Optimal Restoration of Spermatogenesis following Testosterone Therapy using hCG and FSH.

OBJECTIVE: To study improvements in spermatogenesis in men with a history of testosterone therapy using a novel fertility treatment regimen. DESIGN: A single-center retrospective cohort analysis. SUBJECTS: Seventy-seven men with previous testosterone use seeking fertility treatment from January 2020 to March 2024. EXPOSURE: A treatment regimen of 3000IU human Chorionic Gonadotropin (hCG) and 75IU Follicle Stimulating Hormone (FSH) three times a week was utilized. MAIN OUTCOME MEASURES: The primary outcome measured was change in sperm concentration during hCG/FSH therapy. The secondary outcome measured was whether concurrent testosterone therapy during hCG/FSH therapy affected recovery of spermatogenesis. RESULTS: Within the entire cohort (n=77), 74% of men demonstrated improvements in their sperm concentrations. There was not a significant difference in recovery of sperm concentration in men who stayed on testosterone therapy during hCG/FSH reboot (No testosterone therapy [n=50], 74% improved vs. Concurrent testosterone therapy [n=27], 74% improved). CONCLUSION: We report optimal recovery of spermatogenesis with hCG/FSH therapy in infertile men with a history of testosterone use. Concurrent testosterone therapy does not impede hCG/FSH-mediated spermatogenic recovery.

Immediate effects of propofol on mood: a randomized comparison of two doses in a cohort with depression.

RATIONALE: The intravenous anesthetic propofol is known to induce positive mood effects during routine clinical use, suggesting it might be repurposed as an antidepressant, but also raising concerns about abuse potential. How propofol's acute effects vary by dose and with repeated infusions is unknown. OBJECTIVES: This exploratory analysis aimed to (1) compare the immediate mood effects of propofol administered at two different doses, (2) describe how those mood effects change with repeated infusions, and (3) evaluate whether acute mood improvement predicts later antidepressant response. METHODS: Twenty-four adults with moderate-to-severe treatment-resistant depression were randomized into two dosing groups. Six low- or high-dose propofol infusions were administered under blinded conditions over a two-week period. Self-reported mood states were recorded before and after each infusion using the Positive and Negative Affect Schedule (PANAS-X). Abuse potential was evaluated with the Drug Effects Questionnaire (DEQ-5). RESULTS: At the first infusion, propofol induced acute improvements in PANAS-X Sadness, Fear, Joviality, and Serenity scales (p < 0.002), independent of dose. Over the series of six infusions, acute changes in Sadness, Fear, and Joviality, but not Serenity, diminished with infusion number (p < 0.002). The DEQ-5 "want more" rating decreased across infusions (p = 0.002). Changes in PANAS-X scales with the first infusion did not predict later improvement in depression severity (p > 0.05). CONCLUSION: Cumulative changes in mood states observed with repeated infusions suggest that propofol engages adaptive mechanisms in mood circuitry. Subjective responses with repeated infusions do not indicate increasing potential for abuse in this patient population.

Lithiation Induced Phases in 1T'-MoTe2 Nanoflakes.

Multiple polytypes of MoTe2 with distinct structures and intriguing electronic properties can be accessed by various physical and chemical approaches. Here, we report electrochemical lithium (Li) intercalation into 1T'-MoTe2 nanoflakes, leading to the discovery of two previously unreported lithiated phases. Distinguished by their structural differences from the pristine 1T' phase, these distinct phases were characterized using in situ polarization Raman spectroscopy and in situ single-crystal X-ray diffraction. The lithiated phases exhibit increasing resistivity with decreasing temperature, and their carrier densities are two to 4 orders of magnitude smaller than the metallic 1T' phase, as probed through in situ Hall measurements. The discovery of these gapped phases in initially metallic 1T'-MoTe2 underscores electrochemical intercalation as a potent tool for tuning the phase stability and electron density in two-dimensional (2D) materials.

Gene Coexpression and miRNA Regulation: A Path to Early Intervention in Colorectal Cancer.

Early diagnosis and intervention are pivotal in reducing colorectal cancer (CRC) incidence and enhancing patient outcomes. In this study, we focused on three genes, AQP8, GUCA2B, and SPIB, which exhibit high coexpression and play crucial roles in suppressing early-stage CRC. Our objective was to identify key miRNAs that can mitigate CRC tumorigenesis and modulate the coexpression network involving these genes. We conducted a comprehensive analysis using large-scale tissue mRNA data from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus to validate the coexpression of AQP8, GUCA2B, and SPIB, and to assess their diagnostic and prognostic significance in CRC. The mRNA-miRNA interactions were examined using MiRNet and the Encyclopedia of RNA Interactomes. Furthermore, using various molecular techniques, we conducted miRNA inhibitor transfection experiments in HCT116 cells to evaluate their effects on cell growth, migration, and gene/protein expression. Our findings revealed that, compared with normal tissues, AQP8, GUCA2B, and SPIB exhibited high coexpression and were downregulated in CRC, particularly during tumorigenesis. OncoMirs, hsa-miR-182-5p, and hsa-miR-27a-3p, were predicted to regulate these genes. MiRNA inhibition experiments in HCT116 cells demonstrated the inhibitory effects of miR-27a-3p and miR-182-5p on GUCA2B mRNA and protein expression. These miRNAs promoted the proliferation of CRC cells, possibly through their involvement in the GUCA2B-GUCY2C axis, which is known to promote tumor growth. While the expressions of AQP8 and SPIB were barely detectable, their regulatory relationship with hsa-miR-182-5p remained inconclusive. Our study confirms that hsa-miR-27a-3p and hsa-miR-182-5p are oncomiRs in CRC. These miRNAs may contribute to GUCY2C dysregulation by downregulating GUCA2B, which encodes uroguanylin. Consequently, hsa-miR-182-5p and hsa-miR-27a-3p show promise as potential targets for early intervention and treatment in the early stages of CRC.

Sinorhizobium meliloti BR-bodies promote fitness during host colonization.

Biomolecular condensates, such as the nucleoli or P-bodies, are non-membrane-bound assemblies of proteins and nucleic acids that facilitate specific cellular processes. Like eukaryotic P-bodies, the recently discovered bacterial ribonucleoprotein bodies (BR-bodies) organize the mRNA decay machinery, yet the similarities in molecular and cellular functions across species have been poorly explored. Here, we examine the functions of BR-bodies in the nitrogen-fixing endosymbiont Sinorhizobium meliloti, which colonizes the roots of compatible legume plants. Assembly of BR-bodies into visible foci in S. meliloti cells requires the C-terminal intrinsically disordered region (IDR) of RNase E, and foci fusion is readily observed in vivo, suggesting they are liquid-like condensates that form via mRNA sequestration. Using Rif-seq to measure mRNA lifetimes, we found a global slowdown in mRNA decay in a mutant deficient in BR-bodies, indicating that compartmentalization of the degradation machinery promotes efficient mRNA turnover. While BR-bodies are constitutively present during exponential growth, the abundance of BR-bodies increases upon cell stress, whereby they promote stress resistance. Finally, using Medicago truncatula as host, we show that BR-bodies enhance competitiveness during colonization and appear to be required for effective symbiosis, as mutants without BR-bodies failed to stimulate plant growth. These results suggest that BR-bodies provide a fitness advantage for bacteria during infection, perhaps by enabling better resistance against the host immune response.

Biphasic regulation of miR-17∼92 transcription during hypoxia: roles of HIF1 and p53 hyperphosphorylation at ser15.

We have reported previously that during hypoxia exposure, the expression of mature miR-17∼92 was first upregulated and then downregulated in pulmonary artery smooth muscle cells (PASMC) and in mouse lungs in vitro and in vivo. Here, we investigated the mechanisms regulating this biphasic expression of miR-17∼92 in PASMC in hypoxia. We measured the level of primary miR-17∼92 in PASMC during hypoxia exposure and found that short-term hypoxia exposure (3% O2, 6 h) induced the level of primary miR-17∼92, whereas long-term hypoxia exposure (3% O2, 24 h) decreased its level, suggesting a biphasic regulation of miR-17∼92 expression at the transcriptional level. We found that short-term hypoxia-induced upregulation of miR-17∼92 was hypoxia-inducible factor 1α (HIF1α) and E2F1 dependent. Two HIF1α binding sites on miR-17∼92 promoter were identified. We also found that long-term hypoxia-induced suppression of miR-17∼92 expression could be restored by silencing of p53. Mutation of the p53-binding sites in the miR-17∼92 promoter increased miR-17∼92 promoter activity in both normoxia and hypoxia. Our findings suggest that the biphasic transcriptional regulation of miR-17∼92 during hypoxia is controlled by HIF1/E2F1 and p53 in PASMC: during short-term hypoxia exposure, stabilization of HIF1 and induction of E2F1 induce the transcription of miR-17∼92, whereas during long-term hypoxia exposure, hyperphosphorylation of p53 suppresses the expression of miR-17∼92.NEW & NOTEWORTHY We showed that the biphasic transcriptional regulation of miR-17∼92 during hypoxia is controlled by two distinct mechanisms: during short-term hypoxia exposure, induction of HIF1 and E2F1 upregulates miR-17∼92. Longer hypoxia exposure induces hyperphosphorylation of p53 at ser15, which leads to its binding to miR-17∼92 promoter and inhibition of its expression. Our findings provide novel insights into the spatiotemporal regulation of miR-17∼92 that may play a role in the development of human lung diseases including pulmonary hypertension (PH).

Factors associated with longer survival among older medicare patients after diagnosis of supratentorial primary brain malignancies: a retrospective cohort study.

OBJECTIVES: Despite recent advances, the prognosis for primary malignant brain tumors (PMBTs) remains poor. Some commonly prescribed medications may exhibit anti-tumor properties in various cancers, and neurodegenerative diseases may activate pathways that counteract gliomagenesis. Our study is focused on determining if there is a correlation between the use of metformin, beta-blockers, angiotensin converting enzyme inhibitors (ACEIs), and angiotensin receptor blockers (ARBs), or the presence of Parkinson's disease (PD), and the survival rates following a diagnosis of a PMBT. METHODS: This analysis of the 100% Texas Medicare Database identified patients aged 66+ years diagnosed with a supratentorial PMBT from 2014-2017. Cox proportional hazards regression was employed to analyze survival following diagnosis and associations of survival with surgical intervention, radiation, PD diagnosis, and prescription of metformin, beta-blockers, ACEIs, or ARBs. RESULTS: There were 1,943 patients who met study criteria, and the median age was 74 years. When medication utilization was stratified by none, pre-diagnosis only, post-diagnosis only, or both pre- and post-diagnosis (continuous), continuous utilization of metformin, beta-blockers, ACEIs, or ARBs was associated with prolonged survival compared to no utilization (hazard ratio [HR]:0.45, 95% CI:0.33-0.62; HR:0.71. 95% CI:0.59-0.86; HR:0.59, 95% CI:0.48-0.72; and HR:0.45, 95% CI:0.35-0.58 respectively). PD was also associated with longer survival (HR:0.59-0.63 across the four models). DISCUSSION: Our study suggests that metformin, beta-blockers, ACEIs, ARBs, and comorbid PD are associated with a survival benefit among geriatric Medicare patients with supratentorial PMBTs.

Neurosurgery at Baylor Scott & White Health: Recent History and a Decade of Neurosurgery Residency Training.

Neurosurgery at Baylor Scott & White Memorial Hospital in Temple, Texas began as a division in the Department of Surgery many decades ago. The hospital has long served as the flagship tertiary referral center for the Baylor Scott & White healthcare system, which merged in 2013 with Baylor University Medical Center, a hospital system based in Dallas. It is now the largest non-profit hospital system as well as the most awarded hospital system by the US News and World Report within the state of Texas. The Department of Neurosurgery was established at Baylor Scott & White Memorial Hospital in the 2006-2007 academic year. Between then and 2014, four neurosurgeons served as department chair or interim chair: Dr. Robert Buchanan, Dr. Gerhard Friehs, Dr. Ibrahim El Nihum, and Dr. David Garrett Jr. In 2014, Dr. Jason Huang was appointed chairman after a national search and established the neurosurgery residency program in 2015. The department has undergone tremendous growth under the leadership of Dr. Huang, and the residency program is a priority of the department. Surgical excellence is honed at primarily three campuses: Baylor Scott & White Memorial Hospital, Baylor Scott & White McLane Children's Medical Center, and Baylor Scott & White Medical Center - Hillcrest. In this editorial, we provide a brief history of the institution, a recent history of the neurosurgical presence at Baylor Scott & White Memorial Hospital in Temple, Texas, and briefly describe the program's future directions under the continued leadership of Dr. Jason Huang.

In Situ and Operando X-ray Scattering Methods in Electrochemistry and Electrocatalysis.

Electrochemical and electrocatalytic processes are of key importance for the transition to a sustainable energy supply as well as for a wide variety of other technologically relevant fields. Further development of these processes requires in-depth understanding of the atomic, nano, and micro scale structure of the materials and interfaces in electrochemical devices under reaction conditions. We here provide a comprehensive review of in situ and operando studies by X-ray scattering methods, which are powerful and highly versatile tools to provide such understanding. We discuss the application of X-ray scattering to a wide variety of electrochemical systems, ranging from metal and oxide single crystals to nanoparticles and even full devices. We show how structural data on bulk phases, electrode-electrolyte interfaces, and nanoscale morphology can be obtained and describe recent developments that provide highly local information and insight into the composition and electronic structure. These X-ray scattering studies yield insights into the structure in the double layer potential range as well as into the structural evolution during electrocatalytic processes and phase formation reactions, such as nucleation and growth during electrodeposition and dissolution, the formation of passive films, corrosion processes, and the electrochemical intercalation into battery materials.

Astrocytic calcium waves: unveiling their roles in sleep and arousal modulation.

Neuron-astrocyte interactions are vital for the brain's connectome. Understanding astrocyte activities is crucial for comprehending the complex neural network, particularly the population-level functions of neurons in different cortical states and associated behaviors in mammals. Studies on animal sleep and wakefulness have revealed distinct cortical synchrony patterns between neurons. Astrocytes, outnumbering neurons by nearly fivefold, support and regulate neuronal and synaptic function. Recent research on astrocyte activation during cortical state transitions has emphasized the influence of norepinephrine as a neurotransmitter and calcium waves as key components of ion channel signaling. This summary focuses on a few recent studies investigating astrocyte-neuron interactions in mouse models during sleep, wakefulness, and arousal levels, exploring the involvement of noradrenaline signaling, ion channels, and glutamatergic signaling in different cortical states. These findings highlight the significant impact of astrocytes on large-scale neuronal networks, influencing brain activity and responsiveness. Targeting astrocytic signaling pathways shows promise for treating sleep disorders and arousal dysregulation. More research is needed to understand astrocytic calcium signaling in different brain regions and its implications for dysregulated brain states, requiring future human studies to comprehensively investigate neuron-astrocyte interactions and pave the way for therapeutic interventions in sleep- and arousal-related disorders.

Pterional Craniotomy With Anterior Clinoidectomy for the Resection of a Sphenoid Ridge Meningioma: A Case Report and Two-Dimensional Operative Video.

The pterional craniotomy with anterior clinoidectomy is a surgical technique used to resect sphenoid ridge meningiomas. It involves drilling the bone of the anterior clinoid process to gain access to the skull base, including the cavernous sinus and petrous apex particularly. This approach offers several advantages, including excellent exposure of the surgical site, minimal brain retraction, and the ability to visualize and protect critical neurovascular structures. We present a case of a 59-year-old woman presented with headache, dizziness, blurry vision, and unsteady gait for several months. The brain magnetic resonance imaging with gadolinium contrast showed a large space-occupying homogeneously-enhancing lesion at the left skull base, displacing the surrounding structures, including the frontal lobe, temporal lobe, and brainstem. Herein, we present the intraoperative video on a case in which the pterional craniotomy with anterior clinoidectomy that can allow the exposure and resection of the tumor extending into the posterior fossa was utilized for the resection of a large left sphenoid ridge meningioma with brain stem compression.

Exploring Spinal Subarachnoid Hemorrhage: A Neurosurgical Case Series.

Spinal subarachnoid hemorrhage (SSAH) is a rare condition that can cause spinal cord or nerve root compression and permanent neurologic damage. The reported etiologies include trauma, vascular malformations or aneurysms, coagulopathies, neoplasms, autoimmune disease, and spontaneous hemorrhage. If there is evidence of neurologic deterioration, it is commonly managed as a surgical emergency, but cases of conservative management have also been reported. In this case series, we present three patients who suffered from SSAH. The first was a spontaneous cervical SSAH that occurred following cardiac catheterization, the second was a spontaneous thoracolumbar SSAH in a patient with a known history of coagulopathy, and the third was a thoracolumbar SSAH that was caused by a dural arteriovenous fistula (dAVF). All three patients exhibited neurologic deficits and thus underwent emergent decompression and hematoma evacuation. The patient with the dAVF also required open ligation of the fistula. Following surgical intervention, all three patients regained at least partial neurologic function, but one patient developed symptomatic arachnoid cysts that required further intervention. The presented case series highlights the importance and time-sensitivity of surgical decompression in patients experiencing neurologic deficits from SSAH. These cases underscore the urgency of timely neurosurgical intervention to mitigate neurologic impairment and add insights to the existing literature on this rare condition.

Propofol for treatment resistant depression: A randomized controlled trial.

Background: Anesthetic agents including ketamine and nitrous oxide have shown antidepressant properties when appropriately dosed. Our recent open-label trial of propofol, an intravenous anesthetic known to elicit transient positive mood effects, suggested that it may also produce robust and durable antidepressant effects when administered at a high dose that elicits an electroencephalographic (EEG) burst-suppression state. Here we report findings from a randomized controlled trial ( NCT03684447 ) that compared two doses of propofol. We hypothesized greater improvement with a high dose that evoked burst suppression versus a low dose that did not. Methods: Participants with moderate-to-severe, treatment-resistant depression were randomized to a series of 6 treatments at low versus high dose (n=12 per group). Propofol infusions were guided by real-time processed frontal EEG to achieve predetermined pharmacodynamic criteria. The primary and secondary depression outcome measures were the 24-item Hamilton Depression Rating Scale (HDRS-24) and the Patient Health Questionnaire (PHQ-9), respectively. Secondary scales measured suicidal ideation, anxiety, functional impairment, and quality of life. Results: Treatments were well tolerated and blinding procedures were effective. The mean [95%-CI] change in HDRS-24 score was -5.3 [-10.3, -0.2] for the low-dose group and -9.3 [-12.9, -5.6] for the high-dose group (17% versus 33% reduction). The between-group effect size (standardized mean difference) was -0.56 [-1.39, 0.28]. The group difference was not statistically significant (p=0.24, linear model). The mean change in PHQ-9 score was -2.0 [-3.9, -0.1] for the low dose and -4.8 [-7.7, -2.0] for the high dose. The between-group effect size was -0.73 [-1.59, 0.14] (p=0.09). Secondary outcomes favored the high dose (effect sizes magnitudes 0.1 - 0.9) but did not generally reach statistical significance (p>0.05). Conclusions: The medium-sized effects observed between doses in this small, controlled, clinical trial suggest that propofol may have dose-dependent antidepressant effects. The findings also provide guidance for subsequent trials. A larger sample size and additional treatments in series are likely to enhance the ability to detect dose-dependent effects. Future work is warranted to investigate potential antidepressant mechanisms and dose optimization.

Getting under the skin? Influences of work-family experiences on personality trait adaptation and reciprocal relationships.

The literature on personality trait development has mainly focused on influences of life experiences in one single life domain (e.g., work or family) separate from one another and has primarily examined personality development in early life stages. Thus, less attention has been devoted to influences from interplays across different life domains and personality development in middle and late adulthood. Synthesizing the literature on personality science and organizational research, we built a theoretical model and investigated what, how, and why the interplay between two central life domains-work and family-may be related to personality trait development of people at their middle and late life stages, and more important, change-related reciprocal relationships between personality traits and work-family experiences. Generally, convergent findings with data from two longitudinal studies (National Survey of Midlife in the United States, maximum N = 3,192, three waves; and Health and Retirement Study, maximum N = 1,133, three waves except anxiety) revealed that work-to-family conflict, family-to-work conflict, work-to-family facilitation, and family-to-work facilitation mostly had lagged effects on changes of Conscientiousness, Extraversion, and Neuroticism, and the influences were generally channeled through changes of anxiety. Personality traits also had lagged influences on changes of work-family experiences, with some influences deteriorating over time. Change-related reciprocal relationships were recorded mainly between Neuroticism and Extraversion with work-family experiences. Some selection effects were larger than socialization effects. Our research contributes to the personality and the work-family literature and represents a useful example of cross-fertilization of research in different areas of psychology to advance personality research. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A Comprehensive Phylogenetic Analysis of SARS-CoV-2: Utilizing a Novel and Convenient In-House RT-PCR Method for Characterization without Virus Culture and BSL-3 Facilities.

We developed a convenient method for amplifying the complete SARS-CoV-2 sequence using in-house RT-PCR without virus culture. Forty-one stored throat swabs and blood specimens were collected from eight SARS-CoV-2 infections at multiple time points. Total RNA was extracted using the QIAamp viral RNA mini kit and pooled for higher RNA levels. Only those positive specimens by commercial real-time RT-PCR (RT-qPCR) were selected and amplified by in-house RT-PCR for complete sequences, followed by sequencing. Phylogenetic trees and exploratory analyses were performed using MEGA 11 and Simplot 3.5.1 software. Swab samples had significantly higher total RNA concentrations than plasma (p < 0.01). Positive results were found mainly in swabs, but one was found in plasma. Successful gene amplification depended on Ct values (Ct < 38). A non-synonymous substitution was found in ORF1ab/Nsp3 (at NC045512.2 position 6312, C to A) and most spike protein mutations occurred in the S1 subunit (residues 14-685). The proposed method is time-saving and reliable for rapid genomic analysis. Increasing sample volume and pooling them for RNA extraction increases RNA concentration without culture. Combining nucleotide sequences from specific variable regions of the genome is more efficient than conventional methods.

H3G34-Mutant Gliomas-A Review of Molecular Pathogenesis and Therapeutic Options.

The 2021 World Health Organization Classification of Tumors of the Central Nervous System reflected advances in understanding of the roles of oncohistones in gliomagenesis with the introduction of the H3.3-G34R/V mutant glioma to the already recognized H3-K27M altered glioma, which represent the diagnoses of pediatric-type diffuse hemispheric glioma and diffuse midline glioma, respectively. Despite advances in research regarding these disease entities, the prognosis remains poor. While many studies and clinical trials focus on H3-K27M-altered-glioma patients, those with H3.3-G34R/V mutant gliomas represent a particularly understudied population. Thus, we sought to review the current knowledge regarding the molecular mechanisms underpinning the gliomagenesis of H3.3-G34R/V mutant gliomas and the diagnosis, treatment, long-term outcomes, and possible future therapeutics.