Cold-induced urticaria in children: A multicenter, retrospective cohort study.

Background: Studies of cold-induced urticaria (ColdU) in pediatric patients are limited and not well characterized. Objective: The objective of the study was to investigate the characteristics of ColdU in children. Methods: A multicenter, retrospective chart review was performed in children ages ≤18 years diagnosed with ColdU at 11 pediatric allergy and immunology centers in Turkey between September 1, 2010, and August 31, 2022. Results: A total of 83 children with ColdU were included, 54.2% were girls, and the mean age of symptom onset was 8.8 years. The median duration of ColdU at the time of diagnosis was significantly higher in the girls than in the boys (1.0 years [0.0-13.8 years] versus 0.3 years [0.0-15.0 years]; p = 0.007). All the patients underwent an ice cube test, and 71.1% were found positive (typical ColdU). The mean ± standard deviation age of onset was significantly higher in the patients with typical ColdU versus atypical patients (9.4 ± 4.5 years versus 7.3 ± 4.5 years; p = 0.041). Swimming alone and in combination with the wind were significantly the most reported triggers in patients with cold-induced anaphylaxis (ColdA) when compared with patients with ColdU and with nonanaphylactic symptoms (70.0% versus 28.9% [p = 0.022], and 50.0% versus 4.1% [p < 0.001], respectively). Only patients with other chronic urticaria were found to be associated with the development of typical ColdU (p = 0.036). The median total serum immunoglobulin E (IgE) was significantly higher in typical ColdU than in atypical patients (72.5 IU/mL [3.86 - 2500 IU/mL] versus 30.0 IU/mL [0.83 - 1215 IU/mL]; p = 0.007); however, total serum IgE differences were not found to affect ColdU resolution between the two groups (p = 0.204). The resolution was documented in 30.4%. Conclusion: Those who were boys and had a positive ice cube test result could have an association with earlier onset of ColdU. Those swimming alone on a windy day were at highest risk for ColdA. It is still unclear what characteristics are associated with the resolution of ColdU, and this warrants further investigation.

Evaluation of the Clinical Characteristics of Patients with Food Protein-Induced Enterocolitis Syndrome: A Multicenter Study.

INTRODUCTION: Food protein-induced enterocolitis syndrome (FPIES) is a rare non-IgE, cell-mediated food allergy disorder. We aimed to report the demographic characteristics, clinical features, and management of pediatric patients with FPIES. METHODS: This retrospective study included all children diagnosed with FPIES at the pediatric allergy departments of the participating twelve study centers from January 2015 to November 2020. RESULTS: A total of 73 patients (39 males, 53.4%) with a male/female ratio of 1.1 were included in the study. The median (interquartile ranges) age at symptom onset was 6 months (0.5-168, 4-9.5). The most frequent offending foods were cow's milk, egg's yolk, fish, and egg's white, identified in 38.4% (n = 28), 32.9% (n = 24), 21.9% (n = 16) and 20.5% (n = 15) of the patients, respectively. The total number of reported FPIES episodes was 290 (3.9 episodes per child). Oral food challenge (OFC) was performed in 54.8% (n = 40) of the patients, and tolerance was detected in 17 OFCs (42.5%) at a median age of 15 months (range 8-132 months). CONCLUSION: FPIES is a non-IgE-mediated food hypersensitivity that commonly affects infants and is often misdiagnosed. The pathophysiology of the disease remains unclear and the low awareness of FPIES among physicians and parents highlights the need for more education.

Urtica dioica-Derived Phytochemicals for Pharmacological and Therapeutic Applications.

Urtica dioica belongs to the Urticaceae family and is found in many countries around the world. This plant contains a broad range of phytochemicals, such as phenolic compounds, sterols, fatty acids, alkaloids, terpenoids, flavonoids, and lignans, that have been widely reported for their excellent pharmacological activities, including antiviral, antimicrobial, antihelmintic, anticancer, nephroprotective, hepatoprotective, cardioprotective, antiarthritis, antidiabetic, antiendometriosis, antioxidant, anti-inflammatory, and antiaging effects. In this regard, this review highlights fresh insight into the medicinal use, chemical composition, pharmacological properties, and safety profile of U. dioica to guide future works to thoroughly estimate their clinical value.

The Therapeutic Potential of Anthocyanins: Current Approaches Based on Their Molecular Mechanism of Action.

Anthocyanins are natural phenolic pigments with biological activity. They are well-known to have potent antioxidant and antiinflammatory activity, which explains the various biological effects reported for these substances suggesting their antidiabetic and anticancer activities, and their role in cardiovascular and neuroprotective prevention. This review aims to comprehensively analyze different studies performed on this class of compounds, their bioavailability and their therapeutic potential. An in-depth look in preclinical, in vitro and in vivo, and clinical studies indicates the preventive effects of anthocyanins on cardioprotection, neuroprotection, antiobesity as well as their antidiabetes and anticancer effects.

Berberis Plants-Drifting from Farm to Food Applications, Phytotherapy, and Phytopharmacology.

The genus Berberis includes about 500 different species and commonly grown in Europe, the United States, South Asia, and some northern areas of Iran and Pakistan. Leaves and fruits can be prepared as food flavorings, juices, and teas. Phytochemical analysis of these species has reported alkaloids, tannins, phenolic compounds and oleanolic acid, among others. Moreover, p-cymene, limonene and ocimene as major compounds in essential oils were found by gas chromatography. Berberis is an important group of the plants having enormous potential in the food and pharmaceutical industry, since they possess several properties, including antioxidant, antimicrobial, anticancer activities. Here we would like to review the biological properties of the phytoconstituents of this genus. We emphasize the cultivation control in order to obtain the main bioactive compounds, the antioxidant and antimicrobial properties in order to apply them for food preservation and for treating several diseases, such as cancer, diabetes or Alzheimer. However, further study is needed to confirm the biological efficacy as well as, the toxicity.

Dioscorea Plants: A Genus Rich in Vital Nutra-pharmaceuticals-A Review.

Dioscorea species, known as "Yams," belong to family Dioscoreaceae. This genus consists of more than 600 species distributed from Africa, Asia, the Caribbean's South America, and the South Pacific islands. Their organoleptic properties make them the most widely used carbohydrate food and dietary supplements. The underground and/or aerial tubers represent valuable sources of proteins, fats, and vitamins for millions of people in West Africa. This review gives a shot of secondary metabolites of Dioscorea plants, including steroids, clerodane diterpenes, quinones, cyanidins, phenolics, diarylheptanoids, and nitrogen-containing compounds. This review collected the evidence on biological properties of description Dioscorea, including in-vitro and in-vivo studies. Dioscorea species contain promising bioactive molecules i.e. diosgenin that support their different biological properties, including antioxidant, hypoglycaemic, hypolipidemic, anti- antimicrobial, inflammatory, antiproliferative, androgenic, estrogenic, and contraceptive drugs. Indeed, besides its nutrient values, Dioscorea is a potential source of bioactive substances of interest in the prevention/treatment of several diseases, and thus represents a great challenge in developing countries. However, ethnomedicinal potential should be validated and further researches on pharmacological properties and phytochemical composition should be carried out. Particularly, doing some studies to convert the preclinical results to clinical efficacy should be guaranteed. Dioscorea, Food plant, Traditional use, Phytochemistry, Pharmacological activities.

Resveratrol: A Double-Edged Sword in Health Benefits.

Resveratrol (3,5,4'-trihydroxy-trans-stilbene) belongs to polyphenols' stilbenoids group, possessing two phenol rings linked to each other by an ethylene bridge. This natural polyphenol has been detected in more than 70 plant species, especially in grapes' skin and seeds, and was found in discrete amounts in red wines and various human foods. It is a phytoalexin that acts against pathogens, including bacteria and fungi. As a natural food ingredient, numerous studies have demonstrated that resveratrol possesses a very high antioxidant potential. Resveratrol also exhibit antitumor activity, and is considered a potential candidate for prevention and treatment of several types of cancer. Indeed, resveratrol anticancer properties have been confirmed by many in vitro and in vivo studies, which shows that resveratrol is able to inhibit all carcinogenesis stages (e.g., initiation, promotion and progression). Even more, other bioactive effects, namely as anti-inflammatory, anticarcinogenic, cardioprotective, vasorelaxant, phytoestrogenic and neuroprotective have also been reported. Nonetheless, resveratrol application is still being a major challenge for pharmaceutical industry, due to its poor solubility and bioavailability, as well as adverse effects. In this sense, this review summarized current data on resveratrol pharmacological effects.

Medicinal Plants Used in the Treatment of Human Immunodeficiency Virus.

Since the beginning of the epidemic, human immunodeficiency virus (HIV) has infected around 70 million people worldwide, most of whom reside is sub-Saharan Africa. There have been very promising developments in the treatment of HIV with anti-retroviral drug cocktails. However, drug resistance to anti-HIV drugs is emerging, and many people infected with HIV have adverse reactions or do not have ready access to currently available HIV chemotherapies. Thus, there is a need to discover new anti-HIV agents to supplement our current arsenal of anti-HIV drugs and to provide therapeutic options for populations with limited resources or access to currently efficacious chemotherapies. Plant-derived natural products continue to serve as a reservoir for the discovery of new medicines, including anti-HIV agents. This review presents a survey of plants that have shown anti-HIV activity, both in vitro and in vivo.

An evaluation of vitamin D levels in children with seasonal allergic rhinitis during pollen season.

BACKGROUND: Serum vitamin D levels have not been studied in children with seasonal allergic rhinitis (SAR). The aim of this study was to evaluate the vitamin D levels of children with SAR and to compare them to levels in healthy children during pollen season. METHODS: This study was conducted in 100 children with SAR and 100 healthy controls. Clinical and laboratory evaluations and vitamin D analyses of all the participants were performed between the months of April and July. Pollen sensitization was detected in the patient group using a skin prick test. 25(OH)D3 levels were compared between the patient and control groups. Associations among the patient 25(OH)D3 levels and their demographic, clinical, and laboratory characteristics were analyzed. RESULTS: Overall, 72% of the patients were male, the median age was 12.35 years (range: 6-17.8 years), and the median body mass index value was 19.15 (range: 13.6-27.8). There were no differences between the patients and healthy controls in terms of gender, age, or body mass index. The mean levels of 25(OH)D3 (20.78±6) in patients were higher than those of the controls (17.92±4). In the patient group, no associations were found among 25(OH)D3 levels, demographic characteristics, atopy test results, atopy history, severity of rhinitis, and the total four symptoms score (all P>.05). CONCLUSIONS: During pollen season, children with SAR may have higher vitamin D levels than healthy controls. The presence of asthma and/or atopic dermatitis in addition to SAR did not change this result.

Students' unchanging smoking habits in urban and rural areas in the last 15 years.

BACKGROUND: Smoking is the main preventable public health problem particularly for youth worldwide. The aim of the present study was to determine the prevalence of smoking habits among students at secondary and high schools, and to compare the findings with those of a study conducted 15 years ago in the same area. METHODS: In this cross-sectional study 6212 students (51.2% female; 48.8% male) were selected randomly from rural and urban areas in Samsun. All students completed a face-to-face questionnaire. RESULTS: The overall prevalence of smoking was 13.0% (male students, 18.1%; female students, 8.2%). The mean starting age of smoking was 14.1 ± 1.5 years. Prevalence of smoking was 15.7% in urban areas and 8.1% in rural areas. The most important factors for starting smoking were social group and families. Compared with a study conducted 15 years previously in the same area for male students, smoking prevalence was increased in rural, but decreased in urban areas. CONCLUSIONS: Smoking prevalence in students in Samsun was similar to that in a study conducted 15 years previously. It is important to use anti-smoking campaigns directly targeted at teenager and they should be fully informed of the harmful effects of smoking.

Hemophagocytic bone marrow aplasia with plasma cells in a RAG2-deficient SCID case after a nonconditioned transplantation from a fully matched sibling.

We report a RAG2-deficient patient with severe combined immunodeficiency and hemophagocytic bone marrow aplasia with plasma cells after a nonconditioned transplantation from a fully matched sibling. After engraftment, disseminated BCGosis appeared because of graft versus host disease prophylaxis. On the 55th day, eosinophilia, neutropenia, and thrombocytopenia developed. Aplasia, hemophagocytic histiocytes, and plasma cells were found on his bone marrow with very high level of serum immunoglobulin E. We could not discriminate exactly whether BCGosis or alloimmune response is the cause of hemophagocytic aplasia with plasma cells. Despite the second hematopoietic stem cell transplantation with a reduced intensity conditioning regime, his marrow aplasia did not recover and he died. This case suggests that BCGosis might be associated with hemophagocytic marrow aplasia with plasma cells in an alloimmune reaction.

Impact of laryngopharyngeal and gastroesophageal reflux on asthma control in children.

OBJECTIVE: A prospective study was carried out to determine the sensitivity and specificity of reflux symptoms and laryngeal findings to diagnose laryngopharyngeal reflux (LPR) and gastro-esophageal reflux (GER) in children with asthma by comparing the results of double probe pH monitorization and to determine the difference between controlled and uncontrolled asthma in terms of GER and LPR coexistence. METHODS: A total of 50 patients (23 girls, mean age 10.8±0.4 years) with mild to moderate persistent asthma were included in this study. The patients were divided in two groups according to the asthma control status as controlled (n=27) vs. uncontrolled asthma (n=23). All patients completed the reflux symptom questionnaire and then they underwent flexible fiberoptic laryngoscopy and 24h double probe (pharyngeal and esophageal) pH monitorization. Laryngopharyngeal and gastroesophageal reflux were defined according to the double probe pH meter results. RESULTS: The prevalences of LPR and GER were 70% and 46% in asthmatic patients, respectively. The reflux symptom score and LPR disease index were not useful to predict LPR or GER. There was no association between asthma control status and LPR and GER. Vocal nodule seems to be a valuable sign to evaluate LPR in asthmatic children. CONCLUSIONS: The reflux symptom score and LPR disease index do not seem reliable to diagnose LPR and GER in children with asthma. The frequency of LPR and GER are independent of asthma control, atopy and long acting beta agonist usage.

Sodium nitroprusside and toxic epidermal necrolysis.

Sodium nitroprusside (SNP) is one of the most widely used parenteral antihypertensive agents in severe hypertension management. Toxic epidermal necrolysis (TEN) is a rare, mostly drug-induced, severe muco-cutoneous reaction with various complications and high mortality. A fifteen years old girl who is on hemodialysis for chronic renal insufficiency and was hospitalized for emergency management of hypertension, developed a diffuse maculopapular rash within minutes after SNP infusion. In 72 hours, approximately 40% of the body surface was involved with skin detachment indicating epidermal necrolysis and a skin biopsy confirmed the diagnosis of TEN. To the best of our knowledge there is no report of an association of SNP and TEN in the English literature and the clinical data exemplifying consequent IgE and non-IgE mediated hypersensitivity reactions are scanty. With this report we wanted to present a rare complication of SNP infusion indicating another rare occurrence of sequential IgE and non-IgE mediated hypersensitivity reactions.

Foreign body aspiration in childhood: evaluation of diagnostic parameters.

BACKGROUND: Foreign body aspiration (FBA) is one of the most important preventable causes of childhood mortality and morbidity. OBJECTIVE: The aim of this study was to define the clinical and radiological features of FBA and investigate the diagnostic value of various parameters used to diagnose FBA. METHODS: The medical records of 147 children who were admitted to the hospital with a diagnosis of suspected FBA were examined. The sensitivity and specificity of the parameters used for the diagnosis of FBA and their predictive values were calculated. RESULTS: Of the patients, 75.5% were younger than 3 years, and 61.2% were male. Peak incidence was found in 18 months. A negative bronchoscopy rate of 19.7% was found, and 92.6% of these patients were younger than 3 years. The parameter with the highest diagnostic value was the presence of aspiration history (the sensitivity and positive and negative predictive values were 97%, 89%, and 80%, respectively). No significant difference was found in the classic triad of FBA (sudden onset of cough, wheezing, and unilaterally decreased breath sounds) between patients with and without FBA. The specificity and positive predictive value of the classic triad were high, and the sensitivity and negative predictive value were low (85% and 78%, and 13% and 19%, respectively). CONCLUSIONS: Especially, male children younger than 3 years have an increased risk of FBA. Neither clinical symptoms nor the radiological findings alone are sufficiently specific and sensitive in diagnosing FBA. The most important factor for diagnosis is the presence of aspiration history.

Congenital goitrous hypothyroidism, deafness and iodide organification defect in four siblings: Pendred or pseudo-Pendred syndrome?

Pendred syndrome (PDS) is an autosomal recessive disorder characterized by congenital deafness, goiter and iodide organification defect. Presence of inner ear malformations is essential for the clinical diagnosis. Most individuals with PDS are clinically and biochemically euthyroid. Mutations in the PDS gene encoding pendrin protein have been shown to be associated with PDS. It has been recently demonstrated that some families with features of PDS do not have the inner ear malformations and mutations in the PDS gene. This condition has been named as "pseudo-Pendred syndrome" (pseudo-PDS), and has been hypothesized to be of autoimmune origin. Here we report four siblings who have goiter, severe hypothyroidism, a positive perchlorate discharge test and sensorineural deafness, but not the inner ear abnormality which is diagnostic for PDS. We suggest that thyroid peroxidase (TPO) gene should be analyzed in pseudo-PDS patients with congenital goitrous hypothyroidism and deafness.

A comparative study of electrocoagulation and coagulation of aqueous suspensions of kaolinite powders.

Removal of kaolinite particles from their synthetically prepared suspensions was studied by electrocoagulation and coagulation to investigate the effect of such operating parameters as initial pH, coagulant dosage, applied voltage, current density, and time. Coagulation was more effective in a wider pH range (pH 5-8) than electrocoagulation which yielded optimum effectiveness in a relatively narrower pH range around 9, where, in both methods, these pH values corresponded to near-zero zeta potentials of kaolinite particles. The mechanism for both coagulation methods was aggregation through charge neutralization and/or enmeshment in aluminum hydroxide precipitates. The kinetics of electrocoagulation was very fast (<10 min) in approaching a residual turbidity, which could be modeled with a second-order rate equation.

A parametric comparative study of electrocoagulation and coagulation using ultrafine quartz suspensions.

This paper attempts to compare electrocoagulation using aluminum anodes and stainless steel cathodes with conventional coagulation by aluminum sulfate dosing on aqueous suspensions of ultrafine quartz. Several key parameters affecting the efficiency of electrocoagulation and coagulation were investigated with laboratory scale experiments in search of optimal parameter values. Optimal values of the parameters were determined on the basis of the efficiency of turbidity removal from ultrafine quartz suspensions. The parameters investigated in the study were suspension pH, electrical potential, current density, electrocoagulation time, and aluminum dosage. A comparison between electrocoagulation and coagulation was made on the basis of total dissolved aluminum, revealing that electrocoagulation and coagulation were equally effective at the same aluminum dosage for the removal of quartz particles from suspensions. Coagulation, however, was more effective in a wider pH range (pH 6-9) than electrocoagulation which yielded optimum effectiveness in a relatively narrower pH range around 9, where, in both methods, these pH values corresponded to near-zero zeta potentials of quartz particles. Furthermore, experimental results confirmed that electrocoagulation could display some pH buffering capacity. The kinetics of electrocoagulation was very fast (<10 min) in approaching a residual turbidity, which could be modeled with a second-order rate equation.

Newly identified c-KIT receptor tyrosine kinase ITD in childhood AML induces ligand-independent growth and is responsive to a synergistic effect of imatinib and rapamycin.

Activating mutations of c-KIT lead to ligand-independent growth. Internal tandem duplications (ITDs) of exon 11, which encodes the juxtamembrane domain (JMD), are constitutively activating mutations found in 7% of gastrointestinal stromal tumors (GISTs) but have not been described in childhood acute myeloid leukemia (AML). DNA and cDNA from 60 children with AML were screened by polymerase chain reaction (PCR) for mutations of the JMD. A complex ITD (kit cITD) involving exon 11 and exon 12 was identified with a relative frequency of 7% (4/60). The human kit cITDs were inserted into the murine c-Kit backbone and expressed in Ba/F3 cells. KIT cITD induced factorindependent growth and apoptosis resistance, and exhibited constitutive autophosphorylation. KIT cITD constitutively activated the PI3K/AKT pathway and phosphorylated STAT1, STAT3, STAT5, and SHP-2. Imatinib (IM) or rapamycin (Rap) led to complete inhibition of growth, with IC50 values at nanomolar levels. IM and Rap synergistically inhibited growth and surmounted KIT cITD-induced apoptosis resistance. IM but not LY294002 inhibited phosphorylation of STAT3 and STAT5, suggesting aberrant cross talk between PI3K- and STAT-activating pathways. The findings presented may have immediate therapeutic impact for a subgroup of childhood AML-expressing c-KIT mutations.

Formation of caspase-3 complexes and fragmentation of caspase-12 during anisomycin-induced apoptosis in AKR-2B cells without aggregation of Apaf-1.

Treatment of AKR-2B fibroblasts with anisomycin (10 microM) led to a rapid disintegration of the cells (t1/2 = 5 h) which was complete after 24 h. Cell death was associated with typical hallmarks of apoptosis like membrane blebbing, exposure of phophatidylserine on the cell surface, nuclear condensation and specific cleavage of rRNA. However, there was no dissipation of the mitochondrial potential and no intranucleosomal fragmentation. By affinity labeling with YVK(-bio)D.aomk in combination with immunostaining against activated caspase-3 analyzed by 2-D gel electrophoresis it was shown that caspase-3 is the dominant executioner caspase. Gel filtration experiments of cytosolic extract analyzed by Western blotting revealed the formation of high-molecular-weight complexes of caspase-3 (600 kDa and 250 kDa, respectively), but there was no complex formation of Apaf-1. Anisomycin treatment led to a strong activation of the stress kinases p38 kinases and the jun kinases, that was not sufficient for the activation of caspase-3 which required much higher concentrations. By using the selective inhibitors SB 203580 for p38 kinases and SP 600125 for c-jun kinases, respectively, it is shown that activation of these kinases is not necessary for cell death induced by anisomycin in AKR-2B cells. Furthermore, we disclose the activation of caspase-12 in AKR-2B cells following the addition of anisomycin. Caspase-12 zymogen present as a cytosolic complex (> 600 kDa) is activated by anisomycin leading to an uncomplexed cleaved enzyme. Since anisomycin treatment did neither lead to stress of the endoplasmic reticulum nor to a breakdown of intracellular Ca(2+)-stores, alternative pathways involved in the activation of caspases are discussed.