(1) Background: Cardiorespiratory fitness (CRF) is a prognostic factor regarding long time morbidity and mortality. To assess CRF the well-known gold standard is cardiopulmonary exercise testing (CPET), which is a time consuming and expensive test. Therefore, alternative methods for routine evaluation of CRF are needed for the general population as well as for specific patient groups such as children and young adults with congenital heart disease. The Stair Climbing Test (SCT) is a simple and resource saving test reported in the current literature. This test is used in various settings to assess different health associated risk factors including cardiorespiratory fitness, muscular resilience, therapy effectiveness or pre- and postoperative morbidity and mortality.

Elizabethkingia anophelis is an opportunistic pathogen causing lifethreatening infections in humans, particularly in immunocompromised patients, neonates and elderly. Infections caused by this species are exceptionally challenging to treat due to its multiresistance to antimicrobials. We report a case of central line-associated bloodstream infection by E. anophelis in a 2.5-year-old girl with acute lymphoblastic leukemia successfully treated with a combination of piperacillin/tazobactam and amikacin. The literature was also reviewed on paediatric infections caused by E. anophelis. Accurate identification with MALDI-TOF, or using molecular techniques, is crucial because of varying susceptibilities among species. Early, accurate diagnosis and prompt effective treatment optimize outcomes.

Furthermore, the nasal congestion typical of rhinitis can contribute to upper airway obstruction and sleep-disordered breathing. A vicious circle is created between asthma and sleep-disordered breathing: uncontrolled asthma and sleep-disordered breathing can worsen each other. In children with genetic obesity, despite alterations in the immune system, fewer allergies are found compared to the general population. The causes of this reduced allergenicity are unclear but probably involve genetic, immunological, and environmental factors. Further studies are needed to understand the mechanisms. The study emphasizes the importance of jointly evaluating and managing allergies, obesity, and sleep-disordered breathing in children, considering their close interconnection.

Severe early childhood caries remains the most common chronic disease affecting children. Its multifactorial etiology has established a controversy about which risk factors were more significant to its development. Therefore our study aimed through meticulous statistical analysis to arrange the “well agreed upon” common risk factors in order of significance, to aid the clinician in tailoring an adequate preventive program for this affected age group. The study reshuffled the risk factors contributing to severe early childhood caries and placed them in the order of their significance as follows: snacking of sugary food several times a day, increased number of siblings to 3 or more, night feeding, child self-employed brushing, mother caries experience, 2 siblings, on demand feeding, once/day sugary food, sharing utensils, 1 Sibling, male gender, father’s education, late first child dental visit, brushing time, mother’s education, no dental visit, decreased brushing frequency & no night brushing.

Lower cutoff levels in screening programs have led to an increase in the proportion of detected cases with transient hypothyroidism, leading to increase of the overall incidence of primary congenital hypothyroidism (CH) in several countries. We have performed retrospective evaluation on the data from 251,008 (96.72%) neonates screened for thyroid-stimulating hormone (TSH) level in dried blood spot specimens taken 48 hours after birth, between 2002 and 2015, using DELFIA method. A TSH value of 15 mIU/L was used as the cutoff point until 2010 and 10 mIU/L thereafter. Primary CH was detected in 127 newborns (1/1976) of which 81.1% had permanent and 18.9% had transient CH. The incidence of primary CH was increased from 1/2489 until to 2010 to 1/1585 thereafter (p=0.131). However, the incidence of permanent CH was slightly increased (p=0.922), while the transient CH incidence had 8-fold increasing after lowering the TSH cutoff level (p<0.001). In cases with permanent CH, we observed lower frequency for thyroid dysgenesis (82.7 vs. 66.7%) and higher frequency for normal in-situ thyroid gland (17.3 vs. 33.3%), for the period with reduced TSH cutoff value. Our findings support the impact of lower TSH cutoff on the increasing incidence of congenital hypothyroidism.

Expression of miR-21 has been found to be altered in almost all types of cancers and it has been classified as an oncogenic microRNA. In addition, expression of tumor suppressor gene RECK is associated with miR-21 overexpression in high-grade cervical lesions. In the present study we analyze the role of miR-21 in RECK gene regulation in cervical cancer cells. To identify the downstream cellular target genes of upstream miR-21, we silenced endogenous miR-21 expression using siRNAs. We analyzed the expression of miR-21 and RECK, as well as functional effects on cell proliferation and migration. We found that in cervical cancer cells there was an inverse correlation between miR-21 expression and RECK mRNA and protein expression. SiRNAs to miR-21 increased luciferase reporter activity in construct plasmids containing the RECK-3′-UTR microRNA response elements MRE21-1, MRE21-2, and MRE21-3. The role of miR-21 in cell proliferation was also analyzed and cancer cells transfected with siRNAs exhibited a markedly reduced cell proliferation and migration. Our findings indicate that miR-21 post-transcriptionally down-regulates the expression of RECK to promote cell proliferation and cell migration inhibition in cervical cancer cell survival. Therefore, miR-21 and RECK may be potential therapeutic targets in gene therapy for cervical cancer.

In pediatric burn care, achieving swift healing with minimal complications remains paramount. This investigation assesses polyhexamethylene biguanide (PHMB)'s role in managing superficial partial-thickness burns in children, focusing on the effects of various patient-specific factors on recovery. Through a retrospective analysis of 27 pediatric cases treated with PHMB, we explored the impact of age, burn size, dressing frequency, treatment delay, cold therapy application, and analgesic usage on the duration until reepithelialization. Notably, the majority of patients benefited from early cold therapy, yet only 1 in 3 patients received analgesics. The study reveals a mean healing time of 8.78 days, with the extent of the burn showing a strong correlation to recovery speed. Most treatments were managed outpatient, evidenced by a negligible average hospital stay. Impressively, the intervention recorded no complications. Our findings endorse PHMB as a promising treatment for second-degree burns in young patients, offering healing efficiency on par with or surpassing traditional methods, without increasing complication risks. This investigation underscores the necessity for continued exploration into the optimal application of prehospital interventions and the comprehensive benefits of PHMB in pediatric burn management, advocating for future research aimed at assessing long-term outcomes, including scar quality and patient satisfaction.

Aim: To evaluate the panmacular subthreshold micropulse laser treatment results among patients with central serous chorioretinopathy (CSC) and their correlation with functional and morphological parameters. Material and methods: The examined group included 10 non-treated and 41 treated patients with acute, recurrent, and chronic CSC (13 F, 38 M, mean age 44.11±6.5) and 14 healthy controls (6 F, 8 M, mean age 45±9.3). The BCVA examination, ophthalmoscopy, microp-erimetry, angio-OCT and OCT were performed. The medical history regarding chronic general disorders and known risk factors were recorded. Results: Complete resorption of SRF was obtained in 100% aCSC, 86.66% cCSC, and 63.63% r CSC. BCVA and RetSens significantly improved most of the patients treated in aCSC. The lowest BCVA and RetSens, but the largest pachyvessel and disease duration, were found in rCSC. A strong negative correlation between final BCVA and disease duration was found. No patient demonstrated laser lesions following treatment. Conclusions: The panmacular MPLT therapy leads to long-term enhancement of functional and morphological parameters in all CSC patients. The acute CSC patients showed the most significant improvement. The procedure is safe and could be considered a preferred treatment option for all active CSC cases. Timely treatment is crucial for beneficial outcomes.

Introduction. Intra-abdominal cystic formations represent heterogeneous pathologies with varied localization and clinical manifestation. The first challenge of a giant intra-abdominal cystic lesion is identifying the organ of origin. The clinical presentation of intra-abdominal cystic lesions varies from acute manifestations to non-specific symptoms or accidental discovery. Case presentation: A 2-year-old girl presents to the emergency unit with a fever of 38.5 Celsius, loss of appetite, and apathy. The investigations showed a gigantic intra-abdominal mass whose organ belonging could not be specified. Postoperatively, a giant mesenteric lymphangioma was evident, which was completely excised. Discussions Giant cystic formations modify the anatomical reports and become space-replacing formations, and the starting point is even more challenging to assess preoperatively. Nevertheless, the careful evaluation of the characteristics of the formation, the effect on the adjacent organs, the age of the patient, and the clinical picture can provide elements of differential diagnosis.

Background: By 2025, road traffic injuries are projected to rank third in the global burden of disease, posing a significant challenge that affects health, social well-being, and economic aspects. According to data from the Romanian Police National Statistics Center, there has been an average of 342 traffic accidents per year involving pediatric patients over the past 10 years. Materials and Methods: A retrospective research study was conducted, encompassing 358 cases of road traffic accidents identified for the study. Data collection was conducted at "St. Mary’s" Emergency Hospital for Children in Iasi, Romania, from January 2015 to December 2022. To facilitate statistical analyses, participants were categorized into three specific age groups, correlating between the anatomical region affected and different types of accidents was examined, and the classification of injury types was determined based on the characteristics of the harm inflicted. Results: An oscillating trend is observed from 2015 to 2020, with its lowest value recorded in 2017 at around 6.8% and its peak in 2019 at 20.1%. Notably, post-pandemic (Covid-19), the cases underwent a substantial decline of approximately 50%. At least 78.7% of those who did not undergo orthopedic reduction required surgery, whereas among those who underwent orthopedic reduction, only 23.4% needed surgery. Regarding the frequency of complications 7,9% of the total cases experienced complications. Conclusion: The increased frequency of pediatric traffic accidents is attributed to the extensive services provided by "St. Mary’s" Emergency Hospital for Children, Iasi, to a significant number of patients from both rural and urban areas across the seven counties of the Moldova, Romania.

Injury to the peritoneum during surgery is followed by a healing process that frequently results in the attachment of adjacent organs by a fibrous mass, referred to commonly as adhesions. Because injuries to the peritoneum during surgery are inevitable, one must understand the mechanisms of adhesion formation to prevent its occurrence. This requires a thorough understanding of the molecular sequence that results in the attachment of injured peritoneum and the development of fibrous tissue. Recent data show that fibroblasts from the injured peritoneum may play a critical role in forming adhesion tissues. Therefore, identifying changes in gene expression patterns in the peritoneal fibroblasts during the process may provide clues to the mechanisms by which adhesion develops. This review presents many papers discussing genes implied in peritoneal adhesion.

Background:Fontan completion is the last stage of univentricular repair, which drains the inferior vena cava against gravity to a higher-pressure pulmonary arterial circulation. The passivity and anti-gravity nature of this circulation render a failing Fontan, not an uncommon encounter, twenty years ago, Rodefeld and colleagues, decided to explore the feasibility of vascular pumps to support the passive nature of Fontan circulation, and since then, trials are still ongoing, and we aimed through this review to wrap up the results of these trials. Methods:A literature review has been conducted, to identify any in vivo or in vitro trial of a Fontan assist device. Several outcome parameters determined whether the trial will be included or not in this review, including, the flow rate of a pump if applicable, the number of compressions per minute if a compression device has been used, the resultant flow rate, the inferior and superior vena cava pressures, associated with each setting of the respective device, and any evidence of hemolysis or clotting within the circuit. Results:A total of ten trials have been included, with 23 different settings. Three designs have been identified, out of which two fall within the pump design, namely the connecting chamber and the intravascular pump designs; only one trial explored the possible use of a compression device. The commonest design encountered in in-vivo trials was the intravascular pump (67%). No reports of significant hemolysis or thrombosis were found. An increasing flow rate beyond 5L/min was associated with a negative outcome in the connecting chamber design, increasing upstream pressure in the SVC, while intravascular pumps did not display this limitation. Conclusion:Univentricular heart patients are a relatively small population, with very extensive needs, despite twenty years of trials, no study has yet concluded the optimal design or settings for a Fontan assist device. In this review, we identified that the intravascular pump remains the most practical design, due to its easy mode of insertion, and that it is not faced with the limitation or risk of increasing upstream resistance. There is still a long way to conclude its use as other designs such as compression devices have not yet been fully studied.

Pediatric psychology action in the pediatric clinical-surgical high complexity unit has become increasingly necessary. It allows for the possibility of integrating complex pediatric clinical-surgical operations by reducing painful effects on the emotional world of children and adolescents. The pediatric psychologist in a pediatric unit continuously oversees children and adolescents (C/A) throughout the entire therapeutic process, extending activity to parents and healthcare personnel. In ill children and adolescents, physical pain and psychological suffering follow, with minimal temporary variations, the same clinical path with continuous changes which put a strain on the ability of children, adolescents, parents and healthcare staff to cope with stress.

Background: Gastrointestinal parasitic infections are one of the global health concerns in developing countries like Bangladesh. Among them, Cryptosporidium spp. plays an essential role in causing diarrhea, malnutrition, and poor cognitive function, especially in children. The study was conducted to identify the frequency of cryptosporidium cases and other parasitic agents. Methods: A Cross-sectional observational study was conducted among 219 hospitalized children with diarrhea. The conventional microscopic technique was applied for parasitic detection. A particular staining procedure was performed to identify oocysts of Cryptosporidium spp. And PCR was conducted to determine the SSU rRNA and gp60 gene of Cryptosporidium. Results: Cyst of Giardia, ova of Ascaris lumbricoides (AL), Trichuris trichiura (TT), AL, and TT were identified in 2.3%, 1.4%, 0.5%, and 0.9% samples by wet mount preparation. The distribution of Cryptosporidium spp. was 1.4% and 4.1%, which was detected by the staining method and nested PCR. Factors independently associated with Cryptosporidium infection are unsafe water, lack of regular hand washing, and insufficiency of exclusive breastfeeding. Conclusions: This is the first report to detect the frequency of Cryptosporidium and other intestinal parasites and associated factors in Chattogram city of Bangladesh.

Depressive disorder in childhood and adolescence is a highly prevalent mood disorder that tends to recur throughout life. Untreated mood disorders can adversely impact a patient's quality of life and cause socioeconomic loss. Thus, an accurate diagnosis and appropriate treatment is crucial. However, until now, diagnoses and treatments are conducted according to clinical symptoms. Objective and biological validation are lacking. This may result in a poor outcome for patients with depressive disorder. Research has been conducted to identify the biomarkers that are related to depressive disorder. Cumulative evidence has revealed that certain immunologic biomarkers in-cluding brain-derived neurotrophic factor (BDNF) and cytokines, gastrointestinal biomarkers, hormones, oxidative stress, and certain hypothalamus-pituitary axis biomarkers are associated with depressive disorder. This article reviews the biomarkers related to the diagnosis and treatment of pediatric depressive disorders. To date, clinical biomarker tests are not yet available for diagnosis or for the prediction of treatment prognosis. However, cytokines such as Interleukin-2, interfer-on-gamma, tumor necrosis factor-alpha, and BDNF have shown significant results in previous studies of pediatric depressive disorder. These biomarkers have the potential to be used for diagnosis, prognostic assessment, and group screening for those at high risk.

Introduction Blunt carotid injuries (BCI) in pediatric trauma are quite rare. Due to the low number of cases, only a few reports and studies have been conducted on this topic. This review will discuss how frequent BCI/ BCVI on pediatric patients after blunt trauma is, what routine diagnostics look like, if a CT/ CTA scan on pediatric patients after blunt trauma is always necessary and if there are any negative health effects? Methods This literature review includes reviews, systematic reviews, case reports and original studies in english language between 1999 and 2020 that have dealt with pediatric blunt trauma and the diagnostics of BCI and BCVI. Furthermore, publications on the risk of radiation exposure on children were included in the study. For literature research, Medline (PubMed) and the Cochrane library were used. Results Pediatric BCI/ BCVI, shows an overall incidence between 0.03 – 0.5% of confirmed BCI/ BCVI cases due to pediatric blunt trauma. 1.1 – 3.5% of pediatric blunt trauma patients underwent CTA to detect BCI. Only 0.17 – 1.2% of all CTA scans shows a positive diagnosis for BCI. In children, the median volume CT dose index on a non-contrast head CT is 33 milligray, a computed tomography angiography needs at least 138 mGy. A cumulative doses of about 50 mGy almost triples the risk of leukemia, and doses of about 60 mGy triples the risk of brain cancer. Discussion Knowing that a BCI could have extensive neurologic consequences for children, it is necessary to evaluate routine pediatric diagnostics after blunt trauma. Computed tomography scans (CT) and computed tomography angiography (CTA) are mostly used in routine BCI diagnostics. However, since radiation exposure in children should be as low as reasonably achievable, it should be asked if other diagnostic methods could be used to identify risk groups. Trauma guidelines and clinical scores like the McGovern score are reflect established BCI screening options, as well as using duplex ultrasound.

Background: Endoscopic sphincterotomy (EST) has been employed for the endoscopic treatment of common bile duct stones (CBDSs), and a high success rate of stone removal has been reported. However, EST is associated with the risk of bleeding, perforation, and sphincter of Oddi function disruption. To avoid these risks, endoscopic papillary balloon dilation (EPBD) is an option for CBDS. Sphincter of Oddi function preservation decreases long-term biliary infection and gallstone recurrence. EPBD may have advantages in children who require a long follow-up. However, there have been few reports on pediatric cases, particularly in infants. Methods: From September 2017 to December 2023, we performed EPBD for four pediatric CBDSs. The patients were aged from 5 months to 8 years; including two infants aged 5 and 6 months. Furthermore, we reviewed the stone removal rate and complications of 545 ESTs performed at high-volume centers and 13 EPBD-reported cases in children with CBDSs. Results: CBDSs of all patients who underwent EPBD in our institution were successfully removed. No bleeding or perforation was noted, and pancreatitis was observed in three patients. In an analysis of 545 ESTs in children, the stone removal rate was high, ranging from 83% to 100% (mean, 96%). The incidence of pancreatitis was 0%–9.6% (mean, 4.4%), and the grade of pancreatitis was almost mild. The bleeding frequency was 1.3%–5.4% (mean, 2.7%). According to the grade of bleeding, seven and four cases were mild (64%) and moderate (36%), respectively, Compared with adult cases who underwent EST, the frequency of pancreatitis and bleeding was almost similar in children.; however once bleeding occur, it has a higher risk of leading to blood transfusion in children. Stone removal by EPBD in children was 100% successful. All complications were pancreatitis, and its frequency was 46% (6/13 patients, including five mild cases and one moderate case), which is higher than that of EST and adult cases who underwent EPBD. In most children with pancreatitis, pancreatic enzyme levels returned to normal within 2–3 days following EPBD, and no severe cases caused by EPBD were reported. Conclusions: CBDS removal by EPBD in children has a high success rate with very low risk of bleeding and perforation. Although pancreatitis frequently occurs, most cases are mild. Sphincter of Oddi function preservation by EPBD is expected to prevent long-term stone recurrence and biliary tract infection, and EPBD is considered an effective method for CBDS removal in children.

Critical aortic valve stenosis (CAVS) is a life-threatening cardiac disease of the newborn requiring urgent treatment. First-line therapy is still controversial. The aim of our study was (1) to analyze retrospectively the patients of our institution who underwent balloon aortic valvuloplasty (BAV) due to CAVS, and (2) to describe techniques for improved feasibility of the intervention using microcatheters and retrieval loops. Twelve patients underwent 23 BAVs: 1 BAV was performed in 3 patients, 2 BAVs in 7 patients, and 3 BAVs in 2 patients. Trans-valvular pressure gradient (Δp) and left ventricular shortening fraction (LVSF) improved significantly in the first two interventions; first BAV: Δp from 73.7 ±34.5 mmHg to 39.8 ±11.9 mmHg (p=0.003) and LVSF from 22.3 ± 13.5 % to 31.6 ±10.2 % (p=0.001); second BAV: Δp from 73.2 ±33.3 mmHg to 35.0 ± 20.2 mmHg (p&lt;0.001) and LVSF from 26.7 ±9.6 % to 33.3 ±7.4 % (p=0.004). Cardiac surgery during the neonatal period was avoided for all children; median time to valve surgery was 5.75 years. Few complications occurred: mild to moderate aortic regurgitation, one remediable air embolism, and one intimal injury of the ascending aorta. We conclude that BAV is a successful primary treatment for CAVS resulting in left ventricular relief, stabilization of the neonate, and a time gain until cardiac surgery.

The clinical features of increasing muscle weakening are shared by a diverse set of illnesses known as muscular dystrophies. In early childhood, males with Duchenne muscular dystrophy (DMD) exhibit proximal muscle weakening and calf enlargement, making it the most frequent X-linked disease of muscular dystrophy in children. Development of motor skills is typically delayed, and wheelchair confinement eventually leads to early death from heart or lung problems. In terms of function, ambulation, quality of life, and life expectancy, treatment approaches like corticosteroid therapy and intermittent positive pressure breathing have improved. This is a case report of a 6-year-old kid who had early ambulatory stage Duchenne Muscular Dystrophy and complained to the neuro-physiotherapy department about frequent falls, walking difficulties, and dyspnea when walking. Other grievances included being unable to get off the ground and having trouble ascending stairs. He had physiotherapy and dynamic neuromuscular stabilization for his complaints. The main goals of treatment were educating the family, respiratory training, preventing ankle plantar flexors, maintaining strength, balance and gait training.

The ultimate goal of our review is to draw clinician’s attention, especially of those who are managing pediatric patients with permanent, long-standing, ventriculoperitoneal or, less commonly, ventriculo-atrial shunts. This specific subgroup of patients may eventually suffer from severe, intractable headaches which may negatively impair their quality of daily living. In the absence of any other clinical condition that could be attributed as the cause of the headache, shunt overdrainage should not be overlooked but, on the contrary, should be seriously taken into consideration in the therapeutic armamentarium of such cases, that are difficult to be handled.

This review summarizes the most recent developments of research on protozoan parasite infections ac-quired through food and drinking water and is aimed at gathering updated knowledge on the risk factors, illnesses caused, and measures for prevention. Reports included dated from 2019 to the present and regarded recent outbreaks and cases of severe infec-tions, prevalence in different population segments and food handlers, and occurrence in food and drinking water. Cryptosporidium spp., Entamoeba histolytica, Giardia intestinalis, Trypanosoma cruzi and Toxoplasma gondii were the microorganisms most frequently involved in large outbreaks and/or severe infections, while Cyclospora cayetanensis was most frequently involved in single case reports. Cystoisospora belli was implied in severe infections in immunocompromised patients, while Blastocystis homi-nis, Sarcocystis spp., Dientamoeba fragilis, Endolimax nana and Pentatrichomonas hominis appeared to be less relevant for number of symptomatic infections and pathogenic potential. A progressive improvement in surveillance of protozoan infections and infection sources was highlighted, especially in developed countries. The apparent increase in cases was concomitant with the implementa-tion of reporting systems and the application of molecular diagnostic methods that represent valuable in-struments for establishing epidemiological links and preventing or limiting outbreaks. The pathogenic role and sources of infection should be better elucidated for some species.

Food-borne transmission is a recognized route for many viruses associated with gastrointestinal, hepatic or neurological diseases. Therefore, it is essential to identify new bioactive compounds with broad-spectrum antiviral activity is needed to exploit innovative solutions against these hazards. Lately, antimicrobial peptides (AMPs) have been recognized as promising antiviral agents. Indeed, while the antibacterial and antifungal effects of these molecules have been widely reported, their use as potential antiviral agents has not yet been fully investigated. Herein, the antiviral activity of previously identified or newly designed AMPs, was evaluated against the non-enveloped RNA viruses, Hepatitis A virus (HAV), and Murine Norovirus (MNV), a surrogate for human Norovirus. Moreover, specific assays were performed to recognize at which stage of the viral infection cycle the peptides could function. Results showed that almost all peptides displayed virucidal effects with about 90% of infectivity reduction on HAV or MNV. However, the decapeptide RiLK1 demonstrated, together with its antibacterial and antifungal properties, a notable reduction in viral infection for both HAV and MNV, possibly through direct interaction with viral particles or inhibition of the viral bonding to the cell receptors. Hence, RiLK1 could represent a versatile ‘antimicrobial agent effective against various foodborne pathogens including viruses, bacteria, and fungi.

This research ventures into the critical public health challenge of childhood obesity by exploring the dynamic interplay between psychological well-being and Body Mass Index (BMI) throughout various developmental stages of childhood. It delves into how emotional regulation, attachment dynamics, and social relationships correlate with obesity from early childhood to adolescence. Highlighting key findings, such as the negative correlation between psychological resilience and higher BMI in young children, the impact of social relationships on obesity risk during pre-adolescence, and the link between adaptive emotional strategies and higher BMI in adolescents, this study brings to the fore the nuanced relationship between psychological factors and obesity. Utilizing the interdisciplinary process of bioinformatics, this research synergizes psychometric and biomedical data to unearth psychological markers critical for crafting targeted, age-appropriate interventions. This study advocates for a holistic healthcare approach, emphasizing the integration of psychological support within obesity prevention and management strategies, thereby underscoring the indispensable role of psychological factors in the fight against childhood obesity. The application of bioinformatics methods to analyze complex datasets demonstrates how collaboration across medical specialties can enrich our understanding and response to childhood obesity, contributing significantly to the development of comprehensive, bioinformatics-enhanced healthcare solutions.

Recent studies have demonstrated a relationship between poor vitamin D status and respiratory infections and diarrhea among young children. Acute lower respiratory infections (ALRI) and diarrhea are among the two most important causes of death in under-5 children. In this analysis, we examine the extent to which vitamin-D deficiency (<10 ng/ml) predicts these outcomes using data from a randomized controlled trial (RCT) of daily folic acid and/ or vitamin B12 supplementation for six months in 6 to 30 months old children conducted in Delhi, India. Of the 960 subjects who had vitamin-D concentrations measured, 331(34.5%) were vitamin-D deficient. We found, after controlling for relevant potential confounders (age, sex, breastfeeding status, wasting, stunting, underweight, anemia status at base line and season), the risk of ALRI was significantly higher among vitamin-D deficient (OR 1.26; 95% CI: 1.03 to 1.55) compared to vitamin-D-replete children in the six months follow-up period. Vitamin-D status was not significantly associated with episodes of diarrhea and clinical pneumonia. The extent of causal relationship of vitamin-D status and ALRI needs to be explored in further studies.

Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) is one of the most controversial diseases in pediatric rheumatology. Despite its first description being published more than 25 years ago as the sudden and rapid onset of obsessive-compulsive disorder (OCD) and/or tic disorder symptoms as complications of a Group A beta-hemolytic Streptococcus (GAS) infection, precise epidemiological data are still lacking, and there are no strong recommendations for its treatment. Recent advances in the comprehension of PANDAS pathophysiology are largely attributable to animal model studies and the understanding of the roles of Ca++/calmodulin-dependent protein kinase (CaM kinase) II, disrupted dopamine re-lease in the basal ganglia, and striatal cholinergic interneurons. The diagnosis of PANDAS should be made after an exclusion process and should include prepubescent children with a sudden onset of OCD and/or a tic disorder, with a relapsing/remitting disease course, a clear temporal association between GAS infection and onset or exacerbation of symptoms, and the association with other neurological abnormalities such as motoric hyperactivity and choreiform movements. Antibiotic medications are the primary therapeutic modality. Nonetheless, there is a paucity of randomized studies and validated data, resulting in a scarcity of solid recommendations.

(1) Background: Sudden Infant Death Syndrome (SIDS) represents unexplained and sudden deaths during the sleep of infants under one year of age, despite thorough investigation. Screening for prolonged QTc or Long QT Syndrome (LQTS) should be conducted on all newborns to reduce the incidence of SIDS. Neonatal electrocardiogram (ECG) could identify congenital heart defects (CHD) early, especially those not detected at birth. Infants with prolonged QT intervals typically undergo genetic analysis for Long QT Syndrome; (2) Methods: The study involved infants aged 20-40 days, born clinically healthy, with initial ECG screening. Infants with prenatal diagnoses or signs/symptoms of CHD identified immediately after birth, as well as those who underwent ECG or echocardiogram for other clinical or historical indications, were excluded from the study. The data were analyzed using SPSS version 22.0; (3) Results: Of the 42,200 infants involved, 2,245 were enrolled, with 39.9% being males. Subsequently, 164 children (37.8% males) with prolonged QT intervals underwent further diagnostic investigations. Genetic mutations were identified in 11 out of 18 tested children. The most common mutations were LQT1 (54.5%), LQT2 (36.4%), and LQT3 (1 patient). Medications used included propranolol (39.8%), nadolol (22.2%), inderal (11.1%), metoprolol (11.1%), and no treatment (16.7%). The most common abnormalities were focal right bundle branch block (54.5%), left axis deviation (9.2%), and nonspecific ventricular repolarization abnormalities (7.1%). Multiple anomalies were found in 0.47% of children with focal right bundle branch block. Structural abnormalities were associated with specific features in 267 patients (11.9%), primarily isolated patent foramen ovale (PFO) at 61.4%; (4) Conclusions: The screening has proven effective in early diagnosing Long QT Syndrome and other cardiac rhythm anomalies, with additional benefits in detecting mutations and/or QTc prolongations in family members. Identifying other ECG abnormalities and congenital heart malformations further enhances the benefits of the screening.

(1) Background: Sleep disordered breathing represent a growing public health concern, especially among children and adolescents. Full-night polysomnography is considered the gold standard for diagnosing obstructive sleep apnea. Our goals are to identify personal and environmental risk factors for the onset and persistence of sleep respiratory disorders. We also want to investigate the differences in neuropsychological profiles; (2) Methods: This is an observational, retrospective cohort study. We collected information on adenoidectomy or adenotonsillectomy. We reviewed the clinical history and preoperative visits and collected data through a telephone questionnaire. Pediatric Sleep Questionnaire (PSQ) and the Pediatric Quality of Life Inventory (PedsQL) are questionnaires used for screening sleep respiratory disorders in children. The data were statistically analyzed it using SPSS version 22.0 for Windows (SPSS Inc., Chicago, IL); (3) Results: The study involved 138 patients, but only 100 parents participated. A higher percentage of patients with sleep disordered breathing were observed to have mothers who smoked during pregnancy. A smaller proportion of patients with sleep disordered breathing had a habit of using a pacifier. A rise in physical results is associated with a reduction in the PSQ at follow-up (p=0.051). An increase of overall academic achievement is associated with an average decrease in the PSQ at follow-up (p&lt;0.0001). A more significant proportion of patients undergoing adenotonsillectomy were observed to have a history of prematurity and cesarean birth (4) Conclusions: These results provide essential information on the effectiveness and effects of adenotonsillectomy intervention compared to adenoidectomy intervention and the factors associated with SDB in children undergoing these interventions.

Arboviruses are infections caused by arboviruses that may be either symptomatic or asymptomatic, according to individuals' resistance and immune response, which dietary patterns can influence. Thus, this study aimed to investigate the possible association between the occurrence of clinical manifestations of arboviruses and the dietary pattern of the population studied. The study was conducted in a rural population in the metropolitan area of Belém, Pará State, Brazil. The sampling consisted of 95 individuals during a febrile outbreak. Two investigations were conducted: clinical-epidemiological-dietary and laboratory investigation based on blood samples taken for arbovirus analysis. Out of the 95 individuals studied, more than half (57.89%) showed clinical manifestations. Following the laboratory serology (HI and IgM ELISA) analyses, viral isolation in C6/36 cells, and viral genome detection (RT-qPCR), the final diagnosis of the cases was 47.37% Oropouche Fever, 2.11% Oropouche Fever and Chikungunya Fever, and 1.05% Mayaro Fever. Regarding dietary pattern, as for the comparison analyses, statistical significance was observed between dietary pattern and classification regarding the presence of symptoms (p<0.05); after the correspondence analysis, symptomatic cases were more associated with a bad dietary pattern, while asymptomatic cases were more associated with a good dietary pattern.

Pediatric onset multiple sclerosis (POMS), characterized by the onset of multiple sclerosis before the age of 18, is gaining increased recognition. Approximately 5 percent of MS cases manifest before the age of 18, with less than 1 percent occurring before the age of 10. Despite its rarity, pediatric MS exhibits distinct characteristics, with an association between younger age at onset and a comparatively slower disease progression. Despite this slower progression, individuals with POMS historically reach disability milestones at earlier ages than those with adult-onset multiple sclerosis. While various immunomodulatory agents demonstrate significant benefits in MS treatment, such as reduced relapse rates and slower accumulation of brain lesions on magnetic resonance imaging (MRI), the majority of disease-modifying therapies (DMTs) commonly used in adult MS lack evaluation through pediatric clinical trials. Current evidence is predominantly derived from observational studies. This comprehensive review aims to consolidate existing knowledge on the mechanisms of action, efficacy, safety profiles, and recommended dosages of available DMTs specifically in the context of pediatric MS. Furthermore, the review outlines recent advancements and explores potential medications still in developmental stages, providing a thorough overview of the current landscape and future prospects for treating POMS.

Elevated immunoglobulin E (IgE) levels are commonly associated with allergies. However, high IgE levels are also found in several other infectious and non-infectious disorders. Elevated IgE levels typically suggest allergies, eczema, or recurrent skin infections. Very high IgE levels are uncommon in patients with active eczema but typically reflect a monogenic atopic condition or inborn immune defects with an atopic phenotype. The aim of our research is to identify if the possible cause of high IgE levels is also dependent on external factors, age, or associated recurrent pathologies such as infections. To answer this question, we performed a one-year retrospective study that included 200 hospitalized children who had at least two viral or bacterial infections in the six months preceding hospitalization. Measurements of IgE and allergen panels (respiratory and digestive) using blood samples revealed that individuals who tested positive for the body’s synthesis of hyperimmunoglobulin E were not observably allergic to any potential allergens despite having higher total serum IgE. According to the results, there was a strong correlation between elevated IgE serum levels and a history of infectious diseases among the patients.

Methicillin-resistant Staphylococcus aureus (MRSA) infections, in particular biofilm-organized bacteria, remain a clinical challenge and a serious health problem. Rifabutin (RFB), an antibiotic of the rifamycins class, has shown in previous work excellent anti-staphylococcal activity. Here, we proposed to load RFB in liposomes aiming to promote the accumulation of RFB at infected sites and consequently enhancing the therapeutic potency. Two clinical isolates of MRSA, MRSA-C1 and MRSA-C2, were used to test the developed formulations, as well as the positive control, vancomycin (VCM). RFB in free and liposomal forms displayed high antibacterial activity, with minimal inhibitory concentrations (MIC) ranging from 0.009-0.013 μg/mL and MBIC50 values ranging from 0.008-0.012 μg/mL, in planktonic and biofilm bacteria, respectively. Confocal microscopy studies demonstrated the rapid internalization of unloaded and RFB-loaded liposomes in the bacterial biofilm matrix. In murine models of systemic MRSA-C1 infection, Balb/c mice were treated with RFB formulations and VCM at 20 and 40 mg/kg of body weight, respectively. Obtained data proved the superior therapeutic effectiveness of RFB formulations compared to Control and VCM groups even using a two-fold lower therapeutic dose as demonstrated by significantly reduced bacterial burden and growth index values in major organs. In addition, RFB formulations were the only formulations associated with 100% survival. Globally, this study emphasizes the potential of RFB nanoformulations as an effective and safe approach against MRSA infections.

Vascular anomalies are a diverse group of abnormal blood vessel developments that can occur at birth or shortly afterward. Embolization and sclerotherapy have been utilized as a treatment option for these malformations but may cause moderate to severe pain. This study aims to evaluate the utilization of peripheral nerve blocks in opioid consumption, pain scores, and length of stay. A retrospective chart review was conducted at the UPMC Children's Hospital of Pittsburgh for all patients who underwent embolization and sclerotherapy between 2011 and 2020. Patient data was collected to compare opioid consumption, pain scores, and length of stay. Eight hundred fifty-four procedures were performed on 347 patients. The morphine milligram equivalent per kilogram mean ratio between groups was 0.9 (0.86, 0.95) with a p-value of &lt;0.001. The pain score mean ratio was –1.17 (–2.2, -0.1) and a p-value of 0.027. Length of stay had a mean ratio of 0.94 (0.4, 2) and a p-value of 0.875. By decreasing opioid consumption and postoperative pain scores, peripheral nerve blocks may have utility in patients undergoing embolization and sclerotherapy while not clinically increasing the length of stay for patients. Their use should be individualized and carefully discussed with the interventional radiologist.

Objective: The causes of vertigo and dizziness in children are diverse and require attention from various specialists. Numerous authors have reported that the commonest type of vertigo in children is migraine-associated vertigo (vestibular migraine and benign paroxysmal vertigo of childhood - BPV). We aimed to check whether this could be applied to our group of patients. Materials and methods: A retrospective case series of 257 consecutive pediatric vertigo and diz-ziness patients referred to the tertiary pediatric ENT clinic from 2015 to 2020. Patients received a complete audiovestibular workup and were referred to pediatric neurologists and other special-ists depending on the signs and symptoms. Results: Of 257 children aged 1-17 years, almost one fifth of them, 49/257 (19.1 %) had a central type of vertigo, 20/257 of them (7.8%) had benign paroxysmal vertigo of childhood and 4/257 (1.6%) had a migrainous type of vertigo. Most of the children, 112/257 (43.6%), remained unclas-sified, without a final diagnosis. Conclusion: Due to the numerous possible causes, a child presenting with dizziness and vertigo requires a multidisciplinary approach. In the majority of cases, vertigo spells are self-limiting. They stop spontaneously and sometimes remain clinically undiagnosed. The most prevalent reasons for pediatric vertigo may be temporary hemodynamic (vaso-vagal) and psychological imbalance.

Viral co-infections, where a host is infected by multiple viruses simultaneously, are common in the human population. Human viral co-infections can lead to complex interactions between viruses and the host immune system, affecting the clinical outcome and posing challenges for treatment. Understanding the types, mechanisms, impacts, and identification methods of human viral co-infections is crucial for the prevention and control of viral diseases. In this review, we first introduce the significance of studying human viral co-infections and summarize the current research progress and gaps in this field. We then classify human viral co-infections into four types based on the pathogenic properties and species of the viruses involved. Next, we discuss the molecular mechanisms of viral co-infections, focusing on virus-virus interactions, host immune responses, and clinical manifestations. We also summarize the experimental and computational methods for identifying viral co-infections, emphasizing the latest advances in high-throughput sequencing and bioinformatics approaches. Finally, we highlight the challenges and future directions in human viral co-infection research, aiming to provide new insights and strategies for the prevention, control, diagnosis, and treatment of viral diseases. This review provides a comprehensive overview of the current knowledge and future perspectives on human viral co-infections, and underscores the need for interdisciplinary collaborations to address this complex and important topic.

Alzheimer´s disease (AD) is characterized by the brain deposition of senile plaques composed by amyloid-β peptides (Aβ) that increase inflammation. An endogenous peptide derived from the insulin-like growth factor (IGF)-I, glycine-proline-glutamate (GPE) has IGF-I-sensitizing and neuroprotective actions. Here, we examined the effects of GPE on Aβ levels and hippocampal inflammation generated by the intracerebroventricular infusion of Aβ25-35 during 2 weeks (300 pmol/day) in ovariectomized rats and the signaling-related pathways and levels of Aβ-degrading enzymes associated with these GPE-related effects. GPE prevented the Aβ-induced increase in the phosphorylation of p38 mitogen-activated protein kinase and the reduction in activation of signal transducer and activator of transcription 3, insulin receptor substrate-1 and Akt, as well as on interleukin (IL)-2 and IL-13 levels in the hippocampus. The functionality of somatostatin, measured as the percentage of inhibition of adenylate cyclase activity and the levels of insulin-degrading enzyme were also preserved by GPE co-treatment. These findings indicate that GPE co-administration may protect from Aβ insult by changing hippocampal cytokine content and somatostatin functionality through regulation of leptin- and IGF-I-signaling pathways that could influence the reduction in Aβ levels through modulation of levels and/or activity of Aβ proteases.

Bio-absorbable stents are a novel tool which relieve stenosis and then resorb as the patient grows, avoiding obligatory re-intervention. This case describes the novel use of an iron bio-absorbable stent in a child with surgically repaired Tetralogy of Fallot who post-operatively developed a severely stenotic right ventricular outflow tract.

Background: clubfoot is a common congenital deformity. The Ponseti technique, involving early corrective manipulations followed by the application of long leg casts and Achilles tenotomy, is widely accepted as the preferred treatment. Rapid healing of the tendon after surgery has been documented, but the aspect regarding tendon structure and properties is not known. Three cases of Achilles tendon rupture in adolescent previously treated for clubfoot have been described in the literature. Since rupture is a rare event in this age group a possible correlation with previous surgery has been hypothesized. The primary aim of the study was to compare the ultrasound findings of the Achilles tendon, in patients treated for clubfoot, between patients treated with casting alone and the ones who underwent surgery (percutaneous tenotomy or Z-plasty lengthening). Methods: 22 asymptomatic patients, (34 feet) median age 12 years, previously treated for clubfoot, were recruited for this study; the patients underwent an Achilles tendon ultrasound examination during a follow-up outpatient visit. Results: a greater thickness and structural alterations with presence of hypoechoic areas of the operated tendons compared to those treated with plaster alone were observed (p value: 0.0498 and

Background: DICER1, cancer predisposition syndrome (CPS), seems to escape timely diagnosis in pediatric patients. Case report 1: A 16-year-old female patient was referred to the endocrinology ward due to a large goiter. Her medical history indicated normal sexual maturation, with menarche occurring at 13.5 years. Over the past 2.5 years, she developed pronounced androgenic symptoms, including a deepened male voice, facial, back and neckline acne, hirsutism, and menstrual irregularities leading to secondary amenorrhoea. A thyroid ultrasound identified a multinodular goiter with cystic-solid lesions containing calcifi-cations. An abdominal ultrasound identified a 5.7x6.9 cm solid mass in the right adnexal region, displacing the uterus to the left. Histopathological examination confirmed a Sertoli-Leydig cell tumor. The patient was subjected to total thyroidectomy. Histopathology revealed benign follicular cell-derived neoplasms. Thyroid follicular nodular disease was diagnosed bilaterally. DNA analysis using NGS, confirmed by the Sanger method, revealed a pathogenic heterozygotic variant c.2953>T [p.Gln985*] in exon 18 of DICER1 gene. Case report 2: A 12-year-old male patient was admitted to the pediatric surgery unit due to a 33 ml goiter. A month prior to admission, the patient discovered a palpable nodule in his neck, accompanied by hoarseness. An ultrasound revealed a multinodular goiter. Molecular analysis revealed a pathogenic heterozygotic variant c.2782C>T [p.Gln928Ter] in exon 17 of DICER1 gene. Subsequently, a total thyroidectomy was performed, and histopathological examination revealed thyroid follicular nodu-lar disease bilaterally. Conclusion: Multinodular goiter, although rare in pediatric population, when accompanied by characteristic ultrasound and histopathological features, and by additional features such as androgen excess, warrants exclusion of DICER1 syndrome.

The present study was performed to examine that transforming growth factor beta (TGF-β) in root-surrounding tissues on deciduous teeth during the physiological root resorption regulates the differentiation induction into odontoclast. We prepared root-surrounding tissues with (R) or without (N) physiological root resorption scraped off at three regions (R1-R3 or N1-N3) from the cervical area to the apical area of the tooth and measured both TGF-β and the tartrate-resistant acid phosphatase (TRAP) activities. The TGF-β activity level was increased in N1-N3, whereas the TRAP activity was increased in R2 and R3. In vitro experiments for RANKL-mediated osteoclast differentiation revealed that TGF-β in N1-N3 and R1-R3 enhanced the TRAP activity in RAW264 cells. A genetic study indicated that the mRNA level of TGF-β1 in N1 and N2 was significantly increased, and corresponded with that of osteoprotegerin (OPG). In contrast, the expression level of receptor activator of NF-κB ligand (RANKL) was increased in R2 and R3. Our findings suggest that TGF-β is closely related to the regulation of OPG induction and RANKL-mediated odontoclast differentiation depending on the timing of RANKL and OPG mRNA expression in the root-surrounding tissues of deciduous teeth during physiological root resorption.

Alzheimer’s disease (AD) is a chronic neurodegenerative disease associated with the overproduction and accumulation of amyloid-β peptide and hyperphosphorylation of tau proteins in the brain. Despite extensive research on the amyloid-based mechanism of AD pathogenesis, the underlying cause of AD remains poorly understood. No disease-modifying therapies currently exist, and numerous clinical trials have failed to demonstrate any benefits. The recent discovery that the amyloid-β peptide has antimicrobial activities supports the possibility of an infectious aetiology of AD and suggests that amyloid-β plaque formation might be induced by infection. AD patients have a weakened blood-brain barrier and immune system and are thus at elevated risk of microbial infections. Such infections can cause chronic neuroinflammation, production of the antimicrobial amyloid-β peptide, and neurodegeneration. Various pathogens, including viruses, bacteria, fungi, and parasites have been associated with AD. Most research in this area has focused on individual pathogens, with herpesviruses and periodontal bacteria being most frequently implicated. The purpose of this review is to highlight the potential role of multi-pathogen infections in AD. Recognition of the potential coexistence of multiple pathogens and biofilms in AD's aetiology may stimulate the development of novel approaches to its diagnosis and treatment. Multiple diagnostic tests could be applied simultaneously to detect major pathogens, followed by anti-microbial treatment using antiviral, antibacterial, antifungal, and anti-biofilm agents.

Aim: The purpose of this study was to collect prevalence data of Hypomineralized Second Primary Molars (HSPM) and Molar Incisor Hypomineralization (MIH) among pediatric patients treated by dental practitioners in Northern Italy and assess the practitioners’ awareness of these conditions. Methods: A cross-sectional pilot study was conducted using a structured online questionnaire administered through Google Forms. The survey comprised 10 single-choice questions addressing the prevalence of opacities affecting molars and an index of HSPM and MIH in caries-free children aged 6-9 years, categorized by percentage. Results: A total of 315 dentists participated in the survey, yielding a response rate of 31.5%. The majority of respondents (59%) reported HSPM prevalence in 1-25% of their patients, while 18% observed no opacity in any of their patients. MIH was observed in HSPM patients in 1-25% and 25-50% of cases, as reported by 44% and 31% of respondents, respectively. Among non-HSPM patients, MIH was observed in 1-25% of children (reported by 74% of respondents). Conclusion: The findings from this pilot survey show substantial agreement with existing prevalence data on HSPM and MIH reported in the literature. The co-occurrence rate of HSPM and MIH defects supports the hypothesis of HSPM potentially serving as a predictor of MIH. The study underscores a significant need to enhance awareness of these defects for early diagnosis and effective management. Additionally, there is a call for the promotion of standardized diagnostic protocols to obtain more accurate epidemiological data.

Opossums, native to the Americas, are unique marsupials with over 100 species. The Common Opossum and Virginia Opossum are notable species. They are nocturnal, omnivorous, and adapt to various habitats. Their reproduction involves a short gestation and marsupial pouch development. Despite their ecological benefits like seed dispersal and insect control, their proximity to human habitats exposes them to pathogens, posing public health risks. These include protozoa, helminths, and arthropods that can spread zoonotic parasites and vector-borne diseases. The marsupial immune system, including opossums, is complex, rivaling eutherian mammals. Key immune genes were identified in the grey short-tailed opossum genome. CD1 protein and VpreB surrogate light chain were also found. Marsupials are proposed as ideal models for studying developmental immunology. A West Indian opossum (Didelphis marsupialis) was found and examined. Blood tests revealed abnormalities, including a low white blood cell count and signs of anemia. The results contribute to understanding the species’ health and adaptability in the wild.

Congenital heart disease (CHD) is a prevalent congenital disorder diagnosed with high frequency, affecting approximately 0.8% to 1.2% of all live births. Research has demonstrated that the use of pulse oximetry and clinical examination as a screening tool for CHD diagnosis has proven extremely valuable. We conducted a retrospective longitudinal study over a 3-year period that involved screening 1188 newborns admitted to the NICU during the first 72 hours of life within this timeframe. 201 newborns were diagnosed with CHD. Almost all (n=198) had a positive screening test during the 72-hour period, while 3 had a negative screening test, but were later diagnosed using echocardiography. The prevalence rate was 16.67%. A confusion matrix was constructed with 198 true positives (TP), 3 false negatives (FN), no false positives (FP), and 987 true negatives (TN). The sensitivity of the screening test was 98.51%, while the specificity 100%, with no false positives. In our study, a total of 9 deaths occurred. Using the Kaplan-Meier method, the survival probability appeared to be slightly above 0.9 (95.5%), indicating that almost all patients survived past 72 hours after being diagnosed with CHD. Pulse oximetry is an effective, low cost and easy-to-use method and a useful tool to assess and lead to the diagnosis of CHD.

According to the World Health Organization, approximately 20 million people worldwide are infected annually with the hepatitis E virus (HEV). There are 4 main genotypes of HEV. Genotype 1 and genotype 2 are common in developing countries and are transmitted by contaminated water from a fecal-oral route. Genotype 3 and genotype 4 are common in developed countries and can lead to occasional transmission to humans by undercooked meat. Hepatitis E virus 1 and HEV3 can lead to fulminant hepatitis, and HEV3 can lead to chronic hepatitis and cirrhosis in immunocompromised patients. The majority of patients with HEV infection are asymptomatic and usually have spontaneous viral clearance without treatment. However, infection in immunocompromised individuals can lead to chronic HEV infection. Both acute and chronic HEV infections can have extrahepatic manifestations. No specific treatment is required for acute HEV infection, no treatment has been approved in chronic infection and no HEV vaccine has been approved by the (United States) Food and Drug Administration. This review focuses on the molecular virology (HEV life cycle, genotypes, model systems, zoonosis), pathogenesis, clinical manifestation, and treatment of chronic HEV infection, especially in immunocompromised patients, to provide clinicians a better understanding of the global distribution of these infections and the significant effect they can have on immunocompromised patients.

Turner syndrome (TS) is caused by a complete or partial absence of an X or Y chromosome, including chromosomal mosaicism, affecting 1 in 2,500 female live births. Sister chromatid exchange (SCE) is used as a sensitive indicator of spontaneous chromosome instability. Cells from mosaic patients constitute useful material for SCE evaluations as they grow under the influence of the same genetic background and endogenous and exogenous factors. We evaluated proliferation dynamics and SCE frequencies of 45,X and 46,XN cells of 17 mosaic TS patients. In two participants, 45,X cells exhibited a proliferative disadvantage in relation to 46,XN cells after 72h of cultivation. The analysis of mean PI showed significant differences between 45,X and 46,XN lineages; however there were no intraindividual differences. On the other hand, mean SCE frequencies showed no differences between the two lineages, but there were intraindividual differences in 5 patients. The absence of mean SCE frequency differences between 45,X and 46,XN lineages may indicate that both were equally unstable, as more than 70% of the 46,XN lineages had an anomalous karyotype. However, 46,XN had a higher mean PI, suggesting that the amount of cells with a karyotype distinct from 45,X may increase with time in mosaic TS women.

Pulmonary arterial hypertension is a rare disease with high mortality despite recent therapeutic advances. The disease is caused by both genetic and environmental factors, and likely gene x environment interactions. While PAH can manifest across the lifespan, pediatric-onset disease is particularly challenging because it is frequently associated with a more severe clinical course and comorbidities including lung/heart developmental anomalies. In light of these differences, it is perhaps not surprising that emerging data from genetic studies of pediatric-onset PAH indicate that the genetic basis is different than that of adults. There is a greater genetic burden in children, with rare genetic factors contributing to at least 36% of pediatric-onset idiopathic PAH (IPAH) compared to ~11% of adult-onset IPAH. De novo variants are frequently associated with PAH in children, and contribute to at least 15% of all pediatric cases. The standard of medical care for pediatric PAH patients is based on extrapolations from adult data. However, the increased etiologic heterogeneity, poorer prognosis and increased genetic burden for pediatric-onset PAH calls for a dedicated pediatric research agenda to improve molecular diagnosis and clinical management. A genomics-first approach will improve the understanding of pediatric PAH and how it is related to other rare pediatric genetic disorders.

Polyelectrolyte-drug complexes are interesting alternatives to improve unfavourable drugs properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use as inhalable formulations. Particulate-solid HA-VAN25 complex by spray drying from an aqueous dispersion was obtained. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern by X-ray was observed. The powder density, geometric size and morphology showed a suitable aerosolization and aerodynamic performance of the powder, indicating the capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 hours. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus, showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN25 exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment.

Hereditary polyposis syndromes are rare but potentially devastating conditions which require multidisciplinary care from an early age. Societal guidelines serve as the framework for disease diagnosis, surveillance and treatment. Guidelines are based on expert opinion and ideally are evidence-based; however, recommendations may vary among different societies and can result in discordant care. This paper aims to summarize key differences in management based on societal guidelines for pediatric polyposis syndromes and identify some of the factors which may contribute to divergence in care.

Flaviviruses are a group of positive sense single-stranded RNA viruses predominantly transmitted by arthropods (mainly mos-quitoes), that cause severe endemic infections and epidemics on a global scale. It represents a major cause of systemic morbidity and death that are expanding worldwide. Among this group, Dengue fever, West Nile virus, Yellow Fever, Japanese Encephalitis, and recently Zika virus have been linked to a spectrum of ocular manifestations. The latter encompass subconjunctival hemor-rhage and conjunctivitis, anterior and posterior uveitis (inclusive of vitritis, chorioretinitis, and retinal vasculitis), maculopathy, retinal hemorrhages, and optic neuritis. Clinical diagnosis of these infectious diseases is primarily based on epidemiological data, history, systemic symptoms and signs, and the pattern of ocular involvement. Diagnosis confirmation relies on laboratory testing, including RT-PCR and serological testing. Ocular involvement typically follows a self-limited course but can result in irreversible visual impairment. Effective treatment for flavivirus infections is currently unavailable. Prevention remains the mainstay for arthropod vector and zoonotic disease control. Effective vaccines are available only for Yellow Fever virus, Dengue virus and Japanese Encephalitis virus. This review comprehensively summarizes the current knowledge regarding the ophthalmic mani-festations of the foremost flavivirus-associated human diseases.

Chronic pain is a serious health concern and potentially debilitating condition, leading to anxiety, depression, reduced productivity and functionality, and poor quality of life. This condition can be even more detrimental and incapacitating in the pediatric patient population. In low and middle income countries (LMICs), pain services are inadequate or unavailable, leaving most of the world's pediatric population with chronic pain untreated. Many of these children in LMICs are suffering without treatment, and often die in pain. Awareness and advocacy for this population must be prioritized. We reviewed the available literature on the chronic pediatric pain burden in LMICs, barriers to treatments, and current efforts to treat these patients.

Iron deficiency (ID) is by far the most common nutritional disorder in developing and developed countries. When left untreated, ID leads to anemia. Although the usual recommended treatment for iron deficiency anemia (IDA) is oral iron therapy with countless products, such therapy necessitates administration for &gt;3-6 months with questionable patient compliance since most oral iron products have an unpleasant metallic aftertaste and cause intestinal side effects. In addition, in certain gastrointestinal conditions, such as inflammatory bowel diseases or untreated gluten-sensitive enteropathy, oral iron therapy is contraindicated or unsuccessful. Intravenous iron is considered safe in adults, where adverse events are mild and easily managed. The experience with parenteral iron in children is much more limited and many pediatricians appear reluctant to use it because of uncorroborated fears of serious anaphylactic reactions. In the current article, we thoroughly review the available pediatric literature on the use of all commercially available parenteral iron products except ferumoxytol, which was recently removed from the market. We conclude that parenteral iron appears to be safe in children, it works faster than oral iron and the newer third-generation products allow replacement of the total iron deficit at a single setting.

Spinal Cord Injury in children can be a devastating condition in children with profound implications for their overall health and quality of life. In this review we aim to provide a concise overview of the key aspects associated with SCI in pediatric population. Firstly, we discuss the etiology and epidemiology of SCI in children, highlighting the diverse range of causes. We explore the unique anatomical and physiological characteristics of the developing spinal cord that contribute to the specific challenges faced by pediatric patients. Next, we delve into the clinical presentation and diagnostic methods, emphasizing the importance of prompt and accurate diagnosis to facilitate appropriate interventions. Furthermore, we approach the multidisciplinary management of pediatric SCI, encompassing acute medical care, surgical interventions, and ongoing supportive therapies. Finally, we explore emerging research and innovative therapies in the field and we emphasize the need for continued advancements in understanding and treating SCI in children to improve their functional independence and overall quality of life.

The cavovarus deformity is characterized by a pathologic longitudinal arch elevation caused by a severe hindfoot varus and forefoot equinus deformity. This disorder includes multiple anomalies and therapies and affects 25% of the population. Cavus feet usually indicate neurologic illness, which affects sensory and motor nerves. Clinical and radiological evaluations are needed to establish each patient's optimum therapy. Failure to identify a neurologic illness may lead to inappropriate surgical treatment, recurrence, and reconstructive failure. In progressive anomalies, surgical procedures must be performed quickly in a phased protocol to prevent the malalignment from worsening. Soft tissue surgeries, osteotomies, and arthrodesis are surgical options for patients. To aid and lead practitioners in selecting the most appropriate therapy for their patients daily, we have included the most common therapeutic options currently available in this article.

Pediatric obstructive sleep apnea (OSA) has significant negative effects on health and behavior in childhood including depression, failure to thrive, neurocognitive impairment, and behavioral issues. It is strongly associated with an increased risk for chronic adult disease such as obesity and diabetes, accelerated atherosclerosis, and endothelial dysfunction. Accumulating evidence suggests that adult-onset non-communicable diseases may originate from early life through a process by which an insult applied at a critical developmental window causes long-term effects on the structure or function of an organism. Recently, much attention has been paid to the role of epigenetic mechanisms in the pathogenesis of adult disease susceptibility. Epigenetic mechanisms that influence adaptive variability include histone modifications, non-coding RNAs, and DNA methylation. This review will highlight what is currently known about the phenotypic associations of epigenetic modifications in pediatric OSA and will emphasize the importance of epigenetic changes as both modulators of chronic disease and potential therapeutic targets.

In all mammals, the circulating pool of MLT is synthesized in the pineal gland, during the night darkness hours. Its main function is that of synchronizing the organism in the photoperiod. In contrast, extra-pineal MLT is synthesized in peripheral organs, does not follow any circadian rhythm nor circulates and plays a detoxifying and cytoprotective action. Circulating MLT may stimulate both innate and acquired immune responses by its circadian action and by activating high affinity receptors on immunocompetent cells. Extra-pineal MLT may have anti-oxidant and anti-inflammatory effects dampening the innate immune response. These two seemingly divergent roles may be considered as two faces of the same coin. In fact, the integration of both circulating and extra-pineal MLT functions might generate a balanced and effective immune response against microbial pathogens. The studies described in this review investigated the effect of exogenous MLT in various models of infectious diseases using extremely different doses and treatment schedules. None of them evaluated the possibility to integrate the non-circadian anti-inflammatory effect with the circadian immunoenhancing action of MLT. As a consequence, in spite that most studies agree that MLT has a beneficial effect against infections, it seems difficult to draw any definite conclusion about its possible therapeutic use.

The rapid rise in research and development following the discovery of photodynamic therapy to establish novel photosensitizers and overcome the limitations of the technology soon after its clinical translation has given rise to a few significant milestones. These include several novel generations of photosensitizers, the widening of the scope of applications, leveraging of the offerings of nanotechnology for greater efficacy, selectivity for the disease over host tissue and cells, the advent of combination therapies with other similarly minimally invasive therapeutic technologies, the use of stimulus-responsive delivery and disease targeting, and greater penetration depth of the activation energy. Brought together, all these milestones have contributed to significant enhancement of what is still arguably a novel technology. Yet the major applications of photodynamic therapy still remain firmly located in neoplasms, from where most of the new innovations appear to launch to other areas, such as microbial, fungal, viral, acne, wet age-related macular degeneration, atherosclerosis, psoriasis, environmental sanitization, pest control, and dermatology. The core value proposition of combinations of photodynamic therapy is that they enhance the leading alternative and are proposed to overcome challenges of the leading clinical anticancer and antibacterial methods, mainly due to its inherent barriers against the emergence of resistance and its rapid development of targeted and high precision therapy. Combinations with chemotherapy and radiotherapy and demonstrated applications in mop-up surgery adventitiously promise to repurpose these top three clinical tools. This review will navigate the vast and increasing innovations that have been created so as to obviate novel areas of further innovation.

Predominantly antibody deficiencies (PAD) represent the most common type of primary immu-nodeficiencies in humans, characterized by a wide variation in disease onset, clinical manifesta-tions, complications and outcome. Considering that the prevalence of PAD in Greece is unknown and there is limited knowledge on clinical and laboratory characteristics of affected patients, we conducted a nationwide study, including 153 patients (male/female: 66/87; median age: 43.0 years; range: 7.0-77.0) diagnosed and/or followed-up between April 2007 to September 2023. Furthermore, we classified our cohort into five Groups according to their medical history, im-munoglobulin levels, and CTLA4-mutational status: 123 had common variable immunodeficien-cy (CVID), 12 with CVID-like disease (with a history of a previous B-cell depletion immunother-apy for autoimmune or malignant disease), seven with combined IgA and IgG subclass deficien-cies, five with immune dysregulation syndrome and CTLA4 defects, and six with unclassified hypogammaglobulinemia. We demonstrated a remarkable delay of PAD diagnosis, several years after the onset of related symptoms (median: 9.0 years, range: 0-43.0). Family history of PAD was only 11.8%, with the majority of patients considered sporadic cases. Most patients were diag-nosed in the context of a diagnostic work-up for recurrent infections, or recurrent/resistant auto-immune cytopenias. Interestingly, ten patients (5.6%) had no history of infection, diagnosed due to either recurrent/resistant autoimmunity, or during a work-up of their medical/family history. Remarkable findings included an increased prevalence of lymphoproliferation (60.1%) and atopy (24.2%), while 39 patients (25.5%) developed bronchiectasis and 16 (10.5%) granulomatous dis-ease. Patients with CTLA4 defects displayed a variable clinical phenotype at diagnosis, with four patients diagnosed during a work-up of re-current infections, while one also displayed a massive splenomegaly. Cancer was a common complication in our cohort (25 patients, 16.3%), with B-cell malignancies representing the most common neoplasms (56.7%). Our findings indicate the necessity of awareness about PAD and their complications, aiming for early diagnosis and appropriate management of affected patients

Introduction: Obstructive Sleep Apnea (OSA) is a respiratory condition identified by the partial or complete obstruction of the upper air passages during sleep. These episodes can lead to complications in neurobehavioral and cognitive domains and cardiovascular issues, especially in children. The involvement of OSA in ocular health during adulthood has been reported, but it remains a topic of debate in pediatric cases. Objective: This review aims to analyze the correlation between OSAS and ocular health in children. Specifically, it investigates the effects of OSA on ocular structures and conditions and explores potential improvements through treatment. Subjects and Methods: The research employed three search engines: PUBMED/MEDLINE, SCOPUS, and WebOfScience. After initial identification, 120 irrelevant articles were excluded. Of these, 10 pertained to the adult population, and 110 focused on the pediatric population. Following a careful selection process and the application of enrollment criteria, six relevant articles were included, all in English, focusing on the effects of OSA on children's eyes. Among these, three studies explored correlations with choroidal alterations, while three investigated retinal and optic nerve changes. Two studies analyzed post-otorhinolaryngological intervention ocular changes. Results: OSA leads to increased intraocular pressure and reduced optic nerve thickness in adults, but treatment alleviates this condition. An immediate correlation between OSA and optic nerve thickness in children does not readily emerge, although age appears to play a role. Pediatric patients with OSA exhibit corneal anomalies and an increase in optic nerve thickness, possibly due to intermittent hypoxia. Studies indicate that OSA can influence retinal vascular density in children, with an increase observed after treatment and reduced choroidal thickness in cases of adenotonsillar hypertrophy. Conclusion: This literature review has highlighted how OSA in children can significantly impact ocular health, with observed alterations in the optic nerve, choroid, retina, and cornea. While the direct correlation with the optic nerve may not always be evident, OSA can elevate intraocular pressure and lead to structural changes. However, treatment appears to bring about improvements. The necessity for regular monitoring to detect potential adverse effects underscores the importance of promptly addressing childhood OSA.

Acute myeloid leukemia (AML) is a hematological malignancy that is the culmination of genetic and epigenetic alterations in the hematopoietic progenitor cells, leading to uncontrolled proliferation at the expense of normal hematopoiesis and bone marrow exhaustion. Although the outcomes for pediatric AML have improved in recent decades, at least one third of children still have relapses. Recent studies have notably highlighted the important role of dysregulated epi-genetic mechanisms in myeloid leukemogenesis. Epigenetic modifications are frequently reversible compared to genetic alterations, thus providing opportunities for targeted epigenetic therapy. In this review, we summarize the landscape of epigenetic alterations and the progress to date in epigenetic targeted therapy, and focus on the future role of epigenetic abnormalities in predicting relapse and the precision therapy in pediatric AML.

Genetic disorders are preeminent determinants of infant mortality. The inherited pediatric-onset genetic disorders have consequential stress on child growth and development: several congenital, complex and rare disorders with indistinguishable clinical symptoms where diagnosis always remains a challenging task. Traditional diagnosis methods include biochemical tests followed by chromosomal microarray and sequencing of a single gene or panel of genes. These methods had several limitations, but with the advent of whole-exome sequencing (WES), genetic testing has become cost-effective and transformative. Exome sequencing has been known for its effectiveness, which appropriately elucidates and distinguishes the heterogeneous disorders to avoid misdiagnosis and decode the underlying genetic alterations. WES has led to discovering genes and genomic variants in a broad spectrum of diseases, including autism, epilepsy, congenital heart diseases, neurodevelopmental diseases, cancer, nephrotic disorders, neural tube defects and fetal structural anomalies. WES is significant in producing immense genomic biomarkers that can be made as appropriate pharmacogenomic targets for drug therapy. In this article, we analyze the recent exploration of WES technology to revolutionize not only the process of genetic variation and disease detection but also the convention of preventative and targeted drug discovery.

During the period of health emergency linked to the current COVID-19 pandemic, the management of children's oral health presents specific problems related to the infectious spread of the disease. These problems must be faced on the one hand by acting on the oral health prevention methods, and on the other by implementing specific protocols relating both to the conditions of oral pathologies that normally do not represent an emergency, and to those clinical situations that fall into the category of pediatric dental emergencies. In this perspective, in addition to defining rigorous and highly effective infection control protocols in the dental settings, it is of fundamental importance to work on remote communication and education aimed at maintaining the oral health of the children. This article, after an analysis of the risk factors from COVID-19 associated with pediatric dental treatment, presents a series of considerations on potential oral prevention strategies and on the management of emergency and non-emergency dental procedures in a context of disease transmission control, proposing new approaches and models of treatment based also on remote interaction techniques which will then retain their usefulness even at the end of the current emergency period.

Abstract: The SARS-CoV-2 pandemic has reemphasized the urgent need for broad-spectrum antiviral therapies. We developed a computational workflow using scRNA-Seq data to assess cellular metabolism during viral infection. With this workflow we predicted the capacity of cells to sustain SARS-CoV-2 virion production in patients and found a tissue-wide induction of metabolic pathways that support viral replication. Expanding our analysis to influenza A and dengue viruses, we identified metabolic targets and inhibitors for potential broad-45 spectrum antiviral treatment. These targets were highly enriched for known interaction partners of all analyzed viruses. Indeed, phenformin, an NADH:ubiquinone oxidoreductase inhibitor, suppressed SARS-CoV-2 and dengue virus replication. Atpenin A5, blocking succinate dehydrogenase, inhibited SARS-CoV-2, dengue virus, respiratory syncytial virus, and influenza A with high selectivity indices. In vivo, phenformin showed antiviral activity against SARS-CoV-2 in a Syrian hamster model. Our work establishes host metabolism as druggable for broad-spectrum antiviral strategies, providing invaluable tools for pandemic preparedness.

Mycobacterium abscessus is a non-tuberculous mycobacteria notoriously known for causing severe, chronic infections. Treatment of these infections is challenging due to either intrinsic or acquired resistance of M. abscessus to multiple antibiotics. Despite prolonged poly-antimicrobial therapy, treatment of M. abscessus infections often fails, leading to progressive morbidity and eventual mortality. Great research efforts are invested in finding new therapeutic options for M. abscessus. Clofazimine and rifabutin are known anti-mycobacterial antibiotics, repurposed for use against M. abscessus. Novel antimicrobials active against M. abscessus include delamanid, pretomanid and PIPD1 and the recently approved beta-lactamase inhibitors avibactam, relebactam and vaborbactam. Previously unused antimicrobial combinations e.g. vancomycin-clarithromycin and dual beta-lactam therapy have been shown to have synergistic effect against M. abscessus in experimental models, suggesting their possible use in multiple-drug regimens. Finally, engineered phage therapy has been reported to be clinically successful in a severe case of disseminated M. abscessus infection. While many of these experimental therapeutics have shown activity against M. abscessus in vitro, as well as intracellular and/or animal models, most have little if any evidence of effect in humans infections. Clinical studies of M. abscesssus treatments are needed in order to reliably determine the value of their incorporation in therapeutic regimens.

Coronavirus disease 2019 (COVID-19), can manifest with ocular symptoms. These symptoms can be divided into isolated events attributed to COVID-19 and those occurring in multisystem inflammatory syndrome in children (MIS-C), a newly diagnosed disease entity associated with COVID-19 infection. Currently, the literature lacks specific guidelines and treatment regimens for COVID-19 ocular symptoms, especially in children.

Necrotizing enterocolitis (NEC) is a major cause of neonatal morbidity and mortality. Although the specific etiology is unknown, previous research shows that maternal environment may be a contributing factor. Gestational stress may lead to the development of NEC by interfering with the barrier function of the intestinal epithelial barrier. The migration of cells from the crypts to the tips of the villi is crucial in maintaining the integrity of the epithelial barrier. Previously, the Martin lab found that pups from psychologically stressed pregnant dams were more susceptible to NEC-like injury. We have also shown that investigated how stress signaling and zinc impact intestinal epithelial wound healing. Through a scratch assay, human Caco-2 cell migration was studied over 24 hours, and the percent wound healing was calculated. We found that only hydrocortisone at the 30 ug/ml concentration led to an inhibition of wound healing, and that zinc was unable to rescue hydrocortisone mediated inhibition.

Although migraine belongs to the main causes of disability worldwide the mechanisms of its pathogenesis are poorly known, which is among the reasons that this disease is underdiagnosed and undertreated. As migraine diagnosis is based on the subjective assessment of symptoms, there is a need to establish objective markers of its occurrence and severity. Tryptophan (TRP) metabolism has been associated with the pathogenesis of neurological and psychiatric disorders. In the present work, we investigated an association between migraine and the urine concentration of TRP and its metabolites 5-hydroxyindoleacetic acid (5-HIAA), kynurenine (KYN), kynurenic acid (KYNA) and quinolinic acid (QA) in 21 low-frequency episodic migraine patients and 32 controls. Migraine patients displayed lower urinary levels of 5-HIAA and KYNA, but KYN and QA were enhanced as compared with the controls. Consequently, the patients were characterized by different values of the 5-HIAA/TRP, KYN/TRP, KYNA/KYN, and KYNA/QA ratios. Furthermore, urinary concentration of 5-HIAA was negatively correlated with Migraine Disability Assessment score, monthly migraine, and monthly headache days. A negative correlation between Patient Health Questionnaire 9 scores assessing depression. In conclusion, the urinary 5-HIAA level may be an easy-to-determine marker of migraine occurrence and severity and may contribute to the identification of migraine patients with depression.

Until recently, no disease-specific health-related quality of life (HRQoL) instrument existed for pediatric traumatic brain injury (TBI). In this revalidation study, the psychometric properties and the validity of the final German version of the 35-item QOLIBRI-KID/ADO questionnaire were examined in 300 children and adolescents. It is the first self-reported TBI-specific instrument for measuring pediatric HRQoL in individuals aged 8–17 years. The six-factor model fits the data adequately. Internal consistencies were excellent for the total score and satisfactory to excellent for the scale scores. Intraclass correlations indicated good test-retest reliability. Construct validity was supported by overlaps between the QOLBRI-KID/ADO and the PedsQL, which measures generic HRQoL. Discriminant validity indicated that HRQoL was significantly lower in older children and girls, and in those with anxiety, depression, and post-concussion symptoms than in comparison groups, replicating the results of the questionnaire’s first development study. Our results suggest that the QOLIBRI-KID/ADO is a valid and reliable multidimensional instrument for assessing disease-specific HRQoL after pediatric TBI in clinical and research settings, which can additionally be used across the lifespan in combination with the adult version. This may help to improve care, treatment, daily functioning and HRQoL after TBI.

Pediatric brain tumors are the most common solid tumors in children, causing the highest number of cancer-related deaths at young ages. Although existing therapies have improved the 5-year overall survival rate of PBT patients, some high-risk brain tumors continue to resist current treatments. Additionally, the survivors endure devastating long-term side effects, including cognitive defects and sensory and endocrinal dysfunctions. In the past two decades, immunotherapies have evolved significantly, with great success in many cancers. Immunotherapies developed specifically for PBTs also show promising results. Currently, scores of clinical trials are underway to evaluate the safety and feasibility of a wide-range of immunotherapeutics for PBTs, and this review overviews the most recent advances, including the exciting progress made toward treating medulloblastoma, pediatric glioma, and ependymoma. We summarized the cutting-edge immunotherapies under development, including immune checkpoint blockade, chimeric antigen receptor (CAR)-T cell therapy, natural killer (NK)-cell therapy, cancer vaccines, and oncolytic virus therapy. We find that the results from the recently concluded or ongoing clinical trials on safety and feasibility are very encouraging; however, non-responsiveness and tumor recurrence still haunt them. While this review judges the scope of the current immunotherapies, it also lays out strategies to find alternate solutions for persisting issues.

Modern drugs have changed epilepsy, which affects people of all ages. But for young people with epilepsy, the framework of drug development has stalled. In the wake of the thalidomide catastrophe, the misconception emerged that for people <18y antiseizure medications (ASMs) need separate proof of efficacy and safety (E&S), overall called “pediatric drug development.” This has been corrected to some extent. Authorities accept that ASMs are effective in <18y as well, but they still require "extrapolation of efficacy," as if minors were another species. In our view, the real problem is less that relevant parts of pediatric clinical epilepsy research over the past decades were useless, but that this has hampered research on meaningful challenges. We do not need to show that ASMs work also before the 18th birthday. But we need to learn how to best use ASMs to prevent brain damage in young patients and optimize ASMs use considering a broader range of aspects

Tuberculosis (TB) remains the leading cause of death from a single infectious agent. Among children, TB can have a wide range of non-specific clinical and radiological manifestations becoming a challenging diagnosis, particularly in areas with a low prevalence. We present the case of a 14 month-old female with a history of fever of unknown origin (FUO) and later diagnosed with miliary tuberculosis.

Cancer is the second biggest cause of death in children. With the development of chemotherapy, there is a substantial increase in overall survival rate over recent 30 years. However, the overall mortality rate in children with cancer still remains 25%, and many survivors experience a decline in overall quality of life and long-term adverse effects caused by treatments. Although cancer cells share common characteristics, pediatric cancers are different from adult cancers in their prevalence, mutation load, and drug response. Therefore, there is an urgent unmet need to develop therapeutic approaches specifically designed for children with cancer. Nanotechnology can potentially overcome the deficiencies of conventional methods of administering chemotherapy and ultimately improve clinical outcomes. The nanoparticle-based drug delivery systems can decrease the toxicity of therapy, provide a sustained or controlled drug release, improve pharmacokinetic properties of loading contents, and achieve a targeted drug delivery with achievable modifications. Further, therapeutic approaches based on combining nanoformulated drugs with novel immunotherapeutic agents are emerging. In this review, we discuss the recently developed nanotechnology-based strategies for treating blood and solid pediatric cancers.

Objectives: To investigate the value of early lactate dynamic monitoring index in predicting prognosis of patients with sepsis and septic shock. Methods: We performed our test on 50 patients. Out of 50 patients, 28 are male, and 22 are female. Prospectively studied pediatric patients with septic shock were performed. Vital signs, Lactate clearance, were obtained at presentation 6 h, 12 h, 24 h over the first 48 h of hospitalization. The therapy received, outcome parameters of mortality and duration of hospitalization were recorded. Results: The statistical data and comparative analysis showed that an average of 16.88 days after admission, 5 patients have died, 17 patients are poorly prognosis leaves the hospital, and the remaining 28 are recovered and discharged. The primary outcome variable of mean 16 days hospitalization mortality rate was 10%. Poor prognosis 34% and fully recovery 56 % were observed. In this retrospective cohort study, a lactate level of more than 2.5mmol/L was the best threshold to predict 28-day mortality among severe sepsis and septic shock patients. In our research, we found mean LC 6 h 3.08mmol/L, and after 48 h mean it is 1.79mmol/L. Significant LC 6 h found, which is 8.08mmol/L in the death group patient where 48 h mmol/L shows significant high. Poor prognosis also presents a clinical increase of lactate level high in the LC 6 h analysis, which is 3.32mmol/L. Recovered patients showed a significant improvement after administering treatment depending on the patient organ involvement and good decrease of lactate reports achieved, which is 1.20mmol/L, where admission reports show it was 1.91mmol/L in LC 6 h. Mean Heart rate 94/51mmhg, pulse 119, temperature 39℃, respiratory rate 32.26, and urine output 456 ml recorded during our study. Death patient shows a remarkable detonation of those reports but has a significant clinical report with the recovered patients. Conclusion: The early lactate dynamic monitoring index has a high value in predicting sepsis and septic shock patients' prognosis, thus worth popularizing.

Viruses are the most common congenital infections and an important cause of fetal malformations, morbidity, and mortality. The effects of these infections, which are transmitted in-utero (transplacentally), during childbirth or in the puerperium depend on the timing of the infections. These vary from miscarriages (usually with infections in very early pregnancy), congenital malformations (where the infections occur during organogenesis) and morbidity (with infections occurring late in pregnancy, during childbirth or after delivery). The most common of these viruses are cytomegalovirus, hepatitis, parvovirus B-19, rubella, varicella and zika. There are currently very few efficacious antiviral agents licensed for use in pregnancy and therefore for most of these infections, prevention by means of immunisation (where there is a vaccine), administration of immunoglobulins to those exposed to the virus to offer passive immunity or appropriate measures to avoid being infected would be options to minimise the infections and their consequences. In this review, we discuss the current understanding of some of the congenital infections and their consequences on both the mother and fetus and their management focusing mainly on prevention.

Human Immunodeficiency Virus (HIV) infection and its latent recurrent infection make vaccine development a significant challenge for traditional vaccines; however, the mRNA delivery of multiepitope antigens capable of creating antibodies against the surface proteins of HIV-1 and HIV-2 along with their respective Nef proteins, responsible for the latent infection can bring a most effective, as well as affordable solution to the unresolved epidemics of HIV. In this paper, we present the complete design of a multiepitope vaccine to prevent acute infections and inactivate Nef proteins that block the MHC-1 and MHC-2 pathways to hide the virus for later reinfection.

Alzheimer’s Disease (AD), a progressive and debilitating condition, is reported to be the most common type of dementia, with at least 55 million people believed to be currently affected. Many causation hypotheses of AD exist, yet the intriguing link between viral infection and its possible contribution to the known etiology of AD has become an attractive focal point of research for the field and a challenging study task. In this review, we will explore the historical perspective and milestones that led the field to investigate the viral connection to AD. Specifically, several viruses such as Herpes Simplex Virus 1 (HSV-1), Zika virus (ZIKV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), along with several others mentioned, include the various viruses presently considered within the field. We delve into the strong evidence implicating these viruses in the development of AD. We will also extend beyond these mere associations by carefully analyzing the potential mechanisms by which viruses may contribute to AD pathology. This includes but is not limited to direct neuronal infections, dysregulation of immune responses, and the impact on protein processing. Controversies and challenges of the viral-AD relationship emerge as we tease out these potential mechanisms considered. Looking forward, we emphasize the future directions the field should take to tackle the remaining unanswered questions and the glaring research gaps that persist. Overall, this review aims to provide a comprehensive survey of the past, present, and future of the potential link between viral infections and their association with AD development.

The increase in incidence of superficial fungal infections combined with the emergence of antifungal resistance represents both a global health challenge and a considerable economic burden. Recently, dermatophytes, the main culprit causing superficial fungal infections, have started to exhibit antifungal resistance. This can be observed in some of the most common species such as Trichophyton rubrum and Trichophyton mentagrophytes. Importantly, the new subspecies, known as Trichophyton indotineae, has been reported to show high resistance to terbinafine, a first-line treatment for dermatophyte infections. Compounding these issues is the realization that diagnosing the causative infectious agents requires using molecular analysis that goes beyond the conventional macroscopic and microscopic methods. These findings emphasize the importance of conducting antifungal susceptibility testing to select the appropriate antifungal necessary for successful treatment. Implementing these changes may improve clinical practices that combat resistant dermatophyte infections.

Burns is a pervasive and oppressive basic care issue. In children, burn injuries are a major reason for bleakness and mortality. The quirks in the physiology of liquid and electrolyte taking care of, the vital necessity and the distinctions in the different body extends in children direct that the pediatric wounds administration ought to be brought with an alternate point of view than for adults. Notwithstanding, for the intensivist, challenges regularly exist that muddle quiet help and adjustment. Moreover, burn injuries are mind-boggling and can show exceptional challenges that require deep-rooted recovery. Investigation in burn wound care has yielded progressions that will keep on improving practical recuperation. What's more, pain management all through this period is essential. Managing these wounds requires escalated therapeutic treatment for multi-organ dysfunction, and forceful surgical treatment to forestall sepsis and other inconveniences. The biological therapeutic bilayered skin substitutes with a long shelf life that recapitulates the normal barrier function of the intact human skin and stimulate wound repair and skin regeneration. A definitive objective is to accomplish a perfect skin substitute that gives a successful and without scar wound recuperating. This review article features the headway in pediatric burn wounds with an emphasis on the pathophysiology and treatment of burn wounds.

The dawn of Artificial Intelligence (AI) in healthcare stands as a milestone in medical innovation. A plethora of different medical fields are heavily involved and pediatric emergency medicine is no exception. These new tools do not merely provide more advanced and efficient systems for patients’ diagnosis, management and treatment. They rather concern a strict shift from traditional methods based upon broad categories towards a more personalized healthcare. AI offers many promises in pediatric emergency medicine with a wide range of applications involving clinical decision making, patients’ flows management and prioritization. Main barriers to a widespread diffusion involve technological challenges but also ethical issues and the paucity of extensive datasets in pediatric contexts. We conducted a narrative review structured in two parts. The first part explores the theoretical principles of AI, providing all the necessary background to feel confident with these new state-of-the-art tools. The second part presents an informative analysis of AI models in pediatric emergencies, pointing out the actual applications and challenges until future feasible research perspectives.

Acute lymphoblastic leukemia is the most common malignancy in children and is characterized by numerous genetic and epigenetic abnormalities. Epigenetic mechanisms, which involve DNA methylations and histone modifications, result in the heritable silencing of genes without a change in their coding sequence. Emerging studies are increasing our understanding of the epigenetic role of leukemogenesis and have demonstrated the potential of DNA methylations and histone modifications as a biomarker for lineage and subtypes classification, predicting relapse, and disease progression in ALL. Epigenetic abnormalities are relatively reversible when treated with some small molecule-based agents compared to genetic alterations. In this review, we conclude the genetic and epigenetic characteristics in ALL and discuss the future role of DNA methylation and histone modifications in predicting relapse, finally focus on the individual and precision therapy targeting epigenetic alterations.

Abstract: Background: epileptic encephalopathies (EE) are characterized by severe drug-resistant seizures, early-onset, and unfavorable developmental outcome. We describe a cohort of pediatric patients with EE who underwent intravenous methylprednisolone (IVMP) pulse therapy to examine its efficacy/tolerability. Methods: This is a retrospective study from 2020 to 2023. Inclusion criteria were: ≤18 years at the time of IVMP pulse therapy and at least 6 months of follow-up. Efficacy and outcome, defined as seizure reduction >50% (responder rate), were evaluated at 6 and 9 months of therapy, and 6 months after therapy suspension; quality of Life (QoL) was also assessed. Variables predicting positive post-IVMP outcomes were identified using statistical analysis. Results: Twenty-one patients were included. The responding rate was 85.7% at 6 and 9 months of therapy, and 80.9% at 6 months after therapy suspension. Genetic etiology and encephalopathy related to status epilepticus during NREM sleep (ESES) were predictive of efficacy (p=0.0475). The fourth month of therapy was the minimum time point to establish the effectiveness of the treatment. All patients showed improvements in QoL, EEG tracing and postural-motor development. No relevant adverse events were observed. Conclusions: Our study confirms the efficacy and tolerability of pulse IVMP treatment in pediatric patients with EE, especially with genetic etiology and ESES. The fourth month of therapy was the minimum time point to establish its effectiveness. QoL, EEG and postural-motor development also showed improvement.

Porcine parvovirus (PPV) 1 is a major causative pathogen of reproductive failure, and porcine circovirus (PCV) 2 is an etiological pathogen causing PCV-associated and PCV diseases worldwide. PPV2–6 and PCV3 were recently identified as newly emerging viruses with unknown pathogeneses. However, little is known of PPV1–6 and PCV3 effects or their co-infections with PCV2. In this study, we examined 926 samples (272 aborted pig fetuses and 654 pig lung tissues) from domestic pig farms for the presence of PPV1–6 or PCV3 and for PCV2 co-infection with these seven viruses. The prevalence of PPV and PCV was significantly greater in lung tissue samples than aborted pig fetus samples. PPV3–6 were detected for the first time in Korean domestic pigs. Co-infection rates with PCV2 and other viruses were significantly higher in abattoir samples than that in aborted pig fetus samples. Concurrent infections are more common than single infection in pig population and nu-merous infectious pathogens such as PPV and PCV2 can impact the respiratory diseases. Fur-thermore, Korean PPV1 strain (PPV1-82) was identical to the virulent PPV-27a strain in this respect. Our results describe, for the first time the prevalence of PPV1–6 and PCV3 infections and their co-infection rates with PCV2 in Korean domestic pigs.

The world is in the grips of the COVID-19 pandemic. Public health measures that can reduce the risk of infection and death in addition to quarantines are desperately needed. This article reviews the roles of vitamin D in reducing risk of respiratory tract infections, knowledge about the epidemiology of influenza and COVID-19, and how vitamin D supplementation might be a useful measure to reduce risk. Through several mechanisms, vitamin D can reduce risk of infections. Those mechanisms include inducing cathelicidins and defensins that can lower viral replication rates and reducing concentrations of pro-inflammatory cytokines that produce the inflammation that injures the lining of the lungs, leading to pneumonia, as well as increase concentrations of anti-inflammatory cytokines. Several observational studies and clinical trials reported that vitamin D supplementation reduced risk of influenza, whereas others did not. Evidence supporting the role of vitamin D in reducing risk of COVID-19 includes that the outbreak occurred in winter, a time when 25-hydroxyvitamin D [25(OH)D] concentrations are lowest; that the number of cases in the Southern Hemisphere near the end of summer are low; that vitamin D deficiency has been found to contribute to acute respiratory distress syndrome, and that case-fatality rates increase with age and with chronic disease comorbidity, both of which are associated with lower 25(OH)D concentration. To reduce risk of infection, it is recommended that people at risk of influenza and/or COVID-19 consider taking 10,000 IU/d of vitamin D₃ for a few weeks to rapidly raise 25(OH)D concentrations, followed by 5000 IU/d. The goal should be to raise 25(OH)D concentrations above 40–60 ng/ml (100–150 nmol/l). For treatment of people who become infected with COVID-19, higher vitamin D₃ doses might be useful. Randomized controlled trials and large population studies should be conducted to evaluate these recommendations.

Escherichia coli is the main pathogen responsible for extraintestinal infections. A total of 196 clinical E. coli consecutively isolated during 2016 in Spain (100 from Lucus Augusti hospital in Lugo) and France (96 from Beaujon hospital in Clichy) were characterized. Phylogroups, clonotypes, sequence types (STs), O:H serotypes, virulence factor (VF)-encoding genes and antibiotic resistance were determined. Approximately 10% of the infections were caused by ST131 isolates in both hospitals and approximately 60% of these infections were caused by isolates belonging to only 10 STs (ST10, ST12, ST58, ST69, ST73, ST88, ST95, ST127, ST131, ST141). ST88 isolates were frequent especially in Spain while ST141 isolates significantly predominated in France. The 23 ST131 isolates displayed four clonotypes: CH40-30, CH40-41, CH40-22 and CH40-298. Only 13 (6.6%) isolates were carriers of ESBL enzymes. However, 37.2% of the isolates were multidrug-resistant (MDR). Approximately 40% of the MDR isolates belonged to only four of the dominant clones (B2-CH40-30-ST131, B2-CH40-41-ST131, C-CH4-39-ST88 and D-CH35-27-ST69). Among the remaining MDR isolates two isolates belonged to B2-CH14-64-ST1193 i.e the new global emergent MDR clone. To our knowledge, it is the first identification of this emergent clone in Spain. Moreover, a hybrid ExPEC/enteroaggregative isolate belonging to A-CH11-54-ST10 clone was identified.

Background. Our knowledge regarding the epidemiology of pediatric cardiomyopathy is based on large national population studies reporting an annual incidence of 1 case per 100 000 children with a higher incidence observed in infancy and among selected populations. The aim is to document the epidemiology of pediatric cardiomyopathy in a Mediterranean population. Methods. Children younger than 18 years of age, living on the Mediterranean island of Crete, Greece and evaluated during 20 years since the establishment of tertiary pediatric cardiology services (2002-2022) were included in this retrospective study. Results. A total of 40 children were included, corresponding to an average annual incidence of pediatric cardiomyopathy of 1.59 cases (95% CI: 1.4-2,3) and a prevalence of 26 cases per 100.000 children. In decreasing order of frequency most cases corresponded to dilated cardiomyopathy (50%) followed by hypertrophic (42.5%), arrhythmogenic (5%) and restrictive (2.5%). An etiology was identified in 40%, including a genetic diagnosis in 22.5%. Conclusion. The incidence of pediatric cardiomyopathy in the Mediterranean island of Crete is higher compared with that reported previously for other Caucasian populations. Further study is needed to investigate the exact prevalence and specific genetic factors associated with the epidemiology of pediatric cardiomyopathy in Mediterranean populations.

Shape of supracondylar fracture of the humeral of pediatric patients is analysed with Procrustes method. XR–images of fractures are considered both in anterio-posterior (AP) view (66 images) and in a lateral (L) view (24 images). Applying Procrustes method for both views mean images are constructed and compared. Variability of shapes is quantified with a shape principal component analysis. Non-parametric tests (permutational and bootstrap) do not indicate statistical difference between Procrustes mean shapes in anterio-posterior and lateral projections. It is shown, however, that AP and L shapes of humeral fractures differ in their variability quantified by shape principal components.

Complementary and alternative treatment approaches are becoming more common among children with chronic conditions. The pravelance of CAM use among US adults was estimated to be around 42% in 2015, and around 44% to 50% among adults with neurologic disorders. Studies report children with chronic illnesses such as cancer, asthma, attention-deficit/hyperactivity disorder (ADHD), genetic disorders, and other neurodevelopmental disorders are treated with complementary and alternative treatments at higher rates. Dietary therapies are gaining increasing popularity in the mainstream population, due to the heavy media involvement. Although, majority of “fad” diets do not have enough supporting evidence, some dietary therapies have been utilized for decades and have numerous published studies. The objective of this review is to describe the dietary interventions used in children with the specific chronic conditions, to evaluate their efficacy based on published data, and to encourage pharmacist involvement in the management and care of such patients.

Colpodella species are free-living opportunistic pathogens that cause human and animal infections and use ticks and flies as vectors. Trophozoite and cyst stages of Colpodella species can be distinguished from stages of the prey Parabodo caudatus using Sam-Yellowe’s trichrome staining. Colpodella species obtain nutrients by attaching to their prey, aspirating the prey’s cytoplasmic contents into a posterior food vacuole and encysting. It is unclear whether both trophozoite and cyst stages are present during infection. Molecular techniques identified Colpodella species in all reported infections. However, no morphological information was reported to aid life cycle stage identification in hosts. This review discusses the increased incidence of Colpodella infection in animals and in vectors and the need to identify stages used for transmission and pathogenesis. The potential for zoonotic infections through tick and fly bites is a public health concern. We previously used Sam-Yellowe’s trichrome staining to identify life cycle stages of Colpodella sp. In order to gain a better understanding of transmission and pathogenesis, identifying Colpodella life cycle stages in infected tissue and in vectors will provide important insights regarding nutrient uptake in hosts by determining whether attachment of trophozoites to host cells occurs, and identifying trophozoites and cysts in infected hosts.

Urinary infections are very prevalent in pregnant women and are a cause for great concern con-sidering the negative impacts they can have on both, the mother and the baby. The objectives were characterize urinary infections associated with pregnant women, study the most prevalent strains in urinary infections in pregnant women and analyze the antibiogram of the most prevalent strains in infections in pregnant women. A retrospective observational study was carried out on all posi-tive urine cultures from pregnant women between January 2018 and December 2022 at a Hospital Center in the Center of Portugal, totaling 201 samples. Data were collected with computer support, including age, origin, previous antibiotic therapy, catheterization, isolated bacteria and tested an-tibiotic therapy. The majority of pregnant women were in the third trimester of pregnancy and came from the External Consultation. The most identified bacteria was Escherichia coli, followed by Streptococcus agalactiae. Regarding the interaction with antibiotics, Escherichia coli showed total sensitivity to one antibiotic, while Streptococcus agalactiae showed sensitivity to four anti-biotics in 2022. This work contributes to the knowledge of urinary infections in pregnant women in the center of the country, being a contribution to the continued improvement of the care provided

Catheter-associated bloodstream infection (CVC-BSI) is a significant cause of morbidity and mortality among hemodialysis patients. In our center was a notable increase in CVC associated with patient age and morbidity. This 10-year retrospective study investigated catheter-associated bloodstream infections (CVC-BSI) in hemodialysis patients. We recorded a total of 67 bacteremia episodes in 52 patients, predominantly linked to Gram-positive microorganisms, particularly Staphylococcus aureus, the study found a mean age of 68 years, 74.6% males, and 88% with tun-neled jugular catheters. Notably, catheter removal occurred in 65.7% of cases, more frequently in Gram-positive instances. Two episodes of endocarditis and five ICU admissions were reported. The study identified a higher incidence in the summer and a significant decrease in bacteremia from 2017, coinciding with the introduction of Tauro-LockTM. Despite enhanced preventive measures during the COVID-19 pandemic, there was no significant impact on catheter infection rates. This research emphasizes the importance of early catheter removal, highlights seasonal variations in incidence, and suggests a potential positive influence of Tauro-LockTM on de-creasing CVC-BSI rates in hemodialysis units.

Febrile infections are a common cause of presentation to the emergency department (ED) in chil-dren. While viral infections are usually self-limiting, sometimes bacterial illnesses may lead to sepsis and severe complications. Inflammatory biomarkers such as C reactive protein (CRP) and procalcitonin are usually the first blood exams performed in the ED to differentiate bacterial and viral infections; the better understanding of immunochemical pathways has nowadays led to the discovery of new and more specific biomarkers that could play a role in the emergency setting. The aim of this narrative review is to provide the most recent evidence on biomarkers and predictor models combining them for serious bacterial infections (SBI) diagnosis in febrile children. Litera-ture analysis showed that inflammatory response is a complex mechanism in which many bio-chemical and immunological factors contribute to host response in SBI. CRP and procalcitonin still represent the most used biomarkers in the pediatric ED for the diagnosis of SBI. Their sensibility and sensitivity increase when combined and for this reason it is reasonable to take them both into consideration in the evaluation of a febrile children. The potential of machine learning tools, who represent a real novelty in medical practice, in conjunction with routine clinical and biological in-formation, may improve accuracy of diagnosis and target therapeutic options in SBI. However, studies on this matter are not yet validated in younger populations, making their relevance in pe-diatric precision medicine still uncertain. More data from further researches are needed to improve clinical practice and decision making using these new technologies.

Staphylococcus aureus (S. aureus), particularly Methicillin-resistant S. aureus (MRSA), is a life-threatening pathogen that causes a variety of infections in hospital and community settings. It poses a significant risk and challenge for global health that hinders our ability to control and treat bacterial infections. Recently, the emergence and spread of variant strains of bacteria, misuse of the limited available options of effective antibiotics, spread of fake drugs, and climate change that increased the contact between humans and animals’ populations carrying different bacterial has significantly increased the incidence of Multi-Drug Resistance strains (MDR). This in turn, has created a severe problem in the infection control treatment of S. aureus infected patients. Treatment options for MRSA infection are increasingly limited and complicated. Unfortunately, different strains of MRSA are showing tolerance and resistance toward vancomycin, which is the standard of care for complicated MRSA. Therefore, it is crucial now to invest developing new effective anti-biotics and synergies, develop and implement national action plans for the management of an-tibiotic resistance, as well as improving our understanding of the antimicrobial resistance mechanisms. Here, in this review we explain the main mechanisms of antibiotic resistance in MRSA and describes different approaches to manipulate it in MRSA, providing a basis for de-signing effective drugs, and shedding some light on the evolution of S. aureus.

In the continued battle against one of the oldest enemies known to mankind, Mycobacterium tuberculosis (MTB), the emergence of drug resistance among children poses multiple challenges for early detection and treatment. Molecular diagnostics and newer drugs like bedaquiline and delamanid have strengthened the armamentarium and helped design convenient, safe and child-friendly therapeutic regimens against drug-resistant tuberculosis (TB). Preventive strategies like treatment of TB infection among children living in close contact with patients with drug-resistant TB and effective vaccines against TB are currently in the investigative stages of development and implementation. In addition to the implementation of recent novel diagnostics and treatment modalities, effective psychosocial and nutritional support, as well as dedicated monitoring for compliance and adverse effects, are crucial determinants for successful treatment outcomes in these children.

Although researchers have proposed various indentation size effect (ISE) models, these models often involve different form and number of parameters that can make our wonder which is the best in existed ISE models. Three types of ISE test data, namely, normal ISE, reverse ISE and transition of normal to reverse ISE, are used to evaluate the sixteen ISE models. The comparatively study indicates that H-J, N-G-Fs, N-G-H, N-G-A and N-G-Qs models can accurately predict the normal ISE. The reason for this is that the friction stress that is not related to dislocation activities or the indentation size effect of plastic zone has been introduced into these models. Therefore, these two factors should be considered in future ISE models. The sixteen ISE models are originally proposed to describe the normal ISE of different materials. However, to our surprise, some of these models are able to capture the reverse ISE and the transition of normal to reverse ISE of different materials. The determination coefficients (DC) of the sixteen ISE models are also determined for different materials. For reverse ISE, the highest DC value for NiCSi, TC4 and PED Ni are given by the EXP, N-G-Fs and N-G-A models, respectively. For the transition of normal to reverse ISE, the N-G-YC, N-G-Fs, and N-G-H models produce the maximum DC for ZrO2, Cu and Y2O3-ZrO2, respectively. Moreover, the mean DC of the N-G-Fs model is the maximum among the sixteen ISE models, followed by the N-G-H model, but they cannot accurately predict the reverse ISE. Therefore, the N-G-Fs and N-G-H models should be further modified to accurately predict the reverse ISE.

(1) Background: Trichosporon species have emerged as important opportunistic fungal pathogens, with Trichosporon asahii being the leading and most frequent cause of invasive disease. (2) Methods: We performed a global review focused on invasive trichosporonosis in neonates and pediatric patients with malignancies or hematologic disorders. We reviewed case reports and case series of trichosporonosis due to T. asahii published since 1994, year of the revised taxonomic classification. (3) Results: Twenty-four cases of invasive trichosporonosis were identified in neonates with presence of central venous catheter and use of broad-spectrum antibiotics recognized as main predisposing factors. Thirty-two cases were identified in children with malignancies or hematologic disorders, predominantly with severe neutropenia. Trichosporon asahii was isolated from blood in 24/32 (75%) pediatric cases. Cutaneous involvement was frequently observed in invasive trichosporonosis. Micafungin was the most commonly used prophylactic agent (9/22; 41%). Ten patients receiving prophylactic echinocandins were identified with breakthrough infections. Favorable outcome was reported in 12/16 (75%) pediatric patients receiving targeted monotherapy with voriconazole or combined with liposomal amphotericin B. Overall mortality in neonates and children with malignancy was 67% and 60%, respectively. (4) Conclusions: Voriconazole is advocated for the treatment of invasive trichosporonosis given the intrinsic resistance to echinocandins and poor susceptibility to polyenes.

Epigenetic mechanisms, including post-translational modifications of DNA and histones that influence chromatin structure, regulate gene expression during normal development, and are also involved in carcinogenesis and cancer progression. The histone methyltransferase G9a (euchromatic histone lysine methyltransferase 2, EHMT2), which mostly mediates mono- and dimethylation by histone H3 lysine 9 (H3K9), influences gene expression involved in embryonic development and tissue differentiation. Overexpression of G9a has been observed in several cancer types, and different classes of G9a inhibitors have been developed as potential anticancer agents. Here, we review the emerging evidence suggesting the involvement of changes in G9a activity in brain tumors, namely glioblastoma (GBM), the main type of primary malignant brain cancer in adults, and medulloblastoma (MB), the most common type of malignant brain cancer in children. We also discuss the role of G9a in neuroblastoma (NB) and the drug development of G9a inhibitors.

The body of evidence available in paediatrics population is limited for making clinical decisions regarding pharmacotherapy optimization of tacrolimus. The objective of this study was to estimate the frequency of CYP3A5 genetic polymorphisms and their relationship with tacrolimus requirements in paediatric population. This was a longitudinal cohort study, with two-year follow-up of 77 patients under 18 who had liver transplant over the period 2009-2012 at the Paediatric Hospital J. P Garrahan. Tacrolimus levels from day 5 to 2-year post-transplant were obtained from hospital records of routine therapeutic drug monitoring. The genotyping of CYP3A5 (CYP3A5*1/*3 or *3/*3) were performed in liver biopsies of both the donor and the recipient. Recipients frequency of CYP3A5 *1 expression was 37.1% and 32.2% for Donors. Patient who received an organ expresser showed lower Co/dose especially after 90 days post-surgery. The role of each polymorphism is different according to days after transplantation proceeds and it must be taken into account to optimize the benefits of TAC therapy during the post-transplant induction and maintenance phase.

Background: Annual influenza epidemics are a serious public health problem, causing particularly severe morbidity and mortality in high-risk groups. The study aimed to understand Poles' attitudes and beliefs towards influenza vaccinations in the flu season of 2022–2023, analyze preferences and unmet needs regarding influenza vaccinations, and examine the perception and acceptance of the influenza vaccine among individuals at risk of flu complications. Methods: A cross-sectional survey-based study was carried out on a sample of 1446 respondents. The Google Forms questionnaire was created and disseminated electronically using social media and e-mail. The pre-test was performed at the beginning of the project. Results: The majority of respondents (71%) could identify "high-risk groups" recommended for influenza vaccination. Furthermore, it was observed that individuals aged 21 to 59 demonstrated a higher level of knowledge in this regard compared to those below 20 and above 65 years old, and individuals with higher and medium education levels were much better at identifying risk groups for influenza virus infection. The majority of respondents (52.01%) reported receiving influenza vaccination at some point in the past, with 32.12% receiving it in the 2022–2023 flu season and 41.09% in the 2021–2022 season. The majority of respondents declaring acceptance of the vaccine for the 2022-2023 season were in the high-risk group. Only 17.28% of respondents declared receiving both influenza and SARS-CoV-2 vaccines in the 2022-2023 season, with the vast majority being respondents from the "high-risk group" (p

The disproportionate incidences of COVID-19-related hospitalization and mortality for different age groups and various underlying health conditions is a result of a complex social predisposition to the exposure, resistance, and tolerance for the infection. Based on the observed data as well as the molecular mechanisms for viral entry and replication, cellular senescence related to aging, obesity, hypertension, and diabetes appears to be strongly correlated with the SARS-CoV-2 infections resulting in higher COVID-19 related complications and mortality. Establishing such a correlation may allow us to better explain the pathobiology as well as the differential nature of the SARS-CoV-2 infections and consider targeted control and therapeutic strategies to combat the disease.

There is an important role non-human primates (NHP) play in biomedical research. Phylogenetic proximity of any of the NHP species to Homo sapiens assures that much better translatability of research outcomes from model studies involving human diseases can be achieved than from those generated with other pre-clinical systems. Our group and others used during past two decades NHPs in research directed towards viral and autoimmune disorders of the gastrointestinal tract. This review summarizes progress made in the area of enteric viral infections and its applicability to human disease.

Background: Micronutrients has roles in strengthening and maintaining immune function, but its supplementation and/or deficiency effects on respiratory tract infections are inconclusive. This review aims to systematically assess the associations between micronutrient supplementation or deficiency, with novel coronavirus incidence and disease severity. Methods: Systematic literature searches conducted in 5 electronic databases identified 751 unique studies, of which 33 studies (5 supplementation studies, 1 supplementation and deficiency study, and 27 deficiency studies) were eventually included in this review. Proportions of incidence and severity outcomes in each group, and adjusted summary statistics with their relevant 95% confidence intervaIs (CI) were extracted. Data from 19 studies were pooled in meta-analysis using the generic inverse variance method. Findings: A total of 360,346 patients across 16 countries, with a mean age between 32 and 87.7 years, were involved across 33 studies. All studies were on COVID-19 infections. In individuals without micronutrient deficiency, there was a significant reduction on odds of COVID-19 incidence (pooled OR: 0.37, 95% CI: 0.18, 0.78), and ICU admissions or severe/critical disease onset (pooled OR: 0.26, 95% CI: 0.08, 0.89). Insignificant protective effects were observed on other outcome measures – mortality, ICU admission, progression to respiratory-related complications, severe/critical disease onset or requiring respiratory support and hospitalization rate. Conclusion: The absence of micronutrient deficiency significantly reduced COVID-19 incidence and clinical deterioration in hospitalized patients. Usage of micronutrients as prophylaxis and complementary supplement in therapeutic management of COVID-19 patients may be a promising and cost-effective approach warranting in-depth investigation.