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 / Impacto de la pandemia de COVID-19 en los pacientes con dermatitis atópica

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 (AU)

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 (AU)

[Artículo traducido] Impacto de la pandemia de COVID-19 en los pacientes con dermatitis atópica / Impact of COVID-19 Pandemic on Patients with Atopic Dermatitis

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 de 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 (AU)

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 (AU)

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.

[Impact of COVID-19 Pandemic on Patients with Atopic Dermatitis]. / [Artículo traducido] Impacto de la pandemia de COVID-19 en los pacientes con dermatitis atópica.

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.

Optimizing remote ischemic conditioning (RIC) of cutaneous microcirculation in humans: Number of cycles and duration of acute effects.

OBJECTIVE: Non-invasive Remote Ischemic Conditioning (RIC) offers an approach to reduce tissue damage in various organs/tissues. Besides attenuation of Ischemia-Reperfusion injury (I/R), beneficial effects on cutaneous microcirculation of free microsurgical flaps have been reported. Given the recency of this technique, there are considerable gaps in the current understanding of its mechanism of action. As a result, clinical transfer of RIC is prolongated in several fields. We aimed to optimize the RIC protocol by examination of different RIC-cycle numbers and its effect on changes of cutaneous microcirculation and duration. METHODS: 80 subjects were divided into groups (1, 3, 5, 7 RIC cycles). RIC was applied via an inflatable tourniquet. Cutaneous microcirculation was continuously assessed at the contralateral anterior lateral thigh utilizing a ©O2C-device continuously. RESULTS: RIC caused significant and sustained changes in microcirculation. Four hours after completion of RIC, a maximum increase of +80.8% (CI 1.395-2.221) in blood flow and +23.5% (CI 1.098-1.372) in tissue oxygen saturation was measured (three-cycle group). A higher number of applied cycles was accompanied with significant higher mean pain. CONCLUSION: Acute improvement of cutaneous microcirculation due to RIC lasted for at least 4 h after completion of the RIC-protocol. Dose-dependent effects of RIC are likely. With regard to the increase in pain, we recommend a RIC protocol of 3 cycles for future clinical application.

[Soft tissue sarcomas: limb salvage using reconstructive plastic surgery techniques]. / Weichgewebssarkome: Extremitätenerhalt durch plastisch-rekonstruktive Verfahren.

The treatment of choice for soft tissue sarcomas with local involvement is still the complete surgical removal into healthy tissue. The aim of surgery is to achieve tumor-free resection margins in the sense of a R0 resection. No other treatment option can equally replace this important oncological condition. The enormous development in the field of reconstructive plastic surgery and in particular the advances in flap techniques and microsurgery enable limb salvage and the functional reconstruction even in the case of extensive tumors.

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.

Estimation of influenza and severe acute respiratory illness incidence (burden) in three provinces of the Islamic Republic of Iran, 2012 and 2013.

There are few estimates of influenza burden in the WHO Region for the Eastern Mediterranean. In this study we estimated the burden of severe acute respiratory infection (SARI) and influenza-associated SARI (F-SARI) in selected provinces of Islamic Republic of Iran, the trends of SARI and confirmed cases of influenza (F-SARI) over 12 months (seasonality), and the age groups most at risk. Using the electronic Iranian influenza surveillance system and data of cases in sentinel hospitals of 3 selected provinces, we estimated the monthly trend (seasonality) of incidence for SARI and F-SARI, overall incidence of SARI and F-SARI and their disaggregation by age with the aid using the Monte Carlo technique. The age groups most at-risk were children aged under 2 years and adults older than 50 years.

Estimation of influenza and severe acute respiratory illness incidence [burden] in three provinces of the Islamic Republic of Iran, 2012 and 2013

There are few estimates of influenza burden in the WHO Region for the Eastern Mediterranean. In this study we estimated the burden of severe acute respiratory infection [SARI] and influenza-associated SARI [F-SARI] in selected provinces of Islamic Republic of Iran, the trends of SARI and confirmed cases of influenza [F-SARI] over 12 months [seasonality], and the age groups most at risk. Using the electronic Iranian influenza surveillance system and data of cases in sentinel hospitals of 3 selected provinces, we estimated the monthly trend [seasonality] of incidence for SARI and F-SARI, overall incidence of SARI and F-SARI and their disaggregation by age with the aid using the Monte Carlo technique. The age groups most at-risk were children aged under 2 years and adults older than 50 years

Peu d'estimations sont disponibles sur la charge de la grippe dans la Région OMS de la Méditerranée orientale. Dans la présente étude, nous avons estimé la charge de morbidité due aux infections respiratoires aiguës sévères [IRAS] et aux IRAS associés à la grippe dans certaines provinces de la République islamique d'Iran, ainsi que les tendances des IRAS et des cas de grippe confirmés sur 12 mois [saisonnalité], et les groupes d'âge les plus exposés. En utilisant le système électronique iranien de surveillance de la grippe et les données relatives aux cas des hôpitaux sentinelles de trois provinces sélectionnées, nous avons estimé la tendance mensuelle [saisonnalité] de l'incidence des IRAS et des IRAS dus à la grippe, l'incidence globale des IRAS et des IRAS dues à la grippe et leur ventilation par âge grâce à la méthode de Monte Carlo. Les groupes d'âge les plus exposés au risque étaient les enfants de moins de 2 ans et les adultes de plus de 50 ans

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.

Mortality from Pandemic Influenza A (H1N1) in Iran.

BACKGROUND: Due to worldwide spread of influenza A (H1N1) virus, the World Health Organization declared the first pandemic of influenza in four decades. This study aims to report the mortality from pandemic influenza A (H1N1) in Iran population and its epidemiologic and clinical characteristics up to December 21, 2009. METHODS: The data were obtained from all provinces and reported to center for disease control of Ministry of Health and Medical Education (MOHME) of Iran through nationwide surveillance system for influenza A (H1N1) was implemented by MOHME since April 2009. RESULTS: Of 3672 confirmed cases of influenza A (H1N1) in Iran between 22 May and 21 December 2009, 140 (3.8%) deaths were reported, mostly in 15-65 year old (yo) age group (67%). The highest admission mortality rate was in > 65 yo group (107 deaths/1000 hospitalized cases). Of decedent patients, 54% had no long term condition or risk factor, 34% had one, 11% had two, and 1% had three. Diabetes mellitus, pregnancy, chronic respiratory diseases and hypertension were the most common underlying conditions. The most common clinical pictures of death were acute respiratory distress syndrome and viral pneumonia. Although 66% of decedent patients received oseltamivir, enough information was not available about time of onset of antiviral therapy. CONCLUSION: As death due to influenza A (H1N1) occurs in all age groups and in those with and without any predisposing factors, we recommend health policy makers to provide influenza vaccination for people with underlying conditions and respiratory hygiene for all people.

Influence of bone thickness on densitometric and ultrasonic parameters, an in vivo study.

DXA and QUS assessments in vivo have been shown to be predictive of osteoporosis and future fractures. In clinical measurements, bone thickness can affect bone mineral density and ultrasound parameters. Previous in vitro studies have demonstrated contradictory reports about relationship between bone mineral density and so ultrasound parameters with bone thickness, separately. In this study, DXA, phalangeal QUS and calcaneus QUS measurements were conducted on rabbit bone in vivo using clinical instruments. We have selected rabbit's bones that have low BMD and more collagen tissue to predict structure not only measures BMD, but is also sensitive to the structure of the bone. To investigate the effect of bone thickness on the measured parameters, two regions of femur and tibia bones (N = 44) were processed: up (1/3 of length) and down (2/3 of length) for BMC, areal BMD, volumetric BMD, AD-SOS, UBPI, BTT, SOS, BUA and SI measurements and bone thickness-corrected SOS and bone thickness corrected BUA. The paired student's t-test analysis of densitometric and ultrasonic characteristics extracted by DXA, Phalangeal and calcaneus quantitative ultrasound showed significant differences (p < 0.05) between densitometric and ultrasonic parameters of two groups of up and down of the femur and two groups of up and down of the tibia, with the exception of SOS and SI (p > 0.05). It shows that BMC, BMD(a), AD-SOS, UBPI, BTT and BUA correlate well with the bone thickness of the tibia and the femur. Among the femur parameters, the highest correlation (r = 0.755) was obtained for BMC parameter. But in the tibia, measurements at AD-SOS, UBPI and BUA inversely correlated with bone thickness, that could be arise from the tibia bone structure. This bone has collagen and non mineral structures more than bone mineral density. Correlation analyses of the bone thickness with the thickness-corrected DXA and ultrasound parameters revealed that corrected BMD (BMD(v)) is independent from thickness, but corrected parameters excluding SOSc and BUA(c) showed significant correlation coefficient than uncorrected. Linear regression analyses were used to examine the relationship between DXA and ultrasound parameters with bone thickness and the regression functions for each parameters (with correlated significant) is given. We concluded that BMD(v), SOS and SI are independent from bone thickness (with range of 5-9 mm). Thus, the ability of these parameters to discriminate low density or osteoporotic bone from normal bone may be limited if differences in bone thickness are not accounted for. This result may be at least in part due to large precision error measurement of the bone thickness, in vivo study.