Examining cut mark residue with SEM to identify metal tool use: An experimental study.

In this manuscript, we explore the potential of studying metal residues in cut marks generated by copper and bronze knives. The method was developed in the forensic sciences for use with modern metals in order to identify microscopic particles of metal tools on bone surfaces. However, the study of residues in archaeological materials can be challenging due to the ways in which the bone remains may have been manipulated, both in the past and in more recent times. Using a scanning electron microscope (SEM), we detected microscopic fragments of bronze and copper knives along with contamination both inside and outside of the cut marks made by those knives. Copper and bronze residues were identified embedded in the bone inside the incisions and, in two cases, they left greenish stains caused by metal oxidation. In contrast, modern contamination of undetermined origin was found unattached to the bone and had a chemical composition not compatible with that of the knives. The amount of residue was influenced by the quantity of soft tissue between the bone and the knife during the butchering tasks. Bone cooking does not seem to influence the preservation of the residues. We anticipate that the approach used in this first exploratory study will emerge as a promising method for identifying the use of metal tools in archaeological bone remains.

Women show a positive response to platelet-rich plasma despite presenting more painful knee osteoarthritis than men.

PURPOSE: The purpose of this study was to evaluate the impact of gender on the efficacy of platelet-rich plasma (PRP) in patients with knee osteoarthritis (KOA), comparing their short-term response between men and women. METHODS: Four hundred-eighteen patients (529 knees) were included. Patients were treated with three injections of PRP on a weekly basis. Blood and PRP samples were randomly tested. Patients were asked to complete the knee injury and osteoarthritis outcome score (KOOS) and 12-item short form survey (SF-12), at baseline and 6 months. Success rates were calculated according to a reduction in the pain score of at least 9.3 points [minimal clinically important improvement (MCII)]. Comparative tests and multivariate regression were performed. RESULTS: The PRP had a platelet concentration factor of 2.0X compared to blood levels, with no leucocytes or erythrocytes. KOOS scores showed an increase from baseline to 6 months (p < 0.0001). There was an increase in the physical component summary (PCS) (p < 0.0001) and mental component summary (MCS) (p < 0.01) of the SF-12. The number of knees of women with MCII was 156 out of 262 (59.6%), whereas the number of knees of men was 136 out of 267 (50.9%) (p = 0.0468). Women had worse baseline scores on pain (p = 0.009), PCS (p < 0.0001) and MCS (p < 0.0001). CONCLUSION: Although the symptomatology generated by KOA was worse in women when compared to men, treatment with repeated injections of PRP was effective, ultimately achieving a higher improvement in women providing comparable final follow-up outcomes between men and women. LEVEL OF EVIDENCE: Level IV.

The limestone spheroids of 'Ubeidiya: intentional imposition of symmetric geometry by early hominins?

Spheroids are one of the least understood lithic items yet are one of the most enduring, spanning from the Oldowan to the Middle Palaeolithic. Why and how they were made remains highly debated. We seek to address whether spheroids represent unintentional by-products of percussive tasks or if they were intentionally knapped tools with specific manufacturing goals. We apply novel three-dimensional analysis methods, including spherical harmonics and surface curvature, to 150 limestone spheroids from 'Ubeidiya (ca 1.4 Ma), presently the earliest Acheulean occurrence outside of Africa, to bring a new perspective to these enigmatic artefacts. We reconstruct the spheroid reduction sequence based on trends in their scar facets and geometry, finding that the spheroid makers at 'Ubeidiya followed a premeditated reduction strategy. During their manufacture, the spheroids do not become smoother, but they become markedly more spherical. They approach an ideal sphere, a feat that likely required skilful knapping and a preconceived goal. Acheulean bifaces are currently thought to represent the earliest evidence of hominins imposing a premeditated, symmetrical shape on stone. The intentional production of sphere-like objects at 'Ubeidiya similarly shows evidence of Acheulean hominins desiring and achieving intentional geometry and symmetry in stone.

The OARSI Joint Effort Initiative: Priorities for osteoarthritis management program implementation and research 2024-2028.

Objective: The Joint Effort Initiative (JEI) is an international collaboration of clinicians, researchers, and consumer organisations with a shared vision of improving the implementation of osteoarthritis management programs (OAMPs). This study aimed to identify JEI's future priorities and guide direction. Design: A two-part international survey to prioritise topics of importance to our membership and research stakeholders. Survey one presented a list of 40 topics under 5 themes. Consenting participants were asked to choose their top three topics in each theme. A short list of 25 topics was presented in survey two. Participants were asked to rank the importance (100-point NRS scale, 100 â€‹= â€‹highest priority). Response frequency (median, IQR) was used to rank the top priorities by theme. Results: Ninety-five participants completed survey one (61% female, 48% clinicians) and 57 completed survey two. The top ranked topic/s were:i. Promotion and advocacy: support training for health professionals (median 85, IQR 24).ii. Education and training: incorporating behaviour change into OAMPs (80, 16), advanced OA skills (80, 30), and integration of OA education into clinical training (80, 36).iii. Improving OAMPs delivery: regular updates on changes to best-evidence OA care (84, 24).iv. Future research: improve uptake of exercise, physical activity, and weight-loss (89, 16).v. Enhancing relationships, alliances, and shared knowledge: promote research collaborations (81, 30), share challenges and opportunities for OAMP implementation (80, 23). Conclusions: These topics will set the JEI's research and collaboration agenda for the next 5 years and stimulate ideas for others working in the field.

Randomized, double-blind, placebo-controlled study to evaluate the effect of treatment with an SPMs-enriched oil on chronic pain and inflammation, functionality, and quality of life in patients with symptomatic knee osteoarthritis: GAUDI study.

BACKGROUND: Specialized pro-resolving mediators (SPMs), including 18-HEPE, 17-HDHA, and 14-HDHA are recognized as potentially therapeutic in inflammatory diseases because SPMs regulate the inflammation process, which leads to, for example; swelling and the sensation of pain. In osteoarthritis (OA), chronic pain is described as the symptom that reduces patients´ quality of life (QoL). The GAUDI study evaluated the efficacy of SPMs supplementation in reducing pain in the symptomatic knee of OA patients. METHODS: This randomized, multicenter, double-blind, and placebo-controlled parallel-group pilot study was performed in Spain and conducted on adults 18-68 years old diagnosed with symptomatic knee OA. Patients were enrolled in the study for up to 24 weeks, which included a 12-week intervention period and a follow-up visit on week 24. The primary endpoint was pain change measured through a Visual Analog Scale (VAS). Secondary endpoints included: Pain change evaluation, stiffness, and function according to the WOMAC index; assessment of constant, intermittent, and total pain according to the OMERACT-OARSI score; evaluation of changes in health-related QoL parameters; the use or not of concomitant, rescue, and anti-inflammatory medication; and safety and tolerability assessments. RESULTS: Patients were enrolled in the study from May 2018 to September 2021. VAS pain score was evaluated in the per protocol population (n = 51 patients), in which we observed a statistically significant reduction after 8 weeks (p = 0.039) and 12 weeks (p = 0.031) of treatment in patients consuming SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). In line with the OMERACT-OARSI score, intermittent pain was reduced after 12 weeks with statistical significance (p = 0.019) in patients treated with SPMs (n = 23 subjects) vs. placebo (n = 28 subjects). Functional status as WOMAC score did not significantly change after SPMs or placebo consumption. Notably, patients consuming SPMs showed improvements in all five aspects of the EUROQoL-5, including a significant improvement in the usual-activities dimension. None of the patients required rescue medication, nor were any adverse events reported. CONCLUSIONS: These findings suggest that sustained SPMs consumption reduces pain in OA patients while also improving their Quality of Life. These results also support the safety profile of SPMs supplementation. Trial registration NCT05633849. Registered 1 December 1 2022. Retrospectively registered, https://clinicaltrials.gov/ct2/show/study/NCT05633849.

Small Synthetic Hyaluronan Disaccharide BIS014 Mitigates Neuropathic Pain in Mice.

Neuropathic pain (NP) is a challenging condition to treat, as the need for new drugs to treat NP is an unmet goal. We investigated the analgesic potential of a new sulfated disaccharide compound, named BIS014. Oral administration (p.o.) of this compound induced ameliorative effects in formalin-induced nociception and capsaicin-induced secondary mechanical hypersensitivity in mice, but also after partial sciatic nerve transection (spared nerve injury), chemotherapy (paclitaxel)-induced NP, and diabetic neuropathy induced by streptozotocin. Importantly, BIS014, at doses active on neuropathic hypersensitivity (60 mg/kg/p.o.), did not alter exploratory activity or motor coordination (in the rotarod test), unlike a standard dose of gabapentin (40 mg/kg/p.o.) which although inducing antiallodynic effects on the NP models, it also markedly decreased exploration and motor coordination. In docking and molecular dynamic simulation studies, BIS014 interacted with TRPV1, a receptor involved in pain transmission where it behaved as a partial agonist. Additionally, similar to capsaicin, BIS014 increased cytosolic Ca2+ concentration ([Ca2+]c) in neuroblastoma cells expressing TRPV1 receptors; these elevations were blocked by ruthenium red. BIS014 did not block capsaicin-elicited [Ca2+]c transients, but inhibited the increase in the firing rate of action potentials in bradykinin-sensitized dorsal root ganglion neurons stimulated with capsaicin. Perspective: We report that the oral administration of a new sulfated disaccharide compound, named BIS014, decreases neuropathic pain from diverse etiology in mice. Unlike the comparator gabapentin, BIS014 does not induce sedation. Thus, BIS014 has the potential to become a new efficacious non-sedative oral medication for the treatment of neuropathic pain.

Psychosocial and individual factors affecting Quality of Life (QoL) in patients suffering from Achilles tendinopathy: a systematic review.

BACKGROUND: Achilles tendinopathy (AT) is a joint condition that causes functional restrictions and pain. This condition negatively impacts patients' social connectedness and psychological well-being, reducing their quality of life (QoL). This review aims to summarise the current information on QoL in patients suffering from AT from different angles: compared to a healthy population, reported individual factors that influence it and the effects of some AT interventions on QoL. METHODS: A systematic review was conducted at PubMed, Cochrane, Google Scholar, and PsycINFO using tendinopathy and QoL-related keywords up to November 2021. Articles were included if they compared QoL to demographic factors such as age or gender, lifestyle factors (physical activity levels), comorbidity factors (diabetes, obesity), and/or a control group. RESULTS: Three hundred twenty-nine articles were reviewed; 23 met the inclusion criteria. SF-36, EQ-5D, and VISA-A were the most common instrument used. Patients with AT reported low QoL when compared to no AT population. When women were compared to men, women reported worse QoL. The patients who participated in different exercise programs (strengthening and stretching) showed improvements in QoL. Surgical AT intervention improved QoL, although results varied by age. CONCLUSION: AT has a substantial impact on QoL. In AT patients, QoL is also influenced by specific individual factors, including gender and physical activity. Exercise, education, and surgical treatment improve QoL. We suggest more research on AT patients to better understand the aspects leading to poor QoL.

Risk of ischaemic stroke among new users of glucosamine and chondroitin sulphate: a nested case-control study.

Background: Several studies have reported that the use of chondroitin sulphate (CS) and glucosamine may reduce the risk of acute myocardial infarction. Although it is thought that this potential benefit could be extended to ischaemic stroke (IS), the evidence is scarce. Objective: To test the hypothesis that the use of prescription glucosamine or CS reduces the risk of IS. Design: Case-control study nested in an open cohort. Methods: Patients aged 40-99 years registered in a Spanish primary healthcare database (BIFAP) during the 2002-2015 study period. From this cohort, we identified incident cases of IS, applying a case-finding algorithm and specific validation procedures, and randomly sampled five controls per case, individually matched with cases by exact age, gender and index date. Adjusted odds ratios (AORs) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of glucosamine or CS were considered. Results: A total of 13,952 incident cases of IS and 69,199 controls were included. Of them, 106 cases (0.76%) and 803 controls (1.16%) were current users of glucosamine or CS at index date, yielding an AOR of 0.66 (95% CI: 0.54-0.82) (for glucosamine, AOR: 0.55; 95% CI: 0.39-0.77; and for CS, AOR: 0.77; 95% CI: 0.60-0.99). The reduced risk among current users was observed in both sexes (men, AOR: 0.69; 95% CI: 0.49-0.98; women, AOR: 0.65; 95% CI: 0.50-0.85), in individuals above and below 70 years of age (AOR: 0.69; 95% CI: 0.53-0.89 and AOR: 0.59; 95% CI: 0.41-0.85, respectively), in individuals with vascular risk factors (AOR: 0.53; 95% CI: 0.39-0.74) and among current/recent users of nonsteroidal anti-inflammatory drugs (NSAIDs) (AOR: 0.71; 95% CI: 0.55-0.92). Regarding duration, the reduced risk was observed in short-term users (<365 days, AOR: 0.61; 95% CI: 0.48-0.78) while faded and became nonsignificant in long-term users (>364 days AOR: 0.86; 95% CI: 0.57-1.31). Conclusions: Our results support a protective effect of prescription CS and glucosamine in IS, which was observed even in patients at vascular risk. Mini abstract: Our aim was to analyse whether the use of glucosamine or chondroitin sulphate (CS) reduces the risk of ischaemic stroke (IS). We detected a significant decrease.

Documento de expertos sobre el uso apropiado de los SYSADOA en situaciones clínicas controvertidas / Experts Document About an Adequate Utilization of SYSADOAs in Controversial Clinical Situations

Antecedentes y objetivo: Los SYSADOA (del inglés, symptomatic slow-acting drugs for osteoarthritis) orales son compuestos naturales que han demostrado ser útiles y seguros en el tratamiento de la artrosis (AO). Sin embargo, su uso en ciertas situaciones clínicas carece aún de evidencia científica y recomendaciones claras. El objetivo de este trabajo fue conocer la opinión de un grupo de expertos sobre el uso de los SYSADOA en el tratamiento de la AO en situaciones clínicas controvertidas. Materiales y métodos: Siguiendo el método del uso apropiado mediante la técnica Delphi, se valoraron 206 consultas concretas, estructuradas en 24 preguntas clínicas. Un panel de expertos, compuesto por un total de 15 especialistas, respondió a las dos rondas de consulta a través de una plataforma online. Los resultados se analizaron y debatieron en una reunión presencial con los coordinadores y el comité científico. Según el porcentaje de panelistas que coincidieron en los mismos, se clasificaron los resultados en términos de unanimidad, consenso, mayoría y discrepancia. Resultados: Se consensuaron los siguientes puntos: (1) el fenotipo del paciente condiciona el uso de los SYSADOA orales; (2) los SYSADOA orales se consideran adecuados en la AO primaria (rodilla, mano y cadera) y en algunos tipos de AO secundaria; no se consideran adecuados en AO erosiva de manos, hombro, columna y tobillo; (3) los SYSADOA orales pueden ser prescritos a pacientes con riesgo o enfermedad cardiovascular, enfermedad digestiva, hipertensión, dislipemia, enfermedad vascular periférica, diabetes tipo 2 y, a excepción de diacereína, en pacientes con reflujo esofágico. No se obtuvo acuerdo en la prescripción de los SYSADOA orales en pacientes con enfermedad hepática y renal.(AU)

Background and objective: SYSADOAs (symptomatic slow-acting drugs for osteoarthritis) are natural compounds that have been shown to be useful and safe in the treatment of osteoarthritis (OA). However, their use in certain clinical situations still lacks scientific evidence and clear recommendations. The objective of this work was to learn the opinion of a group of experts regarding the appropriate use of SYSADOA in the treatment of OA in controversial clinical situations. Materials and methods: Following the Delphi technique, 206 specific consultations, structured in 24 clinical questions, were evaluated. A panel of experts composed of a total of 15 specialists, answered the two rounds of consultation through an online platform. The results were analysed and discussed in a face-to-face meeting with the coordinators and the scientific committee. According to the percentage of panellists who agreed on their findings, the results were classified in terms of unanimity, consensus, majority and discrepancy. Results: The following points were agreed upon: (1) the patient's phenotype determines the use of SYSADOAs; (2) SYSADOAs are considered appropriate in primary OA (knee, hand and hip) and in some types of secondary OA; they are not considered appropriate in OA of the shoulder, spine, ankle and erosive OA of the hands; (3) SYSADOAs may be prescribed for patients at risk of or with cardiovascular disease, digestive disease, hypertension, dyslipaemia, peripheral vascular disease, type 2 diabetes and, excluding diacerein, for patients with oesophageal reflux. No agreement was obtained on the prescription of SYSADOAs for patients with hepatic and renal disease. Conclusions: There is limited literature on the use of SYSADOAs for the treatment of OA in controversial situations. Through this work it has been possible to establish the position of a group of experts regarding clinical situations for which there is no scientific evidence concerning their use.(AU)

Experts document about an adequate utilization of SYSADOAs in controversial clinical situations.

BACKGROUND AND OBJECTIVE: SYSADOAs (Symptomatic Slow-Acting Drugs for Osteoarthritis) are natural compounds that have been shown to be useful and safe in the treatment of osteoarthritis (OA). However, their use in certain clinical situations still lacks scientific evidence and clear recommendations. The objective of this work was to learn the opinion of a group of experts regarding the appropriate use of SYSADOA in the treatment of OA in controversial clinical situations. MATERIALS AND METHODS: Following the Delphi technique, 206 specific consultations, structured in 24 clinical questions, were evaluated. A panel of experts composed of a total of 15 specialists, answered the two rounds of consultation through an online platform. The results were analysed and discussed in a face-to-face meeting with the coordinators and the scientific committee. According to the percentage of panellists who agreed on their findings, the results were classified in terms of unanimity, consensus, majority and discrepancy. RESULTS: The following points were agreed upon: (1) the patient's phenotype determines the use of SYSADOAs; (2) SYSADOAs are considered appropriate in primary OA (knee, hand and hip) and in some types of secondary OA; they are not considered appropriate in OA of the shoulder, spine, ankle and erosive OA of the hands; (3) SYSADOAs may be prescribed for patients at risk of or with cardiovascular disease, digestive disease, hypertension, dyslipaemia, peripheral vascular disease, type 2 diabetes and, excluding Diacerein, for patients with oesophageal reflux. No agreement was obtained on the prescription of SYSADOAs for patients with hepatic and renal disease. CONCLUSIONS: There is limited literature on the use of SYSADOAs for the treatment of OA in controversial situations. Through this work it has been possible to establish the position of a group of experts regarding clinical situations for which there is no scientific evidence concerning their use. This work may contribute towards improving the management protocols of SYSADOAs in the treatment of OA and offer a useful approach in uncertain situations.

A patients' view of OA: the Global Osteoarthritis Patient Perception Survey (GOAPPS), a pilot study.

BACKGROUND: Globally, osteoarthritis (OA) is the third condition associated with disability. There is still poor treatment in OA but science holds the key to finding better treatments and a cure. It is essential to learn what's important to patients from them to implement the most effective OA management. The OA Patients Task Force, conducted the Global OA Patient Perception Survey (GOAPPS)-the first global survey made by patients to analize the quality of life (QoL) & patient perceptions of care. The goal was to collect data on OA patients' perception of OA to understand patients' needs and expectations to improve OA management. METHODS: Observational, cross-sectional study by online survey data collection from six countries, translated into three languages. The questionnaire was comprised of 3 sections: patient demographics and clinical symptomology characteristics; relationship with physicians: perception of attention, treatment, and information provided; and OA impact on daily activity and QoL. The results of the survey were evaluated using the Limited Data Set. The survey results were analyzed using descriptive statistics to characterize the patients' answers. Additionally, Cronbach's alpha was calculated to determine internal consistency validity. RESULTS: A total of 1512 surveys were completed in 6 countries. 84.2% of respondents reported pain/tenderness and 91.1% experienced limitations to physical activities. 42.3% of patients were not satisfied with their current OA treatment. 86% had comorbidities, especially hypertension, and obesity. 51.3 and 78% would like access to additional drug or additional non-drug/non-surgical treatments respectively. 48.2% of patients perceived their QoL to be affected by OA. The Cronbach's alpha was 0.61. CONCLUSIONS: OA has a significant impact on patients' daily activities and their desire to play an active role in managing this disease. Patients are seeking additional treatments, especially no pharmacological/no surgical treatments stressing the need for investing in clinical research, implementing OA preventive measures, and managing interventions to improve the healthcare value chain in OA.

Experts Document About an Adequate Utilization of SYSADOAs in Controversial Clinical Situations. / Documento de expertos sobre el uso apropiado de los SYSADOA en situaciones clínicas controvertidas.

BACKGROUND AND OBJECTIVE: SYSADOAs (symptomatic slow-acting drugs for osteoarthritis) are natural compounds that have been shown to be useful and safe in the treatment of osteoarthritis (OA). However, their use in certain clinical situations still lacks scientific evidence and clear recommendations. The objective of this work was to learn the opinion of a group of experts regarding the appropriate use of SYSADOA in the treatment of OA in controversial clinical situations. MATERIALS AND METHODS: Following the Delphi technique, 206 specific consultations, structured in 24 clinical questions, were evaluated. A panel of experts composed of a total of 15 specialists, answered the two rounds of consultation through an online platform. The results were analysed and discussed in a face-to-face meeting with the coordinators and the scientific committee. According to the percentage of panellists who agreed on their findings, the results were classified in terms of unanimity, consensus, majority and discrepancy. RESULTS: The following points were agreed upon: (1) the patient's phenotype determines the use of SYSADOAs; (2) SYSADOAs are considered appropriate in primary OA (knee, hand and hip) and in some types of secondary OA; they are not considered appropriate in OA of the shoulder, spine, ankle and erosive OA of the hands; (3) SYSADOAs may be prescribed for patients at risk of or with cardiovascular disease, digestive disease, hypertension, dyslipaemia, peripheral vascular disease, type 2 diabetes and, excluding diacerein, for patients with oesophageal reflux. No agreement was obtained on the prescription of SYSADOAs for patients with hepatic and renal disease. CONCLUSIONS: There is limited literature on the use of SYSADOAs for the treatment of OA in controversial situations. Through this work it has been possible to establish the position of a group of experts regarding clinical situations for which there is no scientific evidence concerning their use. This work may contribute towards improving the management protocols of SYSADOAs in the treatment of OA and offer a useful approach in uncertain situations.

Subspheroids in the lithic assemblage of Barranco León (Spain): Recognizing the late Oldowan in Europe.

The lithic assemblage of Barranco León (BL), attributed to the Oldowan techno-complex, contributes valuable information to reconstruct behavioral patterning of the first hominins to disperse into Western Europe. This archaic stone tool assemblage comprises two, very different groups of tools, made from distinct raw materials. On the one hand, a small-sized toolkit knapped from Jurassic flint, comprising intensively exploited cores and small-sized flakes and fragments and, on the other hand, a large-sized limestone toolkit that is mainly linked to percussive activities. In recent years, the limestone macro-tools have been the center of particular attention, leading to a re-evaluation of their role in the assemblage. Main results bring to light strict hominin selective processes, mainly concerning the quality of the limestone and the morphology of the cobbles, in relation to their use-patterning. In addition to the variety of traces of percussion identified on the limestone tools, recurrences have recently been documented in their positioning and in the morphology of the active surfaces. Coupled with experimental work, this data has contributed to formulating hypothesis about the range of uses for these tools, beyond stone knapping and butchery, for activities such as: wood-working or tendon and meat tenderizing. The abundance of hammerstones, as well as the presence of heavy-duty scrapers, are special features recognized for the limestone component of the Barranco León assemblage. This paper presents, for the first time, another characteristic of the assemblage: the presence of polyhedral and, especially, subspheroid morphologies, virtually unknown in the European context for this timeframe. We present an analysis of these tools, combining qualitative evaluation of the raw materials, diacritical study, 3D geometric morphometric analysis of facet angles and an evaluation of the type and position of percussive traces; opening up the discussion of the late Oldowan beyond the African context.

Global management of patients with knee osteoarthritis begins with quality of life assessment: a systematic review.

BACKGROUND: Knee osteoarthritis (KOA) is a prevalent form of chronic joint disease associated with functional restrictions and pain. Activity limitations negatively impact social connectedness and psychological well-being, reducing the quality of life (QoL) of patients. The purpose of this review is to summarize the existing information on QoL in KOA patients and share the reported individual factors, which may influence it. METHODS: We conducted a systematic review examining the literature up to JAN/2017 available at MEDLINE, EMBASE, Cochrane, and PsycINFO using KOA and QOL related keywords. Inclusion criteria were QOL compared to at least one demographic factor (e.g., age, gender), lifestyle factor (e.g., functional independence), or comorbidity factor (e.g., diabetes, obesity) and a control group. Analytical methods were not considered as part of the original design. RESULTS: A total of 610 articles were reviewed, of which 62 met inclusion criteria. Instruments used to measure QoL included: SF-36, EQ-5D, KOOS, WHOQOL, HAS, AIMS, NHP and JKOM. All studies reported worse QoL in KOA patients when compared to a control group. When females were compared to males, females reported worse QOL. Obesity as well as lower level of physical activity were reported with lower QoL scores. Knee self-management programs delivered by healthcare professionals improved QoL in patients with KOA. Educational level and higher total mindfulness were reported to improve QoL whereas poverty, psychological distress, depression and lacking familial relationships reduce it. Surgical KOA interventions resulted in good to excellent outcomes generally; although, results varied by age, weight, and depression. CONCLUSION: KOA has a substantial impact on QoL. In KOA patients, QoL is also influenced by specific individual factors including gender, body weight, physical activity, mental health, and education. Importantly, education and management programs designed to support KOA patients report improved QoL. QoL data is a valuable tool providing health care professionals with a better comprehension of KOA disease to aid implementation of the most effective management plan.

Predictive modeling of therapeutic response to chondroitin sulfate/glucosamine hydrochloride in knee osteoarthritis.

BACKGROUND: In the present study, we explored potential protein biomarkers useful to predict the therapeutic response of knee osteoarthritis (KOA) patients treated with pharmaceutical grade Chondroitin sulfate/Glucosamine hydrochloride (CS+GH; Droglican, Bioiberica), in order to optimize therapeutic outcomes. METHODS: A shotgun proteomic analysis by iTRAQ labelling and liquid chromatography-mass spectrometry (LC-MS/MS) was performed using sera from 40 patients enrolled in the Multicentre Osteoarthritis interVEntion trial with Sysadoa (MOVES). The panel of proteins potentially useful to predict KOA patient's response was clinically validated in the whole MOVES cohort at baseline (n = 506) using commercially available enzyme-linked immunosorbent assays kits. Logistic regression models and receiver-operating-characteristics (ROC) curves were used to analyze the contribution of these proteins to our prediction models of symptomatic drug response in KOA. RESULTS: In the discovery phase of the study, a panel of six putative predictive biomarkers of response to CS+GH (APOA2, APOA4, APOH, ITIH1, C4BPa and ORM2) were identified by shotgun proteomics. Data are available via ProteomeXchange with identifier PXD012444. In the verification phase, the panel was verified in a larger set of KOA patients (n = 262). Finally, ITIH1 and ORM2 were qualified by a blind test in the whole MOVES cohort at baseline. The combination of these biomarkers with clinical variables predict the patients' response to CS+GH with a specificity of 79.5% and a sensitivity of 77.1%. CONCLUSIONS: Combining clinical and analytical parameters, we identified one biomarker that could accurately predict KOA patients' response to CS+GH treatment. Its use would allow an increase in response rates and safety for the patients suffering KOA.

The genomic history of the Iberian Peninsula over the past 8000 years.

We assembled genome-wide data from 271 ancient Iberians, of whom 176 are from the largely unsampled period after 2000 BCE, thereby providing a high-resolution time transect of the Iberian Peninsula. We document high genetic substructure between northwestern and southeastern hunter-gatherers before the spread of farming. We reveal sporadic contacts between Iberia and North Africa by ~2500 BCE and, by ~2000 BCE, the replacement of 40% of Iberia's ancestry and nearly 100% of its Y-chromosomes by people with Steppe ancestry. We show that, in the Iron Age, Steppe ancestry had spread not only into Indo-European-speaking regions but also into non-Indo-European-speaking ones, and we reveal that present-day Basques are best described as a typical Iron Age population without the admixture events that later affected the rest of Iberia. Additionally, we document how, beginning at least in the Roman period, the ancestry of the peninsula was transformed by gene flow from North Africa and the eastern Mediterranean.

Chondroitin Sulfate Inhibits Monocyte Chemoattractant Protein-1 Release From 3T3-L1 Adipocytes: A New Treatment Opportunity for Obesity-Related Inflammation?

Monocyte chemoattractant protein-1 (MCP-1) overproduction from inflamed adipose tissue is a major contributor to obesity-related metabolic syndromes. 3T3-L1 embryonic fibroblasts were cultured and differentiated into adipocytes using an established protocol. Adipocytes were treated with lipopolysaccharide (LPS) to induce inflammation and thus MCP-1 release. At the same time, varying concentrations of chondroitin sulfate (CS) were added in a physiologically relevant range (10-200 µg/mL) to determine its impact on MCP-1 release. Chondroitin sulfate, a natural glycosaminoglycan of connective tissue including the cartilage extracellular matrix, was chosen on the basis of our previous studies demonstrating its anti-inflammatory effect on macrophages. Because the main action of MCP-1 is to induce monocyte migration, cultured THP-1 monocytes were used to test whether CS at the highest physiologically relevant concentration could inhibit cell migration induced by human recombinant MCP-1. Chondroitin sulfate (100-200 µg/mL) inhibited MCP-1 release from inflamed adipocytes in a dose-dependent manner (P < .01, 95% confidence interval [CI]: -5.89 to -3.858 at 100 µg/mL and P < .001, 95% CI: -6.028 to -3.996 at 200 µg/mL) but had no effect on MCP-1-driven chemotaxis of THP-1 monocytes. In summary, CS could be expected to reduce macrophage infiltration into adipose tissue by reduction in adipocyte expression and release of MCP-1 and as such might reduce adipose tissue inflammation in response to pro-inflammatory stimuli such as LPS, now increasingly recognized to be relevant in vivo.

Efectos del condroitín sulfato sobre la respuesta cerebral a la estimulación dolorosa en pacientes con artrosis de rodilla. Estudio de resonancia magnética funcional aleatorizado, doble ciego y controlado con placebo / Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study

Introducción: La artrosis de rodilla es causa de dolor e incapacidad funcional. Uno de los problemas para evaluar la eficacia de los analgésicos ha sido la falta de medidas objetivas de dolor, aunque la resonancia magnética funcional (RMf) ha surgido como un medio útil para objetivar la respuesta del cerebro a la estimulación dolorosa. Hemos investigado el efecto del condroitín sulfato (CS) sobre la respuesta del cerebro a la estimulación dolorosa de la rodilla en pacientes con artrosis mediante RMf. Métodos: Veintidós pacientes recibieron CS (800mg/día) y 27 placebo y fueron evaluados inicialmente y después de 4 meses de tratamiento. En cada sesión de RMf se aplicó presión dolorosa sobre la interlínea de la rodilla y en la superficie de la rótula. El resultado se cuantificó como la atenuación de la respuesta cerebral a la estimulación dolorosa de la rodilla. Resultados: La RMf de la maniobra rotuliana mostró una reducción de la activación en la región de la sustancia gris periacueductal del mesencéfalo significativamente mayor durante el tratamiento con CS que en la condición de placebo. El grupo de CS, pero no el de placebo, mostró además una reducción de la activación en la representación cortical de la pierna tras el tratamiento. No se observaron efectos del CS con presión dolorosa sobre la interlínea de la rodilla. Conclusiones: La RMf fue sensible para objetivar los efectos del CS sobre la respuesta del cerebro a la presión dolorosa sobre el cartílago rotuliano-femoral, que es un resultado coherente con la acción conocida del CS sobre la regeneración de los condrocitos. El presente trabajo muestra nuevamente la utilidad de la RMf para objetivar los efectos del tratamiento en el dolor de origen artrósico (AU)

Introduction: Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI. Methods: Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain. Results: fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test. Conclusions: fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration. The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain (AU)

Effects of chondroitin sulfate on brain response to painful stimulation in knee osteoarthritis patients. A randomized, double-blind, placebo-controlled functional magnetic resonance imaging study. / Efectos del condroitín sulfato sobre la respuesta cerebral a la estimulación dolorosa en pacientes con artrosis de rodilla. Estudio de resonancia magnética funcional aleatorizado, doble ciego y controlado con placebo.

INTRODUCTION: Knee osteoarthritis is causing pain and functional disability. One of the inherent problems with efficacy assessment of pain medication was the lack of objective pain measurements, but functional magnetic resonance imaging (fMRI) has emerged as a useful means to objectify brain response to painful stimulation. We have investigated the effect of chondroitin sulfate (CS) on brain response to knee painful stimulation in patients with knee osteoarthritis using fMRI. METHODS: Twenty-two patients received CS (800mg/day) and 27 patients placebo, and were assessed at baseline and after 4 months of treatment. Two fMRI tests were conducted in each session by applying painful pressure on the knee interline and on the patella surface. The outcome measurement was attenuation of the response evoked by knee painful stimulation in the brain. RESULTS: fMRI of patella pain showed significantly greater activation reduction under CS compared with placebo in the region of the mesencephalic periaquecductal gray. The CS group, additionally showed pre/post-treatment activation reduction in the cortical representation of the leg. No effects of CS were detected using the interline pressure test. CONCLUSIONS: fMRI was sensitive to objectify CS effects on brain response to painful pressure on patellofemoral cartilage, which is consistent with the known CS action on chondrocyte regeneration. The current work yields further support to the utility of fMRI to objectify treatment effects on osteoarthritis pain.

Mesenchymal Stem Cells as Therapeutics Agents: Quality and Environmental Regulatory Aspects.

Mesenchymal stem cells (MSCs) are one of the main stem cells that have been used for advanced therapies and regenerative medicine. To carry out the translational clinical application of MSCs, their manufacturing and administration in human must be controlled; therefore they should be considered as medicine: stem cell-based medicinal products (SCMPs). The development of MSCs as SCMPs represents complicated therapeutics due to their extreme complex nature and rigorous regulatory oversights. The manufacturing process of MSCs needs to be addressed in clean environments in compliance with requirements of Good Manufacturing Practice (GMP). Facilities should maintain these GMP conditions according to international and national medicinal regulatory frameworks that introduce a number of specifications in order to produce MSCs as safe SCMPs. One of these important and complex requirements is the environmental monitoring. Although a number of environmental requirements are clearly defined, some others are provided as recommendations. In this review we aim to outline the current issues with regard to international guidelines which impact environmental monitoring in cleanrooms and clean areas for the manufacturing of MSCs.