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1.
Surg Endosc ; 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38951238

RESUMO

BACKGROUND: Adrenalectomy for pheochromocytoma (PHEO) is challenging because of the high risk of intraoperative hemodynamic instability (HDI). This study aimed to compare the incidence and risk factors of intraoperative HDI between laparoscopic left adrenalectomy (LLA) and laparoscopic right adrenalectomy (LRA). METHODS: We retrospectively analyzed two hundred and seventy-one patients aged > 18 years with unilateral benign PHEO of any size who underwent transperitoneal laparoscopic adrenalectomy at our hospitals between September 2016 and September 2023. Patients were divided into LRA (N = 122) and LLA (N = 149) groups. Univariate and multivariate logistic regression analyses were used to predict intraoperative HDI. In multivariate analysis for the prediction of HDI, right-sided PHEO, PHEO size, preoperative comorbidities, and preoperative systolic blood pressure were included. RESULTS: Intraoperative HDI was significantly higher in the LRA group than in the LLA (27% vs. 9.4%, p < 0.001). In the multivariate regression analysis, right-sided tumours showed a higher risk of intraoperative HDI (odds ratio [OR] 5.625, 95% confidence interval [CI], 1.147-27.577, p = 0.033). The tumor size (OR 11.019, 95% CI 3.996-30.38, p < 0.001), presence of preoperative comorbidities [diabetes mellitus, hypertension, and coronary heart disease] (OR 7.918, 95% CI 1.323-47.412, p = 0.023), and preoperative systolic blood pressure (OR 1.265, 95% CI 1.07-1.495, p = 0.006) were associated with a higher risk of HDI in both LRA and LLA, with no superiority of one side over the other. CONCLUSION: LRA was associated with a significantly higher intraoperative HDI than LLA. Right-sided PHEO was a risk factor for intraoperative HDI.

2.
Oxf Med Case Reports ; 2024(6): omae062, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38860015

RESUMO

Ceftriaxone is a third-generation cephalosporin. Due to its wide range of activity and acceptable safety profile, it is frequently prescribed to paediatric patients. However, there are several documented cases of reports of uncommon adverse events, such as cholecystitis, linked to the use of ceftriaxone. This study discusses the case of an 8-year-old female patient who developed cholecystitis, an inflammation of the gallbladder, after being treated with ceftriaxone. The patient presented with right upper quadrant pain, associated with nausea. Imaging studies showed the presence of stones and shadowing sludge, leading to acute inflammation of the gallbladder. Prompt cessation of ceftriaxone and supportive treatment led to the resolution of cholecystitis and the complete disappearance of the sludge and stones. The study highlights that early identification and withdrawal of the antibiotic can lead to successful therapy and the avoidance of unnecessary surgical procedures.

3.
Biomed Pharmacother ; 177: 116929, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38889644

RESUMO

Acute kidney injury (AKI) is a devastating consequence of sepsis, accompanied by high mortality rates. It was suggested that inflammatory pathways are closely linked to the pathogenesis of lipopolysaccharide (LPS)-induced AKI. Inflammatory signaling, including PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-κB, NLRP3/caspase-1 and Fractalkine/CX3CR1 are considered major forerunners in this link. Alirocumab, PCSK9 inhibitor, with remarkable anti-inflammatory features. Accordingly, this study aimed to elucidate the antibacterial effect of alirocumab against E. coli in vitro. Additionally, evaluation of the potential nephroprotective effects of alirocumab against LPS-induced AKI in rats, highlighting the potential underlying mechanisms involved in these beneficial actions. Thirty-six adult male Wistar rats were assorted into three groups (n=12). Group I; was a normal control group, whereas sepsis-mediated AKI was induced in groups II and III through single-dose intraperitoneal injection of LPS on day 16. In group III, animals were given alirocumab. The results revealed that LPS-induced AKI was mitigated by alirocumab, evidenced by amelioration in renal function tests (creatinine, cystatin C, KIM-1, and NGAL); oxidative stress biomarkers (Nrf2, HO-1, TAC, and MDA); apoptotic markers and renal histopathological findings. Besides, alirocumab pronouncedly hindered LPS-mediated inflammatory response, confirmed by diminishing HMGB1, TNF-α, IL-1ß, and caspase-1 contents; the gene expression of PCSK9, RAGE, NF-ᴋB and Fractalkine/CX3CR1, along with mRNA expression of TLR4, MYD88, and NLRP3. Regarding the antibacterial actions, results showed that alirocumab displayed potential anti-bacterial activity against pathogenic gram-negative E. coli. In conclusion, alirocumab elicited nephroprotective activities against LPS-induced AKI via modulation of Nrf2/HO-1, PCSK9, HMGB1/RAGE/TLR4/MYD88/NF-ᴋB/NLRP3/Caspase-1, Fractalkine/CX3R1 and apoptotic axes.

4.
Transplant Cell Ther ; 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38852784

RESUMO

Upfront autologous stem cell transplantation (auto-SCT) remains standard of care for eligible patients with newly diagnosed multiple myeloma (NDMM), although recently its role has been questioned. The aim of the study was to evaluate trends in patient characteristics, treatment, and outcomes of NDMM who underwent upfront auto-SCT over three decades. We conducted a single-center retrospective analysis of patients with NDMM who underwent upfront auto-SCT at MD Anderson Cancer Center between 1988 to 2021. Primary end points were progression-free survival (PFS) and overall survival (OS). Patients were grouped by the year of auto-SCT: 1988-2000 (n = 249), 2001-2005 (n = 373), 2006-2010 (n = 568), 2011-2015 (n = 815) and 2016-2021 (n = 1036). High-risk cytogenetic abnormalities were defined as del (17p), t (4;14), t (14;16), and 1q21 gain or amplification by fluorescence in situ hybridization. We included 3041 MM patients in the analysis. Median age at auto-SCT increased from 52 years (1988-2000) to 62 years (2016-2021), as did the incidence of high-risk cytogenetics from 15% to 40% (P < .001). Comorbidity burden, as measured by a Hematopoietic Cell Transplantation-Specific Comorbidity Index (HCT-CI) of >3, increased from 17% (1988-2000) to 28% (2016-2021) (P < .001). Induction regimens evolved from predominantly chemotherapy to immunomodulatory drug (IMiD) and proteasome inhibitor (PI) based regimens, with 74% of patients receiving IMiD-PI triplets in 2016-2021 (39% bortezomib, lenalidomide and dexamethasone (VRD) and 35% carfilzomib, lenalidomide and dexamethasone [KRD]). Response rates prior to auto-SCT steadily increased, with 4% and 10% achieving a ≥CR and ≥VGPR compared to 19% and 65% between 1988-2000 and 2016-2021, respectively. Day 100 response rates post auto-SCT improved from 24% and 49% achieving ≥CR and ≥VGPR between 1988-2000 to 41% and 81% between 2016-2021, respectively. Median PFS improved from 22.3 months between 1988-2000 to 58.6 months between 2016-2021 (HR 0.42, P < .001). Among patients with high-risk cytogenetics, median PFS increased from 13.7 months to 36.8 months (HR 0.32, P < .001). Patients aged ≥65 years also had an improvement in median PFS from 33.6 months between 2001 and 2005 to 52.8 months between 2016-2021 (HR 0.56, P = .001). Median OS improved from 55.1 months between 1988-2000 to not reached (HR 0.41, P < .001). Patients with high-risk cytogenetics had an improvement in median OS from 32.9 months to 66.5 months between 2016-2021 (HR 0.39, P < .001). Day 100 non-relapse mortality from 2001 onwards was ≤1%. Age-adjust rates of second primary malignancies were similar in patients transplanted in different time periods. Despite increasing patient age and comorbidity burden, this large real-world study demonstrated significant improvements in the depth of response and survival outcomes in patients with NDMM undergoing upfront auto-SCT over the past three decades, including those with high-risk disease.

5.
Case Rep Obstet Gynecol ; 2024: 2017479, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38716061

RESUMO

Background: Intrauterine contraceptive devices (IUCDs) are considered to be an effective way of preventing unwanted pregnancies. However, one significant complication associated with IUCDs is uterine perforation especially at the time of insertion and could reach the peritoneal cavity and the viscus of the adjacent organs. Intravesical migration is extremely rare. Case Presentation. We report a 41-year-old woman who was diagnosed with IUCD intravesical migration after she presented to our hospital complaining of persistent lower urinary tract symptoms. Laparoscopic removal was done after the failure of cystoscopic extraction. Conclusion: The IUCD must be monitored continuously by the gynaecologist, and suspicions of intravesical migration must be considered in those presenting with persistent, unexplained lower urinary tract symptoms.

6.
BMC Oral Health ; 24(1): 584, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38773504

RESUMO

BACKGROUND: Apical surgery with standard retrograde maneuvers may be challenging in certain cases. Simplifying apical surgery to reduce operating time and streamline retrograde manipulation is an emerging need in clinical endodontics. AIM OF THE STUDY: The aim of the study was to compare the bacterial sealing ability of a calcium silicate-based sealer with the single cone technique combined with root end resection only, and calcium silicate-based sealer as a retrograde filling versus MTA retrofilling, and to analyze bacterial viability using confocal laser scanning microscope (CLSM). MATERIALS AND METHODS: In this in vitro experimental study, 50 extracted human maxillary incisor teeth were instrumented and randomly divided into five groups: three experimental groups, a positive control group, and a negative control group (n = 10/group). In the experimental groups, the roots were obturated using the single cone technique (SCT) and a calcium silicate-based sealer. In group 1, the roots were resected 3 mm from the apex with no further retrograde preparation or filling. In groups 2 and 3, the roots were resected, retroprepared, and retrofilled with either a calcium silicate-based sealer or MTA, respectively. Group 4 (positive control) was filled with a single gutta-percha cone without any sealer. In group 5 (negative control), the canals were left empty, and the roots were sealed with wax and nail varnish. A bacterial leakage model using Enterococcus faecalis was employed to assess the sealing ability over a 30-day period, checking for turbidity and analyzing colony forming units (CFUs) per milliliter. Five specimens from each group were examined using CLSM for bacterial viability. Data for the bacterial sealing ability were statistically analyzed using chi-squared and Kruskal-Wallis tests. RESULTS: The three experimental groups did not show significant differences in terms of bacterial leakage, or bacterial counts (CFUs) (P > 0.05). However, significant differences were observed when comparing the experimental groups to the positive control group. Notably, the calcium silicate-based sealer, when used as a retrofilling, yielded the best sealing ability. CLSM imaging revealed viable bacterial penetration in all the positive control group specimens while for the experimental groups, dead bacteria was the prominent feature seen. CONCLUSION: Within the limitations of this study, it could be concluded that the bacterial sealing ability of calcium silicate-based sealer with the single cone technique combined with root end resection only and calcium silicate-based sealer as a retrograde filling were comparable with MTA retrofilling during endodontic surgical procedures.


Assuntos
Compostos de Cálcio , Materiais Restauradores do Canal Radicular , Silicatos , Silicatos/uso terapêutico , Compostos de Cálcio/uso terapêutico , Humanos , Materiais Restauradores do Canal Radicular/farmacologia , Materiais Restauradores do Canal Radicular/uso terapêutico , Óxidos/farmacologia , Óxidos/uso terapêutico , Combinação de Medicamentos , Compostos de Alumínio/uso terapêutico , Técnicas In Vitro , Microscopia Confocal , Infiltração Dentária/microbiologia , Obturação Retrógrada/métodos , Enterococcus faecalis/efeitos dos fármacos , Viabilidade Microbiana , Incisivo , Apicectomia/métodos
7.
PLoS One ; 19(5): e0303314, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38739668

RESUMO

BACKGROUND: Globally, hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death due to a lack of early predictive and/or diagnostic tools. Thus, research for a new biomarker is important. LncRNAs play a functional role in target gene regulation and their deregulation is associated with several pathological conditions including HCC. OBJECTIVE: This study aimed to explore the diagnostic potential of two LncRNAs MALAT1 and CASC2 in HCC compared to the routinely used diagnostic biomarker. MATERIALS AND METHODS: The current study is a case-control study carried out at Fayoum University Hospital and conducted on 89 individuals. The study included three groups of 36 HCC patients on top of HCV(HCC/HCV), 33 HCV patients, and 20 healthy volunteers as a control group. All study subjects were subjected to radiological examinations. The determination of CBC was performed by the automated counter and liver function tests by the enzymatic method were performed. In addition, HCV RNA quantification and the expression level of two LncRNAs (MALAT1 and CASC2) were performed by qRT-PCR. RESULTS: The results revealed a statistically significant difference between study groups regarding liver function tests with a higher mean in HCC/HCV group. Also, serum MALAT1 significantly up-regulated in HCV (11.2±2.8) and HCC/HCV (4.56±1.4) compared to the control group. Besides, serum CASC2 levels in the HCV group were significantly upregulated (14.9±3.6), while, downregulated in the HCC group (0.16± 0.03). Furthermore, The ROC analysis for diagnostic efficacy parameters indicated that CASC2 has higher accuracy (94.6%) and sensitivity (97.2%) for HCC diagnosis than AFP with an accuracy of (90.9%), sensitivity (69.4%), and MALAT1 showed an accuracy of (56.9%), sensitivity (72.2%). CONCLUSION: Our study results indicated that CASC2 is a promising biomarker and is considered better and could help in HCC diagnosis on top of HCV than MALAT1 and the routine biomarker AFP.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular , Neoplasias Hepáticas , RNA Longo não Codificante , Proteínas Supressoras de Tumor , Humanos , RNA Longo não Codificante/genética , RNA Longo não Codificante/sangue , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/virologia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos de Casos e Controles , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/sangue , Proteínas Supressoras de Tumor/genética , Hepatite C/complicações , Hepatite C/virologia , Hepatite C/diagnóstico , Hepatite C/genética , Hepacivirus/genética , Idoso , Regulação Neoplásica da Expressão Gênica , Adulto , Curva ROC , Relevância Clínica
8.
Cureus ; 16(5): e60421, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38756717

RESUMO

Introduction Since the polished and fitting surface of the denture base may promote the colonization of microorganisms, it is essential to know how the different types of denture bases prevent or encourage the adhesion of microorganisms. This study aimed to compare the microbial adhesion to the polished and fitting surfaces of thermoplastic nylon, thermoplastic acetal, and thermoplastic acrylic denture bases in Kennedy Class Ⅰ, partially edentulous patients. Materials and methods Thirteen patients were included in the study. The group consisted of eight males (61.54%) and five females (38.46%), with an age range of 41-50 years (mean age 46.1 years). Three types (groups) of removable partial dentures will be made for each patient using different thermoplastic denture base materials: thermoplastic nylon; thermoplastic acetal; and thermoplastic acrylic. The polished and fitting surfaces of the denture bases were swabbed after a one-month follow-up period. Microbial adhesion was evaluated by counting the microorganisms' colony-forming units (CFU) in the collected specimens. The data were collected and statistically analyzed. Results The study revealed no statistically significant difference in microbial adhesion to both polished and fitting surfaces between all types of studied thermoplastic denture base materials. However, the results showed that for the polished surface, the microbial adhesion median of thermoplastic acrylic denture base (40.5 CC x 102/ml) was higher than that of thermoplastic acetal (29.0 CC x 102/ml) and thermoplastic nylon (16.0 CC x 102/ml). Regarding the fitting surface, the microbial adhesion median of thermoplastic acrylic (51.0 CC x 102/ml) is higher than that of thermoplastic acetal (41.0 CC x 102/ml) and thermoplastic nylon (23.0 CC x 102/ml). Conclusion The thermoplastic nylon denture base materials showed less microbial adhesion among the studied thermoplastic materials, so it may be recommended to be used as a denture base material for individuals at high risk of denture stomatitis.

9.
Nano Lett ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38608187

RESUMO

Germanium-tin (Ge1-xSnx) semiconductors are a front-runner platform for compact mid-infrared devices due to their tunable narrow bandgap and compatibility with silicon processing. However, their large lattice parameter has been a major hurdle, limiting the quality of epitaxial layers grown on silicon or germanium substrates. Herein, we demonstrate that 20 nm Ge nanowires (NWs) act as effective compliant substrates to grow extended defect-free Ge1-xSnx alloys with a composition uniformity over several micrometers along the NW growth axis without significant buildup of the compressive strain. Ge/Ge1-xSnx core/shell NWs with Sn content spanning the 6-18 at. % range are achieved and processed into photoconductors exhibiting a high signal-to-noise ratio at room temperature with a cutoff wavelength in the 2.0-3.9 µm range. The processed NW devices are integrated in an uncooled imaging setup enabling the acquisition of high-quality images under both broadband and laser illuminations at 1550 and 2330 nm without the lock-in amplifier technique.

10.
Science ; 384(6694): eadf5489, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38662826

RESUMO

Tubulin, one of the most abundant cytoskeletal building blocks, has numerous isotypes in metazoans encoded by different conserved genes. Whether these distinct isotypes form cell type- and context-specific microtubule structures is poorly understood. Based on a cohort of 12 patients with primary ciliary dyskinesia as well as mouse mutants, we identified and characterized variants in the TUBB4B isotype that specifically perturbed centriole and cilium biogenesis. Distinct TUBB4B variants differentially affected microtubule dynamics and cilia formation in a dominant-negative manner. Structure-function studies revealed that different TUBB4B variants disrupted distinct tubulin interfaces, thereby enabling stratification of patients into three classes of ciliopathic diseases. These findings show that specific tubulin isotypes have distinct and nonredundant subcellular functions and establish a link between tubulinopathies and ciliopathies.


Assuntos
Axonema , Centríolos , Cílios , Transtornos da Motilidade Ciliar , Tubulina (Proteína) , Animais , Humanos , Camundongos , Axonema/metabolismo , Centríolos/metabolismo , Cílios/metabolismo , Transtornos da Motilidade Ciliar/genética , Transtornos da Motilidade Ciliar/metabolismo , Mutação , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Tubulina (Proteína)/genética , Tubulina (Proteína)/metabolismo , Masculino , Feminino , Camundongos Knockout
12.
Cureus ; 16(3): e56029, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38606220

RESUMO

Morgagni hernias are uncommon diaphragmatic defects and are commonly found incidentally as a congenital defect. Acquired Morgagni hernias have been documented in the pediatric population, making them extremely uncommon. Thoracic segmental spinal anesthesia (TSSA) may be used as a successful substitute for general anesthesia, especially in cardiovascularly compromised patients like our patient who had heart failure with reduced ejection fraction (HFrEF), and this is one of the very few documented cases of acquired Morgagni hernia laparoscopic repair surgery done by this anesthesia method. An 80-year-old woman presented with a complaint of left lower chest and left upper quadrant pain. Acute coronary artery syndrome was ruled out. She underwent a coronary artery bypass graft in 2009, complicated two months later by mediastinitis, which is believed to be the cause of the acquired diaphragmatic defect in our patient. Chest and abdominal CT showed a large anterior Morgagni-type diaphragmatic hernia, in which the left hemithorax and anterior mediastinum were both occupied by a herniated transverse colon. Under regional anesthesia, which was done by injecting anesthesia in the spinal space between thoracic spinal vertebrae T8 and T9 and second injections in the epidural space at the level between thoracic epidural T9 and T10, which is neuraxial anesthesia. The repair of the diaphragmatic hernia was done by suturing the mesh into the proper position. We report the first known case of laparoscopic repair of a Morgagni hernia in an adult patient with HFrEF and other comorbidities.

13.
Nat Genet ; 56(3): 395-407, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38429495

RESUMO

In digenic inheritance, pathogenic variants in two genes must be inherited together to cause disease. Only very few examples of digenic inheritance have been described in the neuromuscular disease field. Here we show that predicted deleterious variants in SRPK3, encoding the X-linked serine/argenine protein kinase 3, lead to a progressive early onset skeletal muscle myopathy only when in combination with heterozygous variants in the TTN gene. The co-occurrence of predicted deleterious SRPK3/TTN variants was not seen among 76,702 healthy male individuals, and statistical modeling strongly supported digenic inheritance as the best-fitting model. Furthermore, double-mutant zebrafish (srpk3-/-; ttn.1+/-) replicated the myopathic phenotype and showed myofibrillar disorganization. Transcriptome data suggest that the interaction of srpk3 and ttn.1 in zebrafish occurs at a post-transcriptional level. We propose that digenic inheritance of deleterious changes impacting both the protein kinase SRPK3 and the giant muscle protein titin causes a skeletal myopathy and might serve as a model for other genetic diseases.


Assuntos
Doenças Musculares , Peixe-Zebra , Animais , Humanos , Masculino , Conectina/genética , Conectina/metabolismo , Músculo Esquelético , Doenças Musculares/genética , Doenças Musculares/metabolismo , Doenças Musculares/patologia , Mutação , Peixe-Zebra/genética
14.
Sensors (Basel) ; 24(2)2024 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-38276361

RESUMO

LiDAR sensors, pivotal in various fields like agriculture and robotics for tasks such as 3D object detection and map creation, are increasingly coupled with thermal cameras to harness heat information. This combination proves particularly effective in adverse conditions like darkness and rain. Ensuring seamless fusion between the sensors necessitates precise extrinsic calibration. Our innovative calibration method leverages human presence during sensor setup movements, eliminating the reliance on dedicated calibration targets. It optimizes extrinsic parameters by employing a novel evolutionary algorithm on a specifically designed loss function that measures human alignment across modalities. Our approach showcases a notable 4.43% improvement in the loss over extrinsic parameters obtained from target-based calibration in the FieldSAFE dataset. This advancement reduces costs related to target creation, saves time in diverse pose collection, mitigates repetitive calibration efforts amid sensor drift or setting changes, and broadens accessibility by obviating the need for specific targets. The adaptability of our method in various environments, like urban streets or expansive farm fields, stems from leveraging the ubiquitous presence of humans. Our method presents an efficient, cost-effective, and readily applicable means of extrinsic calibration, enhancing sensor fusion capabilities in the critical fields reliant on precise and robust data acquisition.


Assuntos
Agricultura , Algoritmos , Humanos , Calibragem , Evolução Biológica , Fazendas
15.
Orphanet J Rare Dis ; 19(1): 15, 2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38221620

RESUMO

BACKGROUND: Multiple acyl-CoA dehydrogenase deficiency (MADD) is an autosomal recessive disorder resulting from pathogenic variants in three distinct genes, with most of the variants occurring in the electron transfer flavoprotein-ubiquinone oxidoreductase gene (ETFDH). Recent evidence of potential founder variants for MADD in the South African (SA) population, initiated this extensive investigation. As part of the International Centre for Genomic Medicine in Neuromuscular Diseases study, we recruited a cohort of patients diagnosed with MADD from academic medical centres across SA over a three-year period. The aim was to extensively profile the clinical, biochemical, and genomic characteristics of MADD in this understudied population. METHODS: Clinical evaluations and whole exome sequencing were conducted on each patient. Metabolic profiling was performed before and after treatment, where possible. The recessive inheritance and phase of the variants were established via segregation analyses using Sanger sequencing. Lastly, the haplotype and allele frequencies were determined for the two main variants in the four largest SA populations. RESULTS: Twelve unrelated families (ten of White SA and two of mixed ethnicity) with clinically heterogeneous presentations in 14 affected individuals were observed, and five pathogenic ETFDH variants were identified. Based on disease severity and treatment response, three distinct groups emerged. The most severe and fatal presentations were associated with the homozygous c.[1067G > A];c.[1067G > A] and compound heterozygous c.[976G > C];c.[1067G > A] genotypes, causing MADD types I and I/II, respectively. These, along with three less severe compound heterozygous genotypes (c.[1067G > A];c.[1448C > T], c.[740G > T];c.[1448C > T], and c.[287dupA*];c.[1448C > T]), resulting in MADD types II/III, presented before the age of five years, depending on the time and maintenance of intervention. By contrast, the homozygous c.[1448C > T];c.[1448C > T] genotype, which causes MADD type III, presented later in life. Except for the type I, I/II and II cases, urinary metabolic markers for MADD improved/normalised following treatment with riboflavin and L-carnitine. Furthermore, genetic analyses of the most frequent variants (c.[1067G > A] and c.[1448C > T]) revealed a shared haplotype in the region of ETFDH, with SA population-specific allele frequencies of < 0.00067-0.00084%. CONCLUSIONS: This study reveals the first extensive genotype-phenotype profile of a MADD patient cohort from the diverse and understudied SA population. The pathogenic variants and associated variable phenotypes were characterised, which will enable early screening, genetic counselling, and patient-specific treatment of MADD in this population.


Assuntos
Deficiência Múltipla de Acil Coenzima A Desidrogenase , Humanos , Pré-Escolar , Deficiência Múltipla de Acil Coenzima A Desidrogenase/diagnóstico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/tratamento farmacológico , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Mutação/genética , África do Sul , Genótipo , Riboflavina/uso terapêutico , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Fatores de Troca do Nucleotídeo Guanina/uso terapêutico , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/genética , Proteínas Adaptadoras de Sinalização de Receptores de Domínio de Morte/metabolismo
16.
Egypt J Immunol ; 31(1): 106-115, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38224275

RESUMO

Colorectal cancer (CRC) is linked to high mortality, mainly when discovered in its advanced stages. Several studies have pointed to the role of epigenetic factors in CRC and other cancers. Long non-coding RNAs (lncRNAs) are involved in the initiation, progression, metastasis, and modulation of the response to chemotherapeutic modalities of CRC as vital contributors to epigenetic mechanisms. Colon cancer-associated transcript-1 (CCAT1) is one of the lncRNAs that have been dysregulated in serum samples, providing a non-invasive route for diagnosing CRC patients. This study aimed to determine the role of CCAT1 expression as diagnostic and prognostic markers. We tested the associations of CCAT1 expression with serum carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9). The study included three groups: 41 patients with colorectal cancer, 39 patients with precancerous benign colorectal diseases, and 20 normal control individuals. CEA and CA 19-9 were measured by an immunoassay automated system. The expression level of CCAT1 was assessed by a real-time polymerase chain reaction. There was a statistically significant elevation of serum CEA levels in patients with CRC compared to patients with precancerous benign colorectal diseases. Furthermore, there was no statistically significant difference in serum CA 19-9 levels between all groups (p = 0.102). Interestingly, CCAT1 expression was significantly upregulated in the blood of CRC patients compared to the precancerous benign colorectal diseases group (p = 0.009) and the control group (p <0.001). Also, expression of CCAT1 was significantly elevated in patients with precancerous benign colorectal diseases compared to the control group (p=0.004). In conclusion, measuring the expression level of CCAT1 is more advised than assessment of CEA and CA 19-9 for the early diagnosis and prognosis of colorectal cancer.


Assuntos
Neoplasias do Colo , Lesões Pré-Cancerosas , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Reação em Cadeia da Polimerase em Tempo Real , Antígeno Carcinoembrionário
17.
Int J Gynecol Pathol ; 2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38289148

RESUMO

SUMMARY: Netrin-1, an epithelial-secreted protein, plays a key role in placental formation through the promotion of cytotrophoblast proliferation and placental vascular development. These effects are mediated through several receptors, including the deleted in colorectal cancer (DCC) receptor. Placenta accreta spectrum (PAS) is an exaggerated trophoblastic invasion into the uterine myometrium. The exact etiology is unknown, but it is believed that increased trophoblastic invasion, defect decidualization, and/or abnormal angiogenesis might play a role. Our study aimed to investigate the suggested role of macrophage-induced netrin-1/DCC/vascular endothelial growth factor (VEGF) signaling in PAS pathogenesis. A total of 29 women with PAS (as cases) and 29 women with normal pregnancies (as controls) were enrolled in the study. At delivery, placental tissues of both groups were collected and processed for the evaluation of placental netrin-1 level by enzyme-linked immunoassay technique and immunohistochemical analysis of tissue DCC receptor. Placental tissue netrin-1 level of PAS cases showed a statistically significantly higher value than those in the normal group. Significant overexpression of DCC receptors, VEGF, and enhanced macrophage recruitment was noted in PAS cases in comparison to the normal placenta. Macrophage-induced netrin-1/DCC/VEGF signaling might be involved in PAS pathogenesis through the enhancement of trophoblastic angiogenesis.

18.
Sci Rep ; 14(1): 1613, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238419

RESUMO

In this paper, a new class of distributions called the T-X[Formula: see text] family of distributions for bounded-(0,1)-and unbounded-[Formula: see text]-supported random variables is suggested. Some special sub-models of the proposed family are utilized. A new sub-model is selected to be studied in details. The statistical properties of the suggested family including quantile function, moments, moment generating function, order statistics and Rényi entropy are discussed. The maximum likelihood method is provided to estimate the parameters of the distribution and a Monte Carlo simulation study is used. The discretized T-X[Formula: see text] family provided many sub-families and sub-models. In addition, eight real data sets are utilized to demonstrate the flexibility of the proposed continuous and discrete family's multiple sub models.

19.
Int J Oral Maxillofac Surg ; 53(3): 251-257, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37758642

RESUMO

This retrospective analysis was performed to investigate whether clindamycin remains the preferred antibiotic for penicillin-allergic patients with odontogenic infections. The medical records of 311 patients admitted to the study department with odontogenic infections between 2018 and 2022 and treated with either intravenous amoxicillin-clavulanic acid (Augmentin) or intravenous clindamycin were analyzed. The Augmentin-treated group included 268 patients (86.2%) and the clindamycin-treated group included 43 patients (13.8%). Severity parameters did not differ significantly between the two groups, except for a higher prevalence of abscesses in the clindamycin-treated group (58.1% vs 41.0% in the Augmentin-treated group; P = 0.035). The clindamycin-treated group required a longer duration of intravenous antibiotics (P = 0.001) and had a higher rate of treatment failure (14.0% vs 2.2%; P = 0.002) when compared to the Augmentin-treated group, with a seven-fold increased risk of treatment failure. Moreover, significantly more isolated organisms in the clindamycin-treated group were resistant to clindamycin (P = 0.015); these were all Streptococcus anginosus group. Given the higher risk of treatment failure with clindamycin, it is necessary to choose the antibiotic treatment for penicillin-allergic patients carefully. A detailed history and allergy testing followed by combination therapy is recommended, especially in severe cases.


Assuntos
Clindamicina , Penicilinas , Humanos , Penicilinas/uso terapêutico , Clindamicina/uso terapêutico , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Estudos Retrospectivos , Antibacterianos/uso terapêutico
20.
J Endocrinol Invest ; 47(4): 983-994, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37831337

RESUMO

AIM: Although macrovascular complications represent the leading cause of mortality in type 1 diabetes mellitus (T1DM), the prevalence of subtle macrovascular affection including peripheral artery disease (PAD) among children with T1DM and its genetic predictors remains to be unraveled. Increasing evidence suggests a link between adiponectin rs1501299 and chemerin rs17173608 gene polymorphism and atherogenesis, and insulin resistance. Hence, this study assess the prevalence of these variants among children with T1DM in comparison to healthy controls and their association with macrovascular complications, namely PAD and hyperlipidemia. METHODS: Fifty children with T1DM and 50 matched controls underwent a thorough assessment including adiponectin rs1501299 and chemerin rs17173608 gene polymorphisms, fasting lipids, glycated hemoglobin (HbA1c), and ankle-brachial index (ABI). Cochran-Armitage trend test was used to decide the risk allele and evaluate the association between the candidate variant and PAD using a case-control design. RESULTS: Children with T1DM were found to have significantly higher ABI (p = 0.011) than controls. Chemerin gene polymorphism was detected in 41 children with T1DM (82.0%), while adiponectin gene polymorphism was detected in 19 children (38.0%). Children with T1DM having GG chemerin variant and those having TT adiponectin variant had significantly higher cholesterol with significantly lower HDL-C and ABI than those having the other two variants (p < 0.005). Children with T1DM having abnormal ABI had significantly higher chemerin G (p = 0.017) and adiponectin T (p = 0.022) alleles than those with normal ABI. Cholesterol and ABI were independently associated with chemerin and adiponectin gene polymorphism by multivariable regression analysis. CONCLUSION: Children with T1DM having chemerin and adiponectin gene polymorphisms have significantly higher cholesterol and ABI than those without these polymorphisms and controls. TRIAL REGISTRATION: The Research Ethics Committee of Ain Shams University, approval number R 31/2021.


Assuntos
Diabetes Mellitus Tipo 1 , Doença Arterial Periférica , Criança , Humanos , Adiponectina , Colesterol , Polimorfismo de Nucleotídeo Único
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