Endoplasmic reticulum stress and inflammation in the central nervous system

Persistent endoplasmic reticulum (ER) stress is thought to drive the pathology of many chronic disorders due to its potential to elicit aberrant inflammatory signaling and facilitate cell death. In neurodegenerative diseases, the accumulation of misfolded proteins and concomitant induction of ER stress in neurons contributes to neuronal dysfunction. In addition, ER stress responses induced in the surrounding neuroglia may promote disease progression by coordinating damaging inflammatory responses, which help fuel a neurotoxic milieu. Nevertheless, there still remains a gap in knowledge regarding the cell-specific mechanisms by which ER stress mediates neuroinflammation. In this review, we will discuss recently uncovered inflammatory pathways linked to the ER stress response. Moreover, we will summarize the present literature delineating how ER stress is generated in Alzheimer?s disease, Parkinson?s disease, Amyotrophic Lateral Sclerosis, and Multiple Sclerosis, and highlight how ER stress and neuroinflammation intersect mechanistically within the central nervous system. The mechanisms by which stress-induced inflammation contributes to the pathogenesis and progression of neurodegenerative diseases remain poorly understood. Further examination of this interplay could present unappreciated insights into the development of neurodegenerative diseases, and reveal new therapeutic targets

The use of interpretive phenomenological analysis in couple and family therapy research

This article proposes a research methodology that is newer to the field of couple and family therapy research called Interpretive Phenomenological Analysis (IPA). Researchers exploring couple and family therapy research continue to establish the efficacy of couple and family interventions in a context that favors a positivist view of phenomena. This research continues to be critical for establishing the role of couple and family therapy in the field of mental health as well as further clarifying which interventions are best for specific clinical issues and when. IPA offers researchers the opportunity to explore how couples and families make meaning of their experiences from an intersubjective perspective. Meaning making is central to understanding couples and families as well as part of the many clinical approaches to working with couples and families. Despite the importance of meaning, few research methodologies allow for this central concept in couple and family therapy to be the focus of exploration. The following article outlines one such methodology and the possible use of IPA in couple and family therapy research

Genetic Background of Prop1df Mutants Provides Remarkable Protection Against Hypothyroidism-Induced Hearing Impairment

Hypothyroidism is a cause of genetic and environmentally induced deafness. The sensitivity of cochlear development and function to thyroid hormone (TH) mandates understanding TH action in this sensory organ. Prop1df and Pou1f1dw mutant mice carry mutations in different pituitary transcription factors, each resulting in pituitary thyrotropin deficiency. Despite the same lack of detectable serum TH, these mutants have very different hearing abilities: Prop1df mutants are mildly affected, while Pou1f1dw mutants are completely deaf. Genetic studies show that this difference is attributable to the genetic backgrounds. Using embryo transfer, we discovered that factors intrinsic to the fetus are the major contributor to this difference, not maternal effects. We analyzed Prop1df mutants to identify processes in cochlear development that are disrupted in other hypothyroid animal models but protected in Prop1df mutants by the genetic background. The development of outer hair cell (OHC) function is delayed, but Prestin and KCNQ4 immunostaining appear normal in mature Prop1df mutants. The endocochlear potential and KCNJ10 immunostaining in the stria vascularis are indistinguishable from wild type, and no differences in neurofilament or synaptophysin staining are evident in Prop1df mutants. The synaptic vesicle protein otoferlin normally shifts expression from OHC to IHC as temporary afferent fibers beneath the OHC regress postnatally. Prop1df mutants exhibit persistent, abnormal expression of otoferlin in apical OHC, suggesting delayed maturation of synaptic function. Thus, the genetic background of Prop1df mutants is remarkably protective for most functions affected in other hypothyroid mice. The Prop1df mutant is an attractive model for identifying the genes that protect against deafness

Gender associated differences in determinants of quality of life in patients with COPD: a case series study

BACKGROUND: The influence of gender on the expression of COPD has received limited attention. Quality of Life (QoL) has become an important outcome in COPD patients. The aim of our study was to explore factors contributing to gender differences in Quality of Life of COPD patients. METHODS: In 146 men and women with COPD from a pulmonary clinic we measured: Saint George's Respiratory Questionnaire (SGRQ), age, smoking history, PaO(2), PaCO(2), FEV(1), FVC, IC/TLC, FRC, body mass index (BMI), 6 minute walk distance (6MWD), dyspnea (modified MRC), degree of comorbidity (Charlson index) and exacerbations in the previous year. We explored differences between genders using Mann-Whitney U-rank test. To investigate the main determinants of QoL, a multiple lineal regression analysis was performed using backward Wald's criteria, with those variables that significantly correlated with SGRQ total scores. RESULTS: Compared with men, women had worse scores in all domains of the SGRQ (total 38 vs 26, p = 0.01, symptoms 48 vs 39, p = 0.03, activity 53 vs 37, p = 0.02, impact 28 vs 15, p = 0.01). SGRQ total scores correlated in men with: FEV(1)% (-0.378, p < 0.001), IC/TLC (-0.368, p = 0.002), PaO(2 )(-0.379, p = 0.001), PaCO(2 )(0.256, p = 0.05), 6MWD (-0.327, p = 0.005), exacerbations (0.366, p = 0.001), Charlson index (0.380, p = 0.001) and MMRC (0.654, p < 0.001). In women, the scores correlated only with FEV(1)% (-0.293, p = 0.013) PaO(2 )(-0.315, p = 0.007), exacerbations (0.290, p = 0.013) and MMRC (0.628, p < 0.001). Regression analysis (B, 95% CI) showed that exercise capacity (0.05, 0.02 to 0.09), dyspnea (17.6, 13.4 to 21.8), IC/TLC (-51.1, -98.9 to -3.2) and comorbidity (1.7, 0.84 to 2.53) for men and dyspnea (9.7, 7.3 to 12.4) and oxygenation (-0.3, -0.6 to -0.01) for women manifested the highest independent associations with SGRQ scores. CONCLUSION: In moderate to severe COPD patients attending a pulmonary clinic, there are gender differences in health status scores. In turn, the clinical and physiological variables independently associated with those scores differed in men and women. Attention should be paid to the determinants of QoL scores in women with COPD

What evidence exists on the links between natural climate solutions and climate change mitigation outcomes in subtropical and tropical terrestrial regions? A systematic map protocol

Background Natural climate solutions (NCS)—actions to conserve, restore, and modify natural and modified ecosystems to increase carbon storage or avoid greenhouse gas (GHG) emissions—are increasingly regarded as important pathways for climate change mitigation, while contributing to our global conservation efforts, overall planetary resilience, and sustainable development goals. Recently, projections posit that terrestrial-based NCS can potentially capture or avoid the emission of at least 11 Gt (gigatons) of carbon dioxide equivalent a year, or roughly encompassing one third of the emissions reductions needed to meet the Paris Climate Agreement goals by 2030. NCS interventions also purport to provide co-benefits such as improved productivity and livelihoods from sustainable natural resource management, protection of locally and culturally important natural areas, and downstream climate adaptation benefits. Attention on implementing NCS to address climate change across global and national agendas has grown—however, clear understanding of which types of NCS interventions have undergone substantial study versus those that require additional evidence is still lacking. This study aims to conduct a systematic map to collate and describe the current state, distribution, and methods used for evidence on the links between NCS interventions and climate change mitigation outcomes within tropical and sub-tropical terrestrial ecosystems. Results of this study can be used to inform program and policy design and highlight critical knowledge gaps where future evaluation, research, and syntheses are needed. Methods To develop this systematic map, we will search two bibliographic databases (including 11 indices) and 67 organization websites, backward citation chase from 39 existing evidence syntheses, and solicit information from key informants. All searches will be conducted in English and encompass subtropical and tropical terrestrial ecosystems (forests, grasslands, mangroves, agricultural areas). Search results will be screened at title and abstract, and full text levels, recording both the number of excluded articles and reasons for exclusion. Key meta-data from included articles will be coded and reported in a narrative review that will summarize trends in the evidence base, assess gaps in knowledge, and provide insights for policy, practice, and research. The data from this systematic map will be made open access

"Now I know the terrain": phenomenological exploration of CFTs learning on evidence-based practice

Couple and family therapists are rarely the focus of research yet are critical for positive outcomes in therapy. The attempts to integrate evidence-based approaches into the practice of couple and family therapy have been controversial resulting in passionate and at times divisive dialogue. The aims of this research project were to explore what do couple and family therapists experience when learning an evidence-based approach to working with couples and families. A total of 14 couple and family therapists were interviewed about their experience with learning an evidence-based approach. The research was guided methodologically by interpretive phenomenological analysis. Three themes emerged from the participants’ experiences including: the supports and challenges in learning; the embodiment of a therapy practice; and the experience of shame while learning

Instructional Models for Course-Based Research Experience (CRE) Teaching

The course-based research experience (CRE) with its documented educational benefits is increasingly being implemented in science, technology, engineering, and mathematics education. This article reports on a study that was done over a period of 3 years to explicate the instructional processes involved in teaching an undergraduate CRE. One hundred and two instructors from the established and large multi-institutional SEA-PHAGES program were surveyed for their understanding of the aims and practices of CRE teaching. This was followed by large-scale feedback sessions with the cohort of instructors at the annual SEA Faculty Meeting and subsequently with a small focus group of expert CRE instructors. Using a qualitative content analysis approach, the survey data were analyzed for the aims of inquiry instruction and pedagogical practices used to achieve these goals. The results characterize CRE inquiry teaching as involving three instructional models: 1) being a scientist and generating data; 2) teaching procedural knowledge; and 3) fostering project ownership. Each of these models is explicated and visualized in terms of the specific pedagogical practices and their relationships. The models present a complex picture of the ways in which CRE instruction is conducted on a daily basis and can inform instructors and institutions new to CRE teaching

Models of classroom assessment for course-based research experiences

Course-based research pedagogy involves positioning students as contributors to authentic research projects as part of an engaging educational experience that promotes their learning and persistence in science. To develop a model for assessing and grading students engaged in this type of learning experience, the assessment aims and practices of a community of experienced course-based research instructors were collected and analyzed. This approach defines four aims of course-based research assessment—(1) Assessing Laboratory Work and Scientific Thinking; (2) Evaluating Mastery of Concepts, Quantitative Thinking and Skills; (3) Appraising Forms of Scientific Communication; and (4) Metacognition of Learning—along with a set of practices for each aim. These aims and practices of assessment were then integrated with previously developed models of course-based research instruction to reveal an assessment program in which instructors provide extensive feedback to support productive student engagement in research while grading those aspects of research that are necessary for the student to succeed. Assessment conducted in this way delicately balances the need to facilitate students’ ongoing research with the requirement of a final grade without undercutting the important aims of a CRE education