A major functional role of synovial fluid is to reduce the rate of cartilage fatigue failure under cyclical compressive loading.

OBJECTIVE: Based on our recent study, which showed that cartilage fatigue failure in reciprocating sliding contact results from cyclical compressive forces, not from cyclical frictional forces, we hypothesize that a major functional role for synovial fluid (SF) is to reduce the rate of articular cartilage fatigue failure from cyclical compressive loading. DESIGN: The rate of cartilage fatigue failure due to repetitive compressive loading was measured by sliding a glass lens against an immature bovine cartilage tibial plateau strip immersed in mature bovine SF, phosphate-buffered saline (PBS), or SF/PBS dilutions (50% SF and 25% SF; n = 8 for all four bath conditions). After 24 h of reciprocating sliding (5400 cycles), samples were visually assessed, and if damage was observed, the test was terminated; otherwise, testing was continued for 72 h (16,200 cycles), with solution refreshed daily. RESULTS: All eight samples in the PBS group exhibited physical damage after 24 h, with an average final surface roughness of Rq= 0.210 ± 0.067 mm. The SF group showed no damage after 24 h; however, two of eight samples became damaged after 72 h, producing a significantly lower average surface roughness than the PBS group (Rq=0.059 ± 0.030 mm; p < 10-4). For the remaining groups, at 72 h, one of eight samples was damaged in the 50% SF group, and five of eight samples were damaged in the 25% SF group. CONCLUSIONS: The results strongly support our hypothesis, showing that decreased amounts of SF in the testing bath produce increased rates of fatigue failure in cartilage that was subjected to reciprocating sliding contact.

Systematic review - Adjuvant radiotherapy of the vulva in primary vulvar cancer.

OBJECTIVE: Adjuvant radiotherapy to the vulva in vulvar squamous cell carcinoma (VSCC) is frequently performed albeit strong evidence is lacking. This systematic review aims to summarize the current literature on this topic. METHODS: 19 retrospective studies were included and analyzed, focusing on the primary outcome of local recurrence. RESULTS: The publications present conflicting results. While the benefit of adjuvant radiotherapy to the groins in case of node-positive VSCC is well established, the indication criteria and effectiveness of adjuvant radiotherapy to the vulva remain unclear. Based on the studies included in this review, the current evidence suggests that adjuvant radiotherapy to the vulva might not significantly reduce the risk of recurrence or only in certain subgroups. CONCLUSION: Most of the studies do not consider individual risk factors such as HPV status, resection margin, lymph node stage, grading and others. As a result, the comparability and reliability of these findings are limited. This review aims to highlight the need of further research addressing the risk stratification, considering both oncologic risk factors and adverse events.

Parous women perform less moderate to vigorous physical activity than their nulliparous peers: a population-based study in Denmark.

OBJECTIVES: The World Health Organization (WHO) highlights parous women as a key population for monitoring trends of physical activity (PA). We aimed to estimate the proportion of Danish women non-adhering to WHO PA guidelines in parous women compared with nulliparous women and to describe leisure-time PA intensity in each of these groups. STUDY DESIGN: Cross-sectional study. METHODS: This population-based study builds on a sample of 27,668 women aged 16-40 years from the Danish National Health Survey 2021. These data were linked with childbirth data from the Danish National Birth Registry. The primary outcome was self-reported weekly hours of moderate to vigorous leisure-time PA (MVPA) dichotomized into: (i) adhering to WHO guidelines for MVPA or (ii) not adhering to WHO guidelines for MVPA. Binomial regression analysis was used to calculate prevalence proportions (PP) and prevalence proportion ratios (PPR). RESULTS: Of the 27,668 women, a total of 20,022 were included; 9338 (46.6%) parous women and 10,684 (53.4%) nulliparous women. The PP of women non-adhering to WHO PA guidelines was 63.8% (95% CI 62.9-64.8) for parous and 51.3% (95% CI 50.4-52.3) for nulliparous women, corresponding to a PPR of 1.24 (95% CI 1.21; 1.27). CONCLUSIONS: The proportion of parous women who did not adhere to WHO PA guidelines for MVPA was 24% higher than that of nulliparous women. This highlights parous women as a subgroup of the adult population at increased risk of non-adherence to WHO PA guidelines. These findings call for future research to inform new strategies aiming to promote PA in parous women.

Immature bovine cartilage wear is due to fatigue failure from repetitive compressive forces and not reciprocating frictional forces.

OBJECTIVE: Wear of articular cartilage is not well understood. We hypothesize that cartilage wears due to fatigue failure in repetitive compression instead of reciprocating friction. DESIGN: This study compares reciprocating sliding of immature bovine articular cartilage against glass in two testing configurations: (1) a stationary contact area configuration (SCA), which results in static compression, interstitial fluid depressurization, and increasing friction coefficient during reciprocating sliding, and (2) a migrating contact area configuration (MCA), which maintains pressurization and low friction while producing repetitive compressive loading in addition to reciprocating sliding. Contact pressure, sliding duration, and sliding distance were controlled to be similar between test groups. RESULTS: SCA tests exhibited an average friction coefficient of µ=0.084±0.032, while MCA tests exhibited a lower average friction coefficient of µ=0.020±0.008 (p<10-4). Despite the lower friction, MCA cartilage samples exhibited clear surface damage with a significantly greater average surface deviation from a fitted plane after wear testing (Rq=0.125±0.095 mm) than cartilage samples slid in a SCA configuration (Rq=0.044±0.017 mm, p=0.002), which showed minimal signs of wear. Polarized light microscopy confirmed that delamination damage occurred between the superficial and middle zones of the articular cartilage in MCA samples. CONCLUSIONS: The greatest wear was observed in the group with lowest friction coefficient, subjected to cyclical instead of static compression, implying that friction is not the primary driver of cartilage wear. Delamination between superficial and middle zones implies the main mode of wear is fatigue failure under cyclical compression, not fatigue or abrasion due to reciprocating frictional sliding.

Traditional risk factors and nodal yield-still relevant with high-quality risk-adapted adjuvant treatment for locally advanced head and neck cancer?

OBJECTIVE: Patients with locally advanced head and neck cancer (LAHNC) often undergo multimodal therapy including radical resection of the primary tumor and neck dissection (ND) followed by risk-adapted adjuvant radio(chemo)therapy (R(C)T). Quality parameters influencing local control and survival of these patients have been postulated: resection status (R status), extranodal extension (ENE), interval to adjuvant treatment ≤6 weeks, R(C)T given when indicated, and nodal yield (NY) ≥18 lymph nodes per neck. For other solid tumors the trend is towards less extensive lymph node surgery to avoid toxicity such as lymphedema, damage to peripheral nerves, dysesthesia, or paresthesia. The present study aims to investigate whether the number of nodes removed during neck dissection for LAHNC is still predictive for outcome when patients receive risk-adapted adjuvant treatment according to current guidelines. METHODS: Between 2008 and 2015, 468 patients with LAHNC undergoing R(C)T with curative intent were prospectively registered in a database (UICC III/IV). Among them, 359 patients received adjuvant treatment and 295 underwent neck dissection. There were 119 (40%) patients with an oropharyngeal primary, 49 (17%) with cancer of the larynx/hypopharynx, 88 (30%) of the oral cavity, and 39 (13%) of the nasal/paranasal sinuses and cancer of unknown primary (CUP). Median follow-up was 45.6 months. Histopathology revealed an R1 status in 65 (22%) cases and ENE in 93 (31%) cases. 150 (51%) patients received RCT; the median time to adjuvant treatment from the day of tumor resection was 44 days (35-54) and overall treatment time (OTT; time from surgery to the last day of R(C)T) was 90 days (82-101). Factors influencing disease-free survival (DFS) were adjusted and analyzed using CART analysis (removed nodes, number of positive nodes, body mass index (BMI), ENE, T and N classification, R status, and primary site). Local control (LC), distant metastases-free survival (DMFS), and overall survival (OS) were analyzed using Kaplan-Meier statistics and multivariate analysis (MVA) for factors predictive for DFS and OS. RESULTS: CART analysis (Classification and Regression Trees) showed that T classification (T3/4) is the most important predictor for DFS, followed by age (> 61 years) and BMI (< 17.4). Primary site (OPC vs. other) and number of removed nodes (< 17) were shown to be less important for DFS, while ECE, N classification, and R status seem to be of little relevance. MVA revealed number of positive nodes, non-OPC, and T3/4 to be negative predictive factors for DFS. For OS, the number of positive nodes and non-OPC primary were predictive. Five-year rates were 86.1% for LC, 87.9% DMFS, 76.5% DFS, and 67.2% for OS. CONCLUSION: In this patient cohort, the number of removed nodes is not relevant for DFS and OS, while the number of positive nodes and T classification have a negative impact on these endpoints. The high-risk factors positive resection margin and ECE seem to lose their negative impact on DFS and OS. High-quality care in head and oncology is only possible within a close multidisciplinary team and network.

An analysis of the level of evidence behind treatments recommended by the Danish Medicines Council.

OBJECTIVES: We aimed to investigate the quality of evidence and the expected added clinical value of treatments recommended by the Danish Medicines Council (DMC). STUDY DESIGN: This was an observational study. METHODS: The DMC prepares reports on drugs considered for possible new standard treatments in Danish hospitals. These reports evaluate the available evidence on efficacy and safety. The quality of evidence is systematically rated by the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) criteria, and estimates of added clinical value are presented. The recommendations take into account expected economic implications of new treatments. The publicly available reports up until December 29, 2021, were downloaded from the DMC Web page. Reports on drugs marked "recommended" were included. Data on quality of evidence, expected clinical value, and economic implications were imputed in a Microsoft Excel spreadsheet. RESULTS: Seventy-nine reports were included in the analysis. In 79% of these, the quality of evidence was rated low (24%) or very low (55%), whereas no recommendations were based on evidence rated as high quality. Three (5%) of recommended treatments were expected to add large clinical value. CONCLUSIONS: Most recommendations by the DMC are based on evidence formally rated as low or very low quality by GRADE, and no recommendations were based on evidence rated as high quality. The added clinical value of the treatments was often not documented and rarely large. Continued attention to improve the clinical evidence behind national recommendations is necessary.

Integration of radiation oncology teaching in medical studies by German medical faculties due to the new licensing regulations : An overview and recommendations of the consortium academic radiation oncology of the German Society for Radiation Oncology (DEGRO).

The new Medical Licensing Regulations 2025 (Ärztliche Approbationsordnung, ÄApprO) will soon be passed by the Federal Council (Bundesrat) and will be implemented step by step by the individual faculties in the coming months. The further development of medical studies essentially involves an orientation from fact-based to competence-based learning and focuses on practical, longitudinal and interdisciplinary training. Radiation oncology and radiation therapy are important components of therapeutic oncology and are of great importance for public health, both clinically and epidemiologically, and therefore should be given appropriate attention in medical education. This report is based on a recent survey on the current state of radiation therapy teaching at university hospitals in Germany as well as the contents of the National Competence Based Learning Objectives Catalogue for Medicine 2.0 (Nationaler Kompetenzbasierter Lernzielkatalog Medizin 2.0, NKLM) and the closely related Subject Catalogue (Gegenstandskatalog, GK) of the Institute for Medical and Pharmaceutical Examination Questions (Institut für Medizinische und Pharmazeutische Prüfungsfragen, IMPP). The current recommendations of the German Society for Radiation Oncology (Deutsche Gesellschaft für Radioonkologie, DEGRO) regarding topics, scope and rationale for the establishment of radiation oncology teaching at the respective faculties are also included.

Objective and subjective rapid frailty screening tools in people with HIV.

OBJECTIVES: As people with HIV (PWH) age, the prevalence of frailty increases. Rapid screening tests to identify frailty within HIV outpatient settings are required to identify at-risk individuals. We undertook a service evaluation to assess three short frailty assessments in PWH. METHODS: We assessed two objective [gait speed (GS), timed-up-and-go test (TUGT)] and one subjective [the self-reported health questionnaire (SRH)] frailty screening tools in PWH aged > 40 years attending a single HIV outpatient department. Factors associated with positive frailty screening tests (defined as GS < 0.8 m/s, TUGT ≥ 10 s and SRH score < 6) were assessed using logistic regression models. ETHICAL CONSIDERATIONS: This was a service evaluation and was approved as a service evaluation by the Imperial College Healthcare NHS trust HIV clinical research committee (February 2020). All participants were given verbal information and were able to terminate the screening tests at any time. RESULTS: Of 84 PWH approached, 80 individuals completed all screening tests (median age = 56 years, range: 40-80) with a positive frailty screening prevalence in 19%, 33% and 20% for GS, TUGT and SRH, respectively. All tests were considered acceptable to participants. Factors statistically significantly associated with frailty included age (GS and TUGT), detectable HIV RNA (TUGT), number of comorbidities (GS and TUGT), presence of polypharmacy (GS and TUGT) and total number of concomitant medication (GS and SRH). CONCLUSIONS: Rates of positive screening tests for frailty are dependent on screening tool used, with all three tools being acceptable to participants. Objective measures of frailty screening (GS and TUGT) are more closely associated with clinical parameters than is a subjective measure of frailty screening (SRH).

Fungal quinones: diversity, producers, and applications of quinones from Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium.

Quinones represent an important group of highly structurally diverse, mainly polyketide-derived secondary metabolites widely distributed among filamentous fungi. Many quinones have been reported to have important biological functions such as inhibition of bacteria or repression of the immune response in insects. Other quinones, such as ubiquinones are known to be essential molecules in cellular respiration, and many quinones are known to protect their producing organisms from exposure to sunlight. Most recently, quinones have also attracted a lot of industrial interest since their electron-donating and -accepting properties make them good candidates as electrolytes in redox flow batteries, like their often highly conjugated double bond systems make them attractive as pigments. On an industrial level, quinones are mainly synthesized from raw components in coal tar. However, the possibility of producing quinones by fungal cultivation has great prospects since fungi can often be grown in industrially scaled bioreactors, producing valuable metabolites on cheap substrates. In order to give a better overview of the secondary metabolite quinones produced by and shared between various fungi, mainly belonging to the genera Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium, this review categorizes quinones into families such as emodins, fumigatins, sorbicillinoids, yanuthones, and xanthomegnins, depending on structural similarities and information about the biosynthetic pathway from which they are derived, whenever applicable. The production of these quinone families is compared between the different genera, based on recently revised taxonomy. KEY POINTS: • Quinones represent an important group of secondary metabolites widely distributed in important fungal genera such as Aspergillus, Penicillium, Talaromyces, Fusarium, and Arthrinium. • Quinones are of industrial interest and can be used in pharmacology, as colorants and pigments, and as electrolytes in redox flow batteries. • Quinones are grouped into families and compared between genera according to the revised taxonomy.

Inflammation and joint destruction may be linked to the generation of cartilage metabolites of ADAMTS-5 through activation of toll-like receptors.

OBJECTIVE: Links between pain and joint degradation are poorly understood. We investigated the role of activation of Toll-like receptors (TLR) by cartilage metabolites in initiating and maintaining the inflammatory loop in OA causing joint destruction. METHODS: Synovial membrane explants (SMEs) were prepared from OA patients' synovial biopsies. SMEs were cultured for 10 days under following conditions: culture medium alone, OSM + TNFα, TLR2 agonist - Pam2CSK4, Pam3CSK4 or synthetic aggrecan 32-mer, TLR4 agonist - Lipid A. Release of pro-inflammatory and degradation biomarkers (acMMP3 and C3M) were measured by ELISA in conditioned media along with IL-6. Additionally, human cartilage was digested with ADAMTS-5, with or without the ADAMTS-5 inhibiting nanobody - M6495. Digested cartilage solution (DCS) and synthetic 32-mer were tested for TLR activation in SEAP based TLR reporter assay. RESULTS: Western blotting confirmed TLR2 and TLR4 in untreated OA synovial biopsies. TLR agonists showed an increase in release of biomarkers - acMMP3 and C3M in SME. Synthetic 32-mer showed no activation in the TLR reporter assay. ADAMTS-5 degraded cartilage fragments activated TLR2 in vitro. Adding M6495 - an anti-ADAMTS-5 inhibiting nanobody®, blocked ADAMTS-5-mediated DCS TLR2 activation. CONCLUSION: TLR2 is expressed in synovium of OA patients and their activation by synthetic ligands causes increased tissue turnover. ADAMTS-5-mediated cartilage degradation leads to release of aggrecan fragments which activates the TLR2 receptor in vitro. M6495 suppressed cartilage degradation by ADAMTS-5, limiting the activation of TLR2. In conclusion, pain and joint destruction may be linked to generation of ADAMTS-5 cartilage metabolites.

Influence of radiation dose to pharyngeal constrictor muscles on late dysphagia and quality of life in patients with locally advanced oropharyngeal carcinoma.

BACKGROUND AND OBJECTIVE: Patients with oropharyngeal carcinoma (OPC) often have difficulty swallowing, which may affect quality of life (QoL). Radiation dose to constrictor muscles plays an important role. METHODS: 54 patients with locally advanced OPC were evaluated after intensity-modulated radiotherapy. Data were collected at standardized intervals using the EORTC questionnaires QLQ-C30 and QLQ-HN35 within two years. The pharyngeal constrictors (superior, middle, and inferior) were each contoured as an organ at risk. Influence of dose to the constrictors (≥55 Gy vs. <55 Gy) on late dysphagia and QoL was analyzed using the t­test. RESULTS: Late radiation-induced dysphagia depends significantly on the dose to the lower pharyngeal constrictor. At a dose of ≥55 Gy, 14 (64%) patients developed dysphagia grade ≤2 and 8 (36%) patients grade ≥3. At a dose of <55 Gy, the distribution at the end of radiotherapy (RT) was similar: 22 (69%) patients with dysphagia grade ≤2, 10 (31%) with grade ≥3. There was no dose-dependent difference in the severity of dysphagia in the acute phase (p = 0.989). There were differences 18 months after the end of RT: ≥55 Gy: 19 (86%) patients showed dysphagia grade ≤2; 3 (14%) grade ≥3. At <55 Gy, 31 (97%) patients developed grade ≤2, 1 (3%) grade ≥3 (18 months: p = 0.001; 24 months: p = 0.000). Late dysphagia is also dependent on the dose level of the middle constrictor muscle (6 months: p = 0.000; 12 months: p = 0.005, 18 months: p = 0.034). After 24 months, there was no significant difference (p = 0.374). CONCLUSION: Radiation dose to the upper constrictor muscle appears to be of little relevance. The middle and lower constrictor should be given special consideration to avoid late dysphagia. Long-term QoL is independent on radiation dose.

The association between physical activity and self-reported health in older adults: lessons implied by lifestyle factors.

Physical activity (PA) has been evidenced to be associated with self-reported health, but studies providing this evidence have failed to incorporate some relevant covariates, especially those pertinent to an African sample. This study examined the association between PA and self-reported health, with relevant lifestyle factors, comorbidities, and personal characteristics treated as covariates in this assessment. The study population was retired and working older people aged 60 years or more in Accra, Ghana. A total of 686 individuals responded to self-reported questionnaires. Pearson's chi-square test and binary logistic regression were used to present findings. Our data indicated that older adults who participated in moderate PA for more than 60 minutes were 7 times (OR=7,41; p=0,000) more likely to report good health compared with those who were active for less than 30 minutes. Similarly, those who participated in vigorous PA for 60 or more minutes were 5 times (OR=4,52; p=0,003) more likely to report good health compared with those who were active for less than 30 minutes. It is concluded that PA is likely to better enhance self-reported health when older people avoid sedentary behaviour, reduce their frequency of smoking, and modify their diet, but our covariate adjustment suggests that alcohol intake does not necessarily mar self-reported health.

The impact of local control on overall survival after stereotactic body radiotherapy for liver and lung metastases from colorectal cancer: a combined analysis of 388 patients with 500 metastases.

BACKGROUND: The aim of this analysis was to model the effect of local control (LC) on overall survival (OS) in patients treated with stereotactic body radiotherapy (SBRT) for liver or lung metastases from colorectal cancer. METHODS: The analysis is based on pooled data from two retrospective SBRT databases for pulmonary and hepatic metastases from 27 centers from Germany and Switzerland. Only patients with metastases from colorectal cancer were considered to avoid histology as a confounding factor. An illness-death model was employed to model the relationship between LC and OS. RESULTS: Three hundred eighty-eight patients with 500 metastatic lesions (lung n = 209, liver n = 291) were included and analyzed. Median follow-up time for local recurrence assessment was 12.1 months. Ninety-nine patients with 112 lesions experienced local failure. Seventy-one of these patients died after local failure. Median survival time was 27.9 months in all patients and 25.4 months versus 30.6 months in patients with and without local failure after SBRT. The baseline risk of death after local failure exceeds the baseline risk of death without local failure at 10 months indicating better survival with LC. CONCLUSION: In CRC patients with lung or liver metastases, our findings suggest improved long-term OS by achieving metastatic disease control using SBRT in patients with a projected OS estimate of > 12 months.

Home-based color card screening for biliary atresia: the first steps for implementation of a nationwide newborn screening in Germany.

INTRODUCTION: Biliary atresia is a rare neonatal disease and the most common indication for pediatric liver transplantation. Kasai portoenterostomy is the initial treatment, aiming to prevent liver transplantation. Beyond age at Kasai, few prognostic factors are known. Multiple countries have established screening methods to reduce the age at Kasai and recent analysis shows significant better outcomes for screening cohorts. In 2016, we established a decentralized stool color card screening in Lower Saxony and we present our first 2 years of experiences. METHODS: In cooperation with a major German health insurance company and the Medical Association of Lower Saxony, we established the screening project, printed 120,000 color cards, and distributed them to all maternity hospitals. Program advertises were printed in newspapers and medical journals. After the first year, the project was evaluated. Thirty maternity hospitals and local practitioners were contacted via telephone, Internet, intranet, and pediatric journals. RESULTS: One out of seventy-six maternity hospitals (1.3%) refused to participate in the screening. 30 hospitals (40%) were contacted and 93.5% of the interviewed staff reported that stool color cards were handed out regularly and discussed with the parents. Only 20% of local practitioners assessed neonatal cholestasis to be a relevant problem during daily practice, and 55% regarded a stool color card screening to be useful. CONCLUSIONS: In the second year, we extended the screening project to outpatient maternity clinics. Based on the responses of local practitioners, we regard the voluntary screening as insufficient and we have contacted the Federal Joint Committee for the initiation of a nationwide obligatory stool color card screening.

[Staging of liver fibrosis in biliary atresia : Comparison of Chevallier and Ishak score as well as automated evaluation]. / Staging der Leberfibrose bei Gallengangatresie : Vergleich von Chevallier- und Ishak-Score sowie automatisierter Auswertung.

BACKGROUND: Biliary atresia (BA) is a rare disease of the newborn, resulting in liver cirrhosis due to obliterative cholangiopathy. Liver biopsies are commonly performed in order to confirm the diagnosis and in order to stage fibrosis. OBJECTIVES: The present study intended to analyze two established scores for evaluating liver fibrosis focusing on the interobserver variability as well as the prognostic reliability towards the time of liver transplantation. MATERIALS AND METHODS: Liver biopsies of BA patients between 2012 and 2015 were evaluated retrospectively by two pathologists at the Hannover Medical School (MHH) and the RWTH Aachen University Hospital. Fibrosis was measured using Ishak and Chevallier scores. Furthermore, a computerized automatically algorithm-based analyzation (ABAA) was performed. Results were evaluated towards the time point of liver transplantation and hepatoportoenterostomy (HPE). RESULTS: Overall, 34 liver biopsies were analyzed. The Ishak score showed a remarkable interobserver variability (ΚW = 0.68) while the Chevallier score was proven to have a poor interobserver variability (Fleiss' Κappa = -0.01). However, both scores were correlated positively, as was the ABAA (p < 0.001). Regarding prognostic reliability, ROC analyses of the Ishak score revealed the best validity towards an early liver transplantation within 12 months (AUC 0.813, p = 0.011). In addition, an increased Ishak score ≥4 reduced the survival time with the native liver (hazard ratio 6.6 [95% CI 1.9-23.3]). CONCLUSIONS: The Ishak score was revealed to have the best interobserver variability as well as prognostic validity towards an early liver transplantation in BA patients. Due to its easy applicability, the Ishak score was proven superior in comparison to the Chevallier score and ABAA. Therefore, use of the Ishak score is recommended in daily clinical routine for analyzing liver biopsies in BA patients.

The association between social capital factors and sedentary behaviour among older adults: Does the built environment matter?

Evidences in the literature uphold social capital factors, namely social networks and support as a buffer against sedentary behaviour. A recent school of thought also contends that the built environment supports these factors to reduce sedentary behaviour. This study examined the role of the built environment in the association between the said social capital factors and sedentary behaviour. Participants of the study were 504 volunteer older adults in Accra, Ghana. A self-reported questionnaire was used to gather data, and structural equation modelling was used to present findings through Amos. The structural model through which the associations were tested produced a good fit (χ2=231,32; p=0,198). The study confirmed that the built factors are directly and indirectly (via social capital factors) associated with sedentary behaviour. «Road structure and safety¼ and «health and paramedical services¼ directly reduced sedentary behaviour, while «public security services¼ was positively associated with sedentary behaviour. All the built environmental factors, except «care and recreational homes¼, influenced sedentary behaviour through the social capital factors. We conclude that built environmental factors reinforce social capital to reduce sedentary behaviour, but this support may also increase sedentary time if the built environment is not well structured.

Injuries, dislocations, and poor health perceived by older adults to result from vigorous physical activity: implications for active living, health promotion, and gerontology.

This study examines older adults' perceptions about their participation in vigorous physical activity (VPA) and the association between VPA and self-related health. A total of 686 older adults responded to self-reported questionnaires, and Pearson's ꭓ2 test and binary logistic regression were used to present findings. About 74% of older adults reported experiencing dislocations, fractures, or/and other forms of injury in intense physical activities lasting 30 minutes or more a day. After controlling for relevant socio-demographic factors, older adults who participated in VPA for 30 or more minutes a day were less likely (OR=0,129; p=0,000) to report good health compared with those who participated in VPA for less than 30 minutes. It is concluded that VPA in older populations can result in casualties that may compel older adults to underrate their health, which can discourage active living habits in older populations and discredit PA/health promotion programs.

[Studies on radiotherapy of head and neck cancer : Highlights of the 2019 ASCO Annual Meeting]. / Strahlentherapeutische Studien bei Kopf-Hals-Tumoren : Highlights der ASCO-Jahrestagung 2019.

BACKGROUND: Radiotherapy is an important treatment option in patients with head and neck. At this year's annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago, results of several studies on radiotherapy in patients with head and neck cancer were presented. MATERIALS AND METHODS: All abstracts and presentations from this year's ASCO Annual Meeting on radiotherapy in patients with head and neck cancer were screened and the most interesting results selected for further review. RESULTS: The ORATOR trial compared primary surgery in patients with oropharyngeal carcinoma (OPSCC) with primary radiochemotherapy (RCT), particularly in terms of swallowing, for which superiority of RCT was demonstrated. Furthermore, results were presented on the question of optimal cisplatin dosage in patients receiving adjuvant RCT. Higher cisplatin doses showed better outcome. In patients with nasopharyngeal carcinoma (NPC), neoadjuvant chemotherapy before RCT is a comparable alternative to RCT followed by adjuvant chemotherapy. In addition, results of studies were presented that examined the tolerability of combining immunotherapy with radiotherapy in the first-line setting. CONCLUSION: The data presented show promising approaches for the further development of radiotherapy, particularly in terms of combined RCT as well as the optimal sequencing and dosing of systemic therapies.

Spermatogonial quantity in human prepubertal testicular tissue collected for fertility preservation prior to potentially sterilizing therapy.

STUDY QUESTION: Does chemotherapy exposure (with or without alkylating agents) or primary diagnosis affect spermatogonial quantity in human prepubertal testicular tissue? SUMMARY ANSWER: Spermatogonial quantity is significantly reduced in testes of prepubertal boys treated with alkylating agent therapies or with hydroxyurea for sickle cell disease. WHAT IS KNOWN ALREADY: Cryopreservation of spermatogonial stem cells, followed by transplantation into the testis after treatment, is a proposed clinical option for fertility restoration in children. The key clinical consideration behind this approach is a sufficient quantity of healthy cryopreserved spermatogonia. However, since most boys with malignancies start therapy with agents that are not potentially sterilizing, they will have already received some chemotherapy before testicular tissue cryopreservation is considered. STUDY DESIGN, SIZE, DURATION: We examined histological sections of prepubertal testicular tissue to elucidate whether chemotherapy exposure or primary diagnosis affects spermatogonial quantity. Quantity of spermatogonia per transverse tubular cross-section (S/T) was assessed in relation to treatment characteristics and normative reference values in histological sections of paraffin embedded testicular tissue samples collected from 32 consecutive boy patients (aged 6.3 ± 3.8 [mean ± SD] years) between 2014 and 2017, as part of the NORDFERTIL study, and in 14 control samples (from boys aged 5.6 ± 5.0 [mean ± SD] years) from an internal biobank. PARTICIPANTS/MATERIALS, SETTING, METHODS: Prepubertal boys in Sweden, Finland and Iceland who were facing treatments associated with a very high risk of infertility, were offered the experimental procedure of testicular cryopreservation. Exclusion criteria were testicular volumes >10 ml and high bleeding or infection risk. There were 18 patients with a diagnosis of malignancy and 14 patients a non-malignant diagnosis. While 20 patients had the testicular biopsy performed 1-45 days after chemotherapy, 12 patients had not received any chemotherapy. In addition, 14 testicular tissue samples of patients with no reported testicular pathology, obtained from the internal biobank of the Department of Pathology at Karolinska University Hospital, were included as control samples in addition to reference values obtained from a recently published meta-analysis. The quantity of spermatogonia was assessed by both morphological and immunohistochemical analysis. MAIN RESULTS AND THE ROLE OF CHANCE: The main finding was a significant reduction in spermatogonial cell counts in boys treated with alkylating agents or with hydroxyurea for sickle cell disease. The mean S/T values in boys exposed to alkylating agents (0.2 ± 0.3, n = 6) or in boys with sickle cell disease and exposed to hydroxyurea (0.3 ± 0.6, n = 6) were significantly lower (P = 0.003 and P = 0.008, respectively) than in a group exposed to non-alkylating agents or in biobank control samples (1.7 ± 1.0, n = 8 and 4.1 ± 4.6, n = 14, respectively). The mean S/T values of the testicular tissue samples included in the biobank control group and the patient group exposed to non-alkylating agents were within recently published normative reference values. LIMITATIONS, REASONS FOR CAUTION: Normal testicular tissue samples included in this study were obtained from the internal biobank of Karolinska University Hospital. Samples were considered normal and included in the study if no testicular pathology was reported in the analysed samples. However, detailed information regarding previous medical treatments and testicular volumes of patients included in this biobank were not available. WIDER IMPLICATIONS OF THE FINDINGS: This study summarizes, for the first time, spermatogonial quantity in a prepubertal patient cohort just before and after potentially sterilizing treatments. Boys facing cancer and cytotoxic therapies are regarded as the major group who will benefit from novel fertility preservation techniques. There are no previous reports correlating spermatogonial quantity to cumulative exposure to alkylating agents and anthracyclines (non-alkylating agents) and no information about the timing of cytotoxic exposures among this particular patient cohort. For prepubertal boys in whom fertility preservation is indicated, testicular tissue should be obtained before initiation of chemotherapy with alkylating agents, whilst for those with sickle cell disease and treated with hydroxyurea, this approach to fertility preservation may not be feasible. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by grants from The Swedish Childhood Cancer Foundation (PR2016-0124; TJ2016-0093; PR2015-0073, TJ2015-0046) (J.-B.S. and K.J.), the Jane and Dan Olssons Foundation (2016-33) (J.-B.S.), the Finnish Cancer Society (K.J.), the Foundation for Paediatric Research (J.-B.S.), Kronprinsessan Lovisas Förening För Barnasjukvård/ Stiftelsen Axel Tielmans Minnesfond, Samariten Foundation (J.-B.S.), the Väre Foundation for Paediatric Cancer Research (K.J.) and the Swedish Research Council (2012-6352) (O.S.). R.T.M. was supported by a Wellcome Trust Fellowship (09822). J.P.A.-L. and M.K. were supported by the ITN Marie Curie program 'Growsperm' (EU-FP7-PEOPLE-2013-ITN 603568). The authors declare no conflicts of interest. TRIAL REGISTRATION NUMBER: N/A.

Socioeconomic status and quality of life in patients with locally advanced head and neck cancer.

PURPOSE: Socioeconomic aspects play an important role in health care. Patients with locally advanced head and neck cancer (LAHNC) experience detrimental effects on their quality of life (QoL). This prospective study examines QoL differences between patients with different socioeconomic status (SES) after intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: In all, 161 patients were questioned at the end of IMRT and at 12 and 24 months follow-up using the questionnaires of the European Organization for Research and Treatment of Cancer (EORTC) QLQ-30 and QLQ-HN35. Patients' QoL 2 years after IMRT was compared to a population reference sample and QoL of patients from lower, middle, and higher social class 2 years after IMRT was analyzed by ANCOVA using baseline QoL (end of radiation treatment) as a covariate. RESULTS: Patients with high SES report worse QoL at the end of IMRT in the domains global health status (-15.2; p = 0.005), role function (-23.8; p = 0.002), and social function (-19.4; p = 0.023) compared to patients with middle and low SES. QoL improved during the first 12 and 24 months. However, 2 years after IMRT, middle and low SES patients report lower QoL in the domains global health status, physical function, and role function, and report a higher general (fatigue, pain, dyspnea) and head and neck cancer-specific symptom burden (pain, swallowing, senses, speech, social eating, opening mouth, and felt ill) than patients with high SES. CONCLUSION: After IMRT for LAHNC, patients with high SES report worse QoL compared to patients with middle or low SES. There is a marked improvement within the first 24 months in many domains. However, the magnitude of improvement in patients with middle or low SES is significantly smaller compared to patients with high SES.