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.

Brachio-cervical inflammatory myopathy associated with systemic sclerosis. Case series and review of literature.

This study was aimed at describing a case series of brachio-cervical inflammatory myopathy (BCIM) associated with systemic sclerosis (SSc), due to its rarity and limited coverage in published data. Another aim was to provide a literature review. We reported four cases of BCIM-SSc from our tertiary center. In addition, we researched the literature and found six articles featuring 17 patients who fit this phenotype. We pooled all cases and reported their features. Most patients were female and had limited SSc, and the median time of BCIM presentation was three years after SSc diagnosis. Asymmetric muscle involvement, scapular winging, dropped head, axial weakness, camptocormia, dysphagia, and dermatomyositis stigmas were common features. All patients had esophageal involvement. Most had positive antinuclear antibody results, a scleroderma pattern in their capillaroscopy images, elevated serum creatine phosphokinase, myopathic electrophysiology, and muscle involvement in magnetic resonance imaging. Muscle histopathological findings varied widely, but in general all showed the presence of lymphoid infiltrates, muscle atrophy, increased MHC-I expression, MAC deposits, vasculopathy, and muscle fiber necrosis. The response to immunosuppressive therapy was highly irregular. BCIM-SSc is a rare disorder that shares many similar phenotypes among the described cases, but has a highly heterogeneous response to treatment. At present, more data on the physiopathology, clinical features, and treatment is still needed.

Influence of slow sand filter cleaning process type on filter media biomass: backwashing versus scraping.

Biomass was assessed as a new approach for evaluating backwashed slow sand filters (BSF). Slow sand filtration (SSF) is a simple technology for water treatment, where biological mechanisms play a key role in filtration efficiency. Backwashed slow sand filters were previously recommended for small-scale filters (~1 m² of filtration area) as an alternative to conventional filters that are usually cleaned by scraping (ScSF). Biomass was never evaluated in BSF, which is a gap in the knowledge of this technology, considering the importance of its biological mechanisms. Therefore, for the first time, two filters operating under the same conditions were used to compare the influence of backwashing on biomass; one filter was cleaned by backwashing and the other by scraping. Biomass along the filter media depth (40 cm) was assessed by different techniques and compared in terms of cellular biomass (by chloroform fumigation), volatile solids, bacterial community (by 16S rRNA gene sequencing), and observations by scanning electron and fluorescence microscopy. Filters were also monitored and compared regarding filtered water quality and headloss; their differences were related to the different cleaning processes. Overall, filtered water quality was acceptable for slow sand filter standards (turbidity < 1 NTU and total coliform removal > 1 log). However, headloss developed faster on scraped filters, and biomass was different between the two filters. Backwashing did not significantly disturb biomass while scraping changed its surface sand layers. Cell biomass was more abundant and spread across the filtration depth, related to lower headloss, turbidity, and cyanobacterial breakthrough. These results agreed with the water quality and microscopy observations. The bacterial community was also less stratified in the backwashed filter media. These results expand the knowledge of backwashing use in slow sand filters, demonstrating that this process preserves more biomass than scraping. In addition, biomass preservation can lead to bacterial selectivity and faster filter ripening. Considering the importance of biomass preservation on slow sand filtration and its biological filtration mechanisms, the results presented in this paper are promising. The novel insight that BSF can preserve biomass after backwashing may contribute to increasing its application in small communities.

Warm-Season (C4) Turfgrass Genotypes Resistant to Spittlebugs (Hemiptera: Cercopidae).

Screening for resistance to insect pests is one of the early stages of grass breeding programs. Pasture spittlebugs are sap-sucking insects that potentially cause severe damage to turfgrasses, including the loss of functional quality and perenniallity. The Brazilian flora has a large number of grass species with wide morphological variability and adaptability to different soil and climate conditions that can potentially be used as lawns. However, no study has screened turfgrass genotypes for resistance to spittlebug attack. In this study, we evaluated the intra- and interspecific variability of 35 turfgrass genotypes in the genera Paspalum, Axonopus, and Zoysia for resistance to the pasture spittlebugs, Deois flavopicta (Stal) and Notozulia entreriana (Berg) (Hemiptera: Cercopidae), as measured by damage scores, densities of nymphs and adults, and level of antibiosis resistance. Genotypes were grouped into three groups using cluster analysis and principal component analysis: GroupI had genotypes associated with low damage scores and high density of adult spittlebugs; GroupII had genotypes with intermediate damage scores and low density of nymphs and adults; and GroupIII was formed by genotypes with high damage scores and high nymph density. Intra- and interspecific genotypic variability was related to antibiosis resistance and morphological variation among genotypes with some indicating nonpreference resistance and others indicating tolerance resistance. Our results indicate that besides antibiosis resistance studies, it is essential to evaluate the morphological variability of grass genotypes when screening for resistance to insects. Further studies are needed to elucidate the intraspecific variability of Paspalum notatum Flüggé genotypes for resistance to spittlebug attack.

Frequências de cortes em nove leguminosas forrageiras tropicais herbáceas cultivadas ao sol e sob plantação florestal / Cutting frequencies of nine herbaceous tropical forage legumes cultivated under full sun light and under a forest plantation

O objetivo deste trabalho foi estudar a produção e o valor nutritivo de nove espécies de leguminosas forrageiras herbáceas tropicais, cultivadas sob dois níveis de irradiação luminosa e seis frequências de corte na estação chuvosa, em Anhembi (SP), Brasil. Parcelas puras foram estabelecidas ao sol e sob plantação de Eucalyptus grandis, com 8 anos de idade, com 1.000 árvores/ha, que interceptou mais de 80% da radiação luminosa incidente. Avaliou-se a taxa de acúmulo de matéria seca, a proteína bruta e a digestibilidade in vitro da matéria seca em amostras de plantas colhidas em intervalos de 30, 60, 90 e 180 dias, com cortes adicionais aos 120 e 150 dias. Sob pleno sol, as leguminosas testadas toleraram cortes mais frequentes (intervalos de 30 - 90 dias), exceto o Lablab. Na sombra, o grau de tolerância variou conforme a espécie; em termos de produção de MS e de persistência, a Centrosema e a Puerária se destacaram dentre as demais leguminosas comparadas, quando os cortes foram realizados em intervalos de 60 dias, enquanto o Arachis e o Estilosantes foram os mais produtivos quando os cortes ocorreram em intervalos de 120 dias, mantendo o valor nutricional. O Alysicarpus e a Aeschynomene não persistiram sob o nível de sombreamento que prevaleceu nesse experimento.

The aim of this study was to evaluate the production and nutritive value of nine tropical legumes under two light intensities and six cutting regimens in the wet season, in Anhembi (SP) - Brazil. Pure stands were established in full light and under an eight-year-old eucalyptus plantation with 1.000 plants per hectare. The trees intercepted over80% of the incident radiation. Dry matter herbage accumulation, dry matter in vitro digestibility and crude protein under the cutting intervals 30, 60, 90 and 180 days, with additional cuttings at 120 and 150 days were evaluated. With the exception of Lablab, all other tested legume species tolerated higher cutting frequency under when grown under full sun light then under shade. The degree of shade-tolerance varied according to the species; Centrosema and Pueraria produced well at cutting intervals of 60 days, showing higher dry matter production and persistence while Arachis and Stylosanthes showed better results under longer cutting intervals, keeping the nutritional value, and can be indicated for differential grazing. Alysicarpus and Aeschynomene did not persist under the prevailing conditions.

Comparison between the anterior and posterior approach for transfer of the spinal accessory nerve to the suprascapular nerve in late traumatic brachial plexus injuries.

OBJECTIVE: To evaluate the transfer of the spinal accessory nerve to the suprascapular nerve through the anterior or posterior approach in patients with late traumatic brachial plexus injuries. METHODS: This study includes patients with late brachial plexus injuries that underwent a spinal accessory-to-suprascapular nerve transfer. They were divided into two equal groups, A and B, in which the spinal accessory nerve was transferred to the suprascapular nerve, respectively, through the anterior or posterior approach. Narakas's scale for assessment of the abduction of the arm and rotation of the shoulder was used. RESULTS: We studied 20 male patients with an age ranging from 18 to 42 years. In groups A and B, the mean age was 28 ± 5.5 and 26 ± 7.7 years, respectively. The time interval between injury and surgery was 9.5 ± 1.6 and 10.9 ± 2.5 months for groups A and B (p = 0.12), respectively. In the 20 patients in groups A and B, we obtained a strength of shoulder abduction at 30°, respectively, M3 (in 4 and 5), M2 (in 4 and 2), M1 (in 2 and 2) and M0 (in zero and 1) (p = 0.5). Regarding external rotation, group A showed M2 in only one patient and M0 in nine, while in group B, M3, in four; M2, in three; and M0, in three. In group B, the best results were observed in relation to the recovery of external rotation (p = 0.008). CONCLUSIONS: Better results in terms of external arm rotation were obtained when spinal accessory-to-suprascapular nerve transfer was performed using the posterior approach.

LTBI screening in rheumatoid arthritis patients prior to anti-TNF treatment in an endemic area.

SETTING: Recommendations for screening for latent tuberculous infection (LTBI) in patients eligible for anti-tumour necrosis factor (TNF) agents remain unclear in endemic regions. OBJECTIVE: To evaluate the long-term efficacy of LTBI screening and treatment in patients with rheumatoid arthritis (RA) receiving TNF blockers. DESIGN: A total of 202 RA patients were screened for LTBI before receiving anti-TNF treatment using the tuberculin skin test (TST), chest X-ray (CXR) and history of exposure to tuberculosis (TB). All subjects were regularly followed at 1- to 3-month intervals. RESULTS: Eighty-five patients (42%) were treated with a single anti-TNF agent, while 117 patients (58%) changed anti-TNF agents once or twice. LTBI screening was positive in 66 patients, 44 were TST-positive, 23 had a history of TB exposure and 14 had an abnormal CXR. Exposure alone accounted for LTBI diagnosis in 14 patients with a negative TST. LTBI patients were treated with isoniazid (300 mg/day) for 6 months, and none developed TB. During follow-up, TST was repeated in 51 patients. Conversion was observed in 5; 3 were diagnosed with LTBI and 2 with active TB respectively 14 and 36 months after receiving anti-TNF treatment, suggesting new TB exposure. CONCLUSION: LTBI screening and treatment before anti-TNF treatment is effective in endemic areas and reinforces the importance of establishing contact history for diagnosing LTBI in RA patients.

Complete asynapsis resulting in 2n pollen formation in Paspalum jesuiticum Parodi (Poaceae).

Cytological investigation revealed complete asynapsis during microsporogenesis in 2 wild accessions of Paspalum jesuiticum collected in distinct Brazilian regions. Both accessions were hexaploid (2n = 6x = 60) and 60 univalents could be counted at diakinesis. In this phase, the majority of meiocytes exhibited univalents with both chromatids. After alignment at the metaphase plate, the chromatids segregated to the poles. Only 1 meiotic division (equational) occurred, and after cytokinesis, a dyad with 2n microspores was formed. The genetic constitution of the 2n gametes was equivalent to that of first division restitution (FDR). Since recombination did not occur, 100% transmission of parental heterozygosity could be expected from the FDR 2n gametes. The meiotic behavior of both accessions suggested that they resulted from a recent natural hybridization event. The potential use of the 2n gametes in Paspalum breeding programs has been discussed.

Microsporogenesis in Paspalum conspersum Schrad. (Virgata group) with different ploidy levels.

Knowledge about the cytology and reproductive behavior of a species is indispensable for hybridization programs. This is especially true for species belonging to the genus Paspalum, among which apomixis and a wide range of ploidy levels are frequently found. Paspalum conspersum Schrad. is a robust and warm-season perennial bunchgrass native to South America. Previous studies have indicated that both tetraploid and hexaploid races exist in this species; however, only information related to tetraploids has been applied to another taxon. In this study, a cytological investigation in two Brazilian accessions collected in different regions revealed tetraploidy in the accession BRA-012823 (2n = 4x = 40), with chromosome pairing in bivalents and normal meiosis and tetrad formation, and pentaploidy (2n = 5x = 50) in the accession BRA-022748, which presented total asynapsis. In this latter accession, 50 univalents could be scored at diakinesis. After alignment at the metaphase plate, sister chromatids segregated to the poles. Only one meiotic division (equational) occurred, and after cytokinesis, 100% of the dyads that formed had 2n microspores. The meiotic behavior during microsporogenesis, which showed 10 delayed univalents to reach the metaphase plate, suggests that this accession is a recent natural hybrid constituted by a parental genome with 40 chromosomes and another with 10 chromosomes. The potential usage of these accessions in Paspalum breeding has been discussed.

Aspectos produtivos e sanitários de vacas mestiças leiteiras tratadas com produtos homeopáticos / Productive and sanitary aspects of crossbred milking cows receiving homeopathic products

Nos dias de hoje, a população mundial exige o consumo de alimentos de qualidade, sem resíduos de produtos químicos. Desempenho (produção e qualidade do leite, peso e condição corporal) e sanidade (mastite e infestação por ecto e endoparasitas) foram acompanhados em oito vacas leiteiras mestiças de um rebanho de 40 (20%), que recebeu diariamente produtos homeopáticos comerciais no concentrado para o controle de endo e ectoparasitas e mastite. No período de nove meses, que correspondeu a toda uma lactação, não houve necessidade de medicar com produtos alopáticos nenhuma vaca do rebanho, o que demonstrou ser possível criar vacas leiteiras mestiças não utilizando produtos químicos para o combate a parasitas (carrapato, mosca-do-chifre e verminose), ou antibióticos para o controle de mastite, e sem interferir na produtividade dos animais.

Nowadays the world population demands food of good quality, without any residues from chemical products. Eight cows from a herd of 40, which were consuming commercial homeopathic medicines at the daily concentration for control of endoand ectoparasites, were monitored in terms of their performance (production and quality of milk, body score and body weight) and sanitary aspects (parasites infestation and mastitis) during the lactation period. It was not necessary to give any allopathic (conventional) medicines to control mastitis or parasites (ticks, horn-fly, verminosis) in any cow of the herd during the nine months of the lactation period. The results showed that it is possible to produce milk without using chemical products, and not interfering in the productivity of the crossbred animals.

Microsatellite loci for Paspalum atratum (Poaceae) and cross-amplification in other species.

PREMISE OF THE STUDY: Paspalum atratum is a perennial, cespitose, tropical grass native to Central and South America. This species belongs to a polyploid complex (Plicatula group) little known at the genetic level. The characterized microsatellite markers provide new informative tools for further studies of the hybridization, mating systems, and structure of the population. • METHODS AND RESULTS: Using the microsatellite-enriched library method, we isolated and characterized 19 microsatellite markers from P. atratum. Eleven of them were polymorphic, showing a variable degree of variation, while eight were monomorphic in the samples analyzed. Additionally, the transferability of these microsatellite markers was tested in other species. • CONCLUSIONS: These results suggest that the characterized markers have enough discriminatory potential to be used in genetic characterizations of Paspalum taxa, which are based on an understanding of their mating systems and genetic structure, as well as in understanding the evolutionary processes involved in the evolution of groups of Paspalum.

A phase I trial of the bombesin/gastrin-releasing peptide (BN/GRP) antagonist RC3095 in patients with advanced solid malignancies.

Bombesin/gastrin-releasing peptides (BN/GRP) were shown to bind selectively to cell surface receptors, stimulating the growth of various types of malignancies in murine and human models. The novel BN/GRP synthetic receptor antagonist, RC-3095, was able to produce long-lasting tumor regressions in murine and human tumor models in vitro and in vivo. Animal toxicology studies showed no detectable organ toxicity apart from local irritation at the injection site. The purpose of this study was to determine the safety and feasibility of the administration of RC-3095 by daily subcutaneous injections in patients with advanced and refractory solid malignancies. Twenty-five patients received RC-3095 once or twice-daily at doses ranging from 8 to 96 ug/kg. Dose was escalated in groups of 3-5 patients per dose level. The only toxicity observed was local discomfort in the injection site at the highest doses. A single dose administration of RC-3095 at the highest dose level (96 ug/kg) was tested in a clearly hypergastrinemic individual with the Zollingen-Ellison syndrome and produced a decrease in plasma gastrin down to 50% of basal levels in 6 h. There was no objective tumor responses in patients included in the study. A short-lasting minor tumor response was observed in a patient with a GRP-expressing progressive medullary carcinoma of the thyroid. Due to problems with the analytical method, plasma pharmacokinetic data was obtained only from two patients included at the highest dose level. In these patients, RC-3095 reached plasma concentrations >100 ng/mL for about 8 h, which were within therapeutic levels on the basis of prior data obtained in mice and rats. The plasma elimination half-life was between 8.6-10.9 h. Due to the occurrence of local toxicity at the injection site, the dose escalation procedure could not be fully evaluated up to a maximum tolerated dose. Thus, a recommended dose of RC-3095 for Phase II trials could not be clearly established. Considering the novelty of its mechanism of action and impressive preclinical anti-tumor activity, further studies exploiting new formulations of RC-3095 for human use, such as slow-release preparations, and analogues with a more favorable pharmacokinetics are warranted.

Heterotopic transplantation of glycerin-preserved trachea: effect of respiratory epithelium desquamation on acute rejection.

An effective preservation method and decreased rejection are essential for tracheal transplantation in the reconstruction of large airway defects. Our objective in the present study was to evaluate the antigenic properties of glycerin-preserved tracheal segments. Sixty-one tracheal segments (2.4 to 3.1 cm) were divided into three groups: autograft (N = 21), fresh allograft (N = 18) and glycerin-preserved allograft (N = 22). Two segments from different groups were implanted into the greater omentum of dogs (N = 31). After 28 days, the segments were harvested and analyzed for mononuclear infiltration score and for the presence of respiratory epithelium. The fresh allograft group presented the highest score for mononuclear infiltration (1.78 +/- 0.43, P < or = 0.001) when compared to the autograft and glycerin-preserved allograft groups. In contrast to the regenerated epithelium observed in autograft segments, all fresh allografts and glycerin-preserved allografts had desquamation of the respiratory mucosa. The low antigenicity observed in glycerin segments was probably the result of denudation of the respiratory epithelium and perhaps due to the decrease of major histocompatibility complex class II antigens.

Heterotopic transplantation of glycerin-preserved trachea: effect of respiratory epithelium desquamation on acute rejection

An effective preservation method and decreased rejection are essential for tracheal transplantation in the reconstruction of large airway defects. Our objective in the present study was to evaluate the antigenic properties of glycerin-preserved tracheal segments. Sixty-one tracheal segments (2.4 to 3.1 cm) were divided into three groups: autograft (N = 21), fresh allograft (N = 18) and glycerin-preserved allograft (N = 22). Two segments from different groups were implanted into the greater omentum of dogs (N = 31). After 28 days, the segments were harvested and analyzed for mononuclear infiltration score and for the presence of respiratory epithelium. The fresh allograft group presented the highest score for mononuclear infiltration (1.78 ± 0.43, P <= 0.001) when compared to the autograft and glycerin-preserved allograft groups. In contrast to the regenerated epithelium observed in autograft segments, all fresh allografts and glycerin-preserved allografts had desquamation of the respiratory mucosa. The low antigenicity observed in glycerin segments was probably the result of denudation of the respiratory epithelium and perhaps due to the decrease of major histocompatibility complex class II antigens.

Interaction between repeated restraint stress and concomitant midazolam administration on sweet food ingestion in rats

Emotional changes can influence feeding behavior. Previous studies have shown that chronically stressed animals present increased ingestion of sweet food, an effect reversed by a single dose of diazepam administered before testing the animals. The aim of the present study was to evaluate the response of animals chronically treated with midazolam and/or submitted to repeated restraint stress upon the ingestion of sweet food. Male adult Wistar rats were divided into two groups: controls and exposed to restraint 1 h/day, 5 days/week for 40 days. Both groups were subdivided into two other groups treated or not with midazolam (0.06 mg/ml in their drinking water during the 40-day treatment). The animals were placed in a lighted area in the presence of 10 pellets of sweet food (Froot loops(r)). The number of ingested pellets was measured during a period of 3 min, in the presence or absence of fasting. The group chronically treated with midazolam alone presented increased ingestion when compared to control animals (control group: 2.0 +/- 0.44 pellets and midazolam group: 3.60 +/- 0.57 pellets). The group submitted to restraint stress presented an increased ingestion compared to controls (control group: 2.0 +/- 0.44 pellets and stressed group: 4.18 +/- 0.58 pellets). Chronically administered midazolam reduced the ingestion in stressed animals (stressed/water group: 4.18 +/- 0.58 pellets; stressed/midazolam group: 3.2 +/- 0.49 pellets). Thus, repeated stress increases appetite for sweet food independently of hunger and chronic administration of midazolam can decrease this behavioral effect

Interaction between repeated restraint stress and concomitant midazolam administration on sweet food ingestion in rats.

Emotional changes can influence feeding behavior. Previous studies have shown that chronically stressed animals present increased ingestion of sweet food, an effect reversed by a single dose of diazepam administered before testing the animals. The aim of the present study was to evaluate the response of animals chronically treated with midazolam and/or submitted to repeated restraint stress upon the ingestion of sweet food. Male adult Wistar rats were divided into two groups: controls and exposed to restraint 1 h/day, 5 days/week for 40 days. Both groups were subdivided into two other groups treated or not with midazolam (0.06 mg/ml in their drinking water during the 40-day treatment). The animals were placed in a lighted area in the presence of 10 pellets of sweet food (Froot loops). The number of ingested pellets was measured during a period of 3 min, in the presence or absence of fasting. The group chronically treated with midazolam alone presented increased ingestion when compared to control animals (control group: 2.0 +/- 0.44 pellets and midazolam group: 3.60 +/- 0.57 pellets). The group submitted to restraint stress presented an increased ingestion compared to controls (control group: 2.0 +/- 0.44 pellets and stressed group: 4.18 +/- 0.58 pellets). Chronically administered midazolam reduced the ingestion in stressed animals (stressed/water group: 4.18 +/- 0.58 pellets; stressed/midazolam group: 3.2 +/- 0.49 pellets). Thus, repeated stress increases appetite for sweet food independently of hunger and chronic administration of midazolam can decrease this behavioral effect.

Open clinical study of the efficacy and safety of terbinafine cream 1% in children with tinea corporis and tinea cruris.

BACKGROUND: Topical application of antifungal agents is considered the treatment of choice for dermatomycoses. Most of the available drugs are fungistatic, requiring long term treatment to prevent relapses. Terbinafine is a synthetic antifungal agent that, because of its fungicidal action, provides high cure rates and low relapse rates after short periods of treatment. METHODS: Ninety-seven children ages 2 to 15 years with a suspected diagnosis of tinea corporis and/or tinea cruris were enrolled in this open trial. After mycologic assessment to confirm diagnosis (culture and direct microscopy) terbinafine 1% cream was applied once daily during 1 week. Clinical and mycologic assessments were made at the baseline visit and on Days 7, 14 and 21. Efficacy assessment was based on 88 children (9 patients excluded by protocol violation). RESULTS: Therapy was considered effective in 92.0% (81 of 88) of patients (complete clinical and mycologic cure or mycologic cure with minimum signs and symptoms or clinical improvement, > or = 50%). Tolerability was assessed in 97 patients on an intention-to-treat basis. Adverse reactions were itching 3% (3 of 97), itching associated with erythema exacerbation 1% (1 of 97) and contact dermatitis 1% (1 of 97). CONCLUSION: Terbinafine 1% cream appears to be an effective and well-tolerated treatment for tinea corporis and tinea cruris in children.