Polymorphisms and haplotypes of TOLLIP and MUC5B are associated with susceptibility and survival in patients with fibrotic hypersensitivity pneumonitis.

INTRODUCTION AND OBJECTIVES: Hypersensitivity pneumonitis (HP) is an interstitial lung disease with diverse clinical features that can present a fibrotic phenotype similar to idiopathic pulmonary fibrosis (IPF) in genetically predisposed individuals. While several single nucleotide polymorphisms (SNPs) have been associated with IPF, the genetic factors contributing to fibrotic HP (fHP) remain poorly understood. This study investigated the association of MUC5B and TOLLIP variants with susceptibility, clinical presentation and survival in Portuguese patients with fHP. MATERIAL AND METHODS: A case-control study was undertaken with 97 fHP patients and 112 controls. Six SNPs residing in the MUC5B and TOLLIP genes and their haplotypes were analyzed. Associations with risk, survival, and clinical, radiographic, and pathological features of fHP were probed through comparisons among patients and controls. RESULTS: MUC5B rs35705950 and three neighboring TOLLIP variants (rs3750920, rs111521887, and rs5743894) were associated with increased susceptibility to fHP. Minor allele frequencies were greater among fHP patients than in controls (40.7% vs 12.1%, P<0.0001; 52.6% vs 40.2%, P = 0.011; 22.7% vs 13.4%, P = 0.013; and 23.2% vs 12.9%, P = 0.006, respectively). Haplotypes formed by these variants were also linked to fHP susceptibility. Moreover, carriers of a specific haplotype (G-T-G-C) had a significant decrease in survival (adjusted hazard ratio 6.92, 95% CI 1.73-27.64, P = 0.006). Additional associations were found between TOLLIP rs111521887 and rs5743894 variants and decreased lung function at baseline, and the MUC5B SNP and radiographic features, further highlighting the influence of genetic factors in fHP. CONCLUSION: These findings suggest that TOLLIP and MUC5B variants and haplotypes may serve as valuable tools for risk assessment and prognosis in fibrotic hypersensitivity pneumonitis, potentially contributing to its patient stratification, and offer insights into the genetic factors influencing the clinical course of the condition.

Unresectable stage III non-small cell lung cancer: Insights from a Portuguese expert panel.

INTRODUCTION: The management of unresectable stage III non-small cell lung cancer (NSCLC) is clinically challenging and there is no current consensus on optimal strategies. Herein, a panel of Portuguese experts aims to present practical recommendations for the global management of unresectable stage III NSCLC patients. METHODS: A group of Portuguese lung cancer experts debated aspects related to the diagnosis, staging and treatment of unresectable stage III NSCLC in light of current evidence. Recent breakthroughs in immunotherapy as part of a standard therapeutic approach were also discussed. This review exposes the major conclusions obtained. RESULTS: Practical recommendations for the management of unresectable stage III NSCLC were proposed, aiming to improve the pathways of diagnosis and treatment in the Portuguese healthcare system. Clinical heterogeneity of patients with stage III NSCLC hinders the development of single standardised algorithm where all fit. CONCLUSIONS: A timely diagnosis and a proper staging contribute to the best management of each patient, optimizing treatment tolerance and effectiveness. The expert panel considered chemoradiotherapy as the preferable approach when surgery is not possible. Management of adverse events and immunotherapy as a consolidation therapy are also essential steps for a successful strategy.

Ecotoxicological effects of commercial herbicides on the reproductive system of aquatic arthropod Limnocoris submontandoni (Hemiptera: Naucoridae)

Abstract Worldwide, conventional agriculture makes extensive use of pesticides. Although the effects of herbicides are relatively well known in terms of environmental impacts on non-target organisms, there is very little scientific evidence regarding the impacts of herbicide residues on aquatic arthropods from tropical conservation areas. This study evaluates for the first time the toxicity of the herbicides ametryn, atrazine, and clomazone on the aquatic insect Limnocoris submontandoni (Hemiptera: Naucoridae). The lethal concentration (LC50) of herbicides was evaluated for these insects, as well as the effect of the herbicides on the insects tissues and testicles. The estimated LC50 was 1012.41, 192.42, and 46.09 mg/L for clomazone, atrazine, and ametryn, respectively. Spermatocyte and spermatid changes were observed under the effect of atrazine, and effects on spermatogenesis were observed for some concentrations of clomazone, with apparent recovery after a short time. Our results provide useful information on the effects of herbicide residues in aquatic systems. This information can help minimize the risk of long-term reproductive effects in non-target species that have been previously overlooked in ecotoxicology studies.

Resumo Em todo o mundo, a agricultura convencional faz uso extensivo de pesticidas. Embora os efeitos dos herbicidas sejam relativamente bem conhecidos em termos de impactos ambientais em organismos não-alvo, há pouca evidência científica sobre os impactos de resíduos de herbicidas em artrópodes aquáticos de áreas de conservação tropicais. Este estudo avalia pela primeira vez a toxicidade dos herbicidas ametryn, atrazine e clomazone sobre o inseto aquático Limnocoris submontandoni (Hemiptera: Naucoridae). A concentração letal (LC50) de herbicidas foi avaliada para esses insetos, bem como o efeito dos herbicidas nos tecidos e testículos dos insetos. A LC50 estimada foi de 1012,41, 192,42 e 46,09 mg/L para clomazone, atrazine e ametryn, respectivamente. Alterações nos espermatócitos e espermátides foram observadas sob o efeito de atrazine, e efeitos na espermatogênese foram observados para algumas concentrações de clomazone, com aparente recuperação após um curto período de tempo. Nossos resultados fornecem informações úteis sobre os efeitos de resíduos de herbicidas em sistemas aquáticos. Essas informações podem ajudar a minimizar o risco de efeitos reprodutivos de longo prazo em espécies não-alvo que foram negligenciadas anteriormente em estudos de ecotoxicologia.

Insects and spiders on Acacia mangium (Fabaceae) saplings as bioindicators for the recovery of tropical degraded areas

Abstract Acacia mangium is a pioneer species with fast growth and frequently used in the recovery of degraded areas. The objectives were to evaluate insects and spiders, their ecological indices and interactions on A. mangium saplings in a tropical degraded area in recovering process. The experimental design was completely randomized with 24 replications, with treatments represented by the first and second years after A. mangium seedling planted. Numbers of leaves/branch, branches/sapling, and ground cover by A. mangium saplings, Hemiptera: Phenacoccus sp. and Pachycoris torridus; Hymenoptera: Tetragonisca angustula and Trigona spinipes, Brachymyrmex sp., Camponotus sp. and Cephalotes sp.; Blattodea: Nasutitermes sp. and Neuroptera: Chrysoperla sp.; abundance, species richness of pollinating insects, tending ants, and the abundance of Sternorrhyncha predators were greatest in the second year after planting. Numbers of Hemiptera: Aethalium reticulatum, Hymenoptera: Camponotus sp., Cephalotes sp., Polybia sp., T. angustula, T. spinipes, tending ants, pollinating insects, Sternorrhyncha predators and species richness of tending ants were highest on A. mangium saplings with greatest numbers of leaves or branches. The increase in the population of arthropods with ground cover by A. mangium saplings age increase indicates the positive impact by this plant on the recovery process of degraded areas.

Resumo Acacia mangium é uma espécie pioneira, de rápido crescimento e utilizada na recuperação de áreas degradadas. Os objetivos foram avaliar insetos e aranhas, seus índices ecológicos e interações com plantas de A. mangium em área tropical degradada em processo de recuperação. O delineamento experimental foi inteiramente casualizado com 24 repetições, com os tratamentos representados pelos primeiro e segundo anos após a plantio de A. mangium. Os números de folhas/galhos, galhos/plantas e cobertura do solo por plantas de A. mangium, de Hemiptera: Phenacoccus sp. e Pachycoris torridus; Hymenoptera: Tetragonisca angustula e Trigona spinipes, Brachymyrmex sp., Camponotus sp. e Cephalotes sp.; Blattodea: Nasutitermes sp. e Neuroptera: Chrysoperla sp.; a abundância, riqueza de espécies de insetos polinizadores, formigas cuidadoras e a abundância de predadores de Sternorrhyncha foram maiores no segundo ano após o plantio. Os números de Hemiptera: Aethalium reticulatum, Hymenoptera: Camponotus sp., Cephalotes sp., Polybia sp., T. angustula, T. spinipes, formigas cuidadoras, insetos polinizadores, predadores de Sternorrhyncha e a riqueza de espécies de formigas cuidadoras foram maiores em plantas de A. mangium com maior altura e número de folhas ou galhos. O aumento populacional de artrópodes e da cobertura do solo com o processo de envelhecimento das plantas de A. mangium indicam impacto positivo dessa planta na recuperação de áreas degradadas.

Insects and spiders on Acacia mangium (Fabaceae) saplings as bioindicators for the recovery of tropical degraded areas / Insetos e aranhas em plantas de Acacia mangium (Fabaceae) como bioindicadores na recuperação de área tropical degradada

Abstract Acacia mangium is a pioneer species with fast growth and frequently used in the recovery of degraded areas. The objectives were to evaluate insects and spiders, their ecological indices and interactions on A. mangium saplings in a tropical degraded area in recovering process. The experimental design was completely randomized with 24 replications, with treatments represented by the first and second years after A. mangium seedling planted. Numbers of leaves/branch, branches/sapling, and ground cover by A. mangium saplings, Hemiptera: Phenacoccus sp. and Pachycoris torridus; Hymenoptera: Tetragonisca angustula and Trigona spinipes, Brachymyrmex sp., Camponotus sp. and Cephalotes sp.; Blattodea: Nasutitermes sp. and Neuroptera: Chrysoperla sp.; abundance, species richness of pollinating insects, tending ants, and the abundance of Sternorrhyncha predators were greatest in the second year after planting. Numbers of Hemiptera: Aethalium reticulatum, Hymenoptera: Camponotus sp., Cephalotes sp., Polybia sp., T. angustula, T. spinipes, tending ants, pollinating insects, Sternorrhyncha predators and species richness of tending ants were highest on A. mangium saplings with greatest numbers of leaves or branches. The increase in the population of arthropods with ground cover by A. mangium saplings age increase indicates the positive impact by this plant on the recovery process of degraded areas.

Resumo Acacia mangium é uma espécie pioneira, de rápido crescimento e utilizada na recuperação de áreas degradadas. Os objetivos foram avaliar insetos e aranhas, seus índices ecológicos e interações com plantas de A. mangium em área tropical degradada em processo de recuperação. O delineamento experimental foi inteiramente casualizado com 24 repetições, com os tratamentos representados pelos primeiro e segundo anos após a plantio de A. mangium. Os números de folhas/galhos, galhos/plantas e cobertura do solo por plantas de A. mangium, de Hemiptera: Phenacoccus sp. e Pachycoris torridus; Hymenoptera: Tetragonisca angustula e Trigona spinipes, Brachymyrmex sp., Camponotus sp. e Cephalotes sp.; Blattodea: Nasutitermes sp. e Neuroptera: Chrysoperla sp.; a abundância, riqueza de espécies de insetos polinizadores, formigas cuidadoras e a abundância de predadores de Sternorrhyncha foram maiores no segundo ano após o plantio. Os números de Hemiptera: Aethalium reticulatum, Hymenoptera: Camponotus sp., Cephalotes sp., Polybia sp., T. angustula, T. spinipes, formigas cuidadoras, insetos polinizadores, predadores de Sternorrhyncha e a riqueza de espécies de formigas cuidadoras foram maiores em plantas de A. mangium com maior altura e número de folhas ou galhos. O aumento populacional de artrópodes e da cobertura do solo com o processo de envelhecimento das plantas de A. mangium indicam impacto positivo dessa planta na recuperação de áreas degradadas.

Ecotoxicological effects of commercial herbicides on the reproductive system of aquatic arthropod Limnocoris submontandoni (Hemiptera: Naucoridae) / Efeitos ecotoxicológicos de herbicidas comerciais no sistema reprodutivo do artrópode aquático Limnocoris submontandoni (Hemiptera: Naucoridae)

Abstract Worldwide, conventional agriculture makes extensive use of pesticides. Although the effects of herbicides are relatively well known in terms of environmental impacts on non-target organisms, there is very little scientific evidence regarding the impacts of herbicide residues on aquatic arthropods from tropical conservation areas. This study evaluates for the first time the toxicity of the herbicides ametryn, atrazine, and clomazone on the aquatic insect Limnocoris submontandoni (Hemiptera: Naucoridae). The lethal concentration (LC50) of herbicides was evaluated for these insects, as well as the effect of the herbicides on the insects' tissues and testicles. The estimated LC50 was 1012.41, 192.42, and 46.09 mg/L for clomazone, atrazine, and ametryn, respectively. Spermatocyte and spermatid changes were observed under the effect of atrazine, and effects on spermatogenesis were observed for some concentrations of clomazone, with apparent recovery after a short time. Our results provide useful information on the effects of herbicide residues in aquatic systems. This information can help minimize the risk of long-term reproductive effects in non-target species that have been previously overlooked in ecotoxicology studies.

Resumo Em todo o mundo, a agricultura convencional faz uso extensivo de pesticidas. Embora os efeitos dos herbicidas sejam relativamente bem conhecidos em termos de impactos ambientais em organismos não-alvo, há pouca evidência científica sobre os impactos de resíduos de herbicidas em artrópodes aquáticos de áreas de conservação tropicais. Este estudo avalia pela primeira vez a toxicidade dos herbicidas ametryn, atrazine e clomazone sobre o inseto aquático Limnocoris submontandoni (Hemiptera: Naucoridae). A concentração letal (LC50) de herbicidas foi avaliada para esses insetos, bem como o efeito dos herbicidas nos tecidos e testículos dos insetos. A LC50 estimada foi de 1012,41, 192,42 e 46,09 mg/L para clomazone, atrazine e ametryn, respectivamente. Alterações nos espermatócitos e espermátides foram observadas sob o efeito de atrazine, e efeitos na espermatogênese foram observados para algumas concentrações de clomazone, com aparente recuperação após um curto período de tempo. Nossos resultados fornecem informações úteis sobre os efeitos de resíduos de herbicidas em sistemas aquáticos. Essas informações podem ajudar a minimizar o risco de efeitos reprodutivos de longo prazo em espécies não-alvo que foram negligenciadas anteriormente em estudos de ecotoxicologia.

The schistosomicidal activity of ethanolic extracts from branches, leaves, flowers and fruits of Handroanthus impetiginosus (Mart. ex DC.) Mattos (Bignoniaceae) plant and metabolic profile characterization by UPLC-ESI-QTOF analysis.

Schistosomiasis, caused by Schistosoma mansoni Sambon, 1907, is a severe and widely distributed parasitic disease, affecting about 200 million people worldwide. The disease is recognized by elevated mortality rates, especially among those living in areas of poor sanitation. Currently, the chemotherapeutic treatment is solely based on using the praziquantel drug. Therefore, there is a need for the discovery of new medicines for the treatment of this parasitosis. Thus, this work aimed to evaluate the schistosomicidal activity of ethanolic crude extracts from the branches, leaves, flowers, and fruits of Handroanthus impetiginosus (Mart ex DC.) Masttos and characterize its metabolic profile by UPLC-ESI-QTOF analysis. Evaluation of plant extract on S. mansoni was carried out in adult worms in vitro, in which the mortality rate was quantified, and the damages in the tegument of the worms were monitored. All extracts induced changes in the viability of adult males of S. mansoni, causing the death of the parasites, which was directly dependent of the concentration.

Exploring the potential of Eu3+ and Mn4+ activated LaAlO3 phosphors as red and far-red emitters for horticulture lighting.

The development of efficient red and far-red emitters, for efficient plant absorption in the Photosynthetically Active Radiation (PAR) region, holds significance in contemporary plant growth control. This study focuses on the synthesis and characterization of LaAlO3 as a host material, doped with Eu3+ and Mn4+ ions, using a solid-state reaction method. The investigation encompasses the creation and analysis of both single-doped and co-doped samples, employing techniques including X-ray diffraction (XRD), scanning electron microscopy (SEM), and photoluminescence (PL) spectroscopy. XRD analysis consistently confirmed the perovskite-like structure of all samples, devoid of detectable impurities or major structural changes due to doping. SEM images revealed a uniform distribution of regularly shaped particles for the co-doped sample. The PL spectroscopy showed that the doping led to strong photoluminescence, with the co-doped sample exhibiting the intensity of each of the ions independently neither exhibiting quenching nor energy transfer mechanisms. The excitation spectrum of Eu3+ exhibited a broad charge transfer band at approximately 328 nm, coupled with characteristic f-f excitation bands. On the other hand, the Mn4+ ion's excitation spectrum featured transitions from ground state (4A2g) electrons excited to higher excited states (4T1g, 2T2g, and 4T2g) centered at 350 nm and within the region 250-550 nm. The co-doped sample was excited at a common excitation wavelength of 460 nm and underwent an in-depth examination of its photoluminescent properties, including decay curves analysis and time dependence also. The results from this study suggest that the synthesized phosphor materials exhibit substantial potential for diverse applications, including but not limited to solid-state lighting for efficient plant growth.

Genomic instability in long-term culture of human adipose-derived mesenchymal stromal cells.

Mesenchymal stromal/stem cells stem (MSC) have been widely studied due to their great potential for application in tissue engineering and regenerative and translational medicine. In MSC-based therapy for human diseases, cell proliferation is required to obtain a large and adequate number of cells to ensure therapeutic efficacy. During in vitro culture, cells are under an artificial environment and manipulative stress that can affect genetic stability. Several regulatory agencies have established guidelines to ensure greater safety in cell-based regenerative and translational medicine, but there is no specific definition about the maximum number of passages that ensure the lowest possible risk in MSC-based regenerative medicine. In this context, the aim of this study was to analyze DNA damage and chromosome alterations in adipose-derived mesenchymal stromal cells (ADMSC) until the eleventh passage and to provide additional subsidies to regulatory agencies related to number of passages in these cells. Thus, two methods in genetic toxicology were adopted: comet assay and micronucleus test. The comet assay results showed an increase in DNA damage from the fifth passage onwards. The micronucleus test showed a statistically significant increase of micronucleus from the seventh passage onwards, indicating a possible mutagenic effect associated with the increase in the number of passages. Based on these results, it is important to emphasize the need to assess genetic toxicology and inclusion of new guidelines by regulatory agencies to guarantee the safety of MSC-based therapies for human diseases.

Settleable atmospheric particulate matter affects the swimming performance and aerobic metabolic rate of Nile tilapia (Oreochromis niloticus).

Atmospheric particulate matter (APM) produced by the steel industry comprises a complex mixture of particles that includes a wide variety of metals and metallic nanoparticles. These particles settle out onto areas surrounding the industries. There is evidence that this 'settleable' APM (SePM) may cause air-to-water cross-contamination with significant effects on aquatic biota. Recent investigations have reported sublethal impacts on the gill structure and blood oxygen-carrying capacity of fishes, which raises the hypothesis that there will be consequences for gas exchange capacity and ability to support aerobic activities. Therefore, we investigated the effects of an environmentally relevant level of SePM contamination on swimming performance and associated aerobic metabolic rates in Nile tilapia, Oreochromis niloticus. Short-term exposure (96 h) to SePM reduced critical swimming speed, energetic efficiency of aerobic swimming, standard metabolic rate, maximum metabolic rate, and aerobic scope. The compromised swimming performance could have adverse ecological effects by limiting foraging ability, predator evasion, territorial protection, and migration. The impairments to aerobic capacity could also affect overall fish performance by influencing long-term energy balance and allocation to growth and reproduction. Thus, despite being sublethal, SePM contamination is considerably debilitating, and if its limiting effects are not compensated for in the longer term, this may reduce the survival and fitness of fish populations.

A randomised controlled trial of compression therapies for the treatment of venous leg ulcers (VenUS 6): study protocol for a pragmatic, multicentre, parallel-group, three-arm randomised controlled trial.

BACKGROUND: Venous leg ulcer(s) are common, recurring, open wounds on the lower leg, resulting from diseased or damaged leg veins impairing blood flow. Wound healing is the primary treatment aim for venous leg ulceration, alongside the management of pain, wound exudate and infection. Full (high) compression therapy delivering 40 mmHg of pressure at the ankle is the recommended first-line treatment for venous leg ulcers. There are several different forms of compression therapy available including wraps, two-layer hosiery, and two-layer or four-layer bandages. There is good evidence for the clinical and cost-effectiveness of four-layer bandage and two-layer hosiery but more limited evidence for other treatments (two-layer bandage and compression wraps). Robust evidence is required to compare clinical and cost-effectiveness of these and to investigate which is the best compression treatment for reducing time to healing of venous leg ulcers whilst offering value for money. VenUS 6 will therefore investigate the clinical and cost-effectiveness of evidence-based compression, two-layer bandage and compression wraps for time to healing of venous leg ulcers. METHODS: VenUS 6 is a pragmatic, multi-centre, three-arm, parallel-group, randomised controlled trial. Adult patients with a venous leg ulcer will be randomised to receive (1) compression wraps, (2) two-layer bandage or (3) evidence-based compression (two-layer hosiery or four-layer bandage). Participants will be followed up for between 4 and 12 months. The primary outcome will be time to healing (full epithelial cover in the absence of a scab) in days since randomisation. Secondary outcomes will include key clinical events (e.g. healing of the reference leg, ulcer recurrence, ulcer/skin deterioration, amputation, admission/discharge, surgery to close/remove incompetent superficial veins, infection or death), treatment changes, adherence and ease of use, ulcer related pain, health-related quality of life and resource use. DISCUSSION: VenUS 6 will provide robust evidence on the clinical and cost-effectiveness of the different forms of compression therapies for venous leg ulceration. VenUS 6 opened to recruitment in January 2021 and is currently recruiting across 30 participating centres. TRIAL REGISTRATION: ISRCTN67321719 . Prospectively registered on 14 September 2020.