The relationship between fatigue, pruritus, and thirst distress with quality of life among patients receiving hemodialysis: a mediator model to test concept of treatment adherence.

Hemodialysis is a conservative treatment for end-stage renal disease. It has various complications which negatively affect quality of life (QOL). This study aimed to examine the relationship between fatigue, pruritus, and thirst distress (TD) with QOL of patients receiving hemodialysis, while also considering the mediating role of treatment adherence (TA). This cross-sectional study was carried out in 2023 on 411 patients receiving hemodialysis. Participants were consecutively recruited from several dialysis centers in Iran. Data were collected using a demographic information form, the Fatigue Assessment Scale, the Thirst Distress Scale, the Pruritus Severity Scale, the 12-Item Short Form Health Survey, and the modified version of the Greek Simplified Medication Adherence Questionnaire for Hemodialysis Patients. Covariance-based structural equation modeling was used for data analysis. The structural model and hypothesis testing results showed that all hypotheses were supported in this study. QOL had a significant inverse association with fatigue, pruritus, and TD and a significant positive association with TA. TA partially mediated the association of QOL with fatigue, pruritus, and TD, denoting that it helped counteract the negative association of these complications on QOL. This model explained 68.5% of the total variance of QOL. Fatigue, pruritus, and TD have a negative association with QOL among patients receiving hemodialysis, while TA reduces these negative associations. Therefore, TA is greatly important to manage the associations of these complications and improve patient outcomes. Healthcare providers need to assign high priority to TA improvement among these patients to reduce their fatigue, pruritus, and TD and improve their QOL. Further studies are necessary to determine the most effective strategies for improving TA and reducing the burden of complications in this patient population.

Distribution of Plasma One-Carbon Metabolism Factors and Amino Acids Profile in Depression State Treated with Paroxetine: A Model Study.

OBJECTIVE: Stress may have an important role in the origin and progress of depression and can impair metabolic homeostasis. The one-carbon cycle (1-CC) metabolism and amino acid (AA) profile are some of the consequences related to stress. In this study, we investigated the Paroxetine treatment effect on the plasma metabolite alterations induced by forced swim stress-induced depression in mice. MATERIALS AND METHODS: In this experimental study that was carried out in 2021, thirty male NMRI mice (6-8 weeks age, 30 ± 5 g) were divided into five groups: control, sham, paroxetine treatment only (7 mg/kg BW/day), depression induction, and Paroxetine+depression. Mice were subjected to a forced swim test (FST) to induce depression and then were treated with Paroxetine, for 35 consecutive days. The swimming and immobility times were recorded during the interventions. Then, animals were sacrificed, plasma was prepared and the concentration of 1-CC factors and twenty AAs was measured by spectrophotometry and high-performance liquid chromatography system (HPLC) techniques. Data were analyzed by SPSS, using One-Way ANOVA and Pearson Correlation, and P<0.05 was considered significant. RESULTS: Plasma concentrations of phenylalanine, glutamate, aspartate, arginine, ornithine, citrulline, threonine, histidine, and alanine were significantly reduced in the depression group in comparison with the control group. The Homocysteine (Hcy) plasma level was increased in the Paroxetine group which can be associated with hyperhomocysteinemia. Moreover, vitamin B12, phenylalanine, glutamate, ornithine, citrulline, and glycine plasma levels were significantly reduced in the depression group after Paroxetine treatment. CONCLUSION: This study has demonstrated an impairment in the plasma metabolites' homeostasis in depression and normal conditions after Paroxetine treatment, although, further studies are required.

Oxidative versus reductive stress: a delicate balance for sperm integrity.

Despite the long-standing notion of "oxidative stress," as the main mediator of many diseases including male infertility induced by increased reactive oxygen species (ROS), recent evidence suggests that ROS levels are also increased by "reductive stress," due to over-accumulation of reductants. Damaging mechanisms, like guanidine oxidation followed by DNA fragmentation, could be observed following reductive stress. Excessive accumulation of the reductants may arise from excess dietary supplementation over driving the one-carbon cycle and transsulfuration pathway, overproduction of NADPH through the pentose phosphate pathway (PPP), elevated levels of GSH leading to impaired mitochondrial oxidation, or as a result NADH accumulation. In addition, lower availability of oxidized reductants like NAD+, oxidized glutathione (GSSG), and oxidized thioredoxins (Trx-S2) induce electron leakage leading to the formation of hydrogen peroxide (H2O2). In addition, a lower level of NAD+ impairs poly (ADP-ribose) polymerase (PARP)-regulated DNA repair essential for proper chromatin integrity of sperm. Because of the limited studies regarding the possible involvement of reductive stress, antioxidant therapy remains a central approach in the treatment of male infertility. This review put forward the concept of reductive stress and highlights the potential role played by reductive vs oxidative stress at pre-and post-testicular levels and considering dietary supplementation.

Paroxetine treatment in an animal model of depression improves sperm quality.

Depression in mammals is known to be associated with poor reproductive capacity. In males, it has been associated with decreased efficiency of spermatogenesis as well as the production of spermatozoa of reduced structural and functional integrity. Although antidepressants are effective in correcting depressive states, there is controversy regarding their effectiveness in restoring male reproductive function. Here, using an animal model of depression induced by a forced swim test, we confirmed that depression is accompanied by impaired male reproductive function. We further show that administration of a conventional antidepressant of the serotonin reuptake inhibitor class (paroxetine) impairs male reproductive performance in terms of sperm production and quality when administered to healthy animals. Intriguingly, when paroxetine is administered to "depressed" animals, it resulted in a complete restoration of the animal's ability to produce sperm that appears to be as capable of meeting the parameters evaluated here as those of control animals. The one-carbon cycle (1CC) is one of the most important metabolic cycles that include the methionine and folate cycles and plays a major role in DNA synthesis, amino acids, and also the production of antioxidants. Our results show that depression affects the main components of this cycle and paroxetine on healthy mice increases homocysteine levels, decreases glycine and vitamin B12, while in depressed mice, it increases folate levels and decreases vitamin B12. Thus, paroxetine exerts negative impacts on male reproductive function when administered to healthy animals and it well correlate with the altered sperm parameters and functions of depressed animals, and its mechanism remains to be explored.

Vulnerability of The Male Reproductive System to SARS-CoV-2 Invasion: Potential Role for The Endoplasmic Reticulum Chaperone Grp78/HSPA5/BiP.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) may adversely affect male reproductive tissues and male
fertility. This concern is elicited by the higher susceptibility and mortality rate of men to the SARS-CoV-2 mediated coronavirus disease-19 (COVID-19), compared to the women. SARS-CoV-2 enters host cells after binding to a functional receptor named angiotensin-converting enzyme-2 (ACE2) and then replicates in the host cells and gets released into the plasma. SARS-CoVs use the endoplasmic reticulum (ER) as a site for viral protein synthesis and processing, as well as glucose-regulated protein 78 (Grp78) is a key ER chaperone involved in protein folding by preventing newly synthesized proteins from aggregation.
Therefore, we analyzed Grp78 expression in various human organs, particularly male reproductive organs, using Broad
Institute Cancer Cell Line Encyclopedia (CCLE), the Genotype-Tissue Expression (GTEx), and Human Protein Atlas online
datasets. Grp78 is expressed in male reproductive tissues such as the testis, epididymis, prostate, and seminal vesicle. It can facilitate the coronavirus entry into the male reproductive tract, providing an opportunity for its replication. This link between the SARS-CoV-2 and the Grp78 protein could become a therapeutic target to mitigate its harmful effects on male fertility.

Apoptotic M540 bodies present in human semen interfere with flow cytometry-assisted assessment of sperm DNA fragmentation and oxidation.

BACKGROUND: The use of flow cytometry (FC) to evaluate sperm DNA fragmentation via deoxynucleotidyl transferase terminal fluorescein dUTP nick-end labeling (TUNEL) has shown inconsistencies compared with conventional fluorescent microscopic analyses. It has been hypothesized that the observed discrepancies could be attributed to the presence of apoptotic bodies that can be labeled with merocyanine 540, the so-called M540 bodies. In order to verify this hypothesis and determine the accuracy of our in-house FC-assisted evaluation of spermatozoa parameters, we used FC to evaluate both the fragmentation of sperm DNA using the TUNEL assay and the oxidation of sperm DNA using the 8-OHdG assay on semen samples with or without M540 bodies. RESULTS: We show that the presence of M540 bodies lead to underestimation of both the level of sperm DNA fragmentation and sperm DNA oxidation when using FC assisted detection systems. We also observed that this situation is particularly pertinent in semen samples classified as abnormal with respect to the routine WHO semen evaluation as they appear to contain more M540 bodies than normal samples. CONCLUSIONS: We conclude that M540 bodies interfere with both FC-conducted assays designed to evaluate sperm nuclear/DNA integrity. Exclusion of these contaminants in unprepared semen samples should be performed in order to correctly appreciate the true level of sperm DNA/nuclear damage which is known to be a critical male factor for reproductive success.

RéSUMé: CONTEXTE: L'utilisation de la cytométrie en flux (CF) pour évaluer la fragmentation de l'ADN des spermatozoïdes via la technique TUNEL (Terminal transferase dUTP nick-end labelling) a montré des incohérences par rapport aux analyses conventionnelles par microscopie fluorescente. L'hypothèse a été émise que les divergences observées pourraient être attribuées à la présence de corps apoptotiques qui peuvent être marqués à la mérocyanine 540 (corps M540). Afin de vérifier cette hypothèse et de déterminer la précision de notre évaluation interne des paramètres des spermatozoïdes, nous avons mesuré par CF à la fois la fragmentation de l'ADN des spermatozoïdes en utilisant le test TUNEL et l'oxydation de l'ADN des spermatozoïdes en utilisant le test 8-OHdG sur des échantillons de sperme avec ou sans corps M540. RéSULTATS: Nous montrons que la présence des corps M540 entraîne une sous-estimation du niveau de fragmentation et d'oxydation de l'ADN des spermatozoïdes lors de l'utilisation de systèmes de détection assistée par CF. Nous avons également observé que cette situation est exacerbée dans les échantillons de sperme classés comme anormaux (selon les standards de l'OMS), car ces derniers semblent contenir plus de corps M540 que les échantillons normaux. CONCLUSIONS: Nous concluons que les corps M540 interfèrent avec les deux tests conduits par CF et conçus pour évaluer l'intégrité nucléaire des spermatozoïdes. L'exclusion de ces contaminants dans les échantillons de sperme non préparés devrait être considérée afin d'apprécier correctement le véritable niveau de dommages au noyau spermatique qui est connu pour être un facteur critique pour le succès reproductif.

Analysis of leukocyte and sperm telomere length in oligozoospermic men.

Telomere length is considered one of the most relevant biological markers of genomic stability since it protects DNA from impairment and also ensures chromosome alignment during DNA replication. The negative impact of telomere shortening on sperm quality has been suggested as an important indicator of male infertility. Therefore, we aimed to assess leucocyte and sperm telomere length (LTL&STL), as well as sperm parameters, DNA damage and protamine deficiency in men with oligozoospermia as compared to fertile men. Our results demonstrated a significant reduction in sperm parameters (concentration, motility, morphology), LTL & STL and a significant increase in sperm DNA damage and protamine deficiency in oligozoospermic men compared with fertile individuals. These outcomes revealed that low sperm concentration in men is possibly a sign of impaired meiotic and/or meiotic division during the spermatogenesis process. It is not only associated with proper chromatin packaging but also with telomere length as a key player in the process of mitosis and meiosis, assisting in chromosomal alignment, pairing, synapsis and crossing over during spermatogenesis.

Sperm chromatin integrity in a man with macrocephaly syndrome.

This study reports chromatin status and ICSI outcomes in a case of sperm macrocephaly syndrome(SMS), showing 100% of spermatozoa with abnormal morphology. Percentages of sperm DNA fragmentation for TUNEL (31.7% versus 6.5%), SCSA (33% versus 25%) assays, chromatin maturity tests, CMA3 (58% versus 29%) and aniline blue (63% versus 35%) staining were higher in case sample compared to the fertile sample. Artificial oocyte activation resulted in a similar fertilisation rate between case and control samples (71% versus 66.7%), but the case showed delayed embryo development on day 3 post-insemination. Unlike fertile case, no embryos reached the blastocyst stage. The result of this case study shows that macrocephaly is associated with reduced chromatin maturity and DNA integrity. Although both cases showed a similar chance for fertilisation through artificial chemical activation for only macrocephalic man, the developmental competency is jeopardised in such cases.

Single-blind clinical trial: Sperm selection based on capacity to pass through cumulus oophorous column improves ICSI outcomes.

BACKGROUND: Sperm selection procedures for future strategies that aim to select normal spermatozoa with intact DNA to improve intracytoplasmic sperm injection (ICSI) outcomes are in early developing stage. OBJECTIVES: The objective is to find out whether the sperm selection procedure based on the ability of spermatozoa to traverse the cumulus cells could improve clinical outcomes of ICSI technique in infertile couples with male factor etiology. MATERIALS AND METHODS: For this single-blind clinical trial, mature metaphase II oocytes were retrieved from 150 couples with male factor infertility, male age lower than 45 years and female age under 38 years. These couples were divided into two groups. In control group (n = 75), spermatozoa processed by density gradient centrifugation (DGC) were used to inject the oocytes. In the study group (n = 75), the oocytes were divided into sibling groups. In one sibling group (DGC), the oocytes were inseminated with DGC-processed spermatozoa while in the other group (DGC-CC), they were inseminated with DGC-processed spermatozoa that passed cumulus oophorous column. RESULTS: Mean fertilization and embryo quality were significantly higher in DGC-CC group compared to DGC and control group. In addition, mean of chemical pregnancy (52.27% vs. 34.14%; p = 0.05), clinical pregnancy based on sac (52.27% vs. 32.92%; p = 0.03), clinical pregnancy with heart beat (52.27% vs. 25.60%; p = 0.003) and ongoing pregnancy (43.18% vs. 21.95%; p = 0.02) rates were significantly higher in DGC-CC group compared to control group. CONCLUSION: Sperm selection based on integrated systems such as DGC and ability to pass through cumulus oophorous column could improve clinical outcomes of ICSI in couples with male factor infertility.

Signs of ROS-Associated Autophagy in Testis and Sperm in a Rat Model of Varicocele.

Since autophagy was suspected to occur in the pathological situation of varicocele (VCL), we have attempted to confirm it here using a surgical model of varicocele-induced rats. Thirty Wistar rats were divided into three groups (varicocele/sham/control) and analyzed two months after the induction of varicocele. Testicular tissue sections and epididymal mature sperm were then monitored for classic features of varicocele, including disturbance of spermatogenesis, impaired testicular carbohydrate and lipid homeostasis, decreased sperm count, increased sperm nuclear immaturity and DNA damage, oxidative stress, and lipid peroxidation. At the same time, we evaluated the Atg7 protein content and LC3-II/LC3-1 protein ratio in testis and mature sperm cells, two typical markers of early and late cellular autophagy, respectively. We report here that testis and mature sperm show higher signs of autophagy in the varicocele group than in the control and sham groups, probably to try to mitigate the consequences of VCL on the testis and germ cells.

The effect of dexmedetomidine on spinal anesthesia quality and hemodynamic changes in patients undergoing inguinal hernia repair surgery: intravenous versus intrathecal.

PURPOSE: The aim of this study was to evaluate the quality of spinal anesthesia and hemodynamic parameters of intravenous versus intrathecal dexmedetomidine in patients undergoing inguinal hernia repair surgery under spinal anesthesia. METHODS: Fifty male patients aged 18-70 years with ASA I and II were randomly divided into two groups of 25 patients receiving either intravenous (1 µg/kg infused during 10 min before blockade) or intrathecal (5 µg, added to local anesthetics) dexmedetomidine. The duration of analgesia, sensory and motor blockade levels, the score of pain intensity, post-operative analgesic usage and the level of sedation as well as hemodynamic changes, and complications were recorded. RESULTS: The duration of analgesia in the intrathecal group was significantly longer than intravenous group (403.588 ± 93.706 vs. 274.048 ± 47.266 min; P < 0.001). Duration of the sensory and motor blockade were significantly longer in intrathecal than intravenous group (230.440 ± 26.494 vs. 181.400 ± 28.850 min; P < 0.001 for sensory block, and 253.800 ± 32.637 vs. 205.400 ± 30.921 min; P < 0.001 for motor block). The score of pain intensity was lower in the intrathecal group in the post-operative period (3.680 ± 1.680 vs. 5.520 ± 1.901; P = 0.001 and 2.360 ± 1.320 vs. 3.24 ± 1.69; P = 0.041, respectively, for the time 6 and 12). Ramsay sedation score was higher in the intravenous group during surgery but it was higher in intrathecal group during recovery room period (P < 0.05). Moreover, the incidence of bradycardia was significantly lower in the intrathecal group (0% vs. 36% respectively; P = 0.002). CONCLUSION: Administration of intrathecal dexmedetomidine along with local anesthetics can be recommended to increase the quality of spinal anesthesia with minimal complications.

Evaluation of Oxidative Stress in Testis and Sperm of Rat Following Induced Varicocele.

PURPOSE: Oxidative stress (OS) plays a central role in the pathophysiology of varicocele (VC), however, com-prehensive studies concomitantly assessing semen parameter along with chromatin status, oxidative stress, and enzymatic antioxidants in both testis and sperm are limited. Therefore, this study aims to assess these parameters in varicocelized rats. MATERIALS AND METHODS: For this study, 30 Wistar rats were randomly divided into three groups: Control group (I); sham-operated group (II) and left varicocele group (III). Left varicocele was induced and two months after surgery, we evaluated sperm parameters, persistent histone, DNA integrity and lipid peroxidation in sperm and also oxidant/antioxidant markers in testis. RESULTS: The results showed that sperm concentration, motility, and normal morphology significantly decreased in varicocele group compared to other groups (P < 0.001). Also, we observed a significant increase in persistent histone and DNA damage of sperm cells in varicocele rats (P < 0.05). In addition, oxidant assessment analysis showed that ROS level was higher in testis tissue and sperm cells from the left varicocele rats compared to the control group (P < 0.05). CONCLUSION: This results show that varicocele has a negative effect on spermatogenesis and increased oxidative stress and reduce in antioxidant capacity hand in hand lead to the production of sperm with damaged chromatin which reduces the fertility potential and may jeopardize the future health of the progeny.