Content analysis of Reddit posts about coadministration of selective serotonin reuptake inhibitors and psilocybin mushrooms.

RATIONALE: Treatments with the serotonergic psychedelic psilocybin are being investigated for multiple neuropsychiatric disorders. Because many patients with these disorders use selective serotonin reuptake inhibitors (SSRIs), understanding interactions between psilocybin and SSRIs is critical for evaluating the safety, efficacy, and scalability of psilocybin-based treatments. Current knowledge about these interactions is limited, as most clinical psilocybin research has prohibited concomittant SSRI use. OBJECTIVES: We aimed to explore potential interactions between psilocybin and SSRIs by characterizing peoples' real-world experiences using psilocybin mushrooms and SSRIs together. METHODS: We conducted a systematic search of Reddit for posts describing psilocybin mushroom and SSRI coadministration. We identified 443 eligible posts and applied qualitative content analysis to each. RESULTS: 8% of posts reported negative physical or psychological effects resulting from coadministration. These included 13 reports that may reflect serotonin toxicity, and 1 concerning for a psychotic/manic episode. 54% of posts described reduced intensity of the acute psilocybin experience, but 39% reported unchanged intensity with SSRI coadministration. CONCLUSIONS: Psilocybin's interactions with SSRIs are likely complex and may depend on multiple factors. Prospective studies are needed to evaluate whether psilocybin treatments are reliably safe and effective in the setting of SSRI use.

A 65-Year-Old Woman With No Menopause History: A Case Report.

Menopause is a universal occurrence in a woman's life where menstruation ceases, with an average age of 51.4 years in the United States. Late-onset menopause is defined as menopause after age 55. A thorough PubMed search revealed that there are currently no records of extended cycles through the entirety of a woman's geriatric years. A 65-year-old G2P2 Caucasian woman was admitted to the emergency department (ER) with a possible cerebrovascular accident. During admission, it was noted that the patient had vaginal bleeding. CT scan revealed a large fibroid, and ultrasound revealed an extremely thin endometrium, excluding endometrial pathology. Gynecology was consulted for post-menopausal bleeding, but in interviewing the patient, she was not surprised at her bleeding. Her LH and FSH levels were low, in the premenopausal range. This is a cautionary tale of an appropriate workup, and the importance of taking a gynecologic history, in the geriatric population.

Possible Ovarian and Peritoneal Carcinoma Presenting in a Mediastinal Lymph Node and Pleural Effusion: A Case Report and Review of the Literature.

Ovarian carcinoma often doesn't show noticeable symptoms and is frequently diagnosed at an advanced stage. It is the most fatal cancer within the gynecologic system. Our understanding of ovarian pathology is limited, necessitating the use of multiple markers to accurately detect ovarian cancer, particularly when it presents abnormally, such as in pleural effusion or lymph nodes. A 45-year-old woman presented to the emergency room (ER) due to abdominal pain lasting for two weeks. A computed tomography (CT) scan revealed peritoneal carcinomatosis accompanied by ascites and calcification in the lymph nodes. The likely primary sources were determined to be mucinous adenocarcinomas from either the colon or ovary. Following the CT findings, a fine needle aspiration was conducted on a perigastric lymph node. Histopathology results indicated a "poorly differentiated carcinoma [with] malignant cells present." Subsequently, a PowerPort was inserted, and adjuvant chemotherapy commenced two days later, utilizing a combination of carboplatin, bevacizumab, and paclitaxel. Paracentesis was performed, yielding clear-yellow fluid. However, abdominal fullness gradually increased again after paracentesis. The patient began experiencing more intense abdominal pain, particularly in the left lower quadrant. Surgical exploration revealed widespread disease involvement throughout the intestines. Our patient exhibited an atypical manifestation of ovarian carcinoma, challenging its identification due to ectopic foci and the absence of many distinctly identifiable markers. Through comprehensive testing and a process of elimination, we successfully differentiated ovarian carcinoma from other potential cancers. The conclusive histopathological report, along with a markedly elevated CA-125 level, provided substantial support for the probable final diagnosis of ovarian carcinoma. Despite numerous advancements in staining and identification techniques, the diagnosis of ovarian carcinoma remains inadequately understood. Identifying ovarian carcinoma without clear visualization is often challenging, and further research is warranted to enhance our understanding of pathological methods. Moreover, there is a need to prioritize the development and exploration of ovarian carcinoma screening and testing methods to prevent delayed disease detection.

A Novel Case of Providencia rettgeri Osteomyelitis Presenting in the Frontal Bone.

Osteomyelitis of the skull is a particularly life-threatening condition. Infections are usually at the base of the skull and typically occur following dissemination from another site, such as the external auditory canal. Typical organisms include Pseudomonas and Staphylococcus species. This paper demonstrates an unusual case of osteomyelitis of the frontoparietal bone, as well as the first published case of Providencia rettgeri causing cranial osteomyelitis in humans.

A Rare Presentation of Rhodococcus Equi Bacteremia as a Result of Right Upper Arm Cellulitis: A Case Report and Literature Review.

Rhodococcus equi is an emerging opportunistic pathogen in immunocompromised patients. Owing to its resemblance to Mycobacterium, Nocardia, and Corynebacterium, R. equi is frequently misdiagnosed as a contaminant, which can result in treatment delays. A 65-year-old man with a history of end-stage renal disease (ESRD) presented to the emergency room with pain and increased swelling in his right upper extremity. Shortly after he arrived in the emergency room, his condition deteriorated. Intravenous vancomycin was administered after collecting blood cultures. The blood cultures grew Rhodococcus equi, and oral azithromycin and oral rifampin were added for a 14-day course of treatment. The patient recovered without any further complications and was subsequently discharged home.  R. equi is a partially acid-fast actinomycete that spreads through contact with grazing animals and contaminated soil. R. equi invades macrophages to survive and causes infection within a host. In this particular case, the patient worked on a farm taking care of goats. He was exposed to the bacteria after falling and sustaining multiple lacerations to the right arm. This case is unique due to the development of bacteremia with R. equi, an uncommon cause of bacteremia that led to cardiopulmonary arrest. The treatment with oral azithromycin combined with oral rifampin and intravenous vancomycin was effective for the complete resolution of the infection.

Conditioned place avoidance is associated with a distinct hippocampal phenotype, partly preserved pattern separation, and reduced reactive oxygen species production after stress.

Stress is associated with contextual memory deficits, which may mediate avoidance of trauma-associated contexts in posttraumatic stress disorder. These deficits may emerge from impaired pattern separation, the independent representation of similar experiences by the dentate gyrus-Cornu Ammonis 3 (DG-CA3) circuit of the dorsal hippocampus, which allows for appropriate behavioral responses to specific environmental stimuli. Neurogenesis in the DG is controlled by mitochondrial reactive oxygen species (ROS) production, and may contribute to pattern separation. In Experiment 1, we performed RNA sequencing of the dorsal hippocampus 16 days after stress in rats that either develop conditioned place avoidance to a predator urine-associated context (Avoiders), or do not (Non-Avoiders). Weighted genome correlational network analysis showed that increased expression of oxidative phosphorylation-associated gene transcripts and decreased expression of gene transcripts for axon guidance and insulin signaling were associated with avoidance behavior. Based on these data, in Experiment 2, we hypothesized that Avoiders would exhibit elevated hippocampal (HPC) ROS production and degraded object pattern separation (OPS) compared with Nonavoiders. Stress impaired pattern separation performance in Non-Avoider and Avoider rats compared with nonstressed Controls, but surprisingly, Avoiders exhibited partly preserved pattern separation performance and significantly lower ROS production compared with Non-Avoiders. Lower ROS production was associated with better OPS performance in Stressed rats, but ROS production was not associated with OPS performance in Controls. These results suggest a strong negative association between HPC ROS production and pattern separation after stress, and that stress effects on these outcome variables may be associated with avoidance of a stress-paired context.

Modulation of nigral dopamine signaling mitigates parkinsonian signs of aging: evidence from intervention with calorie restriction or inhibition of dopamine uptake.

Identifying neurobiological mechanisms of aging-related parkinsonism, and lifestyle interventions that mitigate them, remain critical knowledge gaps. No aging study, from rodent to human, has reported loss of any dopamine (DA) signaling marker near the magnitude associated with onset of parkinsonian signs in Parkinson's disease (PD). However, in substantia nigra (SN), similar loss of DA signaling markers in PD or aging coincide with parkinsonian signs. Alleviation of these parkinsonian signs may be possible by interventions such as calorie restriction (CR), which augment DA signaling markers like tyrosine hydroxylase (TH) expression in the SN, but not striatum. Here, we interrogated respective contributions of nigral and striatal DA mechanisms to aging-related parkinsonian signs in aging (18 months old) rats in two studies: by the imposition of CR for 6 months, and inhibition of DA uptake within the SN or striatum by cannula-directed infusion of nomifensine. Parkinsonian signs were mitigated within 12 weeks after CR and maintained until 24 months old, commensurate with increased D1 receptor expression in the SN alone, and increased GDNF family receptor, GFR-α1, in the striatum, suggesting increased GDNF signaling. Nomifensine infusion into the SN or striatum selectively increased extracellular DA. However, only nigral infusion increased locomotor activity. These results indicate mechanisms that increase components of DA signaling in the SN alone mitigate parkinsonian signs in aging, and are modifiable by interventions, like CR, to offset parkinsonian signs, even at advanced age. Moreover, these results give evidence that changes in nigral DA signaling may modulate some parameters of locomotor activity autonomously from striatal DA signaling.

Rate of Inpatient Hypoglycemia Following a 1:1 Dose Interchange Between Concentrated Insulin Glargine to Insulin Detemir.

BACKGROUND: Insulin remains a mainstay of treating hyperglycemia in an acute setting. Insulin glargine 300 units/mL (Toujeo, iGlar300) has a different pharmacokinetic profile than 100 units/mL basal insulins, such as insulin detemir (iDet100) and iGlar100. While conversion from iGlar300 to iGlar100 requires a 20% dose decrease, there is currently no recommended interchange from iGlar300 to iDet100. OBJECTIVE: Compare the incidence of hypoglycemia in patients who received a 1:1 unit interchange from home iGlar300 or iGlar100 to iDet100 while admitted. METHODS: A retrospective study was conducted to evaluate adults within a multi-site network admitted between May and December 2019. Patients were included if they received at least one dose of iDet100 following interchange from home iGlar300 or iGlar100. The primary endpoint was the incidence of hypoglycemic events following a 1:1 interchange of iGlar300 vs. iGlar100 to inpatient iDet100. Secondary outcomes include overall hypoglycemic events, time to hypoglycemia, and doses given before hypoglycemia. RESULTS: Of 615 patients, 394 received a 1:1 unit interchange to iDet100 (52 from iGlar300 and 342 from iGlar100). Incidence of hypoglycemic events was significantly higher in those with a 1:1 interchange from iGlar300 versus iGlar100 (36.5% vs. 18.7%, p = 0.007). Significant differences were observed in overall hypoglycemic events, time to hypoglycemia, and number of doses given before hypoglycemic event. CONCLUSION AND RELEVANCE: A 1:1 unit interchange from iGlar300 to iDet100 led to a higher incidence of hypoglycemic events compared to those interchanged from iGlar100. Dose reduction should be considered when transitioning from home iGlar300 to iDet100 in the inpatient setting.

A bioinspired apparatus for modeling peristaltic pumping in biophysical flows.

In this study, we present a novel, bioinspired experimental apparatus, its construction, data acquisition methodology, and validation for the study of peristaltic flows. The apparatus consists of a series of stepper motor actuators, which deflect a deformable membrane to produce peristaltic flows. We show that this apparatus design has significant advantages over previous designs that have been used to study peristaltic flows by offering a much wider range of modeling capabilities. Comparisons between the capabilities of our apparatus and previous ones show our apparatus spanning a larger range of wavelengthλ, wave speedc, amplitudeA, and waveform (i.e. the apparatus is not constrained to nondispersive waves or to a sinusoidal shape). This large parameter range makes the apparatus a useful tool for biomimetic experimental modeling, particularly for systems that have complex waveforms, such as peristaltic flows in perivascular vessels, arteries, the cochlea, and the urethra. We provide details on the experimental design and construction for ease of reconstruction to the reader. The apparatus capabilities are validated for a large parameter range by comparing experimental measurements to analytic results from (Ibanezet al2021Phys. Rev. Fluids6103101) for high Reynolds number (Re > 1) and (Jaffrin and Shapiro 1971Annu. Rev. Fluid Mech.33-37) for low Reynolds number (Re < 1) applications. We show that the apparatus is useful for biophysical peristaltic studies and has potential applications in other types of studies.

Labelfree mapping and profiling of altered lipid homeostasis in the rat hippocampus after traumatic stress: Role of oxidative homeostasis.

Oxidative and lipid homeostasis are altered by stress and trauma and post-traumatic stress disorder (PTSD) is associated with alterations to lipid species in plasma. Stress-induced alterations to lipid oxidative and homeostasis may exacerbate PTSD pathology, but few preclinical investigations of stress-induced lipidomic changes in the brain exist. Currently available techniques for the quantification of lipid species in biological samples require tissue extraction and are limited in their ability to retrieve spatial information. Raman imaging can overcome this limitation through the quantification of lipid species in situ in minimally processed tissue slices. Here, we utilized a predator exposure and psychosocial stress (PE/PSS) model of traumatic stress to standardize Raman imaging of lipid species in the hippocampus using LC-MS based lipidomics and these data were confirmed with qRT-PCR measures of mRNA expression of relevant enzymes and transporters. Electron Paramagnetic Resonance Spectroscopy (EPR) was used to measure free radical production and an MDA assay to measure oxidized polyunsaturated fatty acids. We observed that PE/PSS is associated with increased cholesterol, altered lipid concentrations, increased free radical production and reduced oxidized polyunsaturated fats (PUFAs) in the hippocampus (HPC), indicating shifts in lipid and oxidative homeostasis in the HPC after traumatic stress.

Practical Strategies for Advanced Practitioners Streamlining the Integration of Oncology Biosimilar Therapies Into Practice.

In oncology practices across the United States, biosimilars-highly similar versions of licensed, innovator (reference) biological medicines-are currently emerging as more affordable therapeutic options. Only after a rigorous product development program, during which a proposed biosimilar is analyzed and compared with its reference biologic to demonstrate comparable clinical efficacy, safety, and tolerability, is biosimilarity supported and licensure granted by the US Food and Drug Administration. Coincidentally, many advanced practitioners (APs) are finding themselves at the forefront of introducing monoclonal antibody (mAb) biosimilars in their oncology practice. Advanced practitioners are often tasked with building the confidence of colleagues and patients who may be unfamiliar with biosimilars, skeptical about integrating them, or have yet to consider mAb biosimilars as a viable and more sustainable cancer treatment option. With this responsibility comes a number of challenges that require APs to become knowledgeable about biosimilars and approaches to their implementation. This review aims to highlight the practical implications of streamlining the integration of biosimilar therapies in an oncology practice.

Pharmahuasca and DMT Rescue ROS Production and Differentially Expressed Genes Observed after Predator and Psychosocial Stress: Relevance to Human PTSD.

Post-traumatic stress disorder (PTSD) is associated with cognitive deficits, oxidative stress, and inflammation. Animal models have recapitulated features of PTSD, but no comparative RNA sequencing analysis of differentially expressed genes (DEGs) in the brain between PTSD and animal models of traumatic stress has been carried out. We compared DEGs from the prefrontal cortex (PFC) of an established stress model to DEGs from the dorsolateral PFC (dlPFC) of humans. We observed a significant enrichment of rat DEGs in human PTSD and identified 20 overlapping DEGs, of which 17 (85%) are directionally concordant. N,N-dimethyltryptamine (DMT) is a known indirect antioxidant, anti-inflammatory, and neuroprotective compound with antidepressant and plasticity-facilitating effects. We tested the capacity of DMT, the monoamine oxidase inhibitor (MAOI) harmaline, and "pharmahuasca" (DMT + harmaline) to reduce reactive oxygen species (ROS) production and inflammatory gene expression and to modulate neuroplasticity-related gene expression in the model. We administered DMT (2 mg/kg IP), harmaline (1.5 mg/kg IP), pharmahuasca, or vehicle every other day for 5 days, following a 30 day stress regiment. We measured ROS production in the PFC and hippocampus (HC) by electron paramagnetic resonance spectroscopy and sequenced total mRNA in the PFC. We also performed in vitro assays to measure the affinity and efficacy of DMT and harmaline at 5HT2AR compared to 5-HT. DMT and pharmahuasca reduced ROS production in the PFC and HC, while harmaline had mixed effects. Treatments normalized 9, 12, and 14 overlapping DEGs, and pathway analysis implicated that genes were involved in ROS production, inflammation, growth factor signaling, neurotransmission, and neuroplasticity.

Improving Health Equity: The Role of the Oncology Advanced Practitioner in Managing Implicit Bias.

Implicit bias (IB) is the involuntary activation of thoughts, feelings, attitudes, or stereotypes that exist outside of conscious awareness. Implicit bias develops early in life and research documents the existence of IB across health-care settings. Negative IB impacts patient-provider interactions, produces inferior patient outcomes, and contributes to health-care disparities. Oncology APs are subject to IB and should be aware of its potential impact on professional practice. This manuscript explores the concept of IB and reviews evidence examining the clinical impact of IB in the oncology setting. Strategies for identifying and mitigating IB are explored. Highlights include the use of the Implicit Association Test and emotional intelligence. Advanced practice implications are discussed and range from self-improvement to organizational transformation.

Ecological Dynamics: Integrating Empirical, Statistical, and Analytical Methods.

Understanding ecological processes and predicting long-term dynamics are ongoing challenges in ecology. To address these challenges, we suggest an approach combining mathematical analyses and Bayesian hierarchical statistical modeling with diverse data sources. Novel mathematical analysis of ecological dynamics permits a process-based understanding of conditions under which systems approach equilibrium, experience large oscillations, or persist in transient states. This understanding is improved by combining ecological models with empirical observations from a variety of sources. Bayesian hierarchical models explicitly couple process-based models and data, yielding probabilistic quantification of model parameters, system characteristics, and associated uncertainties. We outline relevant tools from dynamical analysis and hierarchical modeling and argue for their integration, demonstrating the value of this synthetic approach through a simple predator-prey example.

Improving Outcomes in HER2-Positive Breast Cancer: Analysis and Application of Evolving Data and Best Practices.

Through expert, case-based discussion, Jame Abraham, MD, and Kelley Mayden, MSN, FNP, AOCNP®, presented existing and emerging data for current and investigational therapies for HER2-positive breast cancer and their associated adverse events, in addition to best practices for managing central nervous system metastases.

Developing ocean climate change indicators for the north-central California coast and ocean.

The Ocean Climate Indicators Project, developed for the Greater Farallones National Marine Sanctuary (GFNMS), yielded the first set of physical and biological ocean climate indicators specifically developed for the north-central California coast and ocean region, which extends from Point Arena to Point Año Nuevo and includes the ocean shorelines of the San Francisco metropolitan area. This case study produced a series of physical and biological indicator categories through a best professional judgment (BPJ) process with an interdisciplinary group of over 50 regional research scientists and marine resource managers from a wide range of state and federal agencies, NGOs, and universities. A working group of research scientists and marine resource managers used this set of ocean climate indicators to develop the Ocean Climate Indicators Monitoring Inventory and Plan. The Plan includes monitoring goals and objectives common for eight physical and four biological indicators; specific goals for each indicator; monitoring strategies and activities; an inventory of available monitoring data; opportunities for expanding or improving existing or new monitoring approaches; and case studies with specific examples of the indicators' utility for natural resource management and basic scientific research. Beyond developing indicators that support effective science-based management decisions, this scalable process established and strengthened mutually beneficial connections between scientists and managers, resulting in indicators that had broad support of project participants, were quickly adopted by the GFNMS, and could be used by managers and scientists from this region and beyond.

Evidence-Based Oncology Practice: Competencies for Improved Patient Outcomes.

Oncology advanced practice providers (APP) play a critical role in providing cancer care to patients and families. Given the rate of scientific advancement, APPs are challenged to keep with the pace of science and acquire tools for successful practice. One such tool is evidence-based practice (EBP). Mastery of the competencies is obligatory and will assist APPs with the incorporation of EBP into clinical practice, and thus ensure the highest quality of patient care, forge the best patient outcomes, and reduce health-care expenditures. Advanced practice providers who achieve competency and proficiency have a professional responsibility to mentor others and assume leadership roles to help cement EBP as the standard of care.

Current and future functional imaging techniques for post-traumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a trauma and stressor related psychiatric disorder associated with structural, metabolic, and molecular alternations in several brain regions including diverse cortical areas, neuroendocrine regions, the striatum, dopaminergic, adrenergic and serotonergic pathways, and the limbic system. We are in critical need of novel therapeutics and biomarkers for PTSD and a deep understanding of cutting edge imaging and spectroscopy methods is necessary for the development of promising new approaches to better diagnose and treat the disorder. According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criterion, all forms of traumatic stress-induced disorder are considered acute stress disorder for the first month following the stressor. Only after symptoms do not remit for one month can the disorder be deemed PTSD. It would be particularly useful to differentiate between acute stress disorder and PTSD during the one month waiting period so that more intensive treatments can be applied early on to patients with a high likelihood of developing PTSD. This would potentially enhance treatment outcomes and/or prevent the development of PTSD. Comprehension of the qualities and limitations of currently applied methods as well as the novel emerging techniques provide invaluable knowledge for fast paced development. Conventional methods of studying PTSD have proven to be insufficient for diagnosis, measurement of treatment efficacy, and monitoring disease progression. As the field currently stands, there is no diagnostic biomarker available for any psychiatric disease, PTSD included. Currently, emerging and available technologies are not utilized to their full capacity and in appropriate experimental designs for the most fruitful possible studies in this area. Therefore, there is an apparent need for improved methods in PTSD research. This review demonstrates the current state of the literature in PTSD, including molecular, cellular, and behavioral indicators, possible biomarkers and clinical and pre-clinical imaging techniques relevant to PTSD, and through this, elucidate the void of current practical imaging and spectroscopy methods that provide true biomarkers for the disorder and the significance of devising new techniques for future investigations. We are unlikely to develop a single biomarker for any psychiatric disorder however. As psychiatric disorders are incomparably complex compared to other medical diagnoses, its most likely that transcriptomic, metabolomic and structural and connectomic imaging data will have to be analyzed in concert in order to produce a dependable non-behavioral marker of PTSD. This can explain the necessity of bridging conventional approaches to novel technologies in order to create a framework for further discoveries in the treatment of PTSD.

Home Is Where the HeartWare Is: Preparing Pediatric Patients and Caregivers for Discharge to Home and Integration Into the Community.

The Cardiac Center at The Children's Hospital of Philadelphia has cared for patients with implanted ventricular assist device (VAD) technology since 1998. Historically, patients requiring VAD support were managed exclusively in the Cardiac Intensive Care Unit with the first medically stable transition to the Cardiac Care Unit (step-down) taking place in 2001. Patient management was confined to the inpatient setting, as the primary device used at the time was paracorporeal and not suitable for home use. Continuous-flow devices, such as the HeartWare HVAD, have gained popularity because of miniaturized size and lower profiles of side effects and adverse events, making them more suitable for home use. This article describes a single-center experience with transitioning the VAD-supported pediatric patient to the outpatient setting, highlighting outcomes, strategies, and lessons learned in order to support VAD patients and their caregivers in the hospital and community setting.

Fluorescence photobleaching of microplastics: A cautionary tale.

Fluorescence microscopy is an important step in visual identification of microplastics and is used to highlight white and transparent plastics that are otherwise easily missed or misidentified. Investigators using fluorescence must proceed with caution, however, as fluorescence photobleaching can significantly reduce the fluorescence output of samples within experimentally relevant time frames. We report on the photobleaching rate and subsequent lack of fluorescence recovery of five common plastics. Our results reveal statistically different photobleaching rates across plastic types. In the best-case scenario of low illumination intensity and a robust plastic, initial fluorescence intensity decayed by 10% in just 11(3) s and by 33% in 230(40) s. In all cases, fluorescence failed to recover more than 13(8)% in 3 h. These results indicate that significant bleaching can occur while searching a sample for plastics to identify and that the lack of recovery can compromise samples for further study.