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1.
Pediatrics ; 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38988309

ABSTRACT

We describe the implementation of universal glucose-6-phosphate dehydrogenase (G6PD) screening during the first year of New York State mandated testing, as well as operational challenges and clinical knowledge gained. All infants born at or transferred to our center between June 21, 2022 and June 30, 2023, underwent testing for G6PD enzyme deficiency and were included in the study cohort. Infant blood samples were collected and sent to a reference laboratory for quantitative assay. After initiation of universal screening, a quality improvement initiative was launched to:monitor and improve the suitability of blood sample collection to ensure timely return of results;improve the reliability and validity of the reference laboratory enzyme assay; andestablish accurate reference ranges for G6PD deficiency in newborns.A total of 5601 newborns were included. Within the first year of implementation, the percentage of samples yielding any test result increased from 76% to 85%, and most patients had a G6PD result available within 1 day of discharge. We established a more accurate threshold for G6PD deficiency in newborns of <4.9 U/g Hb and G6PD intermediate of <10.0 U/g Hb. Using the updated reference ranges, 224 patients in our cohort were identified as G6PD deficient or intermediate (4.0%). Through a quality-sensitive process, we identified the importance of a standardized approach, improved sample collection processes, decreased sample turnaround time, and established more accurate reference ranges. We hope our experiences will help others seeking to improve processes and implement similar programs at other institutions.

2.
J Org Chem ; 89(14): 10148-10162, 2024 Jul 19.
Article in English | MEDLINE | ID: mdl-38959521

ABSTRACT

An organocatalytic enantio- and diastereoselective synthesis of hexahydropyrrolo[2,3-b]indole-containing tetrasubstituted α-amino allenoates, exhibiting both axial and central chirality, has been accomplished via cascade dearomatization-cyclization reaction. The γ-addition to ß,γ-alkynyl-α-imino esters provides a library of densely substituted highly enantioenriched allenes in high yields and excellent stereoselectivities. In addition, the scope of this methodology has been extended to tryptophol as well. A scale-up reaction and synthetic transformations of the products were performed to demonstrate the practical usefulness of this approach.

3.
J Phys Chem B ; 128(28): 6816-6829, 2024 Jul 18.
Article in English | MEDLINE | ID: mdl-38959082

ABSTRACT

The effects of two ionic liquids (ILs), 1-butyl-3-methylimidazolium tetrafluoroborate ([bmim]BF4) and 1-butyl-1-methyl pyrrolidinium tetrafluoroborate ([bmp]BF4), on a mixture of phospholipids (PLs) 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC), 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine (DPPE), and 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) (6:3:1, M/M/M, 70% PL) in combination with 30 mol % cholesterol (CHOL) were investigated in the form of a solvent-spread monolayer and bilayer (vesicle). Surface pressure (π)-area (A) isotherm studies, using a Langmuir surface balance, revealed the formation of an expanded monolayer, while the cationic moiety of the IL molecules could electrostatically and hydrophobically bind to the PLs on the palisade layer. Turbidity, dynamic light scattering (size, ζ-potential, and polydispersity index), electron microscopy, small-angle X-ray/neutron scattering, fluorescence spectroscopy, and differential scanning calorimetric studies were carried out to evaluate the effects of IL on the structural organization of bilayer in the vesicles. The ILs could induce vesicle aggregation by acting as a "glue" at lower concentrations (<1.5 mM), while at higher concentrations, the ILs disrupt the bilayer structure. Besides, ILs could result in the thinning of the bilayer, evidenced from the scattering studies. Steady-state fluorescence anisotropy and lifetime studies suggest asymmetric insertion of ILs into the lipid bilayer. MTT assay using human blood lymphocytes indicates the safe application of vesicles in the presence of ILs, with a minimal toxicity of up to 2.5 mM IL in the dispersion. These results are proposed to have applications in the field of drug delivery systems with benign environmental impact.


Subject(s)
Ionic Liquids , Ionic Liquids/chemistry , Imidazoles/chemistry , Phospholipids/chemistry , Cholesterol/chemistry , Lipid Bilayers/chemistry , Surface Properties , 1,2-Dipalmitoylphosphatidylcholine/chemistry
4.
Health Sci Rep ; 7(7): e1950, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38974327

ABSTRACT

Background and Aims: Urban corporate sector relies heavily on workplace well-being, with meditation being a potent stress reduction method that significantly enhances the quality of life (QoL) and wellness. The study aims to assess the effectiveness of meditation on wellness management among corporate employees in India. Methods: The quasi-experimental controlled study design was employed from May to June 2021, which assessed stress, QoL, and wellness indices (satisfaction with life, well-being) with meditation practice as the intervention. The online questionnaire incorporates questions from the Depression, Anxiety, Stress Scale, World Health Organization (WHO) QoL Scale, Five-item Satisfaction with Life scale and WHO-5 Well-being Index. A nonrandom sampling technique selected 146 and 74 subjects in the intervention and control groups, respectively, among the employees of Star health- and allied insurance company. The data was analyzed using SPSS V27 (©IBM SPSS Statistics). The Wilcoxon signed rank test for the dependent groups, and Mann-Whitney U test for the independent groups (between subjects) was performed. Results: Among a total of 220 subjects who enrolled in the recruitment survey, 146 subjects underwent the intervention thus providing a response rate of 66.4%. For the intervention group, the difference (within group) in mean scores between baseline and endline assessment shows a reduction in stress (0.02) and significant improvement in QoL (0.21) and wellness indices (satisfaction with life: 0.21, well-being: 0.24). The difference (between the experimental and control groups) in mean endline scores shows a decrease in stress (0.07), an increase in wellness indices (satisfaction with life: 0.12, well-being: 0.23), and a significant change in the QoL (0.17). Conclusion: Meditation intervention in corporate wellness programs enhances the QoL, wellness, and stress management, establishing the effectiveness of health profile-raising ingenuities at the workplace.

5.
Langmuir ; 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38976366

ABSTRACT

An interesting evolution of the re-entrant interaction has been observed in an anionic silica nanoparticle (NP)-block copolymer (P85) dispersion due to mutually competing effects of temperature and polymer concentration. It has been demonstrated that a rise in the temperature leads to an evolution of attraction in the system, which interestingly diminishes on increasing the polymer concentration. Consequently, the system exhibits a re-entrant transition from repulsive to attractive and back to repulsive at a given temperature but with respect to the increasing polymer concentration, within a selected region of concentration and temperature. The intriguing observations have been elucidated based on the temperature/concentration-dependent modifications in the interactions governing the system, as probed by contrast-variation small-angle neutron scattering. The initial transition from the repulsive to attractive system is attributed to the temperature-driven enhancement in the hydrophobicity of the amphiphilic triblock copolymer (P85) adsorbed on nanoparticles. The strength and range of this attraction are found to be more than van der Waals attraction while relatively less than electrostatic interaction. At higher polymer concentrations, the saturation of polymer adsorption on nanoparticles introduces additional steric repulsion along with electrostatic interaction between their conjugates, effectively reducing the strength of the attraction. However, with a significant increase in temperature (>75 °C), the attraction again dominates the system, which eventually leads to the particle aggregation at all the measured polymer concentrations (>0.1 wt %). Our study provides useful inputs to develop smart NP-polymer composites having capabilities to respond to external stimuli such as temperature/concentration variation.

6.
Orthopedics ; : 1-5, 2024 Jul 10.
Article in English | MEDLINE | ID: mdl-38976846

ABSTRACT

BACKGROUND: Displaced diaphyseal fractures can be reduced using the push-pull technique, wherein a plate is affixed to the distal fragment of the fracture, a post screw is placed proximal to the plate, and a lamina spreader creates distraction. This study evaluated the load to failure and mechanism of failure of bicortical and unicortical post screws during reduction. MATERIALS AND METHODS: Four matched pairs of cadaver legs were subjected to a 2-cm oblique osteotomy simulating a displaced, oblique diaphyseal fracture. A 6-hole compression plate was affixed to the distal fragment with 2 unicortical locking screws, and a 12-mm uni-cortical or 20-mm bicortical screw was inserted as a post screw proximal to the plate. A lamina bone spreader was used to exert a distraction force between the plate and the post screw. A mechanical actuator simulated the distraction procedure until failure. Maximum applied load, displacement, and absorbed energy were recorded and compared across unicortical and bicortical groups by paired t tests. RESULTS: At maximum load, we found statistically significant differences in displacement (P=.003) and energy absorbed (P=.022) between the two groups. All unicortical screws failed through screw toggle and bone cut-out. Bicortical screws failed through bending, with no visible damage to the bone at the screw site. CONCLUSION: When diaphyseal fractures are significantly shortened and require a greater distraction force to achieve reduction, bicortical screws demonstrate a higher mechanical load to failure and increased bone loss from the screw-removal site. A unicortical post screw may be used if minimal distraction is needed. [Orthopedics. 202x;4x(x):xx-xx.].

7.
Cureus ; 16(6): e61946, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38978880

ABSTRACT

Introduction Postoperative wound healing is the most important factor in the outcome of any surgical procedure. Wound healing is a dynamic process involving inflammation, neovascularization, granulation, fibroblast proliferation, re-epithelization, and remodeling. It repairs tissue integrity, restoring the body's natural defense barrier. A hastened wound healing will help in the quicker re-establishment of the body's homeostasis. Carica papaya includes vital nutrients and bioactive substances such as minerals, vitamins, and antioxidants. Its primary active ingredient papain causes the enzymatic debridement of wounds. Hemocoagulase is a thrombin-like serine protease that is mostly employed for its procoagulant and wound-healing characteristics. It is derived from the venom of Bothrops species of snakes. This study aims to compare the wound-healing properties of topical Carica papaya leaf extract and Hemocoagulase after dental extractions. Materials & Methods For 48 patients requiring bilateral therapeutic dental extraction for orthodontic intervention, Carica papaya leaf extract (Caripill 275mg/5ml) was topically applied to the extraction socket on one side, and Hemocoagulase 0.2 CU solution (Botroclot) was applied to the extraction socket on the other side. The bilateral premolars were extracted for orthodontic treatment under local anesthesia. Patients were asked to apply the solution topically twice daily for seven days and were called for review on the seventh day. The assessment of the efficacy of both solutions in post-operative wound healing was the objective of the study. Healing was assessed by using a blinded single observer for all patients using Landry's healing index. Results A total of 48 subjects with 96 sites completed the study, with a mean age of 15.4 years. The study population consisted of 24 males and 24 females, which were evenly distributed among the two study groups. On comparison of wound healing index (WHI) scores between the two groups using the Wilcoxon signed rank test, Group A had a significantly higher mean rank than Group B with regards to the wound healing index score, and the results were statistically significant (p = 0.037). Conclusion It can be concluded from the study that Carica papaya leaf extract showed better wound healing in post-extraction sockets compared to Hemocoagulase. This study presents the promising use of natural extracts such as Carica papaya in wound healing because they are easily accessible to patients, more economical, and have no adverse reactions. More studies that focus on natural extracts to promote wound healing are required in the future.

8.
Soft Matter ; 20(28): 5553-5563, 2024 Jul 17.
Article in English | MEDLINE | ID: mdl-38957095

ABSTRACT

The addition of a surfactant and/or an increase in temperature disrupt the native structure of proteins, where high temperature further results in protein gelation. However, in a mixed protein-surfactant system, surfactant concentration and temperature have been observed to exhibit both mutually associative and counter-balancing effects towards heat-induced gelation of protein-surfactant dispersion. This study is conducted on globular bovine serum albumin (BSA) protein and cationic surfactant dodecyl trimethyl ammonium bromide (DTAB), which interact strongly owing to their oppositely charged nature. The findings reveal that the BSA-DTAB suspension undergoes gelation with increasing temperature but only at lower concentrations of DTAB, where the presence of the surfactant facilitates gelation (associative effect). Conversely, as the surfactant concentration increases beyond a critical value, temperature-driven gelation of the BSA-DTAB system is completely inhibited, despite surfactant-induced protein denaturation (counter-balancing effect). To conceptualize these results, we compared them with observations made in a system comprising protein and a similarly charged surfactant, sodium dodecyl sulfate (SDS). It has been further demonstrated that the anionic surfactant (SDS) can restrict protein gelation at much lower concentration compared to the cationic surfactant (DTAB). The evolution of the structure and interaction during gel formation/inhibition has been examined to understand the underlying mechanism guiding these sol-gel transitions. We present a comprehensive phase diagram, encompassing the solution/gel states of the protein-surfactant dispersion, with respect to the dispersion temperature, surfactant concentration, and ionic behavior (anionic or cationic) of the surfactants.


Subject(s)
Gels , Hot Temperature , Quaternary Ammonium Compounds , Serum Albumin, Bovine , Surface-Active Agents , Surface-Active Agents/chemistry , Serum Albumin, Bovine/chemistry , Gels/chemistry , Cattle , Quaternary Ammonium Compounds/chemistry , Animals , Sodium Dodecyl Sulfate/chemistry
9.
Cureus ; 16(6): e62840, 2024 Jun.
Article in English | MEDLINE | ID: mdl-39036166

ABSTRACT

Background The antecedents of readmission among survivors of intensive care units (ICUs) are complex and comprise an array of elements that impact the rehabilitation process after leaving the ICU. The aforementioned determinants may comprise socioeconomic factors, access to follow-up healthcare, the nature and severity of the initial illness or injury, the presence of comorbidities, the sufficiency of transitional care and rehabilitation services, and patient and family support systems. Added to this, the risk of readmission may be increased by complications that develop during the ICU stay, including but not limited to infections, organ dysfunction, and psychological distress. Comprehending these determinants is of the utmost importance for healthcare providers in order to execute focused interventions that seek to diminish readmission rates, enhance patient outcomes, and elevate the standard of care for survivors of ICUs. Objective The objective of the study is to determine the factors associated with readmission among ICU survivors and the cause of readmission. Methodology This prospective observational study was conducted in a tertiary-level ICU. The duration of the study was one year and we enrolled 108 ICU survivors in our study. We have recorded patient demographic data, comorbidity, primary diagnosis, previous treatment history (vasopressor, sedation), causes of readmission, duration of previous ICU stay, and outcome of readmitted patient (discharge, death, and transfer to lower facility). Result The incidence of readmission in our ICU is 10.4%; 50-70 age groups are more prone to readmission of which the male sex is predominant (64.81%). In our study, hypertension (cardiac, 18.52%) and diabetes mellitus (11.11%) were the most common comorbidities reported in readmitted patients. The majority of patients who get readmission suffered from blunt trauma abdomen. In the majority of readmitted patients, sedation was used in the previous admission for ventilation and patient comfort (66.67%). Most of the readmitted patients (68.51%) have a previous ICU stay of more than five days. Patients were readmitted mainly because of respiratory (30.56%) and neurological (25%) complications. In this study, readmitted patients have high mortality (59.26%). Conclusion In a tertiary care ICU, the incidence rate of readmitted patients was 10.4%. Respiratory and neurological problems were the main cause of readmission. In readmitted patients, mortality was high up to 59.26%. Old age, male sex, prolonged ICU stay, comorbidities like hypertension, blunt trauma abdomen, use of sedation, and prolonged mechanical ventilation in previous ICU admission are major risk factors for ICU readmission.

10.
J Org Chem ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39036827

ABSTRACT

The present paper describes a new and practical approach for the one-pot preparation of O-isopropylidene derivatives and also orthogonally protected S- and O-glycosides from the corresponding unprotected saccharides by employing 2 mol % of a silicomolybdic acid (SMA) cluster as a versatile and biocompatible catalyst. The present protocol is applicable to two-step one-pot tandem transformations, which include the O-isopropylidation, spiroketal functionalization, 4,6-O-arylidene acetalations, and arylidene acetylation processes under relatively mild reaction conditions. One-pot sequential transformations, low catalyst loading, rapid transformation, high to excellent reaction yields, mild reaction conditions, and a nontoxic biocompatible workup procedure are the notable advantages of devised protocol.

11.
Cureus ; 16(5): e59763, 2024 May.
Article in English | MEDLINE | ID: mdl-38846229

ABSTRACT

Odontogenic fibromyxoma typically presents as painless swelling in the jaw, and clinically, it grows slowly, becoming benign and asymptomatic. It causes the cortical plates to expand gradually, which leads to mobility and drifting of the teeth. Root resorption is also common. The tumor is locally aggressive in nature. It is also known to have a high recurrence rate. We present the case of a 30-year-old female patient who was diagnosed and treated for odontogenic fibromyxoma of the maxilla conservatively with enucleation. The radiograph showed a multilocular lesion, which can be confused with ameloblastoma, aneurysmal bone cyst, or odontogenic keratocyst. Hence, with proper clinical, radiographic, and histopathological examination, a correct diagnosis can be made and adequate treatment can be planned.

12.
Org Lett ; 26(23): 4932-4937, 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38825803

ABSTRACT

Herein we report the first use of p-quinone diimide for the aminative dearomatization of 2,3-disubstituted indoles to furnish C3 aza-quaternary chiral indolenines. This approach, which proceeds via an electrophilic 1,6-addition of p-quinone diimide, allows the synthesis of an array of optically active aza-quaternary indolenines with high yields and excellent enantioselectivities. A one-pot approach of the same has also been established to further improve the synthetic accessibility of this protocol.

14.
J Phys Chem B ; 128(27): 6622-6637, 2024 Jul 11.
Article in English | MEDLINE | ID: mdl-38937939

ABSTRACT

Extensive research has been carried out to investigate the stability and function of human serum albumin (HSA) when exposed to surface-active ionic liquids (SAILs) with different head groups (imidazolium, morpholinium, and pyridinium) and alkyl chain lengths (ranging from decyl to tetradecyl). Analysis of the protein fluorescence spectra indicates noticeable changes in the secondary structure of HSA with varying concentrations of all SAILs tested. Helicity calculations based on the Fourier transform infrared (FTIR) data show that HSA becomes more organized at the micellar concentration of SAILs, leading to an increased protein activity at this level. Small-angle neutron scattering (SANS) data confirm the formation of a bead-necklace structure between the SAILs and HSA. Atomistic molecular dynamics (MD) simulation results identify several hotspots on the protein surface for interaction with SAIL, which results in the modulation of protein conformational fluctuation and stability. Furthermore, fluorescence resonance energy transfer (FRET) experiments with the intramolecular charge transfer (ICT) probe trans-ethyl p-(dimethylamino) cinnamate (EDAC) demonstrate that higher alkyl chain lengths and SAIL concentrations result in a significantly increased energy transfer efficiency. The findings of this study provide a detailed molecular-level understanding of how the protein structure and function are affected by the presence of SAILs, with potential implications for a wide range of applications involving protein-SAIL composite systems.


Subject(s)
Ionic Liquids , Molecular Dynamics Simulation , Serum Albumin, Human , Ionic Liquids/chemistry , Humans , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Fluorescence Resonance Energy Transfer , Protein Binding , Protein Conformation , Scattering, Small Angle , Surface-Active Agents/chemistry
15.
Small ; : e2402585, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860560

ABSTRACT

Sodium-ion batteries (SIBs) have emerged as a compelling alternative to lithium-ion batteries (LIBs), exhibiting comparable electrochemical performance while capitalizing on the abundant availability of sodium resources. In SIBs, P2/O3 biphasic cathodes, despite their high energy, require furthur improvements in stability to meet current energy demands. This study introduces a systematic methodology that leverages the meta-heuristically assisted NSGA-II algorithm to optimize multi-element doping in electrode materials, aiming to transcend conventional trial-and-error methods and enhance cathode capacity by the synergistic integration of P2 and O3 phases. A comprehensive phase analysis of the meta-heuristically designed cathode material Na0.76Ni0.20Mn0.42Fe0.30Mg0.04Ti0.015Zr0.025O2 (D-NFMO) is presented, showcasing its remarkable initial reversible capacity of 175.5 mAh g-1 and exceptional long-term cyclic stability in sodium cells. The investigation of structural composition and the stabilizing mechanisms is performed through the integration of multiple characterization techniques. Remarkably, the irreversible phase transition of P2→OP4 in D-NFMO is observed to be dramatically suppressed, leading to a substantial enhancement in cycling stability. The comparison with the pristine cathode (P-NFMO) offers profound insights into the long-term electrochemical stability of D-NFMO, highlighting its potential as a high-voltage cathode material utilizing abundant earth elements in SIBs. This study opens up new possibilities for future advancements in sodium-ion battery technology.

16.
Indian Dermatol Online J ; 15(3): 464-472, 2024.
Article in English | MEDLINE | ID: mdl-38845632

ABSTRACT

Background: Rituximab infusion and dexamethasone-cyclophosphamide pulse (DCP) are the two most popular regimens used in pemphigus vulgaris (PV) in India. Objective: The present study compared the clinical efficacy of rituximab and DCP in Indian PV patients and their effects on serum Th1,2, and 17 cytokine levels. Materials and Methods: A total of 37 patients received DCP (Group A, n = 22) or rituximab (Group B, rheumatoid arthritis protocol (n = 15)) as per patients' preference. They were monitored for clinical response, adverse events (AEs), changes in serum anti-desmoglein-1,3 antibody titers and Th1,2 and 17 cytokine levels at baseline and weeks 20 and 52. Results: The proportion of patients attaining disease control, remission, and relapse in groups A and B were 82% and 93%; 73% and 93%; and 27% and 50%, respectively, after a median duration of 2 months each for disease control; 4 and 4.5 months for remission; and 5 and 7 months for relapse post remission. The musculoskeletal AEs were the highest in the two groups. Significant and comparable decreases in anti-dsg1 and 3 titers from baseline to weeks 20 and 52 were observed in both groups. Th1 and Th17 cytokine levels decreased, while Th2 cytokines increased post-treatment in both groups. However, no correlation was found between change in body surface area of involvement by PV and anti-dsg titers and cytokine levels before and after therapy in both groups. Conclusion: Comparable clinical efficacy between DCP and rituximab was observed.

17.
Ann Hepatol ; 29(4): 101510, 2024.
Article in English | MEDLINE | ID: mdl-38714224

ABSTRACT

INTRODUCTION AND OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease worldwide and can progress to non-alcoholic steatohepatitis (NASH) and, ultimately, cirrhosis. Clostridioides difficile is the most common nosocomial cause of diarrhea and is associated with worse clinical outcomes in other liver diseases, including cirrhosis, but has not been extensively evaluated in concomitant NAFLD/NASH. MATERIALS AND METHODS: We conducted a retrospective cohort study using the National Inpatient Sample database from 2015 to 2017. Patients with a diagnosis of CDI, NAFLD, and NASH were identified using International Classification of Diseases (Tenth Revision) codes. The outcomes of our study include length of stay, hospitalization cost, mortality, and predictors of mortality. RESULTS: The CDI and NASH cohort had a higher degree of comorbidity burden and prevalence of peptic ulcer disease, congestive heart failure, diabetes mellitus, and cirrhosis. Patients with NASH and CDI had a significantly higher mortality rate compared to the CDI only cohort (mortality, 7.11 % vs. 6.36 %; P = 0.042). Patients with CDI and NASH were at increased risk for liver-related complications, acute kidney injury, and septic shock (P < 0.001) compared to patients with CDI only. Older age, intestinal complications, pneumonia, sepsis and septic shock, and liver failure conferred an increased risk of mortality among the CDI and NASH cohort. CONCLUSIONS: Patients with NASH had a higher rate of liver-related complications, progression to septic shock, and mortality rate following CDI infection compared to the CDI only cohort.


Subject(s)
Clostridium Infections , Non-alcoholic Fatty Liver Disease , Humans , Non-alcoholic Fatty Liver Disease/mortality , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/complications , Male , Female , Retrospective Studies , Risk Factors , Middle Aged , Clostridium Infections/mortality , Clostridium Infections/epidemiology , Clostridium Infections/diagnosis , Aged , Clostridioides difficile , United States/epidemiology , Databases, Factual , Length of Stay/statistics & numerical data , Adult , Comorbidity , Hospital Costs , Risk Assessment
18.
Biomed Pharmacother ; 175: 116730, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38749175

ABSTRACT

Acute kidney injury (AKI) disrupts energy metabolism. Targeting metabolism through AMP-activated protein kinase (AMPK) may alleviate AKI. ATX-304, a pan-AMPK activator, was evaluated in C57Bl/6 mice and tubular epithelial cell (TEC) cultures. Mice received ATX-304 (1 mg/g) or control chow for 7 days before cisplatin-induced AKI (CI-AKI). Primary cultures of tubular epithelial cells (TECs) were pre-treated with ATX-304 (20 µM, 4 h) prior to exposure to cisplatin (20 µM, 23 h). ATX-304 increased acetyl-CoA carboxylase phosphorylation, indicating AMPK activation. It protected against CI-AKI measured by serum creatinine (control 0.05 + 0.03 mM vs ATX-304 0.02 + 0.01 mM, P = 0.03), western blot for neutrophil gelatinase-associated lipocalin (NGAL) (control 3.3 + 1.8-fold vs ATX-304 1.2 + 0.55-fold, P = 0.002), and histological injury (control 3.5 + 0.59 vs ATX-304 2.7 + 0.74, P = 0.03). In TECs, pre-treatment with ATX-304 protected against cisplatin-mediated injury, as measured by lactate dehydrogenase release, MTS cell viability, and cleaved caspase 3 expression. ATX-304 protection against cisplatin was lost in AMPK-null murine embryonic fibroblasts. Metabolomic analysis in TECs revealed that ATX-304 (20 µM, 4 h) altered 66/126 metabolites, including fatty acids, tricarboxylic acid cycle metabolites, and amino acids. Metabolic studies of live cells using the XFe96 Seahorse analyzer revealed that ATX-304 increased the basal TEC oxygen consumption rate by 38%, whereas maximal respiration was unchanged. Thus, ATX-304 protects against cisplatin-mediated kidney injury via AMPK-dependent metabolic reprogramming, revealing a promising therapeutic strategy for AKI.


Subject(s)
AMP-Activated Protein Kinases , Acute Kidney Injury , Cisplatin , Mice, Inbred C57BL , Animals , Acute Kidney Injury/chemically induced , Acute Kidney Injury/prevention & control , Acute Kidney Injury/metabolism , Acute Kidney Injury/pathology , AMP-Activated Protein Kinases/metabolism , Mice , Male , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Cells, Cultured , Protective Agents/pharmacology , Phosphorylation , Biphenyl Compounds , Pyrones , Thiophenes
19.
Cochrane Database Syst Rev ; 5: CD011060, 2024 05 28.
Article in English | MEDLINE | ID: mdl-38804265

ABSTRACT

BACKGROUND: The American Academy of Pediatrics and the Canadian Paediatric Society both advise that all newborns should undergo bilirubin screening before leaving the hospital, and this has become the standard practice in both countries. However, the US Preventive Task Force has found no strong evidence to suggest that this practice of universal screening for bilirubin reduces the occurrence of significant outcomes such as bilirubin-induced neurologic dysfunction or kernicterus. OBJECTIVES: To evaluate the effectiveness of transcutaneous screening compared to visual inspection for hyperbilirubinemia to prevent the readmission of newborns (infants greater than 35 weeks' gestation) for phototherapy. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, ICTRP, and ISRCTN in June 2023. We also searched conference proceedings, and the reference lists of included studies. SELECTION CRITERIA: We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, or prospective cohort studies with control arm that evaluated the use of transcutaneous bilirubin (TcB) screening for hyperbilirubinemia in newborns before hospital discharge. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) and 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to evaluate the certainty of evidence. MAIN RESULTS: We identified one RCT (1858 participants) that met our inclusion criteria. The study included 1858 African newborns at 35 weeks' gestation or greater who were receiving routine care at a well-baby nursery, and were randomly recruited prior to discharge to undergo TcB screening. The study had good methodologic quality. TcB screening versus visual assessment of hyperbilirubinemia in newborns: - may reduce readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - probably has little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - may increase the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - probably has little or no effect on the rate of acute bilirubin encephalopathy (RR 0.33, 95% CI 0.01 to 8.18; low-certainty evidence). The study did not evaluate or report cost of care. AUTHORS' CONCLUSIONS: Moderate-certainty evidence suggests that TcB screening may reduce readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening probably has little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening may increase the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening probably has little or no effect on the rate of acute bilirubin encephalopathy compared to visual inspection. Given that we have only identified one RCT, further studies are necessary to determine whether TcB screening can help to reduce readmission and complications related to neonatal hyperbilirubinemia. In settings with limited newborn follow-up after hospital discharge, identifying newborns at risk of severe hyperbilirubinemia before hospital discharge will be important to plan targeted follow-up of these infants.


Subject(s)
Bilirubin , Infant, Premature , Jaundice, Neonatal , Neonatal Screening , Patient Readmission , Randomized Controlled Trials as Topic , Humans , Infant, Newborn , Bilirubin/blood , Jaundice, Neonatal/diagnosis , Jaundice, Neonatal/therapy , Jaundice, Neonatal/blood , Neonatal Screening/methods , Patient Readmission/statistics & numerical data , Bias , Hyperbilirubinemia, Neonatal/diagnosis , Hyperbilirubinemia, Neonatal/therapy , Phototherapy , Term Birth
20.
Int J Pharm ; 658: 124206, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38734276

ABSTRACT

The constraints associated with current cancer therapies have inspired scientists to develop advanced, precise, and safe drug delivery methods. These delivery systems boost treatment effectiveness, minimize harm to healthy cells, and combat cancer recurrence. To design advanced drug delivery vehicle with these character, in the present manuscript, we have designed a self-healing and injectable hybrid hydrogel through synergistically interacting metal organic framework, CuBTC with the poly(vinyl alcohol) (PVA). This hybrid hydrogel acts as a localized drug delivery system and was used to encapsulate and release the anticancer drug 5-Fluorouracil selectively at the targeted site in response to the physiological pH. The hydrogel was formed through transforming the gaussian coil like matrix of PVA-CuBTC into a three-dimensional network of hydrogel upon the addition of crosslinker; borax. The biocompatible character of the hydrogel was confirmed through cell viability test. The biocompatible hybrid hydrogel then was used to encapsulate and studied for the pH responsive release behavior of the anti-cancer drug, 5-FU. The in vitro cytotoxicity of the drug-loaded hydrogel was evaluated against MCF-7 and HeLa cells. The study confirms that the hybrid hydrogel is effective for targeted and sustained release of anticancer drugs at cancer sites.


Subject(s)
Breast Neoplasms , Cell Survival , Drug Delivery Systems , Drug Liberation , Fluorouracil , Hydrogels , Metal-Organic Frameworks , Polyvinyl Alcohol , Humans , Fluorouracil/administration & dosage , Fluorouracil/chemistry , Fluorouracil/pharmacology , Breast Neoplasms/drug therapy , MCF-7 Cells , HeLa Cells , Cell Survival/drug effects , Hydrogels/chemistry , Female , Metal-Organic Frameworks/chemistry , Polyvinyl Alcohol/chemistry , Drug Delivery Systems/methods , Hydrogen-Ion Concentration , Drug Carriers/chemistry , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/chemistry , Antimetabolites, Antineoplastic/pharmacology , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology
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