Recognition of Immune Response for the Early Diagnosis and Treatment of Osteoarthritis

Osteoarthritis is a common and debilitating joint disease that affects up to 30 million Americans, leading to significant disability, reduction in quality of life, and costing the United States tens of billions of dollars annually. Classically, osteoarthritis has been characterized as a degenerative, wear-and-tear disease, but recent research has identified it as an immunopathological disease on a spectrum between healthy condition and rheumatoid arthritis. A systematic literature review demonstrates that the disease pathogenesis is driven by an early innate immune response which progressively catalyzes degenerative changes that ultimately lead to an altered joint microenvironment. It is feasible to detect this infiltration of cells in the early, and presumably asymptomatic, phase of the disease through noninvasive imaging techniques. This screening can serve to aid clinicians in potentially identifying high-risk patients, hopefully leading to early effective management, vast improvements in quality of life, and significant reductions in disability, morbidity, and cost related to osteoarthritis. Although the diagnosis and treatment of osteoarthritis routinely utilize both invasive and non-invasive strategies, imaging techniques specific to inflammatory cells are not commonly employed for these purposes. This review discusses this paradigm and aims to shift the focus of future osteoarthritis-related research towards early diagnosis of the disease process

Pollution and acne: is there a link?

Jean Krutmann,1 Dominique Moyal,2 Wei Liu,3 Sanjiv Kandahari,4 Geun-Soo Lee,5 Noppakun Nopadon,6 Leihong Flora Xiang,7 Sophie Seité2 1IUF – Leibniz Research Institute for Environmental Medicine, Düsseldorf, Germany; 2La Roche Posay Dermatological Laboratories, Asnières, France; 3Department of Dermatology, The General Hospital of Air Force, PLA, Beijing, People’s Republic of China; 4Dr. Kandhari’s Skin & Dental Clinic, New Delhi, India; 5Drs. Woo and Hann Skin Center, Yongsan-gu, Seoul, Korea; 6Division of Dermatology, Faculty of Medicine, Department of Medicine, Chulalongkorn University, Bangkok, Thailand; 7Department of Dermatology, Huashan Hospital, Fudan University, Shanghai, People’s Republic of China Abstract: In recent years, the critical role that inflammation may play in the development and progression of acne has become increasingly recognized. The prevalence of acne is similar between Asian and Caucasian women, but Asian women have a higher prevalence of inflammatory acne. They also report their symptoms exacerbate during periods of high air pollution. The objective of this study was to review the current evidence that links air pollution to worsening of acne symptoms. Firstly, a group of five Asian and three European scientists with expertise in Dermatology reviewed the current literature and described current acne treatment practices in their countries. During this activity, they identified the need for further epidemiological and clinical research. Secondly, additional studies ensued which provided evidence that acne symptoms might exacerbate in regions of high ambient air pollution. Based on these findings, the authors suggest that people with acne should protect the natural barrier function of their skin with emollients and ultraviolet (UV)A/UVB protection. Keywords: pollution, acne, Asia, epidemiology, pathophysiolog

Labor Induction Outcomes with Outpatient Misoprostol for Cervical Ripening among Low-Risk Women

OBJECTIVE: In 2012, two Kaiser Permanente Northern California (KPNC) hospitals began offering outpatient cervical ripening with oral misoprostol under a study protocol. We evaluated inpatient time from admission to delivery and adverse maternal and neonatal outcomes associated with outpatient use of misoprostol for cervical ripening among low-risk women with term pregnancies. STUDY DESIGN: We conducted a retrospective cohort study comparing three groups: women who received misoprostol (1) outpatient, under a study protocol; (2) inpatient, at the study sites; and (3) inpatient, at all KPNC hospitals. Data were obtained from between 2012 and 2017. The primary outcome was time from inpatient admission to delivery. Secondarily, we evaluated maternal and neonatal outcomes, including the duration and maximum rate of oxytocin administered, rate of cesarean delivery, incidence of chorioamnionitis and blood transfusion, Apgar scores, and neonatal intensive care unit admissions. Demographic and clinical characteristics and outcomes of the outpatient group were compared with both inpatient misoprostol groups using the appropriate statistical test. Variables included in the regression analysis were either statistically significant in the bivariate analyses or have been reported in the literature to be potential confounders: maternal age at admission, race/ethnicity, body mass index, cervical dilation at initial misoprostol, and parity. RESULTS: We analyzed data from 10,253 patients: (1) 345 outpatients, under a study protocol; (2) 1,374 inpatients, at the study sites; and (3) 9,908 inpatients, at all the Kaiser hospitals. Women in the outpatient group were more likely to be white than both inpatient groups (63.3 vs. 56.3% at study sites and 47.1% in all hospitals,  0.002 and \u3c0.001, respectively); other demographics were clinically comparable. Most women undergoing labor induction were nulliparous; however, a greater proportion in the outpatient group were nulliparous compared with inpatient groups (70.8 vs. 61.8% and 64.3%,  = 0.002 and 0.01). On inpatient admission for delivery, women who received outpatient misoprostol were more likely to have a cervical dilation of ≥3 cm (39.8 vs. 12.5% at study sites and 9.7% at all KPNC hospitals,  \u3c 0.001 for both). The outpatient group had a shorter mean time between admission and delivery (23.6 vs. 29.4 at study sites and 29.8 hours at all KPNC,  \u3c 0.001 for both). The adjusted estimated mean difference between the outpatient and inpatient group at all the Kaiser hospitals in time from admission to delivery was -6.48 hours ( \u3c 0.001), and the adjusted estimated mean difference in cervical dilation on admission was +1.02 cm ( \u3c 0.001). There was no difference in cesarean delivery rates between groups. The rate of chorioamnionitis in the outpatient group was higher compared with inpatients at all hospitals (17.7 vs. 10.6%,  0001), but similar when compared with the inpatients at the study sites (17.7 vs. 15.4%,  = 0.29). CONCLUSION: Outpatient use of misoprostol for cervical ripening under the study protocol was associated with reduced inpatient time from admission to delivery compared with inpatient misoprostol. Although there was a higher rate of chorioamnionitis among outpatients under the study protocol compared with inpatients at all hospitals, there was no difference when compared with inpatients at the study sites. There was no difference in rates of cesarean delivery or maternal or neonatal complications with outpatient misoprostol. KEY POINTS: · Outpatient misoprostol patients had 6.46 fewer hours from admission to delivery compared with inpatients at all hospitals.. · There was no difference in the rate of cesareans between the outpatient versus inpatient misoprostol groups.. · Other maternal and neonatal complications were low and comparable among outpatients and inpatients who received misoprostol; this study was not large enough to assess rare safety outcomes.

Targeting thymidine phosphorylase as a potential therapy for bone loss associated with periprosthetic osteolysis

Macrophages are generally thought to play a key role in the pathogenesis of aseptic loosening through initiating periprosthetic inflammation and pathological bone resorption. The aim of this study was to identify macrophage‐derived factors that promote osteoclast differentiation and periprosthetic bone destruction. To achieve this, we examined the effects of 12 macrophage‐derived factors that were identified by RNA‐seq analysis of stimulated macrophages on osteoclast differentiation. Surprisingly, thymidine phosphorylase (TYMP) was found to trigger significant number of osteoclasts that exhibited resorbing activities on dentine slices. Functionally, TYMP knockdown reduced the number of osteoclasts in macrophages that had been stimulated with polyethylene debris. TYMP were detected in serum and synovial tissues of patients that had been diagnosed with aseptic loosening. Moreover, the administration of TYMP onto calvariae of mice induced pathological bone resorption that was accompanied by an excessive infiltration of inflammatory cells and osteoclasts. The RNA‐seq for TYMP‐induced‐osteoclasts was then performed in an effort to understand action mode of TYMP. TYMP stimulation appeared to activate the tyrosine kinase FYN signaling associated with osteoclast formation. Oral administration of saracatinib, a FYN kinase inhibitor, significantly suppressed formation of bone osteolytic lesions in a polyethylene debris‐induced osteolysis model. Our findings highlight a novel molecular target for therapeutic intervention in periprosthetic osteolysis

\u3ci\u3eDrosophila\u3c/i\u3e Muller F Elements Maintain a Distinct Set of Genomic Properties Over 40 Million Years of Evolution

The Muller F element (4.2 Mb, ~80 protein-coding genes) is an unusual autosome of Drosophila melanogaster; it is mostly heterochromatic with a low recombination rate. To investigate how these properties impact the evolution of repeats and genes, we manually improved the sequence and annotated the genes on the D. erecta, D. mojavensis, and D. grimshawi F elements and euchromatic domains from the Muller D element. We find that F elements have greater transposon density (25–50%) than euchromatic reference regions (3–11%). Among the F elements, D. grimshawi has the lowest transposon density (particularly DINE-1: 2% vs. 11–27%). F element genes have larger coding spans, more coding exons, larger introns, and lower codon bias. Comparison of the Effective Number of Codons with the Codon Adaptation Index shows that, in contrast to the other species, codon bias in D. grimshawi F element genes can be attributed primarily to selection instead of mutational biases, suggesting that density and types of transposons affect the degree of local heterochromatin formation. F element genes have lower estimated DNA melting temperatures than D element genes, potentially facilitating transcription through heterochromatin. Most F element genes (~90%) have remained on that element, but the F element has smaller syntenic blocks than genome averages (3.4–3.6 vs. 8.4–8.8 genes per block), indicating greater rates of inversion despite lower rates of recombination. Overall, the F element has maintained characteristics that are distinct from other autosomes in the Drosophila lineage, illuminating the constraints imposed by a heterochromatic milieu