The liturgical theology of Zaharija Orfelin's work against Roman papacy (Patriarchal library rs 214) in the context of the 18th century confessional-polemical literature in the Metropolitanate of Karlovci

Предмет истраживања овога рада је литургијска теологија у рукописном делу Захарија Орфелина Против Папства римскаго (Патријаршијска библиотека Рс 214), која је преиспитана и сагледана у контексту владајуће конфесионално-полемичке литературе Карловачке митрополије XVIII столећа. Основни циљ је, сходно томе, темељно разумевање полазишта и домета литургијског богословља једног атипичног теолога попут Орфелина и препознавање степена доприноса истог у светлу богословског стваралаштва других полемичких теолога поменуте епохе, примера ради Епископа Дионисија Новаковића и архимандрита Јована Рајића. Истраживање је остварено на тај начин што је подељено у два дела. У првом делу рада, који чине четири поглавља, остварен је истраживачки увид у контекст егзистенцијалних, теолошких и еклисиолошких околности живота православних Срба у Карловачкој митрополији XVIII века. Потом, проучени су веродостојни биографски и библиографски подаци који карактеришу и откривају личност Захарија Орфелина, али и историјске и теолошке претпоставке настанка списа Против Папства римскаго. Стога је последње поглавље првога дела рада посвећено пружању одговора на уводна питања настанка наведеног списа, при чему су предочени досадашњи резултати проучавања дотичног дела и преиспитани аутентичност, назив, време, повод и место настанка рукописа, као и Орфелинова лична библиотека коју је аутор користио приликом процеса писања, да би коначно били размотрени оригиналност, језик, обим и садржина дела. У другом делу рада, састављеном од пет поглавља, извршен је превод са славеносрпског на савремени српски језик целокупне садржине три поглавља обимне двадесет и друге целине списа, као и превод целовите верзије двадесет и четвртог одељка рукописа. Сви преведени делови Орфелиновог дела пропраћени су одговарајућом литургичком и богословском анализом. Релевантност овога истраживања очитује се у томе што доприноси потпунијем и квалитетнијем разумевању теолошких интересовања православних Срба у Карловачкој митрополији XVIII столећа и уједно путева српског полемичког богословља, чији је заслужни представник једна особена личност, али истовремено изузетни полихистор и драгоцени теолог Захарије Орфелин.The subject of this dissertation is the liturgical theology in the manuscript work of Zaharija Orfelin Against Roman Papacy (Patriarchal Library Rs 214), which is re-examined and conceived in the context of the dominant confessional-polemical literature of the 18th century Metropolitanate of Karlovci. Accordingly, its main goal is to attain thorough understanding of the basic presuppositions and overall scope of the liturgical theology of an atypical theologian such as Orfelin and to recognize the degree of its contribution in light of the theological work of other polemical theologians of the time, for instance Bishop Dionisije Novakovic and Archimandrite Jovan Rajic. Research is realized in two separate sections. In the first part of the dissertation, consisting of four chapters, light is shed on the context of existential, theological, and ecclesiological circumstances of the life of Orthodox Serbs in the Karlovci Metropolitanate in the 18th century. Then follows an examination of credible biographic and bibliographic data that both characterizes and reveals Zaharija Orfelin’s person, as well as the historical and theological presuppositions of the composition of Against Roman Papacy. Therefore, the closing chapter of the first section is dedicated to answering the introductory questions revolving around this writing’s composition, presenting thus the results of previous scholarship and revisiting the questions of authenticity, the title, the time and place of the manuscript’s composition, as well as the circumstances leading to it. This also includes the study of Orfelin's personal library, all aiming at the final consideration of this work’s originality, language, scope, and content. The second part of the dissertation, consisting of five chapters, is the translation, from slaveno-serbian into modern Serbian, of three sections from chapter twenty-two and the entirety of chapter twenty-four of the text. All translated parts of Orfelin's work are complemented by appropriate liturgical and theological analysis. The relevance of this research is evident in the fact that it contributes to a more nuanced understanding of theological interests of Orthodox Serbs in the 18th century Karlovci Metropolitanate and better insight into the trajectory of Serbian polemical theology, with Zaharija Orfelin being its worthy representative, as well as an exceptional polymath and cherished theologian

Proinflammatory genotype is associated with the frailty phenotype in the English Longitudinal Study of Ageing

Background: Frailty is a state of increased vulnerability to poor resolution of homeostasis after a stressor event, which increases the risk of adverse outcomes including falls, disability and death. The underlying pathophysiological pathways of frailty are not known but the hypothalamic–pituitary–adrenal axis and heightened chronic systemic inflammation appear to be major contributors. Methods: We used the English Longitudinal Study of Ageing dataset of 3160 individuals over the age of 50 and assessed their frailty status according to the Fried-criteria. We selected single nucleotide polymorphisms in genes involved in the steroid hormone or inflammatory pathways and performed linear association analysis using age and sex as covariates. To support the biological plausibility of any genetic associations, we selected biomarker levels for further analyses to act as potential endophenotypes of our chosen genetic loci. Results: The strongest association with frailty was observed in the Tumor Necrosis Factor (TNF) (rs1800629, P = 0.001198, β = 0.0894) and the Protein Tyrosine Phosphatase, Receptor type, J (PTPRJ) (rs1566729, P = 0.001372, β = 0.09397) genes. Rs1800629 was significantly associated with decreased levels of high-density lipoprotein (HDL) (P = 0.00949) and cholesterol levels (P = 0.00315), whereas rs1566729 was associated with increased levels of HDL (P = 0.01943). After correcting for multiple testing none of the associations remained significant. Conclusions: We provide potential evidence for the involvement of a multifunctional proinflammatory cytokine gene (TNF) in the frailty phenotype. The implication of this gene is further supported by association with the endophenotype biomarker results

LIVING HADIS : RESEPSI MASYARAKAT DESA WARUDUWUR TERHADAP SEDEKAH DALAM TRADISI NADRAN

Tradisi merupakan suatu kebudayaan yang menjadi ciri lokalitas di setiap daerah di masyarakat Indonesia. Nadran merupakan tradisi hasil alkulturasi yang dihasilkan dari perpaduan agama Islam dan Hindu sejak ratusan tahun yang lalu oleh nenek moyang. Dalam perspektif hadis, tradisi nadran ini perlu dikaji bagaimanakah respon hadis Rasulullah terhadap tradisi dan budaya yang sudah berkembang di masyarakat, agar kita sebagai umat Islam bisa menentukan respon yang tepat, bijaksana dan moderat. Dalam Skripsi ini, penulis akan mengupas topik living hadis, dengan fokus khusus pada tradisi Nadran di desa Waruduwur Cirebon. Oleh karena itu rumusan masalah yang mucul adalah bagaimana tradisi Nadran di desa Waruduwur dan bagaimana resepsi masyarakat Waruduwur terhadap hadis Sedekah. Penelitian perpustakaan (library research) dan penelitian lapangan (field research). Menggunakan sumber Primer wawancara tokoh Agama dan tokoh masyarakat dan sumber Sekunder buku, jurnal, laporan penelitian, data statistik, atau informasi yang telah diarsipkan. Dengan menggunakan Metode Kualitatif. Tradisi Nadran di desa Waruduwur terinspirasi dari Hadis sedekah. Masyarakat memahami bahwa sedekah itu wajib, boleh di tentukan waktunya, boleh di bebaskan, boleh di sertai dengan kegiatan- kegiatan itu dalam bentuk Nadran. Masyarakat itu juga mengartikan Hadis itu baik terbawa sedekah, sifatnya sukarela, boleh secara formal atau sembunyi-sembunyi dan boleh dibawakan dengan acara Nadran. Menurut peneliti ada nilai-nilai Living Hadis karena melihat dari setiap kebaikan adalah sedekah, maka nilai silaturahmi, nilai dzikir, pengajian, dan doa, serta diniatkan untuk tolak bala, itu semua termasuk mengamalkan hadis sedekah. Artinya masyarakat Waruduwur memahami hadis sedekah yang mereka terima dari para Kyai dalam bentuk ceramah. Disisi lain tradisi nadran di hari ini sudah bergeser menjadi pesta hura-hura oleh masyarakat Waruduwur. Hal ini terjadi sejak Covid-19, karena sebelum Covid-19 masih ada kegiatan agama seperti ceramah, berdzikir, dan doa

Probiotic Microbes Sustain Youthful Serum Testosterone Levels and Testicular Size in Aging Mice

The decline of circulating testosterone levels in aging men is associated with adverse health effects. During studies of probiotic bacteria and obesity, we discovered that male mice routinely consuming purified lactic acid bacteria originally isolated from human milk had larger testicles and increased serum testosterone levels compared to their age-matched controls. Further investigation using microscopy-assisted histomorphometry of testicular tissue showed that mice consuming Lactobacillus reuteri in their drinking water had significantly increased seminiferous tubule cross-sectional profiles and increased spermatogenesis and Leydig cell numbers per testis when compared with matched diet counterparts This showed that criteria of gonadal aging were reduced after routinely consuming a purified microbe such as L. reuteri. We tested whether these features typical of sustained reproductive fitness may be due to anti-inflammatory properties of L. reuteri, and found that testicular mass and other indicators typical of old age were similarly restored to youthful levels using systemic administration of antibodies blocking pro-inflammatory cytokine interleukin-17A. This indicated that uncontrolled host inflammatory responses contributed to the testicular atrophy phenotype in aged mice. Reduced circulating testosterone levels have been implicated in many adverse effects; dietary L. reuteri or other probiotic supplementation may provide a viable natural approach to prevention of male hypogonadism, absent the controversy and side-effects of traditional therapies, and yield practical options for management of disorders typically associated with normal aging. These novel findings suggest a potential high impact for microbe therapy in public health by imparting hormonal and gonad features of reproductive fitness typical of much younger healthy individuals.National Institutes of Health (U.S.) (Grant P30-ES002109)National Institutes of Health (U.S.) (Grant U01 CA164337)National Institutes of Health (U.S.) (Grant RO1CA108854

The onset of widespread musculoskeletal pain is associated with a decrease in healthy ageing in older people: a population-based prospective study

OBJECTIVE: Chronic musculoskeletal pain is common in older adults but the nature of its relationship with ageing is unclear. The objective for this study was to test the hypothesis that the onset of widespread pain would be associated with a decrease in healthy ageing. METHODS: Population-based prospective cohort study. A "healthy ageing" index was constructed across biomedical, physical, psychosocial and lay components. Analysis was performed with 2949 adults aged 50 years and over who had complete index scores at baseline, 3 and 6-year follow-ups. RESULTS: At three and six year follow-up, 365 (16.8%) and 259 (14.3%) experienced the onset of widespread pain. The onset of widespread pain during the six-year period was associated with a 25% and a 46% decrease in healthy ageing index scores; this decrease was independent of age, sex, education, social networks, smoking status, alcohol consumption and physical inactivity. The decrease in healthy ageing attenuated to 20% and 39% following adjustment for diagnosed musculoskeletal conditions and analgesic and non-steroidal use. CONCLUSIONS: The onset of widespread pain was associated with a decrease in healthy ageing throughout the six-year period. When pain increased over time, the markers of unhealthy ageing increased also. Strong analgesia was associated with unhealthy ageing. Research could now usefully test whether early identification, improved treatment and prevention of pain prior to old age may facilitate healthy ageing

British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice

BACKGROUND: Testosterone deficiency (TD) is an increasingly common problem with significant health implications, but its diagnosis and management can be challenging. AIM: To review the available literature on TD and provide evidence-based statements for UK clinical practice. METHODS: Evidence was derived from Medline, EMBASE, and Cochrane searches on hypogonadism, testosterone (T) therapy, and cardiovascular safety from May 2005 to May 2015. Further searches continued until May 2017. OUTCOMES: To provide a guideline on diagnosing and managing TD, with levels of evidence and grades of recommendation, based on a critical review of the literature and consensus of the British Society of Sexual Medicine panel. RESULTS: 25 statements are provided, relating to 5 key areas: screening, diagnosis, initiating T therapy, benefits and risks of T therapy, and follow-up. 7 statements are supported by level 1, 8 by level 2, 5 by level 3, and 5 by level 4 evidence. CLINICAL IMPLICATIONS: To help guide UK practitioners on effectively diagnosing and managing primary and age-related TD. STRENGTHS AND LIMITATIONS: A large amount of literature was carefully sourced and reviewed, presenting the best evidence available at the time. However, some statements provided are based on poor-quality evidence. This is a rapidly evolving area of research and recommendations are subject to change. Guidelines can never replace clinical expertise when making treatment decisions for individual patients, but rather help to focus decisions and take personal values and preferences and individual circumstances into account. Many issues remain controversial, but in the meantime, clinicians need to manage patient needs and clinical expectations armed with the best clinical evidence and the multidisciplinary expert opinion available. CONCLUSION: Improving the diagnosis and management of TD in adult men should provide somatic, sexual, and psychological benefits and subsequent improvements in quality of life. Hackett G, Kirby M, Edwards D, et al. British Society for Sexual Medicine Guidelines on Adult Testosterone Deficiency, With Statements for UK Practice. J Sex Med 2017;14:1504-1523

Oral abstracts 3: RA Treatment and outcomesO13. Validation of jadas in all subtypes of juvenile idiopathic arthritis in a clinical setting

Background: Juvenile Arthritis Disease Activity Score (JADAS) is a 4 variable composite disease activity (DA) score for JIA (including active 10, 27 or 71 joint count (AJC), physician global (PGA), parent/child global (PGE) and ESR). The validity of JADAS for all ILAR subtypes in the routine clinical setting is unknown. We investigated the construct validity of JADAS in the clinical setting in all subtypes of JIA through application to a prospective inception cohort of UK children presenting with new onset inflammatory arthritis. Methods: JADAS 10, 27 and 71 were determined for all children in the Childhood Arthritis Prospective Study (CAPS) with complete data available at baseline. Correlation of JADAS 10, 27 and 71 with single DA markers was determined for all subtypes. All correlations were calculated using Spearman's rank statistic. Results: 262/1238 visits had sufficient data for calculation of JADAS (1028 (83%) AJC, 744 (60%) PGA, 843 (68%) PGE and 459 (37%) ESR). Median age at disease onset was 6.0 years (IQR 2.6-10.4) and 64% were female. Correlation between JADAS 10, 27 and 71 approached 1 for all subtypes. Median JADAS 71 was 5.3 (IQR 2.2-10.1) with a significant difference between median JADAS scores between subtypes (p < 0.01). Correlation of JADAS 71 with each single marker of DA was moderate to high in the total cohort (see Table 1). Overall, correlation with AJC, PGA and PGE was moderate to high and correlation with ESR, limited JC, parental pain and CHAQ was low to moderate in the individual subtypes. Correlation coefficients in the extended oligoarticular, rheumatoid factor negative and enthesitis related subtypes were interpreted with caution in view of low numbers. Conclusions: This study adds to the body of evidence supporting the construct validity of JADAS. JADAS correlates with other measures of DA in all ILAR subtypes in the routine clinical setting. Given the high frequency of missing ESR data, it would be useful to assess the validity of JADAS without inclusion of the ESR. Disclosure statement: All authors have declared no conflicts of interest. Table 1Spearman's correlation between JADAS 71 and single markers DA by ILAR subtype ILAR Subtype Systemic onset JIA Persistent oligo JIA Extended oligo JIA Rheumatoid factor neg JIA Rheumatoid factor pos JIA Enthesitis related JIA Psoriatic JIA Undifferentiated JIA Unknown subtype Total cohort Number of children 23 111 12 57 7 9 19 7 17 262 AJC 0.54 0.67 0.53 0.75 0.53 0.34 0.59 0.81 0.37 0.59 PGA 0.63 0.69 0.25 0.73 0.14 0.05 0.50 0.83 0.56 0.64 PGE 0.51 0.68 0.83 0.61 0.41 0.69 0.71 0.9 0.48 0.61 ESR 0.28 0.31 0.35 0.4 0.6 0.85 0.43 0.7 0.5 0.53 Limited 71 JC 0.29 0.51 0.23 0.37 0.14 -0.12 0.4 0.81 0.45 0.41 Parental pain 0.23 0.62 0.03 0.57 0.41 0.69 0.7 0.79 0.42 0.53 Childhood health assessment questionnaire 0.25 0.57 -0.07 0.36 -0.47 0.84 0.37 0.8 0.66 0.4

Ethnic differences in male reproductive hormones and relationships with adiposity and insulin resistance in older men

Objectives: To assess ethnic differences in male reproductive hormone levels and to determine whether any differences are explained by adiposity, insulin resistance (IR) or comorbidities in older men. Design: Multi-ethnic cross-sectional observational study. Participants: Community dwelling middle-aged and elderly men residing in the UK aged 40–84 years of South Asian (SA; n = 180), White European (WE; n = 328) or African Caribbean (AC; n = 166) origin. Observations: Measured testosterone (T), calculated free T (cFT), sex hormone-binding globulin and LH in SA, WE and AC men along with an assessment of body composition, IR, lifestyle factors and medical conditions. Results: Age-adjusted mean T and cFT levels were lower in SA men when compared to WE and AC men (mean (SEM) T: SA: 14·0 ± 0·4; WE: 17·1 ± 0·3; AC: 17·2 ± 0·5 nmol/l, P &#60; 0·001; cFT: SA: 283 ± 7; WE: 313 ± 5; AC: 314 ± 8 pmol/l, P &#60; 0·006). Compared to WE and AC men, SA men had higher levels of body fat, IR, comorbidities and diabetes. After adjusting for body fat, IR and other confounders, T levels in SA men remained lower than in WE men (P = 0·04) but ethnic differences in cFT became nonsignificant. LH levels were higher in SA than WE men in age-adjusted and fully adjusted models. Conclusions: T and cFT are lower in SA men than in WE and AC men. Whether ethnic-specific reference ranges for T and cFT might be appropriate in clinical practice requires further investigation. Ethnic differences in cFT, but not T, appear to be, more readily, explained by ethnic differences in adiposity, thus providing insights into potential pathophysiological mechanisms

EAA clinical guideline on management of bone health in the andrological outpatient clinic

Background: Male osteoporosis is now a well-recognized medical disorder with established clinical guidelines for both diagnosis and management. Prevention as well as management of osteoporosis in men consulting the andro- logical outpatient clinic because of low testosterone, how- ever, is not well established. This gap of knowledge is -at least partly- explained by the controversy with respect to the threshold of testosterone needed for skeletal mainte- nance. However, testosterone deficiency may be clearly associated with bone loss as well frailty in men. The aim of the guideline was to provide andrologists with the most updated, evidence based advices on the management of bone disease in men and to make them aware of the potential silent presence of osteoporosis in hypogonadal men. Methods: The GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) system for grading the quality of evidence and the strength of recom- mendations was used to grade recommendations. Results: A total of 32 recommendations were provided concerning clinical evaluation, diagnosis and therapy of male osteoporosis in the andrological patient. Conclusion: Therefore, the management of patients with potential hypogonadism should include a complete bone health assessment, besides clinical and biochemical evalu- ation of gonadal status. Such bone health assessment should include specific items in medical history and phys- ical examination related to fracture risk. Furthermore, dual-energy absorptiometry is indicated to evaluate frac- ture risk in men with confirmed clinical hypogonadism. Regarding treatment, besides general measures to prevent or manage male osteoporosis testosterone replacement can be initiated (as described in guidelines for hypogo- nadism), but data on its efficacy in preventing fractures are lacking. Thus, additional anti-osteoporotic may be needed, especially in men with very low testosterone who are at high risk for bone loss and/or in men not able to receive testosterone replacement