Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses.

The gut microbiome modulates immunotherapy treatment responses, and this may explain why immune checkpoint inhibitors, such as anti-PD-1, are only effective in some patients. Previous studies correlated lipopolysaccharide (LPS)-producing gut microbes with poorer prognosis; however, LPS from diverse bacterial species can range from immunostimulatory to inhibitory. Here, by functionally analysing faecal metagenomes from 112 patients with melanoma, we found that a subset of LPS-producing bacteria encoding immunostimulatory hexa-acylated LPS was enriched in microbiomes of clinical responders.

Prevalence of work hour alcohol use and associated factors among psychiatrists in China.

Background: Since 2012, work-hour alcohol use (WHAU) has been prohibited in China. However, there is a lack of national data on WHAU among healthcare workers, including psychiatrists.

Methods: We collected data from psychiatrists in 41 tertiary psychiatric hospitals using an online questionnaire, which included demographics, work-related factors, WHAU, and the Alcohol Use Disorder Identification Test-Consumption (AUDIT-C).

A Source Control Model for Treatment-Resistant Substance Use Disorder.

We propose applying the "source control" model of infectious disease treatment to the management of treatment-resistant substance use disorder (SUD). We believe that this conceptual framework complements other models for understanding SUD, fills a gap in our current understanding of treatment-resistant SUD, and advances the destigmatization of SUD by reinforcing SUD as a disease similar to other medical conditions. The model also harmonizes the need for multimodal treatment and novel interventions for both acute supportive care and long-term treatment of SUD.

Addressing Confusion and Inconsistencies Surrounding the Provider Role in Medical Cannabis Programs.

More than 40 states in the United States have established medical cannabis programs that authorize the use of cannabis for specific medical conditions. Initially, these medical cannabis programs aimed to offer compassionate care primarily for terminal or rare, untreatable conditions. However, the scope of these programs has broadened to include nonterminal and more common conditions, including various medical and mental disorders.

Examining primary care provider experiences with using a clinical decision support tool for pain management.

Objective: To evaluate primary care provider (PCP) experiences using a clinical decision support (CDS) tool over 16 months following a user-centered design process and implementation.

Materials And Methods: We conducted a qualitative evaluation of the Chronic Pain OneSheet (OneSheet), a chronic pain CDS tool. OneSheet provides pain- and opioid-related risks, benefits, and treatment information for patients with chronic pain to PCPs.

The Patient Experience of Adolescents With Traumatic Injuries: Recommendations for Improvement.

Goal: Positive patient experience is associated with less healthcare utilization, better treatment adherence, increased likelihood of returning to the same hospital, and fewer complaints. However, hospitals have been able to collect few insights into the experiences of pediatric patients due to age limitations. As an exception to that reality, adolescents (aged 12-20 years) are able to share their experiences and recommend improvements, yet little is known about their hospital experiences with traumatic injuries.

The Cardiovascular Side Effects of Electroconvulsive Therapy and Their Management.

Electroconvulsive therapy (ECT) remains stigmatized in the broader medical community because of misunderstandings about treatment procedures, mortality rates, and cardiovascular complications. Electroconvulsive therapy causes periprocedural hemodynamic variability because of the surges in parasympathetic and sympathetic nervous systems after the administration of the electrical charge. Patients experience an increase in cardiac workload, which is potentially dangerous for patients with preexisting heart disease.

Transferrin: Biology and Use in Receptor-Targeted Nanotherapy of Gliomas.

Gliomas constitute 80% of malignant brain tumors. The survival rate of patients diagnosed with malignant gliomas is only 34.4%, as seen in both adults as well as children.

Folate Receptors' Expression in Gliomas May Possess Potential Nanoparticle-Based Drug Delivery Opportunities.

Brain cancer effected around estimated 23 890 adults and 3540 children under the age of 15 in 2020. The chemotherapeutic agents that are already approved by the FDA for brain cancer are proving to be not highly effective because of the interference from the tumor microenvironment as well as their own toxicities. Added to this is the impedance presented by the extremely restrictive permeability of the blood brain barrier (BBB).

LDL receptors and their role in targeted therapy for glioma: a review.

Gliomas are highly lethal forms of cancers occurring in the brain. Delivering the drugs into the brain is a major challenge to the treatment of gliomas because of the highly selectively permeable blood-brain barrier (BBB). Tapping the potential of receptor-mediated drug delivery systems using targeted nanoparticles (NPs) is a sought-after step forward toward successful glioma treatment.

Structural Basis for High-Affinity Trapping of the Na1.7 Channel in Its Resting State by Tarantula Toxin.

Voltage-gated sodium channels initiate electrical signals and are frequently targeted by deadly gating-modifier neurotoxins, including tarantula toxins, which trap the voltage sensor in its resting state. The structural basis for tarantula-toxin action remains elusive because of the difficulty of capturing the functionally relevant form of the toxin-channel complex. Here, we engineered the model sodium channel NaAb with voltage-shifting mutations and the toxin-binding site of human Na1.

Vaginal Hysterectomy Suturing Skills Training Model and Curriculum.

Background: Declining vaginal hysterectomy numbers in obstetrics and gynecology training programs highlights the need for innovative methods to teach vaginal surgical skills. We describe our experience with a vaginal hysterectomy skills simulation curriculum.

Instrument: A low-fidelity bench model was constructed to simulate four vaginal hysterectomy suturing tasks.

Resting-State Structure and Gating Mechanism of a Voltage-Gated Sodium Channel.

Voltage-gated sodium (Na) channels initiate action potentials in nerve, muscle, and other electrically excitable cells. The structural basis of voltage gating is uncertain because the resting state exists only at deeply negative membrane potentials. To stabilize the resting conformation, we inserted voltage-shifting mutations and introduced a disulfide crosslink in the VS of the ancestral bacterial sodium channel NaAb.

OliveNet™: a comprehensive library of compounds from Olea europaea.

Accumulated epidemiological, clinical and experimental evidence has indicated the beneficial health effects of the Mediterranean diet, which is typified by the consumption of virgin olive oil (VOO) as a main source of dietary fat. At the cellular level, compounds derived from various olive (Olea europaea), matrices, have demonstrated potent antioxidant and anti-inflammatory effects, which are thought to account, at least in part, for their biological effects. Research efforts are expanding into the characterization of compounds derived from Olea europaea, however, the considerable diversity and complexity of the vast array of chemical compounds have made their precise identification and quantification challenging.

Association of rare missense variants in the second intracellular loop of Na1.7 sodium channels with familial autism.

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder often accompanied by intellectual disability, language impairment and medical co-morbidities. The heritability of autism is high and multiple genes have been implicated as causal. However, most of these genes have been identified in de novo cases.

F DOSY diffusion-NMR spectroscopy of fluoropolymers.

A new pulse sequence for obtaining F detected DOSY (diffusion ordered spectroscopy) spectra of fluorinated molecules is presented and used to study fluoropolymers based on vinylidene fluoride and chlorotrifluoroethylene. The performance of F DOSY NMR experiments (and in general any type of NMR experiment) on fluoropolymers creates some unique complications that very often prevent detection of important signals. Factors that create these complications include: (1) the presence of many scalar couplings among H, F and C; (2) the large magnitudes of many F homonuclear couplings (especially J ); (3) the large F chemical shift range; and (4) the low solubility of these materials (which requires that experiments be performed at high temperatures).

Reappraisal of lymphatic mapping for midgut neuroendocrine patients undergoing cytoreductive surgery.

Background: We previously reported that midgut neuroendocrine tumors (NETs) often develop alternative lymphatic drainage owing to lymphatic obstructions from extensive mesenteric lymphadenopathy, making intraoperative lymphatic mapping mandatory. We hypothesize that this innovative approach needs a longer term validation.

Methods: We updated our results by reviewing 303 patients who underwent cytoreduction from November 2006 to October 2011.

Species-specific differences in the medial prefrontal projections to the pons between rat and rabbit.

The medial prefrontal cortex (mPFC) of both rats and rabbits has been shown to support trace eyeblink conditioning, presumably by providing an input to the cerebellum via the pons that bridges the temporal gap between conditioning stimuli. The pons of rats and rabbits, however, shows divergence in gross anatomical organization, leaving open the question of whether the topography of prefrontal inputs to the pons is similar in rats and rabbits. To investigate this question, we injected anterograde tracer into the mPFC of rats and rabbits to visualize and map in 3D the distribution of labeled terminals in the pons.

Production of omega-3 eicosapentaenoic acid by metabolic engineering of Yarrowia lipolytica.

The availability of the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) is currently limited because they are produced mainly by marine fisheries that cannot keep pace with the demands of the growing market for these products. A sustainable non-animal source of EPA and DHA is needed. Metabolic engineering of the oleaginous yeast Yarrowia lipolytica resulted in a strain that produced EPA at 15% of dry cell weight.

Use of H/C/F Triple Resonance 3D-NMR to Characterize the Stereosequences in Poly(vinyl fluoride).

Tacticity has an enormous influence on the physical and chemical properties of polymers. There is considerable work using 1D NMR and empirical rules to study the stereosequences in polymers. This work shows that H/C/F 3D NMR experiments can provide superior resolution and atomic connectivity information, so that unambiguous resonance assignments can be made for poly(vinyl fluoride) (PVF).

2D-NMR studies of a model for Krytox® fluoropolymers.

Multiple two-dimensional nuclear magnetic resonance (2D-NMR) techniques have been used to study the structures of Krytox(®) perfluoro(polyalkyl ether) and its mechanism of polymerization. Model compound K(4), containing four Krytox(®) fluoropolymer repeat units, was analyzed to interpret the multiplet patterns in the NMR spectra from the polymer model. (19)F {(13)C}-Heteronuclear single-quantum correlation experiments, performed with delays optimized for (1)J(CF) and (2)J(CF), provided spectra that permitted identification of resonances from individual monomer units.

Spectral separation of gaseous fluorocarbon mixtures and measurement of diffusion constants by 19F gas phase DOSY NMR.

Diffusion-ordered (DOSY) NMR techniques have for the first time been applied to the spectral separation of mixtures of fluorinated gases by diffusion rates. A mixture of linear perfluoroalkanes from methane to hexane was readily separated at 25 degrees C in an ordinary experimental setup with standard DOSY pulse sequences. Partial separation of variously fluorinated ethanes was also achieved.

Lack of cross-resistance to indoxacarb in insecticide-resistant Spodoptera frugiperda (Lepidoptera: Noctuidae) and Plutella xylostella (Lepidoptera: Yponomeutidae).

Two field strains of the fall armyworm, Spodoptera frugiperda (JE Smith), collected from corn in north Florida showed high resistance to carbaryl (626- and 1159-fold) and moderate resistance to parathion-methyl (30- and 39-fold) as compared with a laboratory susceptible strain. A field strain of the diamondback moth, Plutella xylostella (L.) collected from cabbage in north Florida and selected for 20 generations with permethrin showed high resistance to permethrin (987-fold) as compared with a susceptible strain.