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1.
Front Neurol ; 15: 1420530, 2024.
Article in English | MEDLINE | ID: mdl-38978812

ABSTRACT

Background: The recommended treatment for cervical spinal cord injury (cSCI) is surgical decompression and stabilization within 24 h after injury. The aims of the study were to estimate our institutional compliance with this recommendation and identify potential factors associated with surgical delay. Methods: Population-based retrospective database study of patients operated for cSCI in 2015-2022 within the South-East Norway Health Region (3.1 million inhabitants). Data extracted were demographics, injury description, management timeline, place of primary triage [local hospital (LH) or neurotrauma center (NTC)]. Main outcome variables were: (1) time from injury to surgery at NTC, (2) time from injury to admission NTC, and (3) time from admission NTC to surgery. Results: We found 243 cSCI patients having acute neck surgery. Their median age was 63 years (IQR 47-74 years), 77% were male, 48% were ≥65 years old. Primary triage at an LH occurred in 150/243 (62%). The median time from injury to acute surgery was 27.8 h (IQR 15.4-61.9 h), and 47% had surgery within 24 h. The median time from injury to NTC admission was 5.6 h (IQR 1.9-19.4 h), and 67% of the patients were admitted to the NTC within 12 h. Significant factors associated with increased time from injury to NTC admission were transfer via LH, severe preinjury comorbidities, less severe cSCI, time of injury other than night, absence of multiple injuries. The median time from NTC admission to surgery was 16.7 h (IQR 9.5-31.0 h), and 70% had surgery within 24 h. Significant factors associated with increased time from NTC admission to surgery were increasing age and non-translational injury morphology. Conclusion: Less than half of the patients with cSCI were operated on within the recommended 24 h time frame after injury. To increase the fraction of early surgery, we suggest the following: (1) patients with clinical suspicion of cSCI should be transported directly to the NTC from the scene of the accident, (2) MRI should be performed only at the NTC, (3) at the NTC, surgery should commence on the same calendar day as arrival or as the first operation the following day.

2.
Ann Vasc Surg ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-39004279

ABSTRACT

OBJECTIVES: Phlebolymphedema is a challenging condition to manage, with limited options for effective treatment. For patients, this may be debilitating and lead to infection, loss of independence and affect quality of life (QOL). This study aims to evaluate patient-reported outcomes of an advanced pneumatic compression device (APCD) in the treatment of lower extremity phlebolymphedema. METHODS: Patients with diagnosis of lower extremity phlebolymphedema at an acute care facility within the New York City Health and Hospitals Cooperation treated with the Flexitouch (FLX; Tactile Systems Technology, Inc, Minneapolis, Minnesota) APCD from December 2021 to March 2023 were evaluated. Patient-perceived subjective outcomes were assessed via a short questionnaire, with subsequent analysis using Chi-squared test. Primary endpoints were subjective improvements in 1) swelling, 2) pain, and 3) ease of use of device as surrogates for patient satisfaction. Secondary endpoint was subjective patient-reported compliance, obtained by investigating 1) if patients were trained to use device, and 2) if patients were using the device. RESULTS: A total of 52 participants were included in this study, consisting of 30.8% male and 69.2% female patients with a mean age of 71.7 years. While selection criteria did not exclude unilateral disease or alternative etiologies, we note that the entire study population had been diagnosed with bilateral lower extremity lymphedema in the setting of chronic venous insufficiency. Other patient characteristics including race, comorbidities and smoking status were documented in Table 1. Table 2 demonstrates the results of Chi-squared analysis. This study noted significant patient-perceived improvement in swelling and pain (91.4% with P < 0.00001; 85.7% with P = 0.00002 respectively) as well as patient-reported ease of use of the FLX device (85.7% with P = 0.00002). Additional secondary findings included a majority of patients reporting being trained on how to use FLX and also maintaining compliance with the device (69.2% with P = 0.005; 67.3% with P = 0.012 respectively). CONCLUSIONS: FLX APCD use has been found to demonstrate desirable patient-reported outcomes as a general trend. The participants in this study noted statistically significant subjective improvement in swelling and pain, ease of use of device as well as adherence to training and compliance with device. FLX appears to be positively received by patients, and the authors recommend its consideration for management of bilateral lower extremity phlebolymphedema.

3.
Anal Methods ; 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38993062

ABSTRACT

The design and development of a facile synthesis approach to construct novel materials for the rapid adsorption and removal of environmental pollutants are of significant interest. In this work, we report the rational design and facile synthesis of magnetic core-shell-based microporous organic networks, Fe3O4@MON-TBPT-TEB (TTMON, achieved by reacting 2,4,6-tris(p-bromophenyl) triazine and 1,3,5-triethynylbenzene) and Fe3O4@MON-TBPM-DEBP (TDMON, achieved by reacting tetrakis (4-bromophenyl) methane and 4-4'-diethynylbiphenyl). These MONs possessed excellent dispersity, electrostatic attraction as well as plenty of π-π and hydrophobic interaction sites enabled them to efficiently absorb targeted environmental pollutants. TTMON and TDMON exhibited excellent adsorption capacities of 440 and 510 mg g-1, respectively, at 25 °C for 2,4,6-trichlorophenol (TCP). TCP, 2,4-dichlorophenol (DCP), 2-naphthol (2-NT) and 4-nitrophenol (4-NP) from aqueous solution were treated by both MONs, followed by their analysis with high-performance liquid chromatography (HPLC). For TDMON, the proposed SPE-HPLC-UV method showed an LOD of 0.03 µg L-1, LOQ of 0.11 µg L-1, and a wide linear range of 1-1000 µg L-1 for TCP. The adsorption kinetics, thermodynamics, isotherms, effect of pH and humic acid (HA), ionic strength, regeneration, and reusability of the MONs were also studied. The results revealed that the novel-designed MONs have potential applications as efficient adsorbents in sample pretreatment.

4.
Article in English | MEDLINE | ID: mdl-38963236

ABSTRACT

Aging results into disruptive physiological functioning and cellular processes that affect the composition and structure of the plasma membrane. The plasma membrane is the major regulator of ionic homeostasis that regulates the functioning of membrane transporters and exchangers. Coenzyme Q10 is a lipid-soluble antioxidant molecule that declines during aging and age-associated diseases. The present study aims to explore the role of Coenzyme Q10 supplementation to rats during aging on membrane transporters and redox biomarkers. The study was conducted on young and old male Wistar rats supplemented with 20 mg/kg b.w. of Coenzyme Q10 per day. After a period of 28 days, rats were sacrificed and erythrocyte membrane was isolated. The result exhibits significant decline in biomarkers of oxidative stress in old control rats when compared with young control. The effect of Coenzyme Q10 supplementation was more pronounced in old rats. The functioning of membrane transporters and Na+/H+ exchanger showed potential return to normal levels in the Coenzyme Q10 treated rats. Overall, the results demonstrate that Coenzyme Q10 plays an important role in maintaining redox balance in cells which interconnects with membrane integrity. Thus, Coenzyme Q10 supplementation may play an important role in protecting age related alterations in erythrocyte membrane physiology.

5.
Cell ; 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38968937

ABSTRACT

Immune tolerance mechanisms are shared in cancer and pregnancy. Through cross-analyzing single-cell RNA-sequencing data from multiple human cancer types and the maternal-fetal interface, we found B7-H4 (VTCN1) is an onco-fetal immune tolerance checkpoint. We showed that genetic deficiency of B7-H4 resulted in immune activation and fetal resorption in allogeneic pregnancy models. Analogously, B7-H4 contributed to MPA/DMBA-induced breast cancer progression, accompanied by CD8+ T cell exhaustion. Female hormone screening revealed that progesterone stimulated B7-H4 expression in placental and breast cancer cells. Mechanistically, progesterone receptor (PR) bound to a newly identified -58 kb enhancer, thereby mediating B7-H4 transcription via the PR-P300-BRD4 axis. PR antagonist or BRD4 degrader potentiated immunotherapy in a murine B7-H4+ breast cancer model. Thus, our work unravels a mechanistic and biological connection of a female sex hormone (progesterone) to onco-fetal immune tolerance via B7-H4 and suggests that the PR-P300-BRD4 axis is targetable for treating B7-H4+ cancer.

6.
Adv Mater Technol ; 9(3)2024 Feb 05.
Article in English | MEDLINE | ID: mdl-38883438

ABSTRACT

Embedded printing has emerged as a valuable tool for fabricating complex structures and microfluidic devices. Currently, an ample of amount of research is going on to develop new materials to advance its capabilities and increase its potential applications. Here, we demonstrate a novel, transparent, printable, photocrosslinkable, and tuneable silicone composite that can be utilized as a support bath or an extrudable ink for embedded printing. Its properties can be tuned to achieve ideal rheological properties, such as optimal self-recovery and yield stress, for use in 3D printing. When used as a support bath, it facilitated the generation microfluidic devices with circular channels of diameter up to 30 µm. To demonstrate its utility, flow focusing microfluidic devices were fabricated for generation of Janus microrods, which can be easily modified for multitude of applications. When used as an extrudable ink, 3D printing of complex-shaped constructs were achieved with integrated electronics, which greatly extends its potential applications towards soft robotics. Further, its biocompatibility was tested with multiple cell types to validate its applicability for tissue engineering. Altogether, this material offers a myriad of potential applications (i.e., soft robotics, microfluidics, bioprinting) by providing a facile approach to develop complicated 3D structures and interconnected channels.

7.
Cureus ; 16(5): e59627, 2024 May.
Article in English | MEDLINE | ID: mdl-38832148

ABSTRACT

Introduction Esophageal variceal bleeding is a potentially deadly consequence of portal hypertension in patients with cirrhosis. Although upper gastrointestinal endoscopy is still the preferred method for identifying esophageal varices (EV), the present study measured the platelet count to prothrombin time (PLT/PT) ratio for the assessment of portal hypertension and subsequent diagnosis of EVs in patients with chronic liver disease (CLD). Methods This was an observational comparative study conducted in the outpatient department of Patel Hospital, Karachi, Pakistan, using a non-probability consecutive sampling technique. Ethical approval was obtained from the Patel Hospital ethical review committee (PH/IRB/2022/028). An independent sample t-test was used for parametric data, whereas the Mann-Whitney U test was used for non-parametric data. The chi-square test was used to compare the categorical data of patients with and without EV. Receiver operating characteristic (ROC) analysis was performed to evaluate the cutoff values for the PLT/PT ratio, sensitivity, specificity, and area under the curve (AUC). Results The study involved 105 patients with and without EV. Among them, 38 (63.3%) males and 22 (36.7%) females had EV, whereas 30 (66.7%) males and 15 (33.3%) females did not. The platelet (PLT) count was also significantly lower in patients with EV (87.6 ± 59.8) than in those without (176.6 ± 87.7) (p < 0.001). The PLT/PT ratio was significantly lower in patients with EV (median: 5.04, IQR: 3.12-9.21) compared to those without (median: 14.57, IQR: 8.08-20.58) (p < 0.001). The sensitivity and specificity of the PLT/PT ratio for identifying EVs were 97.80% and 83.30%, respectively. Conclusion We found a significantly lower PLT/PT ratio in cases with EV than those without EV. After defining an optimal cutoff, PLT/PT had a high sensitivity in identifying cases with EVs in CLD. Therefore, we conclude that in patients with CLD, the PLT/PT ratio is a noninvasive predictor for the presence of EV.

8.
Sultan Qaboos Univ Med J ; 24(2): 259-267, 2024 May.
Article in English | MEDLINE | ID: mdl-38828256

ABSTRACT

Objectives: This study aimed to determine the rate and severity patterns of bronchopulmonary dysplasia (BPD) and identify antenatal and postnatal factors associated with BPD in preterm infants <32 weeks of gestational age (GA). Methods: This retrospective observational study included preterm neonates <32 weeks of gestation admitted into the neonatal intensive care unit between January 2010 and December 2017 at Sultan Qaboos University Hospital, Muscat, Oman. A data set of antenatal and perinatal factors were collected. BPD was defined as the need for oxygen and/or respiratory support at 36 weeks post-menstrual age (PMA). Infants with and without BPD were compared in their antenatal and perinatal factors. Results: A total of 589 preterm infants <32 weeks were admitted. Among them, 505 (85.7%) survived to 36 weeks' PMA and 90 (17.8%) had BPD. The combined BPD and mortality rate was 28.4%. Grades 1, 2 and 3 BPD constituted 77.8%, 7.8% and 14.4%, respectively. BPD was associated with lower GA, lower birth weight, need for intubation at resuscitation, lower Apgar scores, longer duration of ventilation, surfactant therapy and higher rates of neonatal morbidities. On binary logistic regression analysis, predictors of BPD were longer duration of ventilation, intraventricular haemorrhage (IVH) and necrotising enterocolitis (NEC). Conclusion: In an Omani centre, 17.8% of preterm infants (<32 weeks GA) developed BPD. Various perinatal and neonatal factors were associated with BPD. However, longer duration of ventilation, IVH grades 1 and 2 and NEC stages II and III were significant predictors. Future multicentre research is necessary to provide the overall prevalence of BPD in Oman to help optimise the resources for BPD prevention and management in preterm infants.


Subject(s)
Bronchopulmonary Dysplasia , Gestational Age , Infant, Premature , Humans , Oman/epidemiology , Retrospective Studies , Infant, Newborn , Female , Bronchopulmonary Dysplasia/epidemiology , Risk Factors , Prevalence , Male , Intensive Care Units, Neonatal/statistics & numerical data , Intensive Care Units, Neonatal/organization & administration , Tertiary Care Centers/organization & administration , Tertiary Care Centers/statistics & numerical data , Severity of Illness Index , Pregnancy , Infant
9.
Cureus ; 16(6): e62081, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38868548

ABSTRACT

A patient with multiple comorbidities and an eight-year history of tracheostomy was being treated for tracheitis. At this point, she became incapable of using regular speaking valves, and multiple attempts to reintroduce the speaking valve failed. A Ferrer adjustable speaking valve (FASV) was designed with gradations of outflow closure, allowing air to go through the vocal cords for phonation. The FASV was offered to her through the compassionate use program at the FDA. At 20% initial closure, the patient was able to tolerate the valve and was advanced to 50% closure, at which point she could phonate partially. The use of the valve was terminated at the time of her transfer, 23 days after the initiation of use. This suggests the safety and possible efficacy of using an adjustable speaking valve earlier than regular valves, allowing patients to communicate earlier and further exercise their diaphragms.

10.
Urol J ; 2024 Jun 01.
Article in English | MEDLINE | ID: mdl-38822627

ABSTRACT

PURPOSE: To share our recent experience of the pattern and demography of endemic bladder calculi in children and the outcomes of current management strategies for the removal of bladder calculi in a peri-urban setting. MATERIAL AND METHODS: This retrospective longitudinal study was carried out at a dedicated urology centre. All patients with endemic bladder stones from January 2020 to December 2021 managed at our centre were included in this study. After discharge, each patient was followed up for 1 year. Data analysis was carried out with IBM SPSS v23. Mean and standard deviation were calculated for normally distributed continuous variables; for non-normally distributed continuous variables, median and IQR were calculated; frequency and percentage were calculated for categorical variables. RESULTS: This study included 254 patients, with a male-to-female ratio of 10.5:1. The mean age of the patients was 4.80 ± 2.86 years. Ninety-one percent of the patients belonged to rural areas. Open cystolithotomy (OC) was performed in 11 (4.3%) patients, transurethral cystolithotripsy (TUCL) in 165 (65.0%), and percutaneous cystolithotomy (PCCL) in 78 (30.7%). The mean operative time was 48.8±4.34 minutes for TUCL, 36.18±7.4 minutes for open cystolithotomy, and 38.6±5.2 minutes for PCCL. The most common stone composition was ammonium urate + calcium phosphate (33.1%). The complication rate was 4.8% in TUCL, 12.8% in PCCL, and 27.3% in open cystolithotomy. Stone clearance was 98.1% for TUCL and 100% for both PCCL and OC. CONCLUSION:   Pediatric bladder calculus is still endemic in rural areas of Sindh with poor socioeconomic backgrounds. Timely diagnosis and early intervention with preventive measures can lead to better outcomes and fewer complications. Minimally invasive methods of cystolithotomy have a shorter hospital stay, are more cost-effective, and have fewer complications as compared to open cystolithotomy.

11.
Medicine (Baltimore) ; 103(21): e38124, 2024 May 24.
Article in English | MEDLINE | ID: mdl-38788006

ABSTRACT

Acute kidney injury (AKI) is a common postoperative complication, but there is still a lack of accurate biomarkers. Cardiac surgery-associated AKI is the most common cause of major-surgery-related AKI, and patients requiring renal replacement therapy have high mortality rates. Early diagnosis, intervention, and management are crucial for improving patient prognosis. However, diagnosing AKI based solely on changes in serum creatinine level and urine output is insufficient, as these changes often lag behind actual kidney damage, making early detection challenging. Biomarkers such as tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein-7 (IGFBP-7) have been found to be significant predictors of moderate-to-severe AKI when combined with urine content analysis. This article reviews the mechanism of biomarkers TIMP-2 and IGFBP-7 in AKI and provides a comprehensive overview of the clinical effects of TIMP-2 and IGFBP-7 in cardiac surgery-associated AKI, including prediction, diagnosis, and progression.


Subject(s)
Acute Kidney Injury , Biomarkers , Cardiac Surgical Procedures , Insulin-Like Growth Factor Binding Proteins , Postoperative Complications , Tissue Inhibitor of Metalloproteinase-2 , Humans , Tissue Inhibitor of Metalloproteinase-2/blood , Tissue Inhibitor of Metalloproteinase-2/urine , Acute Kidney Injury/etiology , Acute Kidney Injury/diagnosis , Acute Kidney Injury/blood , Insulin-Like Growth Factor Binding Proteins/blood , Insulin-Like Growth Factor Binding Proteins/urine , Cardiac Surgical Procedures/adverse effects , Biomarkers/blood , Postoperative Complications/etiology , Postoperative Complications/diagnosis , Prognosis
12.
JCI Insight ; 9(12)2024 May 30.
Article in English | MEDLINE | ID: mdl-38814732

ABSTRACT

Influenza poses a persistent health burden worldwide. To design equitable vaccines effective across all demographics, it is essential to better understand how host factors such as genetic background and aging affect the single-cell immune landscape of influenza infection. Cytometry by time-of-flight (CyTOF) represents a promising technique in this pursuit, but interpreting its large, high-dimensional data remains difficult. We have developed a new analytical approach, in silico gating annotating training elucidating (iGATE), based on probabilistic support vector machine classification. By rapidly and accurately "gating" tens of millions of cells in silico into user-defined types, iGATE enabled us to track 25 canonical immune cell types in mouse lung over the course of influenza infection. Applying iGATE to study effects of host genetic background, we show that the lower survival of C57BL/6 mice compared with BALB/c was associated with a more rapid accumulation of inflammatory cell types and decreased IL-10 expression. Furthermore, we demonstrate that the most prominent effect of aging is a defective T cell response, reducing survival of aged mice. Finally, iGATE reveals that the 25 canonical immune cell types exhibited differential influenza infection susceptibility and replication permissiveness in vivo, but neither property varied with host genotype or aging. The software is available at https://github.com/UmichWenLab/iGATE.


Subject(s)
Mice, Inbred BALB C , Mice, Inbred C57BL , Orthomyxoviridae Infections , Single-Cell Analysis , Animals , Mice , Orthomyxoviridae Infections/immunology , Single-Cell Analysis/methods , Lung/immunology , Lung/virology , Lung/pathology , Influenza, Human/immunology , Humans , Disease Models, Animal , Aging/immunology , Aging/genetics , Flow Cytometry/methods , T-Lymphocytes/immunology , Computer Simulation
13.
Metab Brain Dis ; 39(5): 649-659, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38727934

ABSTRACT

Aging is a multifaceted and progressive physiological change of the organism categorized by the accumulation of deteriorating processes, which ultimately compromise the biological functions. The objective of this study was to investigate the anti-aging potential of berberine (BBR) in D-galactose (D-Gal) induced aging in rat models. In this study, male Wistar rats were divided into four groups: The control group was given only vehicle, the BBR group was treated with berberine orally, the D-Gal group was treated with D-galactose subcutaneously and the BBR + D-Gal group was treated with D-galactose and berberine simultaneously. D-galactose exposure elevated the pro-oxidants such as malondialdehyde (MDA) level, protein carbonyl and advanced oxidation protein products (AOPP) in the brain. It decreased the anti-oxidants such as reduced glutathione (GSH) and ferric reducing antioxidant potential (FRAP) in the brain. D-galactose treatment also reduced the mitochondrial complexes (I, II, III and IV) activities and elevated the inflammatory markers such as interleukine-6 (IL-6), tumor necrosis factor- α (TNF-α) and C-reactive protein (CRP). The mRNA expressions of IL-6 and TNF-α in the brain were upregulated following D-galactose exposure. Berberine co-treatment in D-galactose induced aging rat model prevented the alteration of pro-oxidant and anti-oxidant in the brain. Berberine treatment restored the mitochondrial complex activities in the brain and also normalized the inflammatory markers. Based on these findings we conclude that berberine treatment has the potential to mitigate brain aging in rats via stabilizing the redox equilibrium and neuroinflammation.


Subject(s)
Aging , Berberine , Brain , Galactose , Oxidation-Reduction , Oxidative Stress , Rats, Wistar , Animals , Berberine/pharmacology , Berberine/therapeutic use , Male , Brain/drug effects , Brain/metabolism , Oxidation-Reduction/drug effects , Rats , Aging/drug effects , Aging/metabolism , Galactose/toxicity , Oxidative Stress/drug effects , Inflammation/metabolism , Inflammation/drug therapy , Homeostasis/drug effects , Antioxidants/pharmacology
14.
Med Res Rev ; 2024 May 05.
Article in English | MEDLINE | ID: mdl-38704826

ABSTRACT

The development of peptide drugs has made tremendous progress in the past few decades because of the advancements in modification chemistry and analytical technologies. The novel-designed peptide drugs have been modified through various biochemical methods with improved diagnostic, therapeutic, and drug-delivery strategies. Researchers found it a helping hand to overcome the inherent limitations of peptides and bring continued advancements in their applications. Furthermore, the emergence of peptide-drug conjugates (PDCs)-utilizes target-oriented peptide moieties as a vehicle for cytotoxic payloads via conjugation with cleavable chemical agents, resulting in the key foundation of the new era of targeted peptide drugs. This review summarizes the various classifications of peptide drugs, suitable chemical modification strategies to improve the ADME (adsorption, distribution, metabolism, and excretion) features of peptide drugs, and recent (2015-early 2024) progress/achievements in peptide-based drug delivery systems as well as their fruitful implication in preclinical and clinical studies. Furthermore, we also summarized the brief description of other types of PDCs, including peptide-MOF conjugates and peptide-UCNP conjugates. The principal aim is to provide scattered and diversified knowledge in one place and to help researchers understand the pinching knots in the science of PDC development and progress toward a bright future of novel peptide drugs.

15.
Cardiovasc Res ; 2024 May 04.
Article in English | MEDLINE | ID: mdl-38703377

ABSTRACT

AIMS: Diabetes leads to dysregulated macrophage immunometabolism, contributing to accelerated atherosclerosis progression. Identifying critical factors to restore metabolic alterations and promote resolution of inflammation remains an unmet goal. MicroRNAs (miRs) orchestrate multiple signaling events in macrophages, yet their therapeutic potential in diabetes-associated atherosclerosis remains unclear. METHODS AND RESULTS: MiRNA profiling revealed significantly lower miR-369-3p expression in aortic intimal lesions from Ldlr-/- mice on a high-fat sucrose containing (HFSC) diet for 12 weeks. miR-369-3p was also reduced in peripheral blood mononuclear cells (PBMCs) from diabetic patients with coronary artery disease (CAD). Cell-type expression profiling showed miR-369-3p enrichment in aortic macrophages. In vitro, oxLDL treatment reduced miR-369-3p expression in mouse bone marrow-derived macrophages (BMDMs). Metabolic profiling in BMDMs revealed that miR-369-3p overexpression blocked the oxLDL-mediated increase in the cellular metabolite succinate and reduced mitochondrial respiration (OXPHOS) and inflammation (lL-1ß, TNF-a, IL-6). Mechanistically, miR-369-3p targeted the succinate receptor (GPR91) and alleviated the oxLDL-induced activation of inflammasome signaling pathways. Therapeutic administration of miR-369-3p mimics in HFSC-fed Ldlr-/- mice reduced GPR91 expression in lesional macrophages and diabetes-accelerated atherosclerosis, evident by a decrease in plaque size and pro-inflammatory Ly6Chi monocytes. RNA-seq analyses showed more pro-resolving pathways in plaque macrophages from miR-369-3p treated mice, consistent with an increase in macrophage efferocytosis in lesions. Finally, a GPR91 antagonist attenuated oxLDL-induced inflammation in primary monocytes from human subjects with diabetes. CONCLUSION: These findings establish a therapeutic role for miR-369-3p in halting diabetes-associated atherosclerosis by regulating GPR91 and macrophage succinate metabolism.

16.
Indian J Ophthalmol ; 2024 May 20.
Article in English | MEDLINE | ID: mdl-38767558

ABSTRACT

PURPOSE: To assess the safety and efficacy of transzonular moxifloxacin and dexamethasone versus standard postoperative topical drug regimen in phacoemulsification. DESIGN: Nonrandomized prospective study. METHODS: The study included 100 eyes of 100 age and gender-matched individuals with senile cataract undergoing routine phacoemulsification. The patients were consecutively divided into transzonular (TZ = 50) and topical (TP = 50) groups. Both the groups were followed up for 4 weeks and assessed for intraocular inflammation, visual acuity, changes in intraocular pressure (IOP), and any adverse events. RESULTS: The grades of inflammation were significantly lower in TZ as compared to the TP group ( P < 0.001). The IOP remained normal and comparable in both the groups. Most of the patients in the two groups attained a visual acuity of 0.2 or better at the end of the follow-up. No adverse effects and increased rate of endophthalmitis were noted in TZ group. CONCLUSION: A one-time peroperative TZ moxifloxacin and dexamethasone combination is a safe and effective method to control postoperative inflammation after cataract surgery. A word of caution though, due precautions to be exercised to prevent the risk of inflammation and endophthalmitis.

17.
Mol Biol Rep ; 51(1): 694, 2024 May 25.
Article in English | MEDLINE | ID: mdl-38796662

ABSTRACT

BACKGROUND: Curcumin (Curcuma longa) is a well-known medicinal plant that induces autophagy in various model species, helping maintain cellular homeostasis. Its role as a caloric restriction mimetic (CRM) is being investigated. This study explores the potential of curcumin (CUR), as a CRM, to provide neuroprotection in D galactose induced accelerated senescence model of rats through modulation of autophagy. For six weeks, male rats received simultaneous supplementation of D-gal (300 mg/kg b.w., subcutaneously) and CUR (200 mg/kg b.w., oral). METHOD AND RESULTS: The oxidative stress indices, antioxidants, and electron transport chain complexes in brain tissues were measured using standard methods. Reverse transcriptase-polymerase chain reaction (RT-PCR) gene expression analysis was used to evaluate the expression of autophagy, neuroprotection, and aging marker genes. Our results show that curcumin significantly (p ≤ 0.05) enhanced the level of antioxidants and considerably lowered the level of oxidative stress markers. Supplementing with CUR also increased the activity of electron transport chain complexes in the mitochondria of aged brain tissue, demonstrating the antioxidant potential of CUR at the mitochondrial level. CUR was found to upregulate the expression of the aging marker gene (SIRT-1) and the genes associated with autophagy (Beclin-1 and ULK-1), as well as neuroprotection (NSE) in the brain. The expression of IL-6 and TNF-α was downregulated. CONCLUSION: Our findings demonstrate that CUR suppresses oxidative damage brought on by aging by modulating autophagy. These findings imply that curcumin might be beneficial for neuroprotection in aging and age-related disorders.


Subject(s)
Aging , Antioxidants , Autophagy , Brain , Curcumin , Oxidative Stress , Animals , Curcumin/pharmacology , Autophagy/drug effects , Oxidative Stress/drug effects , Brain/drug effects , Brain/metabolism , Brain/pathology , Rats , Aging/drug effects , Male , Antioxidants/pharmacology , Neuroprotective Agents/pharmacology , Mitochondria/drug effects , Mitochondria/metabolism , Galactose/pharmacology , Sirtuin 1/metabolism , Sirtuin 1/genetics , Beclin-1/metabolism , Beclin-1/genetics
18.
Cureus ; 16(4): e58947, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38800214

ABSTRACT

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) outcomes in small centers are commonly considered less favorable than in large-volume centers. New ECMO protocols and procedures were established in our regional community hospital system as part of a cardiogenic shock initiative. This retrospective study aims to evaluate the outcomes of veno-arterial extracorporeal membrane oxygenation (VA ECMO) and extracorporeal cardiopulmonary resuscitation (ECPR) in a community hospital system with cardiac surgery capability and assess whether protocol optimization and cannulation standards result in comparable outcomes to larger centers whether the outcomes of this new ECMO program at the community hospital setting were comparable to the United States averages. METHODS: Our regional system comprises five hospitals with 1500 beds covering southwestern New Jersey, with only one of these hospitals having cardiac surgery and ECMO capability. In May 2021, the new ECMO program was initiated. Patients were screened by a multidisciplinary call, cannulated by our ECMO team, and subsequently treated by the designated team. We reviewed our cardiac ECMO outcomes over two years, from May 2021 to April 2023, in patients who required ECMO due to cardiogenic shock or as a part of extracorporeal cardiopulmonary resuscitation (ECPR). RESULTS: A total of 60 patients underwent cardiac ECMO, and all were VA ECMO, including 18 (30%) patients who required ECPR for cardiac arrest. The overall survival rate for our cardiac ECMO program turned out to be 48% (29/60), with 50% (22/42) in VA ECMO excluding ECPR and 39% (7/18) in the ECPR group. The hospital survival rate for the VA ECMO and ECPR groups was 36% (15/42) and 28% (5/18), respectively. The ELSO-reported national average for hospital survival is 48% for VA ECMO and 30% for ECPR. Considering these benchmarks, the hospital survival rate of our program did not significantly lag behind the national average. CONCLUSIONS: With protocol, cannulation standards, and ECMO management optimized, the VA ECMO results of a community hospital system with cardiac surgery capability were not inferior to those of larger centers.

19.
PLoS One ; 19(5): e0302210, 2024.
Article in English | MEDLINE | ID: mdl-38814963

ABSTRACT

This research investigates the glass cliff effect and the positions held by women in leadership roles, focusing on their impact on operational liquidity. The study delves into the relationship between corporate governance attributes and operational liquidity in 60 non-financial companies listed on the Pakistan Stock Exchange during Covid-19. Utilizing Quine-McCluskey technique and fuzzy set Qualitative Comparative Analysis (fsQCA), it examines the combined effect of Women on the Board, Board Size, Ownership by Blockholders, Board Qualifications and Busy Directors on Operational Liquidity. The necessary condition analysis (NCA) emphasises that firms can operate without reliance on any particular variable taken in the study. The sufficiency analysis provided an expanded understanding of the three conditions leading to the same outcome both before and during the pandemic. This research highlights the significance of the glass cliff effect and emphasizes the pivotal role of women in effectively managing liquidity during times of crisis. Additionally, it provides valuable insights for policymakers regarding the impact of Covid-19 on the interplay between corporate governance characteristics and operational liquidity.


Subject(s)
COVID-19 , Leadership , Humans , Female , COVID-19/epidemiology , Pakistan , SARS-CoV-2 , Pandemics
20.
Biochem Pharmacol ; 223: 116196, 2024 May.
Article in English | MEDLINE | ID: mdl-38588831

ABSTRACT

The Fabkin complex, composed of FABP4, ADK, and NDPKs, emerges as a novel regulator of insulin-producing beta cells, offering promising prospects for diabetes treatment. Our approach, which combines literature review and database analysis, sets the stage for future research. These findings hold significant implications for both diabetes treatment and research, as they present potential therapeutic targets for personalized treatment, leading to enhanced patient outcomes and a deeper comprehension of the disease. The multifaceted role of the Fabkin complex in glucose metabolism, insulin resistance, anti-inflammation, beta cell proliferation, and vascular function underscores its therapeutic potential, reshaping diabetes management and propelling advancements in the field.


Subject(s)
Diabetes Mellitus , Insulin Resistance , Humans , Diabetes Mellitus/drug therapy
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