Musculoskeletal strength, balance performance and self-efficacy in elderly Ving Tsun Chinese martial art practitioners: Implications for fall prevention

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The effects of a 6-month Tai Chi Qigong training program on temporomandibular, cervical and shoulder joint mobility and sleep problems in nasopharyngeal cancer survivors

Introduction. Nasopharyngeal cancer (NPC) survivors often sustain head–neck–shoulder impairments from conventional treatments, which could disturb sleep. This novel study aimed to examine the efficacy of Tai Chi (TC) Qigong in optimizing temporomandibular joint (TMJ), cervical, and shoulder joint mobility and reducing sleep problems in NPC survivors. Methods. Fifty-two NPC survivors participated in the study. The experimental group (n = 25) received 6 months of TC Qigong training (1.5 h/session; 4 sessions/wk including self-practice) while the control group (n = 27) received no training. Cervical side flexion and rotation, shoulder flexion and horizontal flexion range of motion (ROM), mouth opening capacity (interincisor distance), and sleep problems (Medical Outcomes Study Sleep Scale) were assessed at baseline, mid-intervention (3 months), immediately after TC Qigong training, and at 6-month follow-up. Results. Intention-to-treat analysis revealed improvement in cervical side flexion ROM only (P .008) after the TC Qigong training. Deterioration was observed in shoulder flexion ROM and mouth opening capacity in the no-training controls over time (P < .008). Sleep problems also decreased in the TC Qigong group (P < .008), and this effect was most profound during the follow-up period. In addition, improvement in cervical side flexion ROM was associated with a reduction in sleep problems in the experimental group after TC Qigong training (P < .05). Conclusions. The 6-month TC Qigong intervention improved neck mobility, maintained TMJ and shoulder joint mobility, and reduced sleep problems for NPC survivors. TC Qigong could be an effective nonpharmacological intervention for managing progressive trismus, chronic neck and shoulder hypomobility, and reducing sleep problems among NPC survivors.postprin

Characterizing the malignancy and drug resistance of cancer cells from their membrane resealing response

In this report, we showed that two tumor cell characteristics, namely the malignancy and drug-resistance status can be evaluated by their membrane resealing response. Specifically, membrane pores in a number of pairs of cancer and normal cell lines originated from nasopharynx, lung and intestine were introduced by nano-mechanical puncturing. Interestingly, such nanometer-sized holes in tumor cells can reseal ∼ 2-3 times faster than those in the corresponding normal cells. Furthermore, the membrane resealing time in cancer cell lines exhibiting resistance to several leading chemotherapeutic drugs was also found to be substantially shorter than that in their drug-sensitive counterparts, demonstrating the potential of using this quantity as a novel marker for future cancer diagnosis and drug resistance detection. Finally, a simple model was proposed to explain the observed resealing dynamics of cells which suggested that the distinct response exhibited by normal, tumor and drug resistant cells is likely due to the different tension levels in their lipid membranes, a conclusion that is also supported by direct cortical tension measurement.published_or_final_versio

Crystal Structures of Two Aminoglycoside Kinases Bound with a Eukaryotic Protein Kinase Inhibitor

Antibiotic resistance is recognized as a growing healthcare problem. To address this issue, one strategy is to thwart the causal mechanism using an adjuvant in partner with the antibiotic. Aminoglycosides are a class of clinically important antibiotics used for the treatment of serious infections. Their usefulness has been compromised predominantly due to drug inactivation by aminoglycoside-modifying enzymes, such as aminoglycoside phosphotransferases or kinases. These kinases are structurally homologous to eukaryotic Ser/Thr and Tyr protein kinases and it has been shown that some can be inhibited by select protein kinase inhibitors. The aminoglycoside kinase, APH(3′)-IIIa, can be inhibited by CKI-7, an ATP-competitive inhibitor for the casein kinase 1. We have determined that CKI-7 is also a moderate inhibitor for the atypical APH(9)-Ia. Here we present the crystal structures of CKI-7-bound APH(3′)-IIIa and APH(9)-Ia, the first structures of a eukaryotic protein kinase inhibitor in complex with bacterial kinases. CKI-7 binds to the nucleotide-binding pocket of the enzymes and its binding alters the conformation of the nucleotide-binding loop, the segment homologous to the glycine-rich loop in eurkaryotic protein kinases. Comparison of these structures with the CKI-7-bound casein kinase 1 reveals features in the binding pockets that are distinct in the bacterial kinases and could be exploited for the design of a bacterial kinase specific inhibitor. Our results provide evidence that an inhibitor for a subset of APHs can be developed in order to curtail resistance to aminoglycosides

SDOCT Imaging to Identify Macular Pathology in Patients Diagnosed with Diabetic Maculopathy by a Digital Photographic Retinal Screening Programme

INTRODUCTION: Diabetic macular edema (DME) is an important cause of vision loss. England has a national systematic photographic retinal screening programme to identify patients with diabetic eye disease. Grading retinal photographs according to this national protocol identifies surrogate markers for DME. We audited a care pathway using a spectral-domain optical coherence tomography (SDOCT) clinic to identify macular pathology in this subset of patients. METHODS: A prospective audit was performed of patients referred from screening with mild to moderate non-proliferative diabetic retinopathy (R1) and surrogate markers for diabetic macular edema (M1) attending an SDOCT clinic. The SDOCT images were graded by an ophthalmologist as SDOCT positive, borderline or negative. SDOCT positive patients were referred to the medical retina clinic. SDOCT negative and borderline patients were further reviewed in the SDOCT clinic in 6 months. RESULTS: From a registered screening population of 17 551 patients with diabetes mellitus, 311 patients met the inclusion criteria between (March 2008 and September 2009). We analyzed images from 311 patients' SDOCT clinic episodes. There were 131 SDOCT negative and 12 borderline patients booked for revisit in the OCT clinic. Twenty-four were referred back to photographic screening for a variety of reasons. A total of 144 were referred to ophthalmology with OCT evidence of definite macular pathology requiring review by an ophthalmologist. DISCUSSION: This analysis shows that patients with diabetes, mild to moderate non-proliferative diabetic retinopathy (R1) and evidence of diabetic maculopathy on non-stereoscopic retinal photographs (M1) have a 42.1% chance of having no macular edema on SDOCT imaging as defined by standard OCT definitions of DME when graded by a retinal specialist. SDOCT imaging is a useful adjunct to colour fundus photography in screening for referable diabetic maculopathy in our screening population

Stability of domain structures in multi-domain proteins

Multi-domain proteins have many advantages with respect to stability and folding inside cells. Here we attempt to understand the intricate relationship between the domain-domain interactions and the stability of domains in isolation. We provide quantitative treatment and proof for prevailing intuitive ideas on the strategies employed by nature to stabilize otherwise unstable domains. We find that domains incapable of independent stability are stabilized by favourable interactions with tethered domains in the multi-domain context. Stability of such folds to exist independently is optimized by evolution. Specific residue mutations in the sites equivalent to inter-domain interface enhance the overall solvation, thereby stabilizing these domain folds independently. A few naturally occurring variants at these sites alter communication between domains and affect stability leading to disease manifestation. Our analysis provides safe guidelines for mutagenesis which have attractive applications in obtaining stable fragments and domain constructs essential for structural studies by crystallography and NMR

Id-1 stimulates cell proliferation through activation of EGFR in ovarian cancer cells

Increased EGFR (epidermal growth factor receptor) expression has been reported in many types of human cancer and its levels are positively associated with advanced cancers. Recently, upregulation of Id-1 (inhibitor of differentiation or DNA binding) protein was found in over 70% of ovarian cancer samples and correlated with poor survival of ovarian cancer patients. However, the molecular mechanisms responsible for the role of Id-1 in ovarian cancer are not clear. The aim of this study was to investigate the effect of Id-1 on ovarian cancer proliferation and its association with the EGFR pathway. To achieve this, we transfected an Id-1 expression vector into three ovarian cancer cell lines and examined cell proliferation rate by flow cytometry and bromodeoxyuridine staining. We found that ectopic Id-1 expression led to increased cell proliferation demonstrated by increased BrdU incorporation rate and S-phase fraction. The Id-1-induced cell growth was associated with upregulation of EGFR at both transcriptional and protein levels. In contrast, inactivation of Id-1 through transfection of an Id-1 antisense vector resulted in downregulation of EGFR. Our results indicate that increased Id-1 in ovarian cancer cells may promote cancer cell proliferation through upregulation of EGFR. Our findings also implicate that Id-1 may be a potential target for the development of novel strategies in the treatment of ovarian cancer. © 2004 Cancer Research UK.link_to_OA_fulltex

The association between retinal vascular geometry changes and diabetic retinopathy and their role in prediction of progression: an exploratory study

Background: The study describes the relationship of retinal vascular geometry (RVG) to severity of diabetic retinopathy (DR), and its predictive role for subsequent development of proliferative diabetic retinopathy (PDR). Methods. The research project comprises of two stages. Firstly, a comparative study of diabetic patients with different grades of DR. (No DR: Minimal non-proliferative DR: Severe non-proliferative DR: PDR) (10:10: 12: 19). Analysed RVG features including vascular widths and branching angles were compared between patient cohorts. A preliminary statistical model for determination of the retinopathy grade of patients, using these features, is presented. Secondly, in a longitudinal predictive study, RVG features were analysed for diabetic patients with progressive DR over 7 years. RVG at baseline was examined to determine risk for subsequent PDR development. Results: In the comparative study, increased DR severity was associated with gradual vascular dilatation (p = 0.000), and widening of the bifurcating angle (p = 0.000) with increase in smaller-child-vessel branching angle (p = 0.027). Type 2 diabetes and increased diabetes duration were associated with increased vascular width (p = <0.05 In the predictive study, at baseline, reduced small-child vascular width (OR = 0.73 (95 CI 0.58-0.92)), was predictive of future progression to PDR. Conclusions: The study findings suggest that RVG alterations can act as novel markers indicative of progression of DR severity and establishment of PDR. RVG may also have a potential predictive role in determining the risk of future retinopathy progression. © 2014 Habib et al.; licensee BioMed Central Ltd