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Turkish Journal of Medical Sciences 2023People living with human immunodeficiency virus (PLWH) are getting older. Age-related comorbidities in PLWH result in polypharmacy and increase the risk for potential...
BACKGROUND/AIM
People living with human immunodeficiency virus (PLWH) are getting older. Age-related comorbidities in PLWH result in polypharmacy and increase the risk for potential drug-drug interactions (pDDIs). This study aimed to evaluate how the rate of pDDIs would change if the treatment of patients receiving different combined antiretroviral therapies (ARTs) were theoretically changed with dolutegravir/lamivudine (DTG+3TC) or cabotegravir/rilpivirine (CAB+RPV).
MATERIALS AND METHODS
This study was conducted at the infectious disease outpatient clinic of a university hospital as a follow-up of a previous study. The data of PLWH receiving at least 1 comedication other than antiretrovirals (ARVs) were retrospectively reviewed and analyzed. The Drugs.com/Drug Interactions Checker and University of Liverpool HIV Drug Interactions Checker databases were used to identify pDDIs and their severities.
RESULTS
A total of 75 PLWH, of whom 83% were male, with a mean age (± standard deviation) of 46.5 (±12.98) years were included. Polypharmacy was observed in 59 (79%) of the participants; however, with dual ARV options, the probability of polypharmacy was 35 (47%) (p < 0.001). In the Drugs.com database, no significant difference was found in terms of pDDIs between the treatment of current ARTs (64%) and DTG/3TC (%44) (p = 0.06) or CAB/RPV (%64) (p = 0.521). However, in the University of Liverpool database, the current rate of pDDIs (55%) was significantly higher compared to the theoretical treatment of DTG/3TC (40%) (p = 0.029), oral CAB/RPV (48%) (p = 0.003), and injectable CAB/RPV (31%) use (p = 0.006).
CONCLUSION
The results suggest that dual treatment regimens can reduce pDDIs, resulting in better tolerance and probably higher quality of life among PLWH.
Topics: Humans; Drug Interactions; Retrospective Studies; Male; Female; Middle Aged; HIV Infections; Adult; Polypharmacy; Anti-HIV Agents; Lamivudine; Pyridones; Drug Therapy, Combination; Heterocyclic Compounds, 3-Ring; Oxazines; Anti-Retroviral Agents; Piperazines
PubMed: 38813033
DOI: 10.55730/1300-0144.5718 -
Frontiers in Endocrinology 2024In 2022, the Center for Disease Control and Prevention reported that 11.3% of the United States population, 37.3 million people, had diabetes and 38% of the population... (Review)
Review
In 2022, the Center for Disease Control and Prevention reported that 11.3% of the United States population, 37.3 million people, had diabetes and 38% of the population had prediabetes. A large American study conducted in 2021 and supported by many other studies, concluded that about 47% of diabetes patients have peripheral neuropathy and that diabetic neuropathy was present in 7.5% of patients at the time of diabetes diagnosis. In subjects deemed to be pre-diabetes and impaired glucose tolerance there was a wide range of prevalence estimates (interquartile range (IQR): 6%-34%), but most studies (72%) reported a prevalence of peripheral neuropathy ≥10%. There is no recognized treatment for diabetic peripheral neuropathy (DPN) other than good blood glucose control. Good glycemic control slows progression of DPN in patients with type 1 diabetes but for patients with type 2 diabetes it is less effective. With obesity and type 2 diabetes at epidemic levels the need of a treatment for DPN could not be more important. In this article I will first present background information on the "primary" mechanisms shown from pre-clinical studies to contribute to DPN and then discuss mono- and combination therapies that have demonstrated efficacy in animal studies and may have success when translated to human subjects. I like to compare the challenge of finding an effective treatment for DPN to the ongoing work being done to treat hypertension. Combination therapy is the recognized approach used to normalize blood pressure often requiring two, three or more drugs in addition to lifestyle modification to achieve the desired outcome. Hypertension, like DPN, is a progressive disease caused by multiple mechanisms. Therefore, it seems likely as well as logical that combination therapy combined with lifestyle adjustments will be required to successfully treat DPN.
Topics: Humans; Diabetic Neuropathies; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Combined Modality Therapy; Animals; Drug Therapy, Combination
PubMed: 38812811
DOI: 10.3389/fendo.2024.1357859 -
BMC Cardiovascular Disorders May 2024Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF)...
OBJECTIVES
Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology.
METHODS
We enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class - 2, median left ventricular ejection fraction (LVEF) - 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation.
RESULTS
The ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57-69] vs. 55 [42.8-61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208-309] vs. 220 [192-271], p = 0.019) and end-systolic volume (ESV) (183 [147-230] vs. 154 [128-199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2-6] vs. +7.7 [2-12], p < 0.001), while the improvement in the 6MWT (+ 75 [22-108] vs. +80 [10-160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105-120] vs. 120[110-129]; p = 0.032).
CONCLUSION
In this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.
Topics: Humans; Male; Female; Middle Aged; Ventricular Function, Left; Stroke Volume; Aged; Treatment Outcome; Heart Failure; Myocardial Contraction; Recovery of Function; Time Factors; Russia; Exercise Tolerance; Adult; Retrospective Studies; Peptide Fragments; Natriuretic Peptide, Brain; Functional Status
PubMed: 38811946
DOI: 10.1186/s12872-024-03950-8 -
BMC Plant Biology May 2024The biosynthesis of zinc oxide nanoparticles (ZnO NPs) using Enterobacter sp. and the evaluation of their antimicrobial and copper stress (Cu)-reducing capabilities in...
Green-synthesized zinc oxide nanoparticles by Enterobacter sp.: unveiling characterization, antimicrobial potency, and alleviation of copper stress in Vicia faba (L.) plants.
BACKGROUND
The biosynthesis of zinc oxide nanoparticles (ZnO NPs) using Enterobacter sp. and the evaluation of their antimicrobial and copper stress (Cu)-reducing capabilities in Vicia faba (L.) plants. The green-synthesized ZnO NPs were validated using X-ray powder diffraction (XRD); Fourier transformed infrared (FTIR), Ultraviolet-Visible spectroscopy (UV-Vis), Transmission electron microscope (TEM) and scanning electron microscopy (SEM) techniques. ZnO NPs could serve as an improved bactericidal agent for various biological applications. as well as these nanoparticles used in alleviating the hazardous effects of copper stress on the morphological and physiological traits of 21-day-old Vicia faba (L.) plants.
RESULTS
The results revealed that different concentrations of ZnO NPs (250, 500, or 1000 mg L) significantly alleviated the toxic effects of copper stress (100 mM CuSO) and increased the growth parameters, photosynthetic efficiency (Fv/Fm), and pigments (Chlorophyll a and b) contents in Cu-stressed Vicia faba (L.) seedlings. Furthermore, applying high concentration of ZnO NPs (1000 mg L) was the best dose in maintaining the levels of antioxidant enzymes (CAT, SOD, and POX), total soluble carbohydrates, total soluble proteins, phenolic and flavonoid in all Cu-stressed Vicia faba (L.) seedlings. Additionally, contents of Malondialdehyde (MDA) and hydrogen peroxide (HO) were significantly suppressed in response to high concentrations of ZnO NPs (1000 mg L) in all Cu-stressed Vicia faba (L.) seedlings. Also, it demonstrates strong antibacterial action (0.9 mg/ml) against various pathogenic microorganisms.
CONCLUSIONS
The ZnO NPs produced in this study demonstrated the potential to enhance plant detoxification and tolerance mechanisms, enabling plants to better cope with environmental stress. Furthermore, these nanoparticles could serve as an improved bactericidal agent for various biological applications.
Topics: Vicia faba; Zinc Oxide; Copper; Enterobacter; Metal Nanoparticles; Green Chemistry Technology; Nanoparticles; Anti-Bacterial Agents; Stress, Physiological; Antioxidants; Seedlings
PubMed: 38811913
DOI: 10.1186/s12870-024-05150-0 -
BMC Plant Biology May 2024Salinity stress, an ever-present challenge in agriculture and environmental sciences, poses a formidable hurdle for plant growth and productivity in saline-prone regions...
Salinity stress, an ever-present challenge in agriculture and environmental sciences, poses a formidable hurdle for plant growth and productivity in saline-prone regions worldwide. Therefore, this study aimed to explore the effectiveness of trehalose and mannitol induce salt resistance in wheat seedlings. Wheat grains of the commercial variety Sakha 94 were divided into three groups : a group that was pre-soaked in 10 mM trehalose, another group was soaked in 10 mM mannitol, and the last was soaked in distilled water for 1 hour, then the pre soaked grains cultivated in sandy soil, each treatment was divided into two groups, one of which was irrigated with 150 mM NaCl and the other was irrigated with tap water. The results showed that phenols content in wheat seedlings increased and flavonoids reduced due to salt stress. Trehalose and mannitol cause slight increase in total phenols content while total flavonoids were elevated highy in salt-stressed seedlings. Furthermore, Trehalose or mannitol reduced salt-induced lipid peroxidation. Salt stress increases antioxidant enzyme activities of guaiacol peroxidase (G-POX), ascorbate peroxidase (APX), and catalase (CAT) in wheat seedlings, while polyphenol oxidase (PPO) unchanged. Trehalose and mannitol treatments caused an increase in APX, and CAT activities, whereas G-POX not altered but PPO activity were decreased under salt stress conditions. Molecular docking confirmed the interaction of Trehalose or mannitol with peroxidase and ascorbic peroxidase enzymes. Phenyl alanine ammonia layase (PAL) activity was increased in salt-stressed seedlings. We can conclude that pre-soaking of wheat grains in 10 mM trehalose or mannitol improves salinity stress tolerance by enhancing antioxidant defense enzyme and/or phenol biosynthesis, with docking identifying interactions with G-POX, CAT, APX, and PPO.
Topics: Triticum; Trehalose; Seedlings; Mannitol; Salt Tolerance; Molecular Docking Simulation; Antioxidants; Salt Stress; Flavonoids; Phenols
PubMed: 38811894
DOI: 10.1186/s12870-024-04964-2 -
Frontiers in Microbiology 2024is one of the most common pathogens causing hemorrhagic pneumonia in Chinese forest musk deer. Multidrug-resistant is frequently isolated from the lungs of affected...
is one of the most common pathogens causing hemorrhagic pneumonia in Chinese forest musk deer. Multidrug-resistant is frequently isolated from the lungs of affected musk deer in Shaanxi Province, China. With the increasing bacterial drug resistance, commonly used antibiotics have shown limited efficacy against drug-resistant . Therefore, phages have garnered attention as a promising alternative to antibiotics among researchers. In this study, phages vB_PaeP_YL1 and vB_PaeP_YL2 (respectively referred to as YL1 and YL2) were isolated from mixed sewage samples from a farm. YL1 and YL2 exhibit an icosahedral head and a non-contractile short tail, belonging to the family. Identification results demonstrate good tolerance to low temperatures and pH levels, with minimal variation in potency within 30 min of UV irradiation. The MOI for both YL1 and YL2 was 0.1, and their one-step growth curve latent periods were 10 min and 20 min, respectively. Moreover, both single phage and phage cocktail effectively inhibited the growth of the host bacteria , with the phage cocktail showing superior inhibitory effects compared to the single phage. YL1 and YL2 possess double-stranded DNA genomes, with YL1 having a genome size of 72,187 bp and a total G + C content of 55.02%, while YL2 has a genome size of 72,060 bp and a total G + C content of 54.98%. YL1 and YL2 are predicted to have 93 and 92 open reading frames (ORFs), respectively, and no ORFs related to drug resistance or lysogeny were found in both phages. Genome annotation and phylogenetic analysis revealed that YL1 is closely related to vB_PaeP_FBPa1 (ON857943), while YL2 is closely related to vB_PaeP_FBPa1 (ON857943) and Phage26 (NC041907). In a mouse model of hemorrhagic pneumonia, phage cocktail treatment showed better control of the disease and significantly reduced lung bacterial load compared to single phage treatment. Therefore, YL1 and YL2 have the potential for the prevention and treatment of multidrug-resistant infections.
PubMed: 38808279
DOI: 10.3389/fmicb.2024.1396774 -
Biology Direct May 2024Our study aims to identify the mechanisms involved in regulating the response of Rhodoendron Chrysanthum Pall. (R. chrysanthum) leaves to UV-B exposure; phosphorylated...
Our study aims to identify the mechanisms involved in regulating the response of Rhodoendron Chrysanthum Pall. (R. chrysanthum) leaves to UV-B exposure; phosphorylated proteomics and metabolomics for phenolic acids and plant hormones were integrated in this study. The results showed that UV-B stress resulted in the accumulation of salicylic acid and the decrease of auxin, jasmonic acid, abscisic acid, cytokinin and gibberellin in R. chrysanthum. The phosphorylated proteins that changed in plant hormone signal transduction pathway and phenolic acid biosynthesis pathway were screened by comprehensive metabonomics and phosphorylated proteomics. In order to construct the regulatory network of R. chrysanthum leaves under UV-B stress, the relationship between plant hormones and phenolic acid compounds was analyzed. It provides a rationale for elucidating the molecular mechanisms of radiation tolerance in plants.
Topics: Ultraviolet Rays; Hydroxybenzoates; Plant Growth Regulators; Rhododendron; Stress, Physiological; Plant Leaves; Proteomics; Signal Transduction; Metabolomics; Phosphorylation
PubMed: 38807240
DOI: 10.1186/s13062-024-00483-0 -
BMC Pulmonary Medicine May 2024Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO) is an appropriate tool to evaluate the physical... (Observational Study)
Observational Study
BACKGROUND
Physical activity is a crucial demand on cystic fibrosis treatment management. The highest value of oxygen uptake (VO) is an appropriate tool to evaluate the physical activity in these patients. However, there are several other valuable CPET parameters describing exercise tolerance (W, VO, VO VO/HR, etc.), and helping to better understand the effect of specific treatment (V, V, V/V etc.). Limited data showed ambiguous results of this improvement after CFTR modulator treatment. Elexacaftor/tezacaftor/ivacaftor medication improves pulmonary function and quality of life, whereas its effect on CPET has yet to be sufficiently demonstrated.
METHODS
We performed a single group prospective observational study of 10 adolescent patients with cystic fibrosis who completed two CPET measurements between January 2019 and February 2023. During this period, elexacaftor/tezacaftor/ivacaftor treatment was initiated in all of them. The first CPET at the baseline was followed by controlled CPET at least one year after medication commencement. We focused on interpreting the data on their influence by the novel therapy. We hypothesized improvements in cardiorespiratory fitness following treatment. We applied the Wilcoxon signed-rank test. The data were adjusted for age at the time of CPET to eliminate bias of aging in adolescent patients.
RESULTS
We observed significant improvement in peak workload, VO, VO, VO, V/VCO slope, V, V, RQ, VO/HR peak and RR peak. The mean change in VOpeak was 5.7 mL/kg/min, or 15.9% of the reference value (SD ± 16.6; p= 0.014). VO improved by 15% of the reference value (SD ± 0.1; p= 0.014), VOimproved by 0.5 (SD ± 0.4; p= 0.01). There were no differences in other parameters.
CONCLUSION
Exercise tolerance improved after elexacaftor/tezacaftor/ivacaftor treatment initiation. We suggest that the CFTR modulator alone is not enough for recovering physical decondition, but should be supplemented with physical activity and respiratory physiotherapy. Further studies are needed to examine the effect of CFTR modulators and physical therapy on cardiopulmonary exercise tolerance.
Topics: Humans; Cystic Fibrosis; Adolescent; Male; Female; Prospective Studies; Pilot Projects; Indoles; Benzodioxoles; Quinolones; Aminophenols; Pyrazoles; Pyridines; Drug Combinations; Cardiorespiratory Fitness; Exercise Test; Pyrroles; Exercise Tolerance; Oxygen Consumption; Child; Pyrrolidines
PubMed: 38807122
DOI: 10.1186/s12890-024-03069-8 -
BMC Plant Biology May 2024Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific...
Davidia involucrata is a woody perennial and the only living species in the Genus Davidia. It is native to southern China where it holds cultural and scientific importance. However, D. involucrata is now an endangered species and its natural range includes low pH soils which are increasingly impacted by acid rain, nitrogen deposition and imbalanced nutrient cycling. The combination of these stresses also poses the additional risk of aluminum (Al) toxicity. Since the responses of D. involucrata to low pH and aluminum toxicity have not been investigated previously, a hydroponic experiment was conducted to examine the growth of one year old D. involucrata saplings after 50 d growth in a range of pH and Al conditions. Plant biomass, morphology, antioxidant enzyme activity, mineral concentrations and plant ecological strategy were compared at pH 5.8 and pH 4.0 without added Al (AlCl) and in 0.1, 0.2 and 0.5 mM Al at pH 4.0. Our results showed that compared with pH 5.8, pH 4.0 (without added Al) not only inhibited root and shoot growth but also limited accumulation of nitrogen (N) and phosphorus (P) in leaves of D. involucrate. However, low Al concentrations (0.1 and 0.2 mM Al) at pH 4.0 partially restored the aboveground growth and leaf N concentrations, suggesting an alleviation of H toxicity by low Al concentrations. Compared with low Al concentrations, 0.5 mM Al treatment decreased plant growth and concentrations of N, P, and magnesium (Mg) in the leaves, which demonstrated the toxicity of high Al concentration. The results based on plant ecological strategy showed that D. involucrate decreased the competitiveness and favored its stress tolerance as pH changed from 5.8 to 4.0. Meanwhile, the competitiveness and stress tolerance of D. involucrata increased and decreased at low Al concentrations, respectively, and decreased and increased at high Al concentration, respectively. These trade-offs in ecological strategy were consistent with the responses of growth and antioxidant enzyme activity, reflecting a sensitive adaptation of D. involucrata to acid and Al stresses, which may aid in sustaining population dynamics. These findings are meaningful for understanding the population dynamics of D. involucrata in response to aluminum toxicity in acid soils.
Topics: Aluminum; Hydrogen-Ion Concentration; Plant Leaves; Plant Roots; Phosphorus; Soil; Nitrogen; Biomass
PubMed: 38807074
DOI: 10.1186/s12870-024-05173-7 -
Plant Cell Reports May 2024Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide,...
Sodium nitroprusside mediates drought stress responses in tomatoes by modulating nitrosative and oxidative pathways, highlighting the interplay between nitric oxide, hydrogen sulfide, and antioxidant systems for enhanced drought tolerance. While nitric oxide (NO), a signalling molecule, enhances plant tolerance to abiotic stresses, its precise contribution to improving tomato tolerance to drought stress (DS) through modulating oxide-nitrosative processes is not yet fully understood. We aimed to examine the interaction of NO and nitrosative signaling, revealing how sodium nitroprusside (SNP) could mitigate the effects of DS on tomatoes. DS-seedlings endured 12% polyethylene glycol (PEG) in a 10% nutrient solution (NS) for 2 days, then transitioned to half-strength NS for 10 days alongside control plants. DS reduced total plant dry weight, chlorophyll a and b, Fv/Fm, leaf water potential (Ψ), and relative water content, but improved hydrogen peroxide (HO), proline, and NO content. The SNP reduced the DS-induced HO generation by reducing thiol (-SH) and the carbonyl (-CO) groups. SNP increased not only NO but also the activity of L-cysteine desulfhydrase (L-DES), leading to the generation of HS. Decreases in S-nitrosoglutathione reductase (GSNOR) and NADPH oxidase (NOX) suggest a potential regulatory mechanism in which -nitrosylation [formation of S-nitrosothiol (SNO)] may influence protein function and signaling pathways during DS. Moreover, SNP improved ascorbate (AsA) and glutathione (GSH) and reduced oxidized glutathione (GSSG) levels in tomato plants under drought. Furthermore, the interaction of NO and HS, mediated by L-DES activity, may serve as a vital cross-talk mechanism impacting plant responses to DS. Understanding these signaling interactions is crucial for developing innovative drought-tolerance strategies in crops.
Topics: Nitroprusside; Solanum lycopersicum; Hydrogen Peroxide; Droughts; Nitric Oxide; Glutathione; Antioxidants; Oxidation-Reduction; Oxidative Stress; Stress, Physiological; Seedlings; Plant Leaves; Nitrosation; Chlorophyll
PubMed: 38806834
DOI: 10.1007/s00299-024-03238-3