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BACKGROUND: Early embryonic aortic arches (AA) are a dynamic vascular structures that are in the process of shaping into the great arteries of cardiovascular system. Previously, a time-lapsed mechanosensitive gene expression map was established for AA subject to altered mechanical loads in the avian embryo. To validate this map, we investigated effects on vascular microstructure and material properties following the perturbation of key genes using an in-house microvascular gene knockdown system. RESULTS: All siRNA vectors show a decrease in the expression intensity of desired genes with no significant differences between vectors. In TGFß3 knockdowns, we found a reduction in expression intensities of TGFß3 (≤76%) and its downstream targets such as ELN (≤99.6%), Fbn1 (≤60%), COL1 (≤52%) and COL3 (≤86%) and an increase of diameter in the left AA (23%). MMP2 knockdown also reduced expression levels in MMP2 (≤30%) and a 6-fold increase in its downstream target COL3 with a decrease in stiffness of the AA wall and an increase in the diameter of the AA (55%). These in vivo measurements were confirmed using immunohistochemistry, western blotting and a computational growth model of the vascular extracellular matrix (ECM). CONCLUSIONS: Localized spatial genetic modification of the aortic arch region governs the vascular phenotype and ECM composition of the embryo and can be integrated with mechanically-induced congenital heart disease models.
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Dietary lipid manipulation has recently been proposed for managing glycogen storage disease (GSD) type IIIa. This study aimed to evaluate the myopathic, cardiac, and metabolic status, physical activity, growth, and dietary compliance of a personalized diet high in protein and fat for 24 months. Of 31 patients with type IIIa GSD, 12 met the inclusion criteria. Of these, 10 patients (mean age 11.2 ± 7.4 years) completed the study. Patients were prescribed a personalized high-protein, high-fat diet, comprising 3.0-3.5 g/kg/day of protein and 3.0-4.5 g/kg/day of fat, constituting 18.5%-28% and 70.5%-75.7% of daily energy, respectively. Dietary compliance was ensured and assessed via the regular administration of questionnaires. Our results revealed consistent and significant decreases of 22%, 54%, and 30% in the creatinine kinase, creatine kinase-myocardial band, and lactate dehydrogenase levels, respectively. Echocardiography revealed improvements in the Z-scores of the left ventricular mass and interventricular septum thickness. A significant increase in body muscle mass was observed, and a higher score was achieved using the Daily Activity Questionnaire. Growth monitoring revealed an arrest in the height-SDS at the 6th and 12th months, followed by subsequent improvement at the end of the second year. A gradual and persistent decline in the periods of hypo- and hyperglycemia has been reported. Biotinidase activity decreased, whereas hepatosteatosis increased and then decreased by the end of the study. Implementing a high-protein, high-fat diet and monitoring key parameters in patients with type IIIa GSD can lead to myopathic and cardiac improvements and increased physical activity.
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BACKGROUND AND AIM: APO CII, one of several cofactors which regulate lipoprotein lipase enzyme activity, plays an essential role in lipid metabolism. Deficiency of APO CII is an ultra-rare autosomal recessive cause of familial chylomicronemia syndrome. We present the long-term clinical outcomes of 12 children with APO CII deficiency. METHODS AND RESULTS: The data of children with genetically confirmed APO CII deficiency were evaluated retrospectively. Twelve children (8 females) with a mean follow-up of 10.1 years (±3.9) were included. At diagnosis, the median age was 60 days (13 days-10 years). Initial clinical findings included lipemic serum (41.6%), abdominal pain (41.6%), and vomiting (16.6%). At presentation, the median triglyceride (TG) value was 4341 mg/dL (range 1277-14,110). All patients were treated with a restricted fat diet, medium-chain triglyceride (MCT), and omega-3-fatty acids. In addition, seven patients (58.3%) received fibrate. Fibrate was discontinued in two patients due to rhabdomyolysis and in one patient because of cholelithiasis. Seven (58.3%) patients experienced pancreatitis during the follow-up period. One female experienced recurrent pancreatitis and was treated with fresh frozen plasma (FFP). CONCLUSIONS: Apo CII deficiency is an ultra-rare autosomal recessive condition of hypertriglyceridemia associated with significant morbidity and mortality. Low-fat diet and MCT supplementation are the mainstays of therapy, while the benefit of TG-lowering agents are less well-defined.
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Biomarcadores , Hipertrigliceridemia , Triglicerídeos , Humanos , Feminino , Masculino , Estudos Retrospectivos , Criança , Resultado do Tratamento , Triglicerídeos/sangue , Fatores de Tempo , Pré-Escolar , Lactente , Biomarcadores/sangue , Hipertrigliceridemia/diagnóstico , Hipertrigliceridemia/terapia , Hipertrigliceridemia/sangue , Hipertrigliceridemia/complicações , Recém-Nascido , Apolipoproteína C-II/genética , Apolipoproteína C-II/deficiência , Apolipoproteína C-II/sangue , Dieta com Restrição de Gorduras , Hipolipemiantes/uso terapêutico , Hiperlipoproteinemia Tipo I/diagnóstico , Hiperlipoproteinemia Tipo I/terapia , Hiperlipoproteinemia Tipo I/genética , Hiperlipoproteinemia Tipo I/sangue , Hiperlipoproteinemia Tipo I/complicações , Fenótipo , Fatores Etários , Ácidos Fíbricos/uso terapêutico , Predisposição Genética para Doença , Fatores de RiscoRESUMO
ABSTRACT: The purpose of this study was to evaluate emotion dysregulation and temperament-character traits in adolescents with functional neurological symptom disorder (FNSD). Forty adolescents with FNSD and 40 healthy adolescents were evaluated by a semiconstructed diagnosis interview, Temperament and Character Inventory (TCI), Difficulties in Emotion Regulation Scale (DERS), Regulation of Emotions Questionnaire (REQ), and Children's Somatization Inventory-24 (CSI-24). The external and internal dysfunctional emotion regulation scores of REQ, all subscales of DERS, except the awareness subscale, and CSI-24 scores were significantly higher in FNSD patients compared with healthy controls. There were significant differences between the groups in terms of harm avoidance and reward dependence subscale scores of TCI. Multiple logistic regression analysis showed that the external dysfunctional emotion regulation strategy, somatization, and reward dependence are significant predictors of FNSD. Our results provide evidence that adolescents with FNSD experience emotional dysregulation and that the differential value of some temperament-character traits in the diagnosis of FNSD.
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Transtorno Conversivo , Temperamento , Criança , Humanos , Adolescente , Caráter , Transtornos Dissociativos , Inventário de PersonalidadeRESUMO
BACKGROUND: Mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) is a rare autosomal recessive disorder due to mutations in the TYMP gene. Clinical findings are characterized by neurologic manifestations and severe gastrointestinal dysfunction. The syndrome is usually fatal, the most effective treatment appears to be hematopoietic stem cell transplantation (HSCT). PROCEDURE: In this retrospective study, we evaluated HSCT that was performed using a reduced toxicity myeloablative conditioning regimen in patients with MNGIE at our center. RESULTS: A total of six allogeneic transplant procedures were performed in four patients. Three patients had fully matched donors, and one patient had a haploidentical donor. Treosulfan-based myeloablative conditioning regimen was applied in five of six transplants. Bone marrow was used as a stem cell source. One patient is being followed up in the 4th year of posttransplant with full chimeric and without graft versus host disease (GVHD). One patient died of acute stage IV gastrointestinal system GVHD. Two patients underwent second transplantation due to engraftment failure, one of which was the patient who had a haploidentical transplant. CONCLUSIONS: Treosulfan-based regimen is well tolerated, although engraftment failure with this conditioning regimen can be a significant problem. We share our haploidentical transplant experience, which will be the first reported case in the literature.
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Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Humanos , Estudos Retrospectivos , Transplante Homólogo/métodos , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Doença Enxerto-Hospedeiro/etiologia , Condicionamento Pré-Transplante/métodosRESUMO
PURPOSE: To compare the effectiveness of proprioceptive neuromuscular facilitation and myofascial release technique in patients with subacromial impingement syndrome on pain, range of motion, muscle strength, quality of life, functionality and disability. METHODS: Thirty patients were randomly divided into two groups: proprioceptive neuromuscular facilitation group (n = 15) and proprioceptive neuromuscular facilitation combined with myofascial release technique group (n = 15). Both treatment methods were performed 3 times a week for 4 weeks. Pain severity was assessed by Visuel Analog Scale, range of motion by a goniometer, muscle strength by digital hand dynamometer, quality of life by Nottingham health profile, functionality by arm, shoulder and hand problems questionnaire, disability by shoulder pain and disability index. All measurements were used before and after treatments. Pain severity, range of motion and muscle strength were also evaluated after the first session. RESULTS: After the treatment, shoulder pain, range of motion, muscle strength, functionality and disability were improved in two groups (p < 0.05). Proprioceptive neuromuscular facilitation showed improvement in pain, whereas myofascial release technique improved pain, physical activity, emotional state, sleep and total dimensions of life quality (p < 0.05). Proprioceptive neuromuscular facilitation was more effective in reducing activity pain, whereas myofascial release technique was more effective in increasing flexion, external and internal rotation range of motion, flexion and abduction muscle strength after the first session (p < 0.05). CONCLUSIONS: The combined application of proprioceptive neuromuscular facilitation and myofascial release technique has a more acute and cumulative positive effect on pain, range of motion, muscle strength, functionality, disability and quality of life in patients with subacromial impingement syndrome.
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Exercícios de Alongamento Muscular , Síndrome de Colisão do Ombro , Humanos , Dor de Ombro/terapia , Qualidade de Vida , Terapia de Liberação MiofascialRESUMO
Invasive fungal infections (IFI) continue to be an important cause of morbidity and mortality in patients with hematological malignancies. Candida and Aspergillus species constitute most of the IFI in these patients.. It has been reported that most of the invasive aspergillosis epidemics are related to the construction works in the hospital. In this study, we aimed to investigate the frequency of IFI in the old and the new hospital building after relocation in patients with hematological malignancies. Of 8042 patients who were hospitalized in the Department of Hematology, Ondokuz Mayis University Faculty of Medicine between January 2015 and September 2019, 412 patients who were initiated antifungal therapy were included in the study. The patients in the hematology clinic, which were moved to the new oncology hospital building in January 2018, were grouped as prior and after relocation, and their demographical data, hematological diagnosis, chemotherapy regimens, mortality, IFI, focus of infection, presence of central venous catheter, antifungal prophylaxis and treatment, galactomannan level, fungal culture and computed tomography (CT) findings were evaluated retrospectively. It was determined that 55% of the patients were male and the median age was 58 (range:18-93). The rate of IFI development was 5.12% (n= 412) and the rate of invasive mold infection was 1.2% (n= 145). The most common hematological disease for which antifungal treatment initiated was acute myeloid leukemia (AML) with a rate of 50% (n= 206/412). Of patients, 73% received induction chemotherapy (42%, first induction, 31% reinduction), 13.4% received consolidation therapy. Invasive mold infection was diagnosed as 40% possible, 59% probable, 1% proven. While patients had similar characteristics such as age, gender, hematological disease, chemotherapy regimens and antifungal prophylaxis prior and after transportation, the rate of development of invasive mold infection was 2.1%, 2.06 / 1000 patient days, before transportation, 1.37% (p= 0.009), 1.15/1000 patient days (p<0.001) after transportation, and it was statistically significantly lower after transportation. The median value of galactomannan antigen was detected as 0.17 (0.02-5.9). Blood cultures revealed 10.3% fungal growth and the most common growth was Candida albicans with 54.8% and Mucor spp. as mold with 3.2%. Large-scale construction works such as renovation, extension and demolition works in old hospital buildings are a permanent condition in different units. Clinicians should be aware of that infections due to opportunistic fungi can be seen in immunosuppressive patients close to such construction sites, and even cause epidemics. It should be kept in mind that these infections, which can progress with serious morbidity and mortality are difficult to treat but can be prevented by infection control measures.
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Neoplasias Hematológicas , Hematologia , Infecções Fúngicas Invasivas , Antifúngicos/uso terapêutico , Candida , Feminino , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Neoplasias Hematológicas/epidemiologia , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Fúngicas Invasivas/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Primary immunodeficiencies are disorders that cause clinical findings ranging from mild diseases to life-threatening diseases in a wide age range. Infections are the most common complications of primary immunodeficiencies. Caspase associated recruitment domain-9 (CARD9) is a protein that plays a role in fungal immune response. CARD9 deficiency is one of the primary immunodeficiency disorders that show autosomal recessive inheritance and can cause different clinical pictures. It has been associated with various fungal infections such as superficial or deep dermatophytosis, invasive pheohifomycosis, cutaneous mucormycosis, extrapulmonary aspergillosis, mucocutaneous or invasive candidiasis. The most common infections in CARD9 deficiency are caused by Candida spp. In this report, a case of Candida albicans meningoencephalitis due to CARD9 deficiency was presented. It was learned from the medical story that a 37 years old male patient had no known disease or drug use, but had recurrent oral candidiasis and cutaneous fungal infections since childhood, and received liposomal amphotericin B treatment with the diagnosis of C.albicans meningoencephalitis two months ago. It was learned that he was discharged with voriconazole treatment after clinical improvement, and he stopped the voriconazole treatment after discharge and did not go for follow-up. The patient, who reapplied 1.5 months after discharge with complaints of headache, vomiting and altered consciousness, did not have fever and neck stiffness, and Kerning and Bruzinski sign was negative. An external ventricular drainage (EVD) catheter was inserted after hydrocephalus was detected in the brain computerized tomography (CT). In the cerebrospinal fluid (CSF) examination, erythrocyte count was detected as 340/mm3, and no leukocytes were seen. CSF protein level was 28 mg/dl, CSF glucose level was 59 mg/dl (simultaneous blood glucose level was 104 mg/dl). There was no yeast or bacteria in CSF Gram staining and no acidfast bacteria in Ziehl-Neelsen staining. It was learned that there was no growth in the Mycobacterium tuberculosis culture made from CSF sample taken at the first admission of the patient. Serum human immunodeficiency virus antibody was negative. Upon learning of fluconazole-susceptible C.albicans growth in the control CSF culture of the patient, the EVD catheter was changed, and liposomal amphotericin B treatment was started. CSF culture was repeated. Fluconazole-susceptible C.albicans continued to grow in CSF cultures repeated in the follow-ups. No pathology in favor of abscess was detected in the brain magnetic resonance imaging. Fluconazole was added to the current liposomal amphotericin B treatment. Having a history of recurrent mucocutaneous fungal infection in the patient and his siblings, whose parents were third-degree relatives, suggested CARD9 deficiency. In the molecular test studied from blood samples, homozygous p.Q295X mutation due to CARD9 deficiency was detected in the patient and his sister. However, the patient died on the 62nd day of hospitalization due to delayed diagnosis, cerebral complications due to recurrent C.albicans meningoencephalitis, and insufficient treatment as a result of failure to receive the granulocyte colony stimulating factor (G-CSF) treatment. Persistent fungal infections that develop in CARD9 deficiency cause serious complications and mortality. Considering the frequency of CARD9 deficiency in the Turkish population and the lack of diagnostic testing in our country, it is thought that there may be many patients who cannot be diagnosed and who progress with mortality or morbidity. In conclusion, this case was presented to emphasize the consideration of CARD9 deficiency in case of persistent invasive fungal infection or recurrent invasive fungal infection after treatment despite effective antifungal treatment in children and adults who do not have known risk factors for invasive fungal infections.
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Candidíase Invasiva , Meningoencefalite , Adulto , Antifúngicos/uso terapêutico , Proteínas Adaptadoras de Sinalização CARD/genética , Proteínas Adaptadoras de Sinalização CARD/metabolismo , Candida albicans/genética , Criança , Humanos , Masculino , Meningoencefalite/diagnóstico , Meningoencefalite/tratamento farmacológico , MutaçãoRESUMO
In the embryonic heart, blood flow is distributed through a bilaterally paired artery system composed of the aortic arches (AAs). The purpose of this study is to establish an understanding of the governing mechanism of microstructural maturation of the AA matrix and its reversibility, toward the desired macroscopic vessel lumen diameter and thickness for healthy, abnormal, and in ovo repaired abnormal mechanical loading. While matrix-remodeling mechanisms were significantly different for normal versus conotruncal banding (CTB), both led to an increase in vessel lumen. Correlated with right-sided flow increase at Hamburger & Hamilton stages 21, intermittent load switching between collagen I and III with elastin and collagen-IV defines the normal process. However, decreases in collagen I, elastin, vascular endothelial growth factor-A, and fibrillin-1 in CTB were recovered almost fully following the CTB-release model, primarily because of the pressure load changes. The complex temporal changes in matrix proteins are illustrated through a predictive finite-element model based on elastin and collagen load-sharing mechanism to achieve lumen area increase and thickness increase resulting from wall shear stress and tissue strain, respectively. The effect of embryonic timing in cardiac interventions on AA microstructure was established where abnormal mechanical loading was selectively restored at the key stage of development. Recovery of the normal mechanical loading via early fetal intervention resulted in delayed microstructural maturation. Temporal elastin increase, correlated with wall shear stress, is required for continuous lumen area growth.NEW & NOTEWORTHY The present study undertakes comparative analyses of the mechanistic differences of the arterial matrix microstructure and dynamics in the three fundamental processes of control, conotruncal banded, and released conotruncal band in avian embryo. Among other findings, this study provides specific evidence on the restorative role of elastin during the early lumen growth process. During vascular development, a novel intermittent load-switching mechanism between elastin and collagen, triggered by a step increase in wall shear stress, governs the chronic vessel lumen cross-sectional area increase. Mimicking the fetal cardiovascular interventions currently performed in humans, the early release of the abnormal mechanical load rescues the arterial microstructure with time lag.
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Aorta Torácica/embriologia , Hemodinâmica , Estresse Mecânico , Animais , Aorta Torácica/metabolismo , Aorta Torácica/fisiologia , Aorta Torácica/ultraestrutura , Embrião de Galinha , Colágeno/metabolismo , Circulação Coronária , Elastina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Curcumin is assumed to be a plant-derived therapeutic drug that triggers apoptotic cell death in vitro and in vivo by affecting different molecular targets such as NF-κB. Phase I/II trial of curcumin alone or with chemotherapeutic drugs has been accomplished in pancreatic, colon, prostate and breast cancer cases. Recently, autocrine growth hormone (GH) signaling-induced cell growth, metastasis and drug resistance have been demonstrated in breast cancer. In this study, our aim was to investigate the potential therapeutic effect of curcumin by evaluating the molecular machinery of curcumin-triggered apoptotic cell death via focusing on NF-κB signaling and polyamine (PA) metabolism in autocrine GH-expressing MCF-7, MDA-MB-453 and MDA-MB-231 breast cancer cells. For this purpose, a pcDNA3.1 (+) vector with a GH gene insert was transfected by a liposomal agent in all breast cancer cells and then selection was conducted in neomycin (G418) included media. Autocrine GH-induced curcumin resistance was overcome in a dose-dependent manner and curcumin inhibited cell proliferation, invasion-metastasis and phosphorylation of p65 (Ser536), and thereby partly prevented its DNA binding activity in breast cancer cells. Moreover, curcumin induced caspase-mediated apoptotic cell death by activating the PA catabolic enzyme expressions, which led to generation of toxic by-products such as H2O2 in MCF-7, MDA-MB-453 and MDA-MB-231 GH+ breast cancer cells. In addition, transient silencing of SSAT prevented curcumin-induced cell viability loss and apoptotic cell death in each breast cancer cells. In conclusion, curcumin could overcome the GH-mediated resistant phenotype via modulating cell survival, death-related signaling routes and activating PA catabolic pathway.
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Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Curcumina/farmacologia , Hormônio do Crescimento Humano/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Poliaminas/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Comunicação Autócrina/efeitos dos fármacos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Curcuma/química , Curcumina/uso terapêutico , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Humanos , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Células MCF-7 , NF-kappa B/metabolismo , Metástase Neoplásica , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêuticoRESUMO
The aim of this study was to examine the psychometric properties of the 5-item Turkish Reduced Morningness-Eveningness Questionnaire (rMEQ) for the first time. The study involved 875 university students in an adaptation and validation study. Participants completed the rMEQ, MEQ, Depression Anxiety Stress Scale-21 (DASS-21), Insomnia Severity Index (ISI), Barratt Impulsiveness Scale Short Form (BIS-SF), and Oxford Happiness Questionnaire Short Form (OHQ-SF). The factor structure, convergent validity, internal consistency, sensitivity, and specificity of the rMEQ were examined. The confirmatory factor analysis showed that the rMEQ had a one-dimensional structure with good fit indices (χ2/df = 2.94, CFI = 0.990, TLI = 0.979, RMSEA = 0.047, and SRMR = 0.019). There was a significantly strong correlation between rMEQ and MEQ. In addition, we found a significantly weak correlation between rMEQ and DASS-21, ISI, BIS-SF, and OHQ-SF. The internal consistency coefficients of rMEQ were Cronbach's α = 0.706 and McDonald's ω = 0.740. The sensitivity and specificity of rMEQ were 83.3%-92.7% for morning types and 86.3%-87.3% for evening types. The Turkish rMEQ has adequate psychometric properties and can be used to assess an individual's chronotype.
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Ritmo Circadiano , Psicometria , Humanos , Feminino , Masculino , Inquéritos e Questionários , Adulto Jovem , Ritmo Circadiano/fisiologia , Adulto , Turquia , Reprodutibilidade dos Testes , Adolescente , Sono/fisiologiaRESUMO
OBJECTIVES: Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty acid oxidation. Three clinical phenotypes, lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form, have been described in CPT II deficiency. The myopathic form is usually mild and can manifest from infancy to adulthood, characterised by recurrent rhabdomyolysis episodes. The study aimed to investigate the clinical features, biochemical, histopathological, and genetic findings of 13 patients diagnosed with the myopathic form of CPT II deficiency at Ege University Hospital. METHODS: A retrospective study was conducted with 13 patients with the myopathic form of CPT II deficiency. Our study considered demographic data, triggers of recurrent rhabdomyolysis attacks, biochemical metabolic screening, and molecular analysis. RESULTS: Ten patients were examined for rhabdomyolysis of unknown causes. Two patients were diagnosed during family screening, and one was diagnosed during investigations due to increased liver function tests. Acylcarnitine profiles were normal in five patients during rhabdomyolysis. Genetic studies have identified a c.338C>T (p.Ser113Leu) variant homozygous in 10 patients. One patient showed a novel frameshift variant compound heterozygous with c.338C>T (p.Ser113Leu). CONCLUSIONS: Plasma acylcarnitine analysis should be preferred as it is superior to DBS acylcarnitine analysis in diagnosing CPT II deficiency. Even if plasma acylcarnitine analysis is impossible, CPT2 gene analysis should be performed. Our study emphasizes that CPT II deficiency should be considered in the differential diagnosis of recurrent rhabdomyolysis, even if typical acylcarnitine elevation does not accompany it.
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Carnitina O-Palmitoiltransferase , Rabdomiólise , Humanos , Carnitina , Carnitina O-Palmitoiltransferase/genética , Estudos Retrospectivos , Rabdomiólise/etiologia , Rabdomiólise/genéticaRESUMO
Aromatic L-amino acid decarboxylase (AADC) deficiency is a disease in which neurological findings are dominant due to deficiencies in neurotransmitter synthesis; hypoglycemia caused by autonomic dysfunction is one of the symptoms that may be encountered. Here we report a mild AADC deficiency presenting with hypoglycemia without a neurological sign. A 4-year-old girl presented with recurrent hypoglycemia. Her growth and development were normal. Plasma insulin and cortisol values were normal in the sample at the time of hypoglycemia. The C8:1-Carnitine elevation was detected in the acylcarnitine profile. The clinic exome panel was performed with the suggestion of a fatty acid oxidation defect. However, a homozygous variant in the DDC gene was detected. On top of that, CSF neurotransmitter analysis revealed low 5-hydroxy indol acetic ( 5 HIAA ) and homovanillic acid ( HVA ) and high 3-O-methyl-dopa and methyltetrahydrofolate ( 5 MTHF ) consistent with AADC deficiency. Plasma AADC enzyme activity was low. The episodes of hypoglycemia were treated with uncooked cornstarch. Our case emphasizes that AADC deficiency should be considered in patients with hypoglycemia.
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OBJECTIVES: Congenital Glycosylation Disorders (CDG) are a large group of inherited metabolic diseases with multi-organ involvement. Herein, we aimed to expand the clinical characteristics of patients with CDG based on our experience with diagnoses and follow-up of CDG patients from different subtypes. METHODS: The clinical and laboratory findings from the last 15 years were reviewed retrospectively in Ege University Child Metabolism and Nutrition Department. RESULTS: There were 8 (57.2â¯%) females and 6 (42.8â¯%) males. Diagnoses of the patients were PMM2-CDG (n=4), PGM1-CDG (n=2), DPAGT1-CDG (n=2), SRD5A3-CDG (n=2), MPI-CDG (n=1), POMT2-CDG (n=1), B3GALNT2-CDG (n=1), DPM1-CDG (n=1). The clinical findings of the patients were dysmorphia (85.7â¯%), developmental delay (85.7â¯%), intellectual disability (85.7â¯%), ocular abnormalities (64.2â¯%), skeletal malformations (64.2â¯%), failure to thrive (57.1â¯%), microcephaly (57.1â¯%), hepatomegaly (35.7â¯%), hearing loss (35.7â¯%), seizures (28.5â¯%), gastrointestinal symptoms (21.4â¯%), endocrine abnormalities (21.4â¯%), and cardiac abnormalities (7.1â¯%). Laboratory findings were abnormal TIEF (92.8â¯%), abnormal liver enzymes (64.2â¯%), decreased protein C (64.2â¯%), decreased antithrombin III (64.2â¯%), decreased protein S (42.8â¯%), hypogammaglobulinemia (35.7â¯%), cerebellar hypoplasia (28.5â¯%), CK elevation (7.1â¯%), and hypoglycemia (7.1â¯%). CONCLUSIONS: This study contributes to the literature by sharing our ultra-rare DPM1-CDG case with less than 20 cases in the literature and expanding the clinical and molecular characteristics of other CDG patients. Hyperinsulinemic hypoglycemia, short stature, hypothyroidism, growth hormone deficiency, hypogammaglobulinemia, pericardial effusion, elevated CK, congenital myasthenia, and anorectal malformation were unique findings that were observed. Cerebello-ocular findings accompanying multi-organ involvement were an essential clue for a possible CDG.
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Agamaglobulinemia , Defeitos Congênitos da Glicosilação , Hipoglicemia , N-Acetilgalactosaminiltransferases , Masculino , Criança , Feminino , Humanos , Seguimentos , Estudos Retrospectivos , Glicosilação , Defeitos Congênitos da Glicosilação/diagnóstico , Defeitos Congênitos da Glicosilação/genética , Proteínas de Membrana/genética , 3-Oxo-5-alfa-Esteroide 4-Desidrogenase , N-Acetilgalactosaminiltransferases/metabolismoRESUMO
OBJECTIVE: Coronavirus disease 2019 (COVID-19) causes significant morbidity and mortality in individuals with chronic disease. There is not enough information about the course of coronavirus disease in lysosomal storage diseases. This study aimed to evaluate coronavirus disease vaccination status and the impact of coronavirus disease on lysosomal storage disease. MATERIALS AND METHODS: The study included 87 lysosomal storage disease patients. The patients' diagnoses were Gaucher, mucopolysaccharidosis I, II, IVA, VI, VII, Fabry, and Pompe. A questionnaire assessing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exposure, coronavirus disease symptoms, and vaccine status was administered in person or by phone calls. RESULTS: The number of coronavirus disease positive patients was 8 (9.1%). Only 2 patients were treated in the intensive care unit. Other coronavirus disease patients had mild symptoms and stayed in-home quarantine. Patients over 12 years of age could receive a COVID-19 vaccine. 63.5% of those aged ≥12 years were vaccinated. CONCLUSION: Lysosomal storage disease patients did not have an increased risk of COVID-19 compared to the healthy population, despite the chronic inflammatory disease. Vaccination of lysosomal storage disease patients will be protective against severe coronavirus disease.
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The intricate, tightly controlled mechanism of wound healing that is a vital physiological mechanism is essential to maintaining the skin's natural barrier function. Numerous studies have focused on wound healing as it is a massive burden on the healthcare system. Wound repair is a complicated process with various cell types and microenvironment conditions. In wound healing studies, novel therapeutic approaches have been proposed to deliver an effective treatment. Nanoparticle-based materials are preferred due to their antibacterial activity, biocompatibility, and increased mechanical strength in wound healing. They can be divided into six main groups: metal NPs, ceramic NPs, polymer NPs, self-assembled NPs, composite NPs, and nanoparticle-loaded hydrogels. Each group shows several advantages and disadvantages, and which material will be used depends on the type, depth, and area of the wound. Better wound care/healing techniques are now possible, thanks to the development of wound healing strategies based on these materials, which mimic the extracellular matrix (ECM) microenvironment of the wound. Bearing this in mind, here we reviewed current studies on which NPs have been used in wound healing and how this strategy has become a key biotechnological procedure to treat skin infections and wounds.
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Lipodystrophy syndromes are rare complex multisystem disorders caused by generalized or partial lack of adipose tissue. Adipose tissue dysfunction in lipodystrophy is associated with leptin deficiency. Lipodystrophy leads to severe metabolic problems. These abnormalities include, but are not limited to, insulin-resistant diabetes, severe hypertriglyceridemia, and lipid accumulation in ectopic organs such as the liver, and are associated with end-organ complications. Metabolic abnormalities can be present at the time of diagnosis or may develop over time as the disease progresses. In addition to metabolic abnormalities, subtype-specific presentations due to underlying molecular etiology in genetic forms and autoimmunity in acquired forms contribute to severe morbidity in lipodystrophy.
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Leptina/deficiência , Lipodistrofia/complicações , Doenças Autoimunes/etiologia , Diabetes Mellitus/etiologia , Cardiopatias/genética , Humanos , Hipertrigliceridemia/etiologia , Resistência à Insulina , Nefropatias/complicações , Metabolismo dos Lipídeos , Lipodistrofia/genética , Lipodistrofia/metabolismo , Lipodistrofia/mortalidade , Fígado/metabolismo , Síndrome Metabólica/etiologia , Doenças Neuromusculares/etiologia , Hepatopatia Gordurosa não Alcoólica/etiologia , Pancreatite/etiologia , SíndromeRESUMO
Human toxocariasis is a parasitic disease transmitted to humans by ingestion of Toxocara spp. larvae. Rural area residents and children have higher risk for this parasitic infection. The disease is frequently asymptomatic; however, it may cause symptoms such as cough, fever, headache, myalgia or other conditions such as lymphadenopathy and granulomatous hepatitis. Albendazole is used for the treatment of toxocariasis diagnosed by serologic and immunological methods. Herein, we report two cases of toxocariasis that were investigated due to hypereosinophilia and lymphadenopathy for a long time.
Assuntos
Eosinofilia/etiologia , Linfadenopatia/etiologia , Toxocaríase/complicações , Albendazol/uso terapêutico , Animais , Anti-Helmínticos/uso terapêutico , Eosinofilia/diagnóstico , Eosinofilia/tratamento farmacológico , Humanos , Linfadenopatia/diagnóstico , Linfadenopatia/tratamento farmacológico , Toxocara , Toxocaríase/diagnóstico , Toxocaríase/tratamento farmacológicoRESUMO
The microstructure for mature vessels has been investigated in detail, while there is limited information about the embryonic stages, in spite of their importance in the prognosis of congenital heart defects. It is hypothesized that the embryonic vasculature represents a disorganized but dynamic soft tissue, which rapidly evolves toward a specialized multi-cellular vascular structure under mechanical loading. Here the microstructural evolution process of the embryonic pharyngeal aortic arch structure was simulated using an in ovo validated long-term growth and remodeling computational model, implemented as an in-house FEBio plug-in. Optical coherence tomography-guided servo-null pressure measurements are assigned as boundary conditions through the critical embryonic stages. The accumulation of key microstructural constituents was recorded through zoom confocal microscopy for all six embryonic arch arteries simultaneously. The total amount and the radial variation slope of the collagen along the arch wall thickness in different arch types and for different embryonic times, with different dimension scales, were normalized and compared statistically. The arch growth model shows that the stress levels around the lumen boundary increase from [Formula: see text] (Stage 18) to a level higher than [Formula: see text] (Stage 24), depending on matrix constituent production rates, while the homeostatic strain level is kept constant. The statistical tests show that although the total collagen levels differentiate among bilateral positions of the same arch, the shape coefficient of the matrix microstructural gradient changes with embryonic time, proving radial localization, in accordance with numerical model results. In vivo cell number (DAPI) and vascular endothelial growth factor distributions followed similar trends.
Assuntos
Aorta Torácica/anatomia & histologia , Aorta Torácica/embriologia , Simulação por Computador , Modelos Anatômicos , Animais , Galinhas , Colágeno Tipo I/metabolismo , Análise de Elementos Finitos , Imageamento Tridimensional , Pressão , Reprodutibilidade dos Testes , Estresse MecânicoRESUMO
INTRODUCTION: Unspecified psychosis, defined with the F29 code in the International Classification of Diseases (ICD) 10th version is commonly used if there is inadequate information to make the diagnosis of a specific psychotic disorder. There is a lack of data about the prevalence, incidence, diagnostic validity and stability of this diagnosis. Therefore, we aimed to evaluate the prevalence and diagnostic consistency of unspecified psychosis in the outpatient unit. METHODS: Patients diagnosed with the ICD-10 F29 code at the first visit and interviewed at least three times between January 2012-2016 in the Psychiatry Outpatient Clinic were included (n=138). Hospital records were reviewed retrospectively and data were analyzed with SPSS 19th version. RESULTS: Mean duration of follow-up was 22.8±14.7 months. The diagnoses at the final follow-up were unspecified psychosis (43%), bipolar disorders (18%), schizophrenia (11%), major depression (7%), and anxiety disorders (4%). No significant difference was found between the follow-up diagnoses in terms of age, duration of follow-up, gender, educational status and marital status. CONCLUSION: The diagnostic stability of unspecified psychosis is low compared to other psychotic disorders. Follow-up studies with larger sample sizes are required to elucidate the the low diagnostic stability of unspecified psychosis.