Effects Of Doses Research Articles

An antioxidant and anti-ER stress combination therapy elevates phosphorylation of α-Syn at serine 129 and alleviates post-TBI PD-like pathology in a sex-specific manner in mice

Clinical studies have shown that traumatic brain injury (TBI) increases the onset of Parkinson's disease (PD) in later life by >50%. Oxidative stress, endoplasmic reticulum (ER) stress, and inflammation are the major drivers of both TBI and PD pathologies. We presently evaluated if curtailing oxidative stress and ER stress concomitantly using a combination of apocynin and tert-butylhydroquinone and salubrinal during the acute stage after TBI in mice reduces the severity of late-onset PD-like pathology. The effect of multiple low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on post-TBI neurodegeneration was also evaluated. The combo therapy elevated the level of phosphorylation at serine 129 (pS129) of α-Syn in the pericontusional cortex of male mice at 72 h post-TBI. Motor and cognitive deficits induced by TBI lasted at least 3 months and the combo therapy curtailed these deficits in both sexes. At 3 months post-TBI, male mice given combo therapy exhibited significantly lesser α-Syn aggregates in the SN and higher TH+ cells in the SNpc, compared to vehicle control. However, the aggregate number was not significantly different between groups of female mice. Moreover, TBI-induced loss of TH+ cells was negligible in female mice irrespective of treatment. The MPTP treatment aggravated PD-like pathology in male mice but had a negligible effect on the loss of TH+ cells in female mice. Thus, the present study indicates that mitigation of TBI-induced oxidative stress and ER stress at the acute stage could potentially reduce the risk of post-TBI PD-like pathology at least in male mice, plausibly by elevating pS129-α-Syn level.

Effect of electron beam irradiation pretreatment and different fatty acid types on the formation, structural characteristics and functional properties of starch-lipid complexes

The effects of different electron beam irradiation doses (2, 4, 8 KGy) and various types of fatty acids (lauric acid, stearic acid, and oleic acid) on the formation, structure, physicochemical properties, and digestibility of starch-lipid complex were investigated. The complexing index of the complexes was higher than 85 %, indicating that the three fatty acids could easily form complexes with starch. With the increase of electron beam irradiation dose, the complexing index increased first and then decreased. The highest complexing index was lauric acid (97.12 %), stearic acid (96.80 %), and oleic acid (97.51 %) at 2 KGy radiation dose, respectively. Moreover, the microstructure, crystal structure, thermal stability, rheological properties, and starch solubility were analyzed. In vitro digestibility tests showed that adding fatty acids could reduce the content of hydrolyzed starch, among which the resistant starch content of the starch-oleic acid complex was the highest (54.26 %). The lower dose of electron beam irradiation could decrease the digestibility of starch and increase the content of resistant starch.

Effect of different gamma-ray doses on the structural, optical, and radiation shielding features of the YBa2Cu3Oy ceramic oxide

Effect of different gamma-ray doses on the structural, optical, and radiation shielding features of the YBa2Cu3Oy ceramic oxide

HMOs Impact the Gut Microbiome of Children and Adults Starting from Low Predicted Daily Doses.

Recent studies suggest that the dietary intake of human milk oligosaccharides (HMOs) provides health benefits from infancy up to adulthood. Thus far, beneficial changes in the adult gut microbiome have been observed at oral doses of 5-20 g/day of HMOs. Efficacy of lower doses has rarely been tested. We assessed four HMO molecular species-2'Fucosyllactose (2'FL), Lacto-N-neotetraose (LNnT), 3'Sialyllactose (3'SL), and 6'Sialyllactose (6'SL)-at predicted doses from 0.3 to 5 g/day for 6-year-old children and adults (n = 6 each), using ex vivo SIFR® technology (Cryptobiotix, Ghent, Belgium). This technology employing bioreactor fermentation on fecal samples enables us to investigate microbial fermentation products that are intractable in vivo given their rapid absorption/consumption in the human gut. We found that HMOs significantly increased short-chain fatty acids (SCFAs), acetate, propionate (in children/adults), and butyrate (in adults) from predicted doses of 0.3-0.5 g/day onwards, with stronger effects as dosing increased. The fermentation of 6'SL had the greatest effect on propionate, LNnT most strongly increased butyrate, and 2'FL and 3'SL most strongly increased acetate. An untargeted metabolomic analysis revealed that HMOs enhanced immune-related metabolites beyond SCFAs, such as aromatic lactic acids (indole-3-lactic acid/3-phenyllactic acid) and 2-hydroxyisocaproic acid, as well as gut-brain-axis-related metabolites (γ-aminobutyric acid/3-hydroxybutyric acid/acetylcholine) and vitamins. The effects of low doses of HMOs potentially originate from the highly specific stimulation of keystone species belonging to, for example, the Bifidobacteriaceae family, which had already significantly increased at doses of only 0.5 g/day LNnT (adults) and 1 g/day 2'FL (children/adults).

The Vasodilator Effect and Mechanism of 18β-glycyrrhetinic Acid on Isolated Pulmonary Artery Rings in Rats

Background: The purpose of this study was to evaluate the effect of 18β-glycyrrhetinic acid (18β-GA) on isolated rat pulmonary artery vascular rings as well as the mechanism that lies behind the diastolic effects of this compound. Methods: To examine the effects of various doses of 18β-GA on resting normal vascular rings, we used isolated rat pulmonary artery vascular rings. The isolated rat pulmonary artery vascular ring was precontracted with phenylephrine (PE) and potassium chloride solution (KCl), which allowed for the observation of the diastolic effects of 18β-GA, as well as the effects of various concentrations of 18β-GA on blocking the four potassium channels of glibenclamide, barium chloride (BaCl2), tetraethylamine (TEA), or 4-aminopyridine; the impact of various 18β-GA concentrations on the pulmonary artery vasodilation effect pre-use of the nitric oxide synthase inhibitors l-nitroarginine methyl ester and indomethacin. Results: It was shown that 18β-GA has concentration-dependent diastolic effects on isolated rat pulmonary vascular rings that have been precontracted with PE and KCl but it has no effect on resting isolated thoracic aortic vascular rings. Conclusion: The two Kir and Kv channels may be connected to the endothelium-dependent vasodilation mechanism of 18β-GA.

The effect of different doses of multi-nutrient fertilisers on macro-element content in two spring triticale cultivars

A field experiment was conducted in the years 2017–2019 at Borki-Wyrki, Zbuczyn Gmina (commune). Three experimental factors were examined in the trial: factor one was spring triticale cultivar (Milewo, Dublet), factor two was mineral fertiliser type (Polifoska 6, Polifoska Krzem) and factor three was mineral fertiliser rate (0, 140, 280 and 420 kg ha–1). Phosphorus, potassium, magnesium, calcium and sodium contents in grain varied in study years as affected by weather patterns. The highest phosphorus, magnesium and sodium contents were determined in the grain of spring triticale cv. Dublet whereas the highest potassium and calcium contents in cv. Milewo grain. The applied fertiliser rates increased mineral contents, excluding magnesium and sodium, in the grain of test cultivars. Chemical composition analysis of grain of the spring triticale cultivars demonstrated that there was no significant effect of fertiliser type on grain quality.

Effect of medroxyprogesterone acetate dose in progestin-primed ovarian stimulation on pregnancy outcomes in poor ovarian response patients with different body mass index levels.

For the poor ovarian response (POR) population, the relationship between medroxyprogesterone acetate (MPA) dose in progestin-primed ovarian stimulation (PPOS) and clinical outcome is still unclear. This study aims to explore the effect of MPA dose in PPOS on clinical outcomes in POSEIDON group 3 and 4 patients with different body mass index (BMI) levels, hoping to provide clinical doctors with better options for controlled ovarian hyperstimulation (COH) programs. This is a retrospective analysis of 253 oocyte retrieval cycles of POSEIDON group 3 and 4 patients who underwent PPOS protocol in IVF/ICSI treatment at the Reproductive Medical Center of Renmin Hospital of Wuhan University from March 2019 to April 2022. The effects of different MPA doses (8 mg/d or 10 mg/d) on pregnancy outcomes were compared in normal BMI (18.5-24 kg/m2) and high BMI (≥24 kg/m2) patients, and multivariate logistic regression analysis was performed to analyze the factors affecting pregnancy outcomes. For normal BMI patients, the 8-mg/d MPA group had a higher embryo implantation rate (33.78% vs. 18.97%, P = 0.012). For high BMI patients, the 10-mg/d MPA group had a higher HCG positive rate (55.00% vs. 25.00%, P = 0.028), clinical pregnancy rate (50.00% vs. 20.00%, P = 0.025), and cumulative pregnancy rate (37.74% vs. 13.79%, P = 0.023) compared with the 8-mg/d MPA group. There was no significant difference in cumulative live birth rate between the 8-mg/d and 10-mg/d MPA groups in patients with normal or high BMI. The results of multivariate logistic regression showed a significant correlation between MPA dose and cumulative pregnancy in the high BMI population (OR = 0.199, 95% CI: 0.046~0.861, P = 0.031). For POR patients with high BMI, 10 mg/d of MPA in the PPOS protocol had a higher cumulative pregnancy rate than 8 mg/d of MPA, but it had no significant effect on the cumulative live birth rate.

Soil Organic Matter and Microbial Biomass Under Cultivation of Urochloa Brizantha Fertilized with Wood Ash in the Cerrado of Mato Grosso

ABSTRACT The use of waste such as wood ash as an alternative fertilizer in agricultural production can result in an improvement in the chemical and biological characteristics of the soil. The objective of this research was to evaluate the effect of doses and management of wood ash application in the organic matter content and biological attributes of the soil in a Cerrado area cultivated with Urochloa brizantha cv BRS paiaguás. The experiment was performed in randomized blocks, in a 5 × 2 striped scheme, with five doses of wood ash (0, 8, 16, 24 and 32 t ha−1) and two application managements (with and without incorporation to the soil) with four repetitions. The variables analyzed were: soil organic matter content, microbial biomass carbon, basal respiration, qCO2 and β-glucosidase activity. During the evaluations it was observed a reduction of 0.36 g kg−1 of organic matter for each ton of ash applied to the soil, regardless of management. This reduction also occurred in microbial biomass carbon and β-glucosidase activity. initially the ash doses elevated the soil respiration and the metabolic quotient, evidencing a small stress in the soil microbiota, however, in the last evaluation the rates of these two variables remained stable. The application of wood ash, in doses ranging from 16 to 24 t ha−1, can be used as soil conditioner and fertilizer in pastures, because it results in better conditions for the soil.

Treating moderate-to-severe menopausal vasomotor symptoms with fezolinetant: analysis of responders using pooled data from two phase 3 studies (SKYLIGHT 1 and 2).

The aims of the study were to further characterize the efficacy of fezolinetant for the treatment of moderate-to-severe vasomotor symptoms (VMS) due to menopause using responder analysis and to investigate whether efficacy, not adjusted for placebo, resulted in clinically meaningful within-patient change. This prespecified analysis used pooled data from two phase 3, randomized, double-blind, placebo-controlled studies (SKYLIGHT 1 and 2). Responders were those experiencing ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. Responder analysis was performed for patient-reported outcome (PRO) measures to evaluate participants achieving a clinically meaningful within-patient change (not placebo adjusted) at week 4 and 12 versus baseline. Single responders were based on outcomes of VMS frequency, Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b Total Score, Menopause-Specific Quality of Life (MENQoL) Total Score, and MENQoL VMS Domain Score. Double and triple responder analyses combined VMS frequency plus one or more of the PRO. Patient Global Impression of Change VMS was deemed a suitable anchor measure for meaningful within-patient change in VMS frequency. A greater proportion of fezolinetant-treated versus placebo-treated participants had ≥50%, ≥75%, ≥90%, or 100% reduction in VMS frequency from baseline to weeks 4 and 12. A greater proportion of responders were observed in the fezolinetant groups versus placebo at week 12 in all four single responder analyses. In the double and triple responder analyses, odds ratios were supportive of a beneficial effect for both doses of fezolinetant versus placebo. Fezolinetant was associated with significantly higher within-patient clinically meaningful improvement in important PRO, including VMS frequency, PROMIS SD SF 8b Total Score, MENQoL Total Score, and MENQoL VMS Domain Score.

Anti-tumor effect of high doses of carbon ions and x-rays during irradiation of Ehrlich ascites carcinoma cells ex vivo

The effect of carbon ions (12C) with the energy of 400 MeV/nucleon on the dynamics of induction and growth rate of solid tumors in mice under irradiation of Ehrlich’s ascites carcinoma cells (EAC) ex vivo at doses of 5–30 Gy relative to the action of equally effective doses of X-ray radiation was studied. The dynamics of tumor induction under the action of 12C and X-rays had a similar character and depended on the dose during 3 months of observation. The value of the latent period, both when irradiating cells with 12C and X-ray, increased with increasing dose, and the interval for tumor induction decreased. The rate of tumor growth after ex vivo irradiation of EAC cells was independent of either dose or type of radiation. The dose at which EAC tumors are not induced within 90 days was 30 Gy for carbon ions and 60 Gy for X-rays. The value of the relative biological effectiveness of carbon ions, calculated from an equally effective dose of 50% probability of tumors, was 2.59.

Repair effect of different doses of human umbilical cord mesenchymal stem cells on white matter injury in neonatal rats

To compare the repair effects of different doses of human umbilical cord mesenchymal stem cells (hUC-MSCs) on white matter injury (WMI) in neonatal rats. Two-day-old Sprague-Dawley neonatal rats were randomly divided into five groups: sham operation group, WMI group, and hUC-MSCs groups (low dose, medium dose, and high dose), with 24 rats in each group. Twenty-four hours after successful establishment of the neonatal rat white matter injury model, the WMI group was injected with sterile PBS via the lateral ventricle, while the hUC-MSCs groups received injections of hUC-MSCs at different doses. At 14 and 21 days post-modeling, hematoxylin and eosin staining was used to observe pathological changes in the tissues around the lateral ventricles. Real-time quantitative polymerase chain reaction was used to detect the quantitative expression of myelin basic protein (MBP) and glial fibrillary acidic protein (GFAP) mRNA in the brain tissue. Immunohistochemistry was employed to observe the expression levels of GFAP and neuron-specific nuclear protein (NeuN) in the tissues around the lateral ventricles. TUNEL staining was used to observe cell apoptosis in the tissues around the lateral ventricles. At 21 days post-modeling, the Morris water maze test was used to observe the spatial learning and memory capabilities of the neonatal rats. At 14 and 21 days post-modeling, numerous cells with nuclear shrinkage and rupture, as well as disordered arrangement of nerve fibers, were observed in the tissues around the lateral ventricles of the WMI group and the low dose group. Compared with the WMI group, the medium and high dose groups showed alleviated pathological changes; the arrangement of nerve fibers in the medium dose group was relatively more orderly compared with the high dose group. Compared with the WMI group, there was no significant difference in the expression levels of MBP and GFAP mRNA in the low dose group (P>0.05), while the expression levels of MBP mRNA increased and GFAP mRNA decreased in the medium and high dose groups. The expression level of MBP mRNA in the medium dose group was higher than that in the high dose group, and the expression level of GFAP mRNA in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the protein expression of GFAP and NeuN in the low dose group (P>0.05), while the expression of NeuN protein increased and GFAP protein decreased in the medium and high dose groups. The expression of NeuN protein in the medium dose group was higher than that in the high dose group, and the expression of GFAP protein in the medium dose group was lower than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the number of apoptotic cells in the low dose group (P>0.05), while the number of apoptotic cells in the medium and high dose groups was less than that in the WMI group, and the number of apoptotic cells in the medium dose group was less than that in the high dose group (P<0.05). Compared with the WMI group, there was no significant difference in the escape latency time in the low dose group (P>0.05); starting from the third day of the latency period, the escape latency time in the medium dose group was less than that in the WMI group (P<0.05). The medium and high dose groups crossed the platform more times than the WMI group (P<0.05). Low dose hUC-MSCs may yield unsatisfactory repair effects on WMI in neonatal rats, while medium and high doses of hUC-MSCs have significant repair effects, with the medium dose demonstrating superior efficacy.

Analysis of X-ray irradiation effects on the mortality values and hemolymph immune cell composition of Apis mellifera and its parasite, Varroa destructor

Varroa destructor is one of the most destructive enemies of the honey bee, Apis mellifera all around the world. Several control methods are known to control V. destructor, but the efficacy of several alternative control methods remains unexplored. Irradiation can be one of these unknown solutions but before practical application, the effectiveness, and the physiological effects of ionizing radiation on the host and the parasite are waiting to be tested. Therefore, the objective of our study was to investigate the effects of different doses (15, 50, 100, and 150 Gy) of high-energy X-ray irradiation through mortality rates and hemocyte composition changes in A. mellifera workers and record the mortality rates of the parasite. The mortality rate was recorded during short-term (12, 24, and 48 h) and long-term periods (3, 6, 12, 18, and 24d).The sensitivity of the host and the parasite in case of the higher doses of radiation tested (50, 100, and 150 Gy) been demonstrated by total mortality of the host and 90 % of its parasite has been observed on the 18th day after the irradiation. V. destructor showed higher sensitivity (1.52-times higher than the adult honey bee workers) at the lowest dose (15 Gy). A. mellifera hemocytes were influenced significantly by radiation dosage and the elapsed time after treatment. The higher radiation doses increased plasmatocyte numbers in parallel with the decrease in prohemocyte numbers. On the contrary, the numbers of granulocytes and oencoytes increased in the treated samples, but the putative effects of the different dosages on the recorded number of these hemocyte types could not be statistically proven. In summary, based on the outcome of our study X-ray irradiation can be deemed an effective tool for controlling phoretic V. destructor. However, further research is needed to understand the physiological response of the affected organisms.

Effects of intermittent overload doses of oral vitamin D3 on serum 25(OH)D concentrations and the incidence rates of fractures, falls, and mortality in elderly individuals: A systematic review and meta-analysis.

Vitamin D is commonly used to prevent and treat osteoporosis, with studies indicating its potential to reduce fractures, falls, and mortality. However, meta-analyses present inconsistent findings regarding its efficacy, particularly reflecting significant variability in data and outcomes related to various dosing regimens. In this meta-analysis, we assessed the impact of high-dose intermittent oral administration of vitamin D3 on serum 25(OH)D levels, fractures, falls, and mortality among elderly individuals. We included 14 randomized controlled trials (RCTs) and employed Review Manager 5.4 for statistical analysis. Our findings indicate that intermittent monthly administration of vitamin D3 (over 800 IU per day) significantly raised serum 25(OH)D levels at all timepoints after six months, maintaining levels above 75 nmol/L throughout the year. This regimen showed no increase in all-cause mortality, with a risk ratio (95% CI) of 0.95 (0.87-1.04). Likewise, it did not significantly reduce the risks of falls and fractures, with risk ratios of 1.02 (0.98-1.05) and 0.95 (0.87-1.04) respectively. Although one-year intermittent administration significantly increased the concentration of 25(OH)D in serum, further research is needed to determine if this method would increase the incidence of falls. Therefore, it is not recommended at this stage due to the lack of demonstrated safety in additional relevant RCTs. This study had been registered at PROSPERO (CRD42022363229).

Effect of different doses of camelina cake inclusion as a substitute of dietary soyabean meal on growth performance and gut health of weaned pigs.

Camelina cake (CAM) is a co-product proposed as an alternative protein source; however, piglet data are still limited. This study aimed to evaluate the effect of different doses of CAM in substitution of soyabean meal on the growth, health and gut health of weaned pigs. At 14 d post-weaning (d0), sixty-four piglets were assigned either to a standard diet or to a diet with 4 %, 8 % or 12 % of CAM. Piglets were weighed weekly. At d7 and d28, faeces were collected for microbiota and polyamine and blood for reactive oxygen metabolites (ROM) and thyroxine analysis. At d28, pigs were slaughtered, organs were weighed, pH was recorded on gut, colon was analysed for volatile fatty acids (VFA) and jejunum was used for morphological and gene expression analysis. Data analysis was carried out using a mixed model including diet, pen and litter as factors; linear and quadratic contrasts were tested. CAM linearly reduced the average daily gain from d0-d7, d0-d14, d0-d21 and d0-d28 (P ≤ 0·01). From d0-d7 increasing CAM linearly decreased feed intake (P = 0·04) and increased linearly the feed to gain (P = 0·004). CAM increased linearly the liver weight (P < 0·0001) and affected the cadaverine (P < 0·001). The diet did not affect the ROM, thyroxine, intestinal pH, VFA and morphology. All doses of CAM increased the α diversity indices at d28 (P < 0·05). CAM at 4 % promoted the abundance of Butyricicoccaceae_UCG-008. Feeding with CAM enhanced resilience in the gut microbiome and can be evaluated as a potential alternative protein source with dose-dependent limitations on piglet growth performance.

Effects of Mild Closed-Head Injury and Subanesthetic Ketamine Infusion on Microglia, Axonal Injury, and Synaptic Density in Sprague-Dawley Rats.

Mild traumatic brain injury (mTBI) affects millions of people in the U.S. Approximately 20-30% of those individuals develop adverse symptoms lasting at least 3 months. In a rat mTBI study, the closed-head impact model of engineered rotational acceleration (CHIMERA) produced significant axonal injury in the optic tract (OT), indicating white-matter damage. Because retinal ganglion cells project to the lateral geniculate nucleus (LGN) in the thalamus through the OT, we hypothesized that synaptic density may be reduced in the LGN of rats following CHIMERA injury. A modified SEQUIN (synaptic evaluation and quantification by imaging nanostructure) method, combined with immunofluorescent double-labeling of pre-synaptic (synapsin) and post-synaptic (PSD-95) markers, was used to quantify synaptic density in the LGN. Microglial activation at the CHIMERA injury site was determined using Iba-1 immunohistochemistry. Additionally, the effects of ketamine, a potential neuroprotective drug, were evaluated in CHIMERA-induced mTBI. A single-session repetitive (ssr-) CHIMERA (3 impacts, 1.5 joule/impact) produced mild effects on microglial activation at the injury site, which was significantly enhanced by post-injury intravenous ketamine (10 mg/kg) infusion. However, ssr-CHIMERA did not alter synaptic density in the LGN, although ketamine produced a trend of reduction in synaptic density at post-injury day 4. Further research is necessary to characterize the effects of ssr-CHIMERA and subanesthetic doses of intravenous ketamine on different brain regions and multiple time points post-injury. The current study demonstrates the utility of the ssr-CHIMERA as a rodent model of mTBI, which researchers can use to identify biological mechanisms of mTBI and to develop improved treatment strategies for individuals suffering from head trauma.

Determination of the Effects of Different Irrigation Levels and Vermicompost Doses on Water Consumption and Yield of Greenhouse-Grown Tomato

This study was conducted in pots under a polycarbonate greenhouse to determine the effects of different irrigation levels and vermicompost doses on the morphological and phenological characteristics, water consumption, water use efficiency, and yield parameters of tomato plants. For this purpose, different irrigation levels of 100%, 75%, 50% (I100: full irrigation, I75, I50) and vermicompost (VC) doses of 0, 10% and 20% (VC0, VC10 and VC20, w/w) were applied as the treatments. The study’s results determined the irrigation levels and vermicompost doses affected the tomato plants’ morphological and fruit quality parameters. The highest and lowest plant water consumption (ET) values for the treatments were determined as 47.8 L (I100VC10) and 21.2 L (I50VC0), respectively. Moreover, irrigation water levels and vermicompost doses significantly influenced the total yield of tomatoes. The highest and lowest total and marketable yields were obtained from the I100VC20 and I50VC0 irrigation levels and vermicompost doses. Similarly, the highest and lowest total water use efficiencies were achieved from the I100VC20 (21.9 g L−1) and I50VC0 (11.0 g L−1) treatments. Furthermore, the highest and lowest marketable water use efficiencies were obtained from the I100VC20 (21.9 g L−1) and I50VC0 (7.8 g L−1) treatments. The yield response factor (ky) was found to be 1.42. Although the highest efficiency was achieved from 100% full irrigation and a 20% vermicompost dose in the study, it is suggested that 75% irrigation level and 10% fertilizer doses can also be applied in places where water is limited and fertilizer is expensive. The results revealed that the appropriate irrigation level and vermicompost doses could reliably be used to enhance tomato yield.

Acute Adverse Effects of Therapeutic Doses of Psilocybin

Psilocybin has been studied in the treatment of depression and anxiety disorders. Clinical studies have mainly focused on efficacy, with systematic reviews showing favorable efficacy; however, none have primarily focused on psilocybin safety. To evaluate the acute adverse effects of psilocybin at therapeutic doses in the treatment of depression and anxiety. MEDLINE via PubMed, Web of Science, and ClinicalTrials.gov were searched for publications available between 1966 and November 30, 2023. Randomized, double-blind clinical trials that reported adverse effects of psilocybin in patients treated for depression and anxiety were screened. Data were independently extracted by 2 authors and verified by 2 additional authors following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guideline. The inverse variance method with the Hartung-Knapp adjustment for the random-effects model was used, with a continuity correction of 0.5 for studies with 0 cell frequencies. Sensitivity analysis was conducted by sequentially removing 1 study at a time to assess the robustness of the results. The primary outcome was considered as the adverse effects of psilocybin at high and moderate (ie, therapeutic) dose regimens and compared with placebo, low-dose psilocybin, or other comparator in the treatment of depression and/or anxiety. Six studies met the inclusion criteria with a total sample of 528 participants (approximately 51% female; median age 39.8 years; IQR, 39.8-41.2). Seven adverse effects were reported in multiple studies and included in the analysis. Among these, headache (relative risk [RR], 1.99; 95% CI 1.06-3.74), nausea (RR, 8.85; 95% CI, 5.68-13.79), anxiety (RR, 2.27; 95% CI, 1.11-4.64), dizziness (RR, 5.81; 95% CI, 1.02-33.03), and elevated blood pressure (RR, 2.29; 95% CI, 1.15- 4.53) were statistically significant. Psilocybin use was not associated with risk of paranoia and transient thought disorder. In this meta-analysis, the acute adverse effect profile of therapeutic single-dose psilocybin appeared to be tolerable and resolved within 48 hours. However, future studies need to more actively evaluate the appropriate management of adverse effects.

Gamma irradiated Cu-doped TiO2 nanoparticles for selective ammonia sensing

In this research, the effect of gamma ray doses on volatile organic compound (VOC) sensing properties of Cu doped TiO2 nanoparticles are studied to further improve the VOC sensing performance. Pure and Cu doped TiO2 nanoparticles have been prepared by sol-gel technique on Au interdigitated plexiglas substrate and irradiated by gamma-rays with doses varying from 1 to 150 KGy. The irradiation was performed by using 60Co as gamma source. The structural, morphology and modifications were analyzed with X-ray diffraction (XRD), scanning electron microscopy (SEM), and Atomic Force Microscopy (AFM) techniques. The sensing performance of these films toward ethanol, methanol, 2-propanol, benzene, toluene, xylene and ammonia vapors has been tested. It was observed that no remarkable sensor response to any vapors except ammonia was observed at room temperature. Changes in sensor’ ammonia sensitivity have been correlated with the gamma radiation dose and Cu doping ratio. Maximum sensing performance was observed with 3% Cu doped TiO2 exposed to gamma radiation dose of 150 kGy.

Use of kersetin and fisetin flavonoids in combination with pregabalin and gabapentin in the treatment of neuropathic pain.

We purposed to explore the consequences of the use quercetin and fisetin alone and in combination with pregabalin and gabapentin, which are used in the management of neuropathic pain, and on neuropathic pain in general. The anti-allodynic effect of various doses (5, 10, and 20 mg/kg) of quercetin and fisetin, both singly and in combination with pregabalin and gabapentin, was evaluated by developing a neuropathic pain model induced by chronic constrictive nerve damage in rats. The effectiveness of these flavonoids was investigated by combining them with gabapentin (50 mg/kg) and pregabalin (15 mg/kg), choosing the effectual dose of 10 mg/kg and the dose of 5 mg/kg, which did not show significant antiallodynic effects. In groups combined with gabapentin and pregabalin, it was determined that they showed a significant antiallodynic effect compared with 50 mg/kg gabapentin and 15 mg/kg pregabalin. In conclusion, in our combination studies, it was observed that the effectiveness of gabapentin and pregabalin, was increased and the duration of effect was prolonged when used with lower doses of flavonoids. Based on these findings; it is possible to say that quercetin and fisetin are potential agents that can be used alone or in combination with other effective treatments to alleviate neuropathic pain.

What are the effects of different doses of pravastatin for lowering lipids?

What are the effects of different doses of pravastatin for lowering lipids?