Unusual Association of Diamond-Blackfan Anemia and Severe Sinus Bradycardia in a Six-Month-Old White Infant: A Case Report and Literature Review.

Diamond-Blackfan anemia is a rare (6-7 million live births), inherited condition manifesting as severe anemia due to the impaired bone marrow production of red blood cells. We present the unusual case of a six month old infant with a de novo mutation of the RPS19 gene causing Diamond-Blackfan anemia who additionally suffers from severe sinus bradycardia. The infant was diagnosed with this condition at the age of four months; at the age of 6 months, she presents with severe anemia causing hypoxia which, in turn, caused severe dyspnea and polypnea, which had mixed causes (hypoxic and infectious) as the child was febrile. After correction of the overlapping diarrhea, metabolic acidosis, and severe anemia (hemoglobin < 3 g/dL), she developed severe persistent sinus bradycardia immediately after mild sedation (before central venous catheter insertion), not attributable to any of the more frequent causes, with a heart rate as low as 49 beats/min on 24 h Holter monitoring, less than the first percentile for age, but with a regular QT interval and no arrhythmia. The echocardiogram was unremarkable, showing a small interatrial communication (patent foramen ovale with left-to-right shunting), mild left ventricular hypertrophy, normal systolic and diastolic function, and mild tricuspid regurgitation. After red cell transfusion and appropriate antibiotic and supportive treatment, the child's general condition improved dramatically but the sinus bradycardia persisted. We consider this a case of well-tolerated sinus bradycardia and foresee a good cardiologic prognosis, while the hematologic prognosis remains determined by future corticoid response, treatment-related complications and risk of leukemia.

Insulin Pump Therapy Efficacy and Key Factors Influencing Adherence in Pediatric Population-A Narrative Review.

Objective: we aimed to highlight the state of the art in terms of pediatric population adherence to insulin pumps. This study intends to underline the significance of identifying and minimizing, to the greatest extent feasible, the factors that adversely affect the juvenile population's adherence to insulin pump therapy. Materials and methods: articles from PubMed, Embase, and Science Direct databases were evaluated using the following search terms: adherence, pump insulin therapy, children, pediatric population, and type 1 diabetes, in combination with several synonyms such as compliance, treatment adherence, pump adherence, patient dropouts, and treatment refusal. Results: A better glycemic control is connected to a better adherence to diabetes management. We identify, enumerate, and discuss a number of variables which make it difficult to follow an insulin pump therapy regimen. Several key factors might improve adherence to insulin pump therapy: efficient communication between care provider and patients (including home-based video-visits), continuous diabetes education, family support and parental involvement, as well as informational, practical assistance, and emotional support from the society. Conclusions: every cause and obstacle that prevents young patients from adhering to insulin pumps optimally is an opportunity for intervention to improve glycemic control and, as a result, their quality of life.

Arrhythmogenic Right Ventricular Cardiomyopathy in Children: A Systematic Review.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by the progressive replacement of the normal myocardium by fibroadipocytic tissue. The importance of an early diagnosis is supported by a higher risk of sudden cardiac death in the pediatric population. We reviewed the literature on diagnosis, risk stratification, and prognosis in the pediatric population with ARVC. In case reports which analyzed children with ARVC, the most common sign was ventricular tachycardia, frequently presenting as dizziness, syncope, or even cardiac arrest. Currently, there is no gold standard for diagnosing ARVC in children. Nevertheless, genetic analysis may provide a proper diagnosis tool for asymptomatic cases. Although risk stratification is recommended in patients with ARVC, a validated prediction model for risk stratification in children is still lacking; thus, it is a matter of further research. In consequence, even though ARVC is a relatively rare condition in children, it negatively impacts the survival and clinical outcomes of the patients. Therefore, appropriate and validated diagnostic and risk stratification tools are crucial for the early detection of children with ARVC, ensuring a prompt therapeutic intervention.

Statins-Beyond Their Use in Hypercholesterolemia: Focus on the Pediatric Population.

Statins are a class of medications primarily used in adults to lower cholesterol levels and reduce the risk of cardiovascular events. However, the use of statins in children is generally limited and carefully considered despite the well-documented anti-inflammatory, anti-angiogenic, and pro-apoptotic effects, as well as their effect on cell signaling pathways. These multifaceted effects, known as pleiotropic effects, encompass enhancements in endothelial function, a significant reduction in oxidative stress, the stabilization of atherosclerotic plaques, immunomodulation, the inhibition of vascular smooth muscle proliferation, an influence on bone metabolism, anti-inflammatory properties, antithrombotic effects, and a diminished risk of dementia. In children, recent research revealed promising perspectives on the use of statins in various conditions including neurological, cardiovascular, and oncologic diseases, as well as special situations, such as transplanted children. The long-term safety and efficacy of statins in children are still subjects of ongoing research, and healthcare providers carefully assess the individual risk factors and benefits before prescribing these medications to pediatric patients. The use of statins in children is generally less common than in adults, and it requires close monitoring and supervision by healthcare professionals. Further research is needed to fully assess the pleiotropic effects of statins in the pediatric population.

Nanotechnology Innovations in Pediatric Cardiology and Cardiovascular Medicine: A Comprehensive Review.

(1) Background: Nanomedicine, incorporating various nanoparticles and nanomaterials, offers significant potential in medical practice. Its clinical adoption, however, faces challenges like safety concerns, regulatory hurdles, and biocompatibility issues. Despite these, recent advancements have led to the approval of many nanotechnology-based products, including those for pediatric use. (2) Methods: Our approach included reviewing clinical, preclinical, and animal studies, as well as literature reviews from the past two decades and ongoing trials. (3) Results: Nanotechnology has introduced innovative solutions in cardiovascular care, particularly in managing myocardial ischemia. Key developments include drug-eluting stents, nitric oxide-releasing coatings, and the use of magnetic nanoparticles in cardiomyocyte transplantation. These advancements are pivotal for early detection and treatment. In cardiovascular imaging, nanotechnology enables noninvasive assessments. In pediatric cardiology, it holds promise in assisting the development of biological conduits, synthetic valves, and bioartificial grafts for congenital heart defects, and offers new treatments for conditions like dilated cardiomyopathy and pulmonary hypertension. (4) Conclusions: Nanomedicine presents groundbreaking solutions for cardiovascular diseases in both adults and children. It has the potential to transform cardiac care, from enhancing myocardial ischemia treatment and imaging techniques to addressing congenital heart issues. Further research and guideline development are crucial for optimizing its clinical application and revolutionizing patient care.

The health mediators-qualified interpreters contributing to health care quality among Romanian Roma patients.

In order to assure optimal care of patients with chronic illnesses, it is necessary to take into account the cultural factors that may influence health-related behaviors, health practices, and health-seeking behavior. Despite the increasing number of Romanian Roma, research regarding their beliefs and practices related to healthcare is rather poor. The aim of this paper is to present empirical evidence of specificities in the practice of healthcare among Romanian Roma patients and their caregivers. Using a qualitative exploratory descriptive design, this study is based on data gathered through three focus groups with 30 health mediators in the counties of Iasi and Cluj (Romania). We identified various barriers to access to healthcare for Roma patients: lack of financial resources and health insurance coverage, lack of cognitive resources or lack of personal hygiene, but also important cultural issues, such as the shame of being ill, family function, disclosure of disease-related information, patient's autonomy, attitudes towards illness and health practices, that should be considered in order to create a culturally sensitive environment in Romanian medical facilities:… The role of the health mediators within the context of cultural diversity is also discussed, as cultural brokers contributing to health care quality among Romanian Roma patients Bridging cultural differences may improve patient-healthcare provider relationships, but may have limited impact in reducing ethnic disparities, unless coupled with efforts of Roma communities to get involved in creating and implementing health policies.

Ethical issues in communication of diagnosis and end-of-life decision-making process in some of the Romanian Roma communities.

Medical communication in Western-oriented countries is dominated by concepts of shared decision-making and patient autonomy. In interactions with Roma patients, these behavioral patterns rarely seem to be achieved because the culture and ethnicity have often been shown as barriers in establishing an effective and satisfying doctor-patient relationship. The study aims to explore the Roma's beliefs and experiences related to autonomy and decision-making process in the case of a disease with poor prognosis. Forty-eight Roma people from two Romanian counties participated in semi-structured interviews, conducted by a research team from the University of Medicine and Pharmacy of Iasi. Participants were recruited among the chronically ill patients and caregivers. The Roma community opposes informing the terminal patients about their condition, the "silence conspiracy" being widely practiced. The family fully undertakes the right of decision making, thus minimizing the patient's autonomy. We identified ethical dilemmas concerning autonomy, lack of patients' real decision-making power, and paternalistic attitudes exerted firstly by the family and, on demand, by the physician. Instead, the Roma patient benefits from a very active support network, being accompanied at the hospital by numerous relatives. The patient's right to make autonomous decisions promoted in the Western countries and stipulated by the Romanian law has diminished value in the Roma community. For the Roma, the understanding of dignity is not simply individual and personal, but it is closely related to their cultural particularities. Ignoring their cultural values could create conflicts between healthcare providers and community.

Can Bioactive Food Substances Contribute to Cystic Fibrosis-Related Cardiovascular Disease Prevention?

Advances in cystic fibrosis (CF) care have significantly improved the quality of life and life expectancy of patients. Nutritional therapy based on a high-calorie, high-fat diet, antibiotics, as well as new therapies focused on CFTR modulators change the natural course of the disease. They do so by improving pulmonary function and growing BMI. However, the increased weight of such patients can lead to unwanted long-term cardiovascular effects. People with CF (pwCF) experience several cardiovascular risk factors. Such factors include a high-fat diet and increased dietary intake, altered lipid metabolism, a decrease in the level of fat-soluble antioxidants, heightened systemic inflammation, therapeutic interventions, and diabetes mellitus. PwCF must pay special attention to food and eating habits in order to maintain a nutritional status that is as close as possible to the proper physiological one. They also have to benefit from appropriate nutritional counseling, which is essential in the evolution and prognosis of the disease. Growing evidence collected in the last years shows that many bioactive food components, such as phytochemicals, polyunsaturated fatty acids, and antioxidants have favorable effects in the management of CF. An important positive effect is cardiovascular prevention. The possibility of preventing/reducing cardiovascular risk in CF patients enhances both quality of life and life expectancy in the long run.

An Up-to-Date Narrative Review on Congenital Heart Disease Percutaneous Treatment in Children Using Contemporary Devices.

BACKGROUND: Congenital heart pathology has a significant burden regarding morbidity and mortality in the pediatric population. Several transcatheter interventions and devices have been designed as an alternative to surgical repair. Percutaneous interventions have been proven to yield good results in most cases but with less stress and trauma than that attributed to surgical treatment, especially in frail pediatric patients. We aimed to review the literature and to investigate the feasibility and efficacy of transcatheter interventions and implantable devices for congenital heart disease management in children. METHODS: We performed a search in Scopus and MEDLINE databases using prespecified keywords to retrieve clinical studies published between 2000 and 2021. RESULTS: This article provides an up-to-date review regarding the applicability of interventional techniques in simple inter-atrial or inter-ventricular defects, and in challenging congenital defects, such as hypoplastic left heart syndrome, tetralogy of Fallot, or coronary artery fistula. Furthermore, we reviewed recent indications for defibrillator and cardiac resynchronization therapy, and new and promising devices currently being tested. CONCLUSION: Transcatheter treatment represents a feasible and efficient alternative to surgical repair of congenital heart defects. Novel devices could extend the indications and possibilities of percutaneous interventions in pediatric patients with congenital heart diseases.

Current Antithrombotic Therapy Strategies in Children with a Focus on Off-Label Direct Oral Anticoagulants-A Narrative Review.

(1) Background: The incidence of thromboembolic events is relatively low in the general population, but it increases in hospitalized children and those who underwent thrombogenic procedures. Although the evidence regarding direct oral anticoagulants (DOACs) in children with venous thromboembolism (VTE) is growing, DOACs were excluded from existing guidelines due to the lack of reliable data at that moment. Therefore, current evidence on VTE management in children needs to be critically reviewed. (2) Methods: We have conducted a literature search in the Scopus, EMBASE, and MEDLINE databases using prespecified keywords to retrieve studies published between 2010 and 2022. (3) Results: Clinical trials highlighted that rivaroxaban and dabigatran had predictable pharmacokinetic and pharmacodynamic profiles in children, similar to those observed in adults. Dabigatran and rivaroxaban had a similar safety profile to standard therapy but improved thrombotic burden and resolution during follow-up. Most studies involving apixaban and edoxaban are ongoing, and results are awaited. (4) Conclusions: Dabigatran and rivaroxaban could be valid therapeutic options for VTE management in children. In the case of apixaban and edoxaban, results from ongoing clinical studies are required before using them in pediatric VTE.

Non-Cardiac Cause of Death in Selected Group Children with Cardiac Pathology: A Retrospective Single Institute Study.

BACKGROUND: Pediatricians and pediatric surgeons often face children with cardiomegaly and dilatative or hypertrophic cardiomyopathies presenting with or without symptoms. Some of these patients have already been diagnosed and received medication, and some present with completely unrelated pathologies. METHODS: We performed a 4-year retrospective study on the causes and mechanisms of death of children with cardiac pathology who died outside the cardiology clinic of our hospital by studying the hospital charts and necropsy reports. All children who were in this situation in our hospital were included. RESULTS: Most children in our study group were infants (81.82%), most were boys (81.82%), and in most cases, the cause or mechanism of death was unrelated to their heart condition, whether it had already been diagnosed or not (one case probably died as a result of a malignant ventricular arrhythmia). Additionally, 27.27% of children died as a consequence of bronchopneumonia, the same percentage died as a consequence of an acquired non-pulmonary disease or after surgery, and 18.18% died as a consequence of congenital malformations. CONCLUSIONS: Cardiac disease needs to be thoroughly investigated using multiple tools for all children presenting with heart failure symptoms, those with heart murmurs, and children scheduled for surgery of any type. The intensive care specialist and surgeon need to be aware of any heart pathology before non-cardiac surgical interventions.

Multiple Faces of Cervical Lesions in Children.

Pediatric sialolithiasis is a rare condition causing tumefaction, induration, redness, and pain of the affected gland. When the submandibular gland is involved, the lesion can be mistaken for an adenopathy. As there are few studies to elucidate this condition in children, we present a rare case of a 16-year-old female with suggestive symptoms, in which initial clinical examination and two ultrasound examinations mistook the lesion for an adenopathy. A computed tomography examination was performed and the correct diagnosis was established. The patient was sent for oro-maxilo-facial examination and sialolithotomy was performed. A 10-mm yellow calculus was extracted and postoperative case evolution was favorable under wide spectrum antibiotherapy, oral nonsteroidal anti-inflammatory therapy and silagog alimentation. Although submandibular adenopathies are much more frequent in the pediatric age group, when faced with a firm, immobile submandibular lesion, the pediatrician should consider the sialolithiasis diagnosis.

Gastroesophageal Reflux in Children with Asthma.

Background: Nowadays it is considered that a specific causal relationship exists between asthma and gastroesophageal reflux (GER), because of the aspiration of gastric refluate which leads to and maintain spasticity even real crisis of paroxystic expiratory dyspnea. This study explores this relationship and evaluates the results after treatment. Methods: 56 children diagnosed with asthma, hospitalized in a regional center of pediatric gastroenterology in Northeast Romania, underwent 24-hour continuous esophageal pH monitoring in order to establish the presence of GER. The Boix-Ochoa score was used to interpret the results. Proton pump inhibitors were administered to those with GER and the patients were reevaluated after 2 months. Results: 39 patients (69.64%) had GER, with a Boix-Ochoa score above normal (N < 11.99), and 17 patients (30.36%) had normal score. After administering proton pump inhibitors for 2 months, 7 patients still had high Boix-Ochoa score (17.95%). The result of this analysis shows that the presence of asthma increases the chance of GER by 2.86 times. Conclusions: In children with asthma we have to look for GER in order to treat, because it can help the treatment of asthma or even solve some cases resistant to standard treatment.

ECG and Biomarker Profile in Patients with Acute Heart Failure: A Pilot Study.

Background: Biomarkers, electrocardiogram (ECG) and Holter ECG are basic, accessible and feasible cardiac investigations. The combination of their results may lead to a more complex predictive model that may improve the clinical approach in acute heart failure (AHF). The main objective was to investigate which ECG parameters are correlated with the usual cardiac biomarkers (prohormone N-terminal proBNP, high-sensitive cardiac troponin I) in patients with acute heart failure, in a population from Romania. The relationship between certain ECG parameters and cardiac biomarkers may support future research on their combined prognostic value. Methods: In this prospective case-control study were included 49 patients with acute heart failure and 31 participants in the control group. For all patients we measured levels of prohormone N-terminal proBNP (NT-proBNP), high-sensitive cardiac troponin I (hs-cTnI) and MB isoenzyme of creatine phosphokinase (CK-MB) and evaluated the 12-lead ECG and 24 h Holter monitoring. Complete clinical and paraclinical evaluation was performed. Results: NT-proBNP level was significantly higher in patients with AHF (p < 0.001). In patients with AHF, NT-proBNP correlated with cQTi (p = 0.027), pathological Q wave (p = 0.029), complex premature ventricular contractions (PVCs) (p = 0.034) and ventricular tachycardia (p = 0.048). Hs-cTnI and CK-MB were correlated with ST-segment modification (p = 0.038; p = 0.018) and hs-cTnI alone with complex PVCs (p = 0.031). Conclusions: The statistical relationships found between cardiac biomarkers and ECG patterns support the added value of ECG in the diagnosis of AHF. We emphasize the importance of proper ECG analysis of more subtle parameters that can easily be missed. As a non-invasive technique, ECG can be used in the outpatient setting as a warning signal, announcing the acute decompensation of HF. In addition, the information provided by the ECG complements the biomarker results, supporting the diagnosis of AHF in cases of dyspnea of uncertain etiology. Further studies are needed to confirm long-term prognosis in a multi-marker approach.

Primary tonsillar tuberculosis in a pediatric patient: Case report and literature review.

RATIONALE: Tuberculosis is an entity that usually affects the lungs, although extrapulmonary sites can also be involved. Tonsils are rarely affected, especially in the absence of pulmonary disease, primary tonsillar tuberculosis being a diagnostic challenge for the clinician. PATIENT CONCERNS: We present the case of a 14-year-old female teenager, presented to our Pediatric Service with a 14-day history of dysphagia, odynophagia and left reflex otalgia associated with a 5 kg weight loss. Clinical examination revealed mild pharyngeal erythema, marked enlargement of the left tonsil infiltrating the lateral pharyngeal wall and the uvula and painful, mobile, nonadherent to deep bilateral latero-cervical adenopathy. DIAGNOSIS: Positive interferon-gamma release assay (QuantiFERON-TB gold). Mantoux test reading was 16 mm. INTERVENTIONS: During hospitalization, the patient received Clindamycin and Gentamicin for 3 days i.v., with discrete relief of symptoms and inflammatory markers. On the 4th day of hospitalization, treatment with Imipenem/Cilastin is started for 7 days in micro-perfusion, with tonsil hypertrophy decrease in size and favorable clinical evolution. OUTCOME: Tonsil hypertrophy decreased in size and patient had a favorable clinical evolution. At discharge, the patient was given a 6-month course of anti-tuberculous drug. LESSONS: The particularity of this case is represented by the rarity of primary tuberculosis of tonsils in children, with unilateral involvement, displaying at the same time a common issue encountered in the current practice: the limitations and the difficult course of setting the diagnosis due to the involvement of relatives in the medical act.

Immunoproliferative small intestinal disease versus colonic monoblastic sarcoma in a 2-year-old boy.

The authors present a case of colonic monoblastic sarcoma, previously treated for other digestive abnormalities (malabsorbtion, Hirschprung's disease). Important similitudes with immunoproliferative small intestinal disease (IPSID) lymphoma were demonstrated for this patient (male, 2-year-old). His main admission complaints were failure to thrive, recurrent episodes of enterocolitis and malabsorbtion syndrome. Some particularities of this case are the young age and the extremely rapid development of the malignant disease in a patient with no previous signs of acute non-lymphoblastic leukemia. The initial diagnosis was of malabsorbtion syndrome, based on the clinical exam at presentation, and then the patient was thought to have a form of Hirschprung's disease, due to a functional intestinal disorder (slow transit). After the necropsy, pathologists diagnosed an immunoproliferative small intestinal disease, and four years later, they performed a more appropriate pathological exam, which explained better clinical symptoms associated to this complex case.

Differential diagnosis difficulties related to infantile hemangioma - case report and literature review.

Infantile hemangioma is a benign vascular tumor that is often present in the cephalic region and can grow rapidly in size, causing serious complications. The hemangioma with oro-maxillofacial sphere localization may often pose differential diagnosis problems, requiring additional investigations. We present the case of a 3-month-old baby who was brought to the Emergency Room for acute respiratory failure and dysphagia caused by the rapid increase in size of a soft palate and lateral pharyngeal wall tumor. The clinical examination revealed a "wine stain" hemangioma in the inter-eyebrow and frontal areas, a hemangioma in the right genial area, 1∕1.5 cm in diameter, growing rather in depth than on the surface, and a purplish-blue tumoral mass with irregular edges, grown in the soft palate and in the right lateral wall of the pharynx, which impaired both eating and breathing. Obstructive phenomena have been aggravated by an acute respiratory infection. Due to the inconsistencies between different medical specialties about the nature of the tumor and the suspicion of malignancy, in order to establish the correct diagnosis and therapeutic management, urgent tumor biopsy was required. After starting oral treatment with Propranolol, the evolution was favorable. Infantile hemangiomas may sometimes be hard to diagnose, requiring additional imaging examinations, and sometimes-pathological examination. Since it may affect a vital function, or the patient's esthetic appearance, or if the tumor has ulcerated, bleeds or got infected, the certain diagnosis and the onset of treatment should be done as soon as possible.

Dying and death in some Roma communities: ethical challenges.

The Roma people have specific values, therefore their views and beliefs about illness, dying and death are important to be known for health care providers caring for members of this community. The aim of this qualitative study based on 48 semi-structured interviews with Roma patients and caregivers in communities in two regions of Romania was to examine their selfdescribed behaviors and practices, their experiences and perceptions of illness, dying and death. Five more important themes about the Roma people facing dying and death have been identified: (1) The perception of illness in the community as reason for shame and the isolation that results from this, as well as the tendency for Roma people to take this on in their self image; (2) The importance of the family as the major support for the ill/dying individual, including the social requirement that family gather when someone is ill/dying; (3) The belief that the patient should not be told his/her diagnosis for fear it will harm him/her and that the family should be informed of the diagnosis as the main decision maker regarding medical treatment; (4) The reluctance of the Roma to decide on stopping life prolonging treatment; (5) The view of death as 'impure'. These results can be useful for health care providers working with members of the Roma community. By paying attention to and respecting the Roma patients' values, spirituality, and relationship dynamics, the medical staff can provide the most suitable healthcare by respecting the patients' wishes and expectations.

[X-linked Bruton congenital agammaglobulinemia. Case report]. / Agamaglobulinemie congenitala legata de x Bruton. Prezentare de caz.

Congenital agamaglobulinemia is a B-cell deficiency caused by tirosin-kinase gene mutations. This article presents the case of a 2 years and 6 months old boy with a history of multiple respiratory infections, which also associates a malabsorbtion syndrome. The patient presented for symptoms of arthritis. After performing protein electrophoresis, the extremely low gamma fraction pointed out a hidden immunodeficiency. Gene analysis was performed in the Department of Pediatric Immunology of Debrecen University, Hungary and thus the final diagnosis was determined. Arthritis and respiratory symptoms improved after immunoglobulin treatment.

[Photosensitivity and generalized idiopathic epilepsies of children]. / Fotosensibilitatea si epilepsiile generalizate idiopatice ale copilului.

UNLABELLED: The aim of this study is to evaluate the frequency of photosensitivity at patients of paediatric age diagnosed with different types of generalized idiophatic epilepsies. MATERIAL AND METHOD: We used a group of 68 children aged 3-18 years diagnosed: 39 patients with childhood absence epilepsy (CAE), 11 with juvenile absence epilepsy (JAE), 10 with epilepsy with grand mal on awakening (EGMA), 8 with juvenile myoclonic epilepsy (JME). EEG was recording without and with stimulation (hyperventilation, intermittent photic stimulation -IPS) after sleep deprivation. For all children with CAE absences and anormal EEG was provoked by hyperventilation and in 12 cases seizures was provoked by IPS. RESULTS: At 4 patients with JAE, EEG show photosensitivity. 5 children with JME have photosensitivity and for one child opening eyes provoked polyspike-wave discharges without clinical correspondent. The EEG of patients with EGMA showed photosensitivity at 6 children. The photosensitivity is frequently associated with generalized idiophatic epilepsies (32.35%) and it is most often seen at girls (54.54%) of puberty age.