The material properties of naked mole-rat hyaluronan.

Hyaluronan (HA) is a key component of the extracellular matrix. Given the fundamental role of HA in the cancer resistance of the naked mole-rat (NMR), we undertook to explore the structural and soft matter properties of this species-specific variant, a necessary step for its development as a biomaterial. We examined HA extracted from NMR brain, lung, and skin, as well as that isolated from the medium of immortalised cells. In common with mouse HA, NMR HA forms a range of assemblies corresponding to a wide distribution of molecular weights. However, unique to the NMR, are highly folded structures, whose characteristic morphology is dependent on the tissue type. Skin HA forms tightly packed assemblies that have spring-like mechanical properties in addition to a strong affinity for water. Brain HA forms three dimensional folded structures similar to the macroscopic appearance of the gyri and sulci of the human brain. Lung HA forms an impenetrable mesh of interwoven folds in a morphology that can only be described as resembling a snowman. Unlike HA that is commercially available, NMR HA readily forms robust gels without the need for chemical cross-linking. NMR HA gels sharply transition from viscoelastic to elastic like properties upon dehydration or repeated loading. In addition, NMR HA can form ordered thin films with an underlying semi-crystalline structure. Given the role of HA in maintaining hydration in the skin it is plausible that the folded structures contribute to both the elasticity and youthfulness of NMR skin. It is also possible that such densely folded materials could present a considerable barrier to cell invasion throughout the tissues, a useful characteristic for a biomaterial.This work was supported by a Cancer Research UK/RCUK Multidisciplinary Project Award (C56829/A22053) to K.R., E.S. and D.F. and a Cancer Research UK Career Establishment Award (C47525/A17348) to W.T.K. F.H. and S.C. were supported by Gates Cambridge Trust scholarships

Racial differences in systemic sclerosis disease presentation: a European Scleroderma Trials and Research group study

Objectives. Racial factors play a significant role in SSc. We evaluated differences in SSc presentations between white patients (WP), Asian patients (AP) and black patients (BP) and analysed the effects of geographical locations.Methods. SSc characteristics of patients from the EUSTAR cohort were cross-sectionally compared across racial groups using survival and multiple logistic regression analyses.Results. The study included 9162 WP, 341 AP and 181 BP. AP developed the first non-RP feature faster than WP but slower than BP. AP were less frequently anti-centromere (ACA; odds ratio (OR) = 0.4, P < 0.001) and more frequently anti-topoisomerase-I autoantibodies (ATA) positive (OR = 1.2, P = 0.068), while BP were less likely to be ACA and ATA positive than were WP [OR(ACA) = 0.3, P < 0.001; OR(ATA) = 0.5, P = 0.020]. AP had less often (OR = 0.7, P = 0.06) and BP more often (OR = 2.7, P < 0.001) diffuse skin involvement than had WP.AP and BP were more likely to have pulmonary hypertension [OR(AP) = 2.6, P < 0.001; OR(BP) = 2.7, P = 0.03 vs WP] and a reduced forced vital capacity [OR(AP) = 2.5, P < 0.001; OR(BP) = 2.4, P < 0.004] than were WP. AP more often had an impaired diffusing capacity of the lung than had BP and WP [OR(AP vs BP) = 1.9, P = 0.038; OR(AP vs WP) = 2.4, P < 0.001]. After RP onset, AP and BP had a higher hazard to die than had WP [hazard ratio (HR) (AP) = 1.6, P = 0.011; HR(BP) = 2.1, P < 0.001].Conclusion. Compared with WP, and mostly independent of geographical location, AP have a faster and earlier disease onset with high prevalences of ATA, pulmonary hypertension and forced vital capacity impairment and higher mortality. BP had the fastest disease onset, a high prevalence of diffuse skin involvement and nominally the highest mortality

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Comparison of the effectiveness of radial extracorporeal shock wave therapy and supervised exercises with neuromuscular inhibition technique in lateral epicondylitis: A randomized-controlled trial

Objectives: The aim of this study was to evaluate and compare the effects of radial extracorporeal shock wave therapy (rESWT) and supervised exercises with neuromuscular inhibition (NMI) technique in improving pain, function, and grip strength in the treatment of patients with lateral epicondylitis (LE). Patients and methods: A total of 50 patients with LE (11 males, 30 females; median age: 46 years; range, 23 to 57 years) whose symptoms persisted for at least three months between February 2015 and August 2015 were included in the prospective, randomized-controlled, clinical study. The patients were divided into two groups as the rESWT group (n=25) receiving a total of three rESWT sessions (once per week with 1.8 bar pneumatic pressure, 10 Hz frequency, and with 2,000 pulses) and the exercise group (n=25) receiving supervised exercises with NMI (three times per week for three weeks). Pain and function were evaluated using Visual Analog Scale, the total Patient-Rated Tennis Elbow Evaluation, the Roles and Maudsley score, while the grip strength was evaluated using a hand dynamometer at one and three months after treatment compared to baseline. Results: A significant improvement was observed in all outcome criteria at one and three months after treatment, compared to baseline, in both the rESWT and exercise groups (p0.05). Conclusion: The rESWT seems to provide no significantly superior benefit than supervised exercises with NMI at least until the three months in the treatment of LE

Manual Lymphatic Drainage May Not Have an Additional Effect on the Intensive Phase of Breast Cancer-Related Lymphedema: A Randomized Controlled Trial

Background:Breast cancer-related lymphedema (BCRL) is a potentially debilitating complication of breast cancer and its treatment. The aim of this study was to determine the efficacy of manual lymphatic drainage (MLD) added to multilayer compressive bandage treatment in addition to an exercise program, on arm volume, subjective symptoms, upper limb functions, and health-related quality of life (HRQoL) in patients with BCRL. Methods:This prospective, randomized, single-blind interventional trial involved 54 patients with BCRL. Eligible patients were randomly allocated to a complex decongestive therapy (CDT) group (n = 27) and a standard therapy (ST) group (n = 27). Both groups participated in a 15-session program (every weekday for 3 weeks) that included compressive multilayer bandaging and exercise training. The patients who were allocated to the CDT group received MLD before bandaging in addition to the ST. Bilateral arm circumferences were measured using a measuring tape at six reference points. Subjective symptoms, such as discomfort, heaviness, and swelling severity were measured using a visual analog scale (VAS). Upper limb functions and HRQoL were assessed using the Quick Disabilities of the Arm, Shoulder and Hand (Quick-DASH) and Lymphedema Functioning, Disability, and Health Questionnaire (Lymph-ICF), respectively. Results:The excess arm volume, percent change of excess arm volume, Quick-DASH scores, and Lymph-ICF subscale scores significantly decreased (p 0.05) in terms of changes in these outcomes. The VAS discomfort (p = 0.015) and VAS heaviness (p = 0.014) scores decreased significantly in the CDT group compared to the ST group. Conclusion:The study findings indicated that both treatment approaches were effective in patients with BRCL. However, no additional effect of MLD was found with regard to percent reduction in arm volume in the intensive treatment period of BRCL

Experimental and numerical investigation of flow and alignment behavior of waste tire-derived graphene nanoplatelets in PA66 matrix during melt-mixing and injection

Homogeneous dispersion of graphene into thermoplastic polymer matrices during melt-mixing is still challenging due to its agglomeration and weak interfacial interactions with the selected polymer matrix. In this study, an ideal dispersion of graphene within the PA66 matrix was achieved under high shear rates by thermokinetic mixing. The flow direction of graphene was monitored by the developed numerical methodology with a combination of its rheological behaviors. Graphene nanoplatelets (GNP) produced from waste-tire by upcycling and recycling techniques having high oxygen surface functional groups were used to increase the compatibility with PA66 chains. This study revealed that GNP addition increased the crystallization temperature of nanocomposites since it acted as both a nucleating and reinforcing agent. Tensile strength and modulus of PA66 nanocomposites were improved at 30% and 42%, respectively, by the addition of 0.3 wt% GNP. Flexural strength and modulus were reached at 20% and 43%, respectively. In addition, the flow model, which simulates the injection molding process of PA66 resin with different GNP loadings considering the rheological behavior and alignment characteristics of GNP, served as a tool to describe the mechanical performance of these developed GNP based nanocomposites