Quantitative Analysis of Mycobacterial and Propionibacterial DNA in Lymph Nodes of Japanese and European Patients with Sarcoidosis

The cause(s) of sarcoidosis is unknown. Mycobacterium spp. are suspected in Europe and Propionibacterium spp. are suspected in Japan. The present international collaboration evaluated the possible etiological links between sarcoidosis and the suspected bacterial species. Formalin-fixed and paraffin-embedded sections of biopsy samples of lymph nodes, one from each of 108 patients with sarcoidosis and 65 patients with tuberculosis, together with 86 control samples, were collected from two institutes in Japan and three institutes in Italy, Germany, and England. Genomes of Propionibacterium acnes, Propionibacterium granulosum, Mycobacterium tuberculosis, Mycobacterium avium subsp. paratuberculosis, and Escherichia coli (as the control) were counted by quantitative real-time PCR. Either P. acnes or P. granulosum was found in all but two of the sarcoid samples. M. avium subsp. paratuberculosis was found in no sarcoid sample. M. tuberculosis was found in 0 to 9% of the sarcoid samples but in 65 to 100% of the tuberculosis samples. In sarcoid lymph nodes, the total numbers of genomes of P. acnes or P. granulosum were far more than those of M. tuberculosis. P. acnes or P. granulosum was found in 0 to 60% of the tuberculosis and control samples, but the total numbers of genomes of P. acnes or P. granulosum in such samples were less than those in sarcoid samples. Propionibacterium spp. are more likely than Mycobacteria spp. to be involved in the etiology of sarcoidosis, not only in Japanese but also in European patients with sarcoidosis.     

Molecular and Cellular Mechanisms of Delayed Fracture Healing in Mmp10 (Stromelysin 2) Knockout Mice

The remodeling of the extracellular matrix is a central function in endochondral ossification and bone homeostasis. During secondary fracture healing, vascular invasion and bone growth requires the removal of the cartilage intermediate and the coordinate action of the collagenase matrix metalloproteinase (MMP)-13, produced by hypertrophic chondrocytes, and the gelatinase MMP-9, produced by cells of hematopoietic lineage. Interfering with these MMP activities results in impaired fracture healing characterized by cartilage accumulation and delayed vascularization. MMP-10, Stromelysin 2, a matrix metalloproteinase with high homology to MMP-3 (Stromelysin 1), presents a wide range of putative substrates identified in vitro, but its targets and functions in vivo and especially during fracture healing and bone homeostasis are not well defined. Here, we investigated the role of MMP-10 through bone regeneration in C57BL/6 mice. During secondary fracture healing, MMP-10 is expressed by hematopoietic cells and its maximum expression peak is associated with cartilage resorption at 14 days post fracture (dpf). In accordance with this expression pattern, when Mmp10 is globally silenced, we observed an impaired fracture-healing phenotype at 14 dpf, characterized by delayed cartilage resorption and TRAP-positive cell accumulation. This phenotype can be rescued by a non-competitive transplant of wild-type bone marrow, indicating that MMP-10 functions are required only in cells of hematopoietic linage. In addition, we found that this phenotype is a consequence of reduced gelatinase activity and the lack of proMMP-9 processing in macrophages. Our data provide evidence of the in vivo function of MMP-10 during endochondral ossification and defines the macrophages as the lead cell population in cartilage removal and vascular invasion. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Ocular Redness Measured with the Keratograph 5M in Patients Using Anti-Glaucoma Eye Drops

Purpose: To examine correlations between ocular redness measured with the new topographer Keratograph 5M and the use of topical anti-glaucoma medication. Methods: A total of 211 eyes of 211 patients with open-angle glaucoma or ocular hypertension on topical medication and 51 eyes of 51 healthy volunteers were recruited over 10 months. Outcome variables were keratograph redness scores (RS): overall, bulbar temporal (BT), bulbar nasal (BN), limbar temporal (LT), and limbar nasal (LN). In each subject, we also recorded the intraocular pressure-lowering eye drops used, daily doses and daily and cumulative preservative concentrations, fluorescein corneal staining score (OXFORD), lower tear meniscus height (Fourier-domain OCT), non-invasive tear film breakup time (Keratograph 5M), and ocular surface disease questionnaire index (OSDI). Results: Higher RS were recorded in the medication than control group (P < 0.01 all scores). Within the medication group, older patients returned greater RS (P < 0.05 all scores). Prostaglandin was a strong predictor of higher scores, except LN RS. A higher OSDI was associated with a higher LN RS (β = 0.007; P < 0.05), while the use of β-blockers was linked to a lower LN RS (β = ?0.225; P < 0.05). The use of ≥3 daily eye drops with preservative gave rise to a higher BN RS and ≥3 daily eye drops to a higher LN RS (β = 0.366, P < 0.01; β = 0.296, P < 0.05, respectively). Conclusion: Keratograph 5M can objectively detect the hyperaemia induced by glaucoma medication. The factors contributing to ocular redness were advanced age, more daily eye drops (nasal sectors), a higher OSDI, and prostaglandin as the medication used.     

Twenty-year trends in the prevalence of Down syndrome and other trisomies in Europe: impact of maternal age and prenatal screening

This study examines trends and geographical differences in total and live birth prevalence of trisomies 21, 18 and 13 with regard to increasing maternal age and prenatal diagnosis in Europe. Twenty-one population-based EUROCAT registries covering 6.1 million births between 1990 and 2009 participated. Trisomy cases included live births, fetal deaths from 20 weeks gestational age and terminations of pregnancy for fetal anomaly. We present correction to 20 weeks gestational age (ie, correcting early terminations for the probability of fetal survival to 20 weeks) to allow for artefactual screening-related differences in total prevalence. Poisson regression was used. The proportion of births in the population to mothers aged 35+ years in the participating registries increased from 13% in 1990 to 19% in 2009. Total prevalence per 10 000 births was 22.0 (95% CI 21.7–22.4) for trisomy 21, 5.0 (95% CI 4.8–5.1) for trisomy 18 and 2.0 (95% CI 1.9–2.2) for trisomy 13; live birth prevalence was 11.2 (95% CI 10.9–11.5) for trisomy 21, 1.04 (95% CI 0.96–1.12) for trisomy 18 and 0.48 (95% CI 0.43–0.54) for trisomy 13. There was an increase in total and total corrected prevalence of all three trisomies over time, mainly explained by increasing maternal age. Live birth prevalence remained stable over time. For trisomy 21, there was a three-fold variation in live birth prevalence between countries. The rise in maternal age has led to an increase in the number of trisomy-affected pregnancies in Europe. Live birth prevalence has remained stable overall. Differences in prenatal screening and termination between countries lead to wide variation in live birth prevalence.     

Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body sizeThe EPIC-InterAct study

Abstract. Beulens JWJ, van der Schouw YT, Bergmann MM, Rohrmann S, B Schulze M, Buijsse B, Grobbee DE, Arriola L, Cauchi S, Tormo M‐J, Allen NE, van der A DL, Balkau B, Boeing H, Clavel‐Chapelon F, de Lauzon‐Guillan B, Franks P, Froguel P, Gonzales C, Halkjær J, Huerta JM, Kaaks R, Key TJ, Khaw KT, Krogh V, Molina‐Montes E, Nilsson P, Overvad K, Palli D, Panico S, Ramón Quirós J, Ronaldsson O, Romieu I, Romaguera D, Sacerdote C, Sánchez M‐J, Spijkerman AMW, Teucher B, Tjonneland A, Tumino R, Sharp S, Forouhi NG, Langenberg C, Feskens EJM, Riboli E, Wareham NJ (University Medical Center Utrecht, The Netherlands; German Institute of Human Nutrition, Potsdam‐Rehbrücke, Germany; German Cancer Research Centre, Heidelberg, Germany; Basque Government, San Sebastian, CIBERESP, Spain; Institut de Biologie de Lille, Lille, France; Murcia Regional Health Council, Murcia, Spain; CIBER Epidemiologia y Salud Publica (CIBERESP), Spain; University of Oxford, Oxford, UK; National Institute of Public Health and the Environment, Bilthoven, The Netherlands; Inserm, CESP Centre for Research in Epidemiology and Population Health, Villejuif Cedex, France; Lund University, Malmö, Sweden; Imperial College, London, UK; Department of Epidemiology, Barcelona, Spain; Danish Cancer Society, Copenhagen, Denmark; University of Cambridge, Cambridge, UK; Fondazione IRCCS Istituto Nazionale Tumori Milan, Milan, Italy; Andalusian School of Public Health, Granada, Spain; School of Public Health, Aarhus, Denmark; Cancer Research and Prevention Institute (ISPO), Florence, Italy; Università Federico II, Napoli, Italy; Consejeria de Salud y Servicios Sanitarios, Oviedo‐Asturias, Spain; Umea University, Umea, Sweden; International Agency for Research of Cancer, Lyon, France; Center for Cancer Prevention (CPO‐Piemonte), Torino, Italy; “Civile ‐ M.P. Arezzo” Hospital, Ragusa, Italy; Addenbrooke’s Hospital, Cambridge, UK; and Wageningen University, Wageningen, The Netherlands). Alcohol consumption and risk of type 2 diabetes in European men and women: influence of beverage type and body size. The EPIC–InterAct study. J Intern Med 2012; 272: 358–370. Objective: To investigate the association between alcohol consumption and type 2 diabetes, and determine whether this is modified by sex, body mass index (BMI) and beverage type. Design: Multicentre prospective case–cohort study. Setting: Eight countries from the European Prospective Investigation into Cancer and Nutrition cohort. Subjects: A representative baseline sample of 16 154 participants and 12 403 incident cases of type 2 diabetes. Interventions: Alcohol consumption assessed using validated dietary questionnaires. Main outcome measures: Occurrence of type 2 diabetes based on multiple sources (mainly self‐reports), verified against medical information. Results: Amongst men, moderate alcohol consumption was nonsignificantly associated with a lower incidence of diabetes with a hazard ratio (HR) of 0.90 (95% CI: 0.78–1.05) for 6.1–12.0 versus 0.1–6.0 g day^?1, adjusted for dietary and diabetes risk factors. However, the lowest risk was observed at higher intakes of 24.1–96.0 g day^?1 with an HR of 0.86 (95% CI: 0.75–0.98). Amongst women, moderate alcohol consumption was associated with a lower incidence of diabetes with a hazard ratio of 0.82 (95% CI: 0.72–0.92) for 6.1–12.0 g day^?1 (P interaction gender <0.01). The inverse association between alcohol consumption and diabetes was more pronounced amongst overweight (BMI ≥ 25 kg m^?2) than normal‐weight men and women (P interaction < 0.05). Adjusting for waist and hip circumference did not alter the results for men, but attenuated the association for women (HR=0.90, 95% CI: 0.79–1.03 for 6.1–12.0 g day^?1). Wine consumption for men and fortified wine consumption for women were most strongly associated with a reduced risk of diabetes. Conclusions: The results of this study show that moderate alcohol consumption is associated with a lower risk of type 2 diabetes amongst women only. However, this risk reduction is in part explained by fat distribution. The relation between alcohol consumption and type 2 diabetes was stronger for overweight than normal‐weight women and men.     

Understanding the relationship between trust in health care and attitudes toward living donor transplant among African Americans with end‐stage renal disease

Transplantation is the favored therapy for patients with end‐stage renal disease (ESRD). Unfortunately, demand for available organs far outpaces the supply. African Americans are disproportionately affected by the ever‐widening gap between organ supply and demand. Additionally, structural, biological, and social factors contribute to feelings of unease some African Americans may feel regarding living donor transplant (LDT). The present research examines the relationship between trust in health care and attitudes toward LDT among African American ESRD patients. We hypothesized that lower trust in health care would be significantly associated with negative attitudes toward LDT, and that this relationship would be moderated by patient attitudes toward dialysis. Data were collected from August 2011 to April 2012 as part of a larger study. Measures included trust (of doctors, racial equity of treatment, and hospitals) and attitudes toward both LDT and dialysis. Bivariate analysis revealed that trust in one's doctor, hospital, and in racial equity in health care was significantly correlated with attitudes toward LDT (r = 0.265; r = 0.131; and r = 0.202, respectively). Additionally, attitudes toward dialysis moderated the relationships between Trust in Doctors/Attitudes toward LDT and Trust in Racial equity of treatment/Attitudes toward LDT. Findings suggest a strong relationship between trust in health care and attitudes toward LDT. These findings also shed light on how dialysis experiences are related to the relationship between trust in health care and attitudes toward LDT.     

Risk Factors Associated With Early Invasive Pulmonary Aspergillosis in Kidney Transplant Recipients: Results From a Multinational Matched Case–Control Study

Risk factors for invasive pulmonary aspergillosis (IPA) after kidney transplantation have been poorly explored. We performed a multinational case–control study that included 51 kidney transplant (KT) recipients diagnosed with early (first 180 posttransplant days) IPA at 19 institutions between 2000 and 2013. Control recipients were matched (1:1 ratio) by center and date of transplantation. Overall mortality among cases was 60.8%, and 25.0% of living recipients experienced graft loss. Pretransplant diagnosis of chronic pulmonary obstructive disease (COPD; odds ratio [OR]: 9.96; 95% confidence interval [CI]: 1.09–90.58; p = 0.041) and delayed graft function (OR: 3.40; 95% CI: 1.08–10.73; p = 0.037) were identified as independent risk factors for IPA among those variables already available in the immediate peritransplant period. The development of bloodstream infection (OR: 18.76; 95% CI: 1.04–339.37; p = 0.047) and acute graft rejection (OR: 40.73, 95% CI: 3.63–456.98; p = 0.003) within the 3 mo prior to the diagnosis of IPA acted as risk factors during the subsequent period. In conclusion, pretransplant COPD, impaired graft function and the occurrence of serious posttransplant infections may be useful to identify KT recipients at the highest risk of early IPA. Future studies should explore the potential benefit of antimold prophylaxis in this group.