Chronic pain is common and frequently interferes with people’s regular functioning and reduces quality of life. Though pharmacological approaches are used most frequently to treat pain-related issues, the side effects of these medications often lead to other problems. Group therapy has been used and studied for decades in treating pain though it’s general efficacy for addressing pain is not clear. Objectives: to determine group therapy’s efficacy for patients with pain-related issues and whether the effects are moderated by study, patient, leader, or group characteristics. Method: potential articles were selected from searches completed in major databases based on a set of inclusion criteria. A random effects meta-analysis was conducted, and potential moderators were analyzed. Results: we analyzed 57 studies representing 8,933 patients receiving group therapy for pain which produced a significant, small effect (g = 0.28) for reducing pain intensity. Various secondary outcomes such as pain frequency, interference with activities of daily living, physical functioning, catastrophizing, self-efficacy, anxiety, depression, and quality of life were also found to improve significantly. Four significant moderating variables were found to include pain measure used, gender composition, number of sessions, and presence of pain diagnosis. Discussion: results are discussed and compared to those of past meta-analyses regarding both chronic pain and group therapy. Implications for practice and research are provided.

Indiana University-Purdue University Indianapolis (IUPUI) / FGF23 is an osteocyte produced hormone necessary for maintaining systemic phosphate handling, and thus bone structure and function in both rare and common disorders such as chronic kidney disease (CKD). FGF23 is a critical factor in CKD, with elevated levels causing alterations in mineral metabolism and increased odds for mortality. However, the mechanisms directing the production of key modulators of skeletal homeostasis and biomineralization within osteocytes, and how this is altered in chronic kidney disease, remain unclear. The experimental focus of this dissertation was to dissect the molecular systems and role of oxygen sensing in the regulated production of FGF23. In CKD, up to 75% of patients have anemia and concomitant marked elevations in FGF23, increasing mortality odds. Anemia is a potent driver of FGF23 secretion, therefore, current and emerging therapies, including recombinant EPO and the hypoxia inducible factorprolyl hydroxylase inhibitors (HIF-PHI) FG-4592 and BAY 85-3934, were used to improve anemia in the adenine diet-induced mouse model of CKD. In the mice with CKD, iFGF23 was markedly elevated in control mice but was attenuated by 65-85% after delivery of EPO or HIF-PHI, with no changes in serum phosphate. This was associated with improved systemic iron utilization and reductions in mRNA markers of renal fibrosis. In osteocyte-like cell cultures treated with HIF-PHI, integrative RNAseq and ATACseq analysis identified candidate genes upregulated in response to mimicked hypoxia, concomitant with elevated Fgf23 expression. These genes were found to be downregulated in CKD bone, therefore, knock-out cells were generated using CRISPR/Cas9 technology. These cells were found to be functionally similar to in vivo conditional knockout models that have enhanced bone mass and elevated FGF23. Taken together, these results further define novel factors involved in the regulation of FGF23 and identify new therapeutic targets. / 2023-05-26

Background: Chronic pain is considered to be a major health issue globally, whereof Italy is one of the highest ranked countries regarding chronic pain prevalence in Europe. Chronic pain has a negative impact on quality of life and functions on a biological, social, and psychological level, which concerns all health professionals. For this reason, health care providers have an important role working with these patients. Aim: This study aims to explore and bring knowledge about Italian physical therapists’ experiences of working with patients with chronic pain. Design: A qualitative method with an exploratory and descriptive design, based on semi structured interviews was used for the purpose of understanding the physical therapists’ experiences of working with patients with chronic pain. Furthermore, the data was analyzed by a qualitative content analysis and had an inductive approach. Results: The analysis generated five categories: The importance of trust and relations, Professional challenges and positive potentials, Physical therapists’ reflection on their own contribution, Physical therapists’ and patients’ different viewpoints and The view on the profession.   Conclusion: This study revealed that Italian physical therapists regard themselves to play a crucial part in the work with patients with chronic pain. It emphasizes the essential parts of the work of gaining the patient’s trust and forming an alliance. Despite the physical therapists’ contribution to these patients, there exist factors that frequently prevent the rehabilitation from being successful. The results could be of value for future physical therapists working with chronic pain. Keywords: Physical therapy, experience, chronic pain, Italy / Bakgrund: Långvarig smärta beräknas vara ett stort globalt hälsoproblem och Italien är ett av de länder i Europa med högst prevalens. Långvarig smärta har en negativ inverkan på livskvalitet och biologiska, sociala samt psykologiska funktioner. Detta berör alla vårdgivare, som har en betydelsefull roll i att upprätthålla och förbättra funktionen samt livskvaliteten hos dessa patienter. Syfte: Denna studie syftar till att utforska och tillföra kunskap om italienska fysioterapeuters upplevelser och erfarenheter av att arbeta med patienter med långvarig smärta. Metod: En kvalitativ metod med explorativ och deskriptiv design, baserad på sju semistrukturerade intervjuer användes i syfte att få djupare förståelse för fysioterapeuters upplevelser och erfarenheter av att arbeta med patienter med långvarig smärta. Vidare, analyserades data med en kvalitativ innehållsanalys med en induktiv ansats. Resultatsammanfattning: Dataanalysen genererade i fem kategorier: The importance of trust and relations, Professional challenges and positive potentials, Physical therapists’ reflection on their own contribution, Physical therapists’ and patients’ different viewpoints och The view on the profession.   Slutsats: Denna studie påvisar att fysioterapeuter i Italien anser sig har en betydelsefull roll för patienter med långvarig smärta. Trots många utmaningar upplevde fysioterapeuterna deras insats som väsentlig för att förbättra patienternas vy på livet och deras livskvalitet. Studien ger insikt i vilka erfarenheter och upplevelser fysioterapeuterna har i arbetet med patientgruppen. Resultatet belyser svårigheter och möjligheter med att arbeta med dessa patienter, vilket kan vara värdefullt för hur fysioterapeuter arbetar med långvarig smärta i framtiden. Nyckelord: Physical therapy, experience, chronic pain, Italy

This dissertation begins with a critical preface that examines the haunted present and its impact on writing for third and fourth generation Holocaust survivors. Then follows a collection of poetry and prose that examine themes of intergenerational trauma, experiences of the Shoah, grief, and chronic illness.

The diagnostic lesions of neurodegenerative tauopathies, such as chronic traumatic encephalopathy (CTE) and Alzheimer’s disease (AD), are located in the cortex, however, white matter pathology is a contributing factor to neurodegeneration. At all stages of disease, white matter axonal and glial morphological abnormalities are present in CTE. Similarly, white matter changes may emerge before cortical pathology in AD. White matter irregularities bear functional consequences, as they are associated to some of the most common and onerous symptoms of these diseases, like cognitive deficits and depression. Individuals with AD present with both reduced white matter integrity and cognitive symptoms starting early in disease progression. In CTE, which is triggered by repetitive head impacts (RHI), individuals are particularly vulnerable to white matter damage as RHI exposure alone is sufficient to injure white matter tracts and induce depression symptoms. In this dissertation, I investigated the cellular and molecular presentation of white matter glial cells, including astrocytes, oligodendrocytes (OLs), and microglia in CTE and AD as compared to controls. To investigate white matter pathology, I examined glial cells on a cellular level. Neuropathologically-verified CTE samples were compared to RHI-experienced controls, with both groups containing samples with and without depressed mood. CTE with depressed mood had reduced myelin and increased neuroinflammatory peripheral cells compared to non-depressed CTE and contained increased numbers of microglia compared to non-depressed CTE and control samples. Using single-nucleus transcriptomics in neuropathologically-verified CTE samples compared to matched RHI-naïve controls, OL loss, iron aggregates, OL iron trafficking dysregulation, and two distinct astrocyte subpopulations were detected in CTE white matter. AD white matter, compared to the same control samples in the same brain region, was also depleted of OLs by single-nucleus transcriptomics. However, OLs did not demonstrate iron-related transcriptional profile like those in CTE and, in further contrast, displayed increased numbers of microglia and astrocytes. Together, these findings implicate previously uncharacterized white matter glia in the neurodegenerative process of CTE and AD and further elucidate the etiology of neurodegeneration-related symptoms in CTE. These findings may aid in the development of therapeutics targeting glial contributions to the pathologic processes of both CTE and AD.

Background: Psychological and physical stress can either enhance or suppress immune functions depending on a variety of factors such as duration and severity of stressful situation. Chronic stress exerts a significantly suppressive effect on immune functions. However, the mechanisms responsible for this phenomenon remain to be elucidated. Autophagy plays an essential role in modulating cellular homeostasis and immune responses. However, it is not known yet whether autophagy contributes to chronic stress-induced immunosuppression. T cell immunoglobulin and mucin domain 3 (Tim-3) has shown immune-suppressive effects and obviously positive regulation on cell apoptosis. Tim-3 combines with Tim-3 ligand galectin-9 to modulate apoptosis. However, its impact on autophagy and chronic stress-induced immunosuppression is not yet identified. Results: We found remarkably higher autophagy level in the spleens of mice that were subjected to chronic restraint stress compared with the control group. We also found that inhibition of autophagy by the autophagy inhibitor 3-methyladenine (3-MA) significantly attenuated chronic stress-induced alterations of pro-inflammatory and anti-inflammatory cytokine levels. We further elucidated that 3-MA dramatically inhibited the reduction of lymphocyte numbers. Moreover, chronic stress dramatically enhanced the expression of Tim-3 and galectin-9. Inhibition of Tim-3 by small interfering RNA against Tim-3 significantly decreased the level of autophagy and immune suppression in isolated primary splenocytes from stressed mice. In addition, α-lactose, a blocker for the interaction of Tim-3 and galectin-9, also decreased the autophagy level and immune suppression. Conclusion: Chronic stress induces autophagy, resulting with suppression of immune system. Tim-3 and galectin-9 play a crucial regulatory role in chronic stress-induced autophagy. These studies suggest that Tim-3 mediated autophagy may offer a novel therapeutic strategy against the deleterious effects of chronic stress on the immune system.

Magister Artium (Development Studies) - MA(DVS) / Poverty in Nigeria has always been examined as a static phenomenon, although empirical studies established that, rather than being static, the poverty levels of individuals can change over time and people can enter and leave a transitory state of poverty. Many individuals live in poverty for a long period of time, the length of which is the defining characteristic of a state of chronic poverty. There has been little or no effort by researchers to distinguish households that are chronically poor from those that are transitorily poor. It is against this background that this study sought to investigate the extent of chronic and transitory poverty among households in Nigeria: specifically, what factors influence chronic and transitory poverty in Nigeria. / 2023

Chronic Granulomatous Disease is the most commonly encountered immunodeficiency involving the phagocyte, and is characterized by repeated infections with bacterial and fungal pathogens, as well as the formation of granulomas in tissue. The disease is the result of a disorder of the NADPH oxidase system, culminating in an inability of the phagocyte to generate superoxide, leading to the defective killing of pathogenic organisms. This can lead to infections with Staphylococcus aureus, Psedomonas species, Nocardia species, and fungi (such as Aspergillus species and Candida albicans). Involvement of vital or large organs can contribute to morbidity and/or mortality in the affected patients. Major advances have occurred in the diagnosis and treatment of this disease, with the potential for gene therapy or stem cell transplantation looming on the horizon. © 2011 Song et al; licensee BioMed Central Ltd.

Global lifespans are longer than ever before and there is an increasing shift towards a more aged global population. Also, the majority of severe disease and deaths in the recent and ongoing COVID-19 pandemic is found in individuals over 60 years of age. Therefore, there is an urgent need to gain insight into how the immune system changes with age; specifically: (1) what are the drivers of chronic, systemic inflammation (‘inflammaging’) that occur in some but not all older individuals and (2) how, in turn, numerical aging and chronic inflammation collide to impact anti-viral immunity and lead to poor infection outcomes. In this body of work, two focused research questions were addressed as part of an overarching goal to determine the links between numerical age, chronic inflammatory status, and immune cell function. First, the role of iNKT cells in the inflammation found with ART-suppressed HIV infection and aging was studied, and second, connections between age and pre-existing immunity to SARS-CoV-2 were investigated. Invariant natural killer T (iNKT) cells are a unique, innate-like T cell subset known to bridge innate and adaptive immune responses and can exert inflammatory and immunosuppressive effector functions. The role of iNKT cells in the chronic inflammation found with ART-suppressed HIV infection and/or normal aging is unclear. Therefore, iNKT cell frequencies and surface phenotypes were measured from a HIV and Aging cohort comprised of ART-suppressed HIV+ subjects and matched uninfected controls stratified by age into younger and older groups and iNKT cell signature were correlated with plasma markers of chronic inflammation. Specific characteristics of iNKT cells were associated with aviremic HIV infection and/or advanced age, and distinct links between iNKT cell signatures and markers of chronic inflammation were found. Further, multivariate analysis (PLS-DA) of the collected dataset revealed that iNKT cell and plasma markers stratified younger from older subjects within both the uninfected and aviremic HIV+ groups. Older age is arguably the strongest predictor of severe clinical outcomes and mortality after SARS-CoV-2 infection. The role of pre-existing, cross-reactive immunity in COVID-19 outcomes is unclear to date. A newly developed, highly sensitive serological assay (the BU ELISA) was used to elucidate links between pre-existing immunity to SARS-CoV-2 and age. We found SARS-CoV-2 receptor binding domain (RBD) and/or nucleocapsid protein (N) reactive antibodies (IgG, IgM, and/or IgA isotypes) in all pre-pandemic subjects tested, with a wide range in antibody levels. SARS-CoV-2 reactive immunoglobulin levels tracked with antibodies specific for analogous viral proteins from endemic coronavirus strains and were lowest in subjects over 70 years of age compared with younger counterparts. In sum, these findings provide evidence of lower pre-existing immunity to SARS-CoV-2 in elderly individuals, and this may account for their poor infection outcomes. In conclusion, the findings in this work provide new insight into the impact of age and chronic inflammation on productive and protective immune responses. These results underscore the need for further investigations into the immune cell mechanisms and inflammaging pathways that subvert healthy aging.

Therapy decision-making for patients with chronic diseases can be difficult. Such patients usually live with their illness(es) all their life, and therapies can only help them improve their condition by managing symptoms, not curing them. Patient-oriented approaches are common to caring for people with chronic conditions because patients’ priorities become relevant means of prioritizing therapies in the absence of a cure. While such type of approach is shown to be effective, it does not leverage evidence on the success of given therapies to achieve specific similar patient goals in the past. Evidence-Based Medicine (EBM) is a concept that was introduced to the medical field in the early 90s to invalidate previously accepted tests and therapies and replace them with new, more powerful, more accurate, more efficacious, and safer ones. Unfortunately, despite the prevalence of patient-oriented approaches for patients with chronic diseases, data collected on patients is not systematically leveraged to support therapy decisions. Combining evidence-based decision-making and patient-oriented approaches could potentially further improve patient outcomes by leveraging the most up-to-date data to recommend and discuss therapy options for patients with chronic conditions. The development and implementation of Learning Health Systems (LHS) is another solution to improving patient outcomes, one that the US Institute of Medicine strongly recommends. The development and implementation of a LHS to support therapy choice for patients with chronic conditions could improve related decisions by fostering continuous learning regarding which therapy may help better achieve which patient goals. However, a learning process that systematically leverages a relevant basis of evidence to support patient-oriented approaches has yet to be defined. As such, this study aims at articulating a learning process for therapy decision-making in the context of chronic conditions. The result is framework and a demonstration of its application using the Goal Attainment Scale (GAS) and synthetic data.