Patients' and therapists' perspective of integrating home and family work roles into rehabilitation following distal radius fracture.

PURPOSE: To explore distal radius fracture (DRF) patients' and hand therapist/occupational therapist/physiotherapists' perceptions of integrating home and family work roles (HFWR) into rehabilitation. METHODS: Eighteen patients and eleven therapists completed a semi-structured telephone interview three months after DRF. Reflexive thematic analysis of the interviews and triangulation of patients' and therapists' themes was performed. RESULTS: The patient interview yielded five themes: the experience of rehabilitation; predetermined expectations of rehabilitation; incorporating HFWR into therapy sessions; varying patient needs for addressing HFWR; and determination to return to valued activities drives behavioral choices. The therapists' interview yielded five themes: The challenges in integrating HFWR into rehabilitation; HFWR addressed when brought up by a patient; working context and referral sources influence the rehabilitation plan; rehabilitation is not explicitly tailored according to sex and gender; and utilizing HFWR as a rehabilitation strategy is perceived beneficial. CONCLUSIONS: Patients have predetermined rehabilitation expectations primarily focused on mobility and strengthening exercises. Therapists and patients agree that adapting home and family work roles is beneficial but was not a major focus for either therapists' or patients' expectations during therapy. An unfavourable environment, patient budget constraints, and limited time were identified as challenges to integrating family roles.

Therapists should proactively discuss and address home and family work roles with patients with distal radius fractures when appropriate.Therapists should tailor rehabilitation plans according to the individual needs and expectations of the patients.Hospitals and clinics should create an environment conducive to addressing home and family work roles, and resources should be allocated for comprehensive rehabilitation programmes.

Tinospora cordifolia chloroform extract inhibits LPS-induced inflammation via NF-κB inactivation in THP-1cells and improves survival in sepsis.

BACKGROUND: Tinospora cordifolia (Willd).Miers is a perennial climbing medicinal shrub that has been traditionally used for the treatment of chronic inflammatory ailments. Our previous pre- clinical studies on anti-inflammatory effects, proved that the chloroform extract of T. cordifolia (CETC) suppressed the LPS induced up-regulation of pro-inflammatory biomarkers, hence, further follow up study was carried out to evaluate whether CETC can exhibit a protective effect against LPS induced lethal endotoxemia in vivo and also to analyze the impact of CETC pre-treatment on the secretion of pro-inflammatory cytokines in vitro by THP-1 cells. METHODS: To corroborate our previous preclinical studies on inflammation, we investigated the mechanism of the anti-inflammatory effect of T. cordifolia on THP-cells which were pre-incubated with CETC (30 min) and stimulated subsequently with LPS (1 µg/ml) for 20 h. Levels as well as gene expressions of various cytokines were compared with that of LPS alone incubated cells. Alongside, in vivo oral anti-inflammatory efficacy against LPS induced endotoxemia study was effectuated, wherein rats were administered with CETC 48, 24, 12 and 1 h prior to the injection of LPS and the survival of rats were monitored upto 10 days. Cytokine levels were quantified by ELISA. Nitrite levels were measured using Griess reagent. Expression of pro-inflammatory proteins was inspected in rat tissues by histochemical and immuno -histochemical examinations. RESULTS: CETC was able to down-regulate the up-regulation of pro-inflammatory biomarkers in THP-1 macrophages though blockade of NF-κB nuclear translocation and could improve the survival rate during endotoxemic episodes with a marked suppression of the tissue expression of pro-inflammatory proteins. CONCLUSION: These findings concomitantly reveal the anti-inflammatory mechanism of CETC and support us to move forward for the development of drugs against disorders resulting from deregulated immune reactions.

What Factors Contribute to Falls-Related Distal Radius Fracture?

Objective: This mixed methods study analyzed the factors that led to a fall in a cohort of patients with distal radius fracture (DRF). Methods: A sample of 1,453 patients (430 men; 1,023 women; age range: 18-89 years) supplemented by new interview data from 29 patients (19 women) were examined. Chi-square and descriptive analysis of quantitative data and descriptive thematic analysis of qualitative data were compared to determine data convergence and divergence. Results: A higher number of DRF were observed in the 45- to 64-year-old group (44%), employed people (48%), in winter months (41%), and in low-energy fractures (75%). Themes emerged from qualitative data on the cause of the fracture, including environmental factors, behavioral factors, physical factors, and sports activities. Conclusion: Reasons for DRF are multifactorial. Preventive strategies with an emphasis on environmental and behavioral factor modifications are likely to decrease the number of DRF.

Author Correction: Immune regulation by oral tolerance induces alternate activation of macrophages and reduces markers of plaque destabilization in Apobtm2Sgy/Ldlrtm1Her/J mice.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Evaluation of the anti-inflammatory activity of Tinospora cordifolia (Willd.) Miers chloroform extract - a preclinical study.

OBJECTIVES: Tinospora cordifolia (Willd.) Miers is an inevitable ingredient of Ayurvedic rasayanas for the treatment of disorders with unregulated inflammation. However, studies regarding the mechanism of anti-inflammatory potential of this plant at the molecular level are lacking. METHODS: In vitro evaluations were conducted in RAW264.7 macrophages which were preincubated with chloroform extract of T. cordifolia (CETC) and subsequently stimulated with LPS. The expressions of COX-2, TNF-α and iNOS genes were analysed by SQRT-PCR and Western blot, cytokines (IL-6, IL-1ß and PGE2 ) levels by ELISA, NF-κB activation and p38 MAPK phosphorylation by Immunoblot and confocal imaging. Anti-inflammatory potential of CETC was validated further in a rat model of carrageenan-induced hind paw edema. Phytochemical characterisation was carried out using the HPLC technique. KEY FINDINGS: The LPS-induced upregulation of proinflammatory biomarkers was significantly prevented by CETC, without inhibiting COX-1. CETC- and LPS-incubated cells showed reduced phosphorylated p38 MAPK levels, and higher levels NF-κB were retained in cytoplasm. Rats pretreated with CETC showed a statistically significant decrease in paw oedema (P ≤ 0.05), and HPLC characterisation detected stigmasterol and ß-sitosterol. The LD50 of CETC lies above 2000 mg/Kg body weight. CONCLUSIONS: These findings encourage us strongly to focus on CETC to develop anti-inflammatory drugs with lower degree of inhibition to the constitutively expressing COX-1.

Preparation of an efficient and safe polymeric-magnetic nanoparticle delivery system for sorafenib in hepatocellular carcinoma.

AIMS: Superparamagnetic iron oxide nanoparticles (SPIONs), as drug delivery vehicles, offer to eliminate the concerns associated with hydrophobic anti-cancer agents. The current study was intended to fabricate a SPION based delivery system for sorafenib that can simultaneously enable targeted delivery of sorafenib and expand its therapeutic index against hepatocellular carcinoma (HCC). MAIN METHODS: Co-precipitation and physical entrapment methods were employed for the synthesis of sorafenib loaded PVA coated SPIONs. Physicochemical characterizations were done using TEM, XRD, FTIR, Raman spectra and VSM measurements. The superior activity of nanoconjugate was demonstrated by AO/EB staining, FACS, immunofluorescence and Western blot. The safety of the sorafenib conjugated nanoparticles were verified in Wistar rats. KEY FINDINGS: The synthesized nanoparticles were in the size range of 5-15 nm. The adsorption of PVA to the SPIONs and the conjugation of sorafenib to the nanocarrier were confirmed by XRD, FTIR and Raman spectra analyses. VSM study ascertained the superparamagnetic nature of the nanoconjugate. Cellular uptake studies suggested its efficient entrapment in HepG2 cells. MTT assay showed that the cytotoxicity of sorafenib loaded PVA/SPIONs was comparable or higher than free sorafenib. The activation of apoptosis and autophagy pathways in HepG2 by the nanoconjugate was evidenced. Acute toxicity testing in Wistar rats supported the safe administration of the nanoconjugate and established its localization in animal tissues by Perl's Prussian Blue reaction. SIGNIFICANCE: The novel combination of sorafenib with PVA/SPIONs showed better anticancer efficiency than free sorafenib demonstrative of its potential in cancer chemotherapy.

Rapid assessment of viable but non-culturable Bacillus coagulans MTCC 5856 in commercial formulations using Flow cytometry.

Accurate enumeration of bacterial count in probiotic formulation is imperative to ensure that the product adheres to regulatory standards and citation in consumer product label. Standard methods like plate count, can enumerate only replicating bacterial population under selected culture conditions. Viable but non culturable bacteria (VBNC) retain characteristics of living cells and can regain cultivability by a process known as resuscitation. This is a protective mechanism adapted by bacteria to evade stressful environmental conditions. B. coagulans MTCC 5856(LactoSpore®) is a probiotic endospore which can survive for decades in hostile environments without dividing. In the present study, we explored the use of flow cytometry to enumerate the viable count of B. coagulans MTCC 5856 under acidic and alkaline conditions, high temperature and in commercial formulations like compressed tablets and capsules. Flow cytometry (FCM) was comparable to plate count method when the spores were counted at physiological conditions. We show that VBNC state is induced in B. coagulans MTCC 5856by high temperature and acidic pH. The cells get resuscitated under physiological conditions and FCM was sensitive to detect the VBNC spores. Flow cytometry showed excellent ability to assess the viable spore count in commercial probiotic formulations of B. coagulans MTCC 5856. The results establish Flow cytometry as a reliable method to count viable bacteria in commercial probiotic preparations. Sporulation as well as existence as VBNC could contribute to the extreme stability of B. coagulans MTCC 5856.

Immune regulation by oral tolerance induces alternate activation of macrophages and reduces markers of plaque destabilization in Apobtm2Sgy/Ldlrtm1Her/J mice.

Atherosclerosis is the leading cause for cardiovascular mortality. We determined the effect of multi-antigenic construct expressing three peptides AHC (ApoB100, HSP60 and outer membrane protein of chlamydia pneumonia) in stabilizing advanced atherosclerosis in Apobtm2Sgy/Ldlrtm1Her/J mice. Atherosclerosis was induced by feeding high fat diet (HFD) to mice for 10 weeks, followed by five oral dosing with purified AHC or ovalbumin on alternate days and continued on HFD for another 10 weeks. Tolerance was associated with significantly higher numbers of regulatory T cells both in aortic sinus and spleen with higher mRNA expression of CTLA4 (3 fold), Foxp3 (1.4 folds) and TGF-ß (1.62) in aorta. Tregs cells were found to induce alternate activation of macrophages to M2 phenotype, with a reduction in plaque inflammation. AHC treatment showed evidence of plaque stabilization as observed by reduction in plaque necrosis in aortic sinus (35.8%) and in brachiocephalic artery (26%), with reduced expression of Tissue factor and MMP9. Macrophage apoptosis was reduced and collagen content was enhanced by treatment. Our results suggest that tolerance to atherogenic peptides increases regulatory T cells which activate M2 macrophages, prevent T cell proliferation and reduce plaque destabilization and inflammatory markers thus providing evidences for plaque stabilization in mice with advanced atherosclerosis.

Oral administration of recombinant Mycobacterium smegmatis expressing a tripeptide construct derived from endogenous and microbial antigens prevents atherosclerosis in ApoE(-/-) mice.

INTRODUCTION: Immunotherapy by inducing oral tolerance to atherogenic self-antigens is gaining importance as an alternative treatment modality for atherosclerosis. The use of live bacterial vectors to express the recombinant antigen in vivo will obviate the need for large-scale purification of recombinant protein and may also augment the efficacy of oral tolerance induction. AIM: The objective of the study was to explore the use of recombinant Mycobacterium smegmatis as a live vector for oral delivery of antigens to induce immune tolerance. METHOD AND RESULTS: We developed a M. smegmatis vector to secrete a recombinant tripeptide construct (AHC; peptides from Apolipoprotein B, Heat-shock protein 60 and Chlamydia pneumoniae outer membrane protein) expressed in a dendroaspin protein scaffold in pJH154 background. Immune response and oral tolerance to the cloned peptides were studied in C57/BL6 mice. The efficacy of this live vaccine to control atherosclerosis was studied in ApoE(-/-) knockout mice in C57/BL6 background. Oral administration of M. smegmatis secreting the cloned AHC antigen was found to induce tolerance to cloned protein and reduce the development of atherosclerosis by 24.0% compared to control. Protection against atherosclerosis was associated with increase in expression of regulatory T cell-associated markers including CTLA4 (1.8-fold), Foxp3 (2.6-fold), TGF-ß (2.8-fold), IL10 (2.9-fold), and reduction in lipids, macrophage infiltration, and expression of inflammatory mediators in aorta. CONCLUSIONS: Our results suggest that M. smegmatis can be developed as an oral carrier of recombinant proteins to treat inflammatory autoimmune diseases.

Regulating Inflammatory Immune Response to Atherogenic Antigens Prevents Development and Progression of Atherosclerosis in New Zealand White Rabbits.

BACKGROUND: Inflammatory immune response to atherogenic self-antigens plays an important role in the development of atherosclerosis. We evaluated the role of oral tolerance to three peptides in controlling atherosclerosis in New Zealand white rabbits. METHODS: Peptides derived from apolipoprotein B (ApoB), heat shock protein 60, and outer membrane protein from Chlamydia pneumoniae were expressed as part of the dendroaspin protein scaffold (AHC). Groups of 3-month-old rabbits were dosed orally with purified AHC protein either before the onset of disease or 2 months after inducing atherosclerosis; they were euthanized at the age of 7 months to study disease development and progression. RESULTS: Oral treatment with AHC resulted in a marked increase in regulatory T cells in the lymphoid organs and reduced the development and progression of atherosclerosis by 48.6% and 28.4%, respectively (P < 0.05). Oral tolerance decreased plaque inflammation, enhanced expression of anti-inflammatory and regulatory markers in the aorta, and attenuated the adaptive immune response to self-antigens. AHC treatment in rabbits with established disease significantly decreased vascular cell adhesion molecule 1 (VCAM-1) (6.2 fold) and monocyte chemoattractant protein-1(MCP-1) (3 fold) expression and reduced the infiltration of macrophages into the aorta. Collagen content and the smooth muscle cell-to-macrophage ratio were higher in treated animals, whereas markers of plaque vulnerability, including matrix metalloproteinase expression, were reduced. CONCLUSIONS: Our results suggest that oral tolerance to multiantigenic AHC molecule restores the immune balance and induces markers of plaque stability in rabbits.

Hypercholesterolemia Induced Immune Response and Inflammation on Progression of Atherosclerosis in Apob(tm2Sgy) Ldlr(tm1Her)/J Mice.

The effect of hypercholesterolemia induced immune response and inflammation on progression of atherosclerosis in ApoB(tm25gy) LDLr(tm1Her) mice, expressing only ApoB100 and deficient in the low density lipoprotein (LDL) receptor, thus closely resembling human cholesterol transport is not well defined. Atherosclerosis was induced by a high cholesterol diet and its progression was studied at 8, 14 and 20 weeks. Antibody response was determined by ELISA. Lymphocytes in spleen and aortic expression of inflammatory markers were studied by flow cytometry, and immunohistochemistry respectively. A rapid increase in plasma LDL levels in the first 8 weeks was followed by the exponential development of atherosclerosis between 8 and 14 weeks. Progression of the disease was accompanied by an accumulation of macrophages and increased expression of IL17 and IFN-γ in the aorta. Hypercholesterolemia resulted in increased immune response to modified lipids and aortic inflammation, with an expansion of Th17 cells in the spleen. Progression of atherosclerosis showed a positive correlation (r = 0.84, P < 0.001) with Th17 cells and a negative correlation with Treg cells (r = 0.83, P < 0.001). IgM antibodies to Ox-LDL and Th17 cells in spleen showed greatest association with disease development. Our results suggest that anti Ox-LDL IgM antibodies, Th17 cells could be developed as a potential marker to study disease progression and to study the effect of therapeutic regulation of inflammation.

Oral dosing with multi-antigenic construct induces atheroprotective immune tolerance to individual peptides in mice.

Inflammatory immune response to self-antigens plays an important role in the development of atherosclerosis. Restoring immune tolerance to self-proteins reduces the pro-inflammatory response. We previously showed that oral tolerance to a combination of two peptides is atheroprotective. In the present study we expressed epitopes from apolipoprotein B 100 (ApoB), human heat shock protein (HSP60) and Chlamydia pneumonia outer membrane protein (Cpn) in a single protein scaffold and used this multi-antigenic construct to induce tolerance to individual peptides by oral route in ApoBtm2Sgy/Ldlrtm1Her/J mice. Antigen specific tolerance to individual peptides was observed in treated animals as seen by an increase in regulatory T cells. Tolerance to the peptides resulted in a 46.5% (p=0.002) reduction in the development of atherosclerosis compared with control. Atheroprotection was associated with a significant (p<0.05) decrease in plaque inflammation and an increase in the expression of immune regulatory markers in the aorta. CD11c+ cells coexpressing CD11b and CD103 increased in lymphoid organs and were found to activate regulatory T cells and reduce effector T-cell response. Adoptive transfer of CD11c+ cells was atheroprotective. Our results suggest that atheroprotection by oral tolerance to a multi-antigenic construct is mediated by antigen specific regulatory T cells and CD11c+ cells with immune regulatory properties.