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Physaria fendleri is a member of the Brassicaceae that produces in its embryos hydroxy fatty acids, constituents of oils that are very valuable and widely used by industry for cosmetics, lubricants, biofuels, etc. Free of toxins and rich in hydroxy fatty acids, Physaria provides a promising alternative to imported castor oil and is on the verge of being commercialized. This study aims to identify important biochemical step(s) for oil synthesis in Physaria, which may serve as target(s) for future crop improvement. To advance towards this goal, the endosperm composition was analysed by LC-MS/MS to develop and validate culture conditions that mimic the development of the embryos in planta. Using developing Physaria embryos in culture and 13C-labeling, our studies revealed that: (i) Physaria embryos metabolize carbon into biomass with an efficiency significantly lower than other photosynthetic embryos; (ii) the plastidic malic enzyme provides 42% of the pyruvate used for de novo fatty acid synthesis, which is the highest measured so far in developing 'green' oilseed embryos; and (iii) Physaria uses non-conventional pathways to channel carbon into oil, namely the Rubisco shunt, which fixes CO2 released in the plastid, and the reversibility of isocitrate dehydrogenase, which provides additional carbon for fatty acid elongation.
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Brassicaceae , Carbono , Carbono/metabolismo , Cromatografia Líquida , Isótopos de Carbono/metabolismo , Espectrometria de Massas em Tandem , Brassicaceae/metabolismo , Ácidos Graxos/metabolismo , SementesRESUMO
INTRODUCTION: Abiraterone and enzalutamide are two androgen receptor pathway inhibitors approved, among others, for the treatment of metastatic castration-resistant prostate cancer in adult men whose disease has progressed on or after a docetaxel-based regimen. Although hematological effects, especially neutropenia, are one of the main complications of other oral antineoplastic drugs, these adverse effects are infrequent in the case of androgen receptor pathway inhibitors. CASE REPORT: We report the case of a patient diagnosed with metastatic castration-resistant prostate cancer who discontinued an androgen receptor pathway inhibitor due to drug-related grade 4 neutropenia. His control blood counts before enzalutamide starting were normal. After one month of treatment, he developed a grade 4 neutropenia, with complete neutrophil count recovery four weeks later. He underwent a bone marrow aspiration, which revealed normocelullar results, and enzalutamide was restarted. Three weeks later, the treatment was eventually discontinued due to neutropenia reappearance. Neutrophil count recovery was achieved one month later. Then, he started treatment with abiraterone, but two weeks later neutropenia reappeared. Abiraterone was withdrawn, and the patient recovered from neutropenia 2 weeks later. MANAGEMENT AND OUTCOMES: This case exposes not only the occurrence of rare toxicity of two individual drugs but also the description of a probable drug-class adverse event not reported before. The patient recovered from neutropenia after the androgen receptor pathway inhibitor was withdrawn, thereby supporting the diagnosis of probable drug-induced neutropenia. DISCUSSION: There is scarce evidence in the literature concerning androgen receptor pathway inhibitor-related neutropenia. However, its life-threatening potential cannot be ignored, so healthcare professionals should be warned of the possibility of the occurrence of such adverse reactions.
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AIM: The objective of this meta-analysis was to evaluate obstetric outcomes in gestational diabetes mellitus (GDM) patients treated with flexible management based on intrauterine ultrasound fetal growth (FMIUFG) or strict maternal glycemic adjustment (SMGA). METHODS: We performed a comprehensive systematic review of electronic databases for randomized clinical trials (RCTs) comparing obstetrics outcomes of singleton GDM patients managed according to FMIUFG or SMGA. The review protocol was registered in PROSPERO (CRD497888). Searches were conducted in PubMed, Embase, Cochrane, and LILACS. Primary outcomes were gestational age at delivery and birth weight. Random-effect model meta-analyses were used to minimize the effects of uncertainty associated with inter-study variability. Results are reported as standardized mean differences (SMDs) or as odds ratios (ORs) and their 95% confidence interval (CI). Heterogeneity between studies was estimated using the I2 statistic. The Cochrane Risk of Bias Scale was used to assess the quality of studies. There were five RCTs with low to moderate risk of bias, including 450 patients managed according to the FMIUFSG and 381 according to the SMGA. RESULTS: The macrosomia (birthweight >4000 g) rate was lower in pregnancies managed according to FMIUFG than SMGA adjustments (OR: 0.34; 95%CI: 0.16, 0.71). There were no significant differences in hypertensive disorder, cesarean section, neonatal intensive care unit admission, and large newborn for gestational age rates. CONCLUSIONS: The macrosomia rate was lower in women managed with the FMIUFG. There were no significant differences in other obstetric and neonate outcomes.
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OBJECTIVES: To evaluate the longevity of resin composite restorations placed in posterior teeth by dental students, using data from electronic records from 2008 to 2019. MATERIALS AND METHODS: Demographic (gender and age) and clinical variables (dental group, position in dental arch, and the number of restored surfaces) were evaluated. The 5-year follow-up was assessed according to the day the restoration was placed. Kaplan-Meier curves were generated to calculate the annual failure rate. Data were analyzed by Chi-Square, Kruskal-Wallis, and Mann-Whitney tests (α = 0.05). RESULTS: In total, 3.883 records relative to return periodicity were analyzed. The final sample consisted of 900 restorations from 479 patients. The majority were females, aged between 31 and 60. In total, 256 failures were reported (success rate = 78%), showing an annual failure rate of 2.05%. The main reasons for failures were restoration replacement (55.5%), endodontics (21.9%), prosthetics (14.5%) and extraction (8.2%). There was a higher risk of failure in restorations involving three or more surfaces (p = 0.000) and in patients over 60 years (p < 0.001). In females (p = 0.030), molars (p = 0.044), and maxillary teeth (p = 0.038) failed in a shorter time. CONCLUSIONS: Resin composite restorations placed in permanent posterior teeth by dental students had high survival rates. The main reason for failure was the replacement of restorations. The age group and the number of restored surfaces significantly affected the success of the restorations. CLINICAL RELEVANCE: The electronic health records over 12 years showed that 78% of the resin restorations in posterior teeth placed by dental students were successful for a minimum of five years.
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Dente Molar , Estudantes de Odontologia , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Resinas Compostas , Assistência OdontológicaRESUMO
Haemorrhoidal disease and anal fissure are the two most frequent entities within benign anal pathology, both of which have a negative impact on patients' quality of life. To date, there is no specific questionnaire in Spanish to assess the impact on quality of life in patients suffering from these conditions. The aim of our study is to validate in Spanish a questionnaire for this purpose, adapting it to our daily clinical practice. The HEMO-FISS-CdV is the Spanish version of the original HEMO-FISS-QoL by Abramowitz. The questionnaire consists of 23 items organised in 4 dimensions (physical, psychological, defecation and sexuality). The reliability of the new tool was assessed by determining internal consistency using Cronbach's alpha and Guttman's coefficient. It was also correlated with the quality of life questionnaire SF12 version 2. The Cronbach's alpha obtained for our questionnaire (HEMO-FISS-CdV) was 0.951 (ICC 95% +-0.016), with a range between 0.935 and 0.967. The Guttman two-half coefficient had a value of 0.910. Patients with internal haemorrhoids, anal fissure or both had higher values on the HEMO-FISS-CdV questionnaire than patients without internal haemorrhoids and these differences were significant (p<0.05). Both diseases have a negative impact on patients' quality of life. The HEMO-FISS-CdV questionnaire provides a tool in Spanish that easily and specifically assesses the impact of haemorrhoidal disease and anal fissure on quality of life.
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Pennycress (Thlaspi arvense L.), a member of the Brassicaceae family, produces seed oil high in erucic acid, suitable for biodiesel and aviation fuel. Although pennycress, a winter annual, could be grown as a dedicated bioenergy crop, an increase in its seed oil content is required to improve its economic competitiveness. The success of crop improvement relies upon finding the right combination of biomarkers and targets, and the best genetic engineering and/or breeding strategies. In this work, we combined biomass composition with metabolomic and transcriptomic studies of developing embryos from 22 pennycress natural variants to identify targets for oil improvement. The selected accession collection presented diverse levels of fatty acids at maturity ranging from 29% to 41%. Pearson correlation analyses, weighted gene co-expression network analysis and biomarker identifications were used as complementary approaches to detect associations between metabolite level or gene expression and oil content at maturity. The results indicated that improving seed oil content can lead to a concomitant increase in the proportion of erucic acid without affecting the weight of embryos. Processes, such as carbon partitioning towards the chloroplast, lipid metabolism, photosynthesis, and a tight control of nitrogen availability, were found to be key for oil improvement in pennycress. Besides identifying specific targets, our results also provide guidance regarding the best timing for their modification, early or middle maturation. Thus, this work lays out promising strategies, specific for pennycress, to accelerate the successful development of lines with increased seed oil content for biofuel applications.
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Brassicaceae , Transcriptoma , Transcriptoma/genética , Ácidos Erúcicos/metabolismo , Melhoramento Vegetal , Brassicaceae/genética , Brassicaceae/metabolismo , Óleos de Plantas/metabolismo , Sementes/genéticaRESUMO
Induction of high photosynthetic capacity is a key acclimation response to high light (HL) for many herbaceous dicot plants; however, the signaling pathways that control this response remain largely unknown. Here, a systems biology approach was utilized to characterize the induction of high photosynthetic capacity in strongly and weakly acclimating Arabidopsis thaliana accessions. Plants were grown for 5 wk in a low light (LL) regime, and time-resolved photosynthetic physiological, metabolomic, and transcriptomic responses were measured during subsequent exposure to HL. The induction of high nitrogen (N) assimilation rates early in the HL shift was strongly predictive of the induction of photosynthetic capacity later in the HL shift. Accelerated N assimilation rates depended on the mobilization of existing organic acid (OA) reserves and increased de novo OA synthesis during the induction of high photosynthetic capacity. Enhanced sucrose biosynthesis capacity increased in tandem with the induction of high photosynthetic capacity, and increased starch biosynthetic capacity was balanced by increased starch catabolism. This systems analysis supports a model in which the efficient induction of N assimilation early in the HL shift begins the cascade of events necessary for the induction of high photosynthetic capacity acclimation in HL.
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Arabidopsis , Arabidopsis/metabolismo , Luz , Fotossíntese/fisiologia , Aclimatação/fisiologia , Plantas/metabolismo , Amido/metabolismo , Folhas de Planta/fisiologiaRESUMO
Leishmania donovani causes anthroponotic visceral leishmaniasis, responsible for about 50,000 annual deaths worldwide. Current therapies have considerable side effects. Drug resistance has been reported and no vaccine is available nowadays. The development of undifferentiated promastigotes in the sand fly vector's gut leads to the promastigote form that is highly infective to the mammalian host. Fully differentiated promastigotes play a crucial role in the initial stages of mammalian host infection before internalization in the host phagocytic cell. Therefore, the study of protein levels in the promastigote stage is relevant for disease control, and proteomics analysis is an ideal source of vaccine candidate discovery. This study aims to get insight into the protein levels during the differentiation process of promastigotes by 2DE-MALDI-TOF/TOF. This partial proteome analysis has led to the identification of 75 proteins increased in at least one of the L. donovani promastigote differentiation and growth phases. This study has revealed the differential abundance of said proteins during growth and differentiation. According to previous studies, some are directly involved in parasite survival or are immunostimulatory. The parasite survival-related proteins are ascorbate peroxidase; cystathionine ß synthase; an elongation factor 1ß paralog; elongation factor 2; endoribonuclease L-PSP; an iron superoxide dismutase paralog; GDP-mannose pyrophosphorylase; several heat shock proteins-HSP70, HSP83-17, mHSP70-rel, HSP110; methylthioadenosine phosphorylase; two thiol-dependent reductase 1 paralogs; transitional endoplasmic reticulum ATPase; and the AhpC thioredoxin paralog. The confirmed immunostimulatory proteins are the heat shock proteins, enolase, and protein kinase C receptor analog. The potential immunostimulatory molecules according to findings in patogenic bacteria are fructose-1,6-diphophate aldolase, dihydrolipoamide acetyltransferase, isocitrate dehydrogenase, pyruvate dehydrogenase E1α and E1ß subunits, and triosephosphate isomerase. These proteins may become disease control candidates through future intra-vector control methods or vaccines.
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Leishmania donovani , Animais , Proteoma , Diferenciação Celular , Proteínas de Choque Térmico , Proteínas de Protozoários/análise , Mamíferos/metabolismoRESUMO
Ocular thelaziosis is a parasitosis distributed mainly in East Asia, but increasingly described in Europe in different domestic and wild animals, including dogs, different wild canids and lagomorphs, and exceptionally in humans. In Spain, in some areas, a high infection prevalence rate has been described in domestic canids, which may lead to an increase in human cases. However, the description of human cases is still exceptional, which suggests that they are probably underdiagnosed. A case of ocular thelaziosis in a 2-year-old girl from an urban environment is described.
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Doenças do Cão , Doenças Parasitárias , Infecções por Spirurida , Thelazioidea , Feminino , Humanos , Animais , Cães , Pré-Escolar , Infecções por Spirurida/diagnóstico , Infecções por Spirurida/epidemiologia , Infecções por Spirurida/veterinária , Doenças do Cão/epidemiologia , Olho , Europa (Continente)/epidemiologiaRESUMO
Earth observation environmental features measured through remote sensing and models of vector mosquitoes species Aedes aegypti and Ae. albopictus provide an advancement with regards to dengue risk in urban environments of subtropical areas of Argentina. The authors aim to estimate the effect of landscape coverage and spectral indices (Normalized Difference Vegetation Index [NDVI], Normalized Difference Water Index [NDWI] and Normalized Difference Built-up Index [NDBI]) on the larvae abundance of Ae. aegypti and Ae. albopictus in Eldorado, Misiones, Argentina using remote satellite sensors. Larvae of these species were collected monthly (June 2016 to April 2018), in four environments: tire repair shops, cemeteries, dwellings and an urban natural park. The proportion of landscape coverage (water, urban areas, bare soil, low vegetation and high vegetation) was determined from the supervised classification of Sentinel-2 images and spectral indices, calculated. The authors developed spatial models of both vector species by generalized linear mixed models. The model's results showed that Ae. aegypti larvae abundance was better modelled by NDVI minimum values, NDBI maximum values and the interaction between them. For Ae. albopictus proportion of bare soil, low vegetation and the interaction between both variables explained better the abundance.
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Aedes , Dengue , Animais , Mosquitos Vetores , Argentina/epidemiologia , Solo , Larva , Dengue/epidemiologia , Dengue/veterináriaRESUMO
Environmental factors such as diet and lifestyle have been shown to influence the development of some intestinal mucosal lesions that may be precursors of colorectal cancer (CRC). The presence of these alterations seems to be associated with misbalanced immunological parameter levels. However, it is still unclear as to which immunological parameters are altered in each phase of CRC development. In this work, we aimed to study the potential relationships of immunological and metabolic parameters with diet in a CRC-related lesion context. Dietary information was obtained using an annual semi-quantitative food-frequency questionnaire (FFQ) from 93 volunteers classified via colonoscopy examination according to the presence of intestinal polyps or adenocarcinoma. Cytokines, chemokines, and adipokines were determined from serum samples. We observed a reduction in adiponectin according to the damage to the mucosa, accompanied by an increase and decrease in C-X-C motif chemokine ligand 10 (CXCL10) and resistin, respectively, in CRC cases. The presence of aberrant crypt foci (ACF) in the polyp group was associated with higher tumor necrosis factor-alpha (TNF-α) concentrations. Vegetables were directly correlated with adiponectin and resistin levels, while the opposite occurred with red meat. A bioactive compound, soluble pectin, showed a negative association with TNF-α. Future dietary strategies could be developed to modulate specific immunological parameters in the context of CRC.
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Neoplasias Colorretais , Resistina , Humanos , Adulto , Neoplasias Colorretais/metabolismo , Adiponectina , Fator de Necrose Tumoral alfa , Dieta , Mucosa Intestinal/metabolismoRESUMO
BACKGROUND AND OBJECTIVES: Melanoma differentiation-associated gene 5 antibody (anti-MDA5) in dermatomyositis (DM) is associated with rapidly progressive interstitial lung disease and poor prognosis. Early diagnosis is key to improving the prognosis of these patients. The aim was to confirm cutaneous characteristics in patients with anti-MDA5 dermatomyositis and to explore new diagnostic markers for the presence of anti-MDA5 (anti-MDA5+ ). PATIENTS AND METHODS: A multicenter cross-sectional retrospective cohort study of 124 patients diagnosed with DM, of which 37 were anti-MDA5+ . Demographic data, laboratory data, and clinical manifestations were collected. RESULTS: Anti-MDA5+ DM is characterized by a distinct mucocutaneous phenotype that includes oral lesions, alopecia, mechanic's hands, palmar and dorsal papules, palmar erythema, vasculopathy, and skin ulceration. We found vasculopathy and digit tip involvement very frequently in anti-MDA5+ patients (p <0.001), being a diagnostic marker of anti-MDA5+ (OR, 12.355; 95% CI 2.850-79.263; p = 0.012 and OR, 7.447; 95% CI 2.103-46.718; p = 0.004, respectively). The presence of ulcers deserves special mention, especially in anti-MDA5+ patients, because in our cohort, up to 97% of the anti-MDA5+ patients had ulcers. CONCLUSIONS: In patients with suspected DM with digit tip involvement or vasculopathy, the presence of anti-MDA5 antibodies must be ruled out, as it may be a clinical predictor.
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Dermatomiosite , Humanos , Estudos Retrospectivos , Helicase IFIH1 Induzida por Interferon , Úlcera , Estudos Transversais , Autoanticorpos , PrognósticoRESUMO
Soybean oil is one of the most consumed vegetable oils worldwide. Genetic improvement of its concentration in seeds has been historically pursued due to its direct association with its market value. Engineering attempts aiming to increase soybean seed oil presented different degrees of success that varied with the genetic design and the specific variety considered. Understanding the embryo's responses to the genetic modifications introduced, is a critical step to successful approaches. In this work, the metabolic and transcriptional responses to AtWRI1 and AtDGAT1 expression in soybean seeds were evaluated. AtWRI1 is a master regulator of fatty acid (FA) biosynthesis, and AtDGAT1 encodes an enzyme catalysing the final and rate-limiting step of triacylglycerides biosynthesis. The events expressing these genes in the embryo did not show an increase in total FA content, but they responded with changes in the oil and carbohydrate composition. Transcriptomic studies revealed a down-regulation of genes putatively encoding for oil body packaging proteins, and a strong induction of genes annotated as lipases and FA biosynthesis inhibitors. Novel putative AtWRI1 targets, presenting an AW-box in the upstream region of the genes, were identified by comparison with an event that harbours only AtWRI1. Lastly, targeted metabolomics analysis showed that carbon from sugar phosphates could be used for FA competing pathways, such as starch and cell wall polysaccharides, contributing to the restriction in oil accumulation. These results allowed the identification of key cellular processes that need to be considered to break the embryo's natural restriction to uncontrolled seed lipid increase.
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Regulação da Expressão Gênica de Plantas , Glycine max , Metabolismo dos Carboidratos/genética , Desenvolvimento Embrionário , Regulação da Expressão Gênica de Plantas/genética , Óleos de Plantas/metabolismo , Plantas Geneticamente Modificadas/genética , Sementes/genética , Sementes/metabolismo , Glycine max/genética , Glycine max/metabolismo , Fatores de Transcrição/genéticaRESUMO
In legumes, symbiotic nitrogen (N) fixation (SNF) occurs in specialized organs called nodules after successful interactions between legume hosts and rhizobia. In a nodule, N-fixing rhizobia are surrounded by symbiosome membranes, through which the exchange of nutrients and ammonium occurs between bacteria and the host legume. Phosphorus (P) is an essential macronutrient, and N2-fixing legumes have a higher requirement for P than legumes grown on mineral N. As in the previous studies, in P deficiency, barrel medic (Medicago truncatula) plants had impaired SNF activity, reduced growth, and accumulated less phosphate in leaves, roots, and nodules compared with the plants grown in P sufficient conditions. Membrane lipids in M. truncatula tissues were assessed using electrospray ionization-mass spectrometry. Galactolipids were found to increase in P deficiency, with declines in phospholipids (PL), especially in leaves. Lower PL losses were found in roots and nodules. Subsequently, matrix-assisted laser desorption/ionization-mass spectrometry imaging was used to spatially map the distribution of the positively charged phosphatidylcholine (PC) species in nodules in both P-replete and P-deficient conditions. Our results reveal heterogeneous distribution of several PC species in nodules, with homogeneous distribution of other PC classes. In P poor conditions, some PC species distributions were observed to change. The results suggest that specific PC species may be differentially important in diverse nodule zones and cell types, and that membrane lipid remodeling during P stress is not uniform across the nodule.
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Medicago truncatula/metabolismo , Lipídeos de Membrana/metabolismo , Fixação de Nitrogênio/fisiologia , Fósforo/deficiência , Rhizobium/fisiologia , Nódulos Radiculares de Plantas/metabolismo , Simbiose/fisiologia , Produtos Agrícolas/química , Produtos Agrícolas/microbiologia , Interações Hospedeiro-Patógeno , Medicago truncatula/microbiologia , Folhas de Planta/química , Folhas de Planta/metabolismo , Nódulos Radiculares de Plantas/química , Nódulos Radiculares de Plantas/microbiologiaRESUMO
Symbiotic nitrogen (N) fixation entails successful interaction between legume hosts and rhizobia that occur in specialized organs called nodules. N-fixing legumes have a higher demand for phosphorus (P) than legumes grown on mineral N. Medicago truncatula is an important model plant for characterization of effects of P deficiency at the molecular level. Hence, a study was carried out to address the alteration in metabolite levels of M. truncatula grown aeroponically and subjected to 4 weeks of P stress. First, GC-MS-based untargeted metabolomics initially revealed changes in the metabolic profile of nodules, with increased levels of amino acids and sugars and a decline in amounts of organic acids. Subsequently, LC-MS/MS was used to quantify these compounds including phosphorylated metabolites in the whole plant. Our results showed a drastic reduction in levels of organic acids and phosphorylated compounds in -P leaves, with a moderate reduction in -P roots and nodules. Additionally, sugars and amino acids were elevated in the whole plant under P deprivation. These findings provide evidence that N fixation in M. truncatula is mediated through a N feedback mechanism that in parallel is related to carbon and P metabolism.
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Medicago truncatula , Cromatografia Líquida , Medicago truncatula/metabolismo , Fixação de Nitrogênio , Fósforo/metabolismo , Nódulos Radiculares de Plantas/metabolismo , Simbiose , Espectrometria de Massas em TandemRESUMO
BACKGROUND: Few studies describe the use of dolutegravir (DTG)-based dual therapies under routine clinical practice. OBJECTIVES: To report real-life data on the use of DTG-based dual therapies in treatment-experienced patients. METHODS: This was an observational, retrospective study. It included all treatment-experienced HIV patients starting a DTG-based dual therapy from 2014 to 2018. The primary end point was to identify the incidence and reasons for the switch. The secondary end points were to assess the effectiveness, safety, adherence, and costs after 48 weeks of treatment (W48). RESULTS: The incidence of the switch to a DTG-based dual therapy increased from 1.6 patients per 1000 patient-years in 2014 to 38.6 in 2018. A total of 241 patients initiated this therapy: 113 (46.9%) patients started DTG plus rilpivirine (RPV), 72 (29.9%), DTG plus lamivudine (3TC), and 68 (28.2%), DTG plus boosted-darunavir (b-DRV). A total of 170 patients completed W48 of follow-up. By intention-to-treat analysis, 89.3% of virologically suppressed (VS) patients (94.3% with DTG plus b-DRV, 91.3% with DTG plus 3TC, and 87.2% with DTG plus RPV) and 56.7% of non-VS patients (71.4% with DTG plus RPV and 52.2% with DTG plus b-DRV) achieved a viral load <50 copies/mL at W48. The protocol-defined virological failure was 6.5%. Overall, 8.8% of patients had early discontinuation. The annual cost increased by 800 per patient ($916). CONCLUSIONS AND RELEVANCE: The use of DTG-based dual therapies has increased in real life, showing a favorable effectiveness and safety profile. Treatment costs increased, except for the switch to DTG plus 3TC.
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Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Infecções por HIV/tratamento farmacológico , Compostos Heterocíclicos com 3 Anéis/efeitos adversos , Humanos , Oxazinas , Piperazinas , Piridonas/uso terapêutico , Estudos Retrospectivos , Carga ViralRESUMO
This international guideline proposes improving clozapine package inserts worldwide by using ancestry-based dosing and titration. Adverse drug reaction (ADR) databases suggest that clozapine is the third most toxic drug in the United States (US), and it produces four times higher worldwide pneumonia mortality than that by agranulocytosis or myocarditis. For trough steady-state clozapine serum concentrations, the therapeutic reference range is narrow, from 350 to 600 ng/mL with the potential for toxicity and ADRs as concentrations increase. Clozapine is mainly metabolized by CYP1A2 (female non-smokers, the lowest dose; male smokers, the highest dose). Poor metabolizer status through phenotypic conversion is associated with co-prescription of inhibitors (including oral contraceptives and valproate), obesity, or inflammation with C-reactive protein (CRP) elevations. The Asian population (Pakistan to Japan) or the Americas' original inhabitants have lower CYP1A2 activity and require lower clozapine doses to reach concentrations of 350 ng/mL. In the US, daily doses of 300-600 mg/day are recommended. Slow personalized titration may prevent early ADRs (including syncope, myocarditis, and pneumonia). This guideline defines six personalized titration schedules for inpatients: 1) ancestry from Asia or the original people from the Americas with lower metabolism (obesity or valproate) needing minimum therapeutic dosages of 75-150 mg/day, 2) ancestry from Asia or the original people from the Americas with average metabolism needing 175-300 mg/day, 3) European/Western Asian ancestry with lower metabolism (obesity or valproate) needing 100-200 mg/day, 4) European/Western Asian ancestry with average metabolism needing 250-400 mg/day, 5) in the US with ancestries other than from Asia or the original people from the Americas with lower clozapine metabolism (obesity or valproate) needing 150-300 mg/day, and 6) in the US with ancestries other than from Asia or the original people from the Americas with average clozapine metabolism needing 300-600 mg/day. Baseline and weekly CRP monitoring for at least four weeks is required to identify any inflammation, including inflammation secondary to clozapine rapid titration.
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Antipsicóticos , Clozapina , Adulto , Antipsicóticos/efeitos adversos , Povo Asiático , Proteína C-Reativa , Clozapina/efeitos adversos , Feminino , Humanos , Masculino , Ácido Valproico/efeitos adversosRESUMO
Wolbachia is a genus of gram-negative endosymbiotic bacterium of maternal transmission, located mainly in the gonads of arthropods, including mosquitoes such as Aedes albopictus. The current distribution of Ae. albopictus in Argentina is restricted to the subtropical northeastern region of the country. Here, we studied the seasonal prevalence of Wolbachia detected in Ae. albopictus larvae and the relationship between the abiotic factors of the larval microhabitat and the infection status, in Eldorado city, Misiones province, subtropical region. The prevalence of Wolbachia infection found was 76.89% (n = 312). From the total samples examined, 52.80% (n = 214) showed double infection with the wAlbA/wAlbB strains, 23.84% (n = 97) infection only with wAlbB, and 0.25% (n = 1) only with wAlbA. The prevalence of double infection did not present statistically significant differences between the sites studied. For single infection, the lowest prevalence value of the wAlbB strain (13.33%) was found in the natural park, whereas the highest was found in the family dwellings and cemeteries. Tire repair shops showed an intermediate value. The wAlbA single infection was identified once. Our results also showed an association between temperature and slightly turbid waters with exposure to the sun in the larval habitats and the probability of infection by Wolbachia.
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Aedes , Rickettsiaceae , Wolbachia , Aedes/microbiologia , Animais , Prevalência , SimbioseRESUMO
WHAT IS KNOWN AND OBJECTIVE: Rosai-Dorfman disease (RDD) is an infrequent entity of unknown aetiology. Currently, there is no clear consensus on the treatment, and nothing has shown definitive safety and efficacy. We describe the case of a woman diagnosed with pulmonary RDD, who responded to thalidomide treatment after failure of four previous lines of systemic chemotherapy. CASE DESCRIPTION: We present the case of a 74-year-old woman diagnosed with pulmonary RDD and autoimmune complications. We decided to use thalidomide as a rescue treatment after the failure of corticosteroids and several chemotherapies. Our patient achieved remission of the disease and remained stable for years. WHAT IS NEW AND CONCLUSION: To the authors' knowledge, this is the first reported case in which thalidomide treatment induced remission in refractory pulmonary RDD. Thalidomide showed a rapid onset of action, with lasting responses, which could make it an exciting option for treating this life-threatening.
Assuntos
Histiocitose Sinusal , Talidomida , Idoso , Feminino , Histiocitose Sinusal/complicações , Histiocitose Sinusal/diagnóstico , Histiocitose Sinusal/tratamento farmacológico , Humanos , Talidomida/uso terapêuticoRESUMO
BACKGROUND: Immune-mediated inflammatory diseases (IMIDs) are systemic conditions associated with a high social and health impact. New treatments have changed the prognosis of IMIDs and have increased patient autonomy in disease management. Mobile apps have enormous potential to improve health outcomes in patients with IMIDs. Although a large number of IMID apps are available, the app market is not regulated, and functionality and reliability remain uncertain. OBJECTIVE: Our aims are to review available apps for patients with IMIDs or caregivers and to describe the main characteristics and functionalities of these apps. METHODS: We performed an observational, cross-sectional, descriptive study of all apps for patients with IMIDs. Between April 5 and 14, 2021, we conducted a search of the App Store (iOS) and Play Store (Android) platforms. We used the names of the different IMIDs as search terms. The inclusion criteria were as follows: content related to IMIDs, English or Spanish language, and user population consisting of patients and health care consumers, including family and caregivers. The variables analyzed were as follows: app name, type of IMID, platform (Android or iOS), country of origin, language, category of the app, cost, date of the last update, size, downloads, author affiliation, and functionalities. RESULTS: We identified 713 apps in the initial search, and 243 apps met the criteria and were analyzed. Of these, 37% (n=90) were on Android, 27.2% (n=66) on iOS, and 35.8% (n=87) on both platforms. The most frequent categories were health and well-being/fitness apps (n=188, 48.5%) and medicine (n=82, 37.9%). A total of 211 (82.3%) apps were free. The mean time between the date of the analysis and the date of the most recent update was 18.5 (SD 19.3) months. Health care professionals were involved in the development of 100 (41.1%) apps. We found differences between Android and iOS in the mean time since the last update (16.2, SD 14.7 months vs 30.3, SD 25.7 months) and free apps (85.6% vs 75.8%; respectively). The functionalities were as follows: general information about lifestyles, nutrition, or exercises (n=135, 55.6%); specific information about the disease or treatment (n=102, 42%); recording of symptoms or adverse events (n=51, 21%); agenda/calendar (n=44, 18.1%); reminder medication (n=41, 16.9%); and recording of patient-reported outcomes (n=41, 16.9%). A total of 147 (60.5%) apps had more than one functionality. CONCLUSIONS: IMID-related apps are heterogeneous in terms of functionality and reliability. Apps may be a useful complement to IMID care, especially inpatient education (their most frequent functionality). However, more than half of the IMID apps had not been developed by health care professionals or updated in the last year.