Does Phonophoresis Using NSAIDs Reduce Osteoarthritis Knee Pain?

Objective: The objective of this selective EBM review is to determine whether or not phonophoresis using NSAIDs reduces osteoarthritis knee pain. Study Design: Systematic review of three double-blind randomized controlled trials published between the years 2013 and 2018. Data Sources: Published peer-reviewed articles obtained through PubMed and Cochrane Collaboration. Articles were selected based on relevance to my clinical question and if they included patient-oriented outcomes. Outcomes Measured: Pain severity was self-reported by patients using a visual analog scale (VAS) on a continuum of 0-100; 0 representing no pain at all and 100 representing the worst pain imaginable. Participants in all three studies reported pain scores at baseline and after completing 2 weeks of treatment. Results: The study conducted by Luksurapan et al. showed a mean change from baseline of 67%, a mean of between group difference of 14.73 +/- 5.78, and a P-value of 0.009.1 The study conducted by Monisha et al. showed a mean change from baseline of 70% and a P-value \u3c 0.00.2 The study conducted by Oktayoglu et al. showed a mean change from baseline of 23 and a Pvalue of \u3c 0.05.3 Conclusion: All three studies in this EBM review demonstrated reduction of mild to moderate osteoarthritis knee pain with the use of phonophoresis using NSAIDs. Additional research may be indicated to further evaluate treatment outcomes with larger and more diverse patient populations, as well as long-term effects of treatment

Interferon-gamma/Hypoxia Primed Mesenchymal Stem Cells for an Improved Immunosuppressive Cell Therapy

Mesenchymal stem cells (MSCs) are promising candidates for treating diverse inflammatory disorders due to their capacity to be immunosuppressive. This phenotype is not present at baseline but develops in response to instructive cues. To date, clinical trials use cells grown in basic culture conditions, anticipating the cells will acquire a useful phenotype in response to in vivo cues. This strategy has failed to produce any FDA approved therapies, based on inconsistent efficacy. This thesis explores whether priming MSCs prior to administration can lead to a more uniformly therapeutic phenotype, and it details the design of an optimal in vitro priming regimen. Because interferon gamma (IFN-γ) is known to induce an anti-inflammatory state in MSCs, hypoxia can confer survival benefits, and both cues coexist in known situations of immune tolerance, we hypothesized dual IFN-γ/hypoxia priming would yield a superior immunosuppressive MSC therapy. We show that priming MSCs with hypoxia or IFN-γ alone improves their ability to inhibit T-cells in vitro, but combining these cues results in additive improvements. We next characterize the proteomic and metabolomic changes MSCs undergo when exposed to single or dual IFN-γ/hypoxia priming. While IFN-γ induces MSCs to suppress inflammation and fibrosis, hypoxia leads to cell adaptations to low oxygen, including upregulation of proteins involved in anaerobic metabolism, autophagy, angiogenesis, and cell migration. Dual priming results in additive effects, with many instances of synergy. Finally, we show initial evidence that dual primed MSCs are better able to inhibit disease progression in a mouse model of acute graft-vs-host disease (GvHD)

Distance-dependent increase in quantum dot photoluminescence by molecular beacons containing dark quenchers

Förster resonance energy transfer is a fluorescence-based technique currently used for numerous biotechnological applications. Although organic fluorophores have traditionally been employed for this method, quantum dots have many unique optical characteristics that make them attractive candidates for this usage. As the present understanding of how quantum dots behave as energy donors is incomplete, it is necessary to conduct further studies towards the physicochemical nature of this phenomenon. Here, we attempt to assess the distance- dependency for quantum dot-based energy transfer by spacing dark quenchers at increasing distances from these nanoparticles’ surfaces.  We describe a surprising finding that quenchers can actually increase the average fluorescence intensity of quantum dot solutions, and we propose a theoretical explanation, which may allow others to more accurately conduct quantitative studies in the future

Engineering of human cardiac muscle electromechanically matured to an adult-like phenotype

Author ManuscriptThe application of tissue-engineering approaches to human induced pluripotent stem (hiPS) cells enables the development of physiologically relevant human tissue models for in vitro studies of development, regeneration, and disease. However, the immature phenotype of hiPS-derived cardiomyocytes (hiPS-CMs) limits their utility. We have developed a protocol to generate engineered cardiac tissues from hiPS cells and electromechanically mature them toward an adult-like phenotype. This protocol also provides optimized methods for analyzing these tissues' functionality, ultrastructure, and cellular properties. The approach relies on biological adaptation of cultured tissues subjected to biomimetic cues, applied at an increasing intensity, to drive accelerated maturation. hiPS cells are differentiated into cardiomyocytes and used immediately after the first contractions are observed, when they still have developmental plasticity. This starting cell population is combined with human dermal fibroblasts, encapsulated in a fibrin hydrogel and allowed to compact under passive tension in a custom-designed bioreactor. After 7 d of tissue formation, the engineered tissues are matured for an additional 21 d by increasingly intense electromechanical stimulation. Tissue properties can be evaluated by measuring contractile function, responsiveness to electrical stimuli, ultrastructure properties (sarcomere length, mitochondrial density, networks of transverse tubules), force-frequency and force-length relationships, calcium handling, and responses to β-adrenergic agonists. Cell properties can be evaluated by monitoring gene/protein expression, oxidative metabolism, and electrophysiology. The protocol takes 4 weeks and requires experience in advanced cell culture and machining methods for bioreactor fabrication. We anticipate that this protocol will improve modeling of cardiac diseases and testing of drugs.NIBIB and NCATS grant EB17103 (G.V.-N.); NIBIB, NCATS, NIAMS, NIDCR, and NIEHS grant EB025765 (G.V.-N.); NHLBI grants HL076485 (G.V.-N.) and HL138486 (M.Y.); NSF grant 16478 (G.V.-N.); the University of Minho MD/PhD program (D.T.); a Japan Society for the Promotion of Science fellowship (K.M.); and the Columbia University Stem Cell Initiative (L.S., M.Y.

Functional vascularized lung grafts for lung bioengineering

End-stage lung disease is the third leading cause of death worldwide, accounting for 400,000 deaths per year in the United States alone. To reduce the morbidity and mortality associated with lung disease, new therapeutic strategies aimed at promoting lung repair and increasing the number of donor lungs available for transplantation are being explored. Because of the extreme complexity of this organ, previous attempts at bioengineering functional lungs from fully decellularized or synthetic scaffolds lacking functional vasculature have been largely unsuccessful. An intact vascular network is critical not only for maintaining the blood-gas barrier and allowing for proper graft function but also for supporting the regenerative cells. We therefore developed an airway-specific approach to removing the pulmonary epithelium, while maintaining the viability and function of the vascular endothelium, using a rat model. The resulting vascularized lung grafts supported the attachment and growth of human adult pulmonary cells and stem cell–derived lung-specified epithelial cells. We propose that de-epithelialization of the lung with preservation of intact vasculature could facilitate cell therapy of pulmonary epithelium and enable bioengineering of functional lungs for transplantation

Parenthood in survivors of Hodgkin lymphoma: an EORTC-GELA general population case-control study.

Contains fulltext : 108966.pdf (publisher's version ) (Open Access)PURPOSE: We investigated the impact of Hodgkin lymphoma (HL) on parenthood, including factors influencing parenthood probability, by comparing long-term HL survivors with matched general population controls. PATIENTS AND METHODS: A Life Situation Questionnaire was sent to 3,604 survivors treated from 1964 to 2004 in successive clinical trials. Responders were matched with controls (1:3 or 4) for sex, country, education, and year of birth (10-year groups). Controls were given an artificial date of start of treatment equal to that of their matched case. The main end point was presence of biologic children after treatment, which was evaluated by using conditional logistic regression analysis. Logistic regression analysis was used to analyze factors influencing spontaneous post-treatment parenthood. RESULTS: In all, 1,654 French and Dutch survivors were matched with 6,414 controls. Median follow-up was 14 years (range, 5 to 44 years). After treatment, the odds ratio (OR) for having children was 0.77 (95% CI, 0.68 to 0.87; P < .001) for survivors compared with controls. Of 898 survivors who were childless before treatment, 46.7% achieved post-treatment parenthood compared with 49.3% of 3,196 childless controls (OR, 0.87; P = .08). Among 756 survivors with children before treatment, 12.4% became parents after HL treatment compared with 22.2% of 3,218 controls with children before treatment (OR, 0.49; P < .001). Treatment with alkylating agents, second-line therapy, and age older than 35 years at treatment appeared to reduce the chances of spontaneous post-treatment parenthood. CONCLUSION: Survivors of HL had slightly but significantly fewer children after treatment than matched general population controls. The difference concerned only survivors who had children before treatment and appears to have more personal than biologic reasons. The chance of successful post-treatment parenthood was 76%

Disordered T cell-B cell interactions in autoantibody-positive inflammatory arthritis

T peripheral helper (Tph) cells, identified in the synovium of adults with seropositive rheumatoid arthritis, drive B cell maturation and antibody production in non-lymphoid tissues. We sought to determine if similarly dysregulated T cell-B cell interactions underlie another form of inflammatory arthritis, juvenile oligoarthritis (oligo JIA). Clonally expanded Tph cells able to promote B cell antibody production preferentially accumulated in the synovial fluid (SF) of oligo JIA patients with antinuclear antibodies (ANA) compared to autoantibody-negative patients. Single-cell transcriptomics enabled further definition of the Tph gene signature in inflamed tissues and showed that Tph cells from ANA-positive patients upregulated genes associated with B cell help to a greater extent than patients without autoantibodies. T cells that co-expressed regulatory T and B cell-help factors were identified. The phenotype of these Tph-like Treg cells suggests an ability to restrain T cell-B cell interactions in tissues. Our findings support the central role of disordered T cell-help to B cells in autoantibody-positive arthritides

Patient characteristics related to the need for peer support in rehabilitation after acquired brain injury: a prospective cohort study in the Netherlands

OBJECTIVE: Peer support facilitates patients and caregivers in adjusting to long-term disabilities. This study aimed to determine which patient characteristics are related to need for peer support during rehabilitation after acquired brain injury (ABI) and investigate factors that explain whether peer support is perceived as meaningful or not. DESIGN: A prospective cohort study over a period of 17 months following patients with ABI during inpatient rehabilitation in the Netherlands. Multivariable logistic modelling was applied to identify patient and intervention characteristics that were related to (1) need for peer support and (2) whether or not peer support was perceived as meaningful. Additional information on duration and subjects of conversation was reported. SETTING: Peer support was provided during inpatient rehabilitation. PARTICIPANTS: 120 patients with ABI >/=18 years were included and assessed at admission, 94 patients were assessed at discharge. Seventy-three percent (n=88) expressed a need for peer support and at discharge 76.6% (n=72) perceived contact as meaningful. RESULTS: Non-Western and single patients perceived a significantly higher need for peer support. Patients younger than 60 and those with time between ABI and discharge of >3 months perceived their contact significantly more meaningful. CONCLUSIONS: Results provide more insight into characteristics of patients with ABI who may benefit from peer support during inpatient rehabilitation. Optimal dosage, length of contact, rehabilitation phase and strategy for the provision of peer support should be investigated as well as the effects for ABI survivors on outcomes such as coping, self-efficacy, depression and health-related quality of life