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1.
Front Netw Physiol ; 4: 1441294, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39258030

RESUMEN

It is increasingly understood that the epilepsies are characterized by network pathology that can span multiple spatial and temporal scales. Recent work indicates that infraslow (<0.2 Hz) envelope correlations may form a basis for distant spatial coupling in the brain. We speculated that infraslow correlation structure may be preserved even with some time lag between signals. To this end, we studied intracranial EEG (icEEG) data collected from 22 medically refractory epilepsy patients. For each patient, we selected hour-long background, awake icEEG epochs before and after antiseizure medication (ASM) taper. For each epoch, we selected 5,000 random electrode contact pairs and estimated magnitude-squared coherence (MSC) below 0.15 Hz of band power time-series in the traditional EEG frequency bands. Using these same contact pairs, we shifted one signal of the pair by random durations in 15-s increments between 0 and 300 s. We aggregated these data across all patients to determine how infraslow MSC varies with duration of lag. We further examined the effect of ASM taper on infraslow correlation structure. We also used surrogate data to empirically characterize MSC estimator and to set optimal parameters for estimation specifically for the study of infraslow activity. Our empirical analysis of the MSC estimator showed that hour-long segments with MSC computed using 3-min windows with 50% overlap was sufficient to capture infraslow envelope correlations while minimizing estimator bias and variance. The mean MSC decreased monotonically with increasing time lag until 105 s of lag, then plateaued between 106 and 300 s. Significantly nonzero infraslow envelope MSC was preserved in all frequency bands until about 1 min of time lag, both pre- and post-ASM taper. We also saw a slight, but significant increase in infraslow MSC post-ASM taper, consistent with prior work. These results provide evidence for the feasibility of examining infraslow activity via its modulation of higher-frequency activity in the absence of DC-coupled recordings. The use of surrogate data also provides a general methodology for benchmarking measures used in network neuroscience studies. Finally, our study points to the clinical relevance of infraslow activity in assessing seizure risk.

2.
Cureus ; 16(8): e66809, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39280426

RESUMEN

Non-obstructive hypertrophic cardiomyopathy, or apical hypertrophic cardiomyopathy (ApHCM), also referred to as Yamaguchi syndrome, is a type of hypertrophic cardiomyopathy (HCM) characterized by significant thickening of the left ventricular apex without blockage in the left ventricular outflow tract. It is a very rare variant of HCM. Patients with non-obstructive HCM often experience symptoms such as chest pain, palpitations, shortness of breath, and syncope, which may resemble those seen in various cardiovascular and non-cardiac conditions. Yamaguchi syndrome presents as a challenging yet manageable condition in the ED. Early recognition, accurate diagnosis, and appropriate management are crucial for better outcomes. We report a case of a young female who presented to the ED with breathlessness and chest pain. The ECG findings suggested acute coronary syndrome (ACS), but echocardiography and cardiac biomarkers indicated otherwise, leading to the diagnosis of Yamaguchi Syndrome.

3.
Cureus ; 16(8): e66161, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39233971

RESUMEN

INTRODUCTION: Midface injuries, which are most common, can result in affectations to adjacent structures, including the nasolacrimal apparatus (NLA), which consists of the lacrimal sac, canaliculi, and nasolacrimal duct. OBJECTIVES: The objectives of this study were to visualise the radiographic patency of the nasolacrimal canal in a computed tomography (CT) scan and assess the type of injury. METHODOLOGY: This was a retrospective study wherein 322 CT scans of facial bones were analysed of patients who presented with midface fractures to the Department of Oral and Maxillofacial Surgery. The bony nasolacrimal canal was visualised on axial and coronal sections and confirmed on sagittal sections. The collapse of the bony nasolacrimal canal was measured using the advanced tools setting in the RadiAnt DICOM Viewer (Medixant, Poznan, Poland). The values were tabulated and statistically analysed. RESULTS: The incidence of NLA involvement in midface fractures was 37.6% (121 out of 322 fractures). The maximal involvement was seen in zygomaticomaxillary complex (ZMC) fractures. The visualisation of the fractures in the CT scan revealed that avulsion of the fossa was seen in 2.5% (eight out of 322 fractures), communication of the fossa or canal in 2.8% (nine out of 322 fractures), and linear fracture of the canal in 32.0% (103 out of 322 fractures). When measured in axial section, the Le Fort III fractures presented with a median of 2.15 mm, naso-orbito-ethmoid (NOE) fractures with a median of 0.90 mm, and fronto-naso-orbito-ethmoid (FNOE) fractures with a median of 1.15 mm. In the coronal section, the type of injuries that showed avulsion of the fossa had a median of 9.00 mm, communication of the fossa or canal showed 6.52 mm and linear fracture of the canal showed a median of 7.00 mm. CONCLUSION: Many a time, the NLA is often neglected during a routine radiographic assessment of a CT scan in patients presenting with maxillofacial injuries. These injuries may not be clinically evident during examination. This might lead to postoperative clinical presentations in a patient. This study shows the various types of injuries to the NLA and its appearance on a CT scan. It also explains the requirement of soft tissue management and the clinical co-relationship of these injuries.

4.
Cureus ; 16(7): e64663, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39149651

RESUMEN

Diabetes mellitus (DM) is a common cause of chronic kidney disease (CKD), leading to the need for renal replacement therapy (RRT). RRT includes hemodialysis (HD), peritoneal dialysis (PD), kidney transplantation (KT), and medical management. As CKD advances, the management of DM may change as medication clearance, effectiveness, and side effects can be altered due to decreasing renal clearance. Medications like metformin that were safe to use early in CKD may build up toxic levels of metabolites in advanced CKD. Other medications, like sodium-glucose co-transporter 2 inhibitors, which work by excreting glucose in the urine, may not be able to work effectively in advanced CKD due to fewer working nephrons. Insulin breakdown may take longer, and both formulation and dosing may need to be changed to avoid hypoglycemia. While DM control contributes to CKD progression, effective DM control continues to be important even after patients have been placed on RRT. Patients on RRT are frequently taken care of by a team of providers, including the primary care physician, both in and outside the hospital. Non-nephrologists who are involved with the care of a patient treated with RRT need to be adept at managing DM in this population. This paper aims to outline the management of type 2 DM in advanced CKD.

5.
Cureus ; 16(6): e61833, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38975460

RESUMEN

Gas gangrene is a lethal necrotic infection resulting in gas production within tissue. It is typically associated with trauma and is especially lethal during pregnancy, resulting in severe maternal infection and fetal death. We report the case of a 31-year-old G3P2 female who presented to the emergency department with abdominal bloating, vaginal cramping, and brown vaginal discharge. Physical examination showed that the patient was hypertensive, tachycardic, and tachypneic, and laboratory examination showed a downtrending beta-human chorionic gonadotropin and leukocytosis, with elevated inflammatory markers. Ultrasound showed copious gas located within the lower abdomen and the fetus was not visualized. Computed tomography (CT) of the abdomen and pelvis showed a gravid uterus with a single fetus and extensive air locules in the fetus, amniotic cavity, and placenta. The findings were consistent with gas gangrene of a mature fetus in the third trimester. Fetal gas gangrene is a potentially lethal condition during pregnancy, and early diagnosis is imperative in management. CT was utilized in this case to outline the increased gas production within the amniotic cavity and fetal organs and proved crucial in determining the next steps of management.

6.
Cureus ; 16(6): e61635, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38966460

RESUMEN

The type of liver cancer that occurs most frequently is hepatocellular carcinoma (HCC). The majority of cases of HCC are secondary to alcoholic cirrhosis or viral hepatitis. The presence of malignant cells with modest nuclear atypia that resemble normal hepatocytes and the lack of bare nuclei in the smears, which shows the neoplastic hepatocytes' capacity, are characteristics of a well-differentiated HCC plasma membrane to tolerate smearing. We present the case of an 83-year-old male patient with a well-differentiated HCC, who had no etiological factors and no signs of alcohol cirrhotic liver, or any symptoms of liver disease which are the main causes of the HCC.

7.
Cureus ; 16(6): e61546, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38962584

RESUMEN

Introduction Optimal repair of the joint line (JL) in total knee arthroplasty (TKA) is critical for knee joint motion reconstruction and ligament balance. Identification of JL may be difficult, particularly in revision or primary cases of severe femoral condylar bone loss. We aimed to define the relationship between the epicondyles and the articular surface (AS) of the femur using computed tomography-based three-dimensional digital templating software. Methods The study included 127 knees with osteoarthritis of the knee below grade 2 on the Kellgren-Lawrence index. A perpendicular line was drawn from the medial and lateral femoral epicondylar processes to the most distal point of the AS, and the distance was measured in the axial and coronal planes. Femoral width was measured as the distance between the medial and lateral epicondyles. All distances described above were converted to a ratio by division with femoral width. Results On the axial plane, the distance from epicondyles to the posterior ASs was 29.4 ± 2.2 mm medially and 21.3 ± 2.1 mm laterally. The width of the distal femur was 75.2 ± 4.2 mm. On the coronal plane, the distances from epicondyles to the distal ASs were 25.2 ± 2.9 mm on the medial side and 21.3 ± 2.5 mm on the lateral side. The ratio of the distance from epicondyles to the distal and posterior ASs divided by the width of the femur was 0.39 ± 0.02, 0.28 ± 0.03, 0.34 ± 0.03, and 0.28 ± 0.03. Conclusions The distance from the epicondyles to the distal and posterior JLs correlates with the distal femur width. These findings may be useful in determining an appropriate JL.

8.
Free Radic Biol Med ; 221: 23-30, 2024 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-38740100

RESUMEN

The pathogenesis of systemic sclerosis (SSC) fibrosis involves the rapid proliferation of skin fibroblasts, and current anti-fibrotic treatments are limited. This study investigated the relationship between ferroptosis and SSC skin fibroblasts. We observed that erastin-induced ferroptosis was suppressed in SSC fibroblasts. RSL3, a direct inhibitor of Glutathione Peroxidase 4 (GPX4), significantly reduced the viability of the fibroblasts, and upregulation of GPX4 in the SSC fibroblasts contributed to ferroptosis resistance. Furthermore, we demonstrated that transferrin receptor 1 (TfR1) was a crucial transporter for iron deposition in the fibroblasts. Collectively, our results highlight that GPX4 inhibition could enhance the sensitivity to ferroptosis by SSC fibroblasts, which showed distinct characteristics of iron metabolism that were not observed in normal fibroblasts in this study. Taken together, these results suggest that targeting ferroptosis could be a therapeutic strategy for the treatment of SSC.


Asunto(s)
Ferroptosis , Fibroblastos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Esclerodermia Sistémica , Piel , Femenino , Humanos , Antígenos CD/metabolismo , Antígenos CD/genética , Carbolinas , Células Cultivadas , Ferroptosis/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Fibroblastos/efectos de los fármacos , Hierro/metabolismo , Fenantridinas/farmacología , Fosfolípido Hidroperóxido Glutatión Peroxidasa/metabolismo , Fosfolípido Hidroperóxido Glutatión Peroxidasa/genética , Piperazinas , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Esclerodermia Sistémica/patología , Esclerodermia Sistémica/metabolismo , Esclerodermia Sistémica/genética , Piel/patología , Piel/metabolismo , Regulación hacia Arriba
9.
Cureus ; 16(4): e58426, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38765358

RESUMEN

Introduction Acute Coronary Syndrome (ACS) is a critical condition characterized by reduced blood flow to the heart and includes various conditions such as ST-elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina. Objectives The aim of this study was to investigate age-related patterns of symptoms and risk factors in ACS patients and to evaluate how diagnostic test results differ among various age groups of ACS patients. Methodology This retrospective study was conducted from May to November of 2023 on patients with acute coronary syndrome admitted to the cardiology ward of Rehman Medical Institute (RMI), Peshawar. The sample size was 137 ACS-diagnosed patients based on the inclusion and exclusion criteria. After getting ethical approval from the institutional ethical approval board, data were collected for the entire year of 2022 based on proforma with the variables demographic data, troponin I level, presented symptoms, and associated co-morbidities of the patients. The inclusion criteria were patients of all genders, patients diagnosed with Acute Coronary Syndrome (ACS), and patients whose records were available in the cardiology department of Rehman Medical Institute.  Results The results show that ACS is more prevalent in the age group of 50-69 years (p=0.037) and is significantly more common in males (p=0.019). Chest pain emerged as the predominant symptom, with a significant association of p=0.029 between chest pain and patients of ACS in the age group 30-49 years. While raised troponin I levels were prevalent across all age groups. Moreover, specific risk factors such as diabetes mellitus, hypertension, and family history of CAD showed the significance of p= 0.04, p=0.006, and p=0.021, respectively, with the age group 50-69 years old. Conclusion This study highlights the importance of considering age and gender in ACS management and provides insights into age-related patterns of symptoms and risk factors, which can contribute to optimizing preventive strategies and improving patient care. Further research is needed to explore the underlying mechanisms and assess long-term outcomes in different age groups.

10.
Front Chem ; 12: 1381144, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736687

RESUMEN

The photo-enhanced electrocatalytic method of oxygen evolution reaction (OER) shows promise for enhancing the effectiveness of clear energy generation through water splitting by using renewable and sustainable source of energy. However, despite benefits of photoelectrocatalytic (PEC) water splitting, its uses are constrained by its low efficiency as a result of charge carrier recombination, a large overpotential, and sluggish reaction kinetics. Here, we illustrate that Nickel telluride (NiTe) synthesized by hydrothermal methods can function as an extremely effective photo-coupled electrochemical oxygen evolution reaction (POER) catalyst. In this study, NiTe was synthesized by hydrothermal method at 145°C within just an hour of reaction time. In dark conditions, the NiTe deposited on carbon cloth substrate shows a small oxygen evolution reaction overpotential (261 mV) at a current density of 10 mA cm-2, a reduced Tafel slope (65.4 mV dec-1), and negligible activity decay after 12 h of chronoamperometry. By virtue of its enhanced photo response, excellent light harvesting ability, and increased interfacial kinetics of charge separation, the NiTe electrode under simulated solar illumination displays exceptional photoelectrochemical performance exhibiting overpotential of 165 mV at current density of 10 mA cm-2, which is about 96 mV less than on dark conditions. In addition, Density Functional Theory investigations have been carried out on the NiTe surface, the results of which demonstrated a greater adsorption energy for intermediate -OH on the catalyst site. Since the -OH adsorption on the catalyst site correlates to catalyst activation, it indicates the facile electrocatalytic activity of NiTe owing to favorable catalyst activation. DFT calculations also revealed the facile charge density redistribution following intermediate -OH adsorption on the NiTe surface. This work demonstrates that arrays of NiTe elongated nanostructure are a promising option for both electrochemical and photoelectrocatalytic water oxidation and offers broad suggestions for developing effective PEC devices.

11.
Surg Oncol ; 54: 102060, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38603927

RESUMEN

BACKGROUND: Circulating tumour DNA (ctDNA), contains tumour-specific gene mutation in blood circulation and could aid in postoperative risk stratification of non-metastatic breast cancer. In this study, we investigated the feasibility of detecting PIK3CA gene mutations in ctDNA in the preoperative (preop) and postoperative period (postop), and its prognostic significance in patients with breast cancer. METHODS: A cohort of patients with breast cancer undergoing curative surgery with available blood samples preoperatively and postoperatively (Post op) at either Post op time period; week 1-2, week 3-4 or weeks 5-12 were enrolled. PIK3CA gene mutations at exons 9 and 20 were detected in ctDNA with High resolution melting (HRM) PCR and Allele specific fluorescence probe-based PCR. RESULTS: A total of 62 patients (age, median (IQR), 51.50 (45.0-65.0) years), with a median follow-up of 90 months (interquartile range (IQR),60-120 months) were enrolled. In total, 25 (40.3%) and 22 (35%) patients with breast cancer had detectable PIK3CA gene mutations in ctDNA in preoperative and postoperative period, respectively. PIK3CA gene mutations in ctDNA in postoperative period (hazard ratio (H.R: 18.05, p = 0.001) were a negative prognostic factor for recurrencefree survival (RFS) and overall survival (OS) (H.R: 11.9, p = 0.01) in patients with breast cancer. Subgroup analysis of ctDNA indicate that positive ctDNA in both preoperative/postoperative period and post op period only were found to have prognostic effect on RFS and OS (RFS; p < 0.0001, O·S; p = 0.0007). Moreover, ctDNA-based detection preceded clinical detection of recurrence in patients with an average lead time of 12 months (IQR:20-28.5 months) across all the breast cancer subtypes. CONCLUSION: We highlighted the prognostic ability of ctDNA in patients with breast cancer in perioperative period. However, future prospective studies are needed to assess the utility of ctDNA in clinical practice.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , ADN Tumoral Circulante , Fosfatidilinositol 3-Quinasa Clase I , Mutación , Recurrencia Local de Neoplasia , Humanos , Fosfatidilinositol 3-Quinasa Clase I/genética , Femenino , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Neoplasias de la Mama/sangre , ADN Tumoral Circulante/genética , ADN Tumoral Circulante/sangre , Persona de Mediana Edad , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/sangre , Anciano , Pronóstico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/sangre , Estudios de Seguimiento , Tasa de Supervivencia , Periodo Posoperatorio , Periodo Preoperatorio
12.
Cureus ; 16(3): e55478, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38571859

RESUMEN

BACKGROUND: Diabetes mellitus (DM) long-term macrovascular and microvascular complications pose significant health risks and increase mortality. In DM patients, metabolic syndrome (MetSy) either precedes or coexists with the condition. Central obesity, poor glycemic control, hypertension, elevated triglycerides (TG), and low high-density lipoproteins (HDL-C) are the components of MetSy. The purpose of this study is to investigate related diabetic microvascular complications in type 1 DM (T1DM) by comparing them with type 2 DM (T2DM), determine potential risk factors, and estimate prevalence based on the diagnosis of MetSy. METHODOLOGY: This study included 160 T1DM and 160 T2DM patients, totaling 320 DM patients. It was carried out from April 20, 2022, to September 31, 2023, at the Sheikh Zayed Hospital, Rahim Yar Khan, in the Outdoor Diabetic Clinic and Medicine Department. A unique questionnaire was utilized to gather socio-demographic, general, clinical, and laboratory data for the MetSy criteria set forth by the International Diabetes Federation (IDF). The blood pressure, BMI, and waist circumference (WC) were measured, while venous fasting blood was used to assess biochemical markers such as HDL-C, TG, and fasting blood sugar. The microvascular diabetes complications were identified using abdominal ultrasound, fundus ophthalmoscopy, and routine laboratory tests. We quantified and analyzed these variables individually for T1DM and T2DM patients with or without MetSy and compared them in the presence or absence of diabetes microvascular complications. RESULTS: MetSy prevalence was 25.62% (41, n=160) for T1DM and 60.62% (97, n=160) for T2DM, totaling 43.12%. Among T1DM patients with MetSy, the majority were married males, aged 36-49 years, with a BMI of 26.69±2.20 kg/m2 and a WC of 85.12±4.23, and 67.5% (108) patients had diabetes microvascular complications. Comparatively, in T2DM with MetSy, the majority were married females aged 50-59 years with a BMI of 29.79 ± 4.65 kg/m² and a large WC of 93.43±4.49, and 75% (123) patients had diabetes microvascular complications. Overall, this study noted significant p-values for hypertension, elevated TG, low HDL-c, high WC, obesity, female gender in T2DM, and above 36 years of age in both groups with MetSy. Diabetic retinopathy (DR) at 32.4% (p<0.001) was the most prevalent T1DM microvascular complication, followed by nephropathy (30.6%), neuropathy (DN) at 28.1%, and gastroparesis (DG) at 22.3%. Whereas in T2DM, the prevalence of DN was 36.3% (p<0.001), followed by DKD (29.3%), DG (28.9%), and DR (24.9%). CONCLUSION: Nearly a quarter of T1DM patients had MetSy, with increasing percentages of overweight and obese patients who are more likely to have DR, DKD, or DN. MetSy affects two-thirds of T2DM patients, with married obese females aged 50-59 being more susceptible than males, who are more likely to suffer DN, DKD, or DG. Risk factors that contribute to the MetSy burden in T1DM and T2DM include hypertension, poor glycemic management, low HDL-C, high TG, and a higher BMI or WC. Increasing age, female gender in T2DM, longer diabetes duration, and co-morbid hypertension were independent predictors of microvascular complications. DR, DN, DKD, and gastroparesis are the most prevalent diabetic microvascular sequelae. The clinical management of diabetic patients with healthy lifestyle adaptations, good glycemic control, antihypertensives, and statins will contribute greatly to MetSy prevention.

13.
Heliyon ; 10(7): e28487, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38596044

RESUMEN

In this study, we assess the feasibility of using Fourier Transform Infrared Photoacoustic Spectroscopy (FTIR-PAS) to predict macro- and micro-nutrients in a diverse set of manures and digestates. Furthermore, the prediction capabilities of FTIR-PAS were assessed using a novel error tolerance-based interval method in view of the accuracy required for application in agricultural practices. Partial Least-Squares Regression (PLSR) was used to correlate the FTIR-PAS spectra with nutrient contents. The prediction results were then assessed with conventional assessment methods (root mean square error (RMSE), coefficient of determination R2, and the ratio of prediction to deviation (RPD)). The results show the potential of FTIR-PAS to be used as a rapid analysis technique, with promising prediction results (R2 > 0.91 and RPD >2.5) for all elements except for bicarbonate-extractable P, K, and NH4+-N (0.8 < R2 < 0.9 and 2 < RPD <2.5). The results for nitrogen and phosphorus were further evaluated using the proposed error tolerance-based interval method. The probability of prediction for nitrogen within the allowed limit is calculated to be 94.6 % and for phosphorus 83.8 %. The proposed error tolerance-based interval method provides a better measure to decide if the FTIR-PAS in its current state could be used to meet the required accuracy in agriculture for the quantification of nutrient content in manure and digestate.

14.
Cureus ; 16(3): e56953, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38665713

RESUMEN

Congenital adrenal hyperplasia (CAH) is caused by genetic defects in the enzymes involved in cortisol biosynthesis in the adrenal gland and, in more than 90% of cases, due to a deficiency in the 21-hydroxylase enzyme. Classical CAH due to 21-hydroxylase deficiency is a severe form of the disease that presents with cortisol deficiency and is further categorized into salt-wasting or simple-virilizing types. Appropriate steroid replacement has been shown to effectively treat patients with classical CAH and prevent complications. Individuals who receive inadequate treatment or fail to comply with their prescribed steroid hormone regimen are susceptible to the development of adrenal myelolipomas. Myelolipomas are benign tumors composed of both adipose and hematopoietic tissues. While documented cases of adrenal myelolipomas exist in medical literature, instances of large bilateral myelolipomas remain exceedingly rare. This case report highlights a 40-year-old female patient with a known history of classical congenital adrenal hyperplasia who presented with unusually large bilateral adrenal myelolipomas. A diagnostic CT scan of the abdomen and pelvis revealed a 13.4 x 10.8 cm myelolipoma on the left adrenal gland and a 10 x 8.6 cm myelolipoma on the right adrenal gland. Prior to her presentation, the patient experienced recurrent nausea and vomiting, along with left upper quadrant pain, over five months. Hormonal assessments indicated significantly elevated serum androgen levels, suggesting inadequate management of her CAH. In this report, we present a rare case of symptomatic bilateral large adrenal myelolipomas, underscoring the significance of adhering to treatment regimens, diagnostic assessments, and management for adrenal myelolipomas in individuals diagnosed with CAH.

15.
Eur J Med Chem ; 269: 116325, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38527378

RESUMEN

By virtue of the drug repurposing strategy, the anti-osteoporosis drug raloxifene was identified as a novel PPARγ ligand through structure-based virtual high throughput screening (SB-VHTS) of FDA-approved drugs and TR-FRET competitive binding assay. Subsequent structural refinement of raloxifene led to the synthesis of a benzothiophene derivative, YGL-12. This compound exhibited potent PPARγ modulation with partial agonism, uniquely promoting adiponectin expression and inhibiting PPARγ Ser273 phosphorylation by CDK5 without inducing the expression of adipongenesis associated genes, including PPARγ, aP2, CD36, FASN and C/EBPα. This specific activity profile resulted in effective hypoglycemic properties, avoiding major TZD-related adverse effects like weight gain and hepatomegaly, which were demonstrated in db/db mice. Molecular docking studies showed that YGL-12 established additional hydrogen bonds with Ile281 and enhanced hydrogen-bond interaction with Ser289 as well as PPARγ Ser273 phosphorylation-related residues Ser342 and Glu343. These findings suggested YGL-12 as a promising T2DM therapeutic candidate, thereby providing a molecular framework for the development of novel PPARγ modulators with an enhanced therapeutic index.


Asunto(s)
PPAR gamma , Clorhidrato de Raloxifeno , Tiofenos , Ratones , Animales , PPAR gamma/metabolismo , Simulación del Acoplamiento Molecular , Reposicionamiento de Medicamentos
16.
Cureus ; 16(2): e53653, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38449968

RESUMEN

Background Epidural hematomas (EDHs), which have a characteristic biconvex shape, are a type of post-traumatic intracranial mass. EDHs and other types of intracranial hematomas are often diagnosed with computed tomography (CT). The volumes of EDHs are important in treatment decisions and prognosis. Their volumes are usually estimated on CT using the "ABC" method, which is based on the ellipsoid shape rather than their biconvex shape. Objective To simulate the biconvex shape, we modeled the geometry of EDHs with two spherical caps. We aim to provide simpler estimation of EDH volumes in clinical settings, and eventually recommend a threshold for surgical evacuation. Methods Applying the relationship between the sphere radius, spherical cap height, and base circle radius, we derived formulas for the shape of an EDH, relating its largest diameter and location to the other two diameters. We also estimated EDH volumes using the spherical cap volume and conventional ABC formulas and then constructed a lookup table accordingly. Results Validation of the model was performed using 14 CT image sets from previously reported patients with EDHs. Our geometric model demonstrated accurate predictions. The model also allows reducing the number of parameters to be measured in the ABC method from three to one, the hematoma length, showcasing its potential as a reliable tool for clinical decision-making. Based on our model, an EDH longer than 7 cm would occupy more than 30 mL of the intracranial volume. Conclusion The proposed model offers a streamlined approach to estimating EDH volumes, reducing the complexity of parameters required for clinical assessments. We recommend a length of 7 cm as a threshold for surgical evacuation of EDHs. This acceleration in decision-making is crucial for managing critically injured patients with traumatic brain injuries. Further validation across diverse patient populations will enhance the generalizability and utility of this geometric modeling approach in clinical settings.

17.
Heliyon ; 10(2): e24654, 2024 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-38304769

RESUMEN

The importance of flexible employment has been highlighted at the policy level in China. In the process of implementing the employment priority strategy, the number of flexible workers in China has exceeded 200 million. Platform-based flexible employment has shown great potentiality in stabilising employment, but as a new form of employment, its employment quality still needs to be improved. Based on the research data, this study identified 14 effective factors influencing the employment quality of platform-based flexible workers and constructed a five-level interpretative structural model (ISM) for the employment quality of platform-based flexible workers. According to the characteristics of different platform types, platform-based flexible employment was divided into business-type and labour-type flexible employment. Then hierarchical logistic regression analysis was conducted on the quality of the two types of flexible workers respectively. The results showed that working hours only had a significant positive effect on the employment quality of business-type flexible workers, while salary and employment injury insurance only had a significant positive effect on the employment quality of labour-type flexible workers. This paper proposed policy recommendations to achieve high-quality employment for flexible workers on different platforms.

18.
Environ Pollut ; 346: 123535, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38365080

RESUMEN

With the development of world industrialization, the environmental pollution of hexavalent chromium [Cr(VI)] is becoming an increasingly serious problem. In particular, the mechanisms by which long-term and low-dose exposure to Cr(VI) leading the development of related cancers are not well understood. As senescent cells gradually lose their ability to proliferate and divide, they will not be malignantly transformed. However, Senescence-associated secretory phenotype (SASP) released by senescent cells into the cellular microenvironment can act on neighboring cells. Since SASP has a bidirectional regulatory role in the malignant transformation of cells. Hence, It is very necessary to identified the composition and function of SASP which secreted by Cr(VI) induced senescent L02 hepatocytes (S-L02). Exosomes, a vesicle-like substances released extracellularly after the fusion of intracellular multivesicular bodies with cell membrane, are important components of SASP and contain a large number of microRNAs (miRNAs). By establishing Cr(VI)-induced S-L02 model, we collected the exosomes from the supernatants of S-L02 and L02 culture medium respectively, and screened out the highly expressed miRNAs in the exosomes of S-L02, namely the new SASP components. Among them, the increase of miR-222-5p was the most significant. It was validated that as SASP, miR-222-5p can inhibit the proliferation of L02 and S-L02 hepatocytes and at the same time accelerate the proliferation and migration ability of HCC cells. Further mechanistic studies revealed that miR-222-5p attenuated the regulatory effect of protein phosphatase 2A subunit B isoform R2-α (PPP2R2A) on Akt via repressing its target gene PPP2R2A, causing reduced expressions of forkhead box O3 (FOXO3a), p27 and p21, and finally increasing the proliferation of HCC cells after diminishing the negative regulation of on cell cycle. This study certainly provides valuable laboratory evidence as well as potential therapeutic targets for the prevention and further personalized treatment of Cr(VI)-associated cancers.


Asunto(s)
Carcinoma Hepatocelular , Cromo , Exosomas , Neoplasias Hepáticas , MicroARNs , Humanos , Exosomas/metabolismo , Hepatocitos , MicroARNs/genética , MicroARNs/metabolismo , Microambiente Tumoral
19.
Cureus ; 16(1): e52687, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38384636

RESUMEN

To evaluate the level of knowledge about radiation dose and possible risks related to computed tomography (CT) scans among patients visiting emergency departments (EDs), a survey was conducted over a two-month period. A total of 357 adult patients (44% men and 56% women) presenting for diagnostic imaging in the ED answered a survey consisting of 15 questions. The survey included questions about the participants' demographics and knowledge of radiation. Most of the respondents (58.5%) reported that the physician did not explain the potential risk of radiation before the procedure. In addition, more than half of the respondents (58.1%) expressed feeling anxious about the potential risk of radiation. Most respondents (84.9%) stated that the potential radiation risk did not affect their decision to proceed with the procedure. Overall, the findings highlight a lack of information about radiation and its potential risks provided to patients prior to the diagnostic procedure. Increasing awareness and understanding of the risks associated with these imaging modalities should be considered essential in modern communities. Efforts should be made to ensure that patients undergoing diagnostic imaging are aware of the radiation risks they may encounter.

20.
G3 (Bethesda) ; 14(3)2024 Mar 06.
Artículo en Inglés | MEDLINE | ID: mdl-38096484

RESUMEN

Plant breeding and genetics play a major role in the adaptation of plants to meet human needs. The current requirement to make agriculture more sustainable can be partly met by a greater reliance on biological nitrogen fixation by symbiotic diazotrophic microorganisms that provide crop plants with ammonium. Select accessions of the cereal crop sorghum (Sorghum bicolor (L.) Moench) form mucilage-producing aerial roots that harbor nitrogen-fixing bacteria. Breeding programs aimed at developing sorghum varieties that support diazotrophs will benefit from a detailed understanding of the genetic and environmental factors contributing to aerial root formation. A genome-wide association study of the sorghum minicore, a collection of 242 landraces, and 30 accessions from the sorghum association panel was conducted in Florida and Wisconsin and under 2 fertilizer treatments to identify loci associated with the number of nodes with aerial roots and aerial root diameter. Sequence variation in genes encoding transcription factors that control phytohormone signaling and root system architecture showed significant associations with these traits. In addition, the location had a significant effect on the phenotypes. Concurrently, we developed F2 populations from crosses between bioenergy sorghums and a landrace that produced extensive aerial roots to evaluate the mode of inheritance of the loci identified by the genome-wide association study. Furthermore, the mucilage collected from aerial roots contained polysaccharides rich in galactose, arabinose, and fucose, whose composition displayed minimal variation among 10 genotypes and 2 fertilizer treatments. These combined results support the development of sorghums with the ability to acquire nitrogen via biological nitrogen fixation.


Asunto(s)
Sorghum , Humanos , Sorghum/genética , Grano Comestible/genética , Estudio de Asociación del Genoma Completo , Fijación del Nitrógeno/genética , Fertilizantes , Fitomejoramiento , Fenotipo
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