Chronic hypoxia remodels the tumor microenvironment to support glioma stem cell growth.

Cerebral organoids co-cultured with patient derived glioma stem cells (GLICOs) are an experimentally tractable research tool useful for investigating the role of the human brain tumor microenvironment in glioblastoma. Here we describe long-term GLICOs, a novel model in which COs are grown from embryonic stem cell cultures containing low levels of GSCs and tumor development is monitored over extended durations (ltGLICOs). Single-cell profiling of ltGLICOs revealed an unexpectedly long latency period prior to GSC expansion, and that normal organoid development was unimpaired by the presence of low numbers of GSCs. However, as organoids age they experience chronic hypoxia and oxidative stress which remodels the tumor microenvironment to promote GSC expansion. Receptor-ligand modelling identified astrocytes, which secreted various pro-tumorigenic ligands including FGF1, as the primary cell type for GSC crosstalk and single-cell multi-omic analysis revealed these astrocytes were under the control of ischemic regulatory networks. Functional validation confirmed hypoxia as a driver of pro-tumorigenic astrocytic ligand secretion and that GSC expansion was accelerated by pharmacological induction of oxidative stress. When controlled for genotype, the close association between glioma aggressiveness and patient age has very few proposed biological explanations. Our findings indicate that age-associated increases in cerebral vascular insufficiency and associated regional chronic cerebral hypoxia may contribute to this phenomenon.

Impact of COVID-19 Pandemic on Patients with Atopic Dermatitis.

Atopic dermatitis (AD) is a chronic skin disease that may be triggered by psychological conditions and several allergens. Patients with AD may be experienced disease exacerbation due to the COVID-19 pandemic lifestyle including home-quarantine and increased stress. We obtained the electronic data of 100 AD patients admitted to our hospital from 2016 to 2019 and called them with specific phone line. Out of 100 patients, 43 were male, and 57 were female (mean age ± SD: 45.85 ± 16.90). Sixty patients (37 females and 23males; mean age: 42.22 ± 14.71) confronted disease flare-up during the COVID-19 era. Exacerbation of AD was correlated with treatment dose alteration, a lengthy history of atopic dermatitis, eczema duration, self-isolation, frequent handwashing, hand disinfection, and POEM scoring (P < 0.05). Regarding the POEM scoring, 61 patients with moderate to severe AD experienced higher anxiety than 39 patients with silent to mild AD (P = 0.013). In this study, most patients experienced disease exacerbation and perceived mild anxiety in this pandemic.

La dermatitis atópica (DA) es una enfermedad cutánea crónica que puede desencadenarse debido a situaciones psicológicas y ciertos alérgenos. Los pacientes con DA pueden haber experimentado una exacerbación de la enfermedad debido al estilo de vida durante la pandemia de la COVID-19, incluyendo el confinamiento domiciliario y el incremento del estrés. Obtuvimos los datos electrónicos de 100 pacientes con DA ingresados en nuestro hospital de 2016 a 2019, y les llamamos con una línea telefónica específica.De los 100 pacientes, 43 eran varones y 57 mujeres (edad media ± DE: 45,85 ± 16,90), de los cuales 60 (37 mujeres y 23 varones, con edad media de 42,22 ± 14,71) experimentaron el brote de la enfermedad durante la etapa de la COVID-19. La exacerbación de la DA guardó relación con la alteración de la dosis de tratamiento, un largo historial de dermatitis atópica, la duración del eccema, el autoaislamiento, la frecuencia del lavado de manos, la desinfección de las manos, y la puntuación POEM (p < 0,05). En lo referente a dicha puntuación, los 61 pacientes con DA de moderada a grave experimentaron mayor ansiedad que los 39 pacientes con DA de silente a leve (p = 0,013).En este estudio muchos pacientes experimentaron exacerbación de la enfermedad y percibieron ansiedad leve durante la pandemia.

Pachyonychia congenita: a case report of a successful treatment with rosuvastatin in a patient with a KRT6A mutation.

Pachyonychia congenita (PC) is a rare autosomal dominant disorder characterized by nail dystrophy and palmoplantar keratoderma with severe plantar pain affecting quality of life. There is no effective treatment. Heterozygous mutations in the keratin genes KRT6A, KRT6B, KRT6C, KRT16 and KRT17 have been reported as a cause of PC. Herein we present a female patient with an amino acid substitution mutation in KRT6A (c.1381G>A, p.Glu461Lys in exon 7) and classic features of PC associated with oral leucokeratosis and follicular hyperkeratosis. We also demonstrate successful treatment of the patient with rosuvastatin. A 3.6-mm reduction in plantar callosity thickness was demonstrated by sonography. Our patient also experienced significant pain relief that allowed her to increase physical activity (Children's Dermatology Life Quality Index score dropped nine points following treatment). Collectively, these improvements suggest that rosuvastatin may offer a promising treatment for PC. What's already known about this topic? Pachyonychia congenita (PC) is an autosomal dominant disease characterized by nail dystrophy and painful plantar keratoderma. Keratolytics, emollients, retinoids and steroids have been used for treatment but with limited benefits. What does this study add? A patient with PC who had a KRT6A mutation was treated with rosuvastatin with significant improvement in plantar hyperkeratosis and pain. Statins could be a promising treatment for PC with long-term safety, but further studies are needed.

Evaluation of Lewis blood group antigens and secretor status in pemphigus vulgaris.

BACKGROUND: There has not been publication of any previous study about the role of secretory status or Lewis phenotypes in the mechanisms of pemphigus vulgaris (PV). AIM: To evaluate the frequencies of secretory status and Lewis phenotypes in patients with PV compared with healthy controls (HCs) in order determine their roles in this autoimmune disease. METHODS: In total, 50 patients and 100 age- and sex-matched HCs were selected to form the study population, and 2 mL blood were collected from each subject to identify their Lewis phenotype. In subjects with the Le(a-b-) phenotype, saliva was also collected to determine secretor status. RESULTS: The frequency of the nonsecretor (NS) phenotypes Le(a+b-) and Le(a-b-) together was significantly higher in patients than in HCs: 34/50 (68%)vs. 26/100 (26%), respectively (P < 0.001). All the patients and HC subjects with the Le (a-b-) phenotype were found to be NS by haemagglutination inhibition assay of saliva samples. CONCLUSION: Based on our results, it seems that Le/b-negative NS individuals are more susceptible to PV.

Non-cultured melanocyte-keratinocyte transplantation for the treatment of vitiligo: a clinical trial in an Iranian population.

BACKGROUND: Non-cultured cellular grafting as a surgical procedure is indicated to treat stable vitiligo, refractory to medical treatment, and is gaining wider acceptance among dermatologists. OBJECTIVE: The aim of this study was to assess the efficacy of non-cultured melanocyte-keratinocyte transplantation (MKT) for the treatment of generalized vitiligo in Iranian patients. METHODS: In this clinical trial, a total of 14 vitiligo patches in eight patients were treated; eight patches with non-cultured MKT and six patches dermabraded alone without application of keratinocyte-melanocyte suspension. Repigmentation was compared at about 4 months post-transplantation. RESULTS: Of the eight lesions treated with non-cultured MKT, four lesions showed 96-100% repigmentation, one lesion 65-95% and three lesions 0-25%. Of the patients who showed excellent results, only one showed a post-inflammatory hyperpigmentation in recipient and control areas. Of the six control lesions, five showed failed repigmentation and one showed post-inflammatory hyperpigmentation. CONCLUSION: Non-cultured MKT is an effective method to treat stable vitiligo. Studies on larger series of vitiligo patients are required to confirm its efficacy.