The role of vitamin D in pediatric systemic lupus erythematosus - a double pawn in the immune and microbial balance.

Having increased popularity during the Covid-19 pandemic, vitamin D3 is currently impressing thanks to the numerous researches aimed at its interactions with the body's homeostasis. At the same time, there is a peak in terms of recommendations for supplementation with it. Some of the studies focus on the link between autoimmune diseases and nutritional deficiencies, especially vitamin D3. Since the specialized literature aimed at children (patients between 0-18 years old) is far from equal to the informational diversity of the adult-centered branch, this review aims to bring up to date the relationship between the microbial and nutritional balance and the activity of pediatric systemic lupus erythematosus (pSLE). The desired practical purpose resides in a better understanding and an adequate, individualized management of the affected persons to reduce morbidity. The center of the summary is to establish the impact of hypovitaminosis D in the development and evolution of pediatric lupus erythematosus. We will address aspects related to the two entities of the impact played by vitamin D3 in the pathophysiological cascade of lupus, but also the risk of toxicity and its effects when the deficiency is over supplemented (hypervitaminosis D). We will debate the relationship of hypovitaminosis D with the modulation of immune function, the potentiation of inflammatory processes, the increase of oxidative stress, the perfusion of cognitive brain areas, the seasonal incidence of SLE and its severity. Finally, we review current knowledge, post-pandemic, regarding the hypovitaminosis D - pSLE relationship.

The Most Recent Insights into the Roots of Gastric Cancer.

Helicobacter pylori (H. pylori) is the most common bacterial infection worldwide, usually being acquired during childhood, and its persistence into adulthood represents one of the main contributors of gastric carcinogenesis. Based on these statements, it would be of great importance to know if the most early premalignant transformation occurs in children or later since, this would enable the development of effective anti-tumorigenesis strategies. The interplay between H. pylori virulence factors, the host's responses modified by this infection, and the gastric microecology are complex and eventually lead to the development of gastric cancer in susceptible individuals. Several biomarkers were identified as major contributors of this long-lasting process, such as pepsinogens, gastrin 17, lipid-, glucose- and iron-metabolism parameters, immunity players, aberrant bacterial DNA methylation, H. pylori virulence factors, and hallmarks of gastric dysbiosis. Several of these biomarkers were also identified in children with H. pylori infection, independently of the presence of premalignant lesions, which were also proven to be present in a subgroup of H. pylori-infected children, especially those carrying extremely virulent strains. Therefore, the most incipient premalignant gastric changes might indeed occur early during childhood, opening a promising research gate for further studies to delineate the border between infection and cancer.

A Cross-Sectional Study of Quality of Life in Patients Enrolled in the Romanian Hereditary Angioedema Registry.

BACKGROUND: Hereditary angioedema (HAE) is a rare potentially life-threatening genetic disorder characterized by recurrent episodes of angioedema without wheals that can affect any part of the body. The unpredictability of the attacks and the risk of passing the disease to the offspring result in significant physical and emotional burdens for patients, with a negative impact on quality of life. Data about the health-related quality of life in HAE patients from Romania are scarce. This study aimed to evaluate the disease-specific quality of life in patients with HAE from Romania and to determine associated factors. METHODS: The study included adult patients with HAE enrolled in the Romanian HAE Registry. Disease-specific quality of life was measured using the Hereditary Angioedema Quality of Life questionnaire, a cross-culturally adapted, internationally validated structured survey. RESULTS: The survey was completed by 94 patients (64.9% females; 35.1% males). The mean age of the participants was 44.9 years (SD 14.1). Most patients (88.3%) had type I HAE and were from urban areas (63.8%). The mean ages at symptom onset and diagnosis were 15.1 (SD 11.1) and 36.1 (SD 14.1) years, respectively. The mean diagnosis delay was 20.5 years (SD 14.2). In the evaluated period, all patients had at least one vial of on-demand treatment at home, and 10 were on long-term prophylaxis treatment. The general and dimensional quality of life scores were slightly above the median values of the reference scales. While the general score was not associated with sex or residence, a statistically significant, negative, weak correlation was detected with diagnostic delay. CONCLUSION: The results suggest that despite the availability of on-demand treatment for all patients, there is a need for other diagnostic and therapeutic interventions to improve the management of the disease and the quality of life for HAE patients from Romania.

Prebiotics, Probiotics, and Synbiotics-A Research Hotspot for Pediatric Obesity.

Childhood obesity is a major public health problem worldwide with an increasing prevalence, associated not only with metabolic syndrome, insulin resistance, hypertension, dyslipidemia, and non-alcoholic fatty liver disease (NAFLD), but also with psychosocial problems. Gut microbiota is a new factor in childhood obesity, which can modulate the blood lipopolysaccharide levels, the satiety, and fat distribution, and can ensure additional calories to the host. The aim of this review was to assess the differences and the impact of the gut microbial composition on several obesity-related complications such as metabolic syndrome, NAFLD, or insulin resistance. Early dysbiosis was proven to be associated with an increased predisposition to obesity. Depending on the predominant species, the gut microbiota might have either a positive or negative impact on the development of obesity. Prebiotics, probiotics, and synbiotics were suggested to have a positive effect on improving the gut microbiota and reducing cardio-metabolic risk factors. The results of clinical trials regarding probiotic, prebiotic, and synbiotic administration in children with metabolic syndrome, NAFLD, and insulin resistance are controversial. Some of them (Lactobacillus rhamnosus bv-77, Lactobacillus salivarius, and Bifidobacterium animalis) were proven to reduce the body mass index in obese children, and also improve the blood lipid content; others (Bifidobacterium bifidum, Bifidobacterium longum, Lactobacillus acidophilus, Lacticaseibacillus rhamnosus, Enterococcus faecium, and fructo-oligosaccharides) failed in proving any effect on lipid parameters and glucose metabolism. Further studies are necessary for understanding the mechanism of the gut microbiota in childhood obesity and for developing low-cost effective strategies for its management.

Cyberbullying in teenagers - a true burden in the era of online socialization.

Cyberbullying represents a major concern worldwide, especially among teenagers with major negative psychological impact. We performed a prospective online questionnaire-based study on 316 teenagers in order to assess the prevalence of cyberbullying in Romania, evaluate its psychosocial consequences, and examine the factors that may predispose them to bullying. Almost 50% of the responders stated that they have been previously bullied, with females having a higher risk of being harassed (P = .0043). Most of the victims were bullied on Facebook, Instagram, and video games. More than 53% of the victims included in our study benefit from help. We found that subjects who have been cyberbullied had a significantly higher risk of having bullied friends (P < .0001). Also, we identified a significant association between the teenagers' relationship with the parents and the incidence of bullying (P = .002). Domestic violence and the male gender were significant risk factors for committing cyberbullying (P = .0014/0.0020). Cyberbullying had a negative impact also on the harasser, and previous victims of cyberbullying had a significantly higher risk of becoming bullied (P < .0001). Also, we found a significant association between the type of substance and the perpetration of aggression (P < .0001). Further studies should focus on designing effective strategies in order to decrease the incidence of this harmful online act of bullying.

Not Every Dyspepsia Is Related to Helicobacter pylori-A Case of Esophageal Inlet Patch in a Female Teenager.

Helicobacter pylori infection is one of the main causes of dyspepsia, but it is not the only cause. Esophageal inlet patches are areas of heterotopic gastric mucosa within the esophagus and are commonly located in the cervical part of the esophagus. We report the case of a 16-year-old female, previously known to display symptoms of anxiety, who was admitted to our clinic for dyspeptic symptoms lasting for approximately 1 month in spite of the treatment with proton pump inhibitors. The clinical exam revealed only abdominal tenderness in the epigastric area, while routine laboratory tests showed no abnormalities. The upper digestive endoscopy revealed a well-circumscribed salmon-pink-colored oval lesion of approximately 10 mm in the cervical esophagus, along with hyperemia of the gastric mucosa and biliary reflux. The histopathological exam established the diagnosis of esophageal inlet patch with heterotopic antral-type gastric mucosa and also revealed regenerative changes within the gastric mucosa. We continued to treat the patient with proton pump inhibitors, as well as ursodeoxycholic acid, with favorable evolution. Although rare or underdiagnosed, esophageal inlet patches should never be underestimated and all gastroenterologists should be aware of their presence when performing an upper digestive examination in a patient with dyspeptic symptoms.

Current Worldwide Trends in Pediatric Helicobacter pylori Antimicrobial Resistance.

Helicobacter pylori (H. pylori) has acquired several resistance mechanisms in order to escape the currently used eradication regimens such as mutations that impair the replication, recombination, and transcription of DNA; the antibiotics capability to interact with protein synthesis and ribosomal activity; the adequate redox state of bacterial cells; or the penicillin-binding proteins. The aim of this review was to identify the differences in pediatric H. pylori antimicrobial-resistance trends between continents and countries of the same continent. In Asian pediatric patients, the greatest antimicrobial resistance was found to metronidazole (>50%), probably due to its wide use for parasitic infections. Aside from the increased resistance to metronidazole, the reports from different Asian countries indicated also high resistance rates to clarithromycin, suggesting that ciprofloxacin-based eradication therapy and bismuth-based quadruple therapy might be optimal choices for the eradication of H. pylori in Asian pediatric population. The scarce evidence for America revealed that H. pylori strains display an increased resistance to clarithromycin (up to 79.6%), but not all studies agreed on this statement. Pediatric patients from Africa also presented the greatest resistance rate to metronidazole (91%), but the results in terms of amoxicillin remain contradictory. Nevertheless, the lowest resistance rates in most of the African studies were found for quinolones. Among European children, the most frequent antimicrobial resistance was also noticed for metronidazole and clarithromycin (up to 59% and 45%) but with a predominance for clarithromycin as compared to other continents. The differences in antibiotic use among continents and countries worldwide is clearly responsible for the discrepancies regarding H. pylori antimicrobial-resistance patterns, emphasizing the crucial role of global judicious antibiotic use in order to control the increasing resistance rates worldwide.

The Crosstalk between Vitamin D and Pediatric Digestive Disorders.

Vitamin D is a cyclopentane polyhydrophenanthrene compound involved mainly in bone health and calcium metabolism but also autophagy, modulation of the gut microbiota, cell proliferation, immune functions and intestinal barrier integrity. The sources of vitamin D include sunlight, diet and vitamin D supplements. Vitamin D3, the most effective vitamin D isoform is produced in the human epidermis as a result of sunlight exposure. Vitamin D undergoes two hydroxylation reactions in the liver and kidney to reach its active form, 1,25-dihydroxyvitamin D. Recent studies highlighted a complex spectrum of roles regarding the wellbeing of the gastrointestinal tract. Based on its antimicrobial effect, it was recently indicated that vitamin D supplementation in addition to standard eradication therapy might enhance H. pylori eradication rates. Moreover, it was suggested that low levels of vitamin D might also be involved in the acquisition of H. pylori infection. In terms of celiac disease, the negative effects of vitamin D deficiency might begin even during intrauterine life in the setting of maternal deficiency. Moreover, vitamin D is strongly related to the integrity of the gut barrier, which represents the core of the pathophysiology of celiac disease onset, in addition to being correlated with the histological findings of disease severity. The relationship between vitamin D and cystic fibrosis is supported by the involvement of this micronutrient in preserving lung function by clearing airway inflammation and preventing pathogen airway colonization. Moreover, this micronutrient might exert anticatabolic effects in CF patients. Inflammatory bowel disease patients also experience major benefits if they have a sufficient level of circulating vitamin D, proving its involvement in both induction and remission in these patients. The findings regarding the relationship between vitamin D, food allergies, diarrhea and constipation remain controversial, but vitamin D levels should be monitored in these patients in order to avoid hypo- and hypervitaminosis. Further studies are required to fill the remaining gaps in term of the complex impact of vitamin D on gastrointestinal homeostasis.

Worldwide Prevalence and Risk Factors of Helicobacter pylori Infection in Children.

Helicobacter pylori is usually acquired during childhood. The reports from the last two decades pointed out a decrease in H. pylori prevalence across geographical areas worldwide compared to previously reported data. Most of the studies performed in America found an overall H. pylori infection prevalence of approximately 50%. The most important risk factors in America include being male, poor adherence or difficult access to treatment, and the lack of in-home water service. Despite the descending trend in prevalence worldwide, the overall prevalence in Africa remains very high (70%). Nevertheless, the prevalence of H. pylori in children without gastrointestinal who underwent screening was reported to be only 14.2%. The main risk factors in Africa are having a traditional pit or no toilet, poverty, birth order, source of drinking water, or being a farmer. Asia seems to have the widest variations in terms of H. pylori prevalence. Several risk factors were reported in Asia to be associated with this infection, such as lower income and educational level, house crowding, rural residence, ethnicity, the use of tanks as water supplies, alcohol drinking, active smoking, eating spicy food or raw uncooked vegetables, poor living conditions and sanitation. The overall prevalence of H. pylori infection in European children is almost 25%. Portugal has the highest prevalence of all European countries at 66.2% in children 13 years of age. The risk factors in European individuals consist of living in rural areas, eating unwashed fruits and vegetables, not washing hands after school, low parental education and unemployment, and short education duration. Further studies are required to identify the precise mechanisms involved in the discrepancies of H. pylori prevalence worldwide.

Rapid LC-MS/MS method for determination of drotaverine in a bioequivalence study.

A liquid chromatography coupled with tandem mass spectrometry method for the quantification of the antispasmodic drug drotaverine in human plasma was developed and validated according to the current bioanalytical guidelines. The internal standard used was imipramine. The separation was performed on a Kinetex C18 50×3mm, 2.6µm column under isocratic conditions using a mobile phase of 65:35 (v/v) formic acid 0.2% (v/v) in water and acetonitrile at 40°C with a flow rate of 0.4ml/min. The detection of drotaverine and the internal standard was performed in multiple reaction monitoring (MRM) mode using an ion trap mass spectrometer with electrospray ionization, operating in positive mode. The human plasma samples (0.24ml) were deproteinized with methanol and aliquots of 4µl from supernatants obtained after centrifugation were directly injected into the chromatographic system. The method shows a good linearity (r(2)>0.997), precision (CV<6.3%) and accuracy (bias<5.4%) over the range of 2.24-448ng/ml drotaverine in plasma. The recovery was between 91 and 98%. The limit of quantification was 2.24ng/ml. The analysis required only a 3.0min run. The developed and validated method for the determination of drotaverine in human plasma was successfully applied in a bioequivalence study, for analyzing approximately 1000 subject's samples.

Determination of free captopril in human plasma by liquid chromatography with mass spectrometry detection.

A new simple, sensitive and selective liquid chromatography coupled with mass spectrometry (LC/MS) method for quantification of captopril after precolumn derivatization with p-bromo-phenacyl-bromide in human plasma was validated. Plasma samples were analysed on a monolithic column (Cromolith Performance-RP 18e, 100 mm x 4.6 mm I.D., 3 microm) under isocratic conditions using a mobile phase of a 40:60 (v/v) mixture of acetonitrile and 0.1% (v/v) formic acid in water. The flow rate was 1 mL/min at the column temperature of 30 degrees C. In these chromatographic conditions, the retention time was 4.4 min for captopril derivative. The detection of the analyte was in MRM mode using an ion trap mass spectrometer with electrospray positive ionisation. The monitored ions were 216, 253, 255, 268, 270 m/z derived from 415 m/z for derivatized captopril. The sample preparation was very simple and consisted in plasma protein precipitation from 0.2 mL plasma using 0.3 mL methanol after the derivatization reaction was completed. Calibration curves were generated over the range of 10-3000 ng/mL with values for coefficient of correlation greater than 0.993 and by using a weighted (1/y(2)) quadratic regression. The values for precision (CV %) and accuracy (relative error %) at quantification limit were less than 9.9% and 3.9%, for within- and between-run, respectively. The mean recovery of the analyte was 99%. Derivatized samples demonstrated good short-term, long-term, post-preparative and freeze-thaw stability. This is the first reported LC-MS/MS method for analysis of captopril in human plasma that uses protein precipitation as sample processing procedure. The method is very simple and allows obtaining a very good recovery of the analyte. The validated LC-MS/MS method has been applied to a pharmacokinetic study of 50mg captopril tablets on healthy volunteers.