Fundamentals of OA. An initiative of Osteoarthritis and Cartilage. Obesity and metabolic factors in OA.

OBJECTIVE: Obesity was once considered a risk factor for knee osteoarthritis (OA) primarily for biomechanical reasons. Here we provide an additional perspective by discussing how obesity also increases OA risk by altering metabolism and inflammation. DESIGN: This narrative review is presented in four sections: 1) metabolic syndrome and OA, 2) metabolic biomarkers of OA, 3) evidence for dysregulated chondrocyte metabolism in OA, and 4) metabolic inflammation: joint tissue mediators and mechanisms. RESULTS: Metabolic syndrome and its components are strongly associated with OA. However, evidence for a causal relationship is context dependent, varying by joint, gender, diagnostic criteria, and demographics, with additional environmental and genetic interactions yet to be fully defined. Importantly, some aspects of the etiology of obesity-induced OA appear to be distinct between men and women, especially regarding the role of adipose tissue. Metabolomic analyses of serum and synovial fluid have identified potential diagnostic biomarkers of knee OA and prognostic biomarkers of disease progression. Connecting these biomarkers to cellular pathophysiology will require future in vivo studies of joint tissue metabolism. Such studies will help reveal when a metabolic process or a metabolite itself is a causal factor in disease progression. Current evidence points towards impaired chondrocyte metabolic homeostasis and metabolic-immune dysregulation as likely factors connecting obesity to the increased risk of OA. CONCLUSIONS: A deeper understanding of how obesity alters metabolic and inflammatory pathways in synovial joint tissues is expected to provide new therapeutic targets and an improved definition of "metabolic" and "obesity" OA phenotypes.

Community Alcohol Partnerships with the alcohol industry: what is their purpose and are they effective in reducing alcohol harms?

Background: Local initiatives to reduce alcohol harms are common. One UK approach, Community Alcohol Partnerships (CAPs), involves partnerships between the alcohol industry and local government, focussing on alcohol misuse and anti-social behaviour (ASB) among young people. This study aimed to assess the evidence of effectiveness of CAPs. Methods: We searched CAP websites and documents, and databases, and contacted CAPs to identify evaluations and summarize their findings. We appraised these against four methodological criteria: (i) reporting of pre-post data; (ii) use of comparison area(s); (iii) length of follow-up; and (iv) baseline comparability of comparison and intervention areas. Results: Out of 88 CAPs, we found three CAP evaluations which used controlled designs or comparison areas, and further data on 10 other CAPs. The most robust evaluations found little change in ASB, though few data were presented. While CAPs appear to affect public perceptions of ASB, this is not a measure of the effectiveness of CAPs. Conclusions: Despite industry claims, the few existing evaluations do not provide convincing evidence that CAPs are effective in reducing alcohol harms or ASB. Their main role may be as an alcohol industry corporate social responsibility measure which is intended to limit the reputational damage associated with alcohol-related ASB.

Phytoremediation of Lead-Contaminated Soil in the Westside of Atlanta, GA.

Phytoremediation has been explored as a cost-effective method to remediate soil Pb contamination. A greenhouse study was conducted to evaluate the efficacy of Vigna unguiculata, Brassica pekinensis, Gomphrena globose, and Helianthus annuus for removing and immobilizing Pb in soil collected from the Westside Lead Superfund site in Atlanta. Plants were cultivated in sampled soil with a Pb concentration of 515 ± 10 mg/kg for 60 days. Soils growing H. annuus were additionally treated with ethylenediaminetetraacetic acid (EDTA) (0.1 g/kg) or compost (20% soil blend) to assess their capabilities for enhancing phytoremediation. Mean post-phytoremediation Pb concentrations in the four plant species were 23.5, 25.7, 50.0, and 58.1 mg/kg dry weight (DW), respectively, and were substantially higher than 1.55 mg/kg DW in respective plant species grown in control soils with no Pb contamination. The highest Pb concentration, translocation factor, and biomass were found in V. unguiculate among four species without soil amendments. H. annuus treated with EDTA and compost resulted in a significant increase in the total Pb uptake and larger biomass compared to non-treated plants, respectively. Although this study found that V. unguiculata was the best candidate for Pb accumulation and immobilization among four species, soil remediation was limited to 54 mg/kg in a growing season. We find that it is critically important to perform phytostabilization in a secure manner, since Pb bioavailability of edible plant parts implies the potential risk associated with their unintentional consumption. Efficiently and effectively remediating Pb-contaminated soils in a low-cost manner needs to be further studied.

Estimating the prevalence of dry eye among Indian patients attending a tertiary ophthalmology clinic.

McMonnies' and Ocular Surface Disease Index (OSDI) questionnaires were used to estimate the prevalence of dry eye among 400 consecutive patients aged >40 years attending the ophthalmology outpatient department of the Lady Hardinge Medical College and associated Smt Sucheta Kriplani Hospital, in New Delhi, India. These estimates were then compared with the results of various clinical tests and examinations of the same patients, including Schirmer's tests, evaluations of tear-film breakup times and fluorescein staining of corneas. Although the overall prevalence of dry eye based on OSDI was 29.25%, there was considerable age- and gender-related variation in this parameter. Compared with the younger patients, those aged >or=80 years were more likely to have OSDI that were indicative of dry eye (41.2%), and the women investigated were more likely to have dry eye (as indicated by OSDI) than the men (27% v. 12%). Occupation, however, appeared to have no effect on the risk of dry eye (P=0.952). Grittiness was the commonest complaint reported. McMonnies' indices (MMI), OSDI and the values recorded in Schirmer's tests were all significantly and positively correlated with the probability of a clinical diagnosis of dry eye (P<0.001 for each). Only patients with a Schirmer's value of <8 mm showed fluorescein staining of the cornea (P<0.005). This appears to be the first report from India in which MMI and OSDI have been significantly correlated with the probability of a clinical diagnosis of dry eye. Although the subjects were recruited in an ophthalmology department and may not have been very representative of the general population of New Delhi, dry-eye syndrome is probably common in the study area and probably has a considerable socio-economic impact. The early detection and timely management of this syndrome is important, as they can help prevent long-term sequelae and sight-threatening complications.

In vitro safety evaluation and anticlastogenic effect of BacoMind on human lymphocytes.

OBJECTIVE: BacoMind (BM) is a standardized extract of Bacopa monnieri, which belongs to the family Scrophulariaceae and is a creeping annual plant found throughout the Indian subcontinent. It has been used by Ayurvedic medicinal practitioners in India for almost 3000 years and is classified as a medharasayana, a substance which improves memory and intellect. With the widespread traditional use as well as scientific validation of Bacopa monnieri for nootropic activity, a bioactive-rich unique phytochemical composition-BacoMind was developed from B. monnieri for use as a cognition and memory enhancing agent. The present study aimed to investigate the in vitro toxicity of this formulation of BacoMind on human lymphocytes and to rule out its possible contribution to mutagenicity. METHODS: In the present investigation the active ingredients present in BM were identified and quantified by high performance liquid chromatography (HPLC) and high performance thin-layer chromatography (HPTLC). Antioxidant and anticlastogenic properties of BM were studied in vitro with and without metabolic activation. Doses of BM were chosen on the basis of mitotic index (MI) and cytokinesis-block proliferation index (CBPI). Clastogenicity assays were performed at 31.2 microg/mL, 62.5 microg/mL, and 125 microg/mL, while the Salmonella reverse mutation assay (Ames test) was performed at doses of 61.72, 185.18, 555.55, 1666.67, and 5000.00 microg/plate. RESULTS: HPLC and HPTLC analysis of BM revealed the presence of bacoside A3, bacopaside I, bacopaside II, jujubogenin isomer of bacopasaponin C, bacosine, luteolin, apigenin, bacosine, and beta-sitosterol D glucoside. BM demonstrated significant antioxidant activity. The number of chromosomal aberrations and the frequency of micronuclei induced by BM were not statistically significant up to a dose of 62.5 microg/mL. A subsequent dose of 125 microg/mL prior to metabolic activation induced mild clastogenicity, but it was found to be biologically insignificant as this effect was not seen post metabolic activation. BM also demonstrated a dose-dependent protection against the clastogens used in this study using the above tests for clastogenicity. Maximum protection was observed in presence of metabolic activation. Moreover, BM demonstrated no mutagenic effect on the tested strains, as observed in the Ames test. CONCLUSION: BM protected human lymphocytes against various clastogens. BM also exhibited high antioxidant activity which might be responsible for the observed protective effects against the clastogens since the used clastogens are known to induce their clastogenic effects via production of oxidative radicals.

A rare case of benign isolated schwannoma in the inferior orbit.

A rare case of unilateral orbital schwannoma arising from the infraorbital nerve is presented. An excision biopsy with complete removal of the mass in the inferior orbit was performed. A definitive diagnosis was made on histopathological examination. The clinical and histological features of schwannoma are discussed. A need for early removal of such tumors is recommended to prevent complications.

Life sciences licensing deals in the second quarter of 2018: updates and trends.

During the second quarter of 2018, Cortellis Competitive Intelligence registered 985 new deals (excluding mergers and acquisitions) with a total disclosed deal value of USD 19.5 billion as part of its ongoing coverage of licensing activity in the life sciences sector compared to 964 and USD 35.6 billion in the first quarter and 1,104 and USD 13.6 billion in the second quarter of 2017. Total deal value in the second quarter did not quite reach the peak of 2014 (paced by Novartis' USD 16 billion purchase of GlaxoSmithKline's oncology portfolio) but eclipsed the previous quarter primarily due to Allogene's USD 2.8 billion license for Cellectis' chimeric antigen receptor T-cell immunotherapy program for cancer.

Life sciences licensing deals in the fourth quarter of 2017: updates and trends.

During the fourth quarter of 2017, Cortellis Competitive Intelligence registered 1,107 new deals (excluding mergers & acquisitions) as part of its ongoing coverage of licensing activity in the life sciences sector compared to 1,043 in the third quarter and 1,035 in the fourth quarter of 2016.

The year's new drugs & biologics, 2017, part II - News that shaped the industry in 2017.

This eagle's-eye overview of the drug industry in 2017 provides insight into some of last year's top stories, including the growing opioid crisis affecting the U.S. and other developed countries and the 2017-2018 influenza epidemic, with a spotlight on the need for a universal flu vaccine. As in previous years, we also review orphan drug development, new agency-supported programs such as PRIME and RMAT, pipeline attrition and drug pricing, as well as pharma/biotech mergers and acquisitions of note. Finally, we take a glimpse into the crystal ball to anticipate the new drugs that will be approved in 2018.

Notable licensing deals in the biopharma industry in the second quarter of 2017.

During the second quarter of 2017, Cortellis Competitive Intelligence added 967 new licensing deals (excluding mergers and acquisition deals) as part of its ongoing coverage of pharmaceutical licensing activity. This meant an 8% decrease on the previous quarter (1,050) and a 3% decrease from the same quarter in 2016 (993). This quarter also showed a significant decline in the number of deals worth more than USD 0.5 billion from the last quarter (7 vs. 17). This article will highlight a number of the most valuable and notable deals forged during the quarter, as well as a selection of deals from some of the most prolific deal makers in the life sciences. An update on milestone, options and terminated deals of significance will also be presented, along with an early outlook on the next quarter's pharmaceutical licensing activity.

Notable licensing deals in the biopharma industry in the third quarter of 2017.

During the third quarter of 2017, Cortellis Competitive Intelligence registered 949 new deals (excluding mergers and acquisitions) added as part of its ongoing coverage of pharmaceutical licensing activity compared to 1,007 in Q2 this year and 1,023 in Q3 the previous year.

Notable deals in the pharmaceutical industry in the fourth quarter of 2016.

During the fourth quarter of 2016, Cortellis Competitive Intelligence had 889 new deals added as part of its ongoing coverage of pharmaceutical licensing activity. This was an increase on both the last quarter (865) but a decrease from the same quarter for the previous year (915). This article will focus on highlighting a number of the most valuable and notable deals forged during the quarter, as well as a selection of deals from some of the most prolific deal makers. An update on milestones, options and terminated deals of significance will also be presented, along with an early outlook on the next quarter's pharmaceutical licensing activity.

Pharma Pricing & Market Access Europe 2016--Health Network Communications' Tenth Annual Conference (February 23-25, 2016--London, UK).

Tighter national budgets and escalating drug prices continue to present challenges for pharmaceutical market access strategies and societal cost of care. As pharmaceutical companies and medical governmental advisory organizations enter tougher negotiations, hospital trusts and other dispensary firms face barriers to receiving the best medical treatment, and as a result patient access is limited. The 2016 HealthNetwork Communications' Pharma Pricing & Market Access Europe meeting brought together pharmaceutical, medical governmental advisory and stakeholders and market access/pricing consultants, to encourage discussions and negotiations into how to improve the drug pricing system and consequential market access strategies while achieving the respective reimbursement and affordability objectives.

Notable deals in the pharmaceutical industry in the second quarter of 2016.

During the second quarter of 2016, Cortellis Competitive Intelligence had 1,014 new deals added as part of its ongoing coverage of pharmaceutical licensing activity. This was on par with the last quarter (1,011) and a substantial increase on the same quarter for the previous 1 year (659). This article will focus on highlighting a number of the most valuable and notable deals forged during the quarter, as well as a selection of deals from some of the most prolific deal makers. An update on milestone, options and terminated deals of significance will also be presented, along with an early outlook on the next quarter's pharmaceutical licensing activity.

European Pharmaceutical Pricing and Reimbursement--SMi's 21st Annual Meeting (October 5-6, 2015--London, UK).

Translating perceived market value for pharmaceutical products into a willingness to pay remains the key factor in ensuring market access and return on investment. How price is managed in the context of new market entrants or new approval settings can create complex challenges, and further complexity is added through diverse global reimbursement structures and the myriad of stakeholders involved at every step of value identification. SMi's 21st Annual Meeting on European Pricing and Reimbursement presented a program focused on the measures being taken by European healthcare systems as they seek to facilitate access to the latest treatments while delivering value for payers and patients. Supporting patient access to life-changing medicines is a challenge, and funders are responding in many different ways; however, while the pharma industry continues to focus its efforts on high cost drugs that treat diseases of the few, the disconnect will be not be resolved. The speakers and delegates at the annual meeting believe success is possible by focusing on value for patients, driven by provider experience, scale and learning. Instead of simply lowering costs, companies, providers and payers can more adequately contribute to the goals of funders as well as the treatment needs of patients.