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1.
Mol Syndromol ; 15(1): 77-82, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38357256

RESUMO

Introduction: Familial glucocorticoid deficiency (FGD) is a rare autosomal recessive disease resulting from isolated glucocorticoid deficiency or unresponsiveness to adrenocorticotropic hormone. Patients with FGD usually present in infancy or early childhood with hyperpigmentation, recurrent infections, and hypoglycemia. The salt-wasting crisis is rare. Case Presentation: A term female neonate was admitted to the neonatal intensive care unit due to respiratory distress. On physical examination, she had generalized hyperpigmentation. Initial laboratory work-up yielded normal serum electrolytes and glucose. Hyponatremia and hyperkalemia emerged on follow-up. The patient was diagnosed as having primary adrenal insufficiency (PAI) with elevated plasma adrenocorticotropin hormone and reduced cortisol levels and hydrocortisone. We started on oral sodium (5 mEq/kg/day) and fludrocortisone (FC) (0.2 mg/day) treatment to the patient. Ultrasonography revealed hypoplastic adrenal glands. Molecular genetic analysis revealed a previously reported homozygous pathogenic variant NM_000529.2: c.560delT (p.V187fs*29) in the MC2R gene. FC dose was tapered to 0.05 mg/day on the third month of life and was stopped at tenth months of age with maintenance of normal serum electrolytes and clinical findings. Conclusion: FGD due to MC2R gene mutation may rarely present with a salt-wasting crisis in the neonatal period. Identifying the causative gene with the pathogenic variant in PAI may serve to individualize a treatment plan.

2.
Ulus Travma Acil Cerrahi Derg ; 30(1): 9-12, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38226575

RESUMO

BACKGROUND: While numerous studies have proposed algorithms for the management of Stapfer Type 2 ERCP perforations, there is limited research on surgical treatment options specifically for this patient group. Our aim is not to propose a new algorithm for these patients but to describe our surgical approach and contribute to the literature with our surgical procedure applied in Stapfer Type 2 ERCP perforation cases. METHODS: Between 2016 and 2023, a total of 12 patients with Stapfer Type 2 ERCP perforations underwent surgery at our hospital. Duodenal diverticulization is a commonly used method in complex duodenal perforation cases. We performed a procedure that involves the removal of the external biliary pathway, hepaticojejunostomy, and a wide Braun anastomosis in addition to the duodenal diverticulization procedure, which we have termed "modified duodenal diverticulization." RESULTS: Eleven out of the 12 patients were discharged successfully without any complications. One patient, who had a late diagnosis, underwent surgery 5 days after ERCP. This patient had ongoing sepsis before the operation, which continued postoperatively and eventually led to multiple organ failure and death. CONCLUSION: There are limited alternatives for the surgical treatment of Type 2 ERCP perforations, and the widely preferred triple ostomy method may not address the underlying pathology necessitating ERCP. The modified duodenal diverticulization method, offering a definitive treatment, can be considered a surgical option for Type 2 ERCP perforations.


Assuntos
Sistema Biliar , Perfuração Intestinal , Humanos , Colangiopancreatografia Retrógrada Endoscópica/efeitos adversos , Estudos Retrospectivos , Duodeno/cirurgia , Anastomose Cirúrgica/efeitos adversos , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia
3.
Liver Int ; 44(3): 811-822, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38230874

RESUMO

BACKGROUND AND AIMS: To systematically review the literature for reports on Wolcott-Rallison syndrome, focusing on the spectrum and natural history, genotype-phenotype correlations, patient and native liver survival, and long-term outcomes. METHODS: PubMed, Livio, Google Scholar, Scopus and Web of Science databases were searched. Data on genotype, phenotype, therapy, cause of death and follow-up were extracted. Survival and correlation analyses were performed. RESULTS: Sixty-two studies with 159 patients met the inclusion criteria and additional 30 WRS individuals were collected by personal contact. The median age of presentation was 2.5 months (IQR 2) and of death was 36 months (IQR 50.75). The most frequent clinical feature was neonatal diabetes in all patients, followed by liver impairment in 73%, impaired growth in 72%, skeletal abnormalities in 59.8%, the nervous system in 37.6%, the kidney in 35.4%, insufficient haematopoiesis in 34.4%, hypothyroidism in 14.8% and exocrine pancreas insufficiency in 10.6%. Episodes of acute liver failure were frequently reported. Liver transplantation was performed in six, combined liver-pancreas in one and combined liver-pancreas-kidney transplantation in two individuals. Patient survival was significantly better in the transplant cohort (p = .0057). One-, five- and ten-year patient survival rates were 89.4%, 65.5% and 53.1%, respectively. Liver failure was reported as the leading cause of death in 17.9% of cases. Overall survival was better in individuals with missense mutations (p = .013). CONCLUSION: Wolcott-Rallison syndrome has variable clinical courses. Overall survival is better in individuals with missense mutations. Liver- or multi-organ transplantation is a feasible treatment option to improve survival.


Assuntos
Diabetes Mellitus Tipo 1 , Diabetes Mellitus , Epífises/anormalidades , Osteocondrodisplasias , Recém-Nascido , Humanos , Lactente , Seguimentos , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Osteocondrodisplasias/genética , eIF-2 Quinase/genética
4.
Trop Anim Health Prod ; 56(1): 18, 2023 Dec 18.
Artigo em Inglês | MEDLINE | ID: mdl-38110568

RESUMO

In pheasants, which are generally raised in large flocks, stocking density is important for their growth and development, normal behavior and welfare. But there is still a lack of information on the optimum stocking density for game birds. This research was conducted on a total of 200 pheasants to examine the effects of low (5 pheasant/m2) and high (10 pheasant/m2) stocking density rearing practices on body weight, morphological development, behavioral characteristics and welfare parameters such as foot-pad dermatitis and plumage quality. When we look at the study results, it was determined that the density of stocking did not make a difference in the first 13 weeks of age, but pheasants reared at low density at the ages of 14-16 weeks reached higher body weight. In terms of body weight at 14, 15, and 16 weeks, the low stocking density group had an average of approximately 41, 71, and 94 g higher than the high stocking density group, respectively (p<0.05). It had been found that low density provides better morphological development. The low group was found to be significantly higher than the high group in terms of ornithological size, wingspan, back length, tail length, head length and head width, 5.9 cm, 2 cm, 1.3 cm, 7.6 cm, 1.7 mm and 1 mm, respectively (p<0.05). Since the animals in the low group had more individual space, they had the opportunity to perch and therefore exhibit more passive behavior. On the other hand, pheasants in the low group exhibited higher levels of aggressive behavior (p<0.05). More foraging behavior was observed in the higher group and the low-density group consumed more feed in the 14th week (p<0.05). But no significant differences were detected between groups in terms of feed consumption in other weeks (p>0.05). A 1.12 point higher score was calculated in the low group compared to the high group, especially in terms of tail feather quality, and as a result, pheasants reared in low stocking density had better plumage quality (p<0.05). It had been determined that as the stocking density decreases in the rearing of pheasants, they exhibit easier flight and roosting behaviors and therefore they were less affected by feather pecking behavior and had better feather quality. In addition, it had been determined that pheasants grow and develop better in this group, which had more rest opportunities. In conclusion, rearing at low stocking density is recommended for better fattening performance and better welfare conditions.


Assuntos
Carne , Codorniz , Animais , Peso Corporal , Agressão , Abrigo para Animais , Galinhas , Criação de Animais Domésticos/métodos
5.
Ulus Travma Acil Cerrahi Derg ; 29(10): 1130-1137, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37791433

RESUMO

BACKGROUND: Burns is one of the most common traumas worldwide. Severely injured burn patients have an increased risk for mortality and morbidity. This study aimed to evaluate well-known risk factors for burn mortality and comparison of six machine learn-ing (ML) Algorithms' predictive performances. METHODS: The medical records of patients who had burn injuries treated at Izmir Bozyaka Training and Research Hospital's Burn Treatment Center were examined retrospectively. Patients' demographics such as age and gender, total burned surface area (TBSA), Inhalation injury (II), full-thickness burns (FTBSA), and burn types (BT) were recorded and used as input features in ML models. Pa-tients were analyzed under two groups: Survivors and Non-Survivors. Six ML algorithms, including k-Nearest Neighbor, Decision Tree, Random Forest, Support Vector Machine, Multi-Layer Perceptron, and AdaBoost (AB), were used for predicting mortality. Several different input feature combinations were evaluated for each algorithm. RESULTS: The number of eligible patients was 363. All six parameters (TBSA, Gender, FTBSA, II, Age, BT) that were included in ML algorithms showed a significant difference (p<0.001). The results show that AB algorithm using all input features had the best predic-tion performance with an accuracy of 90% and an area under the curve of 92%. CONCLUSION: ML algorithms showed strong predictive performance in burn mortality. The development of an ML algorithm with the right input features could be useful in the clinical practice. Further investigations are needed on this topic.


Assuntos
Queimaduras , Humanos , Estudos Retrospectivos , Queimaduras/terapia , Algoritmos , Fatores de Risco , Aprendizado de Máquina
6.
Turk J Chem ; 47(1): 232-241, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37720855

RESUMO

Microfluidic systems have attracted significant interest in recent years as they are extensively employed in lab-on-chip and organ-on-chip research. Their combination with electrochemical platforms offers many advantages, promising a high potential for sensing applications, still the microfluidic-channel integration onto electrodes might induce challenges related to changes in signal-to-noise ratios and mass transport conditions. In this study, we investigated the effect of microfluidic channel integration in redox behavior of thermally deposited gold thin film microelectrodes by voltammetric (CV and SWV) electrochemical measurements. Using different dimensions of PDMS microfluidic channels (i.e. widths of 50, 100, 250, and 500 µm) and a constant electrode dimension (200 µm), we analyzed the relationship between altered electroactive area and electrochemical response against target redox molecules. The increases in electroactive area which were determined by the microfluidic channel sizes were in well-correlation with the obtained CV and SWV redox currents as expected. There was no significant decrease in signal-to-noise ratio in microchannel-integrated electrodes. AFM and SEM characterization demonstrated that thermally deposited thin film electrodes had significantly lower (approximately 25 fold) surface roughness in comparison to commercial screen-printed electrodes. Additionally, we have observed a clear microelectrode-to-macroelectrode transition, from hemispherical to linear (planar) diffusion in other terms, with the increasing channel size.

7.
J Funct Biomater ; 14(6)2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37367293

RESUMO

Implantable electrochemical sensors that enable the real-time detection of significant biomarkers offer huge potential for the enhancement and personalisation of therapies; however, biofouling is a key challenge encountered by any implantable system. This is particularly an issue immediately after implantation, when the foreign body response and associated biofouling processes are at their most active in passivating a foreign object. Here, we present the development of a sensor protection and activation strategy against biofouling, based on coatings consisting of a pH-triggered, dissolvable polymer, that covered a functionalised electrode surface. We demonstrate that reproducible delayed sensor activation can be achieved, and that the length of this delay can be controlled by the optimisation of coating thickness, homogeneity and density through tuning of the coating method and temperature. Comparative evaluation of the polymer-coated and uncoated probe-modified electrodes in biological media revealed significant improvements in their anti-biofouling characteristics, demonstrating that this offers a promising approach to the design of enhanced sensing devices.

8.
J Pediatr Endocrinol Metab ; 36(5): 451-457, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37017079

RESUMO

OBJECTIVES: Metabolically healthy obesity (MHO) has been reported with varying frequencies in children. The reasons of metabolically healthy phenotype in some obese subjects are unclear. Our aim was to identify the frequency of MHO in obese subjects, to assess the potential associations of demographic characteristics, serum uric acid, alanine transaminase (ALT), pediatric nonalcoholic fatty liver disease fibsosis score probability (PNFS p) with MHO status and to evaluate the differences between MHO and metabolically unhealthy obesity (MUO) with regard to metabolic syndrome surrogates. METHODS: 251 consecutive obese subjects (125 females) aged 7-18 years were included. Subjects were classified as having MHO according to Damanhoury's criteria. Several metabolic variables were measured, PNFS p was calculated by using the formula: z=1.1+(0.34*sqrt(ALT))+ (0.002*ALP)-(1.1*log(platelets)-(0.02*GGT). RESULTS: Median age of the subjects was 12.5 yr (range: 7.0-17.0 yr). The frequency of MHO was 41 %. Subjects with MHO were significantly younger, had lower waist circumference (WC) and waist height ratio (WHtR) and lower HOMA-IR than those without MHO(p<0.05 for all). Frequencies of hyperuricemia, hypertransaminasemia, hepatosteatosis and PNFS p values≥8 were similar betwen the groups. When putatively influential factors associated with MHO status were assessed with logistic regression analysis, only WC(ß=1.03) and HOMA-IR(ß=1.166) emerged as significant factors(Nagelkerke R2=0.142). None of the investigated demographic factors were associated with MHO status. CONCLUSIONS: We found a remarkably high frequency of MHO status. Nevertheless, the absence of decreased frequencies of hyperuricemia, hypertransaminasemia and PNFS in subjects with MHO may suggest the need to reconsider the validity of the criteria defining MHO.


Assuntos
Hiperuricemia , Síndrome Metabólica , Obesidade Metabolicamente Benigna , Obesidade Pediátrica , Feminino , Criança , Humanos , Síndrome Metabólica/metabolismo , Obesidade Pediátrica/complicações , Ácido Úrico , Hiperuricemia/complicações , Fenótipo , Fatores de Risco , Índice de Massa Corporal
9.
Int J Pediatr Otorhinolaryngol ; 165: 111454, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36696712

RESUMO

OBJECTIVES: The prevalences of pediatric obesity and its associated comorbidities such as metabolic syndrome (metS) are rising. The aim of this study was to evaluate the association of metS status with sensorineural hearing loss in pediatric obese patients. METHODS: A two-center observationalprospective study was designed. In this study, 252 consecutive treatment-naive pediatric obese patients aged 5.8-17.8 yr in a tertiary pediatric Endocrinology outpatient clinic were prospectively enrolled. Following standard clinical and biochemical evaluations, the obese patients were diagnosed as having metabolic syndrome (metS) or not according to Internetional Diabetes Federation Criteria. All the patients were evaluated with tympanometry and pure tone audiometry tests after otomicroscopic examination. Comparative analyses of audiometric evaluations were performed between metS+ and metS- subgroups of the obese patients. RESULTS: The median age of the patients was 12.5 yr (range: 6.0-17.8 yr) and 56.3% of the patients were male. Metabolic syndrome was diagnosed in 82 (32.5%) patients. Age, gender distribution, history of the ventilation tube, and pubertal stage of the metS + patients and metS- counterparts were not statistically different (p > 0.05 for all). Pure tone hearing thresholds at all frequencies (125, 250, 500, 1k, 2k, 4k, 8k) were significantly higher in the metS + group then the metS- group (p˂0.05 for all). The tympanometry results were not statistically different between the two groups (p˃0.05). Abdominal obesity, hypertension, fasting hyperglycemia and dyslipidemia were not associated with increased hearing thresholds in metS + patients (p˃0.05 for all). CONCLUSION: Metabolic syndrome was associated with increased rates of subclinical hearing loss in our cohort. None of the investigated metS components emerged as a positive association with hearing loss in our cohort. Longitudinal follow-up of our cohort may help probe the causality of the association we found.


Assuntos
Surdez , Perda Auditiva Neurossensorial , Perda Auditiva , Síndrome Metabólica , Obesidade Pediátrica , Humanos , Masculino , Criança , Feminino , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Perda Auditiva Neurossensorial/diagnóstico , Perda Auditiva Neurossensorial/epidemiologia , Perda Auditiva Neurossensorial/etiologia , Perda Auditiva/etiologia , Audição , Obesidade Pediátrica/complicações , Obesidade Pediátrica/diagnóstico , Obesidade Pediátrica/epidemiologia , Surdez/complicações
10.
Oncogene ; 42(9): 679-692, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36599922

RESUMO

Breast cancer stem cells (BCSC) are presumed to be responsible for treatment resistance, tumor recurrence and metastasis of breast tumors. However, development of BCSC-targeting therapies has been held back by their heterogeneity and the lack of BCSC-selective molecular targets. Here, we demonstrate that RAC1B, the only known alternatively spliced variant of the small GTPase RAC1, is expressed in a subset of BCSCs in vivo and its function is required for the maintenance of BCSCs and their chemoresistance to doxorubicin. In human breast cancer cell line MCF7, RAC1B is required for BCSC plasticity and chemoresistance to doxorubicin in vitro and for tumor-initiating abilities in vivo. Unlike Rac1, Rac1b function is dispensable for normal mammary gland development and mammary epithelial stem cell (MaSC) activity. In contrast, loss of Rac1b function in a mouse model of breast cancer hampers the BCSC activity and increases their chemosensitivity to doxorubicin treatment. Collectively, our data suggest that RAC1B is a clinically relevant molecular target for the development of BCSC-targeting therapies that may improve the effectiveness of doxorubicin-mediated chemotherapy.


Assuntos
Neoplasias da Mama , Neoplasias Mamárias Animais , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Mamárias Animais/patologia , Recidiva Local de Neoplasia/patologia , Células-Tronco Neoplásicas/patologia
11.
J Pediatr Hematol Oncol ; 45(5): e660-e661, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-36706297

RESUMO

BACKGROUND: Delayed diagnosis of hypothyroidism may result in atypical presentations. Here, we report a case with decreased serum level and activity of von Willebrand factor due to untreated profound hypothyroidism. OBSERVATION: A 9-year-old girl, presented with prolonged gingival bleeding after dental extraction. Clinical findings of the case were consistent with hypothyroidism, and the laboratory workup results revealed decreased serum level and activity of von Willebrand factor associated with profound hypothyroidism. Restoration of euthyroidism normalized the coagulation parameters. CONCLUSION: Delayed diagnosis of hypothyroidism may lead to atypical presentations such as bleeding diathesis. Profound hypothyroidism should be considered in the differential diagnosis of acquired von Willebrand disease to avoid undue treatment.


Assuntos
Transtornos Hemorrágicos , Hipotireoidismo , Doenças de von Willebrand , Feminino , Humanos , Criança , Fator de von Willebrand , Hipotireoidismo/complicações , Doenças de von Willebrand/complicações , Extração Dentária/efeitos adversos
13.
Turk J Surg ; 38(1): 46-54, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35873746

RESUMO

Objectives: This study aimed to compare the pay for performance system applied nationally in Turkey and in other countries around the world and to reveal the effects of the system applied in our country on the general surgery. Material and Methods: Current literature and countries' programs on the implementation of the pay for performance system were recorded. The results of the Turkish Surgical Association's performance and Healthcare Implementation Communique (HIC) commission studies were evaluated in light of the literature. Results: Many countries have implemented performance systems on a limited scale to improve quality, speed up the diagnosis, treatment, and control of certain diseases, and they have generally applied it as a financial promotion by receiving the support of health insurance companies and nongovernmental organizations. It turns out that surgeons in our country feel that they are being wronged because of the injustice in the current system because the property of their works is not appreciated and they cannot get the reward for the work they do. This is also the reason for the reluctance of medical school graduates to choose general surgery. Conclusion: Authorities should pay attention to the opinions of associations and experts in the related field when creating lists of interventional procedures related to surgery. Equal pay should be given to equal work nationally, and surgeons should be encouraged by incentives to perform detailed, qualified surgeries. There is a possibility that the staff positions opened for general surgery, as well as, all surgical branches will remain empty in the near future.

14.
Ulus Travma Acil Cerrahi Derg ; 28(6): 790-795, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35652868

RESUMO

BACKGROUND: For prediction of mortality and clinical course, various scoring systems had been developed. We choose four well known burn specific scoring systems and a general scoring system that using in Intensive Care Units. The primary outcome of this study was evaluate the predictive performances of this models and define the optimal one for our patient population. METHODS: Variables analyzed were age, gender, burn type, total burned surface area (TBSA), total partial thickness burn area, total full thickness burn area, inhalation injuries, mechanical ventilation supports, blood products usage, total scores of Abbreviated Burn Severity Index (ABSI), revised Baux, Belgian Outcome in Burn Injury, Fatality by Longevity, Acute Physiology and Chronic Health Eval-uation II (APACHE II) score, Measured Extent of burn and Sex (FLAMES) and APACHE II, and their relations with mortality. RESULTS: In our study, a statistically significant relationship was found with mortality between age, TBSA, full thickness burn percent-age, inhalation injury, burn type, and it was similar to literature. Female gender was found to be a significant risk factor for mortality. CONCLUSION: We compared several burn mortality scoring systems and their predictional mortality rates. ABSI scores of patients for estimated mortality rates were similar to our mortality rate. Consequently, it was thought that ABSI was included all mortality-re-lated parameters.


Assuntos
Queimaduras , Índice de Gravidade de Doença , APACHE , Fatores Etários , Queimaduras/mortalidade , Queimaduras por Inalação , Feminino , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos , Fatores de Risco , Fatores Sexuais
15.
J Pediatr Endocrinol Metab ; 35(5): 649-655, 2022 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-35334196

RESUMO

BACKGROUND: Babies born small for gestational age (SGA) are at risk of obesity and metabolic syndrome (MetS). Spexin (SPX) is a novel peptide implicated in food intake and obesity. Spexin levels are lower in obese subjects. This study investigated the potential association of SPX and some obesity related peptides such as leptin and active ghrelin with size at birth and MetS components in prepubertal children born term and either SGA or appropriate for GA (AGA). Secondary aim was to identify whether any of the investigated peptides were associated with MetS components. METHODS: We conducted a cross-sectional study of 37 consecutive (median age: 5.6 y) SGA- and 50 (median age: 5.9 y) AGA-born children. Clinical evaluations were performed using standard methods. Several biochemical variables (SPX, total leptin, and active ghrelin levels) were analyzed. Age-dependent cut-off values were used to define MetS components, including excess adiposity, hypertension, insulin resistance, and dyslipidemia. The associations between the assessed clinical and laboratory variables and MetS components were investigated. RESULTS: Children born SGA had higher frequencies of MetS components than AGA-born peers (p < 0.01). None of the investigated peptides were different between children born SGA and AGA after correcting for body mass index (p > 0.05 for all). Serum SPX levels were lower in children with at least one metS component than those without MetS components (p = 0.018). CONCLUSIONS: Size at birth had no association with serum SPX. Serum SPX levels are decreased in prepubertal children with MetS components.


Assuntos
Síndrome Metabólica , Peso ao Nascer , Pré-Escolar , Estudos Transversais , Feminino , Grelina , Humanos , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional/metabolismo , Insulina , Leptina , Síndrome Metabólica/etiologia , Obesidade , Hormônios Peptídicos
16.
Turk J Surg ; 38(3): 312-313, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36846055

RESUMO

One of the factors that impair anastomosis healing in patients undergoing hepaticojejunostomy is tension of the anastomosis. There may be tension, especially in cases with a short mesojejunum. In cases where the jejunum cannot be brought higher, positioning the liver a little lower may be a solution. We placed a Bakri balloon between the liver and diaphragm to position the liver to a lower level. Here we present a successful hepaticojejunostomy case in which we placed a Bakri balloon to decrease the anastomosis tension.

17.
Biosens Bioelectron ; 197: 113728, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34763151

RESUMO

The development of robust implantable sensors is important in the successful advancement of personalised medicine as they have the potential to provide in situ real-time data regarding the status of health and disease and the effectiveness of treatment. Tissue pH is a key physiological parameter and herein, we report the design, fabrication, functionalisation, encapsulation and protection of a miniaturised, self-contained, electrochemical pH sensor system and characterisation of sensor performance. Notably for the first time in this environment the pH sensor was based on a methylene blue redox reporter which showed remarkable robustness, accuracy and sensitivity. This was achieved by encapsulation of a self-assembled monolayer containing methylene blue entrapped within a Nafion layer. Another powerful feature was the incorporation, within the same implanted device, of a fabricated on-chip Ag/AgCl reference electrode - vital in any electrochemical sensor, but often ignored. When utilised in vivo, the sensor allowed accurate tracking of externally induced pH changes within a naturally occurring ovine lung cancer model, and correlated well with single point laboratory measurements made on extracted arterial blood, whilst enabling in vivo time-dependent measurements. The sensors functioned robustly whilst implanted, and maintained in vitro function once extracted and together, these results demonstrate proof-of-concept of the ability to sense real-time intratumoral tissue pH changes in vivo.


Assuntos
Técnicas Biossensoriais , Azul de Metileno , Animais , Técnicas Eletroquímicas , Concentração de Íons de Hidrogênio , Oxirredução , Ovinos
18.
Horm Res Paediatr ; 94(9-10): 343-352, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34839286

RESUMO

OBJECTIVE: Spexin (SPX) is a novel peptide implicated in food intake and satiety. SPX levels are reduced in obese patients. AIM: This study aimed to compare serum SPX levels in obese adolescents versus healthy controls and to assess the associations of metabolic syndrome (metS) antecedents with serum SPX levels. METHODS: Eighty consecutive obese adolescents aged 10-18 years and 80 healthy peers were enrolled. Anthropometric measurements, pubertal examinations, and clinical blood pressure measurements were performed. Fasting blood samples were drawn for glucose, insulin, lipids, uric acid, alanine aminotransferase (ALT), and SPX. metS was diagnosed using International Diabetes Federation criteria. Associations of serum SPX with clinical and laboratory variables were assessed. RESULTS: Obese adolescents had lower serum SPX levels than healthy peers (50 pg/mL [25-75% IQR: 25-98 pg/mL] and 67.0 pg/mL [25-75% IQR: 32.5-126.0 pg/mL]; respectively, p = 0.035). Twenty (25%) obese adolescents were diagnosed as having metS. Obese adolescents with metS had lower SPX than those without metS (24.5 pg/mL [25-75% IQR: 15.3-49.5 pg/mL] and 69.0 pg/mL [25-75% IQR: 42.0-142.0 pg/mL]; respectively, p < 0.0001). The frequencies of hyperuricemia, IR, and elevated ALT were similar in obese adolescents with metS and those without metS (p > 0.05 for all). Serum uric acid levels were correlated significantly with serum SPX after correcting for BMI and HOMA-IR (r = -0.41, p < 0.05). A serum SPX level at a cutoff level of 49.5 pg/mL predicted the presence of metS in obese adolescents with 75% sensitivity and 71% specificity. CONCLUSIONS: Obese adolescents have reduced SPX levels, and this reduction is more pronounced in those with metS. Further research is needed to verify the utility of SPX as a biomarker in the diagnosis of metS in obese adolescents.


Assuntos
Resistência à Insulina , Síndrome Metabólica , Obesidade Pediátrica , Adolescente , Criança , Humanos , Insulina , Obesidade Pediátrica/complicações , Ácido Úrico
19.
Oncogene ; 40(23): 3929-3941, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33981002

RESUMO

There is overwhelming clinical evidence that the extracellular-regulated protein kinase 5 (ERK5) is significantly dysregulated in human breast cancer. However, there is no definite understanding of the requirement of ERK5 in tumor growth and metastasis due to very limited characterization of the pathway in disease models. In this study, we report that a high level of ERK5 is a predictive marker of metastatic breast cancer. Mechanistically, our in vitro data revealed that ERK5 was critical for maintaining the invasive capability of triple-negative breast cancer (TNBC) cells through focal adhesion protein kinase (FAK) activation. Specifically, we found that phosphorylation of FAK at Tyr397 was controlled by a kinase-independent function of ERK5. Accordingly, silencing ERK5 in mammary tumor grafts impaired FAK phosphorylation at Tyr397 and suppressed TNBC cell metastasis to the lung without preventing tumor growth. Collectively, these results establish a functional relationship between ERK5 and FAK signaling in promoting malignancy. Thus, targeting the oncogenic ERK5-FAK axis represents a promising therapeutic strategy for breast cancer exhibiting aggressive clinical behavior.


Assuntos
Quinase 1 de Adesão Focal/metabolismo , Proteína Quinase 7 Ativada por Mitógeno/metabolismo , Neoplasias de Mama Triplo Negativas/enzimologia , Animais , Antígenos CD/biossíntese , Antígenos CD/genética , Antígenos CD/metabolismo , Caderinas/biossíntese , Caderinas/genética , Caderinas/metabolismo , Adesão Celular/fisiologia , Linhagem Celular Tumoral , Progressão da Doença , Feminino , Xenoenxertos , Humanos , Neoplasias Pulmonares/enzimologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/secundário , Camundongos , Camundongos Nus , Proteína Quinase 7 Ativada por Mitógeno/biossíntese , Proteína Quinase 7 Ativada por Mitógeno/genética , Invasividade Neoplásica , Fosforilação , Prognóstico , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia
20.
Cytokine ; 144: 155578, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34010726

RESUMO

Spexin is a newly described peptide and is known to reduce the uptake of long-chain fatty acids into adipocytes. The serum spexin levels of obese children between the ages of 12-18 are lower. The effect of serum spexin and free 25(OH) vitamin D3 levels on intrauterine development in newborns is unknown. Our aims is to evaluate the effects of spexin and adipocytokin levels in the cord blood of term newborn babies on the weight of the baby according to the gestation age (GA) and anthropometric measurement results. Babies who were born in our hospital and whose GA was ≥37 weeks were evaluated in three groups as appropriate for GA (AGA), small for GA (SGA) and large for GA (LGA). A total of 84 babies, including an equal number of infants in AGA, SGA and LGA groups, were included in the study. Spexin, leptin, active ghrelin, free 25(OH) vitamin D3, glucose, and insulin levels in the cord blood of infants were examined at birth. The results were compared according to GA and birth weight (BW). There was no statistically significant difference between groups in terms of mean spexin, active ghrelin, free 25(OH) vitamin D3, and insulin levels. The mean leptin level was significantly higher in LGA group than SGA and AGA groups (p 0.004). The mean spexin and leptin levels were higher in girls than in boys (respectively p value 0.029, 0.003). Although there is a significant positive correlation between BW, head circumference, height, umbilical circumference, umbilical circumference/height ratio and the mean leptin levels (p < 0.001), there was no significant correlation between mean spexin, active ghrelin, free 25 (OH) vitamin D3, insulin, and glucose levels. This study suggests that spexin may not have an effect on intrauterine development.


Assuntos
Adipocinas/metabolismo , Colestanotriol 26-Mono-Oxigenase/metabolismo , Sangue Fetal/metabolismo , Útero/metabolismo , Antropometria/métodos , Peso ao Nascer/fisiologia , Feminino , Desenvolvimento Fetal/fisiologia , Idade Gestacional , Grelina/metabolismo , Humanos , Recém-Nascido , Insulina/metabolismo , Masculino , Hormônios Peptídicos , Estudos Prospectivos
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