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1.
Ann Med Surg (Lond) ; 86(9): 5476-5480, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39239002

RESUMO

Introduction and importance: Deficiency of adenosine deaminase 2 (DADA2) is a rare autosomal recessive genetic disorder caused by loss-of-function mutations in the adenosine deaminase 2 (ADA2) gene. This condition primarily manifests in pediatric cases before the age of 10 years, with sporadic cases reported in adults. ADA2 is a critical enzyme involved in macrophage differentiation and immune homeostasis. The clinical manifestations of DADA2 vary widely and can affect multiple organ systems. Our case uniquely highlights an infrequent DADA2 manifestation. Case presentation: An 18-year-old female presented with right flank pain, fever, and a history of joint pain, Raynaud's phenomenon, livedo-like rash, and chronic abdominal pain. Physical examination revealed subcapsular hematoma in the right kidney. Further evaluation showed positive serologic tests for rheumatoid factor and antinuclear antibody (ANA). Genetic testing confirmed DADA2 homozygosity. The patient was discharged on the appropriate medications. Clinical discussion: DADA2 is associated with vascular dysfunction and systemic vasculopathy. The clinical manifestations of DADA2 encompass a spectrum of organ involvement, including the skin, nervous system, gastrointestinal system, renal system, and the cardiovascular system. Early recognition and diagnosis are crucial for appropriate management. Conclusion: This case report highlights the diverse clinical presentations of ADA2 deficiency, specifically focusing on bilateral renal subcapsular hematoma. This finding emphasizes the importance of considering DADA2 as a differential diagnosis in patients presenting with unexplained renal manifestations. Increased awareness of the varied clinical presentations of DADA2 will contribute to earlier diagnosis, appropriate management, and improved outcomes in patients affected by this rare genetic disorder.

2.
Pharm Dev Technol ; : 1-9, 2024 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-39231255

RESUMO

OBJECTIVE: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen. METHODS: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit®L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH. RESULTS: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated Cmax (18.35 µg/ml compared to 11.1 µg/ml). CONCLUSION: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release.

3.
J Investig Med High Impact Case Rep ; 12: 23247096241274510, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39230157

RESUMO

Mediastinal mature cystic teratomas are rare benign germ cell tumors that predominantly affect children. Despite their low incidence, they present unique diagnostic and management challenges. Early recognition and appropriate surgical intervention are crucial for optimal outcomes. This case report aims to highlight the importance of prompt diagnosis and management of mediastinal mature cystic teratomas in pediatric patients. We present the case of a 10-year-old female patient who presented with persistent chest pain and dyspnea. Imaging studies, including a chest X-ray and contrast-enhanced chest CT scan, revealed a large, well-circumscribed anterior mediastinal mass with calcifications. The patient underwent a right thoracotomy, resulting in the excision of a 6 × 5 × 5 cm mature cystic teratoma. Histopathological examination confirmed the diagnosis. The patient had an uneventful recovery and was discharged in stable condition. Mediastinal mature cystic teratomas pose diagnostic challenges due to their nonspecific symptoms and heterogeneous imaging characteristics. Differential diagnosis includes other mediastinal masses containing fat and calcifications. Surgical excision is the preferred treatment, although complete removal can be challenging due to adhesions to neighboring structures. Close follow-up is necessary to monitor for recurrence and complications. Mediastinal mature cystic teratomas are rare tumors with variable clinical presentations. Early detection and surgical intervention are crucial for optimal outcomes. These tumors should be included in the list of differential diagnoses for mediastinal masses in pediatric patients.


Assuntos
Neoplasias do Mediastino , Teratoma , Tomografia Computadorizada por Raios X , Humanos , Teratoma/cirurgia , Teratoma/diagnóstico por imagem , Teratoma/diagnóstico , Teratoma/patologia , Feminino , Neoplasias do Mediastino/cirurgia , Neoplasias do Mediastino/patologia , Neoplasias do Mediastino/diagnóstico , Neoplasias do Mediastino/diagnóstico por imagem , Criança , Diagnóstico Diferencial , Toracotomia , Dor no Peito/etiologia , Mediastino/patologia , Mediastino/diagnóstico por imagem , Mediastino/cirurgia
4.
Case Rep Womens Health ; 43: e00647, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39286600

RESUMO

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital condition characterized by renal agenesis, uterine didelphys, and obstructed hemivagina. This report presents the case of a 19-year-old woman who reported lower abdominal pain and offensive vaginal discharge. Imaging revealed a didelphys uterus, two vaginas, two cervixes, hematocolpos, and an absent right kidney. Surgical intervention involved draining the hematocolpos and excising the uterine septum. After surgery, the patient successfully conceived and had a full-term pregnancy, delivering via cesarean section without complications. This case highlights the importance of early diagnosis and surgical management in preventing complications such as endometriosis and infertility. Prompt recognition and treatment are crucial for preserving fertility in patients with HWW syndrome.

5.
Nutrients ; 16(16)2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39203883

RESUMO

BACKGROUND: Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), is a complex disease with increasing global incidence and prevalence. Although dairy consumption has been linked to various chronic diseases, its relationship with IBD remains uncertain. Additionally, there is a lack of data on this topic from Arab countries. This study aimed to investigate the association between dairy consumption and IBD through a case-control study among Arab populations, followed by a meta-analysis of available studies. METHOD: First, we used data from 158 UC patients, 244 CD patients, and 395 controls attending a polyclinic in Riyadh, Saudi Arabia. All participants were aged ≥ 18 years. Logistic regression was used to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of UC and CD for individuals who reported the highest versus the lowest frequencies of dairy consumption. Next, we conducted a meta-analysis, combining our results with those from other eligible studies after searching several databases. We used the I2 statistics to examine statistical heterogeneity across studies and the regression test for funnel plot asymmetry to assess publication bias. RESULTS: The case-control study showed a negative association between frequent dairy consumption and UC (OR (95% CI) = 0.64 (0.41, 1.00)) but not CD (OR (95% CI) = 0.97 (0.65, 1.45)). In the meta-analysis, the highest frequencies of dairy consumption were negatively associated with both UC and CD: ORs (95% CIs) = 0.82 (0.68, 0.98) and 0.72 (0.59, 0.87), respectively. A moderate heterogeneity across studies was noticed in the UC meta-analysis (I2 = 59.58%) and the CD meta-analysis (I2 = 41.16%). No publication bias was detected. CONCLUSIONS: Frequent dairy consumption could protect against the development of UC and CD, suggesting potential dietary recommendations in the context of IBD prevention.


Assuntos
Árabes , Colite Ulcerativa , Doença de Crohn , Laticínios , Dieta , Humanos , Laticínios/estatística & dados numéricos , Estudos de Casos e Controles , Adulto , Feminino , Masculino , Arábia Saudita/epidemiologia , Árabes/estatística & dados numéricos , Colite Ulcerativa/epidemiologia , Doença de Crohn/epidemiologia , Pessoa de Meia-Idade , Dieta/estatística & dados numéricos , Doenças Inflamatórias Intestinais/epidemiologia , Fatores de Risco , Razão de Chances , Adulto Jovem
6.
F1000Res ; 13: 465, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39165351

RESUMO

Background: This study aims to develop a vulnerability map for Surabaya using GIS-based Multi-Criteria Decision Analysis (MCDA) to assess the city's vulnerability to COVID-19. Methods: Six key factors influencing vulnerability were identified and their relative importance determined through the Analytic Hierarchy Process (AHP) pairwise comparison matrix. GIS was utilized to classify Surabaya's vulnerability into five levels: very low, low, medium, high, and very high. Results: The resulting vulnerability map provides essential insights for decision-makers, healthcare professionals, and disaster management teams. It enables strategic resource allocation, targeted interventions, and formulation of comprehensive response strategies tailored to specific needs of vulnerable districts. Conclusions: Through these measures, Surabaya can enhance its resilience and preparedness, ensuring the well-being of its residents in the face of potential emergency outbreaks.


Assuntos
COVID-19 , Cidades , Sistemas de Informação Geográfica , COVID-19/epidemiologia , Humanos , SARS-CoV-2 , Planejamento em Desastres/métodos , Populações Vulneráveis/estatística & dados numéricos , Índia/epidemiologia , Técnicas de Apoio para a Decisão , Pandemias
7.
ACS Omega ; 9(30): 32873-32880, 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39100315

RESUMO

The most prevalent comorbidity among cystic fibrosis (CF) patients is cystic fibrosis-related diabetes (CFRD). CFRD has been linked to one of the worse clinical outcomes and a higher mortality. Improved clinical results have been related to earlier diagnosis and treatment of CFRD. Therefore, the present study aimed to investigate the metabolome of human serum of patients with CFRD. This might aid in identifying novel biomarkers linked with the pathophysiology of CFRD and its diagnosis. The liquid chromatography-high-resolution mass spectrometry (LC-HRMS) metabolomics approach was utilized for serum samples from patients with CF (n = 36) and healthy controls (n = 36). Nine patients in the CF group had CFRD, and 27 were non-CFRD patients (nCFRD). A total of 2328 metabolites were significantly altered in CF compared with the healthy control. Among those, 799 significantly dysregulated metabolites were identified between CFRD and nCFRD. Arachidonic acid (AA), ascorbate, and aldarate metabolism were the most common metabolic pathways dysregulated in CF. l-Homocysteic acid (l-HCA) levels were significantly reduced in CF and CFRD compared to the control and nCFRD, respectively. In addition, gamma-glutamylglycine and l-5-hydroxytryptophan (5-HTP) had the highest discrimination between CFRD and nCFRD with AUC (0.716 and 0.683, respectively). These biomarkers might serve as diagnostic biomarkers and aid in understanding potential metabolic changes linked to CF and CFRD.

8.
Int J Mol Sci ; 25(14)2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39063133

RESUMO

Omics technologies provide useful tools for the identification of novel biomarkers in many diseases, including breast cancer, which is the most diagnosed cancer in women worldwide. We and others have reported a central role for the actin-bundling protein (fascin) in regulating breast cancer disease progression at different levels. However, whether fascin expression promotes metabolic molecules that could predict disease progression has not been fully elucidated. Here, fascin expression was manipulated via knockdown (fascinKD+NORF) and rescue (fascinKD+FORF) in the naturally fascin-positive (fascinpos+NORF) MDA-MB-231 breast cancer cells. Whether fascin dysregulates metabolic profiles that are associated with disease progression was assessed using untargeted metabolomics analyses via liquid chromatography-mass spectrometry. Overall, 12,226 metabolic features were detected in the tested cell pellets. Fascinpos+NORF cell pellets showed 2510 and 3804 significantly dysregulated metabolites compared to their fascinKD+NORF counterparts. Fascin rescue (fascinKD+FORF) revealed 2710 significantly dysregulated cellular metabolites compared to fascinKD+NORF counterparts. A total of 101 overlapped cellular metabolites between fascinKD+FORF and fascinpos+NORF were significantly dysregulated in the fascinKD+NORF cells. Analysis of the significantly dysregulated metabolites by fascin expression revealed their involvement in the metabolism of sphingolipid, phenylalanine, tyrosine, and tryptophan biosynthesis, and pantothenate and CoA biosynthesis, which are critical pathways for breast cancer progression. Our findings of fascin-mediated alteration of metabolic pathways could be used as putative poor prognostic biomarkers and highlight other underlying mechanisms of fascin contribution to breast cancer progression.


Assuntos
Neoplasias da Mama , Proteínas de Transporte , Progressão da Doença , Proteínas dos Microfilamentos , Humanos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Proteínas dos Microfilamentos/metabolismo , Proteínas dos Microfilamentos/genética , Feminino , Linhagem Celular Tumoral , Proteínas de Transporte/metabolismo , Proteínas de Transporte/genética , Metaboloma , Metabolômica/métodos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica
9.
J Clin Immunol ; 44(7): 151, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896336

RESUMO

A cell's ability to survive and to evade cancer is contingent on its ability to retain genomic integrity, which can be seriously compromised when nucleic acid phosphodiester bonds are disrupted. DNA Ligase 1 (LIG1) plays a key role in genome maintenance by sealing single-stranded nicks that are produced during DNA replication and repair. Autosomal recessive mutations in a limited number of individuals have been previously described for this gene. Here we report a homozygous LIG1 mutation (p.A624T), affecting a universally conserved residue, in a patient presenting with leukopenia, neutropenia, lymphopenia, pan-hypogammaglobulinemia, and diminished in vitro response to mitogen stimulation. Patient fibroblasts expressed normal levels of LIG1 protein but exhibited impaired growth, poor viability, high baseline levels of gamma-H2AX foci, and an enhanced susceptibility to DNA-damaging agents. The mutation reduced LIG1 activity by lowering its affinity for magnesium 2.5-fold. Remarkably, it also increased LIG1 fidelity > 50-fold against 3' end 8-Oxoguanine mismatches, exhibiting a marked reduction in its ability to process such nicks. This is expected to yield increased ss- and dsDNA breaks. Molecular dynamic simulations, and Residue Interaction Network studies, predicted an allosteric effect for this mutation on the protein loops associated with the LIG1 high-fidelity magnesium, as well as on DNA binding within the adenylation domain. These dual alterations of suppressed activity and enhanced fidelity, arising from a single mutation, underscore the mechanistic picture of how a LIG1 defect can lead to severe immunological disease.


Assuntos
DNA Ligase Dependente de ATP , Homozigoto , Mutação , Imunodeficiência Combinada Severa , Feminino , Humanos , Masculino , DNA Ligase Dependente de ATP/genética , DNA Ligase Dependente de ATP/metabolismo , Fibroblastos , Simulação de Dinâmica Molecular , Mutação/genética , Imunodeficiência Combinada Severa/genética , Lactente
10.
Int J Impot Res ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886595

RESUMO

Clinically, collagen fleece patching of the penile tunica albuginea (TA) has been successful. However, the histopathological and hemodynamic outcomes are not known. We studied in vivo TachoSil® patching in two beagle dogs weighing 16.8 (16.7-16.9) Kg. Bilateral intracavernous pressures (ICP) response to 10 mg papaverine hydrochloride were measured. A full-thickness defect was created on the left side in TA 1 × 0.5 cm, and four transverse incisions 1 cm long were made on the right side, placed 0.5 cm apart, and covered with TachoSil®. Six months later, ICP measurements were repeated, and the penis was excised for histopathology. Grossly, the graft site was indistinguishable. The mean baseline ICP was 19.3 ± 2.98 mmHg and increased after papaverine injection to a mean peak ICP of 122 ± 26.1 mmHg. The ICP measurement before and after grafting did not show a significant difference in the baseline (p = 0.068) or the peak pressure (p = 0.465). Histologically, minimal foreign body reaction was seen, and the TA was completely regenerated. The underlying cavernous tissue did not show inflammation or necrosis. The study is the first to show the long-term histopathologic regeneration of TA after collagen fleece patching while maintaining the hemodynamic response to papaverine.

11.
Int J Mol Sci ; 25(11)2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38891907

RESUMO

Currently, tandem mass spectrometry-based newborn screening (NBS), which examines targeted biomarkers, is the first approach used for the early detection of maple syrup urine disease (MSUD) in newborns, followed by confirmatory genetic mutation tests. However, these diagnostic approaches have limitations, demanding the development of additional tools for the diagnosis/screening of MUSD. Recently, untargeted metabolomics has been used to explore metabolic profiling and discover the potential biomarkers/pathways of inherited metabolic diseases. Thus, we aimed to discover a distinctive metabolic profile and biomarkers/pathways for MSUD newborns using untargeted metabolomics. Herein, untargeted metabolomics was used to analyze dried blood spot (DBS) samples from 22 MSUD and 22 healthy control newborns. Our data identified 210 altered endogenous metabolites in MSUD newborns and new potential MSUD biomarkers, particularly L-alloisoleucine, methionine, and lysoPI. In addition, the most impacted pathways in MSUD newborns were the ascorbate and aldarate pathways and pentose and glucuronate interconversions, suggesting that oxidative and detoxification events may occur in early life. Our approach leads to the identification of new potential biomarkers/pathways that could be used for the early diagnosis/screening of MSUD newborns but require further validation studies. Our untargeted metabolomics findings have undoubtedly added new insights to our understanding of the pathogenicity of MSUD, which helps us select the appropriate early treatments for better health outcomes.


Assuntos
Biomarcadores , Teste em Amostras de Sangue Seco , Doença da Urina de Xarope de Bordo , Metabolômica , Triagem Neonatal , Humanos , Doença da Urina de Xarope de Bordo/sangue , Doença da Urina de Xarope de Bordo/diagnóstico , Recém-Nascido , Teste em Amostras de Sangue Seco/métodos , Biomarcadores/sangue , Metabolômica/métodos , Masculino , Feminino , Triagem Neonatal/métodos , Metaboloma , Espectrometria de Massas em Tandem
12.
SAGE Open Med ; 12: 20503121241247458, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38711467

RESUMO

Objectives: Epilepsy is a neurological disorder affecting more than 50 million human lives of all ages, its social, physical and psychological implications is of huge concern. The current study and as a continuation of epilepsy knowledge assessment projects conducted by our research team is aimed to assess the knowledge of healthcare workers regarding epilepsy first aid in Saudi Arabia. Methods: A cross-sectional questionnaire-based study was carried out from 2020 to 2021. Results: During the study period, 272 healthcare workers were recruited; participants were males and females from different nationalities in various Saudi Arabian cities, possess diverse qualifications, and belong to several healthcare-related professions. The question, "Did you witness an epileptic seizure"? was answered as "Yes" by 42% of participants, and in response to the question "If you know that this patient struggles during seizure attacks," 58% of respondents stated that they would not call an ambulance. Moreover, the question "Put something in his/her mouth to prevent tongue biting" was incorrectly answered as "Yes" by 42% of respondents, and the question "Try to catch him/her and stop his/her movement" in order to control the attack was answered "Yes" by 21% of respondents. Furthermore, almost 90% of healthcare participants do not know how to use the Vagus Nerve Stimulation device. The mean knowledge score among participants was 23.7; sex, as well as type of higher qualification obtained, was found to be significantly associated with the score of knowledge. Conclusion: Knowledge toward epilepsy and epilepsy first aid among healthcare workers in Saudi Arabia was found fragile. Further research is appreciated to support the current findings.

13.
J Clin Med ; 13(8)2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38673653

RESUMO

Background: Linezolid is used for Gram-positive bacterial infections. Thrombocytopenia is one of its main adverse effects resulting from myelosuppression. Several studies have assessed risk factors that may increase the risk of this adverse effect. However, most studies included patients with hemato-oncologic diseases, which may confound such assessments. This study aimed to investigate risk factors for linezolid-associated thrombocytopenia in patients without hemato-oncologic diseases. Methods: This was a multicenter retrospective case-control study of adult patients treated with linezolid twice daily for ≥3 days. Patients with hemato-oncologic diseases, active dengue fever, active COVID-19, baseline platelet count <100 × 103/mm3, concurrent therapy with trimethoprim/sulfamethoxazole or valproic acid, and a recent platelet transfusion within 7 days were excluded. Thrombocytopenia was defined as a drop in platelet count below 100 × 103/mm3. Results: Out of 158 evaluated patients, 33 developed thrombocytopenia, indicating an incidence rate of 20.9%. Of all the risk factors assessed, creatinine clearance of <60 mL/min and bacteremia/infective endocarditis were significantly associated with linezolid-associated thrombocytopenia (adjusted odds ratios, 3.25 and 5.95; 95% CI 1.12-9.45 and 1.23-28.66; p = 0.031 and 0.026, respectively). End of therapy platelet counts were significantly lower in the cases than in the controls (79 vs. 243 × 103/mm3; p < 0.001). Similarly, the percentage of platelet count change was significantly different (-55.1% vs. -10.2%; p < 0.001). Conclusions: In our study, the incidence rate of linezolid-associated thrombocytopenia was 20.9%, and we found that patients with renal impairment and bacteremia may need close monitoring of platelet counts. Prospective studies are warranted to evaluate the potential need for renal dose adjustment.

14.
Cureus ; 16(2): e53466, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38440027

RESUMO

BACKGROUND: Knowledge and beliefs about osteoporosis have been considered one of the vital parts of early prevention against it. OBJECTIVES: This study aimed to evaluate knowledge and beliefs toward osteoporosis using the Osteoporosis Knowledge Assessment Tool (OKAT) and Osteoporosis Health Belief Scale (OHBS) questionnaires among the public in Jeddah, Saudi Arabia. METHODS: This cross-sectional study was conducted from March 2019 to April 2019 among adults aged 15 years and above. A validated questionnaire was allocated electronically to the participants through social platforms (such as Twitterand WhatsApp) using a convenience sampling technique. RESULTS: A total of 754 participants completed the questionnaire. The majority were females 481 (63.8%). A total of 34 (4.1%) have not heard about osteoporosis before. Respondents scored a total mean of 7.92±3.0for the OKAT questionnaire and a mean score of 126.74±22.38for the OHBS questionnaire. These two scores were significantly associated with age groups and gender (P < 0.05). CONCLUSION: Although there is a relative increase in the knowledge of our sample, the belief towardosteoporosis is evidently lower. Therefore, implementing educational programs that tackle belief perception and other preventive measures such as healthy eating habits, physical activities, and educational materials are needed in the future.

15.
Clin Chim Acta ; 557: 117861, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38490341

RESUMO

BACKGROUND: Glutaric aciduria type-1 (GA-1) is a rare metabolic disorder due to glutaryl coenzyme A dehydrogenase deficiency, causing elevated levels of glutaryl-CoA and its derivatives. GA-1 exhibits symptoms like macrocephaly, developmental delays, and movement disorders. Timely diagnosis through genetic testing and newborn screening is crucial. However, in some cases, transiently elevated level of glutarylcarnitine (C5DC) challenges accurate diagnosis, highlighting the need for alternative diagnostic methods, like mass spectrometry-based untargeted metabolomics, to identify additional biomarkers for distinguishing falsely suspected GA-1 from healthy newborns. METHODOLOGY: DBS samples from falsely suspected GA-1 newborns (n = 47) and matched control were collected through the NBS program. Untargeted metabolomics using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) was performed to enable biomarker and pathway investigations for significantly altered metabolites. RESULTS: 582 and 546 were up- and down-regulated metabolites in transient GA-1. 155 endogenous metabolites displayed significant variations compared to the control group. Furthermore, our data identified novel altered metabolic biomarkers, such as N-palmitoylcysteine, heptacarboxyporphyrin, 3-hydroxylinoleoylcarnitine, and monoacylglyceride (MG) (0:0/20:1/0:0), along with perturbed metabolic pathways like sphingolipid and thiamine metabolism associated with the transient elevated C5DC levels in DBS samples. CONCLUSIONS: A distinct metabolic pattern linked to the transient C5DC elevation in newborns was reported to enhance the prediction of the falsely positive cases, which could help avoiding unnecessary medical treatments and minimizing the financial burdens in the health sector.


Assuntos
Erros Inatos do Metabolismo dos Aminoácidos , Encefalopatias Metabólicas , Glutaril-CoA Desidrogenase/deficiência , Humanos , Recém-Nascido , Glutaril-CoA Desidrogenase/genética , Encefalopatias Metabólicas/diagnóstico , Encefalopatias Metabólicas/genética , Encefalopatias Metabólicas/terapia , Biomarcadores , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/genética , Metabolômica
16.
Cureus ; 16(3): e56210, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38495966

RESUMO

Introduction This study analyzed the number of peer-reviewed publications submitted by matriculants prior to applying for the orthopedic surgery residency. The graduating residency classes of 2023 and 2027 were included in the study to understand the trend of publications, to inform aspiring orthopedic surgeons. Methods The top, middle, and bottom 10 orthopedic surgery residency programs were identified on the Doximity online website. Matriculants were searched on PubMed and Google Scholar for publication contributions. Variables including number of publications, orthopedic publications, first-author authorship, and H-index were analyzed. A logistic regression model was created, and a t-test was conducted to statistically compare the 2027 and 2023 graduating classes. Results Matriculants of the 2023 match had higher numbers of publications, orthopedic surgery-specific publications, first authorships, and h-indices than the matriculants of the 2018 match. Conclusion The average number of publications has been observed to increase over four years, indicating an increase in competition to match into orthopedic surgery residency. Publishing in higher numbers may be a good indicator of an applicant's success in not only matching but also matching into a higher-tier program.

17.
Heliyon ; 10(2): e24406, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38304784

RESUMO

Despite substantial investments in anti-glioblastoma (GBM) drug discovery over the last decade, progress is limited to preclinical stages, with clinical studies frequently encountering obstacles. Angiogenic and histone deacetylase inhibitors (HDACi) have shown profound results in pre-clinical studies. Investigating a multicomponent anti-cancer remedy that disrupts the tumor angiogenic blood vessels and simultaneously disrupts HDACs, while inducing minimal side effects, is critically needed. The crude extracts derived from medicinal plants serve as a renewable reservoir of anti-tumor drugs, exhibiting reduced toxicity compared to chemically synthesized formulations. Calotropis procera is a traditional medicinal plant, and its anticancer potential against many cancer cell lines has been reported, however its antiangiogenic and HDAC inhibitory action is largely unknown. The anticancer activity of methanol leaf extract of C. procera was tested in three types of human glioblastoma cell lines. Wild-type and transgenic zebrafish embryos were used to evaluate developmental toxicity and angiogenic activity. A human angiogenic antibody array was used to profile angiogenic proteins in the U251 GM cell line. A real-time reverse transcriptase polymerase chain reaction (RT PCR) assay was used to detect the differential expression of eleven HDAC genes in U251 cells treated with C. procera extract. The extract significantly reduced the proliferation of all three types of GBM cell lines and the cytotoxicity was found to be more pronounced in U251 GM cells, with an IC50 value of 2.63 ± 0.23 µg/ml, possibly by arresting the cell cycle at the G2/M transition. The extract did not exhibit toxic effects in zebrafish embryos, even at concentrations as high as 1000 µg/ml. The extract also inhibited angiogenic blood vessel formation in the transgenic zebrafish model in a dose-dependent manner. The results from the angiogenic antibody array have suggested novel angiogenesis targets that can be utilized to treat GBM. Real-time RT PCR analysis has shown that C. procrea extract caused an upregulation of HDAC5, 7, and 10, while the mRNA of HDAC1, 2, 3 and 8 (Class I HDACs), and HDAC4, 6, and 9 (Class II) were downregulated in U251 GM cells. The cytotoxicity of the C. procera extract on GBM cell lines could be due to its dual action by regulation of both tumor angiogenesis and histone deacetylases enzymes. Through this study, the C. procera leaf extract has been suggested as an effective remedy to treat GBM with minimal toxicity. In addition, various novel angiogenic and HDAC targets has been identified which could be helpful in designing better therapeutic strategies to manage glioblastoma multiforme in human patients.

19.
Pharmaceuticals (Basel) ; 17(2)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38399383

RESUMO

The doping of engineered nanomaterials (ENMs) is a key tool for manipulating the properties of ENMs (e.g., electromagnetic, optical, etc.) for different therapeutic applications. However, adverse health outcomes and the cellular biointeraction of doped ENMs, compared to undoped counterparts, are not fully understood. Previously, we have shown that doping manganese oxide nanoparticles with ZnO (ZnO-MnO2 NPs) improved their catalytic properties. In this study, we assessed the toxicity of ZnO-MnO2 NPs in Raw 264.7 cells. NPs were prepared via an eco-friendly, co-precipitation method and characterized by several techniques, including transmission and scanning electron microscopy, X-ray diffraction, and Fourier transform infrared. The physicochemical properties of ZnO-MnO2 NPs, including size, morphology, and crystalline structure, were almost identical to MnO2 NPs. However, ZnO-MnO2 NPs showed slightly larger particle aggregates and negative charge in cell culture media. Exposure to ZnO-MnO2 NPs resulted in lower toxicity based on the cell viability and functional assay (phagocytosis) data. Exposure to both NPs resulted in the activation of the cell inflammatory response and the generation of reactive oxygen species (ROS). Despite this, exposure to ZnO-MnO2 NPs was associated with a lower toxicity profile, and it resulted in a higher ROS burst and the activation of the cell antioxidant system, hence indicating that MnO2 NP-induced toxicity is potentially mediated via other ROS-independent pathways. Furthermore, the cellular internalization of ZnO-MnO2 NPs was lower compared to MnO2 NPs, and this could explain the lower extent of toxicity of ZnO-MnO2 NPs and suggests Zn-driven ROS generation. Together, the findings of this report suggest that ZnO (1%) doping impacts cellular biointeraction and the consequent toxicological outcomes of MnO2 NPs in Raw 264.7 cells.

20.
Vaccines (Basel) ; 12(2)2024 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-38400143

RESUMO

Delayed hypersensitivity reactions (DHRs) have been reported in association with COVID-19 vaccines, particularly those that are mRNA-based. Classic DHRs result in induration, erythema, tenderness, and urticaria. However, soft tissue mass is an uncommon complication of a COVID-19 vaccination-associated DHR and is rarely reported in the literature. We present a case of a 49-year-old male who recognized a mildly painful, firm soft tissue mass within the biceps mimicking neoplasm six months after receiving the booster dose of the Moderna vaccine. Non-operative conservative treatment modalities, including heating pads, ice packs, acetaminophen, and ibuprofen, failed to improve the patient's mass. The mass, which proved histologically to be an inflammatory pseudo-tumor, did not recur after complete excision. While there have been many reported cases of DHRs following COVID-19 vaccinations, we present this case to raise awareness of the development of pseudo-tumors as a possible, yet rare, clinical manifestation of DHRs following vaccination.

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