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IntroductionFollowing early cell specification and tenocyte differentiation at the sites of future tendons, very little is known about how tendon maturation into robust load-bearing tissue is regulated. Between embryonic day (E)16 and E18 in the chick, there is a rapid change in mechanical properties which is dependent on normal embryo movement. However, the tissue, cellular and molecular changes that contribute to this transition are not well defined.MethodsHere we profiled aspects of late tendon development (collagen fibre alignment, cell organisation and Yap pathway activity), describing changes that coincide with tissue maturation. We compared effects of rigid (constant static loading) and flaccid (no loading) immobilisation to gain insight into developmental steps influenced by mechanical cues.ResultsWe show that YAP signalling is active and responsive to movement in late tendon. Collagen fibre alignment increased over time and under static loading. Cells organise into end-to-end stacked columns with increased distance between adjacent columns, where collagen fibres are deposited; this organisation was lost following both types of immobilisation.DiscussionWe conclude that specific aspects of tendon maturation require controlled levels of dynamic muscle-generated stimulation. Such a developmental approach to understanding how tendons are constructed will inform future work to engineer improved tensile load-bearing tissues.

Nutritional intake during pregnancy can affect gestational length, fetal development, and impact postnatal growth and health in offspring. Perturbations in maternal nutrition with either an excess or deficiency in nutrients during pregnancy may have harmful effects on the offspring’s development and increase the risk of developing chronic diseases later in life. In pregnancy, nutrients transfer from the mother to the fetus via the placenta. Essential fatty acids, linoleic acid (LA) and alpha linoleic acid (ALA), can only be obtained in the diet. In Western countries, the ratio of LA and ALA in the diet has increased dramatically in recent decades. Some animal and human studies have found a correlation between maternal intake of LA and birth weight; however, the association varies. In contrast, some human studies have demonstrated inconclusive findings regarding the correlation between cord blood levels of LA and birth outcomes. In addition, high dietary LA intake in animal studies in pregnancy increased the production of inflammatory markers such as prostaglandins, leukotrienes, cytokines, and tumour necrosis factor-alpha. This review aims to highlight the effect of high dietary LA intake during pregnancy on birth outcomes, obesity, maternal inflammatory markers, and the transfer of fatty acids across the placenta.

BackgroundThe demand for orthopedic specialist consultations for patients with osteoarthritis in public hospitals is high and continues to grow. Lengthy waiting times are increasingly affecting patients from low socioeconomic and culturally and linguistically diverse backgrounds who are more likely to rely on public health care. ObjectiveThis study aimed to co-design a digital health intervention for patients with OA who are waiting for an orthopedic specialist consultation at a public health service, which is located in local government areas (LGAs) of identified social and economic disadvantage. MethodsThe stakeholders involved in the co-design process included the research team; end users (patients); clinicians; academic experts; senior hospital staff; and a research, design, and development agency. The iterative co-design process comprised several key phases, including the collation and refinement of evidence-based information by the research team, with assistance from academic experts. Structured interviews with 16 clinicians (female: n=10, 63%; male: n=6, 38%) and 11 end users (age: mean 64.3, SD 7.2 y; female: n=7, 64%; male: n=4, 36%) of 1-hour duration were completed to understand the requirements for the intervention. Weekly workshops were held with key stakeholders throughout development. A different cohort of 15 end users (age: mean 61.5, SD 9.7 y; female: n=12, 80%; male: n=3, 20%) examined the feasibility of the study during a 2-week testing period. The System Usability Scale was used as the primary measure of intervention feasibility. ResultsOverall, 7 content modules were developed and refined over several iterations. Key themes highlighted in the clinician and end user interviews were the diverse characteristics of patients, the hierarchical structure with which patients view health practitioners, the importance of delivering information in multiple formats (written, audio, and visual), and access to patient-centered information as early as possible in the health care journey. All content was translated into Vietnamese, the most widely spoken language following English in the local government areas included in this study. Patients with hip and knee osteoarthritis from culturally and linguistically diverse backgrounds tested the feasibility of the intervention. A mean System Usability Scale score of 82.7 (SD 16) was recorded for the intervention, placing its usability in the excellent category. ConclusionsThrough the co-design process, we developed an evidence-based, holistic, and patient-centered digital health intervention. The intervention was specifically designed to be used by patients from diverse backgrounds, including those with low health, digital, and written literacy levels. The effectiveness of the intervention in improving the physical and mental health of patients will be determined by a high-quality randomized controlled trial.

Very little is known about the prevalence of new-onset diabetes after transplant (NODAT) in sub-Saharan and Eastern Africans. Most of the data are related to African Americans and to North and South Africans. The aims of this study were to examine the prevalence of NODAT in Sudanese renal transplant recipients, compare it with the published literature, and identify the risk factors for developing NODAT. In total, 150 patients who received a living-related kidney transplant between January 2015 and January 2016 were included in this study. Patients with diabetic nephropathy and pretransplant diabetes were excluded. Follow-up was for 2 years after the transplant. The variables studied were age, sex, body mass index, a family history of diabetes mellitus (DM), pretransplant steroid therapy, dyslipidemia, and hepatitis C virus infection. Twenty- three patients (15.3%) developed NODAT during the study period. The mean age of the patients who developed NODAT was 39 ± 14 years, and the mean time to develop NODAT was 5.78 ± 5.9 months. In the multivariate analysis, the risk factors for developing NODAT were a family history of DM (P = 0.01) and pretransplant steroid therapy (P = 0.01). The prevalence of NODAT in this study was 15.3%, which is in line with the reported literature from North Africa. However, it was significantly lower than the reported prevalence in African Americans.

Abstract Waldenström macroglobulinaemia (WM) is an incurable chronic B‐cell malignancy, but highly responsive to treatment. Treatments include fixed‐duration chemotherapy and continuous oral chemoimmunotherapy. In this expanding field, it is important to have reliable information on the impact of the various therapies on patients’ quality of life (QoL). Patient reported outcome measures (PROMs) are increasingly recognised as important to understand patient experience of disease beyond traditional clinical outcome measures. Four QoL questionnaires (EORTC QLQ‐C30 [European Organisation for Research and Treatment of Cancer quality of life core questionnaire], BIPQ [Brief Illness Perception Questionnaire], HADS [Hospital Anxiety and Depression Scale], EQ‐5D‐5L [EuroQoL 5‐dimensional descriptive system questionnaire]) are embedded in the UK national WM registry, the Rory Morrison Registry. We reviewed the results from a snapshot of PROMs. As of November 2021, 155 patients completed PROM data with 98% completion rate across all 58 questions. Complete clinical information was available for 52 patients. The majority of QoL questions (69%) failed to elicit a notable median response. Only four questions elicited statistically significant responses when comparing groups, and these were exclusively found in the EuroQoL‐5D‐5L and HADS questionnaires. Our data suggest that widely used questionnaires may not be suitable for patients with WM. We advocate the development of WM‐specific outcome measures to overcome this.

IntroductionDiet-related inflammation is associated with adiposity. Obesity and inflammation in early life may have adverse health outcomes in later life; however, the socio-ecological predictors of a pro-inflammatory diet in childhood and adolescence are not well understood. This rapid scoping review aims to summarise the current state of research from observational studies investigating socio-ecological predictors (childhood, parental, familial, demographic and chronobiological risk factors) and their association with diet-associated inflammation and adiposity in children and adolescents.MethodsThis scoping review will be conducted using the frameworks based on the Joanna Briggs Institute and Arksey and O'Malley and the Population, Concept and Context (PCC) mnemonic. Searches were conducted in OVID Medline, Cinahl and Embase, with adaptations as required. The piloted study selection process will utilise two reviewers for study selection, with reference lists checked for included studies. A third reviewer will moderate disagreements. Data will be extracted by one reviewer and calibrated by a second reviewer.ResultsThe results will be reported using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist and PRISMA-ScR flow diagram. The main findings will be synthesised into themes and concepts narratively. Tables and graphs will present frequencies, study details and categorical descriptions.DiscussionThis scoping review will provide an overview of the research conducted to date regarding predictors of diet-related inflammation in childhood and their associations with adiposity. Better understanding of the factors associated with a more inflammatory diet in childhood may be useful for clinicians and policy makers when designing and implementing health interventions.

Abstract Background The risk of progressive declines in skeletal muscle mass and strength, termed sarcopenia, increases with age, physical inactivity and poor diet. The purpose of this study was to explore and compare associations of sarcopenia components with self-reported physical activity and nutrition in older adults participating in resistance training at Helsinki University Research [HUR] and conventional gyms for over a year, once a week, on average. Methods The study looked at differences between HUR (n = 3) and conventional (n = 1) gyms. Muscle strength (via handgrip strength and chair stands), appendicular lean mass (ALM; via dual energy X-ray absorptiometry) and physical performance (via gait speed over a 4-m distance, short physical performance battery, timed up and go and 400-m walk tests) were evaluated in 80 community-dwelling older adults (mean ± SD 76.5 ± 6.5 years). Pearson correlations explored associations for sarcopenia components with self-reported physical activity (via Physical Activity Scale for the Elderly [PASE]) and nutrition (via Australian Eating Survey). Results No differences in PASE and the Australian Recommended Food Score (ARFS) were observed between HUR and conventional gyms, however HUR gym participants had a significantly higher self-reported protein intake (108 ± 39 g vs 88 ± 27 g; p = 0.029) and a trend to have higher energy intake (9698 ± 3006 kJ vs 8266 ± 2904 kJ; p = 0.055). In both gym groups, gait speed was positively associated with self-reported physical activity (r = 0.275; p = 0.039 and r = 0.423; p = 0.044 for HUR and conventional gyms, respectively). ALM was positively associated with protein (p = 0.047, r = 0.418) and energy (p = 0.038, r = 0.435) intake in the conventional gym group. Similar associations were observed for ALM/h2 in the HUR group. None of the sarcopenia components were associated with ARFS in either gym group. Conclusion Older adults attending HUR and conventional gyms had similar self-reported function and nutrition (but not protein intake). Inadequate physical activity was associated with low gait speed and inadequate nutrition and low protein ingestion associated with low lean mas, even in older adults participating in exercise programs. Optimal physical activity and nutrition are important for maintaining muscle mass and function in older adults.

The aim of this study was to explore the efficacy and safety of obinutuzumab (G)- versus rituximab (R)-chemotherapy in a subgroup of patients with previously untreated marginal zone lymphoma (MZL) in the phase III GALLIUM trial (NCT01332968). Patients had stage III/IV (or stage II with bulky disease), splenic, nodal, or extranodal MZL requiring treatment. Patients were randomized 1:1 to receive G- or R-chemotherapy (cyclophosphamide, doxorubicin, vincristine, and prednisone; cyclophosphamide, vincristine, and prednisone; or bendamustine, allocated at patient level). Patients with complete/partial response at the end of induction (EOI) received G/R maintenance. Investigator-assessed progression-free survival (PFS), other time-to-event endpoints, response, and safety were assessed. Overall, 195 patients with MZL were included in this analysis: G-chemotherapy (n = 99), R-chemotherapy (n = 96). Median observation time: 59.3 months. No meaningful difference was observed between arms for PFS (4-y PFS rates: G-chemotherapy, 72.6%; R-chemotherapy, 64.1%), other time-to-event endpoints, or EOI response rates (by computed tomography [CT; G-chemotherapy, 81.8%; R-chemotherapy, 81.3%] and positron emission tomography CT [G-chemotherapy, 79.2%; R-chemotherapy, 87.5%]). All patients experienced ≥1 adverse event (AE). G-chemotherapy was associated with a higher incidence of grade 3–5 (86.1% versus 77.4%), grade 5 (14.9% versus 9.7%), and serious (66.3% versus 51.6%) AEs versus R-chemotherapy. Both arms had a higher incidence of grade 3–5 and serious AEs than patients with follicular lymphoma (GALLIUM), with G-chemotherapy being less tolerable than R-chemotherapy. Based on the observed tolerability of G-chemotherapy versus R-chemotherapy, and the comparable efficacy of G-chemotherapy and R-chemotherapy in this analysis, G-chemotherapy cannot be recommended as first-line treatment for MZL.

Background: Acutely deteriorating patients are entitled to the best possible care, which includes early recognition and timely appropriate intervention to reduce adverse events, unnecessary admissions to intensive care, and/or cardiac arrest. Aim: To reduce the number of poor outcomes for surgical patients with a National Early Warning Score (NEWS) score ≥7 in our institution by 50%. A poor outcome was defined as: 1. Cardiac arrest 2. NEWS >7 not improving after 72 hours 3. Transfer to intensive care unit >6 hours Methods: Surgical inpatients from a variety of surgical specialties (general, vascular, breast, colorectal, hepatobiliary, and plastic surgery) in a large university teaching hospital were included. Quality improvement tools were used to generate regular dialogue with the clinical teams, resulting in the concept of the surgical safety huddle being proposed. Deteriorating patients were highlighted at the daily huddle and a plan of early intervention was implemented. An incremental approach with continuous PDSA [Plan-Do-Study-Act] cycles and subsequent feedback was adopted on the surgical ward to develop the huddle. Poor patient outcomes were analysed prospectively via chart reviews. Results: Prior to the introduction of the “surgical huddle" 110 patients with NEWS >7 were audited. Twenty-eight of these patients had a poor outcome at 72 hours (25%). Following the introduction of the surgical huddle supported by the deteriorating patient team, 64 patients with NEWS >7 were reviewed. Three of these patients had a poor outcome at 72 hours (4.7%). The introduction of the surgical huddle increased the interval between cardiac arrests more than sixfold on the surgical ward. Discussion: The introduction of the surgical safety huddle supported by the deteriorating patient response team reduced the number of cardiac arrests and poor outcomes in a surgical inpatient cohort.

Osteochondral defects of the ankle (OCD) are being increasingly identified as a clinically significant consequence of injury to the ankle, with the potential to lead to osteoarthritis if left untreated. The aim of this retrospective cohort study was to evaluate a single-stage treatment of OCD, based on bone marrow aspirate (BMA) centrifuged to produce bone marrow concentrate (BMC). In a dual syringe, the concentrate was mixed with thrombin in one syringe, whereas hyaluronan and fibrinogen were mixed in a second syringe. The two mixtures were then injected and combined into the prepared defect. Clinical outcome and quality of life scores (MOXFQ and EQ-5D) were collected at baseline and yearly thereafter. Multilevel models were used to analyse the pattern of scores over time. Ninety-four patients were treated between 2015 and 2020. The means of each of the three components of the MOXFQ significantly improved between baseline and 1 year (p < 0.001 for each component), with no further change from year 1 to year 3. The EQ-5D index also improved significantly from baseline to 1 year, with no evidence for further change. Our results strongly indicate that this BMC treatment is safe for, and well tolerated by, patients with OCD of the ankle as both primary treatment and those who have failed primary treatment. This technique provides a safe, efficacious alternative to currently employed cartilage repair techniques, with favourable outcomes and a low complication rate at 36 months.

Results of RESONATE-2 (PCYC-1115/1116) supported approval of ibrutinib for first-line treatment of chronic lymphocytic leukemia. Extended analysis of RESONATE-2 was conducted to determine long-term efficacy and safety of ibrutinib in older patients with chronic lymphocytic leukemia. A total of 269 patients aged ≥65 years with previously untreated chronic lymphocytic leukemia without del(17p) were randomized 1:1 to ibrutinib (n=136) or chlorambucil (n=133) on days 1 and 15 of a 28-day cycle for 12 cycles. Median ibrutinib treatment duration was 28.5 months. Ibrutinib significantly prolonged progression-free survival versus chlorambucil (median, not reached vs. 15 months; hazard ratio, 0.12; 95% confidence interval, 0.07-0.20; P

Community pharmacist is one of the most prominent and accessible healthcare professions. The community pharmacists’ role in healthcare is evolving, with opportunities being taken to reduce pressure on primary care services. However, the question remains of how well community pharmacists are equipped for this changing role. This was a sequentially designed study using a mix of methods to explore nutrition education among community pharmacists in Northern Ireland. It consisted of two phases. Phase 1 was a cross-sectional exploration to map the attitudes and practice of Northern Ireland (NI) pharmacists towards diet-related health promotion and disease prevention. An online questionnaire with open and closed questions to gain both quantitative and qualitative responses was developed and distributed to community pharmacists practising in NI. A total of 91% considered nutrition important in reducing the global burden of disease. While the majority (89%) believed patients would value nutritional advice from a pharmacist, 74% were not confident in providing advice to a patient with diabetes. From the consensus gained in Phase 1 a nutrition education intervention (Phase 2) for pre-registration pharmacists was developed using the Hardens 10 question system. The training programme was advertised to pre-registration pharmacy students in NI. It was delivered by nutrition experts who have education qualifications. The intervention was evaluated using a before and after questionnaire that assessed knowledge, attitudes, and practice (KAP). Phase 2 did find sustained improvement from the baseline in KAP but there was a decline from immediately post-training to three months post-training. This suggests the need to further embed nutrition education. The education programme was found to be effective for the target population and sets the stage for the development of an implementation strategy for a wider roll-out with evaluation.

Hyaline cartilage and mechanically inferior fibrocartilage consisting of mixed collagen types are frequently found together in repairing articular cartilage. The present study seeks to develop methodology to identify collagen type and other tissue components using Fourier transform infrared (FTIR) spectral evaluation of matrix composition in combination with multivariate analyses. FTIR spectra of the primary molecular components of repair cartilage, types I and II collagen, and aggrecan, were used to develop multivariate spectral models for discrimination of the matrix components of the tissues of interest. Infrared imaging data were collected from bovine bone, tendon, normal cartilage, meniscus and human repair cartilage tissues, and composition predicted using partial least squares analyses. Histology and immunohistochemistry results were used as standards for validation. Infrared fiber optic probe spectral data were also obtained from meniscus (a tissue with mixed collagen types) to evaluate the potential of this method for identification of collagen type in a minimally-invasive clinical application. Concentration profiles of the tissue components obtained from multivariate analysis were in excellent agreement with histology and immunohistochemistry results. Bone and tendon showed a uniform distribution of predominantly type I collagen through the tissue. Normal cartilage showed a distribution of type II collagen and proteoglycan similar to the known composition, while in repair cartilage, the spectral distribution of both types I and II collagen were similar to that observed via immunohistochemistry. Using the probe, the outer and inner regions of the meniscus were shown to be primarily composed of type I and II collagen, respectively, in accordance with immunohistochemistry data. In summary, multivariate analysis of infrared spectra can indeed be used to differentiate collagen type I and type II, even in the presence of proteoglycan, in connective tissues, using both imaging and fiber optic methodology. This has great potential for clinical in situ applications for monitoring tissue repair.