Effects Of Different Doses Research Articles

The causal impact of maternal smoking around birth on offspring ADHD: A two-sample Mendelian randomization study

BackgroundThe previous literature highlights a relationship between maternal smoking around birth (MSAB) and offspring attention-deficit/hyperactivity disorder (ADHD). These studies have focused on the causal effects of MSAB on offspring ADHD. MethodA Mendelian randomization analysis was conducted using summary statistics. Data on MSAB were obtained from a recent study including 391,992 participants. ADHD data were obtained from six sources for 246,888 participants. The present study used five methods to examine the causal impact from outcomes on exposures. The inverse variance weighted (IVW) was the main method of analysis, while the other four methods were supplementary methods. ResultThe IVW revealed that MSAB was a risk factor for offspring ADHD (OR: 2.54; 95 % confidence interval [CI]: 1.61–4.00, p = 6.04 × 10−5). Concerning ADHD in both sexes, MSAB was associated with females (OR = 3.96, 95 % CI: 1.99–7.90, p = 8.98 × 10−5) and males (OR = 3.74, 95 % CI: 1.74–5.72, p = 1.48 × 10−4). In different diagnosis periods for ADHD, MSAB increased the risk of childhood (OR = 3.63, 95 % CI: 2.25–5.87, p = 1.31 × 10−7), late-diagnosed (OR = 2.99, 95 % CI: 1.74–5.14, p = 7.33 × 10−5), and persistent (OR = 4.77, 95 % CI: 1.88–12.14, p = 1.03 × 10−3) ADHD. The final analysis did not reveal heterogeneity. ConclusionsA causal impact of MSAB on offspring ADHD was observed. These findings highlight the need for careful consideration of prenatal exposure (MSAB) during the assessment of offspring ADHD. Additionally, it can provide targeted guidance for prenatal interventions. Future studies should analyze the effects of different doses of maternal smoking on ADHD.

Effect of different doses of Bisphenol A on albino rats' liver: Histological and immunohistochemical study

Effect of different doses of Bisphenol A on albino rats' liver: Histological and immunohistochemical study

Reactive oxygen species may be involved in the distinctive biological effects of different doses of 12C6+ ion beams on Arabidopsis.

Heavy ion beam is a novel approach for crop mutagenesis with the advantage of high energy transfer line density and low repair effect after injury, however, little investigation on the biological effect on plant was performed. 50 Gy irradiation significantly stimulated the growth of Arabidopsis seedlings, as indicated by an increase in root and biomass, while 200 Gy irradiation significantly inhibited the growth of seedlings, causing a visible decrease in plant growth. The Arabidopsis seeds were irradiated by 12C6+. Monte Carlo simulations were used to calculate the damage to seeds and particle trajectories by ion implantation. The seed epidermis received SEM detection and changes in its organic composition were detected using FTIR. Evidence of ROS and antioxidant systems were analyzed. RNA-seq and qPCR were used to detect changes in seedling transcript levels. Monte Carlo simulations revealed that high-dose irradiation causes various damage. Evidence of ROS and antioxidant systems implies that the emergence of phenotypes in plant cells may be associated with oxidative stress. Transcriptomic analysis of the seedlings demonstrated that 170 DEGs were present in the 50 Gy and 200 Gy groups and GO enrichment indicated that they were mainly associated with stress resistance and cell wall homeostasis. Further GO enrichment of DEGs unique to 50 Gy and 200 Gy revealed 58 50Gy-exclusive DEGs were enriched in response to oxidative stress and jasmonic acid entries, while 435 200 Gy-exclusive DEGs were enriched in relation to oxidative stress, organic cyclic compounds, and salicylic acid. This investigation advances our insight into the biological effects of heavy ion irradiation and the underlying mechanisms.

Effect of Different Dose of Chlormequat on Growth and Yield of Okra (Abelmoschus esculentus L.)

A field trial was conducted during Kharif season 2022-23 at the sharadhey Bhagwati singh research farm of Chandra Bhanu Gupta Agriculture P. G. College, B. K. T. Lucknow to find out the “Effect of different dose of chlormequat on growth and yield of okra (Abelmoschus esculentus L.)” .The experiment consisted of 6 treatments concentration of chlormequat (water spray, 250, 500, 750, 1000 and 1250 ppm) replicated three times. Results revealed that growth parameter like days to reproductive phase, number of leaf per plant, number of branches per plant and yield attributes i.e. fruit length, fruit girth, number of fruit per plant, and yield per plant was significantly highest with chlormequat spray T6 (@1250ppm) as compared to rest of the treatment. However, the plant height and days to first floral initiation was significantly reduced with increasing dose of chlormequat and being highest with control. The highest fruit yield (110.22q/ha) was recorded in T6 treatment, which was at par with T5 (102.22 q/ha). whereas the lowest fruit yield hectare was recorded in T1 i.e. control (53.76 q /ha) . The percent increase in yield due to chlormequat @ 1250 ppm was recorded to the tune of 7.78, 27.02, 47.90, 74.37 and 105.02 over dose of 1000 ppm, 750 ppm, 500 ppm, 250 ppm and no chloremequet spray treatments, respectively.

Standardization of pre-sowing seed treatment with selected botanicals on growth, yield and yield attributing traits of linseed (Linum usitatissimum L.)

The present study was aimed to determine the effect of different doses and duration of pongamia, tulsi, moringa and neem leaf extract on growth, yield and yield attributing traits of linseed (cv. GP-I-44). A field study was conducted during rabi 2022-2023 at the field experimentation centre of Department of Genetics and Plant breeding, Sam Higginbottom University of Agriculture Technology and Sciences, Prayagraj. The study was carried out in a Randomized Block Design with 13 treatment combinations in three replications to assess the effect of seed priming with botanicals on linseed seeds under various levels of pongamia leaf extract, tulsi leaf extract, moringa leaf extract and neem leaf extract. The highest recorded yield attributes were observed in T3, where pongamia leaf extract at a concentration of 10% resulted in 114.33 capsules/plant, 8.77 seeds/capsule, 4.5 g/plant, 73.37 g/plot, and 733 kg/ha, with a 1000-seed weight of 8.15 g. Conversely, the lowest values were recorded in T7, with moringa leaf extract at 3% resulting in 105.00 capsules/plant, 7.67 seeds/capsule, 2.4 g/plant, 67.13 g/plot, and 671 kg/ha, with a 1000-seed weight of 7.15 g. Thus, the application of pongamia leaf extract at 10% concentration (T3) emerged as the most effective dosage for priming linseed.

Effect of two different doses of nalbuphine for postoperative analgesia in children with cleft palate: a randomized controlled trial

BackgroundCleft palate repair surgery may result in severe pain in the immediate postoperative period. The aim of this study is to compare the effects of different doses of nalbuphine for postoperative analgesia in children with cleft palate.MethodsFrom November 2019 to June 2021, 90 children (45 males and 45 females, age 9–20 months old, ASA class I—II) were selected for palatoplasty. They were randomly divided into three groups: the control group (Group C), the N1 group (postoperative analgesia with 0.05 mg/kg/h nalbuphine) and the N2 group (postoperative analgesia with 0.075 mg/kg/h nalbuphine). Each group had 30 cases. Nalbuphine was not continuously infused in Group C but was continuously infused in Groups N1 and N2 at rates of 0.05 mg/kg/h and 0.075 mg/kg/h, respectively, for 24 h for postoperative analgesia. The FLACC analgesia score and Ramsay Sedation score were recorded at 10 min (T1), 30 min (T2), 2 h (T3), 12 h (T4) and 24 h (T5) after the operation. Adverse reactions such as nausea, vomiting and respiratory depression were observed and recorded.ResultsCompared with those in Group C, the FLACC scores in the N1 and N2 groups decreased significantly at T1-T5 (p < 0.05); the Ramsay Sedation score in the N1 group was significantly higher at T3 and T4 (p < 0.05), and that in the N2 group was significantly higher at T1-T5 (p < 0.05). Compared with that in the N1 group, the FLACC score in the N2 group was not significantly different, and the Ramsay Sedation score increased significantly at T5 (p < 0.05).ConclusionUsing 0.05 mg/kg/h Nalbuphine continuously for 24 h for postoperative analgesia in children with cleft palate has a better effect and fewer adverse reactions.Trial registrationThis study was registered at ChiCTR1900027385 (11/11/2019).

Effects of Aminomethylphosphonic Acid on the Transcriptome and Metabolome of Red Swamp Crayfish, Procambarus clarkii.

Red swamp crayfish, Procambarus clarkii (P. clarkii), is an important model crustacean organism used in many types of research. However, the effects of different doses of aminomethylphosphonic acid (AMAP) on the transcriptome and metabolites of P. clarkii have not been explored. Thus, this study investigated the molecular and metabolic mechanisms activated at the different exposure dosages of AMAP in P. clarkii to provide new insights into the strategies of P. clarkii in response to the high concentrations of AMAP in the environment. In the present study, the P. clarkii were divided into three groups (control group; low-dosage AMAP exposure; high-dosage AMAP exposure), and hepatopancreatic tissue samples were dependently taken from the three groups. The response mechanisms at the different dosages of AMAP were investigated based on the transcriptome and metabolome data of P. clarkii. Differentially expressed genes and differentially abundant metabolites were identified in the distinct AMAP dosage exposure groups. The genes related to ribosome cell components were significantly up-regulated, suggesting that ribosomes play an essential role in responding to AMAP stress. The metabolite taurine, involved in the taurine and hypotaurine metabolism pathway, was significantly down-regulated. P. clarkii may provide feedback to counteract different dosages of AMAP via the upregulation of ribosome-related genes and multiple metabolic pathways. These key genes and metabolites play an important role in the response to AMAP stress to better prepare for survival in high AMAP concentrations.

The effects of different doses of lanthanum-modified bentonite in combination with a submerged macrophyte (Vallisneria denseserrulata) on phosphorus inactivation and macrophyte growth: A mesocosm study

The combination of chemical phosphorus (P) inactivation and submerged macrophyte transplantation has been widely used in lake restoration as it yields stronger effects than when applying either method alone. However, the dose effect of chemical materials on P inactivation when used in combination with submerged macrophytes and the influences of the chemicals used on the submerged macrophytes growth remain largely unknown. In this study, we investigated P inactivation in both the water column and the sediment, and the responses of submerged macrophytes to Lanthanum modified bentonite (LMB) in an outdoor mesocosm experiment where Vallisneria denseserrulata were transplanted into all mesocosms and LMB was added at four dosage levels, respectively: control (LMB-free), low dosage (570 g m−2), middle dosage (1140 g m−2), and high dosage (2280 g m−2). The results showed that the combination of LMB dosage and V. denseserrulata reduced TP in the water column by 32%–38% compared to V. denseserrulata alone, while no significant difference was observed among the three LMB treatments. Porewater soluble reactive P, two-dimensional diffusive gradient in thin films (DGT)-labile P concentrations, and P transformation in the 0–1 cm sediment layer exhibited similar trends along the LMB dosage gradient. Besides, LMB inhibited plant growth and reduced the uptake of mineral elements (i.e., calcium, manganese, iron, and magnesium) in a dosage-dependent manner with LMB. LMB may reduce plant growth by creating a P deficiency risk for new ramets and by interfering with the uptake of mineral elements. Considering both the dose effect of LMB on P inactivation and negative effect on macrophyte growth, we suggest a “small dosage, frequent application” method for LMB application to be used in lake restoration aiming to recover submerged macrophytes and clear water conditions.

Fe/BC co-conditioners with environmental and economic benefits on composting: reduced NH3 emissions and improved fertilizer quality

The significant volatilization of NH3 during aerobic composting causes nitrogen (N) losses and environmental risks. Both iron (Fe) and biochar (BC) can influence the N conversion process in composting. Fe application can delay the maturation of materials, while biochar can enhance the quality of organic fertilizer. The combination of these two conditioners may help decrease NH3 emissions and improve organic fertilizer quality. Therefore, this study investigates the effects of different doses of FeCl3 and BC on NH3 emissions and organic fertilizer quality during composting. The results demonstrated that Fe/BC co-conditioners reduced the accumulation of NH3 emissions during composting by 11.1–48.2%, increased the total nutrient content by 0.6–15.3%, and enhanced economic and environmental benefits by 0.1–23.6 $ t−1. At the high-temperature stage of composting, Fe/BC co-conditioners decreased the pH by 0.3–1.2, but there was no significant difference compared to the control at the end of composting, and they did not affect compost maturation. The structural equation model analysis suggested that the reduction in NH3 emissions was related to ammonia-oxidizing bacteria (AOB), NH4+–N, and total nitrogen (TN). As a result, the Fe/BC co-conditioners reduced NH3 emissions by lowering the pH at the beginning of composting and increasing the content of NH4+–N. This study concludes that Fe/BC co-conditioners could complement each other to significantly reduce NH3 emissions and improve the quality of organic fertilizers.Graphical

Investigation on the compressive strength and durability properties of alkali-activated slag mortar: Effect of superabsorbent polymer dosage and water content

This paper presents the properties of alkali-activated slag (AAS) mortar additivated with a superabsorbent polymer (SAP) to improve its mechanical and durability properties. The effect of different dosages of SAP (0.0–0.3% with respect to the blast furnace slag weight) and different extra water additions on setting time, autogenous shrinkage, compressive strength, water permeability, frost resistance, heat of hydration, and porosity is presented and discussed. The results highlight the beneficial effect of adding SAP on the mechanical and durability properties of the proposed mixtures. Only at higher percentages of SAP and additional water occur performance drops due to excessive macro-porosity of the system. It is interesting to point out that, in contrast, shrinkage always decreases as the percentages of SAP addition and additional water increase, although it cannot be completely eliminated. Experimental evidence also highlights that significant benefits can be gained from using this material in harsh environments.

Study of oxygen in wines with different proportions of yeast lees

The lees produced during fermentation are known for their ability to consume oxygen. During wine aging, it has a positive effect on the antioxidant and sensory properties of wine. This study focuses on the effects of different doses of fermentation lees on the oxygen consumption and antioxidant activity of wine, which are important for the quality of the final product as well as consumer. The effect on oxygen consumption after bottling, antioxidant activity and phenolic composition was studied for wines of the variety Grüner Veltliner with different proportions of yeast lees. The rate of dissolved oxygen consumption increased with increasing dosages of fermentation lees. The first significant decrease was observed as early as the second day after bottling for all variants above 20 g of fermentation lees in 0.75 L of wine. Total polyphenol content and antioxidant activity also increased with the dose of yeast lees. The major negative parameter for the highest addition of lees was the concentration of volatile acids, which increased from a baseline value of 0.34 g L–1 to 0.45 g L–1.

Zearalenone triggers programmed cell death and impairs milk fat synthesis via the AKT-mTOR-PPARγ-ACSL4 pathway in bovine mammary epithelial cells.

Zearalenone (ZEN), a mycotoxin from Fusarium fungi, impairs fertility and milk production in female animals; however, the mechanisms remain poorly understood. Using the bovine mammary epithelial cells (MAC-T) as the model, this study investigated the impacts of ZEN on programmed cell death (PCD) and milk fat synthesis and explored the underlying mechanism. We found that 10ng/mL prolactin (PRL) notably enhanced the differentiation of MAC-T cells, promoting the expression of genes related to the synthesis of milk fat, protein, and lactose. Next, the toxic effects of different doses of ZEN on the differentiated MAC-T with PRL treatment were determined. 10 and 20 μM ZEN significantly reduced cell viability, induced oxidative stress, and triggered PCD (e.g., apoptosis and necrosis). Notably, ZEN exposure downregulated the mRNA/protein levels of critical factors involved in milk fat synthesis by disrupting the AKT-mTOR-PPARγ-ACSL4 pathway. Interestingly, melatonin (MT), known for its antioxidant properties, protected against the above ZEN-induced effects by enhancing the binding of PPARγ to the promoter regions of ACSL4, which led to the upregulated expression of the ACSL4 gene. These results underscored the potential of MT to mitigate the adverse effects of ZEN on mammary cells, highlighting a way for potential therapeutic intervention.

Different Doses of Dexmedetomidine Reduce Postoperative Sleep Disturbance Incidence in Patients under General Anesthesia by Elevating Serum Neurotransmitter Levels.

Postoperative sleep disturbance is a common issue that affects recovery in patients undergoing general anesthesia. Dexmedetomidine (Dex) has a potential role in improving postoperative sleep quality. We evaluated the effects of different doses of Dex on postoperative sleep disturbance and serum neurotransmitters in patients undergoing radical gastrectomy under general anesthesia. Patients were assigned to the control, NS, and Dex (Dex-L/M/H) groups based on different treatment doses [0.2, 0.4, and 0.6 μg/(kg · h)]. The Athens Insomnia Scale (AIS) and ELISA kits were used to assess sleep disturbance and serum neurotransmitter (GABA, 5-HT, NE) levels before surgery and on postoperative days one, four, and seven. The effects of different doses on postoperative sleep disturbance incidence and serum neurotransmitter levels were analyzed by the Fisher exact test and one-way and repeated-measures ANOVA. Patients had no differences in gender, age, body mass index, operation time, and bleeding volume. Different Dex doses reduced the postoperative AIS score of patients under general anesthesia, improved their sleep, and increased serum levels of 5-HT, NE, and GABA. Furthermore, the effects were dose-dependent within the range of safe clinical use. Specifically, Dex at doses of 0.2, 0.4, and 0.6 μg/(kg · h) reduced postoperative AIS score, elevated serum neurotransmitter levels, and reduced postoperative sleep disturbance incidence. Collectively, Dex has a potential preventive effect on postoperative sleep disturbance in patients undergoing general anesthesia for radical gastrectomy. The optimal dose of Dex is between 0.2 and 0.6 μg/(kg · h), which significantly reduces the incidence of postoperative sleep disturbance and increases serum neurotransmitter levels.

Efeitos da alta dosagem de fitase no desempenho de frangos de corte e na digestibilidade de nutrientes

Abstract The study evaluated the effect of different doses of phytase and two diets (corn and soybean meal, and meat and bone meal) on the performance of broiler chickens and the digestibility of nutrients in feed. A total of 1320 Cobb 500 broilers were used for the performance experiment, 216 Cobb 500 broilers for the metabolism test, and 252 broiler chicks to determine the apparent and standardized digestibility coefficients of amino acids in the diets. The birds were individually weighed and distributed in a completely randomized design, comprising six treatments divided into a 2×3 factorial scheme (two diets and three levels of phytase composing the treatments): vegetable diets with 500, 1000, and 1500 FTU of phytase (T1, T2, T3); and meat and bone meal diets with 500, 1000, and 1500 FTU of phytase (T4, T5, T6). The average final weight gain and weight gain of animals that consumed diets with meat and bone meal and phytase at 500 FTU/kg were similar to those that consumed 1000 FTU/kg of phytase. The digestibility of amino acids for animals that consumed diets with corn and soybean meal and phytase at 500 FTU/kg was similar to those that consumed 1000 FTU/kg; statistically, the level of 1500 FTU/kg was equal to that of 500 FTU/kg. High doses of phytase did not promote improvements in performance and nutrient digestibility, as well as EMAn values; therefore, phytase supplementation at 500 FTU/kg is recommended.

Improving the recipe for wheat bread by introducing various dosages of herbal sage powder

The article includes the results of research on the effect of different dosages of sage powder on quality indicators of wheat flour of the highest grade, dough and baked bread. Insignificant changes in the moisture content of mixture samples, an increase in titratable acidity, and a decrease in the weight fraction of crude gluten with simultaneous strengthening were found. High indicators of finished bread appearance of all experimental samples, good condition of crumb, change of colour, taste and smell with increasing of dosage of sage powder from 0.25 to 2.5 % of flour weight were noted. Physico-chemical indicators of wheat bread quality of all experimental samples were registered within the standardised norms. According to the results of tasting analysis the best sample containing 1.5 % of sage powder from the weight of wheat flour was selected. The selected product had high microbiological parameters at the end of shelf life. It is proposed to use sage powder as a phytoactive additive to improve the quality indicators of bread and give it a functional purpose.

Effect of Aromatase Inhibitor Letrozole on the Placenta of Adult Albino Rats: A Histopathological, Immunohistochemical, and Biochemical Study.

Letrozole, an aromatase inhibitor, has recently been introduced as the preferred treatment option for ectopic pregnancy. To date, no study has investigated the effect of letrozole alone on placental tissue. The present study aimed to evaluate the effect of different doses of letrozole on the placenta of rats and to clarify the underlying mechanism. Sixty pregnant female rats were equally divided into three groups, namely the control group (GI), low-dose (0.5 mg/Kg/day) letrozole group (GII), which is equivalent to the human daily dose (HED) of 5 mg, and high-dose (1 mg/Kg/day) letrozole group (GIII), equivalent to the HED of 10 mg. Letrozole was administered by oral gavage daily from day 6 to 16 of gestation. Data were analyzed using a one-way analysis of variance followed by Tukey's post hoc test and Chi square test. P<0.05 was considered statistically significant. Compared to the GI and GII groups, high-dose letrozole significantly increased embryonic mortality with a high post-implantation loss rate (P<0.001) and significantly reduced the number of viable fetuses (P<0.001) and placental weight (P<0.001) of pregnant rats. Moreover, it significantly reduced placental estrogen receptor (ER) and progesterone receptor (PR) (P<0.001) and the expression of vascular endothelial growth factor (P<0.001), while increasing the apoptotic index of cleaved caspase-3 (P<0.001). Letrozole inhibited the expression of ER and PR in rat placenta. It interrupted stimulatory vascular signals causing significant apoptosis and placental vascular dysfunction. Letrozole in an equivalent human daily dose of 10 mg caused a high post-implantation loss rate without imposing severe side effects.

Effect of different doses of dexmedetomidine as an adjuvant to lignocaine nebulization: A comparative study during awake flexible fiberoptic bronchoscopy.

Mild to moderate sedation during bronchoscopy is essential for patient safety, comfort during and after the procedure, and to facilitate the performance of the bronchoscopist. Dexmedetomidine is a highly selective, centrally acting α-2 agonist used to provide conscious sedation during various procedures. The aim of this study was to compare the efficacy of three different doses of dexmedetomidine nebulization as an adjuvant to lignocaine during bronchoscopy. Ninety American Society of Anesthesiologists physical status I/II patients, aged from 18 to 60 years, scheduled for an elective bronchoscopy, were recruited. They were divided into three groups: 30 patients in each group. Group I: The patient was nebulized with a mixture of 4 ml of 4% lignocaine and dexmedetomidine 0.5 μg/kg. Group II: The patient was nebulized with a mixture of 4% lignocaine, 4 ml, and dexmedetomidine, 1 μg/kg. Group III: The patient was nebulized with 4% lignocaine 4 ml and dexmedetomidine 1.5 μg/kg. The mean cough score was (1.17 ± 0.37), (1.40 ± 0.49), and (1.70 ± 0.75) in group III, group II, and group I, respectively. A significant difference was found between the groups. Patients were more comfortable with a statistically significant difference in the comfort score in group III as compared to group II and group I. Dexmedetomidine nebulization in a dose of 1.5 μg/kg (compared to 1 μg/kg or 0.5 μg/kg) as an adjuvant to lignocaine, provides better bronchoscopy conditions and patient satisfaction.

The effect of different doses of dry biomass of chlorella vulgaris microalgae on the dairy productivity of Zaanen goats

Dairy goat breeding is a new developing branch of animal husbandry in Russia. The prospects for processing goat’s milk are very wide, which is due to an increase in consumer demand for it. Obtaining the maximum amount of products and maintaining animal health is possible with the use of modern feed products. Therefore, an important and urgent task of scientific research is to study the productivity of dairy goats when feeding dry biomass of microalgae Chlorella Vulgaris, which was the purpose of this work. The objects of the study were dairy goats in the type of Zaanen breed. To conduct an experiment based on the principle of groups of analogues, taking into account live weight and age, four groups of female goats (three experimental and one control) of 20 animals each (according to the Ovsyannikov method) were formed. The animals of the control group received the basic household ration, and dry biomass of Chlorella Vulgaris microalgae was introduced into the diet of the experimental groups in doses of 4; 6; 8 g / kg of body weight / day. As a result of the experiment, it was found that the introduction of an experimental drug into the diet of goats increased the average daily milk yield of goats of the first experimental group by 0.02%, the second experimental group by 1.66 and the third experimental group by 3.27%, which allows us to determine the most optimal dose of the introduction of an experimental probiotic drug into the diet of goats, which amounted to 6 g / kg of body weight.

Evaluating the effects of different doses of fimasartan on methotrexate-induced renal inflammation in rats

Evaluating the effects of different doses of fimasartan on methotrexate-induced renal inflammation in rats

Efficacy of photobiomodulation therapy combined with mobile health education in patients with head and neck cancer suffering from chronic xerostomia after radiotherapy: protocol for a three-arm, randomised, placebo-controlled, double-blinded study

IntroductionThe role of photobiomodulation (PBM) therapy for oral tissue damage induced by cancer treatment is currently unclear, and there is low-quality to moderate-quality evidence supporting the use of this approach...