Optimizing lornoxicam-loaded poly(lactic-co-glycolic acid) and (polyethylene glycol) nanoparticles for transdermal delivery: ex vivo/in vivo inflammation evaluation.

Aim: This study focused on developing a topical gel incorporating lornoxicam-loaded poly(lactic-co-glycolic acid) and polyethylene glycol (PLGA-PEG) blend nanoparticles to mitigate gastrointestinal (GIT) side effects and enhance therapeutic efficacy. Materials & methods: Synthesized nanoparticles were subjected to in vitro characterization, ex vivo permeation studies, and acute oral toxicity analysis post-incorporation into the gel using a S/O/W double emulsion solvent. Results & conclusion: The nanoparticles displayed a smooth, spherical morphology (170-321 nm) with increased entrapment efficiency (96.2%). LOX exhibited a permeation rate of 70-94% from the nanoparticle-infused gel, demonstrating favorable biocompatibility at the cellular level. The formulated gel, enriched with nanoparticles, holds promising prospects for drug-delivery systems and promising improved therapeutic outcomes for LOX.

[Box: see text].

Characterization of Exopolysaccharides Having Potential Antiviral Properties from Priestia Aryabattai Strain MK1 and Bacillus sp. Strain MK2.

Viral diseases are a serious threat to humans while the most antiviral drugs have low efficiency and side effects on human health. Therefore, using microbial biopolymers as the drugs alternate to treat viral infections seems cost-effective and human friendly option. In the present study, thirty-four exopolysaccharides (EPSs) producing bacteria were isolated, and EPSs production capacity of five salt-tolerant isolates was determined under 0, 100 and 150 mM NaCl. Among these, two isolates exhibiting high anti-coliphage activity were identified through 16S rRNA gene analysis. Moreover, the EPSs were characterized by Fourier-transform infrared (FTIR) spectroscopy and X-ray diffraction (XRD) analysis, and their composition was determined. Five salt-tolerant bacteria (MK1, MK2, MK10, MK22 and MK29) exhibited higher production of EPSs at 100 mM NaCl compared to that under non-saline control. At 100 mM NaCl, the yield of EPSs ranged between 105 and 330 mg 100 mL-1 broth. The EPSs produced by the isolates MK1 and MK2 exhibited higher anti-coliphage activity (plaque forming unit decreased from 43 × 106 mL-1 to 3 × 106 and 4 × 106 mL-1, respectively), and were comprised of glucose, fructose, galactose, sucrose, lactose and xylose sugars. FTIR spectroscopy depicted that EPSs are mainly composed of hydroxyl, aliphatic, carboxyl, sulfate and phosphate functional groups, which could have bound coliphage and thus conferred higher anti-coliphage activities to the EPSs. Phylogenetic analysis revealed that MK1 and MK2 isolates formed clades within genus Priestia and Bacillus sequences, respectively. High EPSs production capacity of bacterial isolates under saline condition and high anti-coliphage activity of the EPSs implies that bacterial biopolymers could be useful in antiviral drugs therapy.

Thermal and solutal heat transport investigations of second order fluid with the application of Cattaneo-Christov theory.

The present examination of mass and heat communication looks at the impact of induced magnetic field, variable thermal conductivity, and activation energy on the flow of second-order liquid across a stretched surface. The mass-heat transfer is also treated using the Model for generalized Fourier and Fick's Laws. The model equations are transformed as needed to produce a system of nonlinear ODEs, which are then numerically solved with the help of BVP4C integrated MATLAB approach. The heat-mass flow parameters are analyzed by the table and graphs. An increment in the estimations of 2nd grade fluid parameter (ß) with magnetic field parameter (M) increase the speed sketch. For the stronger estimations of Schmidt number (Sc), parameter of magnetic field (M) and Eckert number (Ec) have the growing behavior on the temperature profile.

Development of innovative alkali activated paste reinforced with polyethylene fibers for concrete crack repair.

Concrete structures are susceptible to cracking, which can compromise their integrity and durability. Repairing them with ordinary Portland cement (OPC) paste causes shrinkage cracks to appear in the repaired surface. Alkali-activated binders offer a promising solution for repairing such cracks. This study aims to develop an alkali-activated paste (AAP) and investigate its effectiveness in repairing concrete cracks. AAPs, featuring varying percentages (0.5%, 0.75%, 1%, 1.25%, 1.5%, and 1.75%) of polyethylene (PE) fibers, are found to exhibit characteristics such as strain hardening, multiple plane cracking in tension and flexure tests, and stress-strain softening in compression tests. AAP without PE fibers experienced catastrophic failure in tension and flexure, preventing the determination of its stress-strain relationship. Notably, AAPs with 1.25% PE fibers demonstrated the highest tensile and flexural strength, exceeding that of 0.5% PE fiber reinforced AAP by 100% in tension and 70% in flexure. While 1% PE fibers resulted in the highest compressive strength, surpassing AAP without fibers by 17%. To evaluate the repair performance of AAP, OPC cubes were cast with pre-formed cracks. These cracks were induced by placing steel plates during casting and were designed to be full and half-length with widths of 1.5 mm and 3 mm. AAP both with and without PE fibers led to a substantial improvement in compressive strength, reducing the initial strength loss of 30%-50% before repair to a diminished range of 2%-20% post-repair. The impact of PE fiber content on the compressive strength of repaired OPC cube is marginal, providing more flexibility in using AAP with any fiber percentage while still achieving effective concrete crack repair. Considering economic and environmental factors, along with observed mechanical enhancements, AAPs show promising potential for widespread use in concrete repair and related applications, contributing valuable insights to the field of sustainable construction materials.

Microbiological Evaluation of Commercial Hand Sanitisers Available in Pakistan Using European Standard and Membrane Filtration Method.

OBJECTIVE: To evaluate the antibacterial efficacy of various commercially available alcohol-based hand sanitisers (ABHS) using European standard (EN 1500) method and perform ABHS testing with membrane filtration method. STUDY DESIGN: A Cross-sectional observational study. Place and Duration of the Study: Quality Control Section of the Microbiology Laboratory, The Aga Khan University Hospital, Karachi, Pakistan, from February to April 2023. METHODOLOGY: Efficacy of 14 commercially and widely accessible hand sanitisers was defined as reducing micro-organism growth. It was determined using the EN 1500 European standard test and membrane filtration method. RESULTS: Majority (92.8%) ABHS showed a significant bacterial reduction except one ABHS tested with the EN 1500 method. Only six ABHS products were tested through the membrane filtration method because high viscosity of hand sanitisers was causing damage to filter membranes. CONCLUSION: Continued vigilance in evaluating hand sanitiser's efficacy through robust testing methods is essential to ensure public health and prevent the dissemination of misleading products that may compromise hand hygiene practices. KEY WORDS: Hand sanitisers, European standard, Membrane filtration method, Antibacterial efficacy.

The interplay of group size and flow velocity modulates fish exploratory behaviour.

Social facilitation is a well-known phenomenon where the presence of organisms belonging to the same species enhances an individual organism's performance in a specific task. As far as fishes are concerned, most studies on social facilitation have been conducted in standing-water conditions. However, for riverine species, fish are most commonly located in moving waters, and the effects of hydrodynamics on social facilitation remain largely unknown. To bridge this knowledge gap, we designed and performed flume experiments where the behaviour of wild juvenile Italian riffle dace (Telestes muticellus) in varying group sizes and at different mean flow velocities, was studied. An artificial intelligence (AI) deep learning algorithm was developed and employed to track fish positions in time and subsequently assess their exploration, swimming activity, and space use. Results indicate that energy-saving strategies dictated space use in flowing waters regardless of group size. Instead, exploration and swimming activity increased by increasing group size, but the magnitude of this enhancement (which quantifies social facilitation) was modulated by flow velocity. These results have implications for how future research efforts should be designed to understand the social dynamics of riverine fish populations, which can no longer ignore the contribution of hydrodynamics.

Numerical investigation of the impact of temperature-dependent thermal conductivity and viscosity on thermo-particle heat transfer through stationary sphere and using plume.

Nanofluids have a wide range of applications due to their unique properties, such as enhanced thermal conductivity, convective heat transfer, and mass transfer. These applications can be seen in heat exchangers, cooling systems, and electronic devices to improve thermal performance. To enhance the cooling efficiency and lifespan of electronic devices such as smartphones, televisions, and computers nanofluids are used. These novel types of fluids can be used in energy storage systems, cancer treatment, imaging, and drug deliveryKeeping in mind, the real-time applications in engineering, industry, and science, the current study is carried out. In the present study for heat and mass transportation, the two-phase Buongiorno model for nanofluid is employed to scrutinize Brownian motion and thermophoresis aspects using stationary sphere and plume region. The temperature-dependent viscosity and thermal conductivity effects are encountered in momentum and energy equations, respectively are encountered. The proposed mechanism in the partial differential equations having dimensional form is converted to a non-dimensional form using appropriate dimensionless variables. The solution of the current non-linear and coupled model is obtained using the finite difference method. The numerical solutions presented in graphs and tables indicate that along with heat and mass transfer phenomena are entirely dependent on thermophoresis, Brownian motion, temperature-dependent viscosity, and thermal conductivity. The results indicate that the quantitative behavior of the velocity field is enhanced by increasing values of thermal conductivity variation parameters for both the sphere and the plume region at each position. On the other hand, the reverse trend is noted against the rising magnitudes of the viscosity variation parameter, thermophoresis parameter, and Brownian diffusion parameter. Additionally, the temperature in the plume region declines to enhance thermal conductivity variation parameter. A test for grid independence was performed by considering various grid points. Excellent solution accuracy has been seen as the number of grid points has risen. This ensures the validity and accuracy of the currently employed method. The current results are compared with already published solutions for the validation of the current model for specific cases. It has been noted that there is excellent agreement between both of the results. This close agreement between the results indicates the validation of the current solutions.

A new bicornuate model of rat uterus transplantation.

INTRODUCTION: Uterus transplantation has revolutionized reproductive medicine for women with absolute uterine factor infertility, resulting in more than 40 reported successful live births worldwide to date. Small animal models are pivotal to refine this surgical and immunological challenging procedure aiming to enhance safety for both the mother and the child. MATERIAL AND METHODS: We established a syngeneic bicornuate uterus transplantation model in young female Lewis rats. All surgical procedures were conducted by an experienced and skilled microsurgeon who organized the learning process into multiple structured steps. Animals underwent meticulous preoperative preparation and postoperative care. Transplant success was monitored by sequential biopsies, monitoring graft viability and documenting histological changes long-term. RESULTS: Bicornuate uterus transplantation were successfully established achieving an over 70% graft survival rate with the passage of time. The bicornuate model demonstrated safety and feasibility, yielding outcomes comparable to the unicornuate model in terms of ischemia times and complications. Longitudinal biopsies were well-tolerated, enabling comprehensive monitoring throughout the study. CONCLUSIONS: Our novel bicornuate rat uterus transplantation model provides a distinctive opportunity for sequential biopsies at various intervals after transplantation and, therefore, comprehensive monitoring of graft health, viability, and identification of potential signs of rejection. Furthermore, this model allows for different interventions in each horn for comparative studies without interobserver differences contrary to the established unicornuate model. By closely replicating the clinical setting, this model stands as a valuable tool for ongoing research in the field of uterus transplantation, promoting further innovation and deeper insights into the intricacies of the uterus transplant procedure.

Halotolerant Endophytic Bacteria Regulate Growth and Field Performance of Two Durum Wheat Genotypes with Contrasting Salinity Tolerance Potential.

Soil salinity hampers durum wheat plant growth and development at various stages. The detrimental effects of salinity on plant cellular and physiological processes necessitate strategies to alleviate its negative impact and improve overall crop yield. This study investigates the efficacy of plant growth-promoting rhizobacteria (PGPR) bacteria inoculation in mitigating salinity stress on two durum wheat genotypes with contrasting degrees of salinity tolerance (Tamaroi, salt-sensitive and Line 5004, salt-tolerant) under greenhouse and field conditions. For this purpose, two halotolerant-PGPR strains, Pseudomonas jordanii strain G34 and Oceanobacillus jordanicus strain GSFE11, were utilized for the inoculation. For the greenhouse experiment, the two selected genotypes were subjected to salinity at the flag leaf stage with continuous irrigation with a Hoagland solution supplemented with 50 mM NaCl. Field experiments were conducted across two locations with contrasting salinity levels over two growing seasons. At the end of both experiments, various parameters including total weight, spike weight, grain weight, spike number, spikelet number, grains per spike and thousand kernel weight were measured. The halotolerant PGPRs, P. jordanii strain G34 and O. jordanicus strain GSFE11, proved effective in alleviating salinity-induced adverse effects and enhancing growth under greenhouse and field conditions. However, bacterial inoculation significantly improved growth in the salt-sensitive genotype and such effects were not observed in the tolerant genotype, emphasizing genotype-specific responses. Notably, inoculation with O. jordanicus increased Na+ and Ca2+ uptake in the salt-tolerant "Line 5004" without hindering growth, suggesting one of its potential mechanisms for salt tolerance. This research demonstrates the potential of halotolerant-PGPR inoculation in enhancing durum wheat production in saline environments, but also underscores the importance of understanding genotype-specific responses for tailored interventions.

Depletion of donor dendritic cells ameliorates immunogenicity of both skin and hind limb transplants.

Acute cellular rejection remains a significant obstacle affecting successful outcomes of organ transplantation including vascularized composite tissue allografts (VCA). Donor antigen presenting cells (APCs), particularly dendritic cells (DCs), orchestrate early alloimmune responses by activating recipient effector T cells. Employing a targeted approach, we investigated the impact of donor-derived conventional DCs (cDCs) and APCs on the immunogenicity of skin and skin-containing VCA grafts, using mouse models of skin and hind limb transplantation. By post-transplantation day 6, skin grafts demonstrated severe rejections, characterized by predominance of recipient CD4 T cells. In contrast, hind limb grafts showed moderate rejection, primarily infiltrated by CD8 T cells. Notably, the skin component exhibited heightened immunogenicity when compared to the entire VCA, evidenced by increased frequencies of pan (CD11b-CD11c+), mature (CD11b-CD11c+MHCII+) and active (CD11b-CD11c+CD40+) DCs and cDC2 subset (CD11b+CD11c+ MHCII+) in the lymphoid tissues and the blood of skin transplant recipients. While donor depletion of cDC and APC reduced frequencies, maturation and activation of DCs in all analyzed tissues of skin transplant recipients, reduction in DC activities was only observed in the spleen of hind limb recipients. Donor cDC and APC depletion did not impact all lymphocyte compartments but significantly affected CD8 T cells and activated CD4 T in lymph nodes of skin recipients. Moreover, both donor APC and cDC depletion attenuated the Th17 immune response, evident by significantly reduced Th17 (CD4+IL-17+) cells in the spleen of skin recipients and reduced levels of IL-17E and lymphotoxin-α in the serum samples of both skin and hind limb recipients. In conclusion, our findings underscore the highly immunogenic nature of skin component in VCA. The depletion of donor APCs and cDCs mitigates the immunogenicity of skin grafts while exerting minimal impact on VCA.

Salicylic Acid and Gemma-Aminobutyric Acid Mediated Regulation of Growth, Metabolites, Antioxidant Defense System and Nutrient Uptake in Sunflower (Helianthus annuus L.) Under Arsenic Stress.

Background: Arsenic (As) is a highly toxic and carcinogenic pollutant commonly found in soil and water, posing significant risks to human health and plant growth. Objective: The objectives of this study to evaluate morphological, biochemical, and physiological markers, as well as ion homeostasis, to alleviate the toxic effects of As in sunflowers through the exogenous application of salicylic acid (SA), γ-aminobutyric acid (GABA), and their combination. Methods: A pot experiment was conducted using two sunflower genotypes, FH-779 and FH-773, subjected to As stress (60 mg kg-1) to evaluate the effects of SA at 100 mg L-1, GABA at 200 mg L-1, and their combination on growth and related physiological and biochemical attributes under As stress. Results: The study revealed that As toxicity had a detrimental effect on various growth parameters, chlorophyll pigments, relative water content, total proteins, and nutrient uptake in sunflower plants. It also led to increased oxidative stress, as indicated by higher levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), along with As accumulation in the roots and leaves. However, the application of SA and GABA protected against As-induced damage by enhancing the enzymatic antioxidant defense system. This was achieved through the activation of superoxide dismutase (SOD), catalase (CAT), and peroxidase (POD) activities, as well as an increase in osmolytes. They also improved nutrient acquisition and plant growth under As toxicity. Conclusions: We investigated the regulatory roles of SA and GABA in mitigating arsenic-induced phytotoxic effects on sunflower. Our results revealed a significant interaction between SA and GABA in regulating growth, photosynthesis, metabolites, antioxidant defense systems, and nutrient uptake in sunflower under As stress. These findings provide valuable insights into plant defense mechanisms and strategies to enhance stress tolerance in contaminated environments. In the future, SA and GABA could be valuable tools for managing stress in other important crops facing abiotic stress conditions.

Pervasive influence of heavy metals on metabolic pathways is potentially relieved by hesperidin to enhance the phytoremediation efficiency of Bassia scoparia.

Hesperidin (HSP), a flavonoid, is a potent antioxidant, metal chelator, mediator of signaling pathways, and regulator of metal uptake in plants. The study examined the ameliorative effects of HSP (100 µM) on Bassia scoparia grown under excessive levels of heavy metals (zinc (500 mg kg-1), copper (400 mg kg-1), cadmium (100 mg kg-1), and chromium (100 mg kg-1)). The study clarifies the underlying mechanisms by which HSP lessens metabolic mayhem to enhance metal stress tolerance and phytoremediation efficiency of Bassia scoparia. Plants manifested diminished growth because of a drop in chlorophyll content and nutrient acquisition, along with exacerbated deterioration of cellular membranes reflected in elevated reactive oxygen species (ROS) production, lipid peroxidation, and relative membrane permeability. Besides the colossal production of cytotoxic methylglyoxal, the activity of lipoxygenase was also higher in plants under metal toxicity. Conversely, hesperidin suppressed the production of cytotoxic ROS and methylglyoxal. Hesperidin improved oxidative defense that protected membrane integrity. Hesperidin caused a more significant accumulation of osmolytes, non-protein thiols, and phytochelatins, thereby rendering metal ions non-toxic. Hydrogen sulfide and nitric oxide endogenous levels were intricately maintained higher in plants treated with HSP. Hesperidin increased metal accumulation in Bassia scoparia and thereby had the potential to promote the reclamation of metal-contaminated soils.

Evolutionary trends of respiratory syncytial viruses: Insights from large-scale surveillance and molecular dynamics of G glycoprotein.

Human respiratory syncytial virus (RSV) is an underlying cause of lower respiratory illnesses in children, elderly and immunocompromised adults. RSV contains multiple structural and non-structural proteins with two major glycoproteins that control the initial phase of infection, fusion glycoprotein and the attachment (G) glycoprotein. G protein attaches to the ciliated cells of airways initiating the infection. The hypervariable G protein plays a vital role in evolution of RSV strains. We employed multiple bioinformatics tools on systematically accessed large-scale data to evaluate mutations, evolutionary history, and phylodynamics of RSV. Mutational analysis of central conserved region (CCR) on G protein-coding sequences between 163 and 189 positions revealed frequent mutations at site 178 in human RSV (hRSV) A while arginine to glutamine substitutions at site 180 positions in hRSV B, remained prevalent from 2009 to 2014. Phylogenetic analysis indicates multiple signature mutations within G protein responsible for diversification of clades. The USA and China have highest number of surveillance records, followed by Kenya. Markov Chain Monte Carlo Bayesian skyline plot revealed that RSV A evolved steadily from 1990 to 2000, and rapidly between 2003 and 2005. Evolution of RSV B continued from 2003 to 2022, with a high evolution stage from 2016 to 2020. Throughout evolution, cysteine residues maintained their strict conserved states while CCR has an entropy value of 0.0039(±0.0005). This study concludes the notion that RSV G glycoprotein is continuously evolving while the CCR region of G protein maintains its conserved state providing an opportunity for CCR-specific monoclonal antibodys (mAbs) and inhibitors as potential candidates for immunoprophylaxis.

Beyond the Diagnosis: A Deep Dive Into the End Stage Liver Disease Experience From the Patient Perspective.

INTRODUCTION: End-stage liver disease (ESLD) presents a multifaceted challenge that encompasses not only physical but also emotional, psychological, and social dimensions. This study aims to explore the experiences of ESLD patients within the United States healthcare system. METHODS: Utilizing a convenience sampling methodology, 15 ESLD patients from a tertiary care hospital in the USA participated in semi-structured interviews between April 2023 and January 2024. Data analysis was conducted using MAXQDA 2023, employing a phenomenological approach to identify common themes. RESULTS: The study identified six primary themes: the significance of communication style in diagnosis delivery, the crucial role of family and social support, varied understanding and preferences for palliative care, diverse attitudes towards advanced care planning, preferences for coordinated healthcare experiences, and the emotional and psychological impact of ESLD. CONCLUSION: Our study underscores the complexity of ESLD patient care beyond medical treatment, highlighting the importance of clear communication, empathetic care, and the integration of family and palliative care services.

Identifying alkaline phosphatase inhibitory potential of cyclooxygenase-2 inhibitors: Insights from molecular docking, MD simulations, molecular expression analysis in MCF-7 breast cancer cell line and in vitro investigations.

Alkaline phosphatases (APs, EC 3.1.3.1) belong to a superfamily of biological macromolecules that dephosphorylate many phosphometabolites and phosphoproteins and their overexpression is intricated in the spread of cancer to liver and bones, neuronal disorders including Alzheimer's disease (AD), inflammation and others. It was hypothesized that cyclooxygenase-2 (COX-2) selective inhibitors may possess anti-APs potential and may be involved in anticancer proceedings. Three COX-2 inhibitors including nimesulide, piroxicam and lornoxicam were evaluated for the inhibition of APs using in silico and in vitro methods. Molecular docking studies against tissue nonspecific alkaline phosphatase (TNAP) offered the best binding affinities for nimesulide (-11.14 kcal/mol) supported with conventional hydrogen bonding and hydrophobic interactions. MD simulations against TNAP for 200 ns and principal component analysis (PCA) reiterated the stability of ligand-receptor complexes. Molecular expression analysis of TNAP enzyme in the breast cancer cell line MCF-7 exhibited 0.24-fold downregulation with 5 µM nimesulide as compared with 0.26-fold standard 10 µM levamisole. In vitro assays against human placental AP (hPAP) displayed potent inhibitions of these drugs with IC50 values of 0.52 ±â€¯0.02 µM to 3.46 ±â€¯0.13 µM and similar results were obtained for bovine intestinal AP (bIAP). The data when generalized collectively emphasizes that the inhibition of APs by COX-2 inhibitors provides another target to work on the development of anticancer drugs.

Comparative efficacy of craniotomy versus craniectomy in surgical management of acute subdural hematoma: A systematic review and meta-analysis.

INTRODUCTION: Acute subdural hematoma (ASDH), a predominantly lethal neurosurgical emergency in the settings of traumatic brain injury, requires surgical evacuation of hematoma, via craniotomy or craniectomy. The clinical practices vary, with no consensus over the superiority of either procedure. AIM: To evaluate whether craniotomy or craniectomy is the optimal approach for surgical evacuation of ASDH. METHODS: After a comprehensive search of PubMed, Google Scholar, Scopus, and Cochrane Central Register of Controlled Trials (CENTRAL) up to January 2024, to identify relevant studies, a meta-analysis was performed using a random-effects model, and risk ratios were calculated with 95% confidence intervals (CIs). For quality assessment, the Cochrane risk of bias tool and Newcastle-Ottawa Scale were applied. RESULTS: Out of 2143 potentially relevant studies, 1875 were deemed suitable for screening. Eighteen studies were included in the systematic review. Thirteen studies, in which 1589 patients underwent craniotomy and 1452 patients underwent craniectomy, allowed meta-analysis. Pooled estimates showed that there was no significant correlation of mortality at 6 months (RR 1.14;95 % CI; 0.94-1.38 P = 0.18) and 12 months (RR 1.17; 95 % CI; 0.84-1.63 P = 0.36) with the two surgical modalities. A positive association was observed between improved functional outcomes at 6-months and craniotomy (RR 0.76; 95 % CI; 0.62-0.93 P = 0.008), however, no significant difference was observed between the two treatment groups at 12 months follow-up (RR 0.89; 95 % CI; 0.72-1.09 P = 0.26). Craniotomy reported a significantly higher proportion of patients discharged to home (RR 0.63; 95 % CI; 0.49-0.83 P = 0.0007), whereas incidence of residual subdural hematoma was significantly lower in the craniectomy group (RR 0.70; 95 % CI; 0.52-0.94 P = 0.02). CONCLUSION: Craniectomy is associated with poor clinical outcomes. However, with long-term follow-up, no difference in mortality and functional outcomes is observed in either of the patient populations. On account of equivocal evidence regarding the efficacy of craniectomy over craniotomy in the realm of long-term outcomes, utmost preference shall be directed toward craniotomy as it is less invasive and associated with fewer complications.

Combined Endurance and Resistance Exercise Mitigates Age-Associated Cardiac Dysfunction.

Aging is associated with a decline in cardiac function. Exercise has been shown to effectively reduce the risks of cardiovascular diseases. Here whether a combination of endurance and resistance exercises can improve cardiac function in aged mice during late life is investigated. Through transcriptome analysis, several signaling pathways activated in the hearts of 22-month-old mice after combined exercise, including cardiac muscle contraction, mitophagy, and longevity regulation are identified. Combined exercise training mitigated age-associated pathological cardiac hypertrophy, reduced oxidative stress, cardiac senescence, and enhanced cardiac function. Upstream stimulatory factor 2 (Usf2) is upregulated in the aged mouse hearts with combined exercise compared to sedentary mice. In the human cardiomyocytes senescent model, overexpression of Usf2 led to anti-senescence effects, while knockdown of Usf2 exacerbated cellular senescence. The results suggest that a combination of endurance and resistance exercises, such as swimming and resistance running, can mitigate age-related pathological cardiac remodeling and cardiac dysfunction in late life. These cardioprotective effects are likely due to the activation of Usf2 and its anti-senescence effect. Therefore, Usf2 can potentially be a novel therapeutic target for mitigating age-related cardiac dysfunction.