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Lifestyle-, environmental-, and additional health factors associated with an increased sperm DNA fragmentation: a systematic review and meta-analysis.
Szabó, A, Váncsa, S, Hegyi, P, Váradi, A, Forintos, A, Filipov, T, Ács, J, Ács, N, Szarvas, T, Nyirády, P, et al
Reproductive biology and endocrinology : RB&E. 2023;21(1):5
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The World Health Organization defines infertility as regular unprotected sexual intercourse without achieving conception within a year. In recent years, there has been a growing demand for functional, objective parameters reflecting fertility status more clearly than classical parameters. Of these, sperm DNA fragmentation (SDF) and the DNA fragmentation index – denoting the percentage of sperm with damaged DNA – seem to be of utmost importance. The aim of this study was to investigate all risk factors that may potentially be increasing SDF. This study is a systematic review and meta-analysis of one hundred and ninety articles. The earliest studies were published in 2003, and the latest in 2021. Results show that several modifiable risk factors negatively affect SDF, namely; a. health conditions: varicocele [when veins become enlarged inside the pouch of skin that holds the testicles] and impaired glucose tolerance, b. infections: Chlamydia, c. malignancies: testicular tumours, and d. lifestyle factors: smoking, alcohol consumption and body mass index. Authors conclude that several lifestyle-, environmental-, and additional health factors are associated with increased SDF.
Abstract
INTRODUCTION Infertility affects one in every six couples in developed countries, and approximately 50% is of male origin. In 2021, sperm DNA fragmentation (SDF) testing became an evidence-based test for fertility evaluations depicting fertility more clearly than standard semen parameters. Therefore, we aimed to summarize the potential prognostic factors of a higher SDF. METHODS We conducted a systematic search in three medical databases and included studies investigating any risk factors for SDF values. We calculated mean differences (MD) in SDF with 95% confidence interval (CI) for exposed and non-exposed individuals. RESULTS We included 190 studies in our analysis. In the group of associated health conditions, varicocele (MD = 13.62%, CI: 9.39-17.84) and impaired glucose tolerance (MD = 13.75%, CI: 6.99-20.51) had the most significant increase in SDF. Among malignancies, testicular tumors had the highest impact, with a maximum of MD = 11.3% (CI: 7.84-14.76). Among infections, the overall effects of both Chlamydia and HPV were negligible. Of lifestyle factors, smoking had the most disruptive effect on SDF - an increase of 9.19% (CI: 4.33-14.06). Different periods of sexual abstinence did not show significant variations in SDF values. Age seemed to have a more drastic effect on SDF from age 50 onwards, with a mean difference of 12.58% (CI: 7.31-17.86). Pollution also had a detrimental effect - 9.68% (CI: 6.85-12.52). CONCLUSION Of the above risk factors, varicocele, impaired glucose tolerance, testicular tumors, smoking, pollution, and paternal age of over 50 were associated with the highest SDF. TRIAL REGISTRATION CRD42021282533.
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The impact of diabetes mellitus type 1 on male fertility: Systematic review and meta-analysis.
Facondo, P, Di Lodovico, E, Delbarba, A, Anelli, V, Pezzaioli, LC, Filippini, E, Cappelli, C, Corona, G, Ferlin, A
Andrology. 2022;10(3):426-440
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The relationship between type 2 diabetes mellitus and male hypogonadism is well known, whereas the impact of type 1 diabetes mellitus (DM1) on male fertility and testis functions has been less studied. The aim of this study was to systematically review and discuss the available evidence evaluating paternity rate, male gonadal axis, and sperm parameters in men with DM1. This study is a systematic review and meta-analysis of fourteen studies. Results show: - reduced fertility potential in patients with DM1, as they have a lower number of children compared with unaffected population. In fact, the rate of children is statistically significantly lower among men who had been diagnosed with DM1 at an earlier age, according to a longer duration of the disease. - that men with DM1, compared with controls, have significantly lower normal sperm morphology, progressive motility and a trend toward a reduced semen volume, without difference in total sperm count and concentration. Authors conclude that DM1 might impair reproductive health at different levels, including functional sperm alterations definitively leading to reduced fertility rate in these patients.
Abstract
BACKGROUND Some evidence suggests that diabetes mellitus type 1 (DM1) could affect male fertility, gonadal axis, semen parameters, and spermatogenesis because of effects of hyperglycemia and insulin deficiency. Anyhow, the exact impact of DM1 on male fertility is unclear. OBJECTIVES To review the studies evaluating paternity rate, male gonadal axis, and semen parameters in men with DM1. MATERIALS AND METHODS A review of relevant literature from January 1980 to December 2020 was performed. Only studies published in English reporting data on fatherhood (rate of children by natural fertility), hormonal and seminal parameters were included. Out of 14 retrieved articles, the eight studies evaluating semen parameters were meta-analyzed. RESULTS The rate of children (four studies) was lower than controls among men affected by DM1, especially in men with a longer duration of disease. The data of gonadal hormonal profile in DM1 men (six studies) are very heterogeneous and a neutral effect of DM1 or a condition of subclinical hypogonadism could not be concluded. Meta-analysis showed that men with DM1 (n = 380), compared with controls (n = 434), have significantly lower normal sperm morphology [-0.36% (-0.66; -0.06), p < 0.05, six studies] and sperm progressive motility [33.62% (-39.13; -28.11), p < 0.001, two studies] and a trend toward a lower seminal volume [-0.51 (-1.03; 0.02), p = 0.06, eight studies], without difference in total sperm count and concentration. Data on scrotal ultrasound and sperm DNA fragmentation are too few. No study evaluated other factors of male infertility, such as transrectal ultrasound, semen infections, sperm auto-antibodies, and retrograde ejaculation. DISCUSSION DM1 might impair male fertility and testis functions (endocrine, spermatogenesis), but definition of its actual impact needs further studies. CONCLUSION Men with DM1 should be evaluated with a complete hormonal, seminal, and ultrasound workup to better define their fertility potential and need for follow up of testis functions.
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Melatonin: Roles in influenza, Covid-19, and other viral infections.
Anderson, G, Reiter, RJ
Reviews in medical virology. 2020;30(3):e2109
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Viruses like influenza and coronaviruses change quickly, making it challenging to develop effective treatments and vaccines in a short time frame. Consequently, the use of generic substances that limit viral effects are of high interest. In this paper, the authors summarize a range of mechanisms in which melatonin can alter the impact of virus infections and infection-associated inflammatory overdrive aka cytokine storm. Melatonin, the sleep hormone, is well known for its potent antioxidant and anti-inflammatory action. It seems highly likely that melatonin can modulate the cellular function of all cells, mostly via mitochondrial function. This is particularly relevant in immune cells. For example, the daytime variance in immune function seems to be closely linked with mitochondrial activity and energy production. Other relevant mechanisms described are the antiviral role of melatonin-induced sirtuins - proteins that regulate cellular health-, the impact of viruses on cell coordinating microRNA, the role of the gut microbiome and gut permeability, as well as sympathetic nervous system activation and the protective effects of parasympathetic activation. Also considered are pre-existing health conditions and conditions that are linked with a decline in melatonin along with ageing, all being groups in which severity of viral infections is felt. This paper may be of interest to those who like to explore in more depth the mechanisms behind melatonin and its ability to influence viral disease progression.
Abstract
There is a growing appreciation that the regulation of the melatonergic pathways, both pineal and systemic, may be an important aspect in how viruses drive the cellular changes that underpin their control of cellular function. We review the melatonergic pathway role in viral infections, emphasizing influenza and covid-19 infections. Viral, or preexistent, suppression of pineal melatonin disinhibits neutrophil attraction, thereby contributing to an initial "cytokine storm", as well as the regulation of other immune cells. Melatonin induces the circadian gene, Bmal1, which disinhibits the pyruvate dehydrogenase complex (PDC), countering viral inhibition of Bmal1/PDC. PDC drives mitochondrial conversion of pyruvate to acetyl-coenzyme A (acetyl-CoA), thereby increasing the tricarboxylic acid cycle, oxidative phosphorylation, and ATP production. Pineal melatonin suppression attenuates this, preventing the circadian "resetting" of mitochondrial metabolism. This is especially relevant in immune cells, where shifting metabolism from glycolytic to oxidative phosphorylation, switches cells from reactive to quiescent phenotypes. Acetyl-CoA is a necessary cosubstrate for arylalkylamine N-acetyltransferase, providing an acetyl group to serotonin, and thereby initiating the melatonergic pathway. Consequently, pineal melatonin regulates mitochondrial melatonin and immune cell phenotype. Virus- and cytokine-storm-driven control of the pineal and mitochondrial melatonergic pathway therefore regulates immune responses. Virus-and cytokine storm-driven changes also increase gut permeability and dysbiosis, thereby suppressing levels of the short-chain fatty acid, butyrate, and increasing circulating lipopolysaccharide (LPS). The alterations in butyrate and LPS can promote viral replication and host symptom severity via impacts on the melatonergic pathway. Focussing on immune regulators has treatment implications for covid-19 and other viral infections.
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Anxiety reduction through art therapy in women. Exploring stress regulation and executive functioning as underlying neurocognitive mechanisms.
Abbing, A, de Sonneville, L, Baars, E, Bourne, D, Swaab, H
PloS one. 2019;14(12):e0225200
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Anxiety treatments currently involve medication and changing an individual’s beliefs through cognitive behavioural therapy (CBT). Art therapy (AT) is often used as a CBT treatment strategy, although little is known about its effectiveness. This randomised control trial of 47 adult women with anxiety aimed to understand the role of AT in anxiety treatment over three months. The results showed improvements in self-reported measures of anxiety, the ability to control emotions, memory and the ability to manage tasks with AT, however subjects were just as susceptible to stress following treatment. It was concluded that anxiety reduction was related to improvements in emotions, memory and task management and this was as a result of AT. This study could be used by healthcare professionals to recommend AT to individuals with symptoms of anxiety as part of their treatment management plan.
Abstract
OBJECTIVES To explore possible working mechanisms of anxiety reduction in women with anxiety disorders, treated with art therapy (AT). METHODS A RCT comparing AT versus waiting list (WL) condition on aspects of self-regulation. Stress regulation (heart rate and heart rate variability) and executive functioning (daily behavioural and cognitive performance aspects of executive functioning (EF)) were evaluated in a pre-post design. Participants were women, aged 18-65 years with moderate to severe anxiety symptoms. RESULTS Effectiveness of AT compared to WL was demonstrated in a higher resting HRV post treatment, improvements in aspects of self-reported daily EF (emotion control, working memory, plan/organize and task monitor), but not in cognitive performance of EF, stress responsiveness and down regulation of stress. The decrease in anxiety level was associated with improvements in self-reported daily EF. CONCLUSIONS AT improves resting HRV and aspects of EF, the latter was associated with art therapy-related anxiety reduction.
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A mindfulness-based intervention to increase resilience to stress in university students (the Mindful Student Study): a pragmatic randomised controlled trial.
Galante, J, Dufour, G, Vainre, M, Wagner, AP, Stochl, J, Benton, A, Lathia, N, Howarth, E, Jones, PB
The Lancet. Public health. 2018;3(2):e72-e81
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There has been a recent increase in students accessing university counselling services, though the reasons for this are currently unclear. Mindfulness-based stress reduction has gained increased attention as evidence has shown mindfulness training can improve anxiety and depression. The aim of this trial was to therefore assess whether a mindfulness course, Mindfulness Skills for Students (MSS), would improve university students’ resilience to stress. Participants were randomly assigned to either enrol in the 8-week MSS course alongside mental health support or receive mental health support alone. A total of 449 participants completed the study and self-reported psychological distress was the primary outcome. Students enrolled in MSS showed reduced distress scores during the examination period compared with those receiving support as usual. Based on these results, the authors conclude that offering mindfulness training could be an effective, feasible component of a wider university mental health strategies. Further controlled studies are required to better understand preventative mental health interventions for students.
Abstract
BACKGROUND The rising number of young people going to university has led to concerns about an increasing demand for student mental health services. We aimed to assess whether provision of mindfulness courses to university students would improve their resilience to stress. METHODS We did this pragmatic randomised controlled trial at the University of Cambridge, UK. Students aged 18 years or older with no severe mental illness or crisis (self-assessed) were randomly assigned (1:1), via remote survey software using computer-generated random numbers, to receive either an 8 week mindfulness course adapted for university students (Mindfulness Skills for Students [MSS]) plus mental health support as usual, or mental health support as usual alone. Participants and the study management team were aware of group allocation, but allocation was concealed from the researchers, outcome assessors, and study statistician. The primary outcome was self-reported psychological distress during the examination period, as measured with the Clinical Outcomes in Routine Evaluation Outcome Measure (CORE-OM), with higher scores indicating more distress. The primary analysis was by intention to treat. This trial is registered with the Australia and New Zealand Clinical Trials Registry, number ACTRN12615001160527. FINDINGS Between Sept 28, 2015, and Jan 15, 2016, we randomly assigned 616 students to the MSS group (n=309) or the support as usual group (n=307). 453 (74%) participants completed the CORE-OM during the examination period and 182 (59%) MSS participants completed at least half of the course. MSS reduced distress scores during the examination period compared with support as usual, with mean CORE-OM scores of 0·87 (SD 0·50) in 237 MSS participants versus 1·11 (0·57) in 216 support as usual participants (adjusted mean difference -0·14, 95% CI -0·22 to -0·06; p=0·001), showing a moderate effect size (β -0·44, 95% CI -0·60 to -0·29; p<0·0001). 123 (57%) of 214 participants in the support as usual group had distress scores above an accepted clinical threshold compared with 88 (37%) of 235 participants in the MSS group. On average, six students (95% CI four to ten) needed to be offered the MSS course to prevent one from experiencing clinical levels of distress. No participants had adverse reactions related to self-harm, suicidality, or harm to others. INTERPRETATION Our findings show that provision of mindfulness training could be an effective component of a wider student mental health strategy. Further comparative effectiveness research with inclusion of controls for non-specific effects is needed to define a range of additional, effective interventions to increase resilience to stress in university students. FUNDING University of Cambridge and National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care East of England.
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The association of diabetes-related self-care activities with perceived stress, anxiety, and fatigue: a cross-sectional study.
Zhao, FF, Suhonen, R, Katajisto, J, Leino-Kilpi, H
Patient preference and adherence. 2018;12:1677-1686
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Diabetes treatments rely on the individual’s ability to perform diabetes-related self-care activities (DRSCA), which involves tasks such as medication adherence, regulating diet, physical activity, blood glucose monitoring and foot care, however it appears that many individuals do not perform one or all of these tasks. Reasons why have been investigated, but remain insufficient. In this cross-sectional study of 248 individuals with type 2 diabetes (T2D) DRSCA was investigated in relation to stress, anxiety, and fatigue. The results showed that there was evidence of mid-level performance of DRSCA activities and performing DRSCA activities was likely to reduce stress levels but was not related to anxiety or fatigue. Individuals who had T2D for more than 5 years and women were more likely to have anxiety. Interestingly in contradiction to previous studies, support from outside sources did not affect levels of stress, anxiety and fatigue. It was concluded that improving the level of DRSCA may reduce stress. The fact that the performance of DRSCA was not related to anxiety may be because these activities impose restrictions on patients’ lives. This study could be used by healthcare professionals to understand that the performance of DRSCA may reduce stress levels, however as this study was an observational study, direct causal relationships are hard to determine.
Abstract
PURPOSE Many people with type 2 diabetes (T2DM) do not sustain sufficient diabetes-related self-care activities (DRSCA) in their daily lives. To provide additional information about the positive influence of DRSCA, this study was conducted to examine whether DRSCA were associated with reduced perceived stress, anxiety, and fatigue among people with T2DM and to explore the level of DRSCA, perceived stress, anxiety, and fatigue and their association with background information. PATIENTS AND METHODS This study was a cross-sectional survey including 251 participants aged 18 years and older recruited from two hospitals in the eastern part of China. The study utilized self-report questionnaires that consisted of background information, DRSCA, perceived stress, anxiety, and fatigue. Hierarchical multiple regression analysis was conducted to explore the association of DRSCA with perceived stress, anxiety, and fatigue while adjusting for background information. RESULTS The results indicated that the level of self-care activities, stress, and fatigue was around middle level. The prevalence of anxiety was 19%. A high level of DRSCA was likely to reduce perceived stress but was not linked to anxiety and fatigue. Women were more susceptible to stress and anxiety, and people who had diabetes for >5 years were more likely to have anxiety. The background information included diabetes duration, standardized diabetes education, and high social support, all of which are factors that may influence DRSCA. CONCLUSION The findings suggest that improving the level of DRSCA might effectively reduce perceived stress. The potential benefits of DRSCA can provide both motivational and evaluative data for self-care programs. In addition, the findings show that DRSCA were not linked to anxiety and fatigue, which implies that their positive influence on anxiety and fatigue may be offset by the load of frequent DRSCA. It is suggested that helping patients to make tailored plans to integrate DRSCA into their daily lives is needed. Meanwhile, in the background information, it is suggested that standardized diabetes education and high social support can benefit DRSCA; in improving psychological health, more attention should be paid to women and patients with diabetes duration <5 years.