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Ethylene oxide (E.O) is an epoxide compound, and it has been utilized as a sterilizer or production of ether compounds in several industries. Although the toxic effects of E.O on bacteria and mammals have been reported, its effects on male reproductive toxicity during sperm capacitation are not fully understood. Therefore, this study was designed to evaluate the effects of E.O exposure during sperm capacitation. Boar spermatozoa were treated with various E.O concentrations (0, 0.1, 1, 10, and 100⯵Ð). After exposure, sperm motility, motion kinematics, capacitation status, intracellular ATP levels, cell viability, expression levels of protein kinase A (PKA) activation, and tyrosine phosphorylation were evaluated. Results revealed that E.O exposure significantly decreased sperm motility, motion kinematics, and intracellular ATP levels but significantly increased the capacitated spermatozoa. In addition, the PKA activation and tyrosine phosphorylation were abnormally changed. According to our results, E.O may cause toxic effects on sperm function during capacitation, which induces male reproductive toxicity. Consequently, we suggest that male reproductive toxicity should be considered when using E.O.
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Pesticides serve as essential tools in agriculture and public health, aiding in pest control and disease management. However, their widespread use has prompted concerns regarding their adverse effects on humans and animals. This review offers a comprehensive examination of the toxicity profile of pesticides, focusing on their detrimental impacts on the nervous, hepatic, cardiac, and pulmonary systems, and their impact on reproductive functions. Additionally, it discusses how pesticides mimic hormones, thereby inducing dysfunction in the endocrine system. Pesticides disrupt the endocrine system, leading to neurological impairments, hepatocellular abnormalities, cardiac dysfunction, and respiratory issues. Furthermore, they also exert adverse effects on reproductive organs, disrupting hormone levels and causing reproductive dysfunction. Mechanistically, pesticides interfere with neurotransmitter function, enzyme activity, and hormone regulation. This review highlights the effects of pesticides on male reproduction, particularly sperm capacitation, the process wherein ejaculated sperm undergo physiological changes within the female reproductive tract, acquiring the ability to fertilize an oocyte. Pesticides have been reported to inhibit the morphological changes crucial for sperm capacitation, resulting in poor sperm capacitation and eventual male infertility. Understanding the toxic effects of pesticides is crucial for mitigating their impact on human and animal health, and in guiding future research endeavors.
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Disruptores Endócrinos , Fertilidade , Praguicidas , Humanos , Praguicidas/toxicidade , Praguicidas/efeitos adversos , Masculino , Disruptores Endócrinos/toxicidade , Disruptores Endócrinos/efeitos adversos , Animais , Fertilidade/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Exposição Ambiental/efeitos adversos , Reprodução/efeitos dos fármacos , Capacitação Espermática/efeitos dos fármacosRESUMO
Oridonin, a natural terpenoid isolated from the leaves of Isodon rubescens (Hemsley) H.Hara, is widely used in oriental medicine for its anticancer properties across various cancer types. Despite its prevalent use, the toxic effects of oridonin on male reproduction, particularly its impact on sperm functions and the mechanisms involved, are not well understood. This study aimed to explore the effects and underlying mechanisms of oridonin on sperm functions. We initially treated Duroc boar spermatozoa with varying concentrations of oridonin (0, 5, 50, 75, 100, and 150⯵M) and incubated them to induce capacitation. We then assessed cell viability and several sperm functions, including sperm motility and motion kinematics, capacitation status, and ATP levels. We also analyzed the expression levels of proteins associated with the phosphatidylinositol 3-kinase (PI3K)/phosphoinositide-dependent kinase-1 (PDK1)/protein kinase B (AKT) signaling pathway and phosphotyrosine proteins. Our results indicate that oridonin adversely affects most sperm functions in a dose-dependent manner. We observed significant decreases in AKT, p-AKT (Thr308), phosphatase and tensin homolog (PTEN), p-PDK1, and p-PI3K levels following oridonin treatment, alongside an abnormal increase in phosphotyrosine proteins. These findings suggest that oridonin may disrupt normal levels of tyrosine-phosphorylated proteins by inhibiting the PI3K/PDK1/AKT signaling pathway, which is crucial for cell proliferation, metabolism, and apoptosis, thus potentially harming sperm functions. Consequently, we recommend considering the reproductive toxicity of oridonin when using it as a therapeutic agent.
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Nirmatrelvir (NMV) is a recently developed selective inhibitor of the main protease of Sars-Cov-2 that reduces the severity of infection. Despite its widespread use and various side effects, NMV's effect on male fertility is still unclear. This study was thus established to investigate how NMV affects male fertility. For experiments, Duroc spermatozoa were incubated with various concentrations of NMV (0, 0.1, 1, 10, 50, and 100 µM). Then, sperm motility, motion kinematics, capacitation status, intracellular ATP level, and cell viability were evaluated. In addition, the expression levels of phospho-PKA substrates, tyrosine-phosphorylated proteins, and PI3K/PDK1/AKT signaling pathway-related proteins were measured by western blotting. Our results showed that sperm motility, motion kinematics, proportion of capacitated spermatozoa, and intracellular ATP level were significantly decreased by NMV in a dose-dependent manner. Moreover, PKA activation was significantly suppressed by NMV, and expression levels of PI3K, phospho-PDK1, AKT, and phospho-AKT (Thr308 and Ser473) were significantly increased in a dose-dependent manner. Combining these findings, it is suggested that NMV has detrimental effects on sperm function by inducing abnormal changes in the PI3K/PDK1/AKT signaling pathway, resulting in PKA deactivation. Therefore, there is a need to pay particular attention to its male reproductive toxicity when NMV is administered.
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Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Transdução de Sinais , Motilidade dos Espermatozoides , Espermatozoides , Masculino , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espermatozoides/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Motilidade dos Espermatozoides/efeitos dos fármacos , Animais , Fosfatidilinositol 3-Quinases/metabolismo , Piruvato Desidrogenase Quinase de Transferência de Acetil , Suínos , Trifosfato de Adenosina/metabolismo , Capacitação Espermática/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Avobenzone (AVO), an ultraviolet (UV) filter, is frequently used as an ingredient in personal cosmetics. This UV filter has been found to be easily exposed in swimming pools and beaches, and it has been detected in human urine and blood. Moreover, numerous studies have demonstrated that AVO exhibits endocrine-disrupting properties. Nevertheless, the effects of AVO on male fertility have not yet fully understood. Therefore, this study aimed to assess the effects of AVO on various sperm functions during capacitation. First, boar spermatozoa were treated with various AVO concentrations. After treatment, sperm motility and kinetic characteristics, capacitation status, intracellular adenosine triphosphate (ATP) levels, and sperm viability were evaluated. Moreover, Western blot analysis w.as conducted to evaluate protein kinase A (PKA) activity and tyrosine phosphorylation. As a result, AVO treatment significantly decreased total motility, progressive motility, and several kinetic characteristics at high concentrations (50 and 100⯵M). Furthermore, the capacitation status dose-dependently decreased. Conversely, no significant differences in acrosome reaction, cell viability, and intracellular ATP levels were observed. However, the intracellular ATP level tended to decrease. In addition, AVO dose-dependently induced abnormal changes in PKA activity and tyrosine phosphorylation. Although AVO did not directly exert a toxic effect on cell viability, it ultimately negatively affected sperm functions through abnormal alterations in PKA activity and tyrosine phosphorylation. Thus, the potential implications on male fertility must be considered when contemplating the safe utilization of AVO.
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Propiofenonas , Sêmen , Motilidade dos Espermatozoides , Masculino , Suínos , Animais , Humanos , Fosforilação , Sêmen/metabolismo , Espermatozoides , Tirosina/metabolismo , Trifosfato de Adenosina/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Capacitação EspermáticaRESUMO
Ritonavir (RTV) is an antiviral and a component of COVID-19 treatments. Moreover, RTV demonstrates anti-cancer effects by suppressing AKT. However, RTV has cytotoxicity and suppresses sperm functions by altering AKT activity. Although abnormal AKT activity is known for causing detrimental effects on sperm functions, how RTV alters AKT signaling in spermatozoa remains unknown. Therefore, this study aimed to investigate reproductive toxicity of RTV in spermatozoa through phosphoinositide 3-kinase/phosphoinositide-dependent protein kinase-1/protein kinase B (PI3K/PDK1/AKT) signaling. Duroc spermatozoa were treated with various concentrations of RTV, and capacitation was induced. Sperm functions (sperm motility, motion kinematics, capacitation status, and cell viability) and expression levels of tyrosine-phosphorylated proteins and PI3K/PDK1/AKT pathway-related proteins were evaluated. In the results, RTV significantly suppressed sperm motility, motion kinematics, capacitation, acrosome reactions, and cell viability. Additionally, RTV significantly increased levels of phospho-tyrosine proteins and PI3K/PDK1/AKT pathway-related proteins except for AKT and PI3K. The expression level of AKT was not significantly altered and that of PI3K was significantly decreased. These results suggest RTV may suppress sperm functions by induced alterations of PI3K/PDK1/AKT pathway through abnormally increased tyrosine phosphorylation. Therefore, we suggest people who use or prescribe RTV need to consider its male reproductive toxicity.
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Perfluorooctanoic acid (PFOA) is a perfluorinated compound, a synthesized chemical, and has been used in several industrial products for more than 70 years. Although PFOA is known to exert toxic effects in normal cells, there is no detailed information on its reproductive toxicity and its effects on sperm functions related to protein kinase B (AKT). Therefore, this study was conducted to explore the effects of PFOA on sperm functions via AKT. Boar spermatozoa were incubated with different concentrations of PFOA (0, 0.1, 1, 10, and 100 µM) to induce capacitation. Sperm functions (sperm motility, motion kinematic parameters, capacitation status, cell viability, and intracellular ATP levels) were evaluated. In addition, the expression levels of AKT, phospho-AKT, phospho-PKA, and tyrosine phosphorylated proteins were evaluated by western blotting. Results showed significant decreases in sperm motility and motion kinematic parameters. PFOA treatment significant suppressed spermatozoa capacitation and intracellular ATP levels. Furthermore, it significantly decreased the levels of phospho-PKA and tyrosine phosphorylated proteins. The levels of AKT phosphorylation at Thr308 and Ser473 also significantly decreased. These findings suggest that PFOA diminishes sperm functions during capacitation and induces unnatural phosphorylation in AKT, leading to reproductive toxicity. Therefore, people should be aware of reproductive toxicity when using PFOA.
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Caprilatos , Fluorocarbonos , Proteínas Proto-Oncogênicas c-akt , Sêmen , Animais , Masculino , Trifosfato de Adenosina/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sêmen/metabolismo , Capacitação Espermática , Motilidade dos Espermatozoides , Espermatozoides , Suínos , Tirosina/metabolismoRESUMO
BACKGROUND: In this study, we aimed to compare the effectiveness and adverse reactions of nirmatrelvir/ritonavir and molnupiravir in high-risk outpatients with coronavirus disease 2019 (COVID-19). METHODS: This multicenter prospective observational study evaluated the rate of hospitalization, death, and adverse events within 28 days of oral antiviral agent prescription (molnupiravir, n = 240; nirmatrelvir/ritonavir, n = 240) to 480 nonhospitalized adult patients with COVID-19 from August 2, 2022 to March 31, 2023. RESULTS: Patients receiving molnupiravir had a higher prevalence of comorbidities (85.8% vs. 70.4%; P < 0.001) and a higher Charlson comorbidity index (2.8 ± 1.4 vs. 2.5 ± 1.5; P = 0.009) than those receiving nirmatrelvir/ritonavir. Three patients required hospitalization (nirmatrelvir/ritonavir group, n = 1 [0.4%]; molnupiravir group, n = 2 [0.8%]; P = 1.000). Nirmatrelvir/ritonavir was associated with a higher risk of adverse events than molnupiravir (odds ratio [OR], 1.96; 95% confidence interval [CI], 1.27-3.03), especially for patients aged 65 years and older (OR, 3.04; 95% CI, 1.71-5.39). The severity of adverse events in both groups was mild to moderate and improved after discontinuation of medication. In the molnupiravir group, age ≥ 65 years (OR, 0.43 95% CI, 0.22-0.86) and appropriate vaccination (OR, 0.37; 95% CI, 0.15-0.91) reduced the occurrence of adverse events. CONCLUSION: The rates of hospitalization and death were low and not significantly different between high-risk patients who received either nirmatrelvir/ritonavir or molnupiravir. Although adverse events were more frequent with nirmatrelvir/ritonavir than with molnupiravir, none were severe. Nirmatrelvir/ritonavir can be safely used to treat COVID-19, while molnupiravir could be considered as an alternative treatment option for high-risk groups.
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COVID-19 , Pacientes Ambulatoriais , Adulto , Humanos , Ritonavir/efeitos adversos , Tratamento Farmacológico da COVID-19 , Antivirais/efeitos adversosRESUMO
Deguelin is a natural flavonoid extracted from plants belonging to the Lonchocarpus, Derris, or Tephrosia genera. It inhibits AKT activity in tumors and has the potential to be used as a treatment for malignant tumors. However, the risks associated with the use of deguelin on male fertility have not yet been explained in detail. Therefore, this study was conducted to investigate the effects of deguelin on sperm functions during capacitation. First, boar spermatozoa were exposed to different concentrations of deguelin (0.1, 1, 10, 50, and 100 µM). Next, sperm functional assessments, such as sperm motility, capacitation status, intracellular ATP level, and cell viability, were performed. The expression levels of PI3K/AKT-related proteins and the phosphorylation of their tyrosine residues were also evaluated by western blotting. No significant difference was observed in cell viability; however, deguelin considerably decreased sperm motility and motion kinematics in a dose-dependent manner. Although no significant difference was observed in the capacitation status, acrosome reaction decreased at high concentrations of deguelin (50 and 100 µM). Furthermore, intracellular ATP levels were significantly decreased in all deguelin treatment groups compared with those in the control group. Results of western blotting revealed that deguelin substantially diminished tyrosine phosphorylation. Interestingly, in contrast to previous studies showing that deguelin inhibits AKT activity, our results showed that it increased the expression of PI3K/AKT pathway-related proteins. Collectively, these findings indicate that deguelin exerts negative effects on sperm functions due to abnormal PI3K/AKT signaling activation. We believe that this is the first study to provide evidence that deguelin can regulate sperm functions independent of PI3K/AKT pathway inhibition. Furthermore, its detrimental effects on male fertility should be considered while developing or using deguelin as a therapeutic agent.
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Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Masculino , Animais , Suínos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Flavonoides/toxicidade , Sêmen/metabolismo , Motilidade dos Espermatozoides , Espermatozoides , Fosforilação , Tirosina/metabolismo , Sus scrofa/metabolismo , Trifosfato de Adenosina/metabolismo , Capacitação EspermáticaRESUMO
Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.
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Background: The high infectivity and fatality of COVID-19 has changed the mode of higher education from onsite to online. Although many studies investigated the effectiveness and satisfaction of online education, little is known regarding university students' lived experience of online space during synchronous learning via videoconferencing. Objective: The present study explored how university students experienced online space when engaging in synchronous learning via videoconferencing platforms during the outbreak of the pandemic. Method: The phenomenological approach was chosen to primarily explore students' experience of online space as well as their experience of embodiment and relations to self and others. Interviews were conducted with nine university students who voluntarily participated to share their experience of online space. Results: Three core themes were generated from the descriptions of experiences provided by the participants. For each core theme, two sub-themes were emerged and described. The analysis of the themes demonstrated that online space was experienced as being separate from home but also inseparable because it was an extension of the comforts of home. This inseparableness is also reflected in the virtual classroom where the rectangular screen presented on the monitor is always shared with everyone in the class. Moreover, online space was perceived as having no transitional space in which spontaneity and new encounters occur. Finally, the presence of self and others was experienced differently in online space due to the participants' choices of being seen or heard using their microphones and cameras. This led to a different sense of togetherness in online space. The insights gained from the study were discussed in relation to considerations for online learning in the post-pandemic era. Conclusion: Based on the emerged themes from the results, the current study concluded that the online space created by technologies cannot be a complete substitute for traditional face-to-face classrooms and suggested possible implications for designing and using online space in university education.
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As modern society experiences rapid changes, the unpredictability of the labor market is increasing. University students preparing to join the workforce may experience increased anxiety and stress due to the heightened uncertainty regarding their career plans. Regulating such negative emotions and adjusting to the changing circumstances may influence their career development. Thus, the current study aimed to investigate the relationship between cognitive emotion regulation (CER) - specifically adaptive CER and maladaptive CER - and career decision-making self-efficacy (CDMSE), with career adaptability (CA) as a mediating factor. The path analysis model consisting of adaptive CER, maladaptive CER, CA, and CDMSE was tested with 357 Korean university students who were facing the school-to-work transition. The results of the study were as follows. First, adaptive CER was positively related to CA and CDMSE, while maladaptive CER was negatively related to CA only. Second, CA and CDMSE were positively related. Third, CA partially mediated the relationship between adaptive CER and CDMSE and fully mediated the relationship between maladaptive CER and CDMSE. Based on these results, theoretical and practical implications are proposed, and the limitations of the study are discussed.
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Since COVID-19 began in 2019, therapeutic agents are being developed for its treatment. Among the numerous potential therapeutic agents, ritonavir (RTV), an anti-viral agent, has recently been identified as an important element of the COVID-19 treatment. Moreover, RTV has also been applied in the drug repurposing of cancer cells. However, previous studies have shown that RTV has toxic effects on various cell types. In addition, RTV regulates AKT phosphorylation within cancer cells, and AKT is known to control sperm functions (motility, capacitation, and so on). Although deleterious effects of RTV have been reported, it is not known whether RTV has male reproduction toxicity. Therefore, in this study, we aimed to investigate the effects of RTV on sperm function and male fertility. In the present study, sperm collected from the cauda epididymis of mice were incubated with various concentrations of RTV (0, 0.1, 1, 10, and 100 µM). The expression levels of AKT, phospho-AKT (Thr308 and Ser473), and phospho-tyrosine proteins, sperm motility, motion kinematics, capacitation status, and cell viability were assessed after capacitation. The results revealed that AKT phosphorylation at Thr308 and Ser473 was significantly increased, and the levels of tyrosine-phosphorylated proteins (at approximately 25 and 100 kDa) were significantly increased in a dose-dependent manner. In addition, RTV adversely affected sperm motility, motion kinematics, and cell viability. Taken together, RTV may have negative effects on sperm function through an abnormal increase in tyrosine phosphorylation and phospho-AKT levels. Therefore, individuals taking or prescribing RTV should be aware of its reproductive toxicity.
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Ritonavir , Capacitação Espermática , Animais , Masculino , Camundongos , COVID-19 , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ritonavir/toxicidade , Sêmen/metabolismo , Capacitação Espermática/efeitos dos fármacos , Motilidade dos Espermatozoides , Espermatozoides , Tratamento Farmacológico da COVID-19RESUMO
Glucose-regulated protein 78 (GRP78), which is commonly found in the endoplasmic reticulum (ER), is involved in stabilizing ER proteins and inducing the unfolded protein response. Furthermore, GRP78 is expressed on the surface of most common cancer cells, such as cells of breast, lung, liver, and prostate cancers, and plays a role in apoptosis and cell proliferation via the PI3K/PDK1/AKT signaling pathway. Therefore, various trials have been performed for evaluating cancer treatment by inhibiting GRP78. Moreover, GRP78 is expressed on the surface of spermatozoa; however, its role in spermatozoa physiology remains unclear. Therefore, this study was designed to investigate the effects of GRP78 on sperm function during capacitation and elucidate the underlying mechanisms. Boar spermatozoa were exposed to various concentrations of HA15, a GRP78 antagonist, and sperm kinematic parameters, capacitation status, cell viability, levels of PI3K/PDK1/AKT-pathway related proteins, and tyrosine phosphorylation were evaluated. GRP78 inhibition significantly decreased sperm motility, kinematic parameters, capacitated and acrosome-reacted spermatozoa counts, and cell viability. Moreover, GRP78 expression was significantly decreased in HA15-treated spermatozoa compared to that in the control group, and levels of PI3K/PDK1/AKT-pathway related proteins changed significantly. Furthermore, tyrosine phosphorylation was significantly altered in the HA15-treated group. The results of this study suggest that GRP78 inhibition in cancer therapy may negatively affect sperm function. These results lay a strong foundation for future studies aiming to identify the molecular mechanisms related to GRP78 in spermatozoa.
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Capacitação Espermática , Motilidade dos Espermatozoides , Animais , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/farmacologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sêmen/metabolismo , Espermatozoides , Suínos , Tirosina/metabolismoRESUMO
Ertapenem is one of the carbapenems recommended for treating extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales. However, efficacy data are limited. We compared 30-day mortality rates for patients receiving ertapenem and other carbapenems for treatment of ESBL-producing Enterobacterales bacteremia. A multicenter, retrospective study was performed from January 2013 to December 2020 at three hospitals. Patients who received only members of one group of carbapenems (group 1 or group 2) throughout their treatment for ESBL-producing Escherichia coli or Klebsiella pneumoniae bacteremia were enrolled. To compare 30-day all-cause mortality rates in the two groups, propensity score matching was used to control for selection bias. Subgroup analyses were performed for several subgroups. Secondary outcomes included Clostridioides difficile infection (CDI) and the emergence of multidrug-resistant Gram-negative bacteria within 90 days after initiation of carbapenem treatment. One-to-one propensity score matching yielded 162 pairs of patients from the total of 603 patients included. There was no difference in 30-day mortality rates between ertapenem and the other carbapenems in adjusted analyses (hazard ratio, 0.60 [95% confidence interval [CI], 0.29 to 1.22]) of the propensity score-matched cohorts. A similar result was obtained in a subgroup analysis of patients who suffered severe sepsis or septic shock and those who did not (P = 0.54 for interaction). Emergence of CDI (odds ratio [OR], 0.99 [95% CI, 0.44 to 2.20]) and carbapenem-resistant Enterobacterales (OR, 1.31 [95% CI, 0.51 to 3.53]) did not differ between the two groups. Our study suggests that the efficacy of ertapenem may be comparable to that of the other carbapenems in treatment of ESBL-producing E. coli and K. pneumoniae bacteremia.
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Bacteriemia , Carbapenêmicos , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Carbapenêmicos/uso terapêutico , Ertapenem/uso terapêutico , Escherichia coli , Humanos , Klebsiella pneumoniae , Estudos Retrospectivos , beta-LactamasesRESUMO
Although cryopreservation is an efficient method for maintaining the biological and genetic resources of sperm, the sperm damage during the cryopreservation process cannot be ignored. It should be possible to obtain the most effective cryopreservation performance by accurately grasping the effects of various factors on the cryopreservation of sperm. The previous study demonstrated that a suitable standard protocol for cryopreservation of Korean native brindled cattle (Chikso) does not exist, based on the methods for semen cryopreservation of Chikso differ in each research center. The most obvious difference between most of protocols is the addition of glycerol before and after cooling during the Chikso cryopreserved semen process. Therefore we focused on the effects of glycerol addition time on the quality of cryopreserved Chikso sperm. In the present study, 27 individual Chikso samples were collected by transrectal massage and divided into two parts: the "cryopreservation method A" group (adding glycerol before cooling) and the "cryopreservation method B" group (adding glycerol after cooling). Meanwhile, the values of various sperm parameters were derived from each group, including sperm motility, kinematics, capacitation status, cell viability, and intracellular ATP levels, which we used to compare and evaluate sperm function. The results of this study indicated that during the semen cryopreservation process of the Chikso, the addition of glycerol after cooling yielded superior results in a variety of sperm parameters, such as sperm motility, progressive motility, rapid motility, VCL, VSL, VAP, ALH, capacitation status, viability, and intracellular ATP level after freezing and thawing. Our study is suggested that the glycerol addition time during the cryopreservation process for Chikso should be considered. In addition, our results may be provided reference to develop suitable the cryopreservation procedure of the Chikso sperm.
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Selective androgen receptor modulators (SARMs) are compounds with specific androgenic properties that have been investigated for the treatment of conditions such as muscle wasting disease. The reported androgenic properties have resulted in their use by athletes, and consequently they have been on the World Anti-Doping Agency prohibited list for more than a decade. To minimise the chance of an unattended positive doping test and to avoid potential serious health problems, adequate screening methods for the detection of a wide range of SARMs in these supplements is necessary. In this study, a rapid and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated simultaneously to screen and quantify six SARMs in dietary supplements, with confirmation by liquid chromatography-quadrupole-time of flight mass spectrometry (LC-Q-TOF/MS). The validated method was applied to 60 dietary supplements obtained by on-line and direct purchase from international vendors in 2020. Various SARMs were detected at high concentrations in 20 products which were advertised as having androgenic properties. For example, andarine was present at 7.2% in one product, and GW501516 was found at 3.49% in the another product. Furthermore, MK-677 and YK-11, not disclosed on the label, were detected in some products. YK-11 is easily hydrolysed in just a few hours. Although YK-11 is particularly unstable, such that the protonated ion [M + H]+ at m/z 431 for YK-11 was not detected, mass fragmentation, and a [M+ Na]+ ion at m/z 453.3 confirmed the presence of YK-11. Additionally, hydrolysed YK-11 under acidic conditions was confirmed by NMR spectral data, and 1H NMR and 13C NMR spectral data for YK-11 were in good agreement with literature data. This rapid and accurate LC-MS/MS method can therefore be successfully applied to screen and identify SARMs for the continuous control and supervision of dietary supplements.
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Antagonistas de Receptores de Andrógenos/análise , Suplementos Nutricionais/análise , Cromatografia Líquida , Humanos , Detecção do Abuso de Substâncias , Espectrometria de Massas em TandemRESUMO
We investigated the longevity rates of antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) after a complete ChAdOx1 nCoV-19 vaccination, which are rare and important to estimate their efficacy and establish a vaccination strategy. We assessed the positivity rates and changes of titers before (T0) and at one month (T1), four months (T2), and seven months (T3) after a ChAdOx1 nCoV-19 vaccination using five SARS-CoV-2 antibody assays. A total of 874 serum samples were obtained from 228 (T0 and T1), 218 (T2), and 200 (T3) healthcare workers. The positive rates for all five assays were 0.0-0.9% at T0, 66.2-92.5% at T1, 98.2-100.0% at T2, and 66.0-100.0% at T3. The positive rates at T3 were decreased compared to those at T2. The median antibody titers of all the assays at T3 were significantly decreased compared to those at T2 (860.5 to 232.0 U/mL for Roche total, 1041.5 to 325.5 AU/mL for Abbott IgG, 10.9 to 2.3 index for Siemens IgG, 99.5% to 94.7% for SD Biosensor V1, and 88.5% to 38.2% for GenScript). A third-dose scheme can be considered based on our data generated from five representative assays. Our findings contribute insights into SARS-CoV-2 antibody assays and appropriate vaccination strategies.
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Although novaluron is an insect growth regulator with a low mammalian acute toxicity and a low risk to the environment and nontarget organisms, toxic effects of novaluron have been reported. However, no studies have yet evaluated the effect of novaluron on reproduction. Therefore, we examined the effects of novaluron on sperm functions. The spermatozoa of ICR mice were incubated with various concentrations of novaluron to induce capacitation. Then, sperm motion parameters and capacitation status were evaluated using CASA program and H33258/chlortetracycline staining. In addition, PKA activity and tyrosine phosphorylation were evaluated by Western blotting. After exposure, various sperm motion parameters were significantly decreased in a dose-dependent manner. The acrosome reaction was also significantly decreased in the high concentration groups. Sperm viability was significantly reduced at the highest concentration. In addition, PKA activity and tyrosine phosphorylation were also significantly altered. Thus, novaluron affects sperm viability, sperm motility, and motion kinematics during capacitation. Furthermore, it may promote the reduction in acrosome reactions. The physiological suppression of sperm function may depend on abnormal tyrosine phosphorylation via the alteration of PKA activity. Therefore, we suggest that it is necessary to consider reproductive toxicity when using novaluron as a pesticide.