Tag: pubmed

Zhonghua Nan Ke Xue. 2021 Nov;27(11):969-973.

ABSTRACT

OBJECTIVE: To study the effect of mahogunin ring finger-1 (MGRN1) on the mitophagy of the spermatogonial stem cells (SSC) in mice.

METHODS: SSCs cultured in vitro were divided into three groups: empty vector control, MGRN1 (MGRN1 in SSCs knocked down by RNAi), and MGRN1 + FCCP (inducing mitophagy with carbonyl cyanide p-trifluoromethoxyphenylhydrazone ［FCCP］ in the SSCs with down-regulated MGRN1). The expressions of mitochondrial function-related proteins (Cytochromo c and COX IV) and mitophagy-related proteins (LC3, P62, FUNDC1 and CK2) and the phosphorylation of FUNDC1 were detected by Western blot. Mitochondria and mitochondrial autophagosomes in the SSCs were observed under the electron microscope.

RESULTS: Compared with the empty vector control group, the MGRN1 and MGRN1 + FCCP groups showed significantly down-regulated expressions of Cytochromo c, Cox IV, LC3 and P62, increased phosphorylation level of FUNDC1, and up-regulated expression of CK2 in the SSCs (P < 0.05). No statistically significant differences were found in the expressions of Cytochromo c, Cox IV, LC3, P62 and CK2 or in the phosphorylation level of FUNDC1 between the MGRN1 and MGRN1 + FCCP groups (P > 0.05). Electron microscopy manifested increased mitochondrial damage and reduced mitochondrial autophagosomes in the SSCs in the MGRN1 and MGRN1 + FCCP groups compared with those in the control group.

CONCLUSIONS: MGRN1 affects mitophagy in the SSCs of mice, which may be associated with the effect of CK2 on the phosphorylation of FUNDC1, and its molecular mechanism needs to be further studied.

PMID:37422866

Zhonghua Nan Ke Xue. 2021 Nov;27(11):963-968.

ABSTRACT

OBJECTIVE: To investigate the effects of monobromobiphenyl ether (4-BDE) on the expression of γH2AX in the rat testis, and the possible mechanism of 4-BDE affecting the reproductive function of the male rats.

METHODS: Twenty-four SD male rats were randomly divided into 4 groups: control and low-, medium- and high-dose 4-BDE, the control rats treated intragastrically with olive oil, and the animals in the latter three groups with 4-BDE at 50, 100 and 200 mg/kg/d, respectively, all for 30 consecutive days. Then all the rats were killed and the testis tissues harvested for HE staining, examination of the apoptosis of the cells by TUNEL and determination of the expressions of H2AX mRNA and γH2AX by q-PCR and Western blot.

RESULTS: HE staining manifested occasional reduction or absence of spermatogonial and Sertoli cells in the seminiferous tubules in the medium- and high-dose 4-BDE groups. Compared with the controls, the rats exposed to 4-BDE showed a significant dose-dependent increase in the apoptosis of the testis tissue (P < 0.05), even more significant in the medium- and high-dose 4-BDE groups than in the low-dose group (P < 0.05). There was a dose-effect relationship in the apoptosis index, but with no statistically significant difference between the medium- and high-dose 4-BDE groups (P > 0.05). The results of q-PCR exhibited no statistically significant difference in the expression level of H2AX mRNA either between the control and 4-BDE-exposed rats (P > 0.05) or among the three 4-BDE groups (P > 0.05). The expression of the γH2AX protein was remarkably higher in the 4-BDE groups than in the control (P < 0.05), but not significantly different among the 4-BDE groups (P > 0.05).

CONCLUSIONS: Exposure to 4-BDE at 100 or 200 mg/kg/d damages the structure of seminiferous tubules, increases the apoptosis of testicular cells, significantly up-regulates the expression of the γH2AX protein, and consequently increases DNA double-strand breaks (DSB) in the rat testis. The apoptosis of testicular cells may be related to DSB./.

PMID:37422865

Arch Gynecol Obstet. 2023 Jul 9. doi: 10.1007/s00404-023-07132-3. Online ahead of print.

ABSTRACT

PURPOSE: Hyperandrogenic intrauterine environment may lead to the development of metabolic disorders in offspring in their later life. In this study, we aimed to determine the impact of maternal hyperandrogenism (MHA) on metabolic syndrome (MetS) risk in female offspring in their later life.

METHODS: In this cohort study conducted in Tehran, Iran, female offspring with MHA (n = 323) and without MHA (controls) (n = 1125) were selected. Both groups of female offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. We used age-scaled unadjusted and adjusted Cox regression models to assess the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in female offspring. The software package STATA was used for statistical analysis, and the significance level was set at P < 0.05.

RESULTS: We observed a higher risk of MetS (unadjusted HR (95% CI), 1.36 (1.05-1.77)), (P = 0.02) and (adjusted HR (95% CI), 1.34 (1.00-1.80)), (P = 0.05, borderline)), in female offspring with MHA, compared to controls. The results were adjusted for the potential confounders including body mass index (BMI) at baseline, net changes of BMI, physical activity, education status, and birth weight.

CONCLUSION: Our results suggest that MHA increases the risk of developing MetS in female offspring in their later life. Screening of these female offspring for MetS may be recommended.

PMID:37422863 | DOI:10.1007/s00404-023-07132-3

Int Ophthalmol. 2023 Jul 9. doi: 10.1007/s10792-023-02791-2. Online ahead of print.

ABSTRACT

PURPOSE: The primary aim of this study was to determine the prevalence of HPV in pterygium with polymerase chain reaction (PCR) testing and to investigate the relationship with clinicopathological factors. A secondary aim was to evaluate the relationship between HPV and the recurrence of pterygium.

METHODS: The study included 60 patients. PCR analysis was used to determine the presence of HPV. All the patients were followed up in respect of the development of recurrence. Analyses were performed of patient age, pterygium site, specimen and pterygium size, histopathological findings, HPV status, operation technique and postoperative follow-up findings. In the HPV-positive patients, the relationship between HPV subtypes and other factors was evaluated. To determine the risk factors affecting recurrence rates, multivariate Cox regression analysis was applied subsequent to univariate analysis. In the Cox regression model, HPV status, age, sex, specimen size, size and site of pterygium were included among factors that may affect recurrences rates.

RESULTS: Of the total 60 patients, the HPV-PCR test result could not be analysed in 14 because of an insufficient sample. Of the 46 patients with sufficient material for HPV-PCR analysis, the HPV-PCR result was positive in 15 (32.6%). The HPV subtype most often determined was type 16. No statistically significant relationship was determined between HPV positivity and HPV subtype and age or sex. Recurrence was determined in 10% of all the patients. Of the cases determined with recurrence, 66.7% were HPV positive. According to Kaplan-Meier analysis, the recurrence rates in HPV-positive and HPV-negative patients were 26.7% and 6.5%, respectively. A statistically significant difference was found between two groups in terms of recurrence rates (p: 0.046). According to the results of multivariate Cox regression analysis, though not statistically significant, the risk of recurrence was increased 6.18 times in HPV-positive patients with pterygium compared to HPV-negative ones.

CONCLUSION: HPV infection may have a role in the development of pterygium and recurrence, but may not be sufficient alone. HPV probably has a role in the development of pterygium by acting together with several co-factors in the multi-stage process.

PMID:37422852 | DOI:10.1007/s10792-023-02791-2

Epilepsia Open. 2023 Jul 9. doi: 10.1002/epi4.12787. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to investigate the proportion of patent foramen ovale (PFO) in people with epilepsy (PWE) compared to controls without epilepsy, and to assess whether PWEs with and without PFO exhibit distinctive clinical features.

METHODS: This is a case-control study conducted in a hospital. Contrast transthoracic echocardiography with a venous microbubble bolus and provocative maneuvers (Valsalva and coughing) were used to identify PFO and its right-to-left shunt (RLS) among 741 PWEs and 800 controls without epilepsy. The risk of having PFO in PWEs was explored using multiple matching methods and logistic regression with adjusted congenital factors that may affect the occurrence of PFO.

RESULTS: The proportion of PFO in PWEs and controls were 39.00% and 24.25%, respectively. After 1:1 propensity score matching, the risk of suffering PFO in PWEs was 1.71 times (OR, 1.71; 95%CI, 1.24 – 2.36) higher than that in controls. PWEs also had a higher risk of having a high RLS grade (β_epilepsy = 0.390, p < .001). Among clinical characteristics of PWEs, migraine and drug-resistant epilepsy showed significantly different distributions between those without RLS and those with RLS grade I to III. PWEs with PFO had higher risk of suffering from migraine and drug-resistant epilepsy (OR in migraine, 2.54, 95%CI, 1.65 – 3.95; OR in drug-resistant epilepsy, 1.47, 95%CI, 1.06 – 2.03).

SIGNIFICANCE: The proportionof PFO was found to be higher in PWE than in controls without epilepsy, especially in patients with drug-resistant epilepsy, suggesting potential relationship between the two disorders. Large multicentric study will be needed to confirm this finding.

PMID:37422851 | DOI:10.1002/epi4.12787

JAMA Otolaryngol Head Neck Surg. 2023 Jul 9. doi: 10.1001/jamaoto.2023.1944. Online ahead of print.

ABSTRACT

IMPORTANCE: Due to lack of data from high-powered randomized clinical trials, the differences in functional and survival outcomes for patients with oropharyngeal squamous cell carcinoma (OPSCC) undergoing primary transoral robotic surgery (TORS) vs primary radiation therapy and/or chemoradiation therapy (RT/CRT) are unclear.

OBJECTIVES: To compare 5-year functional (dysphagia, tracheostomy dependence, and gastrostomy tube dependence) and survivorship outcomes in patients with T1-T2 OPSCC receiving primary TORS vs RT/CRT.

DESIGN, SETTING, AND POPULATION: This national multicenter cohort study used data from a global health network (TriNetX) to identify differences in functional and survival outcomes among patients with OPSCC who underwent primary TORS or RT/CRT in 2002 to 2022. After propensity matching, 726 patients with OPSCC met inclusion criteria. In the TORS group, 363 (50%) patients had undergone primary surgery, and in the RT/CRT group, 363 (50%) patients had received primary RT/CRT. Data analyses were performed from December 2022 to January 2023 using the TriNetX platform.

EXPOSURE: Primary surgery with TORS or primary treatment with radiation therapy and/or chemoradiation therapy.

MAIN OUTCOMES AND MEASURES: Propensity score matching was used to balance the 2 groups. Functional outcomes were measured at 6 months, 1 year, 3 years, 5 years, and more than 5 years posttreatment and included dysphagia, gastrostomy tube dependence, and tracheostomy dependence according to standard medical codes. Five-year overall survivorship was compared between patients undergoing primary TORS vs RT/CRT.

RESULTS: Propensity score matching allowed a study sample with 2 cohorts comprising statistically similar parameters with 363 (50%) patients in each. Patients in the TORS cohort had a mean (SD) age of 68.5 (9.9) vs 68.8 (9.7) years in RT/CRT cohort; 86% and 88% were White individuals, respectively; 79% of patients were men in both cohorts. Primary TORS was associated with clinically meaningful increased risk of dysphagia at 6 months (OR, 1.37; 95% CI, 1.01-1.84) and 1 year posttreatment (OR, 1.71; 95% CI, 1.22-2.39) compared with primary RT/CRT. Patients receiving surgery were less likely to be gastrostomy tube dependent at 6 months (OR, 0.46; 95% CI, 0.21-1.00) and 5 years posttreatment (risk difference, -0.05; 95% CI, -0.07 to -0.02). Differences in overall rates of tracheostomy dependence (OR, 0.97; 95% CI, 0.51-1.82) between groups were not clinically meaningful. Patients with OPSCC, unmatched for cancer stage or human papillomavirus status, who received RT/CRT had worse 5-year overall survival than those who underwent primary surgery (70.2% vs 58.4%; hazard ratio, 0.56; 95% CI, 0.40-0.79).

CONCLUSIONS AND RELEVANCE: This national multicenter cohort study of patients undergoing primary TORS vs primary RT/CRT for T1-T2 OPSCC found that primary TORS was associated with a clinically meaningful increased risk of short-term dysphagia. Patients treated with primary RT/CRT had an increased risk of short- and long-term gastrostomy tube dependence and worse 5-year overall survival than those who underwent surgery.

PMID:37422846 | DOI:10.1001/jamaoto.2023.1944

J Pharmacokinet Pharmacodyn. 2023 Jul 9. doi: 10.1007/s10928-023-09872-w. Online ahead of print.

ABSTRACT

Global sensitivity analysis (GSA) evaluates the impact of variability and/or uncertainty of the model parameters on given model outputs. GSA is useful for assessing the quality of Pharmacometric model inference. Indeed, model parameters can be affected by high (estimation) uncertainty due to the sparsity of data. Independence between model parameters is a common assumption of GSA methods. However, ignoring (known) correlations between parameters may alter model predictions and, then, GSA results. To address this issue, a novel two-stages GSA technique based on the δ index, which is well-defined also in presence of correlated parameters, is here proposed. In the first step, statistical dependencies are neglected to identify parameters exerting causal effects. Correlations are introduced in the second step to consider the real distribution of the model output and investigate also the ‘indirect’ effects due to the correlation structure. The proposed two-stages GSA strategy was applied, as case study, to a preclinical tumor-in-host-growth inhibition model based on the Dynamic Energy Budget theory. The aim is to evaluate the impact of the model parameter estimate uncertainty (including correlations) on key model-derived metrics: the drug threshold concentration for tumor eradication, the tumor volume doubling time and a new index evaluating the drug efficacy-toxicity trade-off. This approach allowed to rank parameters according to their impact on the output, discerning whether a parameter mainly exerts a causal or ‘indirect’ effect. Thus, it was possible to identify uncertainties that should be necessarily reduced to obtain robust predictions for the outputs of interest.

PMID:37422844 | DOI:10.1007/s10928-023-09872-w

J Manipulative Physiol Ther. 2023 Jul 6:S0161-4754(23)00027-1. doi: 10.1016/j.jmpt.2023.05.001. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this study was to investigate the immediate effects of Mulligan’s mobilization with movement (MWM) on elbow proprioception.

METHODS: The study included 26 participants in the intervention group and 30 participants in the control group. The intervention group received MWM, while the control group received a sham application. Proprioception was assessed with joint position sense error at baseline, immediately after mobilization, and 30 minutes after mobilization with 70° and 110° of elbow flexion. The hypothesis of interest was the group × time interaction.

RESULTS: At 110° of elbow flexion, group × time interaction was significant (F[2, 108] = 11.48, P = .001). In the paired comparisons, there was a statistically significant difference in favor of the control group in the first measurement (P = .003). No difference was detected in other time points (P = 1.00). At 70° of elbow flexion, there was no significant difference between the time point × group interaction (F[2, 108] = 1.37, P = .10). Therefore, no pairwise comparison was made.

CONCLUSION: In this study of healthy participants, no immediate difference was found between MWM and sham application on elbow proprioception.

PMID:37422752 | DOI:10.1016/j.jmpt.2023.05.001

J Manipulative Physiol Ther. 2023 Jul 7:S0161-4754(23)00023-4. doi: 10.1016/j.jmpt.2023.05.005. Online ahead of print.

ABSTRACT

OBJECTIVE: The purpose of this study was to assess the effect of adding core stability to usual care for pregnant women with lumbar and pelvic girdle (LPG) pain.

METHODS: This was a repeated-measures design randomized controlled trial with blinded outcome assessors. Thirty-five pregnant women with LPG pain were recruited from prenatal health care providers. They were allocated to 2 study groups to receive either usual prenatal care (control group, n = 17) or usual care with core stability exercises focusing on the pelvic floor muscles and deep abdominal muscles (exercise group, n = 18) for 10 weeks. The visual analog scale, score on the Oswestry Disability Index, and the World Health Organization’s Quality of Life Brief Version (WHOQOL-BREF) were evaluated with analysis of variance at pre-intervention, post-intervention, at the end of pregnancy, and 6 weeks after childbirth.

RESULTS: There was a statistically significant interaction of group and time for all outcome measures except for the Social category (P = .18) in the WHOQOL-BREF questionnaire. The analysis of the group within time showed that mean scores in the exercise group were substantially improved at the post-intervention, end of pregnancy, and 6-week follow-up evaluation, except in the Environment category (end of pregnancy: P = .36; 6-week follow-up: P = .75) in the WHOQOL-BREF questionnaire.

CONCLUSION: The results of this study indicate that the addition of core stability exercises was more effective than the usual care alone in pain relief, improving disability, and quality of life of pregnant women with LPG pain.

PMID:37422748 | DOI:10.1016/j.jmpt.2023.05.005

Mayo Clin Proc. 2023 Jul 6:S0025-6196(23)00193-3. doi: 10.1016/j.mayocp.2023.03.024. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the association of early-life tobacco smoke exposure, especially interacting with cancer genetic variants, with adult cancer.

PARTICIPANTS AND METHODS: We examined the associations of in utero tobacco smoke exposure, age of smoking initiation, and their interaction with genetic risk levels with cancer incidence in 393,081 participants from the UK Biobank. Information on tobacco exposure was obtained by self-reported questionnaires. A cancer polygenic risk score was constructed by weighting and integrating 702 genome-wide association studies-identified risk variants. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) for overall cancer and organ-specific cancer incidence.

RESULTS: During 11.8 years of follow-up, 23,450 (5.97%) and 23,413 (6.03%) incident cancers were included in the analyses of in utero exposure and age of smoking initiation, respectively. The HR (95% CI) for incident cancer in participants with in utero exposure to tobacco smoke was 1.04 (1.01-1.07) for overall cancer, 1.59 (1.44-1.75) for respiratory cancer, and 1.09 (1.03-1.17) for gastrointestinal cancer. The relative risk of incident cancer increased with earlier smoking initiation (P_trend<.001), with the HR (95% CI) of 1.44 (1.36-1.51) for overall cancer, 13.28 (11.39-15.48) for respiratory cancer, and 1.72 (1.54-1.91) for gastrointestinal cancer in smokers with initiation in childhood compared with never smokers. Importantly, a positive additive interaction between age of smoking initiation and genetic risk was observed for overall cancer (P_additive=.04) and respiratory cancer (P_additive=.003) incidence.

CONCLUSION: In utero exposure and earlier smoking initiation are associated with overall and organ-specific cancer, and age of smoking initiation interaction with genetic risk is associated with respiratory cancer.

PMID:37422733 | DOI:10.1016/j.mayocp.2023.03.024