Toll-Like Receptor 4, 2, and Interleukin 1 Receptor Associated Kinase4: Possible Diagnostic Biomarkers in Myelodysplastic Syndrome Patients.

Background: Myelodysplastic syndrome (MDS) is a clonal hematologic disorder that requires the integration of morphologic, cytogenetic, hematologic, and clinical findings for a successful diagnosis. Trying to find ancillary tests such as biomarkers improve the diagnosis process. Several studies showed that a disordered immune system is associated with MDS. The chronic activated innate immune system, particularly the Toll-like receptors (TLRs) pathway could be involved in the induction of the inflammation. Materials and Methods: In the present study, we investigated the expression of TLR2, TLR4, and IRAK4 in bone marrow (BM) of MDS patients, the leukemia group, and the healthy group. For this purpose, we assessed the expression of TLR2, TLR4, and IRAK4 by real time-PCR. Results: In line with new findings, we demonstrated that the expression of TLR2, TLR4, and IRAK4 significantly increased in MDS BM compared with the healthy group. Moreover, IRAK4 expression raised significantly in MDS patients compared with other studied hematologic neoplasms. Also, the expression levels of TLR2 and TLR4 significantly increased in MDS in comparison to some studied non-MDS malignancies (P ˂ 0.05). Receiver operating characteristics (ROC) analysis and area under the curve (AUC) suggested that the expression of TLR2, TLR4, and IRAK4 (AUC = 0.702, AUC = 0.75, and AUC = 0.682, respectively) had acceptable diagnostic values to identify MDS from the other understudied leukemias. Conclusion: Overall, the expression of TLR2, TLR4, and IRAK4 could be potential biomarkers for discriminating MDS from some hematologic disorders.

Oncologic Outcomes and Predictors in Patients with Stage PT3aNxM0 Renal Cell Carcinoma Following Radical Nephrectomy.

OBJECTIVE: The objective of this study is to evaluate oncologic outcomes in patients with PT3aNxM0 renal cell carcinoma following radical nephrectomy and also to investigate these outcomes in each specific subgroup of PT3a renal cell carcinoma and to determine predictive factors of recurrence, metastasis, and mortality. MATERIALS AND METHODS: In this retrospective cohort study, we included 94 patients with stage PT3a renal cell carcinoma who had undergone radical nephrectomy from 2011 to 2016. All patients who had survived had at least 60 months of follow-up. Demographic and clinical data were collected; univariable and multivariable Cox proportional hazards regression analysis was performed to identify predictors of metastasis, recurrence, and cancer-related mortality. RESULTS: Patients' mean age was 58.07 ± 11.17 years and 62/94 (65.9%) were male. The mean follow-up time was 48.1 ± 25.5 months. Forty-three patients (45.7%) had experienced cancer-related mortality. The mean cancer-specific survival time was 60.94 months and the mean metastasis-free and local recurrence-free survival times were 57.06 and 88.72 months, respectively. Metastasis and local recurrence had occurred in 42 (44.6%) and 4 (4.25%) patients, respectively. After performing multivariate analysis, higher nuclear Fuhrman's grade (P < .001) and simultaneous involvement of the renal vein and perinephric fat (P < .001) were found to be predictive of cancerrelated mortality. Advanced nuclear Fuhrman's grade was the only independent predictor of metastasis (P=.001). CONCLUSION: Based on our results, advanced nuclear Fuhrman's grade and sarcomatoid change can independently predict mortality in patients with stage PT3aNxM0 renal cell carcinoma. Close monitoring during the follow-up period is recommended in patients with the mentioned risk factors.

In vitro anti-biofilm properties of the peel of fruite wall of acorn against Streptococcus mutans.

Dental caries is a multi-factorial infectious disease. The primary cause is dental plaque, a complex of biofilm. It was postulated that the ethanolic extract of fruite wall of acorn may represent a new substance to prevent caries. Hence, the study was performed to evaluate the effect of ethanolic extract of fruite wall of acorn against biofilm formation by Streptococcus mutans, which is associated with dental plaque. The cytotoxicity of the ethanolic extract was determined against Vero cells resulting in an inhibitory concentration of 50 (IC50) of 55 µg/ml. After bacterial collection, different concentrations under the IC50 from the extract were evaluated against biofilm formation of S. mutans. 3 µg/ml of the extract inhibited the biofilm formation of S. mutans, and 1 to 3 µg/ml caused a decrease in gtfB and brpA biofilm-production genes. This study showed the potency of the ethanolic extract of fruite wall of acorn against biofilm formation by S. mutans.

The effects of type of recovery in resistance exercise on responses of platelet indices and hemodynamic variables.

To examine the effects of two different volume-matched resistance exercise (RE) recovery protocols (passive and active) on platelet indices and hemodynamic variables. Twelve Healthy participants (mean ± SD; 25 ± 3 yrs) completed a traditional resistance exercise (TRE) protocol that included three sets of six repetitions at 80% one repetition maximum (1RM) with two minutes passive recovery between sets, exercises and an interval resistance exercise (IRE) protocol that included three sets of six repetitions at 60%1RM followed by active recovery including six repetitions of the same exercise at 20%1RM. Blood samples for multiple platelet indices were taken before the protocols, immediately-post (IP), and after 1-hour recovery. Hemodynamic variables were measured before, IP, and every five minutes during recovery. Mean platelet volume and platelet large cell ratio P_LCR decreased from baseline to recovery. Heart rate (HR) and rate pressure product (RPP) were augmented at IP following IRE compared to TRE. HR was significantly elevated for 20 minutes after both RE protocols, and RPP recovered by five minutes. Systolic blood pressure was increased at IP compared to baseline and all recovery time points for both RE protocols. Our research demonstrated that both RE protocols, produced transient increases in platelet indices (MPV, and P_LCR) and hemodynamic variables (SBP, HR, and RPP), all of which returned to baseline within an hour. Notably, the IRE protocol elicited a greater increase in HR and RPP compared to the TRE protocol.

Surface-engineered double-layered fabrics for continuous, passive fluid transport.

Textiles with a wicking finish transport moisture away from the skin, such that it is exposed to the environment for fast evaporation, aiding in thermophysiological comfort. Once saturated, such as in highly humid environments or if the wearer dons multiple layers, the efficacy of such a finish is substantially reduced. Here, we develop a new type of fluid transport textile design by combining physical and chemical wettability patterns to transport and remove liquids like sweat. First, a non-toxic, superhydrophobic fabric finish is developed that retains the air permeability of the fabric. Next, two superhydrophobic fabric layers are threaded together, containing wettability channels patterned at the inner/interior side of the fabrics. This design allows for liquid transport through the stitches to the interior channels and keeps both external faces dry. The developed strategy enables directional fluid transport under highly humid conditions, resulting in a ∼20 times faster transport rate than evaporation-based methods. The design principles described here can be used to provide thermophysiological comfort for users in extreme conditions, such as firefighters, law enforcement personnel, and health workers wearing personal protective ensembles.

Correction: Understanding liquid-liquid equilibria in binary mixtures of hydrocarbons with a thermally robust perarylphosphonium-based ionic liquid.

[This corrects the article DOI: 10.1039/D1RA06268A.].

Correction: Ionic liquids of superior thermal stability. Validation of PPh4+ as an organic cation of impressive thermodynamic durability.

[This corrects the article DOI: 10.1039/D0RA03220D.].

Correction: Tuning the melting point of selected ionic liquids through adjustment of the cation's dipole moment.

Correction for 'Tuning the melting point of selected ionic liquids through adjustment of the cation's dipole moment' by Brooks D. Rabideau et al., Phys. Chem. Chem. Phys., 2020, 22, 12301-12311, https://doi.org/10.1039/D0CP01214A.

Correction: Unorthodox crystalline drug salts via the reaction of amine-containing drugs with CO2.

Correction for 'Unorthodox crystalline drug salts via the reaction of amine-containing drugs with CO2' by Mohammad Soltani et al., Chem. Commun., 2019, 55, 13546-13549, https://doi.org/10.1039/C9CC06429J.

Wound healing performance of electrospun PVA/70S30C bioactive glass/Ag nanoparticles mats decorated with curcumin: In vitro and in vivo investigations.

Biocompatible fibrous scaffold containing polyvinyl alcohol (PVA), 70S30C bioactive glass (BG), silver (Ag) nanoparticles and curcumin (Cur) was fabricated through electrospinning method. Scanning electron microscope (SEM) and Field emission scanning electron microscopy (FESEM) were employed to investigate the morphological characteristics of the scaffolds. In addition, biodegradability, hydrophilicity, and contact angle were studied as criteria for evaluating physical properties of the scaffolds. Tensile strength was reported to be 0.971 ± 0.093 MPa. Also, the viability of fibroblasts after 7 days of cell culture was 93.58 ± 1.36 %. The antibacterial activity against Escherichia coli and Staphylococcus aureus bacteria was illustrated using inhibition zones of 13.12 ± 0.69 and 14.21 ± 1.37 mm, respectively. Histological results revealed that tissue regeneration after 14 days of surgery was much higher for the dressing group compared to the blank group. According to the obtained results, the authors introduce the PVA-BG-Ag-Cur scaffold as a promising candidate for skin tissue engineering applications.

Molecular characterization and phylogenetic study of the hemagglutinin-neuraminidase gene of newcastle disease virus isolated from peacock (Pavo cristatus) and Turkey (Meleagris) and its comparison with broiler isolates.

Newcastle disease has been endemic within the Iranian poultry industry for decades. However, the genetic nature of the circulating Hemagglutinin-Neuraminidase (HN) gene among Iranian domesticated bird populations is broadly unexplored. The presented study was carried out to gain insights into the biological and molecular characterization of four complete HN genes isolated from turkey, peacock, and broiler isolates in Iran between 2018 and 2020. The phylogenetic analysis revealed that the isolates belong to the Newcastle disease virus (NDV) subgenotype VII.1.1, previously known as VIIL. Further analysis demonstrated the thermostable substitutions S315P and I369V within the isolates. Finding the N-glycosylation site (NIS) at positions 144-146 and the cysteine residue 123 might influence the fusogenicity abilities of the isolates, while identification of multiple amino acid substitutions in both antigenic sites, especially I514V and E347Q, and the binding sites of the HN protein, raised concern about the pathogenicity of the isolates. In addition, the annual rate of change based on the HN gene of Iranian NDV was calculated at about 1.8088E-3 between 2011 and 2020. In conclusion, a new NDV variant with multiple site mutagenesis is circulating not only among chickens but also in turkey and captive birds such as peafowls, and failure of routine vaccination programs could be attributed to the differences between circulating NDV strains and those used in vaccine manufacturing. Therefore, future legislation aimed at providing vaster vaccination cover and biosecurity plans will be needed to control the spread of circulating NDV strains.

Cyclopropane as an Unsaturation "Effect Isostere": Lowering the Melting Points in Lipid-like Ionic Liquids.

The replacement of unsaturation with a cyclopropane motif as a (bio)isostere is a widespread strategy in bacteria to tune the fluidity of lipid bilayers and protect membranes when exposed to adverse environmental conditions, e.g., high temperature, low pH, etc. Inspired by this phenomenon, we herein address the relative effect of the cyclopropanation, both cis and trans configurations, on melting points, packing efficiency, and order of a series of lipid-like ionic liquids via a combination of thermophysical analysis, X-ray crystallography, and computational modeling. The data indicate there is considerable structural latitude possible when designing highly lipophilic ionic liquids that exhibit low melting points. While cyclopropanation of the lipid-like ionic liquids provides more resistance to aerobic degradation than their olefin analogs, the impact on the melting point decrease is not as pronounced. Our results demonstrate that incorporating one or more cyclopropyl moieties in long aliphatic chains of imidazolium-based ionic liquids is highly effective in lowering the melting points of such materials relative to their counterparts bearing linear, saturated, or thioether side chains. It is shown that the cyclopropane moiety effectively disrupts packing, favoring formation of gauche conformer in the side chains, resulting in enhancement of fluidity. This was irrespective of the configuration of the methylene bridge, although marked differences in the effect of cis- and trans-monocyclopropanated ILs on the melting points were observed.

The effect of a standardized capsule of Aloe vera gel on the quality of life in patients with systolic heart failure: A randomized double-blind placebo-controlled clinical trial.

This trial was designed to evaluate the effect of a standardized capsule of Aloe vera gel (AVG) on the quality of life (QOL) in patients with systolic heart failure (HF). Forty-two patients were randomly divided into two groups to receive either AVG 150 mg or harmonized placebo capsules twice a day for 8 weeks. The patients were evaluated before and after the intervention using the Minnesota Living with Heart Failure Questionnaire (MLHFQ), New York Heart Association (NYHA) functional class, six-minute walk test (6MWT), Insomnia Severity Index (ISI), Pittsburgh Sleep Quality Index (PSQI) and STOP-BANG questionnaires. Post-intervention, AVG group indicated a significant reduction in the total score of MLHFQ (p < 0.001). The changes in MLHFQ and NYHA class were statistically significant after taking medication (p < 0.001 and p = 0.004, respectively). The change of 6MWT in the AVG group was more advanced; however, it was not statistically significant (p = 0.353). Moreover, in the AVG group, the severity of insomnia and obstructive sleep apnea decreased (p < 0.001, p = 0.01 respectively) and the sleep quality improved as well (p < 0.001). There were significantly fewer adverse events reported in the AVG group (p = 0.047). Therefore, AVG combined with standard medical therapy could provide more clinical benefits for patients with systolic HF.

Charge neutralization of the active site glutamates does not limit substrate binding and transport by small multidrug resistance transporter EmrE.

EmrE, a small multidrug resistance transporter from Escherichia coli, confers broad-spectrum resistance to polyaromatic cations and quaternary ammonium compounds. Previous transport assays demonstrate that EmrE transports a +1 and a +2 substrate with the same stoichiometry of two protons:one cationic substrate. This suggests that EmrE substrate binding capacity is limited to neutralization of the two essential glutamates, E14A and E14B (one from each subunit in the antiparallel homodimer), in the primary binding site. Here, we explicitly test this hypothesis, since EmrE has repeatedly broken expectations for membrane protein structure and transport mechanism. We previously showed that EmrE can bind a +1 cationic substrate and proton simultaneously, with cationic substrate strongly associated with one E14 residue, whereas the other remains accessible to bind and transport a proton. Here, we demonstrate that EmrE can bind a +2 cation substrate and a proton simultaneously using NMR pH titrations of EmrE saturated with divalent substrates, for a net +1 charge in the transport pore. Furthermore, we find that EmrE can alternate access and transport a +2 substrate and proton at the same time. Together, these results lead us to conclude that E14 charge neutralization does not limit the binding and transport capacity of EmrE.

Resistance training, gremlin 1 and macrophage migration inhibitory factor in obese men: a randomised trial.

OBJECTIVE: This study aimed to determine how different resistance training protocols affect gremlin 1, macrophage migration inhibitory factor (MIF), cardiometabolic, and anthropometric measures in obese men. METHODS: Forty-four males with obesity (weight: 93.2 ± 2.2 kg, BMI: 32.9 ± 1.2 kg/m2, age: 27.5 ± 9.4 years) were randomly assigned to traditional resistance training (TRT, n = 11), circuit resistance training (CRT, n = 11), interval resistance training (IRT, n = 11) or control (C, n = 11) groups. TRT group performed ten exercises at 50% of 1RM with 14 repetitions for three sets and 30 seconds rest interval between exercises and 1.5 min rest between sets, the CRT protocol included three circuits of 10 exercises, at an intensity of 50% of 1-RM, 14 repetitions with a minimum rest (< 15 s) between exercises and 3 min rest between sets, and the IRT group performed two sets of the same exercises with 50% of 1 RM, and 14 repetitions were followed with active rest of 25% of 1RM and 14 repetitions. All resistance training groups performed 60 min per session resistance exercises, 3 days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of exercise training. RESULTS: Resistance training (TRT, CRT, and IRT) significantly decreased plasma levels of gremlin (TRT from 231.0 ± 5.8 to 210.0 ± 11.6 ng/ml, CRT from 226.0 ± 7.6 to 188.0 ± 7.7 ng/ml and, IRT from 227.0 ± 6.3 to 183.0 ± 9.0 ng/ml, effect size (ES): 0.50), MIF (TRT from 251.0 ± 7.4 to 260.0 ± 6.5 ng/ml, CRT from 248.0 ± 10.9 to 214.0 ± 9.0 ng/ml and, IRT from 247.0 ± 8.9 to 196.0 ± 6.9 ng/ml, ES: 0.55) and CRP (TRT from 28.4 ± 1.7 to 23.3 ± 2.1 nmol/l, CRT from 28.5 ± 2.2 to 21.1 ± 1.8 nmol/l, IRT from 28.1 ± 1.3 to 20.8 ± 1.3 nmol/l, ES: 0.49) compared to the control group (p < .05), but these reduction were greater in the CRT and IRT groups compared to the TRT group (p < .05). CONCLUSION: The CRT and IRT protocols had more beneficial improvement in gremlin 1, MIF, body composition, and cardiometabolic risk factors compared to the beneficial changes produced by TRT protocol.

Comparison of histopathological features, survival, and oncological outcome between patients under and above 55-year-old with prostate cancer who underwent radical prostatectomy.

BACKGROUND: To compare the disease course, histopathological features and survival rates of prostate cancer (PCa) between patients aged ⩽ 55 and > 55 year old. MATERIALS AND METHODS: In this retrospective study, we enrolled 644 patients with organ-confide prostate cancer who had undergone radical prostatectomy from 2005 to 2018. Seventy-six (11.8%) patients were under 55 years of age (group 1) and 568 (88.2%) patients were >55 years old (group 2). RESULTS: Pre-operative hypertension was detected in 4 (5.3%) patients of group 1 and 80 (14.1%) patients of groups 2 (p = 0.029). The mean (±SD) prostate volume was higher in group 2 compared with group 1 (34.1(±8.4) ml vs 54.1(±9.9) ml, p < 0.001). Positive surgery margin was observed in 15 (19.7%) and 58 (10.2%) patients in group 1 and 2, respectively (p = 0.020). Co-existence of diabetes mellitus, mean pre-operative PSA, Gleason's score, and permanent pathology and pathologic stage were similar between the two groups. Log-rank test failed to show any statistical difference in terms of biochemical-relapse free survival, local recurrence-free survival, and metastasis-free survival between the two groups (p = 0.316, 0.441, 0.654, respectively). After performing multivariate analysis, positive surgical margin was the only factor that was independently predictive of biochemical relapse (p < 0.001) and local recurrence/metastasis (p < 0.001). CONCLUSION: No difference was observed in terms of histopathologic features, biochemical relapse, and local recurrence/metastasis-free survival rates between patients younger and older than 55 years of age.

In Vitro Diagnostic Accuracy and Agreement of Dental Microscope and Cone-Beam Computed Tomography in Comparison with Microcomputed Tomography for Detection of the Second Mesiobuccal Canal of Maxillary First Molars.

Objectives: The percentage of failure of endodontically treated maxillary molars is relatively high; one main reason is that the second mesiobuccal canal (MB2) is missing. Some techniques have been proposed for detection of the MB2. This study was aimed at assessing the diagnostic accuracy and agreement of the dental microscope and cone-beam computed tomography (CBCT) in comparison with microcomputed tomography (micro-CT) for detection of the MB2 of maxillary first molars in vitro. Materials and Methods: This in vitro, experimental study evaluated 71 permanent maxillary first molars that were stored in 100% humidity at room temperature. The teeth were mounted in 9 silicone dental arches to the level of their cementoenamel junction (8 teeth in each arch). The blocks underwent CBCT in a XG3D scanner. Access cavity was then prepared, and the teeth were inspected by a surgical microscope for negotiation of the MB2. Also, micro-CT images were obtained from the teeth to serve as the gold standard. CBCT and micro-CT images were observed by two examiners twice with a 2-week interval. Results: The frequency of the MB2 detected by dental microscope was significantly lower than micro-CT (P < 0.001) and CBCT (P = 0.008); no significant difference existed between micro-CT and CBCT in this respect. The sensitivity, specificity, positive predictive value, and negative predictive value of CBCT for detection of MB2 were 92.6%, 100%, 100%, and 81%, respectively. Conclusion: CBCT is superior to the dental microscope for detection of the MB2 of maxillary first molars and can be used for this purpose in the clinical setting with adequate accuracy.

Aloe vera incorporated starch-64S bioactive glass-quail egg shell scaffold for promotion of bone regeneration.

Simultaneous promotion of osteoconductive and osteoinductive characteristics through combining bioactive glasses with natural polymers is still a challenge in bone tissue engineering. Starch, 64S bioactive glass (BG), aloe vera (AV) and quail eggshell powder (QE) were utilized to achieve biodegradable, bioactive, biocompatible and mechanically potent multifunctional scaffolds, using freeze-drying mechanism. Cell viability for starch-BG-AV-QE scaffolds at 3 and 7 day intervals was reported to be over 95 %. Acridine orange staining was employed to study live/dead cells cultured on the scaffolds. The high sufficiency of starch-BG-AV-QE scaffolds in osteogenic differentiation and extracellular matrix mineralization was confirmed through alkaline phosphatase activity and alizarin red staining assessments after 7 and 14 days of cell culture. High compressive strength, managed biodegradability and expression of osteocalcin and osteopontin as late markers of osteogenic differentiation were also reached in the range of 30-75 % for starch-BG-AV-QE scaffolds. Hence, starch-BG-AV-QE scaffolds with ideal physico-mechanical and biological characteristics can be considered as promising candidates for promotion of bone regeneration.

Predictive modeling of Persian walnut (Juglans regia L.) in vitro proliferation media using machine learning approaches: a comparative study of ANN, KNN and GEP models.

BACKGROUND: Optimizing plant tissue culture media is a complicated process, which is easily influenced by genotype, mineral nutrients, plant growth regulators (PGRs), vitamins and other factors, leading to undesirable and inefficient medium composition. Facing incidence of different physiological disorders such as callusing, shoot tip necrosis (STN) and vitrification (Vit) in walnut proliferation, it is necessary to develop prediction models for identifying the impact of different factors involving in this process. In the present study, three machine learning (ML) approaches including multi-layer perceptron neural network (MLPNN), k-nearest neighbors (KNN) and gene expression programming (GEP) were implemented and compared to multiple linear regression (MLR) to develop models for prediction of in vitro proliferation of Persian walnut (Juglans regia L.). The accuracy of developed models was evaluated using coefficient of determination (R2), root mean square error (RMSE) and mean absolute error (MAE). With the aim of optimizing the selected prediction models, multi-objective evolutionary optimization algorithm using particle swarm optimization (PSO) technique was applied. RESULTS: Our results indicated that all three ML techniques had higher accuracy of prediction than MLR, for example, calculated R2 of MLPNN, KNN and GEP vs. MLR was 0.695, 0.672 and 0.802 vs. 0.412 in Chandler and 0.358, 0.377 and 0.428 vs. 0.178 in Rayen, respectively. The GEP models were further selected to be optimized using PSO. The comparison of modeling procedures provides a new insight into in vitro culture medium composition prediction models. Based on the results, hybrid GEP-PSO technique displays good performance for modeling walnut tissue culture media, while MLPNN and KNN have also shown strong estimation capability. CONCLUSION: Here, besides MLPNN and GEP, KNN also is introduced, for the first time, as a simple technique with high accuracy to be used for developing prediction models in optimizing plant tissue culture media composition studies. Therefore, selection of the modeling technique to study depends on the researcher's desire regarding the simplicity of the procedure, obtaining clear results as entire formula and/or less time to analyze.

Effects of Three Different Modes of Resistance Training on Appetite Hormones in Males With Obesity.

Purpose: This study explored the effect of three different modes of resistance training on appetite hormones [leptin, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine-tyrosine (PYY)], cardiometabolic and anthropometric measures in males with obesity. Methods: Forty-four males with obesity (age: 27.5 ± 9.4 yrs.; mean weight: 93.2 ± 2.2 kg, body mass index: 32.9 ± 1.2 kg/m2) were randomized to traditional resistance training (TRT, n = 11), circuit resistance training (CRT, n = 11), interval resistance training (IRT, n = 11) or control (C, n = 11) groups. All resistance training groups received 50 min of supervised training per session, three days per week, for 12 weeks. Measurements were taken at baseline and after 12 weeks of training. Results: Plasma levels of leptin, ghrelin, CCK, and PYY decreased significantly in all three different modalities of resistance training groups when compared to the control group (p < 0.05). GLP-1 increased significantly in both CRT and IRT groups compared to TRT and C groups (p < 0.05). Glucose-dependent insulinotropic polypeptide decreased significantly in CRT and IRT groups compared to the C group (p < 0.05). Adiponectin levels increased significantly in all resistance training groups compared to the C group (p < 0.05). Conclusion: Overall, CRT and IRT protocols had the greatest impact on appetite hormones compared to individuals who engaged in TRT or did not exercise (C).