CD200+ fibroblasts form a pro-resolving mesenchymal network in arthritis.

Fibroblasts are important regulators of inflammation, but whether fibroblasts change phenotype during resolution of inflammation is not clear. Here we use positron emission tomography to detect fibroblast activation protein (FAP) as a means to visualize fibroblast activation in vivo during inflammation in humans. While tracer accumulation is high in active arthritis, it decreases after tumor necrosis factor and interleukin-17A inhibition. Biopsy-based single-cell RNA-sequencing analyses in experimental arthritis show that FAP signal reduction reflects a phenotypic switch from pro-inflammatory MMP3+/IL6+ fibroblasts (high FAP internalization) to pro-resolving CD200+DKK3+ fibroblasts (low FAP internalization). Spatial transcriptomics of human joints indicates that pro-resolving niches of CD200+DKK3+ fibroblasts cluster with type 2 innate lymphoid cells, whereas MMP3+/IL6+ fibroblasts colocalize with inflammatory immune cells. CD200+DKK3+ fibroblasts stabilized the type 2 innate lymphoid cell phenotype and induced resolution of arthritis via CD200-CD200R1 signaling. Taken together, these data suggest a dynamic molecular regulation of the mesenchymal compartment during resolution of inflammation.

Single-cell multi-omics analysis of COVID-19 patients with pre-existing autoimmune diseases shows aberrant immune responses to infection.

In COVID-19, hyperinflammatory and dysregulated immune responses contribute to severity. Patients with pre-existing autoimmune conditions can therefore be at increased risk of severe COVID-19 and/or associated sequelae, yet SARS-CoV-2 infection in this group has been little studied. Here, we performed single-cell analysis of peripheral blood mononuclear cells from patients with three major autoimmune diseases (rheumatoid arthritis, psoriasis, or multiple sclerosis) during SARS-CoV-2 infection. We observed compositional differences between the autoimmune disease groups coupled with altered patterns of gene expression, transcription factor activity, and cell-cell communication that substantially shape the immune response under SARS-CoV-2 infection. While enrichment of HLA-DRlow CD14+ monocytes was observed in all three autoimmune disease groups, type-I interferon signaling as well as inflammatory T cell and monocyte responses varied widely between the three groups of patients. Our results reveal disturbed immune responses to SARS-CoV-2 in patients with pre-existing autoimmunity, highlighting important considerations for disease treatment and follow-up.

Stepwise asynchronous telehealth assessment of patients with suspected axial spondyloarthritis: results from a pilot study.

Patients with axial spondyloarthritis (axSpA) suffer from one of the longest diagnostic delays among all rheumatic diseases. Telemedicine (TM) may reduce this diagnostic delay by providing easy access to care. Diagnostic rheumatology telehealth studies are scarce and largely limited to traditional synchronous approaches such as resource-intensive video and telephone consultations. The aim of this study was to investigate a stepwise asynchronous telemedicine-based diagnostic approach in patients with suspected axSpA. Patients with suspected axSpA completed a fully automated digital symptom assessment using two symptom checkers (SC) (bechterew-check and Ada). Secondly, a hybrid stepwise asynchronous TM approach was investigated. Three physicians and two medical students were given sequential access to SC symptom reports, laboratory and imaging results. After each step, participants had to state if axSpA was present or not (yes/no) and had to rate their perceived decision confidence. Results were compared to the final diagnosis of the treating rheumatologist. 17 (47.2%) of 36 included patients were diagnosed with axSpA. Diagnostic accuracy of bechterew-check, Ada, TM students and TM physicians was 47.2%, 58.3%, 76.4% and 88.9% respectively. Access to imaging results significantly increased sensitivity of TM-physicians (p < 0.05). Mean diagnostic confidence of false axSpA classification was not significantly lower compared to correct axSpA classification for both students and physicians. This study underpins the potential of asynchronous physician-based telemedicine for patients with suspected axSpA. Similarly, the results highlight the need for sufficient information, especially imaging results to ensure a correct diagnosis. Further studies are needed to investigate other rheumatic diseases and telediagnostic approaches.

Real-world usage of digital health applications (DiGA) in rheumatology: results from a German patient survey.

Mobile health applications and digital therapeutics (DTx) aim to improve current patient care. Real-world data on DTx are, however, scarce. The aim of this study was to evaluate the adherence, acceptance, and efficacy of DTx in a clinical routine rheumatology setting. We conducted a prospective observational cohort study assessing the use, adherence, acceptance, and efficacy of the DTx DiGA (Digitale Gesundheitsanwendungen) by survey over 12 weeks. Patients included had to have a rheumatic disease and had been prescribed a DiGA. Acceptance was assessed using the Net promoter score (NPS). 48 patients were prescribed DiGA. Of these, 39/48 (81%) completed the follow-up survey. 21/39 (54%) patients downloaded the DTx and 20/39 (51%) used the DTx at least once. 9/39 (23%) of patients stopped quickly afterward and 5/39 (13%) reported having completed the whole DTx program. Lack of time and commitment were reported as the main reasons for non-use. Overall acceptance of DiGA was high (Net promoter score (NPS) mean (SD) 7.8/10 (2.3)). While the majority of patients (60%) reported no improvement, one subgroup of patients (7/20, 35%) who regularly used an exercise-based DTx for back pain reported symptom improvement. Acceptance of DTx in patients with rheumatic diseases is high, however onboarding to DTx use and adherence to DTx is still challenging in patients with rheumatic diseases. In a subgroup of patients with back pain, however, the use of an exercise-based DTx led to symptom improvement.

COVID-19-Related Death in Patients with Alcohol or Substance Use Disorders.

BACKGROUND: People with substance or alcohol use disorders (SUDs/AUDs) are likely to be more vulnerable to COVID-19 infection than the general population, but the evidence of COVID-19-related mortality in these patients is unclear. OBJECTIVES: The aim of the study was to verify whether patients with AUD and SUD have a higher mortality rate for COVID-19-related mortality compared to the general population. METHOD: We performed a follow-up study to assess mortality in 2020 in a cohort of patients diagnosed for the first time with AUDs or SUDs at the Public Health Services in the metropolitan area of Bologna (Northern Italy) from 2009 to 2019. RESULTS: SUDs/AUDs patients present an excess mortality with respect to the general population for all causes of death and for COVID-19-related mortality. CONCLUSIONS: Our data support the need for prevention strategies in SUDs/AUDs patients such as vaccinations.

Concise report: a minimal-invasive method to retrieve and identify entheseal tissue from psoriatic arthritis patients.

OBJECTIVES: To establish a minimally invasive biopsy technique for the analysis of entheseal tissue in patients with psoriatic arthritis (PsA). METHODS: Human cadavers were used for establishing the technique to retrieve tissue from the lateral humeral epicondyle enthesis (cadaveric biopsies). After biopsy, the entire enthesis was surgically resected (cadaveric resections). Biopsies and resections were assessed by label-free second harmonic generation (SHG) microscopy. The same technique was then applied in patients with PsA with definition of entheseal tissue by SHG, staining of CD45+immune cells and RNA extraction. RESULTS: Entheseal biopsies from five cadavers allowed the retrieval of entheseal tissue as validated by the analysis of resection material. Microscopy of biopsy and resection sections allowed differentiation of entheseal, tendon and muscle tissue by SHG and definition of specific intensity thresholds for entheseal tissue. In subsequent entheseal biopsies of 10 PsA patients: the fraction of entheseal tissue was high (65%) and comparable to cadaveric biopsies (68%) as assessed by SHG microscopy. Furthermore, PsA biopsies showed immune cell infiltration and sufficient retrieval of RNA for further molecular analysis. CONCLUSION: Entheseal biopsy of the lateral epicondyle is feasible in patients with PsA allowing reliable retrieval of entheseal tissue and its identification by SHG microscopy.

Gambling Disorder in an Italian Population: Risk of Suicide Attempts and Associated Demographic-Clinical Factors using Electronic Health Records.

To identify the demographic and clinical characteristics associated with access to Emergency Departments for Suicide Attempt in a cohort of patients with Gambling disorders. We used electronic health records of inpatient and outpatient services to identify individuals who received a diagnosis of gambling disorder (ICD-9 or ICD-10 codes) in the Metropolitan area of Bologna from 2009 to 2019. In this cohort we identified accesses to Emergency Departments for suicide attempt through cross-matching with electronic records. We calculated Crude Suicide Attempt Rates; we also included the demographic-clinical variables in a multivariate Poisson regression. We identified 692 patients with a diagnosis of gambling disorder and a total of 2733 Person Years. The Crude Suicide Attempt Rate per 1000 Person Years was 9.17 (95% CI 6.20-13.58), higher for females and much higher than the general population (incidence rate ratio = 93.72). The multivariate analysis showed a higher risk of suicide attempt in the year following the first contact with a clinical service, in patients younger than 45 years, with alcohol use disorders and personality disorders. This study evidenced a high risk of access to Emergency Departments for suicide attempt in individuals with a diagnosis of gambling disorder and highlighted important demographic and clinical factors that should be considered when evaluating suicide risk in this population.

EUREKA algorithm predicts obstetric risk and response to treatment in women with different subsets of anti-phospholipid antibodies.

OBJECTIVES: aPL, the serum biomarkers of APS, are the most common acquired causes of pregnancy morbidity (PM). This study investigates the impact of aPL positivity fulfilling classification criteria ('criteria aPL') and at titres lower than thresholds considered by classification criteria ('low-titre aPL') on PM and assesses the effectiveness of low-dose aspirin (LDASA), low molecular weight heparin (LMWH) and HCQ in reducing the probability of PM (PPM). METHODS: Longitudinal data on 847 pregnancies in 155 women with persistent aPL at any titre and 226 women with autoimmune diseases and negative aPL were retrospectively collected. A generalized estimating equations model for repeated measures was applied to quantify PPM under different clinical situations. RESULTS: EUREKA is a novel algorithm that accurately predicts the risk of aPL-associated PM by considering aPL titres and profiles. aPL significantly impact PPM when at low titres and when fulfilling classification criteria. PPM was further stratified upon the aPL tests: aCL IgG/IgM and anti-ß2-glycoprotein I (ß2GPI) IgM, alone or combined, do not affect the basal risks of PPM, an increase occurs in case of positive LA or anti-ß2GPI IgG. LDASA significantly affects PPM exclusively in women with low-titre aPL without anti-ß2GPI IgG. The LDASA + LMWH combination significantly reduces PPM in all women with low-titre aPL and women with criteria aPL, except those carrying LA and anti-ß2GPI IgG. In this group, the addition of HCQ further reduces PPM, although not significantly. CONCLUSION: EUREKA allows a tailored therapeutic approach, impacting everyday clinical management of aPL-positive pregnant women.

Pancreatic steatosis on computed tomography is an early imaging feature of pre-diagnostic pancreatic cancer: A preliminary study in overweight patients.

BACKGROUND: The prevalence of pancreatic ductal adenocarcinoma (PDAC) is on the rise, driven by factors such as aging and an increasing prevalence of obesity and diabetes mellitus. To improve the poor survival rate of PDAC, early detection is vital. Recently, pancreatic steatosis has gained novel interest as a risk factor for PDAC. This study aimed to investigate if pancreatic steatosis on computed tomography (CT) is an early imaging feature in patients with pre-diagnostic PDAC. METHODS: A retrospective case-control study was performed. Patients diagnosed with PDAC (2010-2016) were reviewed for abdominal non-contrast CT-imaging 1 month-3 years prior to their diagnosis. Cases were matched 1:4 with controls based on age, gender and imaging date. Unenhanced CT-images were evaluated for pancreatic steatosis (pancreas-to-spleen ratio in Hounsfield Units <0.70) by a blinded radiologist and results were compared between cases and controls. RESULTS: In total, 32 cases and 117 controls were included in the study with a comparable BMI (29.6 and 29.2 respectively, p = 0.723). Pancreatic steatosis was present in 71.9% of cases compared to 45.3% of controls (Odds ratio (OR) 3.09(1.32-7.24), p = 0.009). Adjusted for BMI and diabetes mellitus, pancreatic steatosis on CT remained a significant independent risk factor for PDAC (Adjusted OR 2.70(1.14-6.58), p = 0.037). CONCLUSION: Pancreatic steatosis measured on CT is independently associated with PDAC up to three years before the clinical diagnosis in overweight patients. If these data are confirmed, this novel imaging feature may be used to identify high-risk individuals and to stratify the risk of PDAC in individuals that already undergo PDAC screening.

First report of Phaeoacremonium amygdalinum associated with almond dieback and wood disease in Italy.

In the last 10 years, almond (Prunus dulcis (Mill.) Webb) cultivation areas in the region of Apulia (southern Italy) have increased. A recent survey in young almond orchards recorded characteristic disease symptoms including rapid collapse of branches, chlorosis of leaves (with sudden wilting and death) in June/July, and bud and shoot dieback in December-March. Internal wood symptoms on stems consisted of brown vascular streaking that led to death of young apical shoots within a few weeks. Wood samples were collected and taken to the laboratory, where they underwent disinfection according to Fisher et al. (2002). Fungal isolation techniques were applied, with small pieces of wood tissue (0.5-1.0 cm) placed on potato dextrose agar (PDA; Oxoid Ltd.) supplemented with 300 mg/L streptomycin sulphate, and incubated at 23 ±2 °C in the dark. After 10 days, based on morphological features carried out by microscopic studies, 85% (n = 55) of the resulting fungal colonies (N = 65) were preliminarily attributed to known fungal pathogens of woody tissues, of which 12.4% (n = 8) belonged to the Phaeoacremonium genus. These last were purified by transferring single germinating conidia onto fresh PDA plates. In particular, the conidiophores were mostly short, usually unbranched, erect to flexuous, up to 5-septate, brown to pale brown, verruculose on the lower part, (12-)15.7-41(-55) (av. -29) µm long and 1.6-3.2 (av. 2.1) µm wide (n = 30). Conidia hyaline, oblong ellipsoidal-obovoid or subcylindrical (3-)4-5 µm long and 1.5-3 (av. = 4.4 × 2.1) µm wide (n =30). All Phaeoacremonium isolates were successfully subjected to genomic DNA extraction, according to Carlucci et al. (2013). Partial actin and ß-tubulin genes were amplified with the ACT-513F/ACT-783R (Carbone and Kohn 1999) and T1 (O'Donnell and Cigelnik 1997) and Bt2b (Glass and Donaldson 1995) primers, respectively. Consensus sequences were compared with reference strains (extype) in the GenBank database, using the Basic Local Alignment Search Tool (BLAST). In particular, all isolates showed 99-100% similarity with reference strains of Phaeoacremonium amygdalinum Gramaje, Armengol & L. Mostert (JN191301; JN191305). Actin and ß-tubulin sequences of P. amygdalinum strain Pm10 were deposited in GenBank (MW716265; MW714562). In spring 2020, artificial inoculations with two isolates of P. amygdalinum (Pm10; Pm15) were carried out on 10 healthy, 2-year-old almond seedlings of cv. 'Filippo Cea'. Agar plugs (diameter, 0.3-0.5 cm) taken from 10-day-old cultures grown on PDA at 23 ±2 °C were inserted into small wounds under the bark of the stems (length, 0.4-1.0 cm) made with a sterile scalpel. After inoculation, the wounds were wrapped with wet sterile cotton wool and sealed with Parafilm. Ten almond seedling were used as controls, being inoculated with sterile agar plugs. The experiment was replicated three times. The inoculated young almond plants were grown in pots in a greenhouse without temperature control. After 150 days, the inoculated plants showed decline symptoms and internal longitudinal brown wood streaking (average, length, 2.7-6.4 cm). Phaeoacremonium amygdalinum was reisolated from symptomatic wood of 95% of the experimental almond seedlings, thus fulfilling Koch's postulates. No symptoms were observed on almond seedling used as controls. Phaeoacremonium amygdalinum was first described as a fungal pathogen of almond in Spain (Gramaje et al., 2012). To the best of our knowledge, this is the first report of P. amygdalinum associated with almond dieback disease in Italy. References Carbone I. and Kohn L.M. 1999. Mycologia 91:553. Carlucci A. et al. 2013. Phytopathol. Mediterr. 52:517. Fisher et al 2002. Mycol. Prog. 1:315 Glass N. L. and Donaldson G. C. 1995. J. Cl. Microbiol. 41:1332. Gramaje et al. 2012. Persoonia 28:1. O'Donnell K. and Cigelnik E. 1997. Mol. Phylogenetics Evol 7:103.

First report of Phaeoacremonium oleae and P. viticola associated with olive trunk diseases in Italy.

Over 300 trunk, branch and stem samples with vascular discolouration, necrotic wood and shoot death were collected from olive (Olea europaea) orchards in Lecce, Brindisi, Bari and Foggia provinces (Apulia region, Italy) from October to May from 2013 to 2019. Small chips of symptomatic wood samples were surface sterilised (5% NaOCl, 3 min; 70% ethanol, 30 s), rinsed (sterile distilled water, ×3), and placed onto potato dextrose agar (PDA) plates amended with 500 ppm streptomycin sulphate. After 14 days at 25 °C in the dark, hyphal tips of growing fungi, including different taxa, for instance Phaeoacremonium and Botryosphaeriaceae spp., were transferred to new PDA plates and incubated until sporulation. Monoclonal colonies resembling Phaeoacremonium-like genus (Mostert et al. 2006) were selected for further study, and genomic DNA of 59 representative isolates was extracted (Carlucci et al. 2013). Partial actin and ß-tubulin genes were amplified with primers ACT-513F/ACT-783R (Carbone & Kohn 1999), and T1(O'Donnell & Cigelnik 1997) and Bt2b (Glass & Donaldson 1995), respectively. The sequenced amplicons were compared by BLAST algorithms with reference strains of Phaeoacremonium spp. retrieved from GenBank. Forty-four isolates showed 99% to 100% similarity with reference strains P. italicum, P. minimum, P. parasiticum, P. scolyti and P. sicilianum (Carlucci et al. 2015), nine with P. oleae, and six with P. viticola. Actin and ß-tubulin sequences of P. oleae (Pm14) and P. viticola (Pm34) were submitted to GenBank (MW714561, MW714563; MZ318697, MZ318696). Microscopy of P. oleae isolates showed: conidiophores branched and unbranched, (18.7-)21.9-57.1(-67.8) × (2.9-)3.3-4.7(-5.2) (mean, 38.9×4.1) µm (n=30); conidia oblong-ellipsoidal to obovoid or subcylindrical 3.4 to 5.5 µm long, and 1.5 to 2.4 (mean, 4.6 × 2.2) µm wide (n=30). Microscopy of P. viticola isolates showed: conidiophores subcylindrical, branched at base (6.7-)8.9-27.2(-29.3) × (2.0-)2.6-3.3(-3.7) (mean, 21.4 × 3.2) µm (n=30); conidia oblong-ellipsoidal to obovoid or subcylindrical 3.3 to 6.8 µm long, and 1.1 to 2.2 (mean, 4.2 × 1.6) µm wide (n=30). In spring 2020, artificial inoculations were carried out with P. oleae (Pm14, Pm46) and P. viticola (Pm34, Pm43) strains on 10 healthy, 2-year-old olive seedlings cultivar 'Coratina'. Agar plugs (diameter, 0.3-0.5 cm) from 10-day-old cultures grown on water agar at 23 (±2) °C were inserted under the bark of small wounds in the stems (length, 0.4-1.0 cm) made with a sterile scalpel. After inoculation, the wounds were wrapped with wet sterile cotton wool and sealed with Parafilm. Ten control olive seedlings were inoculated with sterile agar plugs. The experiment was replicated three times. All inoculated young olive plants were grown in pots in a greenhouse without temperature control. After 120 days, inoculated plants showed decline symptoms, and when cut longitudinally, brown streaks were observed in the wood. For P. oleae these streaks measured 3.0-5.5 cm long (standard deviation [SD], 0.9 cm, and for P. viticola they were 1.8-3.5 cm (SD, 0.62). Both fungal species were re-isolated from the symptomatic wood from 85% and 80%, respectively, of these inoculated olive seedlings, fulfilling Koch's postulates. No symptoms were observed from olive seedlings used as control. P. oleae was first described as a fungal pathogen of wild olive (Olea europaea subsp. cuspidate) in South Africa by Spies et al. (2018), and P. viticola as a fungal pathogen of grapevine in France by Dupont et al. (2000). To the best of our knowledge, this is the first report of P. oleae associated with olive trunk disease in Italy, and the first report of P. viticola associated with olive trunk disease worldwide. References: Carbone I. & Kohn L.M. 1999. Mycologia 91:553. Carlucci A. et al. 2015. Eur. J. Plant Pathol. 141:717. Carlucci A. et al. 2013. Phytopathol. Mediterr. 52:517. Dupont et al. 2000. Mycologia 92:499-504. Glass N. L. & Donaldson G. C. 1995. J. Cl. Microbiol. 41: 1332. Mostert L. et al. 2006. Stud. Mycol. 54:1. O'Donnell K. & Cigelnik E. 1997. Mol. Phylogenetics Evol 7:103. Spies et al. 2018. Persoonia 40:26.

The Potential of OMICs Technologies for the Treatment of Immune-Mediated Inflammatory Diseases.

Immune-mediated inflammatory diseases (IMIDs), such as inflammatory bowel diseases and inflammatory arthritis (e.g., rheumatoid arthritis, psoriatic arthritis), are marked by increasing worldwide incidence rates. Apart from irreversible damage of the affected tissue, the systemic nature of these diseases heightens the incidence of cardiovascular insults and colitis-associated neoplasia. Only 40-60% of patients respond to currently used standard-of-care immunotherapies. In addition to this limited long-term effectiveness, all current therapies have to be given on a lifelong basis as they are unable to specifically reprogram the inflammatory process and thus achieve a true cure of the disease. On the other hand, the development of various OMICs technologies is considered as "the great hope" for improving the treatment of IMIDs. This review sheds light on the progressive development and the numerous approaches from basic science that gradually lead to the transfer from "bench to bedside" and the implementation into general patient care procedures.

Mortality Risk among Cocaine Users before and after the Economic Recession: Results of a Longitudinal Study.

BACKGROUND: Studies have highlighted 2 different groups of cocaine users (CUs): "socially integrated" (stable living conditions, regular employment, use cocaine alone or in combination with other psychoactive substances) and "socially marginalized" (socioeconomic and health problems, former or current heroin users, many injecting cocaine). These differences are also found in the elevated mortality risk for CUs, higher among subjects with cocaine and heroin use. This study targeted residents in Northern Italy who turned to a public treatment center for drug addiction following problems caused by primary cocaine use between 1982 and 2016. OBJECTIVES: To estimate mortality risk for subjects who have never used heroin (CUs) compared to that of subjects who have used heroin (HCUs). METHOD: Retrospective cohort study. We selected 1,993 subjects; 18,015 Person Years (PY). RESULTS: Over time, the quota of subjects injecting cocaine and using heroin decreased, while patients not using heroin increased. Both new patients and crude mortality rates (CMR) decreased during the years 2009-2012 and increased in the following period. CMRs were 5.55 per 1,000 PY, higher for HCUs, men and subjects aged over 44 years. Standardized mortality rates were 3.49, higher for women, injecting cocaine and HCUS. Among CUs, most of the deaths were from injury excluding drug related and tumors; among HCUs, from drug-related causes and diseases of the cardiovascular system. CONCLUSION: The study results show a change in the characteristics of SERD clients being treated for primary cocaine use, which are reflected both in mortality risk and causes of death. After a long period of a decrease, mortality risk increased in the period after the economic recession. Aspects concerning the effects of the economic recession on the problematic consumption of cocaine and on the risk of death are discussed.

Management of Thrombotic Antiphospholipid Syndrome.

Persistent serum positivity for antiphospholipid antibodies (aPL) is required to diagnose antiphospholipid syndrome (APS), an autoimmune disease characterized by recurrent vascular thrombosis and/or pregnancy morbidity. The current therapeutic management of patients with thrombotic APS aims at preventing recurrences and long-term complications by attenuating the procoagulant state. There is overall consensus to reserve moderate-intensity anticoagulation to aPL-positive patients with a previous venous thrombosis; the therapeutic options for those with a history of arterial event comprise antiplatelet agents and high-intensity anticoagulation. Unfortunately, thrombotic occurrences might occur despite adequate anticoagulation, carrying a significant burden of morbidity and mortality. The management of refractory thrombotic APS and catastrophic APS is still not clear, warranting the issue of recommendations. Vitamin-K antagonists are limited by significant side effects, and a careful weighting of risks and benefits should be performed to reserve the optimal treatment to each patient. To overcome these limitations, novel oral anticoagulants have been introduced in the market, but their efficacy in thrombotic APS has still to be unraveled. The poor safety profile and the scarce efficacy of drugs acting on the coagulation cascade explain why novel therapeutic approaches are currently under investigation, to identify pharmacological tools specifically counteracting aPL-mediated prothrombotic effects.

Beyond thrombosis: Anti-ß2GPI domain 1 antibodies identify late pregnancy morbidity in anti-phospholipid syndrome.

Antibodies against ß2 glycoprotein I (anti-ß2GPI) have been identified as the main pathogenic autoantibody subset in anti-phospholipid syndrome (APS); the most relevant epitope is a cryptic and conformation-dependent structure on ß2GPI domain (D) 1. Anti-ß2GPI domain profiling has been investigated in thrombotic APS, leading to the identification of antibodies targeting D1 as the main subpopulation. In contrast, scarce attention has been paid to obstetric APS, hence this study aimed at characterizing the domain reactivity with regards to pregnancy morbidity (PM). To this end, 135 women with persistently positive, medium/high titre anti-ß2GPI IgG, without any associated systemic autoimmune diseases and at least one previous pregnancy were included: 27 asymptomatic carriers; 53 women with obstetric APS; 20 women with thrombotic APS; and 35 women with both thrombotic and obstetric complications. Anti-D1 and anti-D4/5 antibodies were tested using a chemiluminescent immunoassay and a research ELISA assay, respectively (QUANTA Flash® ß2GPI Domain 1 IgG and QUANTA Lite® ß2GPI D4/5 IgG, Inova Diagnostics). Positivity for anti-D1 antibodies, but not anti-D4/5 antibodies, was differently distributed across the 4 subgroups of patients (p < 0.0001) and significantly correlated with thrombosis (χ2 = 17.28, p < 0.0001) and PM (χ2 = 4.28, p = 0.039). Patients with triple positivity for anti-phospholipid antibodies displayed higher anti-D1 titres and lower anti-D4/5 titres compared to women with one or two positive tests (p < 0.0001 and p = 0.005, respectively). Reactivity against D1 was identified as a predictor for PM (OR 2.4, 95% confidence interval [CI] 1.2-5.0, p = 0.017); in particular, anti-D1 antibodies were predictive of late PM, conveying an odds ratio of 7.3 (95% CI 2.1-25.5, p = 0.022). Positivity for anti-D1 antibodies was not associated with early pregnancy loss. Anti-D4/5 antibodies were not associated with clinical APS manifestations. As a whole, our data suggest that anti-D1 antibodies are significantly associated not only with thrombosis, but also with late PM, while positive anti-D4/5 antibodies are not predictive of thrombosis or PM.

Mortality Rates and Trends Among Bologna Community Mental Health Service Users: A 13-Year Cohort Study.

The present study aimed to determine mortality rates and trends among community mental health service users in Bologna (Italy) between 2001 and 2013. Standardized mortality ratios (SMRs) were calculated, and Poisson multiple regression analysis was performed. The cohort comprised 42,357 patients, of which 3556 died. The overall SMR was 1.62 (95% confidence interval = 1.57-1.67). SMRs for natural causes of death ranged from 1.25 to 2.30, whereas the SMR for violent deaths was 3.45. Both serious and common mental disorders showed a significant excess of mortality, although higher rates were found in severe mental disorders, especially in personality disorders. Different from most published studies, the overall SMR slightly decreased during the study period. The present study, though confirming that people with mental disorders present a higher risk of mortality, calls for prevention strategies oriented to all psychiatric diagnoses.

Does APS Impact Women's Fertility?

PURPOSE OF REVIEW: This review focuses on the relationship between anti-phospholipid antibodies (aPL) and female infertility by addressing three key questions: (i) how can aPL induce women's infertility?; (ii) are aPL more prevalent among infertile than fertile women?; (iii) do aPL-positive women display reduced fertility? RECENT FINDINGS: According to experimental data, aPL impair female fertility interfering with endometrial decidualization thus with implantation. Some aPL tests are more frequently detected among infertile women compared to controls; the association between aPL and assisted reproduction techniques outcome is not supported by most studies. Two reports suggest a decreased ovarian reserve among aPL-positive patients, while fertility is preserved in women with systemic lupus erythematosus, commonly associated with aPL positivity. Pregnancy rates drop after diagnosis and lupus women have fewer children than wished, due to many disease-related factors. While awaiting definitive conclusions on the relationship between aPL and infertility, rheumatologists should properly counsel female patients to safeguard fertility.

Fungal bioremediation of olive mill wastewater: using a multi-step approach to model inhibition or stimulation.

BACKGROUND: Olive mill wastewaters (OMWWs) possess a strong environmental impact; the use of fungi as tools for bioremediation could be a promising method. RESULTS: Twenty-nine fungi were grown on minimal media supplemented with five different kinds of OMWWs (5-15%). Radial growth was assessed for 21 days and the data were modelled through the Dantigny-logistic like function to estimate τ, i.e. the time to attain half of the maximum diameter. Growth on potato dextrose agar and water agar (WA, minimal medium without supplementation) was used as reference. The differences in τ between PDA/WA and minimal media with OMWWs were modelled through a multi-factorial ANOVA, using the concentration of OMWW, the kind of wastes and fungi as categorical predictors. Finally, a principal component analysis was run to group and divide resistant and sensitive fungi. Some fungi experienced a positive Δτ, thus suggesting an inhibition by OMWW, whereas other isolates were enhanced. CONCLUSIONS: Some isolates (for example Aspergillus ochraceus) showed a promising trend and could be possible candidates for a validation on a real scale. © 2016 Society of Chemical Industry.

Charcoal Canker of Pear, Plum, and Quince Trees Caused by Biscogniauxia rosacearum sp. nov. in Southern Italy.

The genus Biscogniauxia is paraphyletic to members of the family Xylariaceae and includes at least 52 species to date that are mainly pathogens of dicotyledonous angiosperm trees. Most of these are forest trees, such as those in the genera Acacia, Acer, Alnus, Eucalyptus, Fraxinus, Populus, and Quercus, and other species of minor importance. Biscogniauxia spp. have been reported as endophytes or secondary invaders that attack only stressed plants. During a survey in rosaceous orchards in southern Italy, several charcoal cankers were observed and stroma samples were collected. A collection of 31 Biscogniauxia isolates was analyzed. Their phylogenetic relationships were determined through study of the internal transcribed spacer, ß-tubulin, and actin gene sequences. Combining morphological, cultural, and molecular data, a new species of Biscogniauxia is described here as Biscogniauxia rosacearum. This new species was isolated for the first time from rosaceous hosts in Apulia. Pathogenicity tests showed that it causes symptoms on stems when artificially inoculated and produces stromata on the bark surface.

First Consumers, Then Socially Integrated: Results of a Study on 100 Italian Drug Users Who Had Never Turned to Public or Private Addiction Services.

This study, which addressed a per quota sample of 100 socially integrated drug users (SID) residing in Emilia Romagna (Italy) who have never referred to a public/private Addiction Service, has four main aims: (1) to describe the phenomenology of substance use in all its different facets; (2) to identify feared unwanted consequences due to the use of illegal substances and possible behaviors finalized to preventing them; (3) to identify possible common consumption rules; (4) to identify any differences among the SID. Two types of consumers have been compared: the "law-breakers" (i.e. those who have committed an illegal activity to procure money) and the "law-abiders" (no such action).From the interviewees some discontinuous consumption trajectories over time are reported in relation to the different levels of disposable income and the change in the relationship with the substances. Most of these consumers fear being stigmatized or labeled as drug-addicts, and cause themselves physical, psychological or economic harm; instead only a minority fear developing addiction. The most widespread protective behavior is to purchase through trusted direct channels, followed by the attempt to limit the doses and to consume only in positive emotional states. Rules of conduct implemented at a general level by all the consumers were evidenced, which the law-breakers finalize towards a greater attention to their own psycho-physical health and to better handling the effects produced by the substances, while the law-abiders seek to keep their status as consumers secret.