Metformin alters dendrite development and synaptic plasticity in rat cortical neurons.

Synaptic plasticity is crucial as it dynamically molds the strength and connectivity of neural circuits, influencing learning, memory, and the development of neurological disorders. Metformin, a widely prescribed anti-diabetic medication, has been shown to readily cross the blood-brain barrier (BBB) and the placenta. However, its prolonged impact on neuronal morphology and functions remains underexplored. In this study, we investigated the influence of metformin on dendrite development and synaptic plasticity in embryonic brains and primary rat cortical neurons. Our findings reveal a negative modulation of dendrite development by metformin, as evidenced by altered dendritic arborization, impaired dendritic spine morphology and disruptions in synaptic plasticity, suggesting a potential link between metformin exposure and aberrations in neuronal connectivity. In addition, we extend our insights to the impact of maternal metformin exposure on embryonic brains, revealing a significant inhibition of dendrite development in E18.5 rat brains. In conclusion, this study adds to the expanding knowledge base on the non-metabolic effects of metformin, emphasizing the significance of assessing its potential influence on both neuronal structure and function. There is an urgent need for further investigations into the enduring impact of prolonged metformin administration on the structural and functional aspects of neurons.

Metformin inhibits nerve growth factor (NGF)-induced sympathetic neuron differentiation through p35/CDK5 inhibition.

The authors' previous research has shown the pivotal roles of Cyclin-dependent kinase 5 (CDK5) and its regulatory protein p35 in nerve growth factor (NGF)-induced differentiation of sympathetic neurons in PC12 cells. During the process of differentiation, neurons are susceptible to environmental influences, including the effects of drugs. Metformin is commonly used in the treatment of diabetes and its associated symptoms, particularly in diabetic neuropathy, which is characterized by dysregulation of the sympathetic neurons. However, the impacts of metformin on sympathetic neuronal differentiation remain unknown. In this study, we investigated the impact of metformin on NGF-induced sympathetic neuronal differentiation using rat pheochromocytoma PC12 cells as a model. We examined the regulation of TrkA-p35/CDK5 signaling in NGF-induced PC12 differentiation. Our results demonstrate that metformin reduces NGF-induced PC12 differentiation by inactivating the TrkA receptor, subsequently inhibiting ERK and EGR1. Inhibition of this cascade ultimately leads to the down-regulation of p35/CDK5 in PC12 cells. Furthermore, metformin inhibits the activation of the pre-synaptic protein Synapsin-I, a substrate of CDK5, in PC12 differentiation. Additionally, metformin alters axonal and synaptic bouton formation by inhibiting p35 at both the axons and axon terminals in fully differentiated PC12 cells. In summary, our study elucidates that metformin inhibits sympathetic neuronal differentiation in PC12 cells by disrupting TrkA/ERK/EGR1 and p35/CDK5 signaling. This research contributes to uncovering a novel signaling mechanism in drug response during sympathetic neuronal differentiation, enhancing our understanding of the intricate molecular processes governing this critical aspect of neurodevelopment.

Impact of metformin on neocortical development during pregnancy: Involvement of ERK and p35/CDK5 pathways.

Metformin, the most commonly prescribed drug for the treatment of diabetes, is increasingly used during pregnancy to address various disorders such as diabetes, obesity, preeclampsia, and metabolic diseases. However, its impact on neocortex development remains unclear. Here, we investigated the direct effects of metformin on neocortex development, focusing on ERK and p35/CDK5 regulation. Using a pregnant rat model, we found that metformin treatment during pregnancy induces small for gestational age (SGA) and reduces relative cortical thickness in embryos and neonates. Additionally, we discovered that metformin inhibits neural progenitor cell proliferation in the sub-ventricular zone (SVZ)/ventricular zone (VZ) of the developing neocortex, a process possibly mediated by ERK inactivation. Furthermore, metformin induces neuronal apoptosis in the SVZ/VZ area of the developing neocortex. Moreover, metformin retards neuronal migration, cortical lamination, and differentiation, potentially through p35/CDK5 inhibition in the developing neocortex. Remarkably, compensating for p35 through in utero electroporation partially rescues metformin-impaired neuronal migration and development. In summary, our study reveals that metformin disrupts neocortex development by inhibiting neuronal progenitor proliferation, neuronal migration, cortical layering, and cortical neuron maturation, likely via ERK and p35/CDK5 inhibition. Consequently, our findings advocate for caution in metformin usage during pregnancy, given its potential adverse effects on fetal brain development.

Fast Multichannel Inverse Design through Augmented Partial Factorization.

Computer-automated design and discovery have led to high-performance nanophotonic devices with diverse functionalities. However, massively multichannel systems such as metasurfaces controlling many incident angles and photonic-circuit components coupling many waveguide modes still present a challenge. Conventional methods require Min forward simulations and Min adjoint simulations-2Min simulations in total-to compute the objective function and its gradient for a design involving the response to Min input channels. Here, we develop a formalism that uses the recently proposed augmented partial factorization method to obtain both the objective function and its gradient for a massively multichannel system in a single or a few simulations, achieving over 2 orders of magnitude speedup and reduced memory usage. We use this method to inverse design a metasurface beam splitter that separates the incident light to the target diffraction orders for all incident angles of interest, a key component of the dot projector for 3D sensing. This formalism enables efficient inverse design for a wide range of multichannel optical systems.

Total Laryngectomy for Respiratory Complications From Advanced Duchenne Muscular Dystrophy.

Due to respiratory weakness, late-stage Duchenne muscular dystrophy (DMD) patients may suffer from chronic aspiration, which is sometimes treated using tracheostomy. However, definitive laryngectomy has not been described in the literature as an aspiration prevention modality in DMD, especially in patients with contraindications to tracheostomy. A case is presented for a patient with advanced stage Duchenne muscular dystrophy suffering from chronic aspiration pneumonia and excessive oral secretions who became ventilator dependent. A tracheostomy was placed, but was noted to have excessive secretions and high cuff pressures, which have been known to be associated with worsened swallow dysfunction as well as tracheoinnominate fistula. The patient therefore was considered for total laryngectomy, which he underwent successfully. Post-operatively, the patient was noted to have improved subjective quality of life, engaged in an oral diet, and had less secretions surrounding his tracheostoma post-operatively. Aspiration prevention surgeries are done to improve quality of life by improving oral intake, decreasing the need for frequent suctioning, and can sometimes allow for speech. It is important to consider quality of life for DMD patients as more of these patients are living into their 30s with the aid of mechanical ventilation. Laryngectomy is a surgery that can definitively correct chronic aspiration while allowing for oral intake. Laryngoscope, 2024.

Dinaciclib inhibits the growth of acute myeloid leukemia cells through either cell cycle-related or ERK1/STAT3/MYC pathways.

Although immature differentiation and uncontrolled proliferation of hematopoietic stem cells are thought to be the primary mechanisms of acute myeloid leukemia (AML), the pathophysiology in most cases remains unclear. Dinaciclib, a selective small molecule targeting multiple cyclin-dependent kinases (CDKs), is currently being evaluated in oncological clinical trials. Despite the proven anticancer potential of dinaciclib, the differential molecular mechanisms by which it inhibits the growth of different AML cell lines remain unclear. In the current study, we treated HL-60 and KG-1 AML cell lines with dinaciclib and investigated the potential mechanisms of dinaciclib-induced AML cell growth inhibition using flow cytometry and western blotting assays. Data from HL-60 and KG-1 AML cells were validated using human primary AML cells. The results showed that the growth inhibitory effect of dinaciclib was more sensitive in HL-60 cells (IC50: 8.46 nM) than in KG-1 cells (IC50: 14.37 nM). The protein decline in Cyclin A/B and CDK1 and cell cycle arrest in the G2/M phase were more profound in HL-60 cells, corresponding to its growth inhibition. Although the growth inhibition of KG-1 cells by dinaciclib was still pronounced, the cell cycle-associated proteins were relatively insensitive. In addition to cell cycle regulation, the activation/expression of ERK1/STAT3/MYC signaling was significantly reduced by dinaciclib in KG-1 cells compared with that in HL-60 cells. Regarding the results of primary AML cells, we observed ERK1/STAT3/MYC inhibition and cell cycle regulation in different patients. These findings suggest that the cell cycle-associated and ERK1/STAT3/MYC signaling pathways might be two distinct mechanisms by which dinaciclib inhibits AML cells, which could facilitate the development of combination therapy for AML in the future.

Genomic analysis of penicillin-binding proteins and recombination events in an emerging amoxicillin- and meropenem-resistant PMEN3 (Spain9V-3, ST156) variant in Taiwan and comparison with global descendants of this lineage.

From 2008 to 2020, the Taiwan National Notifiable Disease Surveillance System database demonstrated that the incidence of non-vaccine serotype 23A invasive pneumococcal disease (IPD) approximately doubled. In this study, 276 non-repetitive pneumococcal clinical isolates were collected from two medical centers in Taiwan between 2019 and 2021. Of these 267 pneumococci, 60 were serotype 23A. Among them, 50 (83%) of serotype 23A isolates belonged to the sequence type (ST) 166 variant of the Spain9V-3 clone. Pneumococcal 23A-ST166 isolates were collected to assess their evolutionary relationships using whole-genome sequencing. All 23A-ST166 isolates were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299, the newly identified PBP2x-299 in Taiwan. Transformation of the pbp1a, pbp2b, and pbp2x alleles into the ß-lactam-susceptible R6 strain revealed that PBP2x-299 and PBP2b-11 increased the MIC of ceftriaxone and meropenem by 16-fold, respectively. Prediction analysis of recombination sites in PMEN3 descendants (23A-ST166 in Taiwan, 35B-ST156 in the United States, and 11A-ST838/ST6521 in Europe) showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displayed an evolutionary capacity for global dissemination and persistence, increasing IPD incidence, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases, and contributing to high antibiotic resistance. A clonal shift with a highly ß-lactam-resistant non-vaccine serotype 23A, from ST338 to ST166, increased in Taiwan. ST166 is a single-locus variant of the Spain9V-3 clone, which is also called the PMEN3 lineage. All 23A-ST166 isolates, in this study, were resistant to amoxicillin and meropenem, and 96% harbored a novel combination of penicillin-binding proteins (PBPs) (1a:2b:2x):15:11:299. PBP2x-299 and PBP2b-11 contributed to the increasing MIC of ceftriaxone and meropenem, respectively. Prediction analysis of recombination sites in PMEN3 descendants showed that adaptive evolution involved repeated, selectively favored convergent recombination in the capsular polysaccharide synthesis region, PBPs, murM, and folP genome sites. In the late 13-valent pneumococcal conjugate vaccine era, PMEN3 continuously displays the evolutionary capacity for dissemination, leading to an offset in the decrease of pneumococcal conjugate vaccine serotype-related diseases and contributing to high antibiotic resistance.

Clinical trials of new drugs for Alzheimer disease: a 2020-2023 update.

Alzheimer's disease (AD) is the leading cause of dementia, presenting a significant unmet medical need worldwide. The pathogenesis of AD involves various pathophysiological events, including the accumulation of amyloid and tau, neuro-inflammation, and neuronal injury. Clinical trials focusing on new drugs for AD were documented in 2020, but subsequent developments have emerged since then. Notably, the US-FDA has approved Aducanumab and Lecanemab, both antibodies targeting amyloid, marking the end of a nearly two-decade period without new AD drugs. In this comprehensive report, we review all trials listed in clinicaltrials.gov, elucidating their underlying mechanisms and study designs. Ongoing clinical trials are investigating numerous promising new drugs for AD. The main trends in these trials involve pathophysiology-based, disease-modifying therapies and the recruitment of participants in earlier stages of the disease. These trends underscore the significance of conducting fundamental research on pathophysiology, prevention, and intervention prior to the occurrence of brain damage caused by AD.

RAGE potentiates EGFR signaling and interferes with the anticancer effect of gefitinib on NSCLC cells.

The receptor for advanced glycation end-products (RAGE) has been implicated in tumorigenesis, whereas epidermal growth factor receptor (EGFR) signaling plays a vital role in lung cancer progression. Both RAGE and EGFR are transmembrane receptors that transmit intracellular signals through ligand binding, and their downstream signaling cascades show substantial overlap. However, the interplay between these two molecules remains poorly understood. In the present study, we evaluated the correlation between RAGE and EGFR in the tumorigenesis of non-small cell lung cancer (NSCLC) and evaluated the impact of RAGE on the response of NSCLC cells to gefitinib, an EGFR-tyrosine kinase inhibitor (TKI). The expression and activation of EGFR and the phosphorylation of its downstream molecules, signal transducer and activator of transcription 3 (STAT3) and extracellular signal-regulated kinase (Erk), were increased in RAGE-overexpressed A549 (A549-RAGE) cells. Notably, ligand-triggered activation of EGFR signaling was significantly greater in A549-RAGE compared with A549-parental cells. In addition, gefitinib had less effect on the inhibition of EGFR signaling in A549-RAGE cells. These findings were validated in other NSCLC cell lines, H1299 and H1975. Furthermore, upon gefitinib administration, the antiapoptotic marker B-cell lymphoma 2 (Bcl-2) expression was upregulated in A549-RAGE cells, whereas the apoptotic markers Bcl-2 associated X protein (Bax) and Bcl-2 interacting mediator (Bim) remained at lower levels compared with A549-parental cells. Importantly, our findings provide evidence that RAGE interferes with the anticancer effect of gefitinib by modulating the activation of EGFR-STAT3 and EGFR-Erk pathways. Overall, these significant findings deepen our understanding of the intricate relationship between RAGE and EGFR signaling in NSCLC tumorigenesis and provide new considerations for the clinical treatment of NSCLC.NEW & NOTEWORTHY This study represents a pioneering endeavor in comprehending the intricate interplay between RAGE and EGFR signaling within NSCLC. The findings reveal that RAGE serves to enhance EGFR phosphorylation and activation, consequently modulating apoptosis regulators through the EGFR-STAT3 and EGFR-Erk1/2 signaling pathways. Through this mechanism, RAGE potentially imparts resistance to the toxicity induced by EGFR-TKIs in NSCLC cells.

Mindfulness or meditation therapy for Parkinson's disease: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder worldwide. Mindfulness and meditation therapies have been demonstrated as effective alternative treatments for patients with neurological disorders. However, the effects of mindfulness and meditation therapies on PD remain unclear. This meta-analysis investigated the effects of mindfulness and meditation therapies in PD patients. METHODS: A literature search was conducted using PubMed, Embase, Cochrane Library, and ClinicalTrials.gov for randomized controlled trials comparing mindfulness and meditation therapies with control treatments in patients with PD. RESULTS: Nine articles involving eight trials were included, with a total of 337 patients. Our meta-analysis revealed that mindfulness and meditation therapies significantly improved Unified Parkinson's Disease Rating Scale-Part III score (mean difference [MD] = -6.31, 95% confidence interval [95% CI] = -8.57 to -4.05) and cognitive function (standard mean difference [SMD] = 0.62, 95% CI = 0.23 to 1.02). However, no significant differences were discovered between mindfulness therapies and control in gait velocity (MD = 0.05, 95% CI = -0.23 to 0.34), Parkinson's Disease Questionnaire-39 Summary Index (MD = 0.51, 95% CI = -1.12 to 2.14), activities of daily living (SMD = -1.65, 95% CI = -3.74 to 0.45), depression (SMD = -0.43, 95% CI = -0.97 to 0.11), anxiety (SMD = -0.80, 95% CI = -1.78 to 0.19), pain (SMD = 0.79, 95% CI = -1.06 to 2.63), or sleep disturbance (SMD = -0.67, 95% CI = -1.58 to 0.24). CONCLUSION: Mindfulness and meditation therapies may serve as complementary and alternative treatments for PD patients.

Efficacy of Platelet-Rich Plasma Injection on Range of Motion, Pain, and Disability in Patients With Adhesive Capsulitis: A Systematic Review and Meta-analysis.

OBJECTIVE: To investigate the therapeutic effects of platelet-rich plasma (PRP) injection on range of motion, pain, and disability in patients with adhesive capsulitis (AC). DATA SOURCES: The authors performed the literature search in the PubMed, Embase, and Cochrane Library databases in February 2023. STUDY SELECTION: Prospective studies comparing the outcomes of PRP with other intervention in patients with AC. DATA EXTRACTION: The quality of included randomized trials was assessed using the revised Cochrane Risk of Bias (RoB 2.0) tool. The Risk of Bias in Non-Randomized Studies of Interventions tool was applied to assess the quality of nonrandomized trials. The mean difference (MD) or standardized mean difference (SMD) was determined as the effect size for continuous outcomes, and outcome accuracy was determined using 95% confidence intervals (CIs). DATA SYNTHESIS: Fourteen studies involving 1139 patients were included. Our meta-analysis revealed that PRP injection can significantly improve passive abduction (MD=3.91; 95% CI, 0.84-6.98), passive flexion (MD=3.90; 95% CI, 0.15-7.84), and disability (SMD=-0.50; 95% CI, -1.29 to -0.74) within 1 month after intervention. Moreover, PRP injection can significantly improve passive abduction (MD=17.19; 95% CI, 12.38-22.01), passive flexion (MD=17.74; 95% CI, 9.89-25.59), passive external rotation (MD=12.95; 95% CI, 10.04-15.87), pain (MD=-8.40; 95% CI, -16.73 to -0.06), and disability (SMD=-1.02; 95% CI, -1.29 to -0.74) 3 months after intervention. PRP injection can also significantly improve pain (MD=-18.98; 95% CI, -24.71 to -13.26), and disability (SMD=-2.01; 95% CI, -3.02 to -1.00) 6 months after intervention. In addition, no adverse effects of PRP injection were reported. CONCLUSIONS: PRP injection may serve as an effective and safe treatment for patients with AC.

Racial differences in upper airway collapsibility and loop gain in young adult males.

STUDY OBJECTIVES: Previous studies reported that the apnea-hypopnea index was similar in young adult Black and White participants. However, whether this similarity reflects an analogous combination of apneas and hypopneas is unknown. Likewise, the physiological mechanisms underlying this similarity has not been explored. METHODS: 60 Black and 48 White males completed the study. After matching for age and body mass index, 41 participants remained in each group. All participants completed a sleep study. Subsequently, standard sleep indices along with loop gain and the arousal threshold were determined. In addition, airway collapsibility (24 of 60 and 14 of 48 participants) and the hypoxic ventilatory response during wakefulness (30 of 60 and 25 of 48 participants) was measured. RESULTS: The apnea-hypopnea index was similar in Blacks and Whites (p = .140). However, the index was comprised of more apneas (p = .014) and fewer hypopneas (p = .025) in Black males. These modifications were coupled to a reduced loop gain (p = .0002) and a more collapsible airway (p = .030). These differences were independent of whether or not the groups were matched. For a given hypoxic response, loop gain was reduced in Black compared to White males (p = .023). CONCLUSIONS: Despite a similar apnea-hypopnea index, more apneas and fewer hypopneas were evident in young adult Black compared to White males. The physiological mechanisms that contribute to these events were also different between groups. Addressing these differences may be important when considering novel therapeutic approaches to eliminate apnea in Black and White participants.

Protocol to establish a genetically tractable synthetic symbiosis between Sodalis praecaptivus and grain weevils by insect egg microinjection.

We present a protocol to establish a synthetic symbiosis between the mCherry-expressing Sodalis praecaptivus and the grain weevil host, Sitophilus zeamais. We describe steps to isolate grain weevil eggs, followed by microinjecting the bacterial symbiont into insect eggs using a modified Drosophila injection protocol, which leads to localization of bacteria in female insect ovaries. We then detail larval transplantation and visualization of bacteria in live insects using a fluorescence dissection microscope to assess the transgenerational transmission to offspring in weevils. For complete details on the use and execution of this protocol, please refer to Su et al. (2022).1.

Tree-Based Machine Learning Models with Optuna in Predicting Impedance Values for Circuit Analysis.

The transmission characteristics of the printed circuit board (PCB) ensure signal integrity and support the entire circuit system, with impedance matching being critical in the design of high-speed PCB circuits. Because the factors affecting impedance are closely related to the PCB production process, circuit designers and manufacturers must work together to adjust the target impedance to maintain signal integrity. Five machine learning models, including decision tree (DT), random forest (RF), extreme gradient boosting (XGBoost), categorical boosting (CatBoost), and light gradient boosting machine (LightGBM), were used to forecast target impedance values. Furthermore, the Optuna algorithm is used to determine forecasting model hyperparameters. This study applied tree-based machine learning techniques with Optuna to predict impedance. The results revealed that five tree-based machine learning models with Optuna can generate satisfying forecasting accuracy in terms of three measurements, including mean absolute percentage error (MAPE), root mean square error (RMSE), and coefficient of determination (R2). Meanwhile, the LightGBM model with Optuna outperformed the other models. In addition, by using Optuna to tune the parameters of machine learning models, the accuracy of impedance matching can be increased. Thus, the results of this study suggest that the tree-based machine learning techniques with Optuna are a viable and promising alternative for predicting impedance values for circuit analysis.

Clostridium scindens metabolites trigger prostate cancer progression through androgen receptor signaling.

Prostate cancer (PCa) is one of the most common malignancies in men; recently, PCa-related mortality has increased worldwide. Although androgen deprivation therapy (ADT) is the standard treatment for PCa, patients often develop aggressive castration-resistant PCa (CRPC), indicating the presence of an alternative source of androgen. Clostridium scindens is a member of the gut microbiota and can convert cortisol to 11ß-hydroxyandrostenedione (11ß-OHA), which is a potent androgen precursor. However, the effect of C. scindens on PCa progression has not been determined. In this study, androgen-dependent PCa cells (LNCaP) were employed to investigate whether C. scindens-derived metabolites activate androgen receptor (AR), which is a pivotal step in the development of PCa. Results showed that cortisol metabolites derived from C. scindens-conditioned medium promoted proliferation and enhanced migration of PCa cells. Furthermore, cells treated with these metabolites presented activated AR and stimulated AR-regulated genes. These findings reveal that C. scindens has the potential to promote PCa progression via the activation of AR signaling. Further studies on the gut-prostate axis may help unravel an alternative source of androgen that triggers CRPC exacerbation.

Antrodia salmonea Extracts Regulate p53-AR Signaling and Apoptosis in Human Prostate Cancer LNCaP Cells.

Antrodia salmonea (AS) is a genus of Antrodia, an epiphyte of Cunninghamia konishii in Taiwan. AS has been reported to have potential therapeutic effects on different diseases, including diarrhea, abdominal pain, and hypertension. AS has been reported to have anticancer effects on numerous cancer types, such as ovarian carcinoma and triple-negative breast cancer. Our previous studies demonstrated that antrocins and triterpenoids are possibly bioactive compositions. However, the effects of AS on prostate cancer remain unknown. Therefore, we investigated the role of AS in prostate cancer growth, apoptosis, and cell cycle regulation. The results showed that AS extracts significantly inhibited the proliferation of prostate cancer LNCaP cells in a dose-dependent manner and increased the levels of apoptotic markers (cleaved PARP and cleaved caspase 3/8/9). In addition, the cell cycle-related proteins CDK1, CDK2, CDK4, and their respective specific regulators Cyclin B1, Cyclin A, and Cyclin D were also affected. Besides, AS treatment increased p53 protein levels and slowed its degradation in LNCaP cells. Interestingly, we found that AS treatment reduced both total protein and Ser-81 phosphorylation levels of the androgen receptor (AR). Notably, the increase of nuclear p53 was accompanied by the down-regulation of AR, suggesting a reverse regulation between p53 and AR in LNCaP cells was triggered by AS treatment. These findings suggest that AS extracts trigger the apoptosis of prostate cancer cells through the reverse regulation of p53 and AR and elucidate that AS extracts might be a potential treatment for androgen-dependent prostate cancer in the near future.

Feasibility and clinical implications of 3-day bladder diary derived classification of female storage lower urinary tract symptoms.

Our aim was to assess the feasibility of a bladder diary (BD) classification as a surrogate for urodynamic studies in women with storage lower urinary tract symptoms. A total of 3823 women who underwent urodynamic studies were reviewed. Nearly the scores of Patient Perception of Bladder Condition, Indevus Urgency Severity Scale and Overactive Bladder Symptom Score decreased gradually from the overactive bladder (OAB) wet-BD, OAB dry-BD, hypersensitive bladder (HSB) -BD, nocturia-BD to normal-BD groups (all p < 0.001). In addition, there is a trend that the rates of bladder oversensitivity decreased gradually from the OAB wet-BD, OAB dry-BD, HSB-BD, nocturia-BD to normal-BD groups (chi-square test, p < 0.001). Moreover, almost the volumes of first desire to void, normal desire to void, strong desire to void, and urgency increased gradually from the OAB wet-BD, OAB dry-BD, HSB-BD, nocturia-BD to normal-BD groups (all p < 0.001). Thus, this BD classification is correlated significantly with symptom severity, the rate of bladder oversensitivity, and bladder capacity. Nonetheless, a combination of urodynamics, clinical history, and BD is still needed for a thorough diagnosis, but that BD provides an efficient diagnosis in a proportion of patients.

Antrodia salmonea extract inhibits cell proliferation through regulating cell cycle arrest and apoptosis in prostate cancer cell lines.

Antrodia salmonea (AS) is a fungus, which belongs to a fungal family of Taiwanofungus salmoneus with the features of anti-oxidant, anti-inflammatory, and anticancer. Recent studies have shown that AS has anti-cancer functions in ovarian and breast cancer. However, the effects of AS on prostate cancer (PCa) proliferation remain unknown. Therefore, we investigated the role of AS in PCa proliferation through apoptosis, and cell cycle regulation in PCa cell lines. Our results showed that Antrodia salmonea extract (ASE) inhibited PCa cells growth with a dose-dependent manner. In addition, ASE decreased the anchorage-independent growth formation ability in PC3 cells. Moreover, ASE-induced cell growth inhibition in PCa cells (DU145, PC3) was correlated to decreased cell cycle-related proteins such as cyclin A/B and cyclin-dependent kinase CDK1/2/4, and increased cell cycle inhibitor proteins p21. Besides, ASE decreased the total protein level of epidermal growth factor receptor and its downstream signaling pathways Akt and Erk in both PCa cells. We found that apoptotic markers such as cleaved-PARP protein levels increased significantly in DU145 cells indicating ASE might induce apoptosis. In conclusion, our results suggest that ASE may have the ability to induce PCa cell death through regulating cell cycle arrest and apoptosis pathways.

Comparison of cesarean section rates between obstetricians preferring labor induction at early versus late gestational age.

OBJECTIVE: To compare the cesarean section (CS) rates of obstetricians with a preference of labor induction at early versus late gestational age. MATERIAL AND METHODS: Medical records of women who were low risk, nulliparous, singleton pregnancy, and >37 weeks and delivered their babies, were reviewed. Obstetricians, who preferred labor induction at<41 weeks, were allocated to the early induction group; and the other obstetricians were allocated to the late induction group. RESULTS: The late induction group had a higher percentage of labor induction at ≥41 weeks, compared with the early induction group (21% vs. 8%, p = 0.007). The late induction group had a lower CS rate (11.0% vs. 19.1%, p < 0.001). Multivariable Cox proportional hazard model revealed that the early induction group (hazard ratio [HR] = 2.14, p < 0.001), maternal age (HR = 1.04, p = 0.001), premature rupture of membranes (HR = 1.59, p = 0.006), and birth body weight (kg, HR = 2.13, p < 0.001) were independent predictors of CS. In women receiving labor induction (n = 312), birth body weight (kg, HR = 1.72, p = 0.04) was the sole predictor of CS; and there is a trend that the early induction group (HR = 1.54, p = 0.051) has a higher CS rate, compared with the late induction group. However, gestational age at labor induction was not a predictor of CS. CONCLUSION: In low-risk pregnancies, obstetricians preferring labor induction at early gestational age seem to be associated with a higher CS rate, compared with obstetricians preferring labor induction at late gestational age. Nonetheless, the above finding seems to be associated with physician's factor, instead of gestational age at labor induction.