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BACKGROUND: Budesonide and tixocortol pivalate as markers of contact allergy to corticosteroids have been questioned, as they are not able to detect a significant percentage of allergic patients. OBJECTIVES: To investigate the potential role of clobetasol propionate in enhancing corticosteroid sensitisation detection. METHODS: Between January 2022 and December 2023, patients who attended centres involved in the Spanish Registry of Research in Contact Dermatitis and Cutaneous Allergy were tested with an extended baseline series that included budesonide, tixocortol pivalate, clobetasol propionate 0.1% in ethanol and 1% in petrolatum. RESULTS: A total of 4338 patients were tested. Twenty-four patients were allergic to budesonide (0.55%, 95% CI: 0.37-0.82); nine patients were allergic to tixocortol pivalate (0.21%, 95% CI: 0.11-0.39); and 23 patients were allergic to clobetasol (0.53%, 95% CI: 0.35-0.79). Only four of those patients allergic to clobetasol were detected by budesonide and one by tixocortol pivalate. No significant differences in the number of positive tests were found between clobetasol in petrolatum or ethanol. CONCLUSIONS: In Spain budesonide remains the main corticosteroid allergy marker whereas the role of tixocortol pivalate is questionable. The addition of clobetasol propionate to the Spanish baseline series would improve the ability to detect patients allergic to corticosteroids.
Subject(s)
Budesonide , Clobetasol , Dermatitis, Allergic Contact , Humans , Clobetasol/adverse effects , Dermatitis, Allergic Contact/etiology , Dermatitis, Allergic Contact/diagnosis , Budesonide/adverse effects , Spain , Female , Male , Patch Tests , Adult , Middle Aged , Glucocorticoids/adverse effects , Hydrocortisone/analogs & derivativesABSTRACT
This study aimed to evaluate the antimicrobial effect of thymol and carvacrol in inhibiting Escherichia coli and Salmonella serovar Typhimurium inoculated on a fresh green salad through the vapor phase. A film-forming solution was prepared by dissolving starch, sorbitol, and variying concentrations of carvacrol, thymol, and a mixture of both. The film-forming solution containing the respective antimicrobial agent was then added lid, which was sealed rigidly and hermetically to achieve different concentrations (105 mg/L of air of carvacrol, 105 mg/L of air of thymol, and a mixture of 52 mg/L of air of carvacrol and 52 mg/L of air of thymol). Each active package contained fresh green salad inoculated with E. coli or Salmonella serovar Typhimurium. The active packages were then sealed and refrigerated at a temperature of 6 °C for 48 h. Growth/inhibition curves were modelled using the Weibull equation, and consumer acceptance was evaluated. Carvacrol can reduce up to 0.5 log-cycles, while thymol can reach almost 1 log cycle. Blending the components with half the concentration has a synergistic effect, inhibiting up to 2.5 log cycles. Consumer ratings revealed no significant differences between the packages. However, the average score was 5.4 on a 9-point hedonic scale, evaluators' comments did not indicate dislike or a strong taste characteristic of thymol and carvacrol.
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The interferon (IFN) family of immunomodulatory cytokines has been a focus of cancer research for over 50 years with direct and indirect implications in cancer therapy due to their properties to inhibit malignant cell proliferation and modulate immune responses. Among the transcriptional targets of the IFNs is a family of genes referred to as Schlafens. The products of these genes, Schlafen proteins, exert important roles in modulating cellular proliferation, differentiation, immune responses, viral replication, and chemosensitivity of malignant cells. Studies have demonstrated that abnormal expression of various Schlafens contributes to the pathophysiology of various cancers. Schlafens are now emerging as promising biomarkers and potentially attractive targets for drug development in cancer research. Here, we highlight research suggesting the use of Schlafens as cancer biomarkers and the rationale for the development of specific drugs targeting Schlafen proteins.
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Aim: The pathogenesis of chronic diabetes complications has oxidative stress as one of the major elements, and single-nucleotide polymorphisms (SNPs) in genes belonging to antioxidant pathways modulate susceptibility to these complications. Considering that melatonin is a powerful antioxidant compound, our aim was to explore, in a longitudinal cohort study of type 1 diabetes (T1D) individuals, the association of microvascular complications and SNPs in the gene encoding melatonin receptor 1A (MTNR1A). Methods: Eight SNPs in MTNR1A were genotyped in 489 T1D individuals. Besides cross-sectional analyses of SNPs with each one of the microvascular complications (distal polyneuropathy, cardiovascular autonomic neuropathy, retinopathy, and diabetic kidney disease), a longitudinal analysis evaluated the associations of SNPs with renal function decline in 411 individuals followed up for a median of 8 years. In a subgroup of participants, the association of complications with urinary 6-sulfatoxymelatonin (aMT6s) concentration was investigated. Results: The group of individuals with a renal function decline ≥ 5 mL min-1 1.73 m-2 year-1 presented a higher frequency of the A allele of rs4862705 in comparison with nondecliners, even after adjustment for confounding variables (OR = 1.84, 95% CI = 1.20-2.82; p = 0.0046). No other significant associations were found. Conclusions: This is the first study showing an association between a variant in a gene belonging to the melatonin system and renal function decline in the diabetic setting.
Subject(s)
Diabetes Mellitus, Type 1 , Melatonin , Humans , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/genetics , Antioxidants , Receptors, Melatonin , Cross-Sectional Studies , Longitudinal Studies , KidneyABSTRACT
The cervical and thoracic dermal sinuses are rare entities, conforming epithelium-lined tracts that extend from an opening in the skin through a corridor to the layers of the spinal cord. They are commonly detected in early childhood; however, adult reports are singularly rare, especially in cervical regions. We report a very unusual case of a 45-year-old Mexican female who developed progressive left-side weakness and dexterity suffered from childhood, getting worse in the last year. Physical examination revealed a soft, congenital round cystic lesion in the dorsal-midline skin at the level of C4-C5 vertebrae with no previous treatment received. MRI showed a dermal sinus tract at the C4 level from the skin tethering to the spinal cord and syringomyelia. CT scan showed a dysraphism corresponding to spina bifida at the C4 level and an incomplete closure at the C3 and C5 vertebrae. We surgically managed the lesion by microscopic resection with C3-C5 laminectomy preserving strength and sensitivity. Follow-up MRI showed no residual lesion and contained fistula with no further complications. Cervical dermal sinus lesions are unusual entities, even less prevalent in adulthood. It represents a possible delay in diagnosis and an increased rate of complications. Early suspicion of the condition is required to make an accurate diagnosis since it is a potentially treatable lesion with a high risk of sequelae without surgical treatment.
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BACKGROUND: Current frequency and features for positivity to textile dye mix (TDM) in Spain are unknown. OBJECTIVES: To study the frequency, clinical features and simultaneous positivity between TDM, para-phenylenediamine (PPD) and specific disperse dyes. MATERIALS AND METHODS: We analysed all consecutive patients patch-tested with TDM from the Spanish Contact Dermatitis Registry (REIDAC), from 1 January 2019 to 31 December 2022. Within this group, we studied all selected patients patch-tested with a textile dye series. RESULTS: Out of 6128 patients analysed, 3.3% were positive to the TDM and in 34% of them, the sensitization was considered currently relevant. TDM positivity was associated with working as a hairdresser/beautician and scalp, neck/trunk and arm/forearm dermatitis. From TDM-positive patients, 57% were positive to PPD. One hundred and sixty-four patients were patch-tested with the textile dye series. Disperse Orange 3 was the most frequent positive dye (16%). One of every six cases positive to any dye from the textile dye series would have been missed if patch-tested with the TDM alone. CONCLUSIONS: Positivity to TDM is common in Spain and often associated with PPD sensitization. TDM is a valuable marker of disperse dyes allergy that should be part of the Spanish and European standard series.
Subject(s)
Dermatitis, Allergic Contact , Humans , Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Spain/epidemiology , Textiles/adverse effects , Patch Tests , Coloring Agents/adverse effectsABSTRACT
BACKGROUND: A global epidemic of allergic contact dermatitis to (meth)acrylates has been described in relation to the widespread use of manicure products. OBJECTIVES: To evaluate the frequency of sensitization to 2-hydroxyethyl methacrylate (2-HEMA) among consecutively patch tested patients with eczema in Spain; the percentage of current relevance; the MOAHLFA index; and, the potential sources of exposure to (meth)acrylates. METHODS: From January 2019 to December 2022, 2-HEMA 2% pet. was prospectively patch tested in 24 REIDAC (Spanish Allergic Contact Dermatitis Registry) centres. RESULTS: Six thousand one hundred thirty-four patients were consecutively patch tested with 2-HEMA 2% pet. 265/6134 (4.3%) were positive. Positive reactions of current relevance were identified to involve 184/265 (69%). The efficiency (number of patch tests needed to detect relevant positive patch test reactions) was 34 (6134/184). The variable 'occupational' was found to be significantly associated with a higher risk for relevant positive reactions to 2-HEMA (OR: 10.9; 95% CI: 8.1-14.9). CONCLUSION: (Meth)acrylate sensitization is a prevalent health issue in Spain. 2-HEMA 2% pet. has been identified to be a highly effective (meth)acrylate allergy marker in the GEIDAC baseline series. The responsible authorities should implement policies guaranteeing accurate labelling of industrial, medical, and consumer materials while ensuring the enforcement of said labelling through appropriate legal means.
Subject(s)
Dermatitis, Allergic Contact , Dermatitis, Occupational , Humans , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Spain/epidemiology , Methacrylates/adverse effects , Acrylates , Patch TestsABSTRACT
BACKGROUND: There is still limited clinical-practice data on specific clinical and patch test features, as well as on allergen clusters in polysensitization (PS). OBJECTIVES: To determine the frequency, relevance, symptoms duration and risk factors in polysensitized patients and to assess possible allergen aggregation. METHODS: Prospective multicentric study (January 2019-December 2022) conducted in setting of the Spanish Contact Dermatitis Register (REIDAC). Clinical and patch test data of polysensitized and oligosensitized patients were compared, and risk factors of PS were investigated with logistic multivariate regression. Unsupervised hierarchical clustering and network analysis were used to study allergen aggregation in PS. RESULTS: A total of 10,176 patients were analysed. PS was found in 844 (8.3%). Current relevance was significantly higher in polysensitized patients (p < 0.01). Risk factors for PS were atopic dermatitis (OR: 1.58, 95% CI: 1.24-2.02), age (≥60 years vs. ≤24 years, OR: 1.75, 95% CI: 1.25-2.44) and some special locations (legs vs. face OR: 1.54, 95% CI: 1.05-2.25, hands vs. face OR: 1.46, 95% CI:1.15-1.85, arms vs. face OR: 1.49, 95% CI:1.01-2.20, trunk vs. face OR: 1.40, 95% CI:1.06-1.85). Cluster and network analyses revealed specific-allergen clusters and significant associations, including allergens belonging to metals group, fragrances and botanicals group, topical drugs group, rubber allergens and biocides. CONCLUSIONS: This study confirms that PS is structured by discernible patterns of specific-allergen clusters and reinforces significant allergen associations in PS. Cross-reactivity and/or concomitant sensitization could explain the formation of allergen clusters in PS.
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BACKGROUND AND AIMS: Vitamin D deficiency is a global health problem. The determinants of this deficiency have not been evaluated in developing countries such as Mexico. Thus, this study aimed to determine vitamin D intake and sun exposure and its relationship with plasma concentrations of 25-hydroxyvitamin D -25(OH)D- in young adults from Mexico City. METHODS: One hundred fifty five urban adult subjects were enrolled during 2017 and 2018. Sociodemographic, anthropometric, and clinical data, vitamin D intake, and sun exposure habits were collected. Plasma concentrations of 25(OH)D were also determined. RESULTS: The proportion of vitamin D deficiency was significantly higher in women than in men (65.7 vs. 43.4%, p = 0.012). The overall median dietary vitamin D intake was 112 IU/d (less than 20% of the recommended daily intake; RDI). 25-hydroxyvitamin D correlated directly with vitamin D intake, sun exposure score, waist-to-hip ratio, and age; an inverse significant association was found with body fat percentage. A multiple regression analysis was performed; simultaneous and significant (p <0.01) effects of sun exposure score, dietary vitamin D, the season of the year (spring-summer vs. fall-winter), and age were observed on 25(OH)D levels. CONCLUSION: High rates of vitamin D deficiency and insufficiency were observed in young adults from Mexico City. According to the RDI of this vitamin, its consumption, assessed by a 24 h multi-step nutritional questionnaire, was significantly low. A linear multiple regression model identified several predictors of plasma 25(OH)D concentrations. This multiple regression model was statistically validated.
Subject(s)
Sunlight , Vitamin D Deficiency , Female , Humans , Male , Young Adult , Dietary Supplements , Mexico/epidemiology , Vitamin D , Vitamin D Deficiency/epidemiology , VitaminsABSTRACT
BACKGROUND: Monitoring of adverse events induced by cosmetics performed by health authorities, known as cosmetovigilance, has been relied on the collection of case notifications. OBJECTIVES: We aimed to show how a contact dermatitis registry can contribute to the cosmetovigilance of emerging allergens. We used the example of phenylethyl resorcinol, an infrequent allergen with only 6 previous cases reported in Europe and Japan since 2013. METHODS: A systematic search in the Spanish Registry of Contact Dermatitis and Cutaneous Allergy (REIDAC) database was performed to identify patients with positive patch test to phenylethyl resorcinol or cosmetics that contains it between June 2018 and January 2023. We collected the main clinical features of these patients and compared them with those of patients recorded in the registry with similar epidemiological features. RESULTS: Thirteen patients with positive patch test to phenylethyl resorcinol were identified. All the patients were women with a mean age of 42 years (range 32-59) and their lesions were mainly in the face. CONCLUSION: Assessing the importance of infrequent allergens based solely on a case series is difficult. Multicentre registries facilitate the collection of cases and provide appropriate background information for new allergens.
Subject(s)
Benzhydryl Compounds , Cosmetics , Dermatitis, Allergic Contact , Resorcinols , Humans , Female , Adult , Middle Aged , Male , Allergens/adverse effects , Dermatitis, Allergic Contact/diagnosis , Dermatitis, Allergic Contact/epidemiology , Dermatitis, Allergic Contact/etiology , Spain/epidemiology , Retrospective Studies , Cosmetics/adverse effects , Patch Tests/adverse effects , RegistriesABSTRACT
Dorper rams are widely distributed throughout the world under different climatic conditions, however, little is known about their reproductive performance in desert regions. Ten Dorper rams were individually housed and exposed to thermoneutrality for 35 d in spring (23.6 ± 5.6 °C, mean ± SD) and outdoor heat stress (HS) for 35 d in summer (33.6 ± 2.0 °C) to evaluate the effect of seasonal HS on physiological responses, testicular biometry, and seminal quality under desert climatic conditions. Rectal temperature, respiration rate and coat surface temperatures in different body regions were measured every 7 d (0600, 1200, and 1800 h); also, testicular biometry was registered at 0600 h. Semen was collected via an artificial vagina 3 d after physiological variables were measured and seminal traits were evaluated. Rectal temperature, respiration rate and coat surface temperatures were higher (P < 0.01) at each hour of measurement in summer compared to spring. Overall, scrotal length and circumference, as well as testicular volume were higher (P < 0.01) in summer than in spring. Compared to spring conditions, summer HS caused lower (P ≤ 0.05) sperm concentration and viability combined with a higher percentage of sperm abnormalities without affecting ejaculate volume. Both mass and sperm motility were similar between seasons in the first two sampling weeks, and then decreased (P ≤ 0.03) due to summer HS. In conclusion, Dorper rams developed testicle hyperthermia and, consequently, showed poor semen quality due to the high environmental temperatures prevailing in desert regions.
Subject(s)
Semen Analysis , Testis , Female , Male , Sheep , Animals , Testis/physiology , Seasons , Semen/physiology , Desert Climate , Sperm Motility , Sheep, Domestic/physiology , Spermatozoa/physiology , Body Temperature Regulation , Heat-Shock ResponseABSTRACT
Inducing carotid body anoxia through the administration of cyanide can result in oxygen deprivation. The lack of oxygen activates cellular responses in specific regions of the central nervous system, including the Nucleus Tractus Solitarius, hypothalamus, hippocampus, and amygdala, which are regulated by afferent pathways from chemosensitive receptors. These receptors are modulated by the brain-derived neurotrophic factor receptor TrkB. Oxygen deprivation can cause neuroinflammation in the brain regions that are activated by the afferent pathways from the chemosensitive carotid body. To investigate how microglia, a type of immune cell in the brain, respond to an anoxic environment resulting from the administration of NaCN, we studied the effects of blocking the TrkB receptor on this cell-type response. Male Wistar rats were anesthetized, and a dose of NaCN was injected into their carotid sinus to induce anoxia. Prior to the anoxic stimulus, the rats were given an intracerebroventricular (icv) infusion of either K252a, a TrkB receptor inhibitor, BDNF, or an artificial cerebrospinal fluid (aCSF). After the anoxic stimulus, the rats were perfused with paraformaldehyde, and their brains were processed for microglia immunohistochemistry. The results indicated that the anoxic stimulation caused an increase in the number of reactive microglial cells in the hypothalamic arcuate, basolateral amygdala, and dentate gyrus of the hippocampus. However, the infusion of the K252a TrkB receptor inhibitor prevented microglial activation in these regions.
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INTRODUCTION: During the height of the coronavirus disease-19 (COVID-19) pandemic, some renal replacement therapy (RRT) modalities were insufficient, forcing medical centers to diversify the RRT modalities offered. In this study, we reported the outcomes of chronic peritoneal dialysis (PD) patients and acute PD in critically ill patients during COVID-19 pandemic in a tertiary care medical center in Mexico. METHODS: This descriptive, longitudinal, observational, retrospective study included 47 adult patients with atypical pneumonia in a tertiary care medical center in Mexico during the first and second waves of the COVID-19 pandemic. Chronic PD patients and PD incident patients due to acute kidney injury (AKI) were included. RESULTS: Forty-seven patients were studied (29 chronic PD patients and 18 incident PD patients due to AKI); median age was 59 (48-68) years; 63.8% were men. The ultrafiltrate volume per day was 815 (596.1-1,193.2) mL. Overall mortality was 61.7%, 55.2% in chronic PD patients, and 72.2% in PD incident patients due to AKI. A higher Sequential Organ Failure Assessment (SOFA) score, the need for mechanical ventilation at admission, and the requirement for vasopressors were predictors for mortality (p < 0.01). CONCLUSION: In low- and lower-middle-income countries, PD was a valid alternative for RRT during the COVID-19 pandemic. In AKI patients, PD can correct hyperkalemia, acidosis, uremia, and volume overload; however, there was higher mortality in PD incident patients due to AKI. The main risk factors for mortality were a high SOFA score at admission, the need for invasive mechanical ventilation, and the requirement for vasopressors.
Subject(s)
Acute Kidney Injury , COVID-19 , Peritoneal Dialysis , Male , Adult , Humans , Middle Aged , Female , COVID-19/therapy , COVID-19/complications , Pandemics , Retrospective Studies , Mexico/epidemiology , Developing Countries , Intensive Care Units , Peritoneal Dialysis/adverse effects , Renal Replacement Therapy/adverse effects , Acute Kidney Injury/etiology , Acute Kidney Injury/therapy , Acute Kidney Injury/epidemiologyABSTRACT
Introducción: La modificación en los patrones de sueño incrementa la susceptibilidad para la ganancia de peso. Objetivo: Estimar la asociación entre la calidad y la cantidad de horas de sueño por noche con el Índice de Masa Corporal (IMC) en adolescentes universitarios mexicanos. Materiales y métodos: Estudio transversal en estudiantes de nuevo ingreso de Enfermería en una Universidad Pública de México. Muestreo por conveniencia de n=134 estudiantes (1819 años), voluntarios y matriculados en la facultad. La calidad y cantidad de sueño se midió con el Índice de Calidad de Sueño de Pittsburgh. El IMC se calculó con la fórmula estándar. El protocolo fue aprobado por el Comité de Ética de la facultad, los participantes firmaron el Consentimiento Informado. Resultados: Edad promedio de 18,21 años (DE= ,42 años), 82,84% mujeres, 45,52% (IC 95%= 35,46 52,86%) con sobrepeso u obesidad. El 44,02% de los participantes reportó dormir ≤ 6 horas por noche, 50,00% refirió una mala calidad de sueño en las últimas cuatro semanas. Después de ajustar por edad, sexo y ocupación, la calidad del sueño no se asoció con el IMC (OR= 1,01; IC 95%= ,94 1,08; z= ,31; p= ,75); el incremento en el IMC se asoció con una mayor probabilidad de dormir 6 horas o menos (OR= 1,08; IC 95%= 1,01 1,16; z= 2,25; p= ,02). Discusión: Las alteraciones hormonales, los factores conductuales y el entorno pudieran explicar la asociación. Conclusiones: Es recomendable implementar estrategias educativas para mejorar la higiene del sueño en esta población.
Introduction: Changes in sleep patterns increase susceptibility to weight gain. Objective: To estimate the association between the quality and quantity of sleep hours per night and Body Mass Index (BMI) in Mexican college adolescents. Materials and methods: Cross-sectional study conducted among incoming nursing students in a public university in Mexico. Convenience sampling was used, involving n=134 students (18-19 years old), volunteers, and enrolled in the nursing program. Sleep quality and quantity were measured through the Pittsburgh Sleep Quality Index (PSQI). BMI was calculated using the standard formula. The protocol was approved by the School of Nursing Ethics Committee, and the participants signed informed consent. Results: Mean age 18.21 years (SD= .42 years), 82.84% female, 45.52% overweight or obese (95% CI= 35.46 - 52.86%). 44.02% of participants reported sleeping ≤ 6 hours per night, and 50.00% reported poor sleep quality in the past four weeks. After adjustment for age, sex, and occupation, sleep quality was not associated with BMI (OR= 1.01; 95% CI= .94 - 1.08; z= .31; p= .75); increased BMI was associated with a greater likelihood of sleeping 6 hours or less (OR= 1.08; 95% CI= 1.01 - 1.16; z= 2.25; p= .02). Discussion: Hormonal changes, behavioral factors, and the environment may explain the association. Conclusions: It is advisable to implement educational strategies to improve sleep hygiene among this population.
Introdução: A modificação nos padrões de sono aumenta a suscetibilidade ao ganho de peso. Objetivo: Estimar a associação entre a qualidade e a quantidade de sono por noite e o índice de massa corporal (IMC) em adolescentes universitários mexicanos. Materiais e métodos: Estudo transversal de estudantes de enfermagem ingressantes em uma universidade pública no México. Amostragem por conveniência de n=134 estudantes (18-19 anos de idade), voluntários e matriculados na faculdade. A qualidade e a quantidade do sono foram medidas com o Índice de Qualidade do Sono de Pittsburgh. O IMC foi calculado com a fórmula padrão. O protocolo foi aprovado pelo Comitê de Ética da faculdade e os participantes assinaram o Termo de Consentimento Livre e Esclarecido. Resultados: Idade média de 18,21 anos (DP= ,42 anos), 82,84% do sexo feminino, 45,52% (IC 95%= 35,46 - 52,86%) com sobrepeso ou obesidade. 44,02% dos participantes relataram dormir ≤ 6 horas por noite, 50,00% relataram qualidade de sono ruim nas últimas quatro semanas. Após o ajuste para idade, sexo e ocupação, a qualidade do sono não foi associada ao IMC (OR= 1,01; IC 95%= ,94 - 1,08; z= ,31; p= ,75); o aumento do IMC foi associado a uma maior probabilidade de dormir 6 horas ou menos (OR= 1,08; IC 95%= 1,01 - 1,16; z= 2,25; p= ,02). Discussão: Alterações hormonais, fatores comportamentais e o ambiente podem explicar a associação. Conclusões: É aconselhável implementar estratégias educacionais para melhorar a higiene do sono nessa população.
Subject(s)
Sleep , Students, Nursing , Adolescent , Overweight , ObesityABSTRACT
Colpolopha minuta sp. nov. (Orthoptera: Romaleidae) is described from Floresta Nacional do Aripe near Crato in Ceará State, Brazil from 17 specimens collected by Moacyr Alvarenga deposited at the Insect Collection of the University of Michigan Museum of Zoology. This new species is characterized by its small size and brachypterous tegmina compared to other known Colpolopha species. A comparison with other short-winged Colpolopha species is provided. A discussion about some iNaturalist records is provided in order to help us identify possible new records or species in the region.
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Grasshoppers , Orthoptera , Animals , Brazil , Animal Distribution , Animal Structures , Body Size , Organ SizeABSTRACT
Interferons (IFNs) are cytokines with potent antineoplastic and antiviral properties. IFNα has significant clinical activity in the treatment of myeloproliferative neoplasms (MPN), but the precise mechanisms by which it acts are not well understood. Here, we demonstrate that chromatin assembly factor 1 subunit B (CHAF1B), an Unc-51-like kinase 1 (ULK1)-interactive protein in the nuclear compartment of malignant cells, is overexpressed in patients with MPN. Remarkably, targeted silencing of CHAF1B enhances transcription of IFNα-stimulated genes and promotes IFNα-dependent antineoplastic responses in primary MPN progenitor cells. Taken together, our findings indicate that CHAF1B is a promising newly identified therapeutic target in MPN and that CHAF1B inhibition in combination with IFNα therapy might offer a novel strategy for treating patients with MPN. Significance: Our findings raise the potential for clinical development of drugs targeting CHAF1B to enhance IFN antitumor responses in the treatment of patients with MPN and should have important clinical translational implications for the treatment of MPN and possibly in other malignancies.
Subject(s)
Bone Marrow Neoplasms , Myeloproliferative Disorders , Neoplasms , Humans , Myeloproliferative Disorders/drug therapy , Interferon-alpha/pharmacology , Chromatin Assembly Factor-1/geneticsABSTRACT
In this work, the effect of iron(III) in the preparation of a conductive porous composite using a biomass waste-based starch template was evaluated. Biopolymers are obtained from natural sources, for instance, starch from potato waste, and its conversion into value-added products is highly significant in a circular economy. The biomass starch-based conductive cryogel was polymerized via chemical oxidation of 3,4-ethylenedioxythiophene (EDOT) using iron(III) p-toluenesulfonate as a strategy to functionalize porous biopolymers. Thermal, spectrophotometric, physical, and chemical properties of the starch template, starch/iron(III), and the conductive polymer composites were evaluated. The impedance data of the conductive polymer deposited onto the starch template confirmed that at a longer soaking time, the electrical performance of the composite was improved, slightly modifying its microstructure. The functionalization of porous cryogels and aerogels using polysaccharides as raw materials is of great interest for applications in electronic, environmental, and biological fields.