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OBJECTIVES: Glycogen storage disease type V is caused by the mutations in muscle glycogen phosphorylase gene. This is the first report which DL-3-hydroxybutyric acid was used in combination with modified Atkins diet for the treatment of a patient with glycogen storage disease type V and quadriceps femoris shear wave elastography was performed to evaluate the treatment efficacy. CASE PRESENTATION: A 13-year-old girl was referred with fatigue and muscle cramps with exercise and there were no pathological findings in physical examination. Creatine kinase levels with 442â¯U/L. No phosphorylase enzyme activity was detected in muscle biopsy, a homozygous c.1A>G (p.M1V) pathogenic mutation was found in PYGM gene. She was started on DL-3-hydroxybutyric acid and modified Atkins diet at age 16. Her walking and stair climbing capacity increased, the need for rest during exercise decreased. The stiffness of the quadriceps femoris exhibited a reduction. CONCLUSIONS: DL-3-hydroxybutyric acid and modified Atkins diet may provide an alternative fuel and shear wave elastography may be useful in demonstrating treatment efficacy. More clinical and pre-clinical studies are obviously needed to reach more definite conclusions.
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INTRODUCTION: As our field of pathology continues to grow, our trainee numbers are on the decline. To combat this trend, the ASC Diversity, Equity, and Inclusion Committee established the Science, Medicine, and Cytology SumMer Certificate program to improve exposure to pathology/cytopathology with a focus on diversity, equity, and inclusion. Herein, we report our findings of the first 2 years of the program. MATERIALS AND METHODS: An online course was developed targeting students who are underrepresented in medicine at the high school and college level. It consisted of several didactic sessions, presenting the common procedures involving cytopathologists and cytologists. Interviews with cytopathologists were also included. Participants were surveyed for demographic information and provided course evaluations. RESULTS: In the first year of the program (2021), 34 participants completed the program, which increased to 103 in 2022. In both years there was a diversity in participant demographic backgrounds; however, only a minority of participants self-identified as being underrepresented in medicine. A vast majority (>85%) of participants in both years were high school or college students. In 2021, 100% of participants stated that the program format was effective and 94% thought the content was appropriate for their level of education; in 2022 the results were similar. In 2021, 66% considered health care as a potential career; this value increased in 2022 to 83%. In 2021 and 2022, 31% and 38%, respectively, considered cytology as a career. CONCLUSIONS: Evaluations were excellent, generating interest in cytopathology. Barriers in reaching underrepresented minorities exist and additional work is needed. Expansion to a wider audience may increase outreach.
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Sociedades Médicas , Humanos , Feminino , Masculino , Currículo , Estados Unidos , Patologia/educação , Grupos Minoritários/educação , Diversidade Cultural , Patologistas/educação , Adulto , CitologiaRESUMO
The first electrochemical sensor application in the literature is described for the sensitive and selective determination of the selective Janus kinase (JAK)-1 inhibitor abrocitinib (ABR). ABR is approved by the U.S. Food and Drug Administration (FDA) for the treatment of atopic dermatitis. The molecularly imprinted polymer (MIP)-based sensor was designed to incorporate zinc nanoflower (ZnNFs)-graphene oxide (GO) conjugate (ZnNFs@GO), synthesized from the root methanolic extract (RME) of the species Alkanna cappadocica Boiss. et Bal. to improve the porosity and effective surface area of the glassy carbon electrode (GCE). Furthermore, the MIP structure was prepared using ABR as a template molecule, 4-aminobenzoic acid (4-ABA) as a functional monomer, and other additional components. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the surface and structure of the synthesized nanomaterial and MIP-based surface. Among the electrochemical methods, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were preferred for detailed electrochemical characterization, and differential pulse voltammetry (DPV) was preferred for all other electrochemical measurements using 5.0 mM [Fe(CN)6]3-/4- solution as the redox probe. The MIP-based sensor, which was the result of a detailed optimization phase, gave a linear response in the 1.0 × 10-13 - 1.0 × 10-12 M range in standard solution and serum sample. The obtained limit of detection (LOD) and limit of quantification (LOQ) values and recovery studies demonstrated the sensitivity, accuracy, and applicability of the sensor. Selectivity, the most important feature of the MIP-based sensor, was verified by imprinting factor calculations using ibrutinib, ruxolitinib, tofacitinib, zonisamide, and acetazolamide.
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Técnicas Eletroquímicas , Limite de Detecção , Polímeros Molecularmente Impressos , Zinco , Polímeros Molecularmente Impressos/química , Técnicas Eletroquímicas/métodos , Técnicas Eletroquímicas/instrumentação , Zinco/química , Grafite/química , Humanos , Aminoimidazol Carboxamida/análogos & derivados , Aminoimidazol Carboxamida/análise , Aminoimidazol Carboxamida/sangue , Aminoimidazol Carboxamida/química , Nanoestruturas/química , EletrodosRESUMO
Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.
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Asma , Pneumonia , Deficiência de Vitamina D , Camundongos , Animais , Humanos , Vitamina D/farmacologia , Interleucina-2 , Inflamação , Células Th2 , Deficiência de Vitamina D/metabolismo , VitaminasRESUMO
OBJECTIVES: The mitochondrial elongation factor Tu (EF-Tu), encoded by the TUFM gene, is a GTPase, which is part of the mitochondrial protein translation mechanism. If it is activated, it delivers the aminoacyl-tRNAs to the mitochondrial ribosome. Here, a patient was described with a homozygous missense variant in the TUFM [c.1016G>A (p.Arg339Gln)] gene. To date, only six patients have been reported with bi-allelic pathogenic variants in TUFM, leading to combined oxidative phosphorylation deficiency 4 (COXPD4) characterized by severe early-onset lactic acidosis, encephalopathy, and cardiomyopathy. CASE PRESENTATION: The patient presented here had the phenotypic features of TUFM-related disease, lactic acidosis, hypotonia, liver dysfunction, optic atrophy, and mild encephalopathy. CONCLUSIONS: We aimed to expand the clinical spectrum of pathogenic variants of TUFM.
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Fator Tu de Elongação de Peptídeos , Humanos , Acidose Láctica/genética , Mitocôndrias/genética , Mitocôndrias/patologia , Doenças Mitocondriais/genética , Doenças Mitocondriais/patologia , Proteínas Mitocondriais , Mutação , Mutação de Sentido Incorreto , Fator Tu de Elongação de Peptídeos/genética , PrognósticoRESUMO
OBJECTIVES: Gaucher disease (GD) is a lysosomal storage disease caused by glucocerebrosidase (GCase) enzyme deficiency. Gaucher cells transformed from the macrophages by progressive sphingolipid accumulation and infiltrate bone marrow, spleen, liver, and other organs. The accumulation of substrate causes inflammation, compromised cellular homeostasis, and disturbed autophagy. It has been hypothesized that this proinflammatory state of GD leads cytokines and chemokines release. As a result of inflammatory process, the cellular dysfunction caused by disruption of cellular signaling, organelle dysfunction, or autoimmune antibodies may affect endocrine profile of GD patients such as hormone levels, lipid profile, and bone mineral density status. METHODS: A total of 13 patients confirmed to have GD, 12 non-neuronopathic type and one subacute neuronopathic type, were enrolled in our study. RESULTS: The median treatment duration in the enzyme therapy was 13.33 years (9-26 years). At least one endocrinological abnormality was detected in blood tests of nine patients. Hyperinsulinism was the most common finding although fasting blood glucose levels HgbA1c levels were normal in all patients. Two patients had osteopenia, and osteoporosis was detected in two patients. Low HDL levels were detected in six patients, but HDL levels below 23â¯mg/dL associated with disease severity have been detected in two patients who have not receiving enzyme replacement therapy. None of patients had thyroidal dysfunction. CONCLUSIONS: This study had revealed endocrinological abnormalities in GD patients that have not led any severe morbidity in our patients. However, thyroid hormone abnormalities, insulin resistance, or lipid profile abnormalities may cause unpredictable comorbidities. Endocrinological assessment in GD patients in routine follow-up may prevent possible clinical manifestation in long term as well as can define efficacy of ERT on endocrine abnormalities.
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Terapia de Reposição de Enzimas , Doença de Gaucher , Glucosilceramidase , Humanos , Doença de Gaucher/tratamento farmacológico , Doença de Gaucher/sangue , Masculino , Feminino , Adulto , Criança , Adolescente , Adulto Jovem , Glucosilceramidase/uso terapêutico , Seguimentos , Densidade Óssea/efeitos dos fármacos , Doenças do Sistema Endócrino/etiologia , Prognóstico , Biomarcadores/sangue , Biomarcadores/análiseRESUMO
OBJECTIVES: Fabry disease is an X-linked lysosomal disorder caused by decreased or absent alpha galactosidase enzyme. The enzyme deficiency leads to progressive accumulation of globotriaosylceramide (Gb-3) and its deacetylated form lyso-Gb3 in various tissue lysosomes that results in primarily lysosomal deterioration and subsequently mitochondrial, endothelial, and immunologic dysfunctions. METHODS: The endocrinological, metabolic, immunological and HLA status of 12 patients were evaluated. RESULTS: A total of 11 patients (91.6â¯%) had immunologic and/or endocrinologic abnormalities. fT4, anti-TPO, and anti-TG levels were increased in 1, 2, and 2 patients, respectively. Three patients had elevated proinflammatory cytokines. ANA profile, p-ANCA and c-ANCA were positive in 1, 1, and 2 patients, respectively. Tissue transglutaminase antibody was negative in all patients however P5 was diagnosed with Celiac disease at the age of 12 and on gluten free diet. All patients had distinct types of HLA apart from 2 patients with anti-TG and anti-TPO positive and there was no relationship between the HLA types and the autoimmunity biomarkers. CONCLUSIONS: FD may have impact on endocrinologic and immunologic abnormalities even in the patients under ERT, therefore prevalence of these abnormalities may be higher in ERT naïve patients. However, apparently, they are less likely to cause clinical symptoms. Certain HLA alleles may contribute to the direct impact of immunological pathogenesis in FD by developing abnormal autoimmune biomarkers. To the best of our knowledge, this is the first study investigating HLA status of FD patients; therefore further studies are needed to elucidate the underlying mechanism of action.
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Endocrinologia , Doença de Fabry , Humanos , Doença de Fabry/patologia , alfa-Galactosidase , Biomarcadores , Terapia de Reposição de EnzimasRESUMO
Recent evidence links dysfunctional lipid metabolism to the pathogenesis of Parkinson's disease, but the mechanisms are not resolved. Here, we generated a new Drosophila knock-in model of DNAJC6/Auxilin and find that the pathogenic mutation causes synaptic dysfunction, neurological defects and neurodegeneration, as well as specific lipid metabolism alterations. In these mutants, membrane lipids containing long-chain polyunsaturated fatty acids, including phosphatidylinositol lipid species that are key for synaptic vesicle recycling and organelle function, are reduced. Overexpression of another protein mutated in Parkinson's disease, Synaptojanin-1, known to bind and metabolize specific phosphoinositides, rescues the DNAJC6/Auxilin lipid alterations, the neuronal function defects and neurodegeneration. Our work reveals a functional relation between two proteins mutated in Parkinsonism and implicates deregulated phosphoinositide metabolism in the maintenance of neuronal integrity and neuronal survival.
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BACKGROUND AND OBJECTIVE: Pompe disease (PD) is an inherited lysosomal storage disease that progresses with glycogen accumulation in many tissues, due to the deficiency of the acid-alpha glucosidase enzyme. Recombinant alglucosidase alfa (rhGAA) is the only disease-specific treatment option, in the form of enzyme replacement therapy (ERT). Anaphylaxis can develop with rhGAA. There is no study evaluating anaphylaxis and its management in PD in the long term. We aimed to evaluate the development of anaphylaxis and rapid drug desensitization (RDD) with rhGAA in children with PD. MATERIALS AND METHODS: All children diagnosed and followed up in our institution with PD over 12 years between January 2009 and September 2021 were evaluated for development of anaphylaxis and RDD with rhGAA from medical records. RESULTS: Fourteen patients, 64% of whom were female and diagnosed with PD (1 juvenile, 13 infantile types) during the study period included in the study. The median age at diagnosis was 3.2 months (1-40 months). The median follow-up time of the patients was 20 months (1-129 months). Thirteen patients were given rhGAA, one died before ERT. Four (30.8%) patients developed moderate to severe anaphylaxis, and RDD was applied with rhGAA. A total of 390 RDDs have been performed so far without any serious breakthrough reactions during all RDDs. CONCLUSIONS: Anaphylaxis with rhGAA is not rare and RDD with rhGAA is safe and effective in the long term.
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Anafilaxia , Doença de Depósito de Glicogênio Tipo II , Criança , Humanos , Feminino , Lactente , Masculino , alfa-Glucosidases/uso terapêutico , Doença de Depósito de Glicogênio Tipo II/complicações , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , Anafilaxia/terapia , Anafilaxia/tratamento farmacológico , Terapia de Reposição de EnzimasRESUMO
Garnets that common constituent of skarn type iron deposits are wide ranges of chemical compositions, and they are also important as a semi-gemstone mineral. This study has been investigated garnets and inclusions of its formed in contacts of Pertek granitoid and Keban marble by using a combination of multiple techniques including Raman spectrum, electron microprobe, petrography and LA-ICP-MS. The main mineral assemblage observed in the skarn formation is diopside, garnet, quartz, magnetite, calcite and pyrite. The garnets are in size between 1 and 7 cm and have reddish, greenish and light-dark brown colour. The compositions of the garnets are mainly grossular-andradite, andradite-grossular, less grossular and andradite. Increased porosity and horizontal flow of hydrothermal fluids during metasomatism resulted in the formation of garnets of different sizes. Raman spectroscopy studies on garnets show to be that the idiomorphic and semi-idiomorphic garnets are predominantly grosular, andradite and uvarovite in the core. Raman spectroscopy studies on garnets showed to have predominantly grossular, andradite and uvarovite composition in the core of the idiomorphic and semi-idiomorphic garnets. As for the rare earth element (REE) analysis and distribution model, the chondrite-normalized REE patterns of all garnets in the study area have similar trends and generally in the right-slopping shape depleted in HREE and enriched in LREE, mostly controlled by adsorption. High Fe2O3, CaO and MgO contents may cause to high mobility during skarn formation associated with contact metamorphism and cation exchange via hydrothermal fluids (eg uvarovite in the core). All garnets have generally positive Ce and positive Eu anomalies. These results suggest that the garnets in the studya area formed in conditions showing increase in pH and high oxygen fugacity or decrease in temperature in the source of the hydrothermal fluids.
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BACKGROUND: Hepatic glycogen storage diseases are a group of diseases manifesting mainly with hypoglycemia and hepatomegaly. The patients require frequent daytime and nocturnal feedings. Hypoglycemia may cause sensorineural hearing loss and nocturnal feeding is a risk factor for the development of gastroesophageal reflux that may cause chronic otitis media and hearing loss consequently. We aimed to determine the prevalence and characteristics of hearing loss in hepatic glycogen storage diseases. METHODS: A total of 24 patients with hepatic glycogen storage disease (15 glycogen storage disease type I and 9 non type I) and 24 age/sex matched healthy controls were enrolled in the study. Pure tone audiometer, immitansmetry, acoustic reflex measurement, otoacoustic emission test (OAE) and auditory brainstem response (ABR) tests were applied to all participants. RESULTS: Hearing loss was determined in 17/24 patients (12 glycogen storage disease type I and 5 non type I) with pure tone audiometer. Interpretation of all the findings revealed a total of 8 patients had conductive and 9 had mixed hearing loss. All parameters were significantly different than the control group. CONCLUSIONS: This is the first study to comprehensively assess the auditory functions of patients with hepatic glycogen storage disease. Audiological findings determined a significantly increased prevalence of conductive/ mixed type hearing loss in the patient group which is a new finding in the literature. Further studies with extended patient numbers are required to enlighten the underlying pathophysiology.
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Surdez , Doença de Depósito de Glicogênio Tipo I , Perda Auditiva Neurossensorial , Perda Auditiva , Hipoglicemia , Audiometria de Tons Puros , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Doença de Depósito de Glicogênio Tipo I/complicações , Doença de Depósito de Glicogênio Tipo I/diagnóstico , Perda Auditiva/diagnóstico , Perda Auditiva/epidemiologia , Perda Auditiva/etiologia , Humanos , Emissões Otoacústicas Espontâneas/fisiologiaRESUMO
OBJECTIVES: Fructose 1,6 bisphosphatase (FBPase) deficiency is a rare autosomal recessively inherited metabolic disease. It is encoded by FBP1, and the enzyme catalyzes the hydrolysis of fructose-1,6-bisphosphate to fructose 6-phosphate. Patients with recurrent episodes of metabolic acidosis, hypoglycemia, hypertriglyceridemia, and hyperketonemia are present. METHODS: In this study, we describe the clinical, biochemical, and molecular genetic features of six unrelated Turkish patients from six different families who were genetically diagnosed with FBPase deficiency in our clinic between 2008 and 2020. Their clinical and laboratory data were collected retrospectively. Next-generation sequencing (NGS) was performed for the molecular genetic analysis. RESULTS: All patients were hospitalized with recurrent hypoglycemia and metabolic acidosis episodes. Three out of six patients were presented in the neonatal period. The mean age at diagnosis was 26 months. NGS revealed a known homozygous gross deletion including exon 2 in three patients (50%), a known homozygous c.910_911dupTT pathogenic variant in one patient (16%), a novel homozygous c.651_653delCAGinsTAA likely pathogenic variant, and another novel homozygous c.705+5G>A splice site variant. Leukocyte FBPase analysis detected no enzyme activity in the patient with homozygous c.705+5G>A splice site variant. CONCLUSIONS: We identified two novel mutations in this study. One of them is a splice site mutation which is five bases downstream of the exon, and the other one is an indel mutation. Both of the splice site and indel mutations are exceedingly rare in FBP1, and to the best of our knowledge, there are second splice site and indel variants reported in the literature. Exon 2 deletion is the most common mutation consistent with the previous reports in Turkish patients. FBPase is a frequent cause of hypoglycemia and metabolic acidosis, and the widespread use of molecular genetic analysis would contribute to the enlightenment of advanced genetic factors and possible genotype/phenotype correlation.
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Deficiência de Frutose-1,6-Difosfatase , Mutação INDEL , Frutose , Deficiência de Frutose-1,6-Difosfatase/diagnóstico , Deficiência de Frutose-1,6-Difosfatase/genética , Frutose-Bifosfatase/genética , Frutose-Bifosfatase/metabolismo , Humanos , Mutação , Estudos Retrospectivos , Turquia/epidemiologiaRESUMO
Aberrant remodeling of the asthmatic airway is not well understood but is thought to be attributable in part to mechanical compression of airway epithelial cells. Here, we examine compression-induced expression and secretion of the extracellular matrix protein tenascin C (TNC) from well-differentiated primary human bronchial epithelial (HBE) cells grown in an air-liquid interface culture. We measured TNC mRNA expression using RT-qPCR and secreted TNC protein using Western blotting and ELISA. To determine intracellular signaling pathways, we used specific inhibitors for either ERK or TGF-ß receptor, and to assess the release of extracellular vesicles (EVs) we used a commercially available kit and Western blotting. At baseline, secreted TNC protein was significantly higher in asthmatic compared to non-asthmatic cells. In response to mechanical compression, both TNC mRNA expression and secreted TNC protein was significantly increased in both non-asthmatic and asthmatic cells. TNC production depended on both the ERK and TGF-ß receptor pathways. Moreover, mechanically compressed HBE cells released EVs that contain TNC. These data reveal a novel mechanism by which mechanical compression, as is caused by bronchospasm, is sufficient to induce the production of ECM protein in the airway and potentially contribute to airway remodeling.
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Força Compressiva , Células Epiteliais/metabolismo , Vesículas Extracelulares/metabolismo , Pulmão/citologia , Estresse Mecânico , Tenascina/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Tenascina/genéticaRESUMO
INTRODUCTION: Tracheostomy care in children may be challenging, due to lack of knowledge of healthcare providers (HCPs). The aim of this study was to determine the level of knowledge of HCP who follow patients with tracheostomy and to increase this level with theoretical training and training in a simulation laboratory. MATERIALS AND METHODS: ISPAT (IStanbul PAediatric Tracheostomy), a multidisciplinary team for tracheostomy care was established and a training program was prepared. Participants were subjected to theoretical and practical pretests which evaluated their knowledge levels and skills for care, follow-up, and treatment of a patient with tracheostomy. After the theoretical and practical training given to the participants with a simulation model, theoretical and practical posttests were applied. RESULTS: Fifty-one HCP from nine tertiary pediatric clinics in Istanbul were enrolled in the training program. Only six (11.8%) of them had received standardized training programs previously. Regarding the theoretical tests, seven of the 33 questions were indicated as essential. The knowledge level of the participants based on the essential questions significantly increased after the training (p < 0.05 for all of the essential questions). The total number of correct answers and correct answers of three subheadings also significantly increased after the practical training (p < 0.001 for all). Ninety-five percent of the participants assessed the course as good or excellent in general. CONCLUSION: Training in a simulation laboratory in combination with theoretical education can improve the knowledge and skills of the HCP enabling improved care of children with a tracheostomy.
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Pessoal de Saúde , Traqueostomia , Criança , Competência Clínica , Simulação por Computador , Pessoal de Saúde/educação , Humanos , Traqueostomia/educaçãoRESUMO
OBJECTIVES: Enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA) has changed the fatal course of infantile Pompe disease, however, development of anti rhGAA antibodies and infusion-associated reactions (IAR) restrict the tolerability and effectiveness of the treatment. CASE PRESENTATION: We describe a successful concomitant immune tolerance induction (ITI) and desensitization protocols in a cross-reactive immunologic material (CRIM) negative 7-month-old male patient. At the age of 5 months and eighth dose of the ERT, the patient developed IAR and his rhGAA specific IgE was negative however, his rhGAA specific IgG titer was as high as 12,800. ITI therapy to suppress antibody formation and a desensitization protocol was devised to be given concomitantly. At the end of 5-week therapy, his fatigue and weakness improved profoundly and a control antidrug antibody level decreased at 800. At the time of the patient's follow up, he was still on ERT with desensitization at the age of 15 months without any reactions. CONCLUSIONS: This is the first report in the literature applying concomitant ITI and desensitization protocols in a CRIM negative infantile-onset Pompe disease patient successfully, hence the importance of the case.
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Dessensibilização Imunológica/métodos , Terapia de Reposição de Enzimas/efeitos adversos , Doença de Depósito de Glicogênio Tipo II/tratamento farmacológico , alfa-Glucosidases/efeitos adversos , Reações Cruzadas , Humanos , Tolerância Imunológica , Imunoglobulina G/sangue , Lactente , Masculino , alfa-Glucosidases/imunologiaRESUMO
The objective of this study was to determine the impacts of preventable causes of fracture, such as vitamin D deficiency, disturbed calcium homeostasis and obesity on fracture occurrence in minor traumas. In this way, the effects of relevant parameters on fracture may be further elucidated. A prospective case-control study in children aged 2-18 years children with and without fractures was performed. Participants with a pediatric trauma score higher than 10 presenting to minor trauma were included to exclude the significant impact of severe trauma on fracture. The effects of obesity, parameters associated with vitamin D and Ca homeostasis on fracture occurrence were evaluated. Univariate and multivariate analyses were used to test for associations between fracture status and the assessed variables. The relationships between the variables and the odds of fracture occurrence were examined using logistic regression models. The sample consisted of 76 patients and 50 controls. There were no significant differences between the patients and controls in terms of age, sex, trauma type and pubertal period. The patients had a significantly higher mean BMI percentile (61.2 ± 30.7, 36.7 ± 30.7; P < 0.001). Likewise, patients were more likely than controls to have a lower mean 25(OH)D level and mean phosphorus level (respectively, 13.4 ± 7.0, 17.3 ± 7.8; P = 0.004, and 4.6 ± 0.7, 5.1 ± 0.8; P < 0.001). Moreover, fractures were substantially more frequent in children with vitamin D deficiency (<20 ng/mL, χ2: 7.781, df: 1, P = 0.005). In the multivariate logistic model, BMI percentile and vitamin D levels remained significantly associated with increased odds of fracture [1.02 (1.01-1.04), P < 0.001 and 0.93 (0.89-0.98), P = 0.01]. The present study supports an association of high BMI and vitamin D deficiency with an increased odds of fracture occurrence in children. The findings may help physicians to reduce the risk factors of fracture by preventive efforts. Thus, unexpected health costs and morbidity may be minimized.
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Fraturas Ósseas , Deficiência de Vitamina D , Índice de Massa Corporal , Estudos de Casos e Controles , Criança , Fraturas Ósseas/epidemiologia , Fraturas Ósseas/etiologia , Humanos , Fatores de Risco , Vitamina D , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/epidemiologiaAssuntos
Asma/etiologia , Hipersensibilidade Alimentar/etiologia , Interações entre Hospedeiro e Microrganismos/imunologia , Imunomodulação , Microbiota/imunologia , Linfócitos T/imunologia , Animais , Asma/metabolismo , Suscetibilidade a Doenças , Hipersensibilidade Alimentar/metabolismo , Humanos , Linfócitos T/metabolismoRESUMO
Epithelial tissue can transition from a jammed, solid-like, quiescent phase to an unjammed, fluid-like, migratory phase, but the underlying molecular events of the unjamming transition (UJT) remain largely unexplored. Using primary human bronchial epithelial cells (HBECs) and one well-defined trigger of the UJT, compression mimicking the mechanical effects of bronchoconstriction, here, we combine RNA sequencing data with protein-protein interaction networks to provide the first genome-wide analysis of the UJT. Our results show that compression induces an early transcriptional activation of the membrane and actomyosin network and a delayed activation of the extracellular matrix (ECM) and cell-matrix networks. This response is associated with a signaling cascade that promotes actin polymerization and cellular motility through the coordinated interplay of downstream pathways including ERK, JNK, integrin signaling, and energy metabolism. Moreover, in nonasthmatic versus asthmatic HBECs, common genomic patterns associated with ECM remodeling suggest a molecular connection between airway remodeling, bronchoconstriction, and the UJT.
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Asma , Células Epiteliais , Asma/metabolismo , Movimento Celular/genética , Células Epiteliais/metabolismo , Epitélio/metabolismo , Genômica , HumanosRESUMO
OBJECTIVES: Familial hyperphosphatemic tumoral calcinosis is a rare disorder characterized by hyperphosphatemia with recurrent ectopic periarticular calcifications, in addition to other visceral and vascular manifestations, without any inflammatory or neoplastic disorder. The available treatment strategies are limited. Here we report an eight year old female patient with recurrent lesions under the chin, and bilateral hips which are painful and improving of the size of the lesions and hyperphosphatemia. CASE PRESENTATION: The patient was started to the treatment with peroral acetazolamide however the lesion did not regress but a new lesion appeared then we added sevelamer and topical sodium thiosulfate treatment for three months. After the three months of the combination treatment the lesions, there were no pain, no hyperphospahtemia regression/disappearance of the lesions. CONCLUSIONS: This combination treatment or topical sodium thiosulfate use only may be a novel treatment strategy for the patients prospective controlled trials are needed.