Efficacy of Aromatherapy Against Behavioral and Psychological Disturbances in People With Dementia: A Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: Behavioral and psychological symptoms of dementia (BPSD) are common in people with dementia. Aromatherapy may reduce the frequency and severity of BPSD. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy of aromatherapy in relieving BPSD and improving functional ability in people with dementia. DESIGN: Systematic review and meta-analysis. SETTING AND PARTICIPANTS: Patients with dementia receiving aromatherapy. METHODS: A literature search was conducted using PubMed, Embase, and Cochrane Library for RCTs published before March 2024 comparing aromatherapy with control treatments in patients with dementia. RESULTS: There were 15 trials involving 821 patients. Overall, significant reduction in BPSD was observed after 1 month of aromatherapy treatment. Among 15 trials, 9 reported the Cohen-Mansfield Agitation Inventory (CMAI) score, and 7 evaluated the Neuropsychiatric Inventory (NPI) score. The meta-analysis showed significant improvement in CMAI score (weighted mean difference [WMD] -6.31, 95% CI -9.52 to -3.11) and NPI score (WMD -8.07, 95% CI -13.53 to -2.61) in patients receiving 3 to 4 weeks of aromatherapy compared with the control group. Four of the 15 trials reported improvement in depressive mood and 3 trials reported no significant improvement in functional ability. CONCLUSIONS AND IMPLICATIONS: In conclusion, aromatherapy is a safe and viable nonpharmacologic treatment to improve BPSD in people with dementia and its combination with massage showed higher efficacy.

Drosophila ring chromosomes interact with sisters and homologs to produce anaphase bridges in mitosis.

Ring chromosomes are known in many eukaryotic organisms, including humans. They are typically associated with a variety of maladies, including abnormal development and lethality. Underlying these phenotypes are anaphase chromatin bridges that can lead to chromosome loss, nondisjunction and breakage. By cytological examination of ring chromosomes in Drosophila melanogaster we identified five causes for anaphase bridges produced by ring chromosomes. Catenation of sister chromatids is the most common cause and these bridges frequently resolve during anaphase, presumably by the action of topoisomerase II. Sister chromatid exchange and chromosome breakage followed by sister chromatid union also produce anaphase bridges. Mitotic recombination with the homolog was rare, but was another route to generation of anaphase bridges. Most surprising, was the discovery of homolog capture, where the ring chromosome was connected to its linear homolog in anaphase. We hypothesize that this is a remnant of mitotic pairing and that the linear chromosome is connected to the ring by multiple wraps produced through the action of topoisomerase II during establishment of homolog pairing. In support, we showed that in a ring/ring homozygote the two rings are frequently catenated in mitotic metaphase, a configuration that requires breaking and rejoining of at least one chromosome.

The prevalence of overt, occult, and no-demonstrated stress urinary incontinence and their clinical and urodynamic findings in women with advanced-stage cystoceles.

OBJECTIVES: To elucidate the prevalence of overt, occult and no demonstrated (ND) stress urinary incontinence (SUI) in women with advanced-stage cystoceles. STUDY DESIGN: Between November 2011 and January 2017, all women with ≥stage 2 cystoceles were retrospectively enrolled. Overt SUI was diagnosed before the prolapse reduction test, and occult SUI was diagnosed when urine leakage was noted after a reduction test with vaginal gauze. Otherwise, a diagnosis of ND-SUI was made. MAIN OUTCOME MEASURES: The prevalence, clinical and urodynamic findings of overt SUI, occult SUI, and ND-SUI. RESULTS: In 480 enrolled women, 62% had overt SUI, 17% had occult SUI, and 21% had ND-SUI. The occult SUI group had the most advanced prolapse. The pad weight results after prolapse reduction (37.3 ± 44.3 vs. 13.4 ± 21.9, p < 0.05), the bladder capacity (243 ± 54 vs. 273 ± 48, p < 0.001), and questionnaires regarding life quality were significantly different between the overt SUI and the occult SUI groups. Bladder oversensitivity (BO) was the most common urodynamic diagnosis (389/480, 81%), especially in overt SUI, while urodynamic stress incontinence (56/480, 12%) and detrusor overactivity (60/480, 13%) were uncommon. The cutoff value of stage 3 uterine prolapse was the strongest predictor for predicting occult SUI (sensitivity = 30.3%, specificity = 78.5%; area = 0.60, 95% CI: 0.52-0.68). CONCLUSIONS: SUI occurs in a ratio of 3:1:1 among cases with overt, occult, and no demonstrable symptoms. BO is the most common urodynamic diagnosis. Pad test with prolapse reduction remains an important tool, especially for coexistent stage 3 uterine prolapse.

Age-specific prevalence, clinical and urodynamic findings of detrusor underactivity and bladder outlet obstruction in female voiding dysfunction.

OBJECTIVE: Female voiding dysfunction with cystocele have been widely studied, but there are no data regarding women without cystoceles. The present study aimed to evaluate the prevalence of detrusor underactivity (DU) and bladder outlet obstruction (BOO) without cystoceles in a large sample size. METHODS: This was a retrospective cohort study. Between April 1996 and September 2018, 602 neurologically intact women with voiding dysfunction without cystoceles were enrolled. Detrusor pressure (DU) at the maximum flow rate (PdetQmax) <20 cmH2O, maximum flow rate (Qmax) <15 mL/s, and a bladder voiding efficiency <90% and BOO (PdetQmax ≥40 cmH2O and Qmax <12 mL/s) were diagnosed by urodynamic study. Otherwise, a non-DU/BOO diagnosis was made. The prevalence of DU and BOO was the primary outcome. The secondary outcomes were the analyses of the differences between these three groups in objective UDS parameters and subjective questionnaires and bladder diary parameters. RESULTS: This study included 100 (17%) women with DU, 60 (10%) with BOO, and 442 (73%) with a non-DU/BOO diagnosis. DU increased with age, but BOO decreased as age increased. The women in the DU group were older, had higher parity and pad weights, and lower PdetQmax, maximum urethral closure pressure, and functional profile length than the BOO group. The urodynamic findings did not correlate well to subjective questionnaire parameters. None of the symptoms revealed a significant difference between the groups. The retrospective design was the limitation of the study. CONCLUSION: The prevalence of DU increased with age in women with voiding dysfunction without advanced cystoceles. Conversely, BOO decreased with age. Prevalence intersected in the fourth decade. Diagnosis requires urodynamic evaluation, as subjective symptoms are inconclusive.

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.

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.

Metformin inhibits nerve growth factor-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 downregulation of p35/CDK5 in PC12 cells. Furthermore, metformin inhibits the activation of the presynaptic protein Synapsin-I, a substrate of CDK5, in PC12 differentiation. In addition, 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.NEW & NOTEWORTHY This study unveils a novel mechanism influenced by metformin during sympathetic neuronal differentiation. By elucidating its inhibitory effects from the nerve growth factor (NGF) receptor, TrkA, to the p35/CDK5 signaling pathways, we advance our understanding of metformin's mechanisms of action and emphasize its potential significance in the context of drug responses during sympathetic neuronal differentiation.

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, 134:3677-3678, 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.

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.

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.

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.