Predicting the Speed of Response to Omalizumab in Chronic Spontaneous Urticaria.

INTRODUCTION: Two distinct chronic spontaneous urticaria (CSU) endotypes, IgE-mediated autoallergic and IgG-mediated autoimmune, were defined based on the response patterns to omalizumab. However, the coexistence of IgE and IgG autoantibodies in a subset of patients might complicate the prediction of the treatment outcomes. This study aimed to evaluate the effectiveness and safety of omalizumab in CSU patients, focusing on the factors predicting the response patterns. METHODS: This was a retrospective cross-sectional single-center study investigating CSU patients treated with omalizumab for at least 6 months between September 2015 and February 2023. Patients were evaluated regarding demographics, clinical findings, baseline laboratory parameters, treatment outcomes, and side effects. Early and late responders were defined depending on the time for response, within or after 3 months, respectively. RESULTS: Among 82 patients, 75 (91.5%) responded to omalizumab during the first 6 months, classified as early (n = 51) and late responders (n = 24). The IgG anti-thyroid peroxidase (anti-TPO)/total IgE ratio was an independent predictor for determining the speed of response (p < 0.05). Of 29 patients who discontinued omalizumab, 19 (65.5%) experienced relapse with a good response to retreatment (n = 18/19, 94.7%). Early responders relapsed more frequently than late responders (77.3% vs. 28.6%) (p < 0.05). Only mild side effects were observed in a minority of patients (n = 8/82, 9.8%). CONCLUSION: Omalizumab is an effective and safe treatment in CSU. The IgG anti-TPO/total IgE ratio seems a valuable tool to predict the early and late responders, the former having a higher possibility of relapse upon drug withdrawal.

Artificial nail modelling systems in healthcare workers: An emerging risk of contact sensitization to a well-known occupational allergen in an alternative way.

BACKGROUND: Artificial nail modelling systems (ANMS) pose a significant risk for nail stylists and their clients regarding acrylate sensitization, which might jeopardize the use of acrylate-containing medical devices. OBJECTIVES: To evaluate the frequency of artificial nail practices among female healthcare workers (HCWs) compared with controls and assess ANMS-related side effects. METHODS: In this comparative, cross-sectional, single-centre study, a face-to-face interview with 200 female HCWs and 200 age-matched female dermatology patients (controls) was conducted regarding the use of ANMS between March and November 2023. RESULTS: Among 400 participants (median age: 25), 85 (21.3%) have applied ANMS at least once. The prevalence of ANMS application was significantly higher in HCWs (n = 54/200, 27%) compared with controls (n = 31/200, 15.5%) (p < 0.05). Long-lasting nail polish was the most commonly preferred technique (n = 82/85, 96.5%). ANMS were mainly performed in nail studios by nail stylists (n = 79/85, 92.9%), while three participants were using home kits. Nail brittleness was the most frequently reported side effect (n = 19/85, 22.4%). No case of allergic contact dermatitis (ACD) was detected. CONCLUSIONS: The popularity of ANMS among young female HCWs is growing. This striking trend might further put these individuals not only at risk of medical device-related adverse events but also occupational ACD.

The effect of interventions on flat and inverted nipple on breastfeeding: A systematic review.

BACKGROUND: Some methods have been developed to solve flat and/or inverted nipple problems. This study aimed to examine the effects of flat and/or inverted nipple interventions on nipples and breastfeeding. METHODS: Before initiating the review, the protocol was registered in the 'PROSPERO' database. This study was based on the PRISMA-P guideline. Seven databases (Web of Science, PubMed, ScienceDirect, Scopus, The Cochrane Library, TÜBITAK Ulakbim and Google Scholar) were searched, and nine studies were included in this review. RESULTS: Hoffman's exercise, the inverted syringe method, and the nipple exercise was quite effective in increasing breastfeeding success. The rate of exclusive breastfeeding in the first, third, and sixth months of mothers followed up with postpartum multidimensional visits was found to be significantly higher in the intervention group than in the control group (p < 0.05). A study in which a rubber band was applied with the help of an injector on flat and inverted nipples showed that 63% of mothers on the third day and all of them in the first month were able to breastfeed without a rubber band. Hoffman's exercise, the inverted syringe technique, and rubber bands corrected the flat and/or inverted nipple. There were studies reporting complications as a result of nipple interventions. CONCLUSIONS AND IMPLICATIONS: It is necessary to disseminate the information that breastfeeding of mothers with flat and/or inverted nipples can be sustained with various interventions. Furthermore, it is believed that providing mothers with a chance to choose the interventions, and thus, the compliance of mothers to the intervention with the method of their choice may increase the success of the intervention.

Quality, reliability, and popularity of YouTube videos on urticaria: a cross-sectional analysis.

BACKGROUND: Recently, YouTube has been frequently used by non-physicians and physicians to share information and experiences about diseases. This study aims to compare videos uploaded to YouTube about urticaria in terms of quality, reliability, usefulness, and popularity based on the uploaded source. METHODS: YouTube was searched using the keyword "urticaria". From the search returns, we selected the first 60 videos created by physicians and the first 60 videos created by non-physicians. We compared the two sets of videos in terms of reliability, usefulness, quality, and popularity using the Video Power Index (VPI) score, DISCERN score, global quality score (GQS) and usefulness score. RESULTS: The mean DISCERN score, GQS, and usefulness score were statistically significantly higher (P<0.001) for videos uploaded by physicians than those uploaded by non-physicians. Although not statistically significant, the median number of likes and comments, the rate of views, and the VPI scores were higher for videos uploaded by the non-physician group. The mean DISCERN scores, GQS, and usefulness scores were statistically significantly higher (P<0.001) for videos uploaded by specialist physicians (dermatologists and allergists) than for those uploaded by non-specialists. Specialist physicians mentioned medical treatment for the condition more than non-specialists, which was statistically significant (P<0.001). CONCLUSIONS: YouTube videos about urticaria uploaded by physicians, especially specialists, are of higher quality, reliable and useful, but videos uploaded by non-physicians are more popular and have higher viewing rates.

Long-Term Omalizumab Therapy in Patients with Chronic Spontaneous Urticaria: Does it Increase the Risk of COVID-19?

INTRODUCTION: Based on the existing literature, omalizumab (OMZ) is considered a safe treatment modality in chronic spontaneous urticaria (CSU) during the coronavirus disease 19 (COVID-19) era. OBJECTIVES: The aim of this study is to evaluate the effects of OMZ on CSU patients regarding COVID-19 infection. METHODS: In this retrospective study, files of CSU patients using OMZ during the COVID-19 pandemic were reviewed in terms of demographic features, medical history including COVID-19 vaccination status, clinical characteristics, pretreatment laboratory parameters, duration, and dosing regimen of OMZ treatment. Patients with a history of COVID-19 infection while on OMZ therapy and patients without COVID-19 history were compared with respect to these parameters. The urticaria activations following COVID-19 infection or vaccination were also recorded. RESULTS: Sixty-eight patients with CSU (female:male ratio = 1.8:1; mean age = 47.2 ± 15.1 years) continued to receive OMZ treatment. The median duration of OMZ treatment was 12 months (range: 6-60). Twelve patients (17.6%) were diagnosed with COVID-19 showing no exacerbation in urticaria. The duration of OMZ treatment was significantly higher in the group with COVID-19 infection history compared to patients with no history of COVID-19 (P = 0.01). Among 51 patients (75%) vaccinated against COVID-19, urticaria activation occurred in 4 patients without any recurrence following booster vaccinations. CONCLUSIONS: Considering the likelihood of increased COVID-19 infection risk in the setting of long-term OMZ in CSU patients, the duration of OMZ therapy might be kept at a minimum, or a temporary interruption of the treatment period might be preferred, particularly in high-risk patients regarding COVID-19.

Water consumption in 0-6-month-old healthy infants and effective factors: A systematic review / Consumo de agua en lactantes sanos de cero a seis meses y factores efectivos: una revisión sistemática

INTRODUCTION: Early introduction of fluids and water affects the duration of breastfeeding, the infant immune system, and possibly causes infants to consume less breast milk, which may, in turn, affect their nutritional and immune status. OBJECTIVE: This study was carried out to determine water consumption in 0-6-month-old infants and the factors affecting this consumption. MATERIALS AND METHODS: A literature review was conducted in seven electronic databases (Medline, Web of Science, PubMed, ScienceDirect, Scopus, Cochrane Library, and TÜBITAK) for studies published until April 25, 2022, using the keywords: drinking water, infant, and breastfeeding. RESULTS: The systematic review included 13 studies. Five studies were crosssectional, three were descriptive and quasi-experimental, and the others were case-control and cohort studies. It was reported in the examined studies that 86.2% of the infants were around 6 weeks old, 44 % of the infants were 1 month old, 77% were 3 months old, 2.5% were 4 months old, and 2.5 to 85% of the infants were around 6 months old when they first consumed water. The prominent reasons for making the infants drink water are the thought that they need it and cultural reasons. CONCLUSIONS: The exclusive breastfeeding of 0-6-month-old infants is the recommendation of reliable health authorities. Nurses play a key role in implementing this practice. In this systematic review, it was seen that families gave their infants water at varying rates in the 0-6-month period, and the factors affecting this situation were revealed. If nurses determine which factors affect families in terms of the early introduction of fluids, they could be able to plan the necessary education and interventions.

Introducción: La introducción temprana de líquidos y agua afecta la duración de la lactancia, el sistema inmune del lactante y posiblemente hace que los lactantes consuman menos leche materna, lo que a su vez puede afectar su estado nutricional e inmunitario. Objetivo: Este estudio se realizó para determinar el consumo de agua en bebés de cero a seis meses y los factores que inciden en este consumo. Objetivo: Este estudio se realizó para determinar el consumo de agua en bebés de cero a seis meses y los factores que inciden en este consumo. Materiales y métodos: se hizo una revisión de la literatura en siete bases de dato electrónicas (Medline, Web of Science, PubMed, ScienceDirect, Scopus, Cochrane Library y TÜBITAK) para estudios publicados hasta el 25 de abril de 2022, utilizando las palabras clave: agua potable, lactante y lactancia. Resultados: La revisión sistemática incluyó 13 estudios. Cinco fueron estudios transversales, tres fueron descriptivos, cuasiexperimentales y los restantes fueron estudios de casos y controles, y de cohortes. En los estudios examinados se informó que le dieron agua al 86,2 % de los lactantes de seis semanas, al 44 % de los lactantes de un mes, al 77 % de los lactantes de tres meses, al 2,5 % de los lactantes de cuatro meses y al 2,5 % a 85 % de los lactantes de seis meses. Las razones principales para dar agua a los bebés son la idea de que los bebés necesitan agua y razones culturales. Conclusiones: La lactancia materna exclusiva es la recomendación de las autoridades sanitarias para los bebés de cero a seis meses. Las enfermeras juegan un papel clave en la implementación de esta práctica. En esta revisión sistemática se observó que las familias daban agua a sus bebés en proporciones variables durante el período de cero a seis meses y se revelaron los factores que inciden en esta situación. Si las enfermeras determinan qué factores afectan a las familias en cuanto a la introducción temprana de líquidos, podrían planificar las medidas educativas y las intervenciones necesarias.

Water consumption in 0-6-month-old healthy infants and effective factors: A systematic review / Consumo de agua en lactantes sanos de cero a seis meses y factores efectivos: una revisión sistemática

Introduction: Early introduction of fluids and water affects the duration of breastfeeding, the infant immune system, and possibly causes infants to consume less breast milk, which may, in turn, affect their nutritional and immune status. Objective: This study was carried out to determine water consumption in 0-6-month-old infants and the factors affecting this consumption. Materials and methods: A literature review was conducted in seven electronic databases (Medline, Web of Science, PubMed, ScienceDirect, Scopus, Cochrane Library, and TÜBITAK) for studies published until April 25, 2022, using the keywords: drinking water, infant, and breastfeeding. Results: The systematic review included 13 studies. Five studies were crosssectional, three were descriptive and quasi-experimental, and the others were case-control and cohort studies. It was reported in the examined studies that 86.2% of the infants were around 6 weeks old, 44 % of the infants were 1 month old, 77% were 3 months old, 2.5% were 4 months old, and 2.5 to 85% of the infants were around 6 months old when they first consumed water. The prominent reasons for making the infants drink water are the thought that they need it and cultural reasons. Conclusions: The exclusive breastfeeding of 0-6-month-old infants is the recommendation of reliable health authorities. Nurses play a key role in implementing this practice. In this systematic review, it was seen that families gave their infants water at varying rates in the 0-6-month period, and the factors affecting this situation were revealed. If nurses determine which factors affect families in terms of the early introduction of fluids, they could be able to plan the necessary education and interventions.

Introducción. La introducción temprana de líquidos y agua afecta la duración de la lactancia, el sistema inmune del lactante y posiblemente hace que los lactantes consuman menos leche materna, lo que a su vez puede afectar su estado nutricional e inmunitario. Objetivo. Este estudio se realizó para determinar el consumo de agua en bebés de cero a seis meses y los factores que inciden en este consumo. Materiales y métodos. Se hizo una revisión de la literatura en siete bases de dato electrónicas (Medline, Web of Science, PubMed, ScienceDirect, Scopus, Cochrane Library y TÜBITAK) para estudios publicados hasta el 25 de abril de 2022, utilizando las palabras clave: agua potable, lactante y lactancia. Resultados. La revisión sistemática incluyó 13 estudios. Cinco fueron estudios transversales, tres fueron descriptivos, cuasiexperimentales y los restantes fueron estudios de casos y controles, y de cohortes. En los estudios examinados se informó que le dieron agua al 86,2 % de los lactantes de seis semanas, al 44 % de los lactantes de un mes, al 77 % de los lactantes de tres meses, al 2,5 % de los lactantes de cuatro meses y al 2,5 % a 85 % de los lactantes de seis meses. Las razones principales para dar agua a los bebés son la idea de que los bebés necesitan agua y razones culturales. Conclusiones. La lactancia materna exclusiva es la recomendación de las autoridades sanitarias para los bebés de cero a seis meses. Las enfermeras juegan un papel clave en la implementación de esta práctica. En esta revisión sistemática se observó que las familias daban agua a sus bebés en proporciones variables durante el período de cero a seis meses y se revelaron los factores que inciden en esta situación. Si las enfermeras determinan qué factores afectan a las familias en cuanto a la introducción temprana de líquidos, podrían planificar las medidas educativas y las intervenciones necesarias.

Investigation of EGFR and ALK mutation frequency and treatment results in advanced non-small cell lung cancer.

Aim: Lung cancer has opened a new era in cancer treatment by elucidating the tumor's molecular structure and identifying the targetable mutations. Identifying the targeted mutations in lung cancer constitutes one of the main steps of treatment planning. The frequency of EGFR (epidermal growth factor receptor gene) and ALK (anaplastic lymphoma kinase gene) mutations in non-small cell lung cancer (NSCLC) also varies in populations depending on ethnicity, gender, smoking, and histopathological subtype. In general, limited data are available regarding the frequency and regional distribution of these mutations in the Turkish population. Our study aimed to determine the frequency of EGFR and ALK mutations in patients with advanced-stage NSCLC and compare the clinical characteristics, treatment, and survival results of cases with mutations with the group without mutations. Materials and Methods: In our study, 593 patients with advanced-stage NSCLC diagnosis and mutational analyses were evaluated retrospectively. Demographic characteristics, tumor stages (tumor, node, metastasis, TNM), EGFR and ALK analysis results, treatments applied, and survival of the cases were recorded. EGFR analysis, exon 18, 19, 20, and 21 mutations were studied with real-time PCR (RT-PCR) Rotor-Gene system from patients' samples. For ALK analysis, the ALK Break Apart kit (Zytovision GmbH; Germany) was used with the fluorescent in situ hybridization (FISH) method. Results: In our study, EGFR mutation was detected in 63 patients (10.6%) and ALK mutation in 19 patients (3.2%) out of 593 patients. EGFR mutation was observed more frequently in women and non-smokers (P = 0.001, P = 0.003). No correlation was found between the presence of EGFR mutation and metastases regions and recurrence (P > 0.05). ALK mutation was observed more frequently in non-smokers and females (P = 0.001, P = 0.003). Patients with ALK mutations were younger than other groups (P = 0.003). There was also no significant relationship between ALK mutation and metastates regions and recurrence after treatment (P > 0.05). Patients with EGFR or ALK mutations had a longer life span than other cases (P = 0.474). Those who had ALK mutations and received targeted therapy had a longer average life expectancy (P < 0.05). No difference was observed in those who had EGFR mutations and received targeted treatment in terms of survival (P > 0.05). Conclusion: In our study, conducted in the Aegean region of Turkey, the positivity rates of EGFR and ALK mutations were found to be at similar rates with the Caucasian race across the world. EGFR mutation was more common in women, non-smokers, and patients with adenocarcinoma histology. ALK mutation was also detected more frequently in younger patients, women, and non-smokers. Patients with EGFR and ALK mutations had a longer life expectancy than those without the mutation. It was observed that testing patients diagnosed with advanced-stage NSCLC for genetic mutations of the tumor in the first step of the treatment and initiating treatment in patients with mutations provided a significant survival advantage.

The effects of freezing and thawing on mature human milk's contains: A systematic review.

OBJECTIVE: To conduct a systematic review on the effects of freezing and thawing mature human milk at -18 to -20°C for different periods of time on the macronutrients, micronutrients and bioactive content of milk. DESIGN: Before starting the research, the study protocol was recorded in the 'PROSPERO' database. Eleven databases were searched, and eight studies were included in this review. The articles were published between January 2010 and June 2020. MEASUREMENTS AND FINDINGS: Total protein content increased when milk was frozen for 2 days, but this decreased significantly when milk was frozen for >1 week. Total carbohydrate content also increased when milk was frozen for 2 days, and no significant change was observed when milk was frozen for >1 week. Energy content decreased when milk was frozen for >8 weeks. Total fat content decreased as the freezing period of milk increased, and total free fatty acid content increased. Thirty days of freezing led to a non-significant decrease in the vitamin E content of milk. Freezing did not lead to changes in immunological factors in human milk, but decreases in glutathione peroxidase, antioxidant capacity and lactoferrin were observed. KEY CONCLUSIONS: In order to maintain the nutritional and immunological properties of human milk after freezing and thawing, families, especially mothers, should be informed about the effects of storing milk this way. After expressing milk, it is recommended that the date should be written on the freezer bag, so that milk is frozen for a shorter period of time before use.

COVID-19 Among Patients with Psoriasis: A Single-Center Retrospective Cross-Sectional Study.

Objective: Psoriasis patients may have been affected by COVID-19 differently than the normal population due to using different types of treatments, including immunosuppressive agents and biological therapies, the probability of lower effectiveness, and different side effects of the vaccines. This study aimed to evaluate the epidemiologic and clinical features of COVID-19 and the effect of the psoriasis treatment on it. Materials and Methods: Psoriasis patients followed up in our clinic between March 2020 and July 2022 were evaluated in terms of clinicodemographic characteristics, treatment methods, and COVID-19 vaccination status and compared regarding COVID-19 history. Results: A total of 110 patients (female:male ratio=1:1.2) with a mean age of 45.6±14.3 years were evaluated. Thirty patients (27.2%) developed COVID-19 during psoriasis treatment. Unvaccinated patients had COVID-19 (6/11, 55%) more frequently than vaccinated ones (24/99, 24%), but it was not statistically significant (p=0.067). Although patients who received biological therapy were also more frequently infected with SARS-CoV-2 than patients who received other types of therapies (18/53 [34%] versus 12/57 [21%], respectively), the difference was again not statistically significant.A patient with hypertension using acitretin was hospitalized for pulmonary involvement because of COVID-19. No exacerbation of psoriasis was observed in patients who developed COVID-19, while psoriasis flares occurred following COVID-19 mRNA vaccination in two patients. Conclusion: Patients with psoriasis should get vaccinated against COVID-19, as vaccination prevents the disease and does not result in serious side effects. Although using biological agents for the treatment of psoriasis could be related to a higher risk of getting COVID-19, these agents do not increase the risk of severe COVID-19. Therefore, they may be beneficial in reducing the risk of both psoriasis exacerbations and severe COVID-19 due to the cytokine storm among patients using biological for psoriasis.However, large-scale and controlled studies are needed to support our conclusions.

Antimicrobial potential of a ponericin-like peptide isolated from Bombyx mori L. hemolymph in response to Pseudomonas aeruginosa infection.

The main effectors in the innate immune system of Bombyx mori L. are antimicrobial peptides (AMPs). Here, we infected B. mori with varied inoculum sizes of Pseudomonas aeruginosa ATCC 25668 cells to investigate changes in morpho-anatomical responses, physiological processes and AMP production. Ultraviolet-visible spectra revealed a sharp change in λmax from 278 to 285 nm (bathochromic shift) in the hemolymph of infected B. mori incubated for 24 h. Further, Fourier Transform InfraRed studies on the hemolymph extracted from the infected B. mori showed a peak at 1550 cm-1, indicating the presence of α-helical peptides. The peptide fraction was obtained through methanol, acetic acid and water mixture (90:1:9) extraction, followed by peptide purification using Reverse Phase High Performance Liquid Chromatography. The fraction exhibiting antibacterial properties was collected and characterized by Matrix-Assisted Laser Desorption/Ionization-Time of Flight. A linear α-helical peptide with flexible termini (LLKELWTKMKGAGKAVLGKIKGLL) was found, corresponding to a previously described peptide from ant venom and here denominated as Bm-ponericin-L1. The antibacterial activity of Bm-ponericin-L1 was determined against ESKAPE pathogens. Scanning electron microscopy confirmed the membrane disruption potential of Bm-ponericin-L1. Moreover, this peptide also showed promising antibiofilm activity. Finally, cell viability and hemolytic assays revealed that Bm-ponericin-L1 is non-toxic toward primary fibroblasts cell lines and red blood cells, respectively. This study opens up new perspectives toward an alternative approach to overcoming multiple-antibiotic-resistance by means of AMPs through invertebrates' infection with human pathogenic bacteria.

Investigation of the Effect of Human Milk Expression Techniques on Milk Content: A Systematic Review.

BACKGROUND: If the mother and infant cannot meet after birth, it is recommended to express milk and give it to the infant. There was evidence indicating that there might be decrease in essential nutrient values in human milk content depending on the expression technique in literature. The goal of this systematic review was to investigate the effect of human milk expression techniques on the macronutrient milk content and establish an evidence base for future studies. METHODS: Studies investigating the effect of human milk expression techniques on milk content were reviewed without year limitations. A literature review was conducted in six electronic databases (MEDLINE, Web of Science, PubMed, ScienceDirect, CINAHL and Cochrane) until 30 May 2021, using the keywords of breast milk expression techniques, milk content and breast milk pumping. RESULTS: From 258 articles initially screened, we included 6 articles in the systematic review. The fat, protein and lactose content of human milk was analyzed in the studies reviewed. It was concluded that there was no significant effect on the protein (9.7-9.8 g/dl and 2.1-2.1 g/dl, respectively) and lactose (6.50-6.53% and 6.1-6.1 g/dl, respectively) content of milk. However, the fat (58.30, 48.81g/l; 2.6-2.2 g/dl) content was affected. CONCLUSIONS: This study investigated the effect of milk expression techniques on the macronutrient content of human milk, and it was concluded that there was no significant effect on the protein and carbohydrate content of milk. However, the fat content was affected. Limitation of this study is that some factors that might affect the content of human milk were not standardized sufficiently in the included studies.

The association between the histopathological features and microsatellite instability in young patients with urothelial carcinoma of the bladder.

OBJECTIVE: Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. METHODS: A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. RESULTS: Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. CONCLUSIONS: Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.

Sequencing, de novo assembly and annotation of Digitalis ferruginea subsp. schischkinii transcriptome.

There is an increasing demand for elucidating the biosynthetic pathway of medicinal plants, which are capable of producing several metabolites with great potentials for industrial drug production. Digitalis species are important medicinal plants for the production of cardenolide compounds. Advancement on culture techniques is strictly related to our understanding of the genomic background of species. There are a limited number of genomic studies on Digitalis species. The goal of this study is to contribute to the genomic data of Digitalis ferruginea subsp. schischkinii by presenting transcriptome annotation. Digitalis ferruginea subsp. schischkinii has a limited distribution in Turkey and Transcaucasia, and has a high level of lanatoside C, an important cardenolide. In the study, we sequenced the cDNA library prepared from RNA pools of D. ferruginea subsp. schischkinii tissues treated with various stress conditions. Comprehensive bioinformatics approaches were used for de novo assembly and functional annotation of D. ferruginea subsp. schischkinii transcriptome sequence data along with TF families predictions and phylogenetic analysis. In the study, 58,369 unigenes were predicted and unigenes were annotated by analyzing the sequence data in the non-redundant (NR) protein database, the non-redundant nucleotide (NT) database, Gene Orthology (GO), EuKaryotic Orthologous Groups (KOG), Kyoto Encyclopedia of Genes and Genomes (KEGG), SwissProt, and InterPro databases. This study is the first transcriptome data for D. ferruginea subsp. schischkinii.

The association between the histopathological features and microsatellite instability in young patients with urothelial carcinoma of the bladder

SUMMARY OBJECTIVE: Bladder cancer under the age of 40 is extremely rare. Bladder cancer development involves complex and multi-stage processes, one of which is the DNA damage repair mechanism. In this retrospective study, we aimed to evaluate the histopathological features of bladder urothelial carcinoma seen in patients under 40 years of age and tumor microsatellite instability status using immunohistochemistry. METHODS: A total of 50 patients under the age of 40 with urothelial bladder carcinoma from two different centers in the same country were included. Expression of the mismatch repair proteins MLH1, MSH2, MSH6, and PMS2 was analyzed by immunohistochemistry. RESULTS: Age at the time of diagnosis ranged from 17 to 40 years old. Most tumors were non-invasive papillary urothelial carcinoma. Two cases had nuclear loss of MSH-6 and PMS-2. We observed that tumor grade, tumor stage, presence of tumor differentiation, and infiltrative growth pattern of the tumor have significant impact on prognosis, but microsatellite instability does not have an effective role in bladder carcinogenesis in young patients. CONCLUSIONS: Our results indicate that the presence of microsatellite instability is not related to the low tumor grade and stage in urothelial neoplasms in young patients, suggesting that urothelial carcinoma of the bladder in young patients may represent a genetically stable form of neoplasia.

The relation between distant metastasis and genetic change type in stage IV lung adenocarcinoma patients at diagnosis.

INTRODUCTION: Brain metastasis prevalence is higher in patients with positive epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) and C-ROS oncogene 1 (ROS-1) fusion change in lung adenocarcinoma. OBJECTIVES: The purpose of our study is to investigate the relation between the genetic change type and the initial distant metastasis in stage IV lung adenocarcinoma patients with genetic changes. METHODS: The study was conducted between January 2007 and December 2018 in a retrospective fashion with patients who had lung cancer diagnosed as stage IV adenocarcinoma. The relation between genetic mutation change (EGFR, ALK or ROS-1) and distant metastasis was analysed. RESULTS: A total of 845 patients were included in the study. The median age was 62 (28-88). It was determined that lung and pleura metastases were more frequent at a significant level in patients with positive EGFR mutation (P = 0.032, P = 0.004, respectively). In patients with positive ALK fusion change, pleura metastasis was determined to be more frequent (P = 0.001). Multiple metastases were determined to be significantly more in patients with positive ALK fusion change than single metastasis (P = 0.02). CONCLUSION: In patients with EGFR mutant lung adenocarcinoma, lung and pleura metastasis is more frequent and pleura metastasis is more frequent in ALK positive adenocarcinoma. Additionally, multiple organ metastases are higher in ALK positive lung adenocarcinoma.

Efficient Doxorubicin Loading to Isolated Dexosomes of Immature JAWSII Cells: Formulated and Characterized as the Bionanomaterial.

Immature dendritic cells (IDc), 'dexosomes', are promising natural nanomaterials for cancer diagnose and therapy. Dexosomes were isolated purely from small-scale-up production by using t25-cell-culture flasks. Total RNA was measured as 1.43 ± 0.33 ng/106 cell. Despite the fact that they possessed a surface that is highly abundant in protein, this did not become a significant effect on the DOX loading amount. Ultrasonication was used for doxorubicin (DOX) loading into the IDc dexosomes. In accordance with the literature, three candidate DOX formulations were designed as IC50 values; dExoIII, 1.8 µg/mL, dExoII, 1.2 µg/mL, and dExoI, 0.6 µg/mL, respectively. Formulations were evaluated by MTT test against highly metastatic A549 (CCL-185; ATTC) cell line. Confocal images of unloaded (naïve) were obtained by CellMaskTM membrane staining before DOX loading. Although, dexosome membranes were highly durable subsequent to ultrasonication, it was observed that dexosomes could not be stable above 70 °C during the SEM-image analyses. dExoIII displayed sustained release profile. It was found that dynamic light scattering (DLS) and nanoparticle tracking analysis (NTA) results were in good agreement with each other. Zeta potentials of loaded dexosomes have approximately between -15 to -20 mV; and, their sizes are 150 nm even after ultrasonication. IDcJAWSII dexosomes can be able to be utilized as the "BioNanoMaterial" after DOX loading via ultrasonication technique.

The Role of Heredity and the Prevalence of Strabismus in Families with Accommodative, Partial Accommodative, and Infantile Esotropia

Objectives: To investigate the prevalence of strabismus in families of a proband with accommodative, partial accommodative, or infantile esotropia, and to evaluate the mode of inheritance and the role of consanguineous marriages in this prevalence. Materials and Methods: Families of probands with comitant strabismus were invited to participate in the study. The family members of 139 subjects with accommodative, 55 with partial accommodative, and 21 with infantile esotropia agreed to participate. Detailed family trees were constructed. The first- and second-degree relatives were invited for a complete ophthalmological examination, and 518 individuals from 168 families were evaluated. The role of consanguinity, the presence of tropia, phoria (≥8 PD), microtropia, and hypermetropia (≥3.00 D) among first- and second-degree relatives were analyzed. Results: A non-Mendelian pattern was found in 49 families (23%), an autosomal dominant pattern in 39 families (18%), and an autosomal recessive pattern in 6 families (3%). The prevalence of consanguineous marriages among parents of probands was 18.1%, 22.6%, and 14.3% in the accommodative, partial accommodative, and infantile esotropia groups, respectively (p=0.652). The prevalence of strabismus in first-degree relatives was 58.9%, 45.5%, and 38.1%, respectively (p=0.07). The prevalence of microtropia in probands' siblings was significantly higher in the accommodative esotropia group (p=0.034). Conclusion: Sporadic cases and non-Mendelian inheritance were more frequent than autosomal recessive inheritance. Autosomal recessive inheritance was found not to be frequent in consanguineous marriages. The prevalence of strabismus and microtropia was significantly higher in families of esotropia cases than in the general population.

Renal-Hepatic-Pancreatic Dysplasia: An Ultra-Rare Ciliopathy with a Novel NPHP3 Genotype.

Renal-hepatic-pancreatic dysplasia-1 (RHPD1) is an ultra-rare genetic disorder with a high mortality. It is caused by biallelic pathogenic variants in NPHP3 , which encode nephrocytin, an important component of the ciliary protein complex. The NPHP3 -related disease phenotype is diverse with RHPD1, nephronophthisis-3, and Meckel syndrome-7. In this case report, we present a female infant with hepatomegaly, cholestasis, and elevated transaminases who was found to carry a homozygous c.2975C > T variant of NPHP3. This is the first description of this genotype and RHPD1 phenotype in the literature. The patient is currently being closely monitored for the necessity of combined renal and liver transplantation under supportive treatment.

Can fetal fractions in the cell-free DNA test predict the onset of fetal growth restriction?

Objective To investigate the possible predictive value of fetal fraction in the cell-free DNA (cfDNA) test in pregnancies with early- and late-onset fetal growth restriction (FGR). Methods This retrospective study comprised 247 women who were screened using the cfDNA test for aneuploidies during the first or second trimester and had deliveries at our institution from January 2016 to December 2019. The fetal fractions of women with early- (n = 14) and late-onset (n = 83) FGR and those with uncomplicated pregnancies (n = 150) were compared. Results The median fetal fractions for the early-onset FGR, late-onset FGR, and control groups were 5.7 [interquartile range (IQR) 2.65], 7 (IQR 5), and 7.35 (IQR 3.65), respectively. The fetal fractions were significantly lower in the early-onset FGR group than in the late-onset FGR and control groups (P = 0.047 and P = 0.037, respectively). There was no difference in fetal fractions between the late-onset FGR and control groups (P = 1.00). Conclusion As a placenta-related disease, early-onset FGR had lower fetal fractions in the cfDNA test than uncomplicated pregnancies. For clinical use, lower fetal fractions can contribute as a biomarker for screening asymptomatic women for possible placenta-related diseases, such as early-onset FGR. However, more studies are needed to define the "lower" limit.