Diagnosis and treatment of interstitial lung disease related to systemic autoimmune myopathies: a narrative review.

Systemic autoimmune myopathies (SAMs) are rare diseases that lead to muscle inflammation and may be associated with a variety of systemic manifestations. Although there is great heterogeneity in the spectrum of extra-muscular involvement in SAMs, interstitial lung disease (ILD) is the most frequent lung manifestation. SAM-related ILD (SAM-ILD) presents significant variations according to geographic location and temporal trends and is associated with increased morbidity and mortality. Several myositis autoantibodies have been discovered over the last decades, including antibodies targeting aminoacyl-tRNA synthetase enzymes, which are associated with a variable risk of developing ILD and a myriad of other clinical features. In this review, the most relevant topics regarding clinical manifestations, risk factors, diagnostic tests, autoantibodies, treatment, and prognosis of SAM-ILD are highlighted. We searched PubMed for relevant articles published in English, Portuguese, or Spanish from January 2002 to September 2022. The most common SAM-ILD patterns are nonspecific interstitial pneumonia and organizing pneumonia. The combination of clinical, functional, laboratory, and tomographic features is usually sufficient for diagnostic confirmation, without the need for additional invasive methods. Glucocorticoids remain the first-line treatment for SAM-ILD, although other traditional immunosuppressants, such as azathioprine, mycophenolate, and cyclophosphamide have demonstrated some efficacy and, therefore, have an important role as steroid-sparing agents.

The Project Appropriate Birth and a reduction in caesarean section rates: an analysis using the Robson classification system.

OBJECTIVE: The objective of this study was to assess caesarean section (CS) rates before and after the implementation of the Project Appropriate Birth (PPA), based on the Robson ten group classification system. DESIGN: A before-and-after study. SETTING: Maternity hospital in South Brazil. POPULATION: All pregnant women attending from April 2016 to April 2017 (period 1, pre-implementation of PPA) and from June 2017 to June 2018 (period 2, post-implementation of PPA). METHODS: Maternal and obstetric characteristics were evaluated, including Robson's classification, based on the characteristics of pregnancy and childbirth. A chi-square test and crude and adjusted relative rates were used to analyse the study variables. The significance level was set at 5%. MAIN OUTCOME MEASURES: The CS rate for each group, their contribution to the overall CS rate and the differences in these contributions before and after PPA implementation. RESULTS: The CS rates decreased from 62.4 to 55.6%, which represented a 10.9% reduction after the implementation of the PPA. Pregnant women in Robson classification groups 1-4 had a 21.4% reduction in CS rates, ranging from 49.1 to 38.6%. The greatest contributors to the overall CS rates were group 5 and group 2, accounting for more than 60% of the CS deliveries. CONCLUSION: The study results suggest that Project Appropriate Birth had an impact on the reduction of CS rates, especially in Robson classification groups 1 through 4, which indicates that providing mothers with evidence-based interventions for labour and childbirth assistance contributed to reduce CS rates. TWEETABLE ABSTRACT: The Project Appropriate Birth is an innovative project that has demonstrated promising results, suggesting that interventions based on scientific evidence can lead to real changes in childbirth care, contributing to reduce CS rates. The aim of the PPA is to promote activities to improve childbirth care and encourage vaginal delivery. In this study, 6238 pregnant women admitted to the hospital for delivery were included and classified into one of the Robson 10-group classification. Findings revealed a 10.9% reduction in the overall CS rate and a 21.4% reduction for pregnant women in Robson classification groups 1 through 4, after the implementation of the PPA.

The lupus patient traveller: a guide to the rheumatologist.

With an increasing number of international journeys occurring daily, there is also an increase in the need for appropriate medical advice for patients who will undertake such travel. In this context, the lupus patient presents a great challenge to the rheumatologist. However, the demand for such information by patients is low, and it has proven difficult for the medical community to adequately provide it. In this article, we carried out a literature review of the medical recommendations made for the lupus patient in order to guide the rheumatologist through the topic of travel medicine.

Dual immune effect of iNKT cells considering human cutaneous and visceral leishmaniasis: An example of cell plasticity according to different disease scenarios.

Although the semi-invariant natural killer T cells (iNKT) are a small subpopulation of cells in the peripheral blood, they are presumed to play a role in early stages of infection against various pathogens, including protozoa. This work investigates the activation status and cytokine profile of iNKT cells during human Leishmania infantum and Leishmania braziliensis infection. We studied iNKT cells in patients with symptomatic active visceral leishmaniasis (AVL) (n = 8), patients with symptomatic active cutaneous leishmaniasis (ACL) (n = 13), negative endemic controls (NEC) (n = 6) and non-endemic controls (NonEC) (n = 6), with and without total Leishmania antigen stimulus (TLA). The number of iNKT cells in the peripheral blood of patients with ACL and AVL unaltered in relation to control groups. Moreover, the iNKT cells from ACL showed a hyperactivation profile compared to patients with AVL. Additionally, TLA induced IFN-gamma production in iNKT cells from patients with ACL, while in iNKT of patients with AVL, TLA induced a decrease in this cytokine. Higher IL-17 and IL-10 production by iNKT cells from patients with ACL were also observed compared to all other groups. There were no changes in iNKT IL-10-producing cells in AVL after TLA stimulation. However, TLA induced increase in IL-10 in iNKT cells in patients with ACL. These findings suggest that, although iNKT cells showed distinct profiles in patients with ACL and AVL, they play a dual role in immune modulation in both Leishmania infections.

Hyaluronic acid in Pluronic F-127/F-108 hydrogels for postoperative pain in arthroplasties: Influence on physico-chemical properties and structural requirements for sustained drug-release.

In this study, we reported the hyaluronic acid (HA) on supramolecular structure of Pluronic F-127 (PLF-127) and/or Pluronic F-108 (PLF-127) hydrogels, as well as their effects on release mechanisms, looking forward their application as lidocaine (LDC) drug-delivery systems in arthroplastic surgeries. We have studied the HA-micelle interaction using Dynamic Light Scattering (DLS), the micellization and sol-gel transition processes by Differential Scanning Calorimetry (DSC) and Rheology., of PL-based hydrogels and. The presence of HA provided the formation of larger micellar dimensions from ~26.0 to 42.4nm. The incorporation of HA did not change the micellization temperatures and stabilized hydrogels rheological properties (G'>G″), showing no interference on PL-thermoreversible properties. Small-Angle-X-ray Scattering (SAXS) patterns revealed that HA incorporation effects were pronounced for PLF-127 and PLF-108 systems, showing transitions from lamellar to hexagonal phase organization (HA-PLF-127) and structural changes from cubic to gyroid and/or cubic to lamellar. The HA insertion effects were also observed on drug release profiles, since lower LDC release constants (Krel=0.24-0.41mM·h-1) were observed for HA-PLF-127, that presented a hexagonal phase organization. Furthermore, the HA-PL systems presented reduced in vitro cytotoxic effects, pointed out their tendency to self-assembly and possible application as drug delivery systems.

Treating Addiction: Perspectives from EEG and Imaging Studies on Psychedelics.

Despite reports of apparent benefits, social and political pressure beginning in the late 1960s effectively banned scientific inquiry into psychedelic substances. Covert examination of psychedelics persisted through the 1990s; the turn of the century and especially the past 10 years, however, has seen a resurgent interest in psychedelic substances (eg, LSD, ayahuasca, psilocybin). This chapter outlines relevant EEG and brain imaging studies evaluating the effects of psychedelics on the brain. This chapter also reviews evidence of the use of psychedelics as adjunct therapy for a number of psychiatric and addictive disorders. In particular, psychedelics appear to have efficacy in treating depression and alcohol-use disorders.

The Importance of Wild Canids in the Epidemiology of Rabies in Northeast Brazil: A Retrospective Study.

Rabies is an endemic disease in Brazil, where it is considered a serious public health problem. Although the number of human and dog-transmitted cases has declined in recent decades, rabies in wildlife has emerged considerably. Among the sylvatic animals, wild canids have been considered important hosts of the rabies virus. We performed a retrospective study of reported cases of rabies in wild canids and human victims in Ceará state (Northeast Brazil) during 2003 to 2013. Information was provided by governmental laboratories involved in rabies detection and by the Ministry of Health. From January 2003 to December 2013, a total of 11 931 animal samples were examined for rabies. Positivity were detected in 438 samples (3.67%), of which 229 (52.28%) were domestic animals, 105 (23.97%) wild canids and 104 (23.74%) other wild animals (bats, marmosets and raccoons). Approximately 33% of wild canids surveyed (n = 317) were positive for rabies. During the studied period, a total of 1923 attacks on humans by wild canids were registered. Males (n = 1405) were more affected than females (n = 520; 72.98% versus 27.01%), and the median age of all cases was 36.5 years. Injuries to individuals up to 19 years old corresponded to approximately 30% (n = 565) of all cases. Most of the victims lived in rural areas (72.46%; n = 1395), and the majority showed bites (81.13%; n = 1677) or scratches (12.23%; n = 253). Injuries were considered profound (52.1%; n = 1003), superficial (40.91; n = 788) or multiple with severe laceration (6.98%; n = 134). Only 1300 (67.53%) victims were enrolled for the complete rabies post-exposure prophylaxis scheme. Data from the present study confirm that wild canids are important hosts of rabies virus in northeastern Brazil and jeopardize rabies control in this area. Local authorities should focus their efforts in education of health professionals. In addition, strategies should be formulated to preserve wildlife.

Polycaprolactone fibers with self-assembled peptide micro/nanotubes: a practical route towards enhanced mechanical strength and drug delivery applications.

Peptide-based scaffolds are a frontier research area in materials science with widespread impact in biomedical engineering. In this paper, we describe a hybrid material formulated through the conjugation of electrospun polycaprolactone (PCL) fibers and micro/nanotubes of l,l-diphenylalanine (FF-MNTs). Morphology and crystallinity of the composite matrices are investigated using a wide range of analytical techniques including electron microscopy, thermal analyses, X-ray diffraction and micro-tomography. Peptide assemblies are found to produce deep modifications on the microstructure of PCL fibers, impacting average diameters, crystallinity degree and porous size in the polymer network. These changes are correlated with mechanical properties of the resulting scaffolds, whose strength is found to exhibit a brittle-to-ductile transition upon increasing the amount of FF-MNTs and lead to enhanced Young's moduli of polymer fibers. The PCL/FF-MNTs composites were tested for the drug delivery application of a lipophilic drug, benzocaine. In vitro permeation studies have shown that these polymer/peptide hybrids are able to produce a steady release of benzocaine over periods of up to ∼13 hours, much higher than commercially available gel formulations. Enzymatic tests have shown a significant increment in biodegradation rates in PCL/FF-MNTs hybrids containing higher peptide amounts, which exhibited almost 100% weight loss against only 10% found in pure PCL. Our findings indicate that using PCL/FF-MNTs materials is a simple route towards achieving enhanced mechanical strength of PCL networks that have the ability to promote controlled drug delivery from a completely biodegradable matrix.

Ovarian reserve in adult patients with childhood-onset lupus: a possible deleterious effect of methotrexate?

OBJECTIVES: To assess ovarian reserve markers and anti-corpus luteum antibodies (anti-CoL) in adult patients with childhood-onset systemic lupus erythematosus (c-SLE). METHOD: Fifty-seven adult c-SLE female patients and 21 healthy controls were evaluated for anti-CoL. Ovarian reserve was assessed by: follicle stimulating hormone (FSH), luteinizing hormone (LH), oestradiol, anti-Müllerian hormone (AMH), and antral follicle count (AFC). Demographic data, menstrual abnormalities, disease activity, damage, and treatment were also analysed. RESULTS: The median current age was similar in adult c-SLE patients and controls (27.7 vs. 27.7 years, p = 0.414). The medians of AMH (1.1 vs. 1.5 ng/mL, p = 0.037) and AFC (6 vs. 16, p < 0.001) were significantly reduced in SLE patients compared to controls without significant menstrual abnormalities. Anti-CoL were solely observed in c-SLE patients (16% vs. 0%, p = 0.103) and were not associated with demographic data, ovarian reserve parameters, disease activity/damage, and treatment. Further evaluation of c-SLE patients treated with cyclophosphamide revealed a higher median of FSH levels compared to c-SLE patients not treated with cyclophosphamide and controls (8.8 vs. 5.7 vs. 5.6 IU/L, p = 0.032) and lower median AMH (0.4 vs. 1.5 vs. 1.5 ng/mL, p = 0.004) and AFC (4.0 vs. 6.5 vs. 16 IU/L, p = 0.001) levels. Nineteen patients treated exclusively with methotrexate demonstrated a negative correlation between the cumulative dose and AMH levels (p = 0.027, r = -0.507). CONCLUSIONS: The present study demonstrated for the first time that a high cumulative methotrexate dose is a possible cause of subclinical ovarian dysfunction in adult c-SLE patients. Further studies are required to confirm this deleterious effect in other rheumatic diseases, particularly juvenile idiopathic arthritis and idiopathic inflammatory myopathy.

Ovarian reserve in women with primary antiphospholipid syndrome.

OBJECTIVE: The objective of this paper is to evaluate ovarian reserve in primary antiphospholipid syndrome (PAPS) women and the association between ovarian reserve tests and clinical and laboratorial parameters, and anti-corpus luteum antibody (anti-CoL). METHODS: We screened 85 female patients between 18 to 40 years old with APS. Of these, 67 patients were excluded because of association with other autoimmune diseases (n = 42), contraindication or unwillingness to stop hormonal contraceptive (n = 21), current pregnancy or breastfeeding (n = 3) and previous ovarian surgery (n = 1). Therefore, a cross-sectional study was conducted in 18 PAPS patients and 24 healthy women. They were evaluated at early follicular phase with measurement of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol, and anti-Müllerian hormone (AMH) and sonographic antral follicle count (AFC). Serum measurement of anti-CoL was determined by immunoblot analysis. All analyses were performed after at least six months from the last intake of hormonal contraceptive and resumption of menstruation. RESULTS: The mean age was comparable in PAPS and controls (33.0 ± 5.0 vs. 30.4 ± 7.0 years; p = 0.19). Regarding ovarian reserve tests, the frequencies of low AFC (≤10) (56% vs. 22%, p = 0.04) and very low AFC (≤5) (37% vs. 9%, p = 0.04) were significantly higher in PAPS patients than controls. Trends of higher frequencies of reduced (<1.0 ng/ml), low (<0.5 ng/ml) and negligible (<0.2 ng/ml) AMH levels were found in PAPS patients (p = 0.08, p = 0.07 and p = 0.07, respectively). FSH, LH and estradiol were similar in patients and controls. There was no association between low ovarian reserve and specific types of antiphospholipid antibodies. Anti-CoL was solely observed in PAPS patients (11% vs. 0%; p = 0.177) and was not related to ovarian reserve tests. CONCLUSION: Women suffering from PAPS possessed reduced ovarian reserve, with prevalence greater than 50%.

Carotid artery stenting: clinical and procedural implications for near-occlusion stenosis.

INTRODUCTION AND OBJECTIVES: The advisability of implanting a stent in carotid near-occlusion stenosis is a controversial topic. We have assessed procedural and clinical implications of stent implantation for carotid artery disease with near occlusion. METHODS: We included 205 patients who underwent carotid artery revascularisation with a stent. The group of patients with near-occlusion stenosis (n=54)was compared to the rest of the population (n=151). RESULTS: No differences were found between groups for age, sex, and the percentage of symptomatic patients (three-quarters of the population). Carotid stent revascularisation for near-occlusion stenosis presented a high procedural success rate (96%) similar to that of revascularisation processes for other lesions (98%). Stenting in cases of near-occlusion stenosis required increased use of proximal protection (54% vs. 20.5%, P<.001) and predilation (33% vs. 17%, P=.01). The process to repair near-occlusion stenosis cause increased detachment of plaque, as shown by higher percentages of macroscopic plaque captured by protection devices (18.5% vs. 7%, P=.01) and of perioperative ischaemic brain lesions (47% vs 31%, P = .07). At 30 days of follow-up, the tendency toward adverse neurological events (death, major and minor stroke) was higher in the near-occlusion group (9.2% vs. 3.2%, P=.08). CONCLUSIONS: Stent revascularisation for near-occlusion carotid stenosis has a high procedural success rate; however, its higher plaque load was responsible for the increased rate of ischaemic brain lesions and adverse neurovascular events at 30 days post-procedure.

Epidural abscess due to Salmonella enteritidis in a patient with systemic lupus erythematosus.

Increased susceptibility to infection has long been observed among patients with systemic lupus erythematosus, and still represents a chief cause of morbidity and mortality in these patients. This is due in part to the severity of infection and to the difficulty of early diagnosis owing to the similarity between SLE flares and infection. Epidural infection is an uncommon condition, and a most rare condition caused by salmonella, which accounts for a broad spectrum of human illnesses from gastroenteritis and typhoid fever to the asymptomatic carrier state. We report the first case of epidural abscess caused by Salmonella enteritidis in a female with SLE with protean manifestations treated by intravenous antibiotics and surgery with full recovery of neurological symptoms, illustrating the importance of performing an early diagnosis and prompt treatment.

Severe hemorrhagic corpus luteum complicating anticoagulation in antiphospholipid syndrome.

Antiphospholipid syndrome (APS) is a disorder of coagulation that causes thrombosis as well as pregnancy-related complications, occurring due to the autoimmune production of antibodies against phospholipid. Full anticoagulation is the cornerstone therapy in patients with thrombosis history, and this can lead to major bleeding. During a 3-year period, 300 primary and secondary APS patients were followed up at the Rheumatology Division of the authors' University Hospital. Of them, 255 (85%) were women and 180 (60%) were of reproductive age. Three of them (1%) had severe hemorrhagic corpus luteum while receiving long-term anticoagulation treatment and are described in this report. All of them were taking warfarin, had elevated international normalized ratio (>4.0) and required prompt blood transfusion and emergency surgery. Therefore, we strongly recommend that all women with APS under anticoagulation should have ovulation suppressed with either intramuscular depot-medroxyprogesterone acetate or oral desogestrel.

Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images

The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98 percent for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously.

Brain tissue segmentation using q-entropy in multiple sclerosis magnetic resonance images.

The loss of brain volume has been used as a marker of tissue destruction and can be used as an index of the progression of neurodegenerative diseases, such as multiple sclerosis. In the present study, we tested a new method for tissue segmentation based on pixel intensity threshold using generalized Tsallis entropy to determine a statistical segmentation parameter for each single class of brain tissue. We compared the performance of this method using a range of different q parameters and found a different optimal q parameter for white matter, gray matter, and cerebrospinal fluid. Our results support the conclusion that the differences in structural correlations and scale invariant similarities present in each tissue class can be accessed by generalized Tsallis entropy, obtaining the intensity limits for these tissue class separations. In order to test this method, we used it for analysis of brain magnetic resonance images of 43 patients and 10 healthy controls matched for gender and age. The values found for the entropic q index were 0.2 for cerebrospinal fluid, 0.1 for white matter and 1.5 for gray matter. With this algorithm, we could detect an annual loss of 0.98% for the patients, in agreement with literature data. Thus, we can conclude that the entropy of Tsallis adds advantages to the process of automatic target segmentation of tissue classes, which had not been demonstrated previously.

Non-extensive entropy and the extraction of BOLD spatial information in event-related functional MRI.

Functional magnetic resonance imaging (fMRI) data analysis has been carried out recently in the framework of information theory, by means of the Shannon entropy. As a natural extension, a method based on the generalized Tsallis entropy was developed to the analysis event-related (ER-fMRI), where a brief stimulus is presented, followed by a long period of rest. The new technique aims for spatial localization neuronal activity due to a specific task. This method does not require a priori hypothesis of the hemodynamic response function (HRF) shape and the linear relation between BOLD responses with the presented task. Numerical simulations were performed so as to determine the optimal values of the Tsallis q parameter and the number of levels, L. In order to avoid undesirable divergences of the Tsallis entropy, only positive q values were studied. Results from simulated data (with L = 3) indicated that, for q = 0.8, the active brain areas are detected with the highest performance. Moreover, the method was tested for an in vivo experiment and demonstrated the ability to discriminate active brain regions that selectively responded to a bilateral motor task.

Quantitative evaluation of hemodynamic response after hypercapnia among different brain territories by fMRI.

The brain vascular system has an autoregulatory mechanism that maintains blood perfusion within normal limits at the capillary level. Partially due to its clinical importance, it is of interest to better understand the mechanisms involved in vascular regulation. Therefore, using functional magnetic resonance imaging (fMRI), we quantitatively investigated hemodynamic response characteristics of regions supplied by the main cerebral arteries, during two breath holding tests (BHT): after inspiration and after expiration. We used an auto-regressive method capable of estimating four signal parameters: onset delay, full width at half maximum (FWHM), time-to-peak and amplitude. The onset delay was significantly longer for the posterior cerebral artery (PCA) than for middle cerebral artery (MCA) and anterior arteries (ACA). FWHM and time-to-peak were larger in the ACA territory, indicating a slower blood flow in this region. Differences were also observed in the amplitude among the three areas, where MCA and PCA territories showed the smallest and the highest amplitudes, respectively. Moreover, differences were found in amplitude and onset when BHT was performed after inspiration as compared to BHT after expiration. Time-to-peak and FWHM showed no statistical differences between these two challenges. Such results are related to regional anatomical specificities and biochemical mechanisms responsible for vasodilation, such as those related to vascularity and vessel sizes.