A Systematic Review of the Impact of Mitochondrial Variations on Male Infertility

According to current estimates, infertility affects one in four couples trying to conceive. Primary or secondary infertility can be due either to both partners or only to the man or the woman. Up to 15% of infertility cases in men can be attributed to genetic factors that can lead to irreversible partial or complete spermatogenic arrest. The increased use of assisted reproductive technology (ART) has provided not only insights into the causes of male infertility but also afforded a diagnostic tool to detect and manage this condition among couples. Genes control a variety of physiological attributes, such as the hypothalamic–pituitary–gonadal axis, development, and germ cell differentiation. In the era of ART, it is important to understand the genetic basis of infertility so as to provide the most tailored therapy and counseling to couples. Genetic factors involved in male infertility can be chromosome abnormalities or single-gene disorders, mitochondrial DNA (mtDNA) mutations, Y-chromosome deletions, multifactorial disorders, imprinting disorders, or endocrine disorders of genetic origin. In this review, we discuss the role of mitochondria and the mitochondrial genome as an indicator of sperm quality and fertility

Are physicians and clinical pharmacists aware and knowledgeable enough about inappropriate prescribing for elderly patients? Findings from Malaysia

Objectives To assess the knowledge of physicians and clinical pharmacists about inappropriate prescribing for elderly patients, their confidence in prescribing for elderly patients, and their perceptions of barriers to appropriate prescribing in this population. Methods A cross-sectional study using a validated 20-item questionnaire was conducted among physicians (n=78) and clinical pharmacists (n=45) working in the medical wards of two tertiary hospitals in Malaysia. Knowledge was assessed by six clinical vignettes which were developed based on Beers criteria and the STOPP/START criteria. Other domains of the study were investigated using a four-point or five-point Likert scale. Results Of the 82 participants who completed the questionnaire, 65% were physicians, 90.2% had never received training in geriatric medicine, and 70.8% estimated that 25% or more of their patients were elderly. Only six participants (7.3%) had ever used STOPP/START or Beers criteria when prescribing for elderly patients, and 60% of the respondents had never heard of either one of those criteria. The mean score (SD) for the knowledge part was 3.65 (1.46) points, and only 27 participants (22.9%) scored more than four out of a possible six points. Overall, 34% of the participants rated themselves as confident in prescribing for elderly patients, and this was significantly associated with their knowledge score (P=0.02). The mean number (SD) of barriers cited per participant was 6.88 (2.84), with polypharmacy being the most cited barrier. Conclusions The majority of the participants had inadequate knowledge and low confidence regarding recommending medications for elderly patients. Continuing education on geriatric pharmacotherapy may be of value for the hospital physicians and pharmacists

Tobacco smoking and its impact on the expression level of sperm nuclear protein genes: H2BFWT, TNP1, TNP2, PRM1 and PRM2

The aim of this current study was to investigate the influence of tobacco smoke on sperm quality determined by standard parameters, on sperm DNA maturity tested by chromomycin A3 (CMA3) staining, on sperm DNA fragmentation tested by TUNEL assay and on the transcript level of sperm nuclear proteins H2BFWT, PRM1, PRM2, TNP1 and TNP2 genes quantified by RT‐PCR. One hundred forty‐one (141) sperm samples (43 nonsmokers (G.1) and 98 heavy smokers (G.2)) of couples undergoing ICSI were enrolled in this study. In G2, a significant decrease in standard semen parameters in comparison with nonsmokers was shown (p < .01). In contrast, protamine deficiency (CMA3 positivity) and sperm DNA fragmentation (sDF) were significantly higher in G2 than in G1 (p < .01). Furthermore, the studied genes were differentially expressed (p < .01), down‐regulated in the spermatozoa of G.2 compared to that of G.1 (fold change <0.5) and were significantly correlated between each other (p < .01). Moreover, in comparison with G1, the protamine mRNA ratio in G2 was significantly higher (p < .01). It can therefore be concluded that smoking alters mRNA expression levels of H2BFWT, TNP1, TNP2, PRM1 and PRM2 genes and the protamine mRNA ratio and consequently alters normal sperm function

Impact of heavy alcohol consumption and cigarette smoking on sperm DNA integrity

The purposes of the presents study were to investigate the impact of alcohol consumption and cigarette smoking on semen parameters and sperm DNA quality, as well as to determine whether tobacco smoking, or alcohol consumption causes more deterioration of sperm quality. Two hundred and eleven semen samples of men were included in this study. Four groups were studied: heavy smokers (N = 48), heavy drinkers (N = 52), non-smokers (n = 70), and non-drinkers (n = 41). Semen parameters were determined according to WHO guidelines, protamine deficiency assessed by chromomycin (CMA3) staining, and sperm DNA fragmentation (sDF) evaluated by TUNEL assay. Sperm parameters were significantly higher in non-smokers versus smokers and in non-drinkers versus drinkers (p < 0.005). However, protamine deficiency and sDF were significantly lower in non-smokers versus smokers and in non-drinkers versus drinkers (p < 0.0001). No significant difference in the semen analysis parameters was observed between heavy smokers and heavy drinkers (semen volume: 3.20 ± 1.43 vs. 2.81 ± 1.56 ml, semen count: 65.75 ± 31.32 vs. 53.51 ± 32.67 mill/ml, total motility: 24.27 ± 8.18 vs. 23.75 ± 1.75%, sperm vitality: 36.15 ± 18.57 vs. 34.62 ± 16.65%, functional integrity: 41.56 ± 18.57 vs. 45.96 ± 17.98% and the morphologically normal spermatozoa: 28.77 ± 11.82 vs. 27.06 ± 13.13%, respectively). However, protamine deficiency was significantly higher among drinkers than smokers (37.03 ± 9.75 vs. 33.27 ± 8.56%, p = 0.020). The sDF was also significantly higher among drinkers than smokers (22.37 ± 7.60 vs. 15.55 ± 3.33%, p < 0.0001). Thus, cigarette smoking, and heavy alcohol intake can deteriorate sperm quality. However, alcohol consumption deteriorates sperm maturity and damages DNA integrity at significantly higher rates than cigarette smoking

الفلسطينيون: سبعونَ عاماً بين اللجوء و الشتات = The Palestinians: seventy years of refuge and displacement

This study aims to examine the life of the Palestinian refugees which started in 1948 during the Israeli occupation in Palestine. This historical event, commonly known as the Nakba, transformed them from native citizens into refugees, struggling with instability and uncertainty in refugee camps. The study also presents how recent political conflicts in Iraq, Syria and the Gaza Strip have played a key role in forcing the Palestinian refugees to flee again to temporarily live in asylum countries such as Malaysia, taking it as a transitional destination until they are resettled in a third country. This study employed qualitative approach. To obtain relevant data, in-depth interviews were conducted with thirty Palestinian refugee families who currently stay in Malaysia under the mandate of the United Nations High Commissioner for Refugees (UNHCR) in Kuala Lumpur. All respondents were recruited using the purposive sampling technique. Data were transcribed and analyzed using the thematic approach. The findings of this study discovered the following: i) Palestinian refugees have lived in unsteady life from 1948 until today, ii) they have been moving from one transitional destination to another, spending seven decades as refugees particularly in Arab countries and iii) they make Malaysia as a transitional destination while waiting to move to another destination. In short, this article highlighted several issues of Palestinian refugees and their unstable lives as a result of multiple movements. This article too has included various viewpoints about displacement and proposed some recommendations so that many people will understand better the issues of refugee

An additional marker for sperm DNA quality evaluation in spermatozoa of male partners of couples undergoing assisted reproduction technique (IVF/ICSI): Protamine ratio

The aim of this study was to evaluate the relationship between the protamine ratio (P1/P2), DNA fragmentation of spermatozoa and protamine deficiency. Patients were grouped into fertile (G1; n = 151) and sub‐fertile (G2; n = 121). DNA fragmentation in spermatozoa was analysed by a TUNEL assay (terminal deoxynucleotidyl transferase‐mediated deoxyuridine triphosphate nick‐end labelling), and the protamination was determined by CMA3 staining, while Western blot was used to measure protamine P1 and P2. While sperm DNA fragmentation (SDF) and protamine ratio were significantly elevated in G2 compared with G1 (12.31 ± 7.01% vs. 17.5 ± 9.5%; p = .001) and (0.91 ± 0.43 vs. 0.75 ± 0.42; p = .003); respectively, the CMA3 positive showed no difference at all between G1 and G2. In G1, the CMA3 positive correlated negatively with the P1/P2 ratio and SDF (r = −.586, r = −.297; p = .001 respectively). In contrast, the protamine ratio correlated positively with SDF (r = .356; p = .001). In G2, no correlation was observed between CMA3 positive, SDF and the P1/P2 ratio but the P1/P2 ratio showed a positive correlation with SDF (r = .479; p = .001). In conclusion, the spermatozoa DNA deterioration was closely associated with abnormal protamination but showed an association with the protamine ratio, more than with CMA3 positive. Therefore, for the evaluation of DNA damage in spermatozoa, the P1/P2 ratio might act as an additional biomarker

Asthma remodeling: The pathogenic role of matrix metalloproteinase-9

AbstractBackgroundAsthma is an airway inflammatory disease with functional and structural changes, leading to bronchial hyperresponsiveness and airflow obstruction. Pathological repair of the airways leads to these structural changes referred as airway remodeling. Matrix metalloproteinases (MMPs) are extracellular degrading enzymes that play a critical role in the remodeling process.Aim of the studyIs to study matrix metalloproteinase-9 in asthmatic patients, detecting its pathogenic role in airway remodeling.Subjects and methodsSamples of broncho-alveolar lavage (BAL) fluid and bronchoscopic biopsies from 30 asthmatic patients (10 mild, 10 moderate and 10 severe) and 10 healthy volunteers were assessed for the levels of matrix metalloproteinase-9 (MMP-9) total and differential cell count (in BAL fluid), histological airway remodeling changes and immunohistochemical expression of MMP-9 (in mucosal biopsies).ResultsBAL and tissue MMP-9 (going hand in hand with airway remodeling changes) were higher in asthmatic patients and it was significantly increased with increased severity. BAL total cell count is higher in asthmatic patients. BAL eosinophils, neutrophils, lymphocytes as well as MMP-9 positive cell count were higher in asthmatic patients and increased with severity. MMP-9 tissue expression was also strongly inversely correlated with the spirometric parameters in asthmatic patients.ConclusionsMMP-9 plays a role in airway inflammation and airway remodeling in asthma. MMP-9 is an important player in airway remodeling in bronchial asthma and may be the link between inflammation and remodeling processes

The Impact of Heavy Smoking on Male Infertility and Its Correlation with the Expression Levels of the PTPRN2 and PGAM5 Genes

Smoking has been linked to male infertility by affecting the sperm epigenome and genome. In this study, we aimed to determine possible changes in the transcript levels of PGAM5 (the phosphoglycerate mutase family member 5), PTPRN2 (protein tyrosine phosphatase, N2-type receptor), and TYRO3 (tyrosine protein kinase receptor) in heavy smokers compared to non-smokers, and to investigate their association with the fundamental sperm parameters. In total, 118 sperm samples (63 heavy-smokers (G1) and 55 non-smokers (G2)) were included in this study. A semen analysis was performed according to the WHO guidelines. After a total RNA extraction, RT-PCR was used to quantify the transcript levels of the studied genes. In G1, a significant decrease in the standard semen parameters in comparison to the non-smokers was shown (p < 0.05). Moreover, PGAM5 and PTPRN2 were differentially expressed (p ≤ 0.03 and p ≤ 0.01, respectively) and downregulated in the spermatozoa of G1 compared to G2. In contrast, no difference was observed for TYRO3 (p ≤ 0.3). In G1, the mRNA expression level of the studied genes was correlated negatively with motility, sperm count, normal form, vitality, and sperm membrane integrity (p < 0.05). Therefore, smoking may affect gene expression and male fertility by altering the DNA methylation patterns in the genes associated with fertility and sperm quality, including PGAM5, PTPRN2, and TYRO3

Influence of hospitalization on potentially inappropriate prescribing among elderly patients in a Malaysian community

Purpose: To compare the prevalence and type of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) on admission and discharge of patients, and to determine the associated predictors. Methods: This was a prospective observational study conducted in the multidisciplinary medical and surgical units of Hospital Tengku Ampuan Afzan (HTAA), Malaysia. The medications of patients who had been admitted to the hospital from community-dwelling settings were reviewed to identify PIMs/PPOs using version 2 of STOPP/START criteria. A logistic regression model was applied to detect the risk factors associated with PIM or PPO at discharge. Results: Among the 300 patients involved in the study, the prevalence of PIMs was 27 % upon admission, which decreased to 22.3 % at discharge (p = 0.014) with PIMs pertaining to increasing the risk of physical falls in elderly people being the most common for pre- and post-hospitalization. The prevalence of PPOs was 47.6 % upon admission, which increased to 48 % at discharge (p = 0.99), with the omission of musculoskeletal medications being the most common PPOs at admission and discharge. Having a PIM at discharge was associated with the number of discharge medications and the history of falls, whereas having a high comorbidity index score or history of falls was associated with having a PPO at discharge. Conclusion: Hospitalization significantly reduces the prevalence of PIMs, but not PPOs or polypharmacy, among elderly patients. The number of discharge medications and the history of falls are predictors of discharge PIM, whilst high comorbidities and the history of falls were the predictors of discharge PPO. Improving the knowledge of hospital practitioners regarding geriatric pharmacotherapy is required to optimize prescribing in elderly patients during hospitalization