Rituximab treatment in ANCA-associated vasculitis patients: outcomes of a real-life experience from an observational cohort.

Rituximab is a first-line therapy in patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). Among previous studies evaluating its efficacy, the Hispanic/Latino population has been underrepresented. This study aimed to assess the outcomes of AAV patients treated with rituximab in a tertiary care center in Mexico. This is a retrospective cohort study including patients with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), or renal-limited vasculitis (RLV), who received at least one dose of rituximab (induction or maintenance therapy) from January 2014 to October 2020. Demographic, clinical, serological, histopathological, and treatment-related variables were retrieved. Outcomes were the rate of remission at 6 months during induction and the rate of relapses during maintenance. Damage, serious infections, and death were assessed. Differences between patients with and without remission were analyzed. Forty-two patients received rituximab, 34 of them as induction to remission. Twenty-two patients (65%) achieved remission after 6 months. Patients who achieved remission were younger than those who did not (50 vs. 60 years, p = 0.03). During induction, severe infections, most frequently pneumonia, occurred in 9 (26%), and one patient died. Twenty-four patients received rituximab as maintenance; of them, 23 (96%) achieved complete response, and 8 (33%) experienced relapses (median follow-up time 19 months). During maintenance, severe infections (pneumonia) occurred in 5 patients (21%), and 3 of them (13%) died. In this observational cohort study, the outcomes were similar to the ones reported in other populations, whereas severe infections were frequent and associated with mortality. Key Points • In this study, the outcomes of 42 Mexican patients with ANCA-associated vasculitis treated with rituximab were assessed in a real-life setting. • At 6 months, 65% of the patients achieved remission with rituximab, especially those younger than 50 years of age. • During maintenance therapy with rituximab, 96% of the patients achieved complete response, and 33% experienced relapses. • Severe infections, mostly pneumonia, occurred in 26% of patients during induction and 21% of patients during maintenance therapy with rituximab.

KARRIKIN UP-REGULATED F-BOX 1 (KUF1) imposes negative feedback regulation of karrikin and KAI2 ligand metabolism in Arabidopsis thaliana.

SignificanceKarrikins are chemicals in smoke that stimulate regrowth of many plants after fire. However, karrikin responses are not limited to species from fire-prone environments and can affect growth after germination. Putatively, this is because karrikins mimic an unknown signal in plants, KAI2 ligand (KL). Karrikins likely require modification in plants to become bioactive. We identify a gene, KUF1, that appears to negatively regulate biosynthesis of KL and metabolism of a specific karrikin. KUF1 expression increases in response to karrikin or KL signaling, thus forming a negative feedback loop that limits further activation of the signaling pathway. This discovery will advance understanding of how karrikins are perceived and how smoke-activated germination evolved. It will also aid identification of the elusive KL.

KAI2 regulates seedling development by mediating light-induced remodelling of auxin transport.

Photomorphogenic remodelling of seedling growth is a key developmental transition in the plant life cycle. The α/ß-hydrolase signalling protein KARRIKIN-INSENSITIVE2 (KAI2), a close homologue of the strigolactone receptor DWARF14 (D14), is involved in this process, but it is unclear how the effects of KAI2 on development are mediated. Here, using a combination of physiological, pharmacological, genetic and imaging approaches in Arabidopsis thaliana (Heynh.) we show that kai2 phenotypes arise because of a failure to downregulate auxin transport from the seedling shoot apex towards the root system, rather than a failure to respond to light per se. We demonstrate that KAI2 controls the light-induced remodelling of the PIN-mediated auxin transport system in seedlings, promoting a reduction in PIN7 abundance in older tissues, and an increase of PIN1/PIN2 abundance in the root meristem. We show that removing PIN3, PIN4 and PIN7 from kai2 mutants, or pharmacological inhibition of auxin transport and synthesis, is sufficient to suppress most kai2 seedling phenotypes. We conclude that KAI2 regulates seedling morphogenesis by its effects on the auxin transport system. We propose that KAI2 is not required for the light-mediated changes in PIN gene expression but is required for the appropriate changes in PIN protein abundance within cells.

KAI2 promotes Arabidopsis root hair elongation at low external phosphate by controlling local accumulation of AUX1 and PIN2.

Root hair (RH) growth to increase the absorptive root surface area is a key adaptation of plants to limiting phosphate availability in soils. Despite the importance of this trait, especially for seedling survival, little is known about the molecular events connecting phosphate starvation sensing and RH growth regulation. KARRIKIN INSENSITIVE2 (KAI2), an α/ß-hydrolase receptor of a yet-unknown plant hormone ("KAI2-ligand" [KL]), is required for RH elongation.1 KAI2 interacts with the F-box protein MORE AXILLIARY BRANCHING2 (MAX2) to target regulatory proteins of the SUPPRESSOR of MAX2 1 (SMAX1) family for degradation.2 Here, we demonstrate that Pi starvation increases KL signaling in Arabidopsis roots through transcriptional activation of KAI2 and MAX2. Both genes are required for RH elongation under these conditions, while smax1 smxl2 mutants have constitutively long RHs, even at high Pi availability. Attenuated RH elongation in kai2 mutants is explained by reduced shootward auxin transport from the root tip resulting in reduced auxin signaling in the RH zone, caused by an inability to increase localized accumulation of the auxin importer AUXIN TRANSPORTER PROTEIN1 (AUX1) and the auxin exporter PIN-FORMED2 (PIN2) upon Pi starvation. Consistent with AUX1 and PIN2 accumulation being mediated via ethylene signaling,3 expression of 1-AMINOCYCLOPROPANE-1-CARBOXYLATE SYNTHASE 7 (ACS7) is increased at low Pi in a KAI2-dependent manner, and treatment with an ethylene precursor restores RH elongation of acs7, but not of aux1 and pin2. Thus, KAI2 signaling is increased by phosphate starvation to trigger an ethylene- AUX1/PIN2-auxin cascade required for RH elongation.

Bioassays for the Effects of Strigolactones and Other Small Molecules on Root and Root Hair Development.

Growth and development of plant roots are highly dynamic and adaptable to environmental conditions. They are under the control of several plant hormone signaling pathways, and therefore root developmental responses can be used as bioassays to study the action of plant hormones and other small molecules. In this chapter, we present different procedures to measure root traits of the model plant Arabidopsis thaliana. We explain methods for phenotypic analysis of lateral root development, primary root length, root skewing and straightness, and root hair density and length. We describe optimal growth conditions for Arabidopsis seedlings for reproducible root and root hair developmental outputs; and how to acquire images and measure the different traits using image analysis with relatively low-tech equipment. We provide guidelines for a semiautomatic image analysis of primary root length, root skewing, and root straightness in Fiji and a script to automate the calculation of root angle deviation from the vertical and root straightness. By including mutants defective in strigolactone (SL) or KAI2 ligand (KL) synthesis and/or signaling, these methods can be used as bioassays for different SLs or SL-like molecules. In addition, the techniques described here can be used for studying seedling root system architecture, root skewing, and root hair development in any context.

Publisher Correction: Extensive signal integration by the phytohormone protein network.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Extensive signal integration by the phytohormone protein network.

Plant hormones coordinate responses to environmental cues with developmental programs1, and are fundamental for stress resilience and agronomic yield2. The core signalling pathways underlying the effects of phytohormones have been elucidated by genetic screens and hypothesis-driven approaches, and extended by interactome studies of select pathways3. However, fundamental questions remain about how information from different pathways is integrated. Genetically, most phenotypes seem to be regulated by several hormones, but transcriptional profiling suggests that hormones trigger largely exclusive transcriptional programs4. We hypothesized that protein-protein interactions have an important role in phytohormone signal integration. Here, we experimentally generated a systems-level map of the Arabidopsis phytohormone signalling network, consisting of more than 2,000 binary protein-protein interactions. In the highly interconnected network, we identify pathway communities and hundreds of previously unknown pathway contacts that represent potential points of crosstalk. Functional validation of candidates in seven hormone pathways reveals new functions for 74% of tested proteins in 84% of candidate interactions, and indicates that a large majority of signalling proteins function pleiotropically in several pathways. Moreover, we identify several hundred largely small-molecule-dependent interactions of hormone receptors. Comparison with previous reports suggests that noncanonical and nontranscription-mediated receptor signalling is more common than hitherto appreciated.

Knowledge and Practices to Avoid Heat-Related Illness among Hispanic Farmworkers along the Florida-Georgia Line.

Objectives: Farmworkers who harvest and weed field crops are at increased risk for heat exposure and heat-related illness (HRI). The study objectives were to: (1) train crew leaders to use the Occupational Safety and Health Administration (OSHA) heat safety tool app and evaluate the utility of the app from a crew leader perspective; and (2) characterize heat safety knowledge, preventive practices, and perceptions of HRI risk among Hispanic farmworkers.Methods: Before harvest season, six crew leaders completed a 2-hour OSHA heat illness prevention training, including evaluation of a heat safety mobile app. Between August and October 2018, 101 Hispanic farmworkers participated in cross-sectional surveys about heat safety. Survey participants responded to questions about HRI prevention, HRI knowledge, and sociodemographics.Results: Crew leaders using the heat safety app rated the app very highly on relevance, functionality, value and privacy. Farmworkers did not report being overly concerned about HRI based on their survey responses. Nevertheless, 19% of farmworkers had experienced nonspecific symptoms from working in the heat, such as headache, dizziness, and nausea. In the multivariate linear regression model, farmworkers had lower heat safety knowledge scores if they were H-2A visa holders, female, and only "a little bit concerned," compared to others who were "very concerned" about working in the heat.Conclusion: The results of this study indicate the need for continued heat safety training for both crew leaders and farmworkers to reduce the risk of HRI, especially among less experienced farmworkers.

SMAX1/SMXL2 regulate root and root hair development downstream of KAI2-mediated signalling in Arabidopsis.

Karrikins are smoke-derived compounds presumed to mimic endogenous signalling molecules (KAI2-ligand, KL), whose signalling pathway is closely related to that of strigolactones (SLs), important regulators of plant development. Both karrikins/KLs and SLs are perceived by closely related α/ß hydrolase receptors (KAI2 and D14 respectively), and signalling through both receptors requires the F-box protein MAX2. Furthermore, both pathways trigger proteasome-mediated degradation of related SMAX1-LIKE (SMXL) proteins, to influence development. It has previously been suggested in multiple studies that SLs are important regulators of root and root hair development in Arabidopsis, but these conclusions are based on phenotypes observed in the non-specific max2 mutants and by use of racemic-GR24, a mixture of stereoisomers that activates both D14 and KAI2 signalling pathways. Here, we demonstrate that the majority of the effects on Arabidopsis root development previously attributed to SL signalling are actually mediated by the KAI2 signalling pathway. Using mutants defective in SL or KL synthesis and/or perception, we show that KAI2-mediated signalling alone regulates root hair density and root hair length as well as root skewing, straightness and diameter, while both KAI2 and D14 pathways regulate lateral root density and epidermal cell length. We test the key hypothesis that KAI2 signals by a non-canonical receptor-target mechanism in the context of root development. Our results provide no evidence for this, and we instead show that all effects of KAI2 in the root can be explained by canonical SMAX1/SMXL2 activity. However, we do find evidence for non-canonical GR24 ligand-receptor interactions in D14/KAI2-mediated root hair development. Overall, our results demonstrate that the KAI2 signalling pathway is an important new regulator of root hair and root development in Arabidopsis and lay an important basis for research into a molecular understanding of how very similar and partially overlapping hormone signalling pathways regulate different phenotypic outputs.

Elevated Core Temperature in Florida Fernery Workers: Results of a Pilot Study.

With expected increases in extreme weather, there may be a greater risk of injury from extreme heat in outdoor worker populations. To plan for future adaptation measures, studies are needed that can characterize workers' physiologic responses to heat in outdoor settings such as agriculture. The objective of this study was to characterize occupational heat exposure, key vulnerability factors (e.g., gender, energy expenditure), and physiologic heat stress response in a sample of fernery workers. Forty-three fernery workers over 86 workdays were examined regarding heat-related illness (HRI) during the summer months of 2012 and 2013. The key outcome measure was whether a participant's body core temperature (Tc) reached or exceeded 38.0°C (100.4ºF; Tc38). Participants' Tc exceeded 38.0°C on 49 (57%) of the workdays, with 30 of 40 participants reaching or exceeding Tc38 on at least one workday. Adjusting for sex, there was a 12% increase in the odds of Tc38 for every 100 kilocalories of energy expended (OR: 1.12; 95% Confidence Interval [CI]: [1.03, 1.21]). Adjusting for energy expenditure, females had 5 times greater odds of Tc38 compared with males (OR: 5.38; 95% CI: [1.03, 18.30]). These findings provide evidence of elevated Tc in Florida fernery workers, indicating an increased risk of occupational HRI, and the need for policy and interventions to address this health risk.

"I Think the Temperature was 110 Degrees!": Work Safety Discussions Among Hispanic Farmworkers.

Heat-related illness (HRI) among migrant and seasonal farmworkers is an occupational risk addressed through varying mitigation strategies by individual workers and supervisors. The purpose of this pilot study was to describe farmworkers' experience with HRI prevention strategies and assess HRI information seeking preferences, especially the feasibility of using mobile phone apps to access this information. Five focus groups were administered to Hispanic farmworkers in South Carolina. Questions included the following topics: health information seeking preferences; farmworkers' perceptions of occupational risks; coping strategies; past experiences with HRIs; water, rest, and shade practices; access to health care; and any employer-provided training received. There was consensus across the groups that the workers at highest risk for HRIs were either inexperienced or new workers in the fields. Farmworkers ascribed responsibility for one's well-being while working in the heat more as an individual factor than as an employer's responsibility. Farmworkers received training on the OSHA Heat Safety Tool app and provided positive feedback about the educational content and temperature information warnings. These findings suggest the potential for supervisors to take a more active role in heat safety education using mobile technology.

Heat Exposure in Central Florida Fernery Workers: Results of a Feasibility Study.

OBJECTIVE: The objective of this study was to determine the feasibility of field-based biomonitoring of heat-related illness (HRI) phenomena in Florida farmworkers. The authors determined feasibility through participant interviews regarding acceptability, data capture, recruitment and retention, and observed barriers and challenges to implementation. METHODS: Study participants were employed in fernery operations in northeast Central Florida where ornamental ferns are grown and harvested in a seasonally high-heat environment. In this pilot, a total of 43 farmworkers participated during summers 2012 and 2013 and measurements included body core temperature, heart rate, energy expenditure, urine and blood osmolality, and self-reported HRI symptoms. RESULTS: Data capture was approximately 90%. Participants reported that the study methods were nonobtrusive to their work, and that they were comfortable with study measures. CONCLUSIONS: These results open possibilities for characterizing HRI utilizing physiologic biomonitoring in vulnerable occupational groups.

Factors Limiting Formation of Community Forestry Enterprises in the Southern Mixteca Region of Oaxaca, Mexico.

Many studies have considered community-based forestry enterprises to be the best option for development of rural Mexican communities with forests. While some of Mexico's rural communities with forests receive significant economic and social benefits from having a community forestry enterprise, the majority have not formed such enterprises. The purpose of this article is to identify and describe factors limiting the formation of community forestry enterprise in rural communities with temperate forests in the Southern Mixteca region of Oaxaca, Mexico. The study involved fieldwork, surveys applied to Community Board members, and maps developed from satellite images in order to calculate the forested surface area. It was found that the majority of Southern Mixteca communities lack the natural and social conditions necessary for developing community forestry enterprise; in this region, commercial forestry is limited due to insufficient precipitation, scarcity of land or timber species, community members' wariness of commercial timber extraction projects, ineffective local governance, lack of capital, and certain cultural beliefs. Only three of the 25 communities surveyed have a community forestry enterprise; however, several communities have developed other ways of profiting from their forests, including pine resin extraction, payment for environmental services (PES), sale of spring water, and ecotourism. We conclude that community forestry enterprise are not the only option for rural communities to generate income from their forests; in recent years a variety of forest-related economic opportunities have arisen which are less demanding of communities' physical and social resources.

Anti-Inflammatory Activity and Changes in Antioxidant Properties of Leaf and Stem Extracts from Vitex mollis Kunth during In Vitro Digestion.

Vitex mollis is used in traditional Mexican medicine for the treatment of some ailments. However, there are no studies on what happens to the anti-inflammatory activity or antioxidant properties and total phenolic content of leaves and stem extracts of Vitex mollis during the digestion process; hence, this is the aim of this work. Methanolic, acetonic, and hexanic extracts were obtained from both parts of the plant. Extract yields and anti-inflammatory activity (elastase inhibition) were measured. Additionally, changes in antioxidant activity (DPPH and ABTS) and total phenols content of plant extracts before and after in vitro digestion were determined. The highest elastase inhibition to prevent inflammation was presented by hexanic extracts (leaf = 94.63% and stem = 98.30%). On the other hand, the major extract yield (16.14%), antioxidant properties (ABTS = 98.51% and DPPH = 94.47% of inhibition), and total phenols (33.70 mg GAE/g of dried sample) were showed by leaf methanolic extract. Finally, leaf and stem methanolic extracts presented an antioxidant activity increase of 35.25% and 27.22%, respectively, in comparison to their initial values after in vitro digestion process. All samples showed a decrease in total phenols at the end of the digestion. These results could be the basis to search for new therapeutic agents from Vitex mollis.

Bradyrhizobium BclA Is a Peptide Transporter Required for Bacterial Differentiation in Symbiosis with Aeschynomene Legumes.

Nodules of legume plants are highly integrated symbiotic systems shaped by millions of years of evolution. They harbor nitrogen-fixing rhizobium bacteria called bacteroids. Several legume species produce peptides called nodule-specific cysteine-rich (NCR) peptides in the symbiotic nodule cells which house the bacteroids. NCR peptides are related to antimicrobial peptides of innate immunity. They induce the endosymbionts into a differentiated, enlarged, and polyploid state. The bacterial symbionts, on their side, evolved functions for the response to the NCR peptides. Here, we identified the bclA gene of Bradyrhizobium sp. strains ORS278 and ORS285, which is required for the formation of differentiated and functional bacteroids in the nodules of the NCR peptide-producing Aeschynomene legumes. The BclA ABC transporter promotes the import of NCR peptides and provides protection against the antimicrobial activity of these peptides. Moreover, BclA can complement the role of the related BacA transporter of Sinorhizobium meliloti, which has a similar symbiotic function in the interaction with Medicago legumes.

Female farmworkers' perceptions of heat-related illness and pregnancy health.

Although agricultural workers have elevated risks of heat-related illnesses (HRI), pregnant farmworkers exposed to extreme heat face additional health risk, including poor pregnancy health and birth outcomes. Qualitative data from five focus groups with 35 female Hispanic and Haitian nursery and fernery workers provide details about the women's perceptions of HRI and pregnancy. Participants believe that heat exposure can adversely affect general, pregnancy, and fetal health, yet feel they lack control over workplace conditions and that they lack training about these specific risks. These data are being used to develop culturally appropriate educational materials emphasizing health promoting and protective behaviors during pregnancy.

Preventing eye injuries among citrus harvesters: the community health worker model.

OBJECTIVES: Although eye injuries are common among citrus harvesters, the proportion of workers using protective eyewear has been negligible. We focused on adoption of worker-tested safety glasses with and without the presence and activities of trained peer-worker role models on harvesting crews. METHODS: Observation of 13 citrus harvesting crews established baseline use of safety eyewear. Nine crews subsequently were assigned a peer worker to model use of safety glasses, conduct eye safety education, and treat minor eye injuries. Safety eyewear use by crews was monitored up to 15 weeks into the intervention. RESULTS: Intervention crews with peer workers had significantly higher rates of eyewear use than control crews. Intervention exposure time and level of worker use were strongly correlated. Among intervention crews, workers with 1 to 2 years of experience (odds ratio [OR] = 2.89; 95% confidence interval [CI] = 1.11, 7.55) and who received help from their peer worker (OR = 3.73; 95% CI = 1.21, 11.57) were significantly more likely to use glasses than were other intervention crew members. CONCLUSIONS: Adaptation of the community health worker model for this setting improved injury prevention practices and may have relevance for similar agricultural settings.

Estudo comparativo entre duas técnicas de osteotomia no tratamento do hálux valgo: análise clínica e radiográfica / Comparative study between two techniques of osteotomy on the first metatarsal base for the treatment of hallux valgus

Neste estudo prospectivo foi avaliado o tratamento cirúrgico de 19 pacientes, 24 pés, portadores de hálux valgo com deformidade moderada ou grave. Todos os pacientes foram submetidos à reconstrução distal de partes moles pela mesma técnica cirúrgica, sendo empregados dois tipos distintos de osteotomia proximal, para correção do varismo do I metatarsal, efetuados em seqüência randomizada e intercalando-se as duas técnicas. Em 12 pés realizou-se a osteotomia tipo adição e nos outros 12 pés a osteotomia tipo "chevron". A avaliação foi clínica e radiográfica, concluindo-se que o índice de avaliação clínica e as medidas radiográficas, no período pós-operatório, melhoraram significantemente, à exceção da discrepância entre o I e II metatarsais, e que a comparação entre os parâmetros clínicos e radiográficos resultantes dos dois tipos de osteotomias foram equivalentes.

Síndrome da criança espancada: aspectos legais e clínicos: relato de um caso / Battered child syndrome: legal and clinical aspects: report of a case

Os autores apresentam um caso de síndrome da criança espancada. Discutem a patologia com suas peculiaridades, dando enfoque aos aspectos jurídicos e à importância de seu diagnóstico com busca exaustiva, valorizando desta forma a relaçäo entre todas as partes envolvidas, o que pode culminar com o alívio de dor, a diminuiçäo de sofrimento e até mesmo o salvamento de uma vida.