Iron-Tannin Coating Reduces Clearance and Increases Tumor Colonization of Systemically Delivered Bacteria.

Engineered bacteria offer a novel approach to targeted cancer therapy, but challenges remain in delivering enough bacteria safely for effective treatment. Previous efforts have used either a native or synthetic coating to achieve better control over the half-life of bacteria in the body but have limitations in delivery or versatility. In this work, we optimized and evaluated a synthetic coating for probiotic Nissle 1917 to increase its half-life in blood and thereby increase the bioavailability of intravenous doses of bacteria to colonize and treat tumors.

An Anatomical Variant of Bilateral Persistent Median Artery and Bifid Median Nerve: A Cadaveric Case Report.

An 89-year-old Caucasian male cadaver with prostate cancer demonstrated bilateral persistence of the median artery and bifid median nerve (BMN) during upper limb dissection. The persistent median artery (PMA) originated from the common interosseous artery and coursed alongside the median nerve. Proximal to the carpal tunnel, the median nerve bifurcated into medial and lateral branches.

FLT1 activation in cancer cells promotes PARP-inhibitor resistance in breast cancer.

Acquired resistance to PARP inhibitors (PARPi) remains a treatment challenge for BRCA1/2-mutant breast cancer that drastically shortens patient survival. Although several resistance mechanisms have been identified, none have been successfully targeted in the clinic. Using new PARPi-resistance models of Brca1- and Bard1-mutant breast cancer generated in-vivo, we identified FLT1 (VEGFR1) as a driver of resistance.

Neurologic Approach to Radiculopathy, Back Pain, and Neck Pain.

Back pain and neck pain are common in clinical practice, but significant challenges and pitfalls exist in their diagnosis, treatment, and management. From the neurologic standpoint, cervical radiculopathy and lumbosacral radiculopathy are characterized by neck pain or back pain accompanied by sensory and motor symptoms in an arm or leg. The basic neurologic examination is vital, but testing like electromyography and MRI is often needed especially in cases that fail conservative management.

Battle of the sections: Student outcomes and course feedback support combined prosection and dissection laboratory formats to maximize student success.

Gross anatomy laboratories frequently utilize dissection or prosection formats within medical curricula. Practical examination scores are consistent across the formats, yet these examinations assessed larger anatomical structures. In contrast, a single report noted improved scores when prosection was used in the hand and foot regions, areas that are more difficult to dissect.

Vagus nerve damage increases alcohol intake and preference in a nonpreferring rat line: Relationship to vagal regulation of the hypothalamic-pituitary-adrenal axis.

Background: Clinical and preclinical research indicates that gastric weight loss surgeries, such as Roux-en-Y gastric bypass surgery, can induce alcohol use disorder (AUD). While numerous mechanisms have been proposed for these effects, one relatively unexplored potential mechanism is physical damage to the gastric branch of the vagus nerve, which can occur during bypass surgery. Therefore, we hypothesized that direct damage to the gastric branch of the vagus nerve, without altering other aspects of gastric anatomy, could result in increased alcohol intake.

Engineering tumor-colonizing E. coli Nissle 1917 for detection and treatment of colorectal neoplasia.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment. Here, first, we demonstrate selective colonization of colorectal adenomas after oral delivery of probiotic E. coli Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition and orthotopic models of CRC.

Adolescent alcohol disrupts development of noradrenergic neurons in the nucleus of the tractus solitarius and enhances stress behaviors in adulthood in mice in a sex specific manner.

Alcohol use disorders (AUDs) are common mental health issues worldwide and can lead to other chronic diseases. Stress is a major factor in the development and continuation of AUDs, and adolescent alcohol exposure can lead to enhanced stress-responsivity and increased risk for AUD development in adulthood. The exact mechanisms behind the interaction between adolescence, stress, and alcohol are not fully understood and require further research.

Probiotic-guided CAR-T cells for solid tumor targeting.

A major challenge facing tumor-antigen targeting therapies such as chimeric antigen receptor (CAR)-T cells is the identification of suitable targets that are specifically and uniformly expressed on heterogeneous solid tumors. By contrast, certain species of bacteria selectively colonize immune-privileged tumor cores and can be engineered as antigen-independent platforms for therapeutic delivery. To bridge these approaches, we developed a platform of probiotic-guided CAR-T cells (ProCARs), in which tumor-colonizing probiotics release synthetic targets that label tumor tissue for CAR-mediated lysis in situ.

COVID-19 or Cancer Stress? Anxiety and Depressive Symptoms in Patients with Advanced Lung Cancer.

Background: Of all cancer patients, those with lung cancer are among the highest risk for infection, pneumonia, hospitalization, and early death from COVID-19. As cancer stress is ubiquitous, this exploratory study examines patients' COVID-19 stress and cancer stress in relation to their depressive and anxiety symptoms.

Method: Newly diagnosed advanced lung cancer patients (N = 76) completed measures of cancer stress, COVID-19 illness perceptions and stress, and depressive and anxiety symptoms at a single monthly follow-up early in the pandemic (May 2020 to July 2020; Clinicaltrials.

Colorectal cancer detection and treatment with engineered probiotics.

Bioengineered probiotics enable new opportunities to improve colorectal cancer (CRC) screening, prevention and treatment strategies. Here, we demonstrate the phenomenon of selective, long-term colonization of colorectal adenomas after oral delivery of probiotic Nissle 1917 (EcN) to a genetically-engineered murine model of CRC predisposition. We show that, after oral administration, adenomas can be monitored over time by recovering EcN from stool.

Chemokines expressed by engineered bacteria recruit and orchestrate antitumor immunity.

Tumors use multiple mechanisms to actively exclude immune cells involved in antitumor immunity. Strategies to overcome these exclusion signals remain limited due to an inability to target therapeutics specifically to the tumor. Synthetic biology enables engineering of cells and microbes for tumor-localized delivery of therapeutic candidates previously unavailable using conventional systemic administration techniques.

Design of combination therapy for engineered bacterial therapeutics in non-small cell lung cancer.

Synthetic biology enables the engineering of bacteria to safely deliver potent payloads to tumors for effective anti-cancer therapies. However, a central challenge for translation is determining ideal bacterial therapy candidates for specific cancers and integrating them with other drug treatment strategies to maximize efficacy. To address this, we designed a screening and evaluation pipeline for characterization of bacterial therapies in lung cancer models.

Phase I trial of the TNF-α inhibitor certolizumab plus chemotherapy in stage IV lung adenocarcinomas.

We previously identified a chemotherapy-induced paracrine inflammatory loop that paradoxically mitigates the anti-tumor effect of chemotherapy and triggers metastatic propagation in breast and lung cancer models. Therefore, we sought to further validate and translate these findings into patient care by coupling the anti-TNF-α drug certolizumab pegol with standard cisplatin doublet chemotherapy. Here we first validate the anti-metastatic effect of certolizumab in a liver-metastatic Lewis Lung Carcinoma model.

Minocycline Reduces Hypothalamic Microglia Activation and Improves Metabolic Dysfunction in High Fat Diet-Induced Obese Mice.

Obesity is associated with insulin resistance, glucose intolerance, inflammation, and altered neuronal activity in brain regions controlling metabolic functions including food intake, energy expenditure, and glucose homeostasis, such as the hypothalamus. In this study, we tested the hypothesis that inhibiting inflammation with minocycline could reduce adverse metabolic consequences associated with high-fat diet (HFD)-induced obesity in mice and sought to determine if metabolic improvements were associated with reduced hypothalamic microglia activity. Male C57Bl/6J mice were placed on 60% HFD for 12 weeks, with minocycline (40 mg/kg, p.

A programmable encapsulation system improves delivery of therapeutic bacteria in mice.

Living bacteria therapies have been proposed as an alternative approach to treating a broad array of cancers. In this study, we developed a genetically encoded microbial encapsulation system with tunable and dynamic expression of surface capsular polysaccharides that enhances systemic delivery. Based on a small RNA screen of capsular biosynthesis pathways, we constructed inducible synthetic gene circuits that regulate bacterial encapsulation in Escherichia coli Nissle 1917.

Communicating Branches of the Facial Nerve: Descriptions and Clinical Considerations.

Background: Major branching patterns of the facial nerve have been extensively studied because damage to branches of the nerve is associated with complications ranging from weakness to paralysis. However, communicating branches of the facial nerve have received far less attention despite being hypothesized as a means of motor recovery following facial nerve injury.

Objectives: The aim of this study was to characterize the frequency of communicating branches of the facial nerve to provide clarity on their anatomy and clinical correlations.

Cancer Treatment During COVID-19: Resilience of Individuals With Advanced Non-Small Cell Lung Cancer Versus Community Controls.

Background: Among all patients with cancer, those with advanced non-small cell lung cancer (NSCLC) experience the most distress. Although new therapies are improving survival, it is unknown whether receiving immunotherapy or targeted therapy during the COVID-19 pandemic increases patients' psychological vulnerability. To meet clinical needs, knowledge of patients' COVID-19 perceptions and safety behaviors is essential.

Targeting S100A9-ALDH1A1-Retinoic Acid Signaling to Suppress Brain Relapse in EGFR-Mutant Lung Cancer.

Unlabelled: The epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib has significantly prolonged progression-free survival (PFS) in patients with EGFR-mutant lung cancer, including those with brain metastases. However, despite striking initial responses, osimertinib-treated patients eventually develop lethal metastatic relapse, often to the brain. Although osimertinib-refractory brain relapse is a major clinical challenge, its underlying mechanisms remain poorly understood.

Validation of an In-House-Developed GC-MS Method for 5α-Cholestanol According to ISO 15189:2012 Requirements.

Objective: The aim of this study was to validate a gas chromatography-mass spectrometry (GC-MS) method for the measurement of 5α-cholestanol in the clinical laboratory in agreement with ISO 15189:2012.

Materials And Methods: The GC-MS performance was evaluated and proficiency testing data were used to estimate the measurement uncertainty of the method considering the recommendations of international guidelines.

Results: The calibration curves were linear from 6 to 50 μmol/L, with r2 >.

Management of invasive ductal carcinoma in hypermobile Ehlers-Danlos syndrome: a case report.

Literature is sparse regarding the management and long-term outcomes of breast cancer in patients with Ehlers-Danlos syndrome (EDS). Of the EDS subtypes, hypermobile Ehlers-Danlos Syndrome (hEDS) is associated with cardiovascular dysautonomia which manifests as spontaneous episodes of tachycardia and hypotension. Given this clinical autonomic system impact, hEDS is known to have significant intraoperative risk and postoperative complications.

Osteopathic Manipulative Treatment as an Intervention to Reduce Stress, Anxiety, and Depression in First Responders: A Pilot Study.

In this pilot study, we examined the efficacy of Osteopathic Manipulative Treatment (OMT) for improving symptoms of stress, anxiety, and depression (SAD) to determine a correlation between overall improvement in health and quality of life for first responders. Participants received weekly OMT or sham OMT targeting autonomic imbalance. Indicators of SAD were examined pre- and post-study.

Inside the ensemble: unlocking the potential of one-at-a-time experiments with lab-on-a-chip automation.

The advent of technologies that allow the interactions of microscopic particles to be probed "" has paved the way for new experimental avenues of enquiry in colloidal systems. For example, investigating whether a particular pair of colloidal particles isolated from a macroscopic sample might adhere to each other when brought into close proximity is certainly possible. However, given the probabilistic nature of the process (different particles within the ensemble may have slightly different surface charge distributions and asperities, and interaction energies involved can be close to thermal values), it is important that many hundreds or thousands of pairs of particles are tested under each set of experimental conditions of interest.

Optimizing Feedback Frequency in Motor Learning: Self-Controlled and Moderate Frequency KR Enhance Skill Acquisition.

The purpose of this study was to compare the relative effects of self-controlled knowledge of results (SCKR) to other KR schedules of varying relative frequency (25%, 50%, and 100% of acquisition trials) on motor skill learning. Participants received basic instructions on the soccer overhead throw and then performed 50 acquisition trials, during which KR was provided according to the assigned schedule, followed by a retention test, during which no KR was provided. Retention scores were highest for the SCKR and 50% KR frequency groups who shared comparable absolute KR frequency and distribution relative to successful versus unsuccessful trials.

Enhancing the tropism of bacteria via genetically programmed biosensors.

Engineered bacteria for therapeutic applications would benefit from control mechanisms that confine the growth of the bacteria within specific tissues or regions in the body. Here we show that the tropism of engineered bacteria can be enhanced by coupling bacterial growth with genetic circuits that sense oxygen, pH or lactate through the control of the expression of essential genes. Bacteria that were engineered with pH or oxygen sensors showed preferential growth in physiologically relevant acidic or oxygen conditions, and reduced growth outside the permissive environments when orally delivered to mice.