensure food and environmental safety. A modified QuEChERS technique was followed for estimation of fipronil (5% SC) in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS. The initial residues (0.168-0.794 μg g-1) of total fipronil i.e., sum of fipronil and its metabolites (viz., desulfinyl and sulfone) in leaf and soil were dissipated following first order kinetics. About 92-96% of fipronil residues were degraded after 15 days with half-life of 3.4-4.1 days and pre-harvest interval of 19.4-25.7 days in plant. Residues were below level of quantification ( 1) for soil ecological health.Healthful tasty high protein, vegetable, gluten-free snacks are needed for all as well as those sensitive to gluten for in between meals and for after school events. Peanut meal a low value farm by-product was used to increase protein content and to add value for growers. Bile acid binding okra with cholesterol lowering potential and jalapeno, turmeric and ginger with healthy phytonutrients were included to increase vegetable consumption. The objective was to have healthy tasty snacks with ≥24% protein content. Gluten-free, whole grain, high protein, Sorghum-Peanut meal-Okra (SPO) and SPO-Jalapeno, SPO-Turmeric root and SPO-Ginger root snacks were sensory evaluated by 73 volunteers. Physical testing of the snacks included water activity, true and bulk density, texture and proximate analyses. Taste and Odor of the SPO and SPO-Jalapeno snacks were similar and significantly (p ≤ 0.05) higher than SPO-Turmeric root and SPO-Ginger root. Acceptability of SPO and SPO-Jalapeno snacks were both 88%; this value is quite desirable. Acceptability of SPO-Turmeric and SPO-Ginger were only 56 and 51% respectively. Turmeric and ginger have been reported with many health benefits; however these snacks were not preferred by the tasters. Water activity (Aw) of the snacks tested was SPO (0.42) less then SPO-Turmeric (0.52) less then SPO-Jalapeno (0.54) less then SPO-Ginger (0.62). Water activity indicates that all the snacks were crispy and had longer shelf life. Expansion of these snacks was SPO-Ginger root 84%, SPO-Turmeric root 76%, SPO-Jalapeno 42% and SPO only 14%. Data suggest snacks containing spices were fluffy and would give good presentation in packaging. The objective of attaining protein level was clearly attained, as values ranged 24-26%. These snacks are easy to make in house kitchens or by food companies. These healthy snacks offer a gluten-free, high protein, tasty choice for all, including vegetarians and individuals hypersensitive to gluten.Congenital myasthenia syndrome (CMS) is a group of heterogeneous diseases affecting the neuromuscular endplate. CMS has a considerably different phenotypic presentations, with the onset time ranging from early infancy to late adulthood. Here, we report a case of a CMS due to a new DOK7 mutation in a 28-year-old man and two of his sisters, who have a pure limb-girdle weakness. DOK7 CMS has a varying presentation. Typically, the onset occurs in childhood with ptosis, bulbar symptoms, difficulty walking, weakness, and gait abnormality. https://www.selleckchem.com/MEK.html This case sheds light on a novel DOK7 gene mutation with a unique presentation of CMS and provides insight into its unique phenotypic presentation.The purpose of this work has been to analyze, from a structural and functional approach, the families at risk or unprotected by the Family Treatment Teams, inserted in the Public System of Social Services. For this purpose, qualitative research methods and techniques have been used on 26 interdisciplinary reports generated in the most representative cases of family intervention. Significant results have been obtained describing family structures, life-cycle adaptation, pattern repetition across generations, life events and family functioning, and linked patterns. The data reveal that these are families with common problems related mainly to the behaviour of minors and the coverage of basic needs. Negligence is the central element in this type of families as well as the maladjustment to the life cycle of the family system. All this from patterns of repetition linking dysfunctional.This article presents socio-economic, energetic and CO2 emissions' impact by considering a large-scale integrated plant to treat Municipal Solid Waste (MSW) in the Metropolitan Region of São Paulo (MRSP); the most important Brazilian macro-region. As an alternative to landfills, this plant offers a source of renewable energy and a good assessment of benefits the circular economy provides. Based on the most recent interregional economic transactions data, the proposed Input-Output model has shown reductions in the local energy demand (-0.31%), carbon emissions (-3.40%). On the other hand, it has suggested gains in the GDP (+0.21%) and formal job positions (+0.08% or 10.6k) when recyclables are introduced massively in the economy.
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