Assessment of drug-drug interactions among patients with hematologic malignancy: A clinical pharmacist-led study.

INTRODUCTION: Patients with hematologic malignancies often receive multiple medications, leading to potential drug-drug interactions (DDIs). Identifying and managing these DDIs is crucial for ensuring patient safety and effective care. This study aimed to identify and describe DDIs and associated factors in hematologic malignancy patients. METHODS: This prospective interventional study was conducted at a referral center and included hospitalized patients with hematologic malignancies who were receiving at least four concurrent medications. A pharmacist initially compiled a comprehensive list of all medications through patient interviews and medication reviews, and subsequently, identified and categorized potential DDIs using the Lexi-interact® and Micromedex® databases. The clinical pharmacist then evaluated the clinical impact of the identified DDIs in every individual patient and provided appropriate interventions to resolve them. RESULTS: A total of 200 patients met the inclusion criteria for the study, with 1281 DDIs identified across 337 distinct types. The majority of identified DDIs exhibited major severity (52.1%) and pharmacokinetic mechanisms (50.3%), with an unspecified onset (79.4%) and fair evidence (67%). Of the identified DDIs, 81.1% were considered clinically significant, prompting 1059 pharmacotherapy interventions by the clinical pharmacist. Additionally, a significant relationship was observed between the number of drugs used during hospitalization and the occurrence of DDIs (P < 0.001, r = 0.633). CONCLUSION: DDIs are highly prevalent among hospitalized patients with hematologic malignancies, with their occurrence increasing alongside the number of medications administrated. The intervention of a clinical pharmacist is crucial to evaluate the clinical impact of these DDIs and implement effective interventions for their management.

Effects of slow dynamic, fast dynamic, and static stretching on recovery of performance, range of motion, balance, and joint position sense in healthy adults.

INTRODUCTION: Considering the effects of fatigue on athletic performance and the subsequent increase in the probability of injury, the purpose of this study was to compare the effects of slow dynamic, fast dynamic, and static stretching on the recovery of performance, range of motion (ROM), balance, and joint position sense. METHODS: Fifteen collegiate healthy females were involved in four separate sessions of slow dynamic stretching (SDS), fast dynamic stretching (FDS), static stretching (SS), and control condition (CC; without stretching), in a random order with at least 48 h of rest between sessions. After warming up, the individuals performed ROM, balance, joint position sense (JPS) maximum voluntary isometric contraction (MVIC) force as well as countermovement (CMJ) and squat jump (SJ) as pre-tests. After performing the knee fatigue protocol of 4 sets of knee extension and flexion at 60% of 1 repetition maximum (RM) to exhaustion (CC; without stretching) or stretching programs (SDS or FDS or SS), the subjects repeated all the tests at post-test 1 (after 5 min) and post-test 2 (after 60 min). RESULTS: A significantly lower JPS error was detected with SDS while JPS error increased in the SS and control conditions (p < 0.0001). MVIC force significantly increased with SDS and FDS but decreased in control and SS conditions (p < 0.0001). Moreover, a significant decrease in CMJ and SJ height in SS and control conditions was revealed (p < 0.0001). Also, a significant decrease in balance with the control condition was revealed. But only SDS minimized fatigue-induced balance decrements (p < 0.0001). Additionally, the control condition experienced a significant decrease in knee extensor ROM, which contrasted with the significant increase in the quadriceps flexibility with the stretching conditions. CONCLUSIONS: The present results support the idea that SDS may increase quadriceps MVIC force, knee extensor ROM and knee JPS. So according to the present results, it is suggested that the SDS could be implemented and incorporated into a regular recovery program.

Endometrial scratching in unexplained repeated implantation failure causes two competing forces, angiogenesis and anti-angiogenesis: An RCT study.

Background: A significant association between endometrial vascularity and pregnancy has been shown in previous research, while poor vascularization was attributed to repeated implantation failure (RIF). One possible approach to enhance angiogenesis for successful implantation is endometrial scratching (ES). Objective: The purpose was to investigate endometrial responses to scratching by profiling angiogenesis-related gene expression in unexplained RIF participants. Materials and Methods: In this randomized controlled trial study, 20 infertile women with unexplained RIF were assigned to 2 groups by the balanced block randomization method (n = 10/each group): the intervention group (group A) (who received ES in the follicular phase) and the control group (group B). Endometrial biopsy was performed in the secretory phase. Gene expression profiling was performed using a polymerase chain reaction-array kit for human-angiogenic growth factors. The implantation and clinical pregnancy rates were also assessed. Results: Among the angiogenesis-promoting genes, FGF1, FGF13, FGF2, TGFA, ANG, ANGPT1, and VEGFA were significantly upregulated (p < 0.05). IL12A (an angiogenesis-inhibiting cytokine) was significantly upregulated (p < 0.01). In contrast, 15 genes with angiogenesis-related functions, including CXCL11, CXCL13, CXCL3, CXCL5, CXCL6, EREG, FIGF, FST, IL10, LEP, PPBP, PROK1, RHOB, TNF, and TYMP, were downregulated after ES. No significant differences were observed between the intervention (group A) and control (group B) groups in terms of implantation (43.75% vs. 28.57%) or clinical pregnancy rates (75% vs. 57.1%). Conclusion: ES induced significant alterations in the expression of angiogenesis-related genes, with notable up/downregulation of key angiogenic/antiangiogenic factors. These findings enhance our understanding of the molecular responses triggered by ES, underscoring the potential influence of ES on the complex processes of angiogenesis crucial for implantation.

An Approach to Improve Endometrial Receptivity: Is It Beneficial to Flush The Uterine Cavity with Follicular Fluid and Granulosa Cells? A Phase III Randomised Clinical Trial.

BACKGROUND: The follicular fluid (FF) of mature oocytes contains a high concentration of growth factors and cytokines that have the potential to influence implantation in either a paracrine or autocrine manner. During the physiological processes of ovulation, FF enters the fallopian tubes in conjunction with the oocyte. The purpose of this study is to evaluate implantation and clinical pregnancy rates following uterine flushing with FF and granulosa cells in infertile women with moderate male factor infertility after ovum retrieval for intracytoplasmic sperm injection (ICSI). MATERIALS AND METHODS: This phase III randomised clinical trial enrolled 140 women with moderate male factor infertility who intended to undergo ICSI at Royan Infertility Clinic (Tehran, Iran). A computer-generated program and opaque sealed envelopes were used to randomly allocate patients to either an intervention group (n=70) or a control group (n=70). Participants in the intervention group received 2 ml of clear FF (without blood contamination) from 2 to 3 dominant follicles after oocyte retrieval. The control group only underwent uterine cavity catheterisation. RESULTS: The intervention group had a clinical pregnancy rate of 38.5% (25/65) compared to the control group [42.9% (27/63); P=0.719] and an implantation rate of 24.1% compared to the control group (27%; P=0.408). These rates did not differ between the groups. There were no statistically significant differences between the intervention and control groups in terms of pregnancy-related complications-ectopic pregnancy, blighted ovum or anembryonic pregnancy, and abortion. CONCLUSION: Uterine cavity flushing with FF from mature follicles following oocyte retrieval had no effect, either positively or negatively, on clinical pregnancy or implantation rates in women with moderate male factor infertility (registration number: NCT04077970).

Curcumin mitigates acrylamide-induced ovarian antioxidant disruption and apoptosis in female Balb/c mice: A comprehensive study on gene and protein expressions.

Curcumin is known for its antioxidant properties. This study aimed to investigate the impact of curcumin on acrylamide (ACR)-induced alterations in the first-line antioxidant defense of ovarian tissue. Female Balb/c mice were divided into control, ACR (50 mg/kg), ACR/CUR100 (received Acr + curcumin100 mg/kg), and ACR/CUR200 (Acr + curcumin 200 mg/kg) groups, and received oral treatments for 35 days. Evaluation of antioxidant enzyme expression (Sod, Cat, Gpx genes), pro-apoptotic gene expressions (Bax, Caspase 3), and anti-apoptotic gene expression (Bcl2l1) at mRNA and protein levels was done. Percentage of apoptotic cells using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay was performed. The model group (ACR) showed decreased mRNA expression of Sod, Cat, and Gpx genes compared with the control group. Treatment with two different doses of curcumin (CUR100 and CUR200) significantly increased Sod, Cat, and Gpx gene expression, with CUR200 demonstrating significant recovery. SOD, CAT, and GPX protein levels were similar to mRNA expression trends, significantly increased with curcumin administration. Acrylamide exposure significantly increased Bax and Caspase 3 expression and decreased Bcl2l1 gene expression leading to a notable rise in apoptosis in ACR group as compared to the control group. Conversely, curcumin administration, significantly reduced Bax and Caspase 3 expressions, with an increase in Bcl2l1expression, though not statistically significant. TUNEL assay revealed a substantial decrease in apoptosis in curcumin-received groups. In our study, ACR exposure adversely affected ovarian antioxidant defense thereby leading to increased pro-apoptotic markers. Notably, curcumin treatment effectively mitigated these effects, restored antioxidant potential, and reduced acrylamide-induced toxicity in female mouse ovaries.

In vitro effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the expression of genes related to sperm motility and energy metabolism and intracytoplasmic sperm injection outcomes in obstructive azoospermic patients.

BACKGROUND: The presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and its receptor in various testicular cells and spermatozoa suggests a potential role in enhancing spermatogonial and postmeiotic cell development. Moreover, GM-CSF activates the pivotal pathways implicated in sperm motility regulation and glucose metabolism. However, the impact of GM-CSF on testicular biopsies from patients with obstructive azoospermia (OA) remains unexplored. Therefore, this study aimed to investigate the in vitro effects of GM-CSF on the expression of genes related to glucose transporters and signaling pathways, sperm motility, and viability in testicular biopsies. METHODS AND RESULTS: Following testicular sperm extraction from 20 patients diagnosed with OA, each sample was divided into two parts: the experimental samples were incubated with medium containing 2 ng/ml GM-CSF at 37 °C for 60 min, and the control samples were incubated with medium without GM-CSF. Subsequently, the oocytes retrieved from the partner were injected with sperm from the treatment and control groups. The sperm parameters (motility and viability), the expression levels of sperm motility-related genes (PIK3R1, PIK3CA, and AKT1), and the expression levels of sperm energy metabolism-related genes (GLUT1, GLUT3, and GLUT14) were assessed. Furthermore, the fertilization and day 3 embryo development rate and embryo quality were evaluated. Compared with those in the nontreated group, the motility parameters and the mRNA expression levels of PIK3R1, AKT1, and GLUT3 in testicular sperm supplemented with GM-CSF were significantly greater (p < 0.05). However, no significant differences in the mRNA expression of PIK3CA, GLUT1, or GLUT14 were detected. According to the ICSI results, compared with the control group, the GM-CSF treatment group exhibited significantly greater fertilization rates (p = 0.027), Day 3 embryo development rate (p = 0.001), and proportions of good-quality embryos (p = 0.002). CONCLUSIONS: GM-CSF increased the expression of genes related to motility and the energy metabolism pathway and effectively promoted the motility of testis-extracted spermatozoa, consequently yielding positive clinical outcomes.

The effects of two different fatigue protocols on movement quality during anticipated and unanticipated change of directions in female soccer players.

OBJECTIVE: This study compared neuromuscular control under two fatigue protocols during anticipated and unanticipated change of direction (COD) maneuvers and evaluated their effects on the risk of non-contact ACL injuries. METHOD: Forty-five female soccer players (mean age: 22.22 ± 2.24 years; mean height: 166.24 ± 3.33 cm; mean mass: 59.84 ± 5.03 kg) were divided into three groups: functional fatigue (Soccer specific fatigue ptotocol-SOFT90), non-functional fatigue (Bruce protocol), and control group. Before and after the implementation of neuromuscular control fatigue protocols were evaluated using the cutting motion assessment score tool (CMAS). Two-dimensional (2D) videos were recorded during anticipated and unanticipated COD trials for both dominant and non-dominant legs. RESULTS: Significant time effects (p < 0.05) and group-time interactions (p < 0.05) were observed in both anticipated and unanticipated conditions for both dominant and non-dominant legs after the fatigue protocols. The functional fatigue group exhibited higher CMAS changes, indicating poorer movement quality following fatigue. Notably, the non-dominant leg displayed amplified deficits during unanticipated COD maneuvers following the functional fatigue protocol. CONCLUSIONS: Fatigue significantly impairs neuromuscular control, particularly in unanticipated COD situations, which increases the risk of non-contact ACL injuries. To mitigate this risk, coaches, trainers, and medical professionals should prioritize targeted training and injury prevention strategies, focusing on the non-dominant leg during unanticipated COD maneuvers.

Leisure-time and occupational physical activity and risk of cardiovascular disease incidence: a systematic-review and dose-response meta-analysis of prospective cohort studies.

BACKGROUND AND OBJECTIVE: Physical activity has benefits for the cardiovascular system, however, what levels and types of activity provide optimal cardiovascular health is unclear. We aimed to determine the level of physical activity that has the most benefits against cardiovascular diseases (CVD). METHODS: PubMed, Scopus, and Web of Science were searched for prospective cohort studies on leisure-time (LTPA) or occupational physical activity (OPA) as the exposure and major types of CVD (total CVD, coronary heart disease [CHD], stroke, and atrial fibrillation [AF]) incidence as the outcome. Risk of bias of studies was evaluated using the ROBINS-I tool. Summary hazard ratios (HR) were calculated using random-effects pairwise model. RESULTS: A total of 103 studies were included in the analysis. The highest versus the lowest LTPA was associated with a lower risk of overall CVD (HR = 0.81; 95% CI: 0.77-0.86), CHD (HR = 0.83; 0.79-0.88), and stroke (HR = 0.83; 0.79-0.88), but not AF (HR = 0.98; 0.92-1.05). Linear dose-response analyses showed a 10%, 12%, 9%, and 8% risk reduction in CVD, CHD, stroke, and AF incidence, respectively, for every 20 MET-hours/week increase in LTPA. In nonlinear dose-response analyses, there were inverse associations up to 20 MET-hours/week with 19% and 20% reduction in CVD and CHD risk, and up to 25 MET-hours/week with 22% reduction in stroke, with no further risk reduction at higher LTPA levels. For AF, there was a U-shaped nonlinear association with the maximum 8% risk reduction at 10 MET-hours/week of LTPA. Higher levels of OPA were not associated with risk of CVD, CHD, stroke, or AF. CONCLUSIONS: Overall, results showed an inverse dose-response relationship between LTPA and risk of CVD, CHD, stroke, and AF. Running was the most beneficial LTPA but the risk was similar among various LTPA intensities. OPA showed no benefits in total or any type of CVD.

A 30-year trend of dairy consumption and its determinants among income groups in Iranian households.

Introduction: Milk and dairy products provide essential nutrients and have the potential to prevent chronic diseases, thus reducing healthcare costs. However, there is a lack of consistent and updated data on dairy consumption trends in Iran. This study aims to analyze the trends in dairy consumption among Iranian households from 1991 to 2021, focusing on household-level determinants across different expense groups. Methods: The study uses data from the Iranian Household Expenditure and Income Survey conducted annually from 1991 to 2021 to analyze households' dairy consumption. The data includes values and expenses of food and non-food items purchased in the previous month, as well as demographic characteristics of household members. The households were categorized into 10 deciles based on their gross expense. The econometric model used weighted mean per capita milk, yogurt, cheese, and total dairy consumption based on milk equivalent for each decile. The model takes into account changes in income, prices, household composition, education level, occupation, and residency area using panel data. Data preparation and model estimation were performed using RStudio and STATA17 software. Results: Based on the findings, in 1991, per capita milk, yogurt, and cheese consumption were 26.77 kg, 16.63 kg, and 2.42 kg, respectively. By 2021, these figures changed to 22.68 kg, 11.06 kg, and 3.79 kg, reflecting a decrease in milk and yogurt consumption but an increase in cheese consumption. Family size was positively correlated with yogurt consumption and head of the household spouse's job score were positively correlated with milk, yogurt and cheese consumption. Also, the presence of under five-year-old children and older adults members (over the age of 60) in the household was inversely related with yogurt and cheese consumption. Female-headed households tended to purchase more cheese, while their milk purchase level was significantly lower. Residing in urban areas was negatively related to milk, while cheese and total dairy consumption was higher in urban areas. Discussion: The findings highlight the importance of targeted dairy subsidy interventions and educational programs to improve dairy consumption in Iranian households, especially among vulnerable groups. This will require urging policymakers and food system stakeholders for effective strategies that address macro-level factors to promote dairy consumption.

Relationship between dietary glycemic index and glycemic load and sperm-quality parameters in Iranian men: a cross-sectional study.

BACKGROUND: Infertility is a major clinical problem with psychological, financial and medical costs. Male infertility has recently been linked to 50% of childless couples. It is worth mentioning that diet and its components can be manipulated and applied in counseling meetings of infertile men as a modifiable factor. The goal of this study was to determine the correlation of dietary glycemic index (GI) and glycemic load (GL) with sperm-quality parameters in Iranian men. MATERIALS AND METHODS: In this cross-sectional study which was carried from Aug to Nov 2023, after excluding smokers, 322 men who were attending the IVF clinic of Ayatollah Mousavi Hospital for seminal analysis were enrolled. Dietary intake was completed by an expert dietitian through face-to-face interviews with a validated 168-item food frequency questionnaire (FFQ). In the present study, sperm-quality parameters, including motility, concentration, normal morphology, vitality, DNA fragmentation index (DFI), and chromatin maturation of sperm, were analyzed. The relationship between dietary GI and CL and these parameters was assessed. RESULTS: Adjusting for the baseline variables, dietary GI and GL showed positive and negative associations with sperm progressive motility, respectively (p = 0.01 and p < 0.001). Higher dietary GI was associated with lower (p = 0.03); however, a higher dietary GL was associated with higher immotile sperm (p < 0.001). A higher dietary GI was associated with a 77% higher sperm count (p = 0.003). In contrast, higher dietary GL was associated with a lower count (p < 0.001). Higher dietary GI and GL were associated with higher and lower percentages of sperm with normal morphology by 70% and 40%, respectively (p < 0.001 in both). A higher dietary GL was associated with an increase in sperm vitality and DFI of 33% and 53%, respectively (p < 0.001). Higher dietary GI showed a significant negative effect on sperm DFI (p = 0.009). Dietary GI and GL showed significant positive and negative effects on SCMA, respectively (p = 0.002 and p < 0.001). CONCLUSION: A diet with a higher GI showed beneficial effects on more parameters of sperm; however, higher dietary GL showed deleterious effects, except sperm vitality and SCMA. More studies are needed to obtain a concise result.

A novel homozygote nonsense variant of MSH4 leads to primary ovarian insufficiency and non-obstructive azoospermia.

BACKGROUND: Both non-obstructive azoospermia (NOA) and primary ovarian insufficiency (POI) are pathological conditions characterized by premature and frequently complete gametogenesis failure. Considering that the conserved meiosis I steps are the same between oogenesis and spermatogenesis, inherited defects in meiosis I may result in common causes for both POI and NOA. The present research is a retrospective investigation on an Iranian family with four siblings of both genders who were affected by primary gonadal failure. METHODS: Proband, an individual with NOA, was subjected to clinical examination, hormonal assessment, and genetic consultation. After reviewing the medical history of other infertile members of the family, patients with NOA went through genetic investigations including karyotyping and assessment of Y chromosome microdeletions, followed by Whole exome sequencing (WES) on the proband. After analyzing WES data, the candidate variant was validated using Sanger sequencing and traced in the family. RESULTS: WES analysis of the proband uncovered a novel homozygote nonsense variant, namely c.118C>T in MSH4. This variant resulted in the occurrence of a premature stop codon in residue 40 of MSH4. Notably, the variant was absent in all public exome databases and in the exome data of 400 fertile Iranian individuals. Additionally, the variant was found to co-segregate with infertility in the family. It was also observed that all affected members had homozygous mutations, while their parents were heterozygous and the fertile sister had no mutant allele, corresponding to autosomal recessive inheritance. In addition, we conducted a review of variants reported so far in MSH4, as well as available clinical features related to these variants. The results show that the testicular sperm retrieval and ovarian stimulation cycles have not been successful yet. CONCLUSION: Overall, the results of this study indicate that the identification of pathogenic variants in this gene will be beneficial in selecting proper therapeutic strategies. Also, the findings of this study demonstrate that clinicians should obtain the history of other family members of the opposite sex when diagnosing for POI and/or NOA.

Correlation of Dietary Macro- and Micro-Mineral Intake with Seminal Plasma Quality/Quantity and Oxidant/Antioxidant Status in Infertile Compared to the Normal Men: a Case-Control Study.

Male infertility is a global public health issue, but studies on the correlation between the dietary components and sperm quality showed inconclusive results due to the heterogeneous population with different dietary habits and environmental stimuli. Herein, the correlation of dietary macro- and micro-mineral intake was evaluated with quality/quantity and oxidant/antioxidant status of seminal fluid in infertile compared to the healthy men. One hundred twenty men attending to the infertility clinic of Ayatollah Mousavi Hospital in Zanjan City were enrolled. Seminal fluid was extracted, and groups were categorized into the infertile (non-standard) and normal (standard) groups based on the WHO, 2020 criteria. Food frequency questionnaire was completed. Seminal malondialdehyde (MDA) and total antioxidant capacity (TAC) were measured by ELISA kit based on the manufacture's instruction. An independent sample t-test was used to determine differences between the two groups, and linear regression model was used to determine the effect of each dietary macro/micro mineral intake on these parameters. Adjusting for all parameters, dietary selenium increased 3.7-folds the seminal TAC level (p=0.04) and decreased sperm with non-progressive motility by 2.4-folds (p=0.04). Higher manganese intake increased the sperm count by 7.8-folds (p=0.005). Dietary copper decreased sperm vitality and increased sperm with slow motility (OR= -1.7, 95% CI= -59.8, -9.9; p=0.007). Dietary zinc (OR=1.24, p=0.01) and iron (OR=1.5, p=0.02) showed a positive effect on sperm vitality. None of macro and micro minerals showed a significant effect on the seminal MDA level. Daily intake of adequate amounts of micro and macro minerals improves sperm quality and increases the antioxidant capacity of the seminal fluid; however, copper showed a negative correlation that must be evaluated in future studies.

Granulocyte-Macrophage Colony-Stimulating Factor Cytokine Addition After the Freeze-Thawing Process Improves Human Sperm Motility and Vitality in Asthenoteratozoospermia Patients.

The cryopreservation-thawing process of spermatozoa cells has negative impacts on their structure, function, and fertility parameters, which are known as cryoinjury. Asthenozoospermia patients are more susceptible to cryoinjury. Granulocyte-macrophage colony-stimulating factor (GM-CSF) increases sperm glucose uptake via the induction of glucose transporters, resulting in increased sperm motility. This study aimed to investigate the efficiency of GM-CSF supplementation of the cryopreservation media for semen samples of asthenoteratozoospermia patients. The study was carried out on 20 semen samples from infertile men referred to diagnosing semen analysis. To avoid subjective bias, two main sperm motility parameters, including velocity along the curvilinear path and velocity along the straight-line path were considered by the computer-assisted sperm analysis system. Afterward, each semen sample was divided into three equal aliquots and randomly assigned to one of the following groups: group I (control, freezing media only), group II (+GM-CSF, freezing medium supplemented with 2 µL/mL GM-CSF), or group III (GM-CSF added after thawing and washing). Following semen thawing, standard parameters, mitochondrial membrane potential (MMP), and the DNA Fragmentation Index were analyzed. Total sperm motility (progressive and non-progressive) improved significantly in group III samples after a 30-minute incubation with GM-CSF compared with the control group (26.5% ± 3.1% vs. 17.51% ± 2.59%). However, no differences in progressive motility or sperm morphology were found among the three thawed samples. The percentage of vitality was significantly higher in group III compared with the other two groups (28.38% ± 3.4% vs. 22.4% ± 3.08% and 22.14% ± 2.77%, respectively) (p < 0.05). JC-1 levels (a marker of MMP) were not significantly different between the examined groups (44.95% ± 8.26% vs. 36.61% ± 6.95% vs. 46.67% ± 7.7%, for control, group II, and group III, respectively) (p > 0.05). GM-CSF may be advantageous as an additive after freezing, improving total motility and viability after 30 minutes of post-thaw incubation; however, when supplied to the freezing media before cryopreservation, it is unable to protect against cryoinjury.

Methotrexate-induced Severe Pancytopenia in a Patient with Rheumatoid Arthritis: A Case Report and Review of Literature.

Toxicity associated with low doses of methotrexate (MTX) is low, but it may be fatal. Bone marrow suppression and mucositis are among the common side effects of low dose MTX toxicity. Different risk factors have been reported for toxicities associated with low doses of MTX, including accidental use of higher doses, renal dysfunction, hypoalbuminemia, and polypharmacy. In this paper, we present a female patient who had mistakenly used 7.5 mg of MTX daily instead of the same dose of MTX on Thursday and Friday. She was presented with mucositis and diarrhea to the emergency department. Moreover, we searched the databases Scopus and PubMed for available studies and case reports on toxicities associated with MTX dosing errors. The most frequently observed toxicities included gastrointestinal lesions, nausea, vomiting, skin lesions, and bone marrow suppression. Leucovorin, hydration, and urine alkalinization were among the most frequently used treatments. Finally, we summarize the data on the toxicities of low doses of MTX in different diseases.

The test-retest reliability and limits of agreement of the balance evaluation systems test (BESTest) in young people with intellectual disability.

Clinical tests for the assessment of postural balance in people with intellectual disability have been the most commonly used single or multi-item tests, but some tests have been developed, such as the BESTest. The purpose of the study was to evaluate the test-retest reliability and limits of agreement of the Balance Evaluation Systems Test (BESTest) in young people with intellectual disabilities. A descriptive cross-sectional study was conducted with 65 young people (ages 16-25 years) with intellectual disability. The participants completed the BESTest (27 items) twice. Intraclass correlation coefficients (ICC), 95% confidence intervals (CIs), and standard error of measurement (SEM) were calculated to determine the test-retest reliability of the BESTest. The BESTest overall scores' test-retest reliability was rated as excellent (≥ 0.75). Stability limits/verticality and reactive are fair to good (≥ 0.40- < 0.75). Biomechanical constraints, transitions and anticipatory movements, sensory orientation, and gait stability were excellent (≥ 0.75). Current evidence shows that young people with intellectual disabilities have impaired postural balance. However, there appears to be a lack of assessment tools that reliably evaluate the postural balance of this population. The results from this investigation show that BESTest provides "excellent reliability" (≥ 0.75) to assess postural balance in young people with intellectual disability.

The Effect on Flexibility and a Variety of Performance Tests of the Addition of 4 Weeks of Soleus Stretching to a Regular Dynamic Stretching Routine in Amateur Female Soccer Players.

The purpose of this study was to investigate the effects of 4 weeks of soleus stretching on ankle flexibility and dynamic balance, as well as selected monitoring and performance tests in soccer. Forty-five healthy female soccer players were randomly divided into a regular stretching group, a regular stretching group with soleus stretching, and a control group. Dynamic stretching protocols were performed for 4 weeks during three sessions per week as part of routine exercises. The regular group stretched three muscle groups (i.e., gastrocnemius, quadriceps, and hamstrings), while the regular + soleus group also stretched the soleus muscle. Before and after the stretching intervention, the ankle range of motion test, Y-balance test, drop jump test, dynamic knee valgus test, and Illinois Agility Running Test were performed. Ankle ROM, Y-balance, and DJ significantly improved in both intervention groups compared to controls. Only the regular + soleus group showed improvement in the Illinois Agility Running Test. Additionally, athletes performing the additional soleus stretching had greater improvements in ankle ROM and DJ but not in DKV or Y-balance. The results showed that adding soleus stretching into regular protocols can provide benefits for female soccer players in terms of performance parameters.

Targeted Amino Acids Profiling of Human Seminal Plasma from Teratozoospermia Patients Using LC-MS/MS.

Identifying the metabolome of human seminal plasma (HSP) is a new research area to screen putative biomarkers of infertility. This case-control study was performed on HSP specimens of 15 infertile patients with teratozoospermia (defined as normal sperm morphology < 4%) and 12 confirmed fertile normozoospermic men as the control group to investigate the seminal metabolic signature and whether there are differences in the metabolome between two groups. HSPs were subjected to LC-MS-MS analysis. MetaboAnalyst5.0 software was utilized for statistical analysis. Different univariate and multivariate analyses were used, including T-tests, fold change analysis, random forest (RF), and metabolite set enrichment analysis (MSEA). Teratozoospermic samples contained seventeen significantly different amino acids. Upregulated metabolites include glutamine, asparagine, and glycylproline, whereas downregulated metabolites include cysteine, γ-aminobutyric acid, histidine, hydroxylysine, hydroxyproline, glycine, proline, methionine, ornithine, tryptophan, aspartic acid, argininosuccinic acid, α-aminoadipic acid, and ß-aminoisobutyric acid. RF algorithm defined a set of 15 metabolites that constitute the significant features of teratozoospermia. In particular, increased glutamine, asparagine, and decreased cysteine, tryptophan, glycine, and valine were strong predictors of teratozoospemia. The most affected metabolic pathways in teratozoospermic men are the aminoacyl-tRNA, arginine, valine-leucine, and isoleucine biosynthesis. Altered metabolites detected in teratozoospermia were responsible for various roles in sperm functions that classified into four subgroups as follows: related metabolites to antioxidant function, energy production, sperm function, and spermatogenesis. The altered amino acid metabolome identified in this study may be related to the etiology of teratozoospermia, and may provide novel insight into potential biomarkers of male infertility for therapeutic targets.

A conceptual model for empowering faculty members of third-generation universities of medical sciences.

Background and objectives: Despite the crucial role of university staff and especially faculty members in moving towards third-generation universities, as well as the necessity of staff empowerment, only a handful of studies have been carried out on staff (especially faculty member) empowerment. This study designed a conceptual model for empowering faculty members of universities of medical sciences and facilitating transition to third-generation universities. Methods: The grounded theory approach was adopted to conduct this qualitative study. A total of 11 faculty members with entrepreneurial experience were selected as the sample using purposive sampling. The data were collected using semi-structured interviews, and the obtained data were entered into qualitative software (MAXQDA 10) for analysis. Results: The concepts identified in the coding process were summarized and classified into five groups and seven main categories. Then the conceptual model was designed with a set of causal factors (including structure of the education system, recruitment, training, and investment), structure and context factors (including structure and relationship), intervening factors (including promotion and ranking systems in universities and lack of mutual trust between industry and university), a core category (characteristics of capable faculty members), and an outcome (third-generation university). Finally, the conceptual model was developed to empower faculty members of third-generation universities of medical sciences. Conclusions: Based on the designed conceptual model, the most important issue in moving towards third-generation universities is "characteristics of capable faculty members." The present findings will help policy makers better understand the major factors affecting faculty member empowerment.

Rescuing fertility during COVID-19 infection: exploring potential pharmacological and natural therapeutic approaches for comorbidity, by focusing on NLRP3 inflammasome mechanism.

The respiratory system was primarily considered the only organ affected by Coronavirus disease 2019 (COVID-19). As the pandemic continues, there is an increasing concern from the scientific community about the future effects of the virus on male and female reproductive organs, infertility, and, most significantly, its impact on the future generation. The general presumption is that if the primary clinical symptoms of COVID-19 are not controlled, we will face several challenges, including compromised infertility, infection-exposed cryopreserved germ cells or embryos, and health complications in future generations, likely connected to the COVID-19 infections of parents and ancestors. In this review article, we dedicatedly studied severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) virology, its receptors, and the effect of the virus to induce the activation of inflammasome as the main arm of the innate immune response. Among inflammasomes, nucleotide oligomerization domain-like receptor protein, pyrin domain containing 3 (NLRP3) inflammasome pathway activation is partly responsible for the inflicted damages in both COVID-19 infection and some reproductive disorders, so the main focus of the discussion is on NLRP3 inflammasome in the pathogenesis of COVID-19 infection alongside in the reproductive biology. In addition, the potential effects of the virus on male and female gonad functions were discussed, and we further explored the potential natural and pharmacological therapeutic approaches for comorbidity via NLRP3 inflammasome neutralization to develop a hypothesis for averting the long-term repercussions of COVID-19. Since activation of the NLRP3 inflammasome pathway contributes to the damage caused by COVID-19 infection and some reproductive disorders, NLRP3 inflammasome inhibitors have a great potential to be considered candidates for alleviating the pathological effects of the COVID-19 infection on the germ cells and reproductive tissues. This would impede the subsequent massive wave of infertility that may threaten the patients.