Effect Of Dose Research Articles

Design of a New Catalyst, Manganese(III) Complex, for the Oxidative Degradation of Azo Dye Molecules in Water Using Hydrogen Peroxide

In the current work, chloro(meso-tetrakis(phenyl)porphyrin) manganese(III) [Mn(TPP)Cl] was synthesized following two steps: the preparation of meso-tetraphenylporphyrin (H⁠2TPP) and the insertion of manganese into the free porphyrin H2TPP. The compounds were characterized using SEM, FT-IR, UV, TGA/DTA, and XRD analyses. Manganese(III) meso-porphyrins exhibited hyper-type electronic spectra with a half-vacant metal orbital with symmetry, such as [dπ:dxz and dyz]. The thermal behavior of [Mn(TPP)(Cl)] changed (three-step degradation process) compared to the initial H2TPP (one-step degradation process), confirming the insertion of manganese into the core of the free porphyrin H2TPP. Furthermore, [Mn(TPP)Cl] was used to degrade calmagite (an azo dye) using H2O2 as an oxidant. The effects of dye concentration, reaction time, H2O2 dose, and temperature were investigated. The azo dye solution was completely degraded in the presence of [Mn(TPP)(Cl)]/H2O2 at pH = 6, temperature = 20 °C, C0 = 30 mg/L, and H2O2 = 40 mL/L. The computed low activation energy (Ea = 10.55 Kj/mol) demonstrated the efficiency of the proposed catalytic system for the azo dye degradation. Overall, based on the synthesis process and the excellent catalytic results, the prepared [Mn(TPP)Cl] could be used as an effective catalyst for the treatment of calmagite-contaminated effluents.

A comprehensive investigation of total ionizing dose effects on bulk FinFETs through TCAD simulation

This study investigates the total-ionizing-dose (TID) effect on bulk FinFETs under ON-state irradiation bias, aiming to analyze the cause and physical mechanism of irradiation enhancement effects. Utilizing technology computer-aided design (TCAD), for the first time, we find that parasitic transistors located at the apex of the shallow trench isolation (STI) oxide significantly contribute to the subthreshold degradation of the device, leading to a notable increase in off-state leakage current. Furthermore, under identical irradiation bias conditions, narrower-fin and shorter-channel devices exhibit a more pronounced increase in off-state leakage current. This escalation is attributed to an increased amount of trapped charge in the STI oxide and the elevated electrostatic potential of the punch-through stop (PTS) layer, respectively. Additionally, higher drain voltage reduces the threshold voltage of the STI parasitic transistors, resulting in an increased off-state current as drain voltage rises. In summary, investigating the TID effect of bulk FinFETs under ON-bias is crucial, as it can provide theoretical support for reinforcing nanostructured devices against irradiation-induced degradation.

General health and social outcomes 50 years after exposure to antenatal betamethasone: follow-up of a randomised controlled trial

BackgroundAntenatal corticosteroids are recommended for women at risk of preterm birth from 24 to 34 weeks’ gestation as they reduce neonatal morbidity and mortality, but evidence regarding their long-term effects on offspring is limited. This study assessed general health and social outcomes 50 years after antenatal exposure to corticosteroids.MethodsWe assessed 424 adult offspring of women who participated in the first randomised, double-blind, placebo-controlled trial of antenatal betamethasone for the prevention of neonatal respiratory distress syndrome. The first 717 mothers received two intramuscular injections of betamethasone (6 mg betamethasone sodium phosphate and 6 mg betamethasone acetate) or placebo given 24 h apart and the subsequent 398 received two injections of double dose betamethasone (12 mg betamethasone sodium phosphate and 12 mg betamethasone acetate) or equivalent volume of placebo. Follow-up included a health questionnaire and consent for access to administrative data sources. Outcome categories included mental health (depression, anxiety, bipolar affective disorder, schizophrenia and treatment or hospital admission for any mental health disorder), general health (chronic kidney disease, cancer diagnosis, bone fracture, oral health, allergies, functional difficulties and physical activity) and social outcomes (educational attainment, employment and criminal convictions). Investigators remained blinded to treatment allocation. Analyses were adjusted for gestational age at entry, sex and clustering.ResultsWe assessed 424 adult offspring (46% of survivors; mean [SD] age 49.3 [1.0] years; 212 [50%] female). There was no difference in mental health, general health and social outcomes between those exposed to betamethasone and those exposed to placebo, with the exception that osteoporotic site fracture in adulthood was more likely to have occurred in the betamethasone group compared with placebo (adjusted relative risk 1.57, 95% CI 1.00, 2.48, p = 0.05). No dose–effect relationship was evident and there was no difference in the proportion with at least one fracture. Follow-up rate and lack of in-person assessments were the main limitations.ConclusionsThere is no evidence that antenatal corticosteroids have clinically important effects on general health and social outcomes up to 50 years of age.

Optimal carbofuran degradation via CWPO in NOM-doped water by a framework Cu-doped aluminate perovskite catalyst derived from aluminum saline slags

This study is the first to propose the synthesis of LayAl1–xCuxO3–δ perovskite catalysts using Al recovered from acid leaching of saline slags. The effect of parameters such as the La/Al molar ratio was explored during the synthetic process. A suite of characterization techniques—including XRF, XRD, N2 adsorption, H2-TPR, FTIR, TGA-DTA, TEM, SEM, EDX, and XPS—confirmed the successful synthesis of high-purity (up to 90 %) perovskites with La and O vacancies, and a high concentration of Cu(I) active sites dispersed within the perovskite lattice. The best catalyst was used to optimize the degradation of carbofuran (CBF) in water doped with synthetic dissolved natural organic matter (NOM) using the Fenton-like catalytic wet peroxide oxidation (CWPO) approach. The effects of catalyst concentration, H2O2 dose, and pH on catalytic performance were investigated. Degradation, mineralization (COD removal), and H2O2 consumption were maximized, while Cu leaching was minimized using a statistical desirability function for multiple responses. Optimal conditions were found to be a catalyst concentration (mg Cu/mg H2O2) of 0.234 (2.0 g L–1), an H2O2 dose of 73.3 % (0.73 times the stoichiometric dose for full COD mineralization), and a remarkable circumneutral pH of 6.2. Under these conditions, degradation reached 94.1 %, and COD mineralization was 51 % under room temperature. Notably, the perovskite catalyst exhibited remarkable stability during reuse in up to three cycles, as demonstrated by the low Cu leaching (<1.30 mg L–1).

The effect of a subclinical dose of esketamine on depression and pain after cesarean section: A prospective, randomized, double-blinded controlled trial.

The aim of this randomized, double-blind placebo-controlled clinical trial was to study the effects of subclinical doses of esketamine on postpartum depression and pain following elective cesarean sections. This randomized, double-blind placebo-controlled trial included 150 pregnant women undergoing elective cesarean sections. After umbilical cord clamping, participants received either subclinical doses of esketamine (0.25 mg/kg, diluted in 10 mL of 0.9% saline) or a placebo (10 mL of 0.9% saline). The primary outcome measures were the incidence of postpartum depression (PPD) and postoperative pain. The Edinburgh Postnatal Depression Scale was used to evaluate PPD on days 3, 7, and 14 postpartum, with an Edinburgh Postnatal Depression Scale score ≥ 10 indicating PPD. Postoperative pain was assessed using the Visual Analog Scale (VAS) at 4, 24, and 48 hours post-surgery. Secondary outcomes included adverse reactions and Ramsay sedation scores at 5 and 15 minutes post-administration. There were no significant differences in the incidence of PPD between the 2 groups on days 3, 7, and 14 postpartum (P > .05). The VAS scores showed significant differences between the 2 groups at 4 and 24 hours postoperatively (P < .05), but not at 48 hours (P > .05). The experimental group had significantly higher adverse reactions and Ramsay sedation scores 5 minutes post-administration compared to the control group (P < .05), but no significant differences were observed upon leaving the operating room (P > .05). Subclinical doses of esketamine did not reduce the incidence of PPD at 14 days postpartum but did significantly lower VAS scores at 24 hours post-surgery. The experimental group experienced temporary increases in adverse reactions and Ramsay sedation scores shortly after administration.

Integrated urban wastewater management through on-site generation and application of ferrous carbonate

Integrated urban water management is an increasingly popular concept that cost-effectively maximizes system-wide performance by holistically considering all aspects of water and wastewater sectors. An innovative technology enabling production of high-quality bioenergy and an iron salt, ferrous carbonate (FeCO3), represents a significant opportunity for integrated urban water management. This study experimentally evaluates the effect of in-sewer FeCO3 dosing on the performance of sewers and the downstream wastewater treatment plants. Two continuous-flow laboratory-scale urban wastewater systems, each consisting of sewer reactors, a sequencing batch wastewater treatment reactor, and an anaerobic digester, were operated in parallel. After establishing comparable performance, one served as the control without any chemical dosing, while the other received a dosing of 10mgFe/L of FeCO3 in its sewer reactors. Compared to the control, the FeCO3-dosed experimental system reduced dissolved sulfide concentrations by 32.2±3.3% (at 0.58±0.05mgS/mgFe, or 1.0molFe/molS) in sewer reactors, decreased phosphate concentrations by 38.3%±3.2% (at 0.37±0.04mgP/mgFe, or 1.5molFe/molP) in sequencing batch reactors, and lowered dissolved sulfide concentrations by 72.0±4.2% (18.9±2.4mgS/L) in the anaerobic sludge digester. Iron accumulated in the sludge and improved sludge settleability by 33.9±5.5% and enhanced dewaterability of anaerobically digested sludge by 15.9±2.0%. The findings indicate multiple benefits from the integrated use of FeCO3, potentially being as a substitute for the currently used iron salts in urban wastewater systems.

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on electrolytes, acid-base, creatinine, and troponin in dogs. Part II

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on electrolytes, acid-base, creatinine, and troponin in dogs. Part II

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on sedation and quality of recovery in dogs. Part I

The effect of a subsequent dose of dexmedetomidine or other sedatives following an initial dose of dexmedetomidine on sedation and quality of recovery in dogs. Part I

The toxicity, repellent, and biochemical effects of four wild plant extracts against Aphis gossypii Glover and Phenacoccus solenopsis Tinsley: HPLC analysis of phenolic compounds

AbstractThe insecticidal and repellent activities of the four wild plant extracts: stinging nettle, Urtica dioica L., white henbane, Hyoscyamus albus L., camphorweeds, Pluchea dioscoridis L., and cocklebur, Xanthium strumarium L. were tested compared to the insecticide spirotetramat against the 3rd nymphal instar of Aphis gossypii Glover and adult females of Phenacoccus solenopsis Tinsley after 24 and 48 h of treatment. Their effects on acetylcholinesterase (AChE) and glutathione-S-transferase (GST) enzyme activities were also assessed to explore their possible mechanisms of action. The phenolic compounds of the plant extracts were investigated by high-performance liquid chromatography (HPLC) analysis. The most abundant compounds in the methanol extract from P. dioscoridis were gallic acid (14.45 µg/mL), and cinnamic acid (11.44 µg/mL); from U. dioica were caffeic acid (15.32 µg/mL) and syringic acid (13.47 µg/mL); from H. albus were syringic acid (7.12 µg/mL) and catechol (5.33 µg/mL); and from X. strumarium were p-coumaric acid (24.53 µg/mL) and pyrogallol (18.35 µg/mL). According to the LC50 values, the contact toxicity of U. dioica, H. albus, P. dioscoridis, and X. strumarium against A. gossypii was 40.3, 60.6, 56.2, and 32.3 mg/L, whereas, the contact toxicity against P. solenopsis was 56.4, 67.5, 64.3, and 36.2 mg/L, compared to the spirotetramat (17.2 and 24.5 mg/L), respectively, at 48 h of treatment. The highest repellency rates were observed with LC50 values for X. strumarium (63.2 and 60.3%), followed by U. dioica (46.2 and 43.5%), P. dioscoridis (45.3 and 42.8%), and H. albus extract (38.8 and 35.2%) compared to the spirotetramat (78.5 and 76.2%) against A. gossypii and P. solenopsis at 24 h, but decreased with time. The AChE and GST activities in pests were significantly inhibited, compared to control and spirotetramat, with dose and time-dependent effects. These findings indicate that tested wild extracts may be suggested as viable alternatives for aphids and mealybugs control.

Combined Toxicity of Multi-Walled Carbon Nanotubes and Cu2+ on the Growth of Ryegrass: Effect of Surface Modification, Dose, and Exposure Time Pattern

The escalating release of multi-walled carbon nanotubes (MWCNTs) into the environment has raised concerns due to their potential ecotoxicological impacts. However, their combined phytotoxicity with heavy metals such as copper (Cu) is still unclear. This study investigated the individual and combined toxic effects of MWCNTs (MWCNT, MWCNT-OH, and MWCNT-COOH) and Cu2+ on ryegrass (Lolium multiflorum), uniquely considering different addition orders. The results show that Cu severely inhibited the growth of ryegrass while MWCNTs exhibited a hormesis effect on ryegrass. When MWCNT and Cu were combined, the malondialdehyde (MDA) content in ryegrass showed a 32.39% increase at 20 mg/L MWCNT exposure, suggesting reduced oxidative stress. However, at the higher concentration of 1000 mg/L, it led to a significant 75.22% reduction in ryegrass biomass. MWCNT-COOH had the most pronounced effect, reducing the total chlorophyll content by 39.76% compared to unmodified MWCNT and by 10.67% compared to MWCNT-OH (500 mg/L). Additionally, pre-induced MWCNTs might alleviate the Cu in the plant by 23.08–35.38% through adsorption in the nutrient solution. Small molecule organic acids and amino acids primarily mediated the response to environmental stress in ryegrass. This research provides crucial insights into understanding the complex interactions of MWCNT and Cu2+ and their combined effects on plant ecosystems.

Response of One-Carbon Biomarkers in Maternal and Cord Blood to Folic Acid Dose During Pregnancy

Background/Objectives: The folate Recommended Daily Allowance (RDA) for pregnant women is 600 μg/day dietary folate equivalents, which is equivalent to approximately 400 μg folic acid. Many prenatal supplements contain much higher doses of folic acid. The body’s ability to reduce synthetic folic acid to the metabolically active form may be exceeded with high levels of supplementation. The objective of this double-blinded randomized controlled intervention trial was to determine changes in unmetabolized folic acid and other biomarkers of folate and one-carbon metabolism in maternal and cord blood in response to a folic acid dose commonly found in prenatal supplements (800 μg/day) compared to the dose equivalent of the RDA (400 μg/day). Methods: Healthy pregnant women were randomized and provided supplements from their first prenatal visit (&lt;12 weeks gestation) through delivery. Maternal blood was collected at baseline and delivery. Umbilical cord blood from the mothers was collected at delivery. Results: A repeated measures analysis of variance revealed that there was a significant group supplemental dose effect (p = 0.0225) on serum unmetabolized folic acid concentration in mothers but no difference in cord blood unmetabolized folic acid concentrations between groups. Mixed effects analysis found a significant overall effect of pre-pregnancy BMI (p = 0.0360) and length of previous folic acid supplementation (p = 0.0281) on serum folate concentrations. No treatment effect was seen in RBC folate concentrations. Choline concentrations were higher in cord blood from the 800 μg/day group compared to the 400 μg/day group, but there was no group effect in maternal choline concentrations. Conclusions: The results indicate that folic acid dose during pregnancy affects certain folate and one-carbon biomarkers, and these effects are not consistent between maternal and cord blood. Potential long-term effects of these results on both mothers and offspring are unknown and merit further investigation.

Characterization of anti-AAV2 neutralizing antibody levels in sheep prior to and following intravitreal AAV2.7m8 injection

AbstractGene augmentation therapy is a promising treatment for incurable, blinding inherited retinal diseases, and intravitreal delivery is being studied as a safe alternative to subretinal injections. Adeno-Associated Viruses (AAV) are commonly-used vectors for ocular gene augmentation therapy. Naturally occurring pre-operative exposure and infection with AAV could result in presence of neutralizing antibodies (NAB’s) in patients’ serum, and may affect the safety and efficacy of treatment. Our aim was to characterize the humoral response against AAV pre- and post-intravitreal delivery of AAV2.7m8 vectors in a naturally-occurring sheep model of CNGA3 achromatopsia. Serial serum neutralization assays were performed to screen sheep for pre-exiting anti-AAV2 NAB’s, and to assess the effect of intravitreal AAV2.7m8 injection on post-operative NAB titers and intraocular inflammation in sheep. The effect of viral dose and transgene type were also assessed. Serological screening revealed pre-operative seropositivity in 21.4% of animals, with age being a risk factor for the presence of anti-AAV2 NAB’s. NAB titers increased following intravitreal AAV administration in the majority of sheep. There was no significant difference in the degree of post-operative serum neutralization between pre-operatively seronegative sheep and those with pre-existing antibodies. However, only sheep with pre-existing antibodies presented with signs of post-operative inflammation. We conclude that pre-existing anti-AAV2 NAB’s do not affect the level of post-operative NAB titers; however, they increase the risk of post-operative ocular inflammation. Our results could have implications for the management of AAV-mediated ocular gene therapies, a technology being increasingly studied and used in patients.

High sodium intake increases interstitial lung disease and pulmonary sarcoidosis based on the Global Burden of Disease study 1999–2019

This study investigated the relationships between dietary sodium intake and the incidence and prevalence of interstitial lung disease (ILD) and pulmonary sarcoidosis using data from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019. This study assessed the strength of the abovementioned relationships via LASSO analysis and a generalized additive model with Poisson regression and determined the nonlinear and lagged effects via a distributed lag nonlinear model (DLNM). In the past three decades, global dietary sodium intake has decreased gradually. Two LASSO and generalized additive analyses both suggested that dietary sodium intake is obviously correlated with the incidence and prevalence of ILD and pulmonary sarcoidosis. The overall exposure‒response curve revealed a dose‒effect relationship between dietary sodium intake and the incidence and prevalence of ILD and pulmonary sarcoidosis. The maximum lag-specific RR of extremely high dietary sodium intake was 1.75 (95% CI: 1.61–1.91, lag 0 year) for incidence and 3.19 (95% CI: 2.24–4.53, lag 0 year) for prevalence relative to the reference. Our study suggests that dietary sodium intake is positively associated with the incidence and prevalence of ILD and pulmonary sarcoidosis. These findings may have important policy implications for dietary sodium intake-reduction strategies to decrease the burden of respiratory diseases and promote public health.

Impact of real-world off-label dose of Apixaban on long-term clinical outcomes in patients with atrial fibrillation and chronic kidney disease

Abstract Background Apixaban represent one of the cornerstone treatments to prevent cardioembolic events in patients with nonvalvular atrial fibrillation (NVAF). However, the choices of Apixaban dose guided by the decision-making process of the physician, which considers specific according to kidney functions are inconsistent in the real-world practice. Objective The objective of the present study is to evaluate the effects of real-world Off-label dose of Apixaban on long-term clinical outcomes in NVAF patients with chronic kidney disease (CKD). Methods Our database of AF patients diagnosed with CKD from 2018 to 2023 was used to obtain laboratory, echocardiography, electrocardiogram (ECG), and clinical outcomes data. Inclusion criteria were all AF patients with CKD using Apixaban. And we compared bleeding, systemic thrombotic events including stroke/systemic embolism and death according to off-label real -world dose of Apixaban. Results Among 635 patients with AF and CKD (76.9±10.4 years), 335 (52.8%) patients took off-label underdosed Apixaban. Difference in the baseline characteristics was not observed among patients including CHA2DS2 VASc score and HASBLED score. During the median 18-month follow-up, a lower incidence of bleeding events (P=0.001) was observed in the off-label underdosed Apixaban group compared to those with standard dose or off-label overdosed Apixaban. However, there was no significant difference of systemic thrombotic events including stroke/systemic embolism and death according to off-label real-world dose of Apixaban (off-label underdose vs. standard dose, P=1.000; off-label overdose vs. standard dose, P=1.000; off-label underdose vs. off-label overdose, P=0.609). In multivariate analysis, HASBLED score was independent risk factors for bleeding events (OR 9.650; CI 1.998-46.622; P=0.005). Conclusions Compared with standard or off-label overdose of Apixaban, off-label underdose of Apixaban was associated with a lower risk of bleeding in patients with AF and CKD, with no difference in the risk of stroke/systemic embolism or death, supporting the apixaban dosing tailored to specific clinical features and drug pharmacokinetics of the Asian patients.

Pharmacometabolomics Approach to Explore Pharmacokinetic Variation and Clinical Characteristics of a Single Dose of Desvenlafaxine in Healthy Volunteers

This study investigated the effects of a single dose of desvenlafaxine via oral administration on the pharmacokinetic parameters and clinical and laboratory characteristics in healthy volunteers using a pharmacometabolomics approach. In order to optimize desvenlafaxine’s therapeutic use and minimize potential adverse effects, this knowledge is essential. Methods: Thirty-five healthy volunteers were enrolled after a health trial and received a single dose of desvenlafaxine (Pristiq®, 100 mg). First, liquid chromatography coupled to tandem mass spectrometry was used to determine the main pharmacokinetic parameters. Next, ultra-performance liquid chromatography–quadrupole time-of-flight mass spectrometry was used to identify plasma metabolites with different relative abundances in the metabolome at pre-dose and when the desvenlafaxine peak plasma concentration was reached (pre-dose vs. post-dose). Results: Correlations were observed between metabolomic profiles, such as tyrosine, sphingosine 1-phosphate, and pharmacokinetic parameters, as well as acetoacetic acid and uridine diphosphate glucose associated with clinical characteristics. Our findings suggest that desvenlafaxine may have a broader effect than previously thought by acting on the proteins responsible for the transport of various molecules at the cellular level, such as the solute carrier SLC and adenosine triphosphate synthase binding cassette ABC transporters. Both of these molecules have been associated with PK parameters and adverse events in our study. Conclusions: This altered transporter activity may be related to the reported side effects of desvenlafaxine, such as changes in blood pressure and liver function. This finding may be part of the explanation as to why people respond differently to the drug.

Very short-term effects of single dose of proprotein convertase subtilisin kexin 9 inhibitor therapy before percutaneous coronary intervention

Abstract Introduction Several pioneering studies have reported that continuous administration of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitor reduces cardiovascular events and plaque volume on intravascular ultrasound and increase the thickness of the fibrous-cap on optical coherence tomography after 52-76 weeks.[1,2] However, the effect of PCSK9 inhibitors in very short period of time has not adequately been evaluated. Purpose This study aimed to investigate the effect of the single dose of PCSK9 inhibitor in regard to serial change of plaque composition in very short period with near-infrared spectroscopy with intravascular ultrasound (NIRS-IVUS). Methods This prospective, single arm, single-center, interventional study included 27 consecutive coronary artery disease patients (silent myocardial ischemia and stable angina) who performed NIRS-IVUS at the time of coronary angiography for diagnosis between June 2021 and August 2023. Maximal lipid-core burden index over any 4-mm segment (max-LCBI4mm) and total lipid-core burden index (T-LCBI) at the target lesions were assessed with NIRS-IVUS and they were administered evolocumab 420mg. After 2 to 6 weeks, percutaneous coronary intervention (PCI) was performed on a standby basis and repeat NIRS-IVUS were performed at PCI. Results The median max-LCBI4mm showed a significant decrease from 387 to 315 (IQR: 268 to 572 and IQR: 221 to 488, respectively; p = 0.02) in a lesion-wise analysis. The median T-LCBI also showed a significant decrease from 160 to 117 (IQR: 105 to 263 and IQR: 65 to 226, respectively; p = 0.02). Minimum lumen area and minimum lumen diameter showed no significant changes. Conclusions Single dose of PCSK9 inhibitor therapy before PCI resulted in significant degression of lipid core plaques identified by NIRS at the target lesion in very short period of time.Changes of max-LCBI4mmChanges of T-LCBI

Intensity-Dependent Effects of Low-Frequency Subthreshold rTMS on Primary Motor Cortex Excitability and Interhemispheric Inhibition in Elderly Participants: A Randomized Trial.

Low-frequency repetitive transcranial magnetic stimulation (LF-rTMS) protocols targeting primary motor cortex (M1) are used in rehabilitation of neurological diseases for their therapeutic potential, safety, and tolerability. Although lower intensity LF-rTMS can modulate M1 neurophysiology, results are variable, and a systematic assessment of its dose effect is lacking. To determine the dose-response of LF-rTMS on stimulated and non-stimulated M1. In a sham-controlled randomized double-blind crossover study the effect of LF-TMS protocols were determined in 20 right-handed older healthy participants. In 3 sessions, 1 Hz rTMS at 80% (rTMS80), 90% (rTMS90) of motor threshold or sham stimulation were applied to left upper extremity M1. Outcome measures were curve parameters of the stimulus-response curve (maximum motor evoked potential [MEPMAX], slope and the intensity to evoke 50% MEPMAX), short-interval intracortical inhibition (SICI), and interhemispheric inhibition (IHI). Within LF-rTMS sessions, rTMS90, increased MEPMAX in the stimulated M1. Furthermore, rTMS90, increased the slope in the non-stimulated M1. LF-rTMS effects on SICI were dependent on the participants' baseline SICI, hemisphere, and intensity of conditioning pulse. Finally, rTMS90 increased whereas rTMS80 decreased IHI, for both IHI directions. These changes were dependent on baseline IHI and hemisphere and were no longer significant when baseline IHI was accounted for. Intensity of subthreshold LF-rTMS has differential effects on excitation and inhibition of stimulated and non-stimulated M1. The effects were small and were only demonstrated within the LF-rTMS sessions but were not different when compared to sham. rTMS related changes in SICI and IHI were dependent on baseline level. NCT02544503, NCT01726218.

Different physical exercise in the treatment of Alzheimer's disease.

Alzheimer's disease (AD) is rapidly becoming one of the most expensive, burdening, and deadly diseases of this century. Up to now, there is still a lack of pharmacotherapy with substantial efficacy, and physical exercise is a promising and low-cost way to aid in delaying the process of AD. The aim of this review is to summarise the efficacy of different physical exercise approaches and doses in the management of AD, including aerobic exercise, resistance exercise and multicomponent exercise. A literature search using MeSH terms for each topic is undertaken using PubMed and the Web of Science Core Collection database, supplemented by hand searching for additional references. Retrieved articles were reviewed, synthesised, and summarised. This review shows that aerobic exercise has been almost unanimously recognised for the improvement of cognition, neuropsychiatric symptoms and activities of daily living. Resistance exercise also shows a good prospect in the above aspects and has a unique advantage in enhancing muscle strength, while multicomponent physical activity does not seen to significantly improve cognitive function. Each type of exercise has a dose effect, but for individuals with AD, the most appropriate exercise dose is still controversial.

Preliminary Insights into Sustainable Control of Solanum lycopersicum Early Blight: Harnessing Arbuscular Mycorrhizal Fungi and Reducing Fungicide Dose

Tomato (Solanum lycopersicum L.) production is constantly threatened by several fungal pathogens, such as Alternaria solani, the causal agent of early blight disease. In this study, a greenhouse experiment was set up to evaluate the biocontrol ability of arbuscular mycorrhizal fungi (AMF) against A. solani in the presence of reduced doses of fungicides (i.e., captan and copper oxychloride). Disease severity, plant growth traits, chlorophyll and phosphorus content, phenolic compounds, and antioxidant activity were assessed. The effects of fungicide dose on AMF were investigated by root colonization, spore density, and mycorrhizal dependence evaluation. AMF-inoculated and fungicide-treated plants reduced disease severity compared to fungicide-treated and non-mycorrhizal plants, in most cases, regardless of the fungicide dose. AMF improved plant growth, especially when combined with copper oxychloride. However, plant fresh weight decreased in plants treated with the lowest dose of captan (25 g 100 L−1). Overall, AMF colonization decreased in plants with high fungicide doses, while the leaf color parameters did not show differences between treatments. The results suggest reducing the fungicide dose using AMF is possible, particularly for copper oxychloride. Further studies will be required to confirm these data. This integrated approach could offer a sustainable alternative to decrease the use of chemical control.

Impact of fluoride and aluminum co-exposure on bone growth and quality in juvenile rats: dose and duration effects

This study aimed to investigate the impact of the dosage and duration of fluoride and aluminum(F and Al) co-exposure on the skeletal growth and bone quality of juvenile rats. Forty-eight 8-week-old Sprague-Dawley rats were randomly assigned to normal control, low F and Al exposure, and high F and Al exposure groups, with 45-day and 90-day subgroups established for each. We measured body length, tibia length, conducted bone histomorphometric analysis of the proximal tibia, performed micro-CT scans and three-point bending tests of the femur. Compared to the age-matched control group, the low F and Al group at 45 days exhibited increased bone formation and stiffness; the low F and Al group at 90 days and the high F and Al group at 45 days showed increases in body length, tibia length, growth plate width, longitudinal bone growth rate, bone turnover, and improved microstructure. Notably, bone elastic stress only elevated in the high F and Al group at 45 days. Conversely, the high F and Al exposure group at 90 days experienced decreases in the aforementioned parameters, with the exception of growth plate width, and displayed abnormal hypertrophic chondrocyte morphology in the growth plate. In summary, long-term exposure to low levels of F and Al and short-term exposure to high levels of F and Al promote bone formation followed by bone resorption in juvenile rats, stimulating bone growth and enhancing bone quality. However, long-term exposure to high levels F and Al results in low bone turnover, slow bone growth, and reduced bone property.