Performance of ChatGPT on USMLE: Potential for AI-assisted medical education using large language models.

We evaluated the performance of a large language model called ChatGPT on the United States Medical Licensing Exam (USMLE), which consists of three exams: Step 1, Step 2CK, and Step 3. ChatGPT performed at or near the passing threshold for all three exams without any specialized training or reinforcement. Additionally, ChatGPT demonstrated a high level of concordance and insight in its explanations. These results suggest that large language models may have the potential to assist with medical education, and potentially, clinical decision-making.

3'UTR shortening of HAS2 promotes hyaluronan hyper-synthesis and bioenergetic dysfunction in pulmonary hypertension.

Pulmonary hypertension (PH) comprises a diverse group of disorders that share a common pathway of pulmonary vascular remodeling leading to right ventricular failure. Development of anti-remodeling strategies is an emerging frontier in PH therapeutics that requires a greater understanding of the interactions between vascular wall cells and their extracellular matrices. The ubiquitous matrix glycan, hyaluronan (HA), is markedly elevated in lungs from patients and experimental models with PH. Herein, we identified HA synthase-2 (HAS2) in the pulmonary artery smooth muscle cell (PASMC) layer as a predominant locus of HA dysregulation. HA upregulation involves depletion of NUDT21, a master regulator of alternative polyadenylation, resulting in 3'UTR shortening and hyper-expression of HAS2. The ensuing increase of HAS2 and hyper-synthesis of HA promoted bioenergetic dysfunction of PASMC characterized by impaired mitochondrial oxidative capacity and a glycolytic shift. The resulting HA accumulation stimulated pro-remodeling phenotypes such as cell proliferation, migration, apoptosis-resistance, and stimulated pulmonary artery contractility. Transgenic mice, mimicking HAS2 hyper-synthesis in smooth muscle cells, developed spontaneous PH, whereas targeted deletion of HAS2 prevented experimental PH. Pharmacological blockade of HAS2 restored normal bioenergetics in PASMC, ameliorated cell remodeling phenotypes, and reversed experimental PH in vivo. In summary, our results uncover a novel mechanism of HA hyper-synthesis and downstream effects on pulmonary vascular cell metabolism and remodeling.

Self-Detachable Through-Metal Acoustic Wireless Power Transfer.

Unlike electromagnetic waves, acoustic vibrations waves can be used to transfer power directly through metal structures without being shielded. In this article, a novel design of a self-detachable acoustic wireless power transfer system that can be used to transfer power through the thickness of a steel plate is presented, which does not require the use of any couplant. Electro-permanent-magnets (EPMs) were used to provide magnetic clamping force along the perimeter of the receiver transducer disk to enhance coupling to the steel plate, while the transmitter transducer was bonded to the other side of the plate. The EPM clamping force can be switched ON/ OFF electronically with low power consumption. Unlike past work reliant on additional bonding materials or liquid/gel couplant, this approach enables the receiver to be attached and detached at will, opening up the possibility of a simple charging pad for unmanned aerial vehicles (UAVs) or other consumer devices for harsh environment applications. Power transfer efficiency up to 63% was achieved, and the effect of varying steel plate thickness and clamping force was also investigated. A finite element model was also constructed to understand the vibration mode shape.

Analgesic efficacy of paraspinal interfascial plane blocks performed with the use of neurophysiology monitoring for posterior cervical laminectomy surgery: a case series.

Posterior cervical spine surgery often requires large posterior midline incision which can result in poorly controlled postoperative pain, arises from iatrogenic mechanical damage, intraoperative retraction and resection to structures such as bone, ligaments, muscles, intervertebral disks, and zygapophysial joints. Local anesthetics may be utilized for infiltration of the surgical wound; however, their analgesic efficacy has not been studied in this surgical approach. Here we report a case series. Given the potential for targeted sensory dorsal ramus nerve blocks to provide better and extended analgesia, we explored the feasibility of using cervical paraspinal interfascial plane (PIP) blocks in conjunction with neurophysiologic monitoring for postoperative analgesia after posterior cervical laminectomy. Our experience with the cervical paraspinal interfascial plane blocks has revealed that they can be used safely without affecting neurophysiologic monitoring and result in better pain control and reduced opiate use in the postoperative period. Cervical PIP blocks may be useful in controlling pain for posterior cervical laminectomy surgery without compromising neurophysiologic monitoring.

Influence of Body Weight and Diabetes Mellitus in Patients With Pulmonary Hypertension.

Pulmonary hypertension (PH) is a complex condition that arises due to pulmonary vascular disease, heart disease, lung disease, chronic thromboembolism, or several rare causes. Regardless of underlying cause, PH increases mortality, yet there are no directed treatments for the most common forms of PH due to left heart or lung disease. Because metabolic factors have been implicated in the pathogenesis of PH, we used a large administrative cohort to assess diabetes and weight, potentially modifiable risk factors, on PH outcome. We analyzed 110,495 veterans diagnosed with PH from January 1, 2003 to September 30, 2015 in the Veterans Health Affairs system. Veterans with PH survived an average of 3.88 [IQR 3.85, 3.92] years after PH diagnosis. Diabetes occurred in 36% and increased risk of death by 31% (95% confidence interval 28% to 33%, multivariate adjusted). Higher body mass index was associated with lower mortality in a J-shaped pattern with highest risk in underweight and normal weight veterans. Improved survival in obesity has been referred to as the obesity paradox in heart failure and other diseases. These data show that lower weight and diabetes are strong risk factors for mortality in PH. Our results underscore the importance of systemic conditions on outcome in PH.

Thoracolumbar Dorsal Ramus Nerve Block Using Continuous Multiorifice Infusion Catheters: A Novel Technique for Postoperative Analgesia After Scoliosis Surgery.

BACKGROUND: This is a brief technical report about a novel regional anesthesia technique in which local anesthetic was deposited around the thoracolumbar dorsal rami nerves via 4 multiorifice pain catheters to obtain analgesia for posterior spinal fusion surgery on scoliosis patients. Scoliosis is the most common deformity of the spine. Currently, most surgeons prefer a dual rod, segmental spinal fixation system that allows multiple anchor points for attachment to the deformed spine. Scoliosis surgery is an extremely painful surgical procedure due to the large incision, surgical trauma to superficial and deep muscles of the back, and the insertion of pedicle screws and metal rods directly into the vertebral column. Postoperative pain management remains very challenging. METHODS: Three patients presented with scoliosis. Intraoperatively, 4 multiorifice catheters were placed lateral to the implanted pedicle screws. Two catheters were placed on each side, and a continuous infusion of 0.2 % ropivacaine was initiated postoperatively to improve the patient's pain control. The catheters remained in place for 48 hours postoperatively and were removed by the surgical team. Gentle traction was applied similar to the way epidural catheters are removed. RESULTS: All 3 patients reported very low pain scores, low doses of opioid consumption, and satisfaction with their pain control throughout their hospitalization. CONCLUSIONS: Our study results suggest that a thoracolumbar dorsal ramus nerve block using continuous multiorifice infusion catheters significantly improved postoperative comfort and pain and that its implementation into a multimodal analgesic regimen is relatively easy to achieve.

Extracellular Superoxide Dismutase Regulates Early Vascular Hyaluronan Remodeling in Hypoxic Pulmonary Hypertension.

Chronic hypoxia leads to pathologic remodeling of the pulmonary vasculature and pulmonary hypertension (PH). The antioxidant enzyme extracellular superoxide dismutase (SOD3) protects against hypoxia-induced PH. Hyaluronan (HA), a ubiquitous glycosaminoglycan of the lung extracellular matrix, is rapidly recycled at sites of vessel injury and repair. We investigated the hypothesis that SOD3 preserves HA homeostasis by inhibiting oxidative and enzymatic hyaluronidase-mediated HA breakdown. In SOD3-deficient mice, hypoxia increased lung hyaluronidase expression and activity, hyaluronan fragmentation, and effacement of HA from the vessel wall of small pulmonary arteries. Hyaluronan fragmentation corresponded to hypoxic induction of the cell surface hyaluronidase-2 (Hyal2), which was localized in the vascular media. Human pulmonary artery smooth muscle cells (HPASMCs) demonstrated hypoxic induction of Hyal2 and SOD-suppressible hyaluronidase activity, congruent to our observations in vivo. Fragmentation of homeostatic high molecular weight HA promoted HPASMC proliferation in vitro, whereas pharmacologic inhibition of hyaluronidase activity prevented hypoxia- and oxidant-induced proliferation. Hypoxia initiates SOD3-dependent alterations in the structure and regulation of hyaluronan in the pulmonary vascular extracellular matrix. These changes occurred soon after hypoxia exposure, prior to appearance of PH, and may contribute to the early pathogenesis of this disease.

Ultrasonic Lamb Waves for Wireless Power Transfer.

Ultrasonic guided plate waves (Lamb waves) can be used to transfer power along the length of metal plates, achieving longer distance wireless power transfer (WPT), while not being impeded by electromagnetic shielding from the metal plate. In this article, a fundamental study on the performance of Lamb wave WPT is presented, including modeling, simulations, and experimental verification. By using Macro-Fiber Composite (MFC), d33 -mode, piezoelectric transducers bonded to a [Formula: see text] mm aluminum plate using an epoxy, power transfer of 0.47 W with 56% overall power transfer efficiency was achieved at a 204-mm distance. The measured frequency response of the power transfer efficiency matches well with the simulated results, and the effects of complex load impedance matching and transducer sizing were investigated. It is shown that the location where the efficiency is maximized roughly corresponds to the zero-order symmetrical mode (S0) standing wave patterns due to reflections from the plate edges. For practical implementation, the effect of using different methods to temporarily or permanently bond the MFC transducers to the metal plate was also investigated, as well as the effect of electrically grounding the metal plate.

Erector spinae plane block unbound: Limits to safety in a patient with laminectomy.

The erector spinae plane (ESP) block has been used to provide analgesia for multiple surgeries involving the abdomen and thorax. Like other plane blocks, the ESP block relies upon normal anatomical boundaries for predictable and safe distribution of local anesthetic. Surgical intervention can alter the anatomy and present new considerations for performing plane blocks. We present a case in which an ESP block was performed for multiple rib fractures in a patient with a recent laminectomy. Laminectomy patients present unique considerations regarding the safety of the ESP block.

Redox Biology of Peroxisome Proliferator-Activated Receptor-γ in Pulmonary Hypertension.

Significance: Peroxisome proliferator-activated receptor-gamma (PPARγ) maintains pulmonary vascular health through coordination of antioxidant defense systems, inflammation, and cellular metabolism. Insufficient PPARγ contributes to pulmonary hypertension (PH) pathogenesis, whereas therapeutic restoration of PPARγ activity attenuates PH in preclinical models. Recent Advances: Numerous studies in the past decade have elucidated the complex mechanisms by which PPARγ in the pulmonary vasculature and right ventricle (RV) protects against PH. The scope of PPARγ-interconnected pathways continues to expand and includes induction of antioxidant genes, transrepression of inflammatory signaling, regulation of mitochondrial biogenesis and bioenergetic integrity, control of cell cycle and proliferation, and regulation of vascular tone through interactions with nitric oxide and endogenous vasoactive molecules. Furthermore, PPARγ interacts with an extensive regulatory network of transcription factors and microRNAs leading to broad impact on cell signaling. Critical Issues: Abundant evidence suggests that targeting PPARγ exerts diverse salutary effects in PH and represents a novel and potentially translatable therapeutic strategy. However, progress has been slowed by an incomplete understanding of how specific PPARγ pathways are critically disrupted across PH disease subtypes and lack of optimal pharmacological ligands. Future Directions: Recent studies indicate that ligand-induced post-translational modifications of the PPARγ receptor differentially induce therapeutic benefits versus adverse side effects of PPARγ receptor activation. Strategies to selectively target PPARγ activity in diseased cells of pulmonary circulation and RV, coupled with development of ligands designed to specifically regulate post-translational PPARγ modifications, may unlock the full therapeutic potential of this versatile master transcriptional and metabolic regulator in PH.

Rapid clearance of heavy chain-modified hyaluronan during resolving acute lung injury.

BACKGROUND: Several inflammatory lung diseases display abundant presence of hyaluronic acid (HA) bound to heavy chains (HC) of serum protein inter-alpha-inhibitor (IαI) in the extracellular matrix. The HC-HA modification is critical to neutrophil sequestration in liver sinusoids and to survival during experimental lipopolysaccharide (LPS)-induced sepsis. Therefore, the covalent HC-HA binding, which is exclusively mediated by tumor necrosis factor α (TNFα)-stimulated-gene-6 (TSG-6), may play an important role in the onset or the resolution of lung inflammation in acute lung injury (ALI) induced by respiratory infection. METHODS: Reversible ALI was induced by a single intratracheal instillation of LPS or Pseudomonas aeruginosa in mice and outcomes were studied for up to six days. We measured in the lung or the bronchoalveolar fluid HC-HA formation, HA immunostaining localization and roughness, HA fragment abundance, and markers of lung inflammation and lung injury. We also assessed TSG-6 secretion by TNFα- or LPS-stimulated human alveolar macrophages, lung fibroblast Wi38, and bronchial epithelial BEAS-2B cells. RESULTS: Extensive HC-modification of lung HA, localized predominantly in the peri-broncho-vascular extracellular matrix, was notable early during the onset of inflammation and was markedly decreased during its resolution. Whereas human alveolar macrophages secreted functional TSG-6 following both TNFα and LPS stimulation, fibroblasts and bronchial epithelial cells responded to only TNFα. Compared to wild type, TSG-6-KO mice, which lacked HC-modified HA, exhibited modest increases in inflammatory cells in the lung, but no significant differences in markers of lung inflammation or injury, including histopathological lung injury scores. CONCLUSIONS: Respiratory infection induces rapid HC modification of HA followed by fragmentation and clearance, with kinetics that parallel the onset and resolution phase of ALI, respectively. Alveolar macrophages may be an important source of pulmonary TSG-6 required for HA remodeling. The formation of HC-modified HA had a minor role in the onset, severity, or resolution of experimental reversible ALI induced by respiratory infection with gram-negative bacteria.

Phased Array Focusing for Acoustic Wireless Power Transfer.

Wireless power transfer (WPT) through acoustic waves can achieve higher efficiencies than inductive coupling when the distance is above several times the transducer size. This paper demonstrates the use of ultrasonic phased arrays to focus power to receivers at arbitrary locations to increase the power transfer efficiency. Using a phased array consisting of 37 elements at a distance nearly 5 times the receiver transducer diameter, a factor of 2.6 increase in efficiency was achieved when compared to a case equivalent to a single large transducer with the same peak efficiency distance. The array has a total diameter of 7 cm, and transmits through air at 40 kHz to a 1.1-cm diameter receiver, achieving a peak overall efficiency of 4% at a distance of 5 cm. By adjusting the focal distance, the efficiency can also be maintained relatively constant at distances up to 9 cm. Numerical models were developed and shown to closely match the experimental energy transfer behavior; modeling results indicate that the efficiency can be further doubled by increasing the number of elements. For comparison, an inductive WPT system was also built with the diameters of the transmitting and receiving coils equivalent to the dimensions of the transmitting ultrasonic phased array and receiver transducer, and the acoustic WPT system achieved higher efficiencies than the inductive WPT system when the transmit-to-receive distance is above 5 cm. In addition, beam angle steering was demonstrated by using a simplified seven-element 1-D array, achieving power transfer less dependent on receiver placement.

Cervical sympathetic blockade for the management of electrical storm.

A 75-year-old man presented with dizziness and fatigue secondary to ventricular and supraventricular arrhythmias. He underwent an elective ablation but continued to suffer from ventricular tachycardia with cardiovascular instability despite antiarrhythmic therapy with multiple agents. The patient continued to develop episodes of ventricular tachycardia and an episode of ventricular fibrillation. Electrical storm encompasses a situation of cardiac instability which may present as several episodes of ventricular tachycardia or ventricular fibrillation in a short period. We performed an ultrasound-guided left stellate ganglion block at the bedside which resulted in abolition of electrical storm. The patient demonstrated sinus rhythm with episodes of sinus tachycardia. Left stellate ganglion block has proven to be a successful mode of treatment for those patients with ventricular tachyarrhythmia resistant to medical management or those who fail atrioventricular node ablation. Ultrasound-guided left stellate ganglion block is a valuable and effective means to providing sympathectomy in the management of electrical storm or ventricular tachyarrhythmias.

TGFß1 mediates alcohol-induced Nrf2 suppression in lung fibroblasts.

BACKGROUND: Chronic alcohol ingestion induces the expression of transforming growth factor beta-1(TGFß1), inhibits nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-mediated activation of the antioxidant response element (ARE), depletes alveolar glutathione pools, and potentiates acute lung injury. In this study, we examined the mechanistic relationship between TGFß1 and Nrf2-ARE signaling in the experimental alcoholic lung. METHODS: Wild-type mice were treated ± alcohol in drinking water for 8 weeks and their lungs were assessed for Nrf2 expression. In parallel, mouse lung fibroblasts were cultured ± alcohol and treated ± sulforaphane (SFP; an activator of Nrf2), ±TGFß1, ±TGFß1 neutralizing antibody, and/or ±activin receptor-like kinase 5 inhibitors (to block TGß1 receptor signaling) and then analyzed for the expression of Nrf2, Kelch-like ECH-associated protein 1 (Keap1) and TGFß1, Nrf2-ARE activity, and the expression of the Nrf2-ARE-dependent antioxidants glutathione s-transferase theta 2 (GSTT2) and glutamate-cysteine ligase catalytic subunit (GCLC). Finally, silencing RNA (siRNA) of Nrf2 was then performed prior to alcohol exposure and subsequent analysis of TGFß1 expression. RESULTS: Alcohol treatment in vivo or in vitro decreased Nrf2 expression in murine whole lung and lung fibroblasts, respectively. In parallel, alcohol exposure in vitro decreased Keap1 gene and protein expression in lung fibroblasts. Furthermore, alcohol exposure increased TGFß1 expression but decreased Nrf2-ARE activity and expression of the ARE-dependent genes for GSTT2 and GCLC. These effects of alcohol were prevented by treatment with SFP; in contrast, Nrf2 SiRNA expression exacerbated alcohol-induced TGFß1 expression. Finally, TGFß1 treatment directly suppressed Nrf2-ARE activity whereas blocking TGFß1 signaling attenuated alcohol-induced suppression of Nrf2-ARE activity. CONCLUSIONS: Alcohol-induced oxidative stress is mediated by TGFß1, which suppresses Nrf2-ARE-dependent expression of antioxidant defenses and creates a vicious cycle that feeds back to further increase TGFß1 expression. These effects of alcohol can be mitigated by activation of Nrf2, suggesting a potential therapy in individuals at risk for lung injury due to alcohol abuse.

Efficient assessment of peripheral blood lymphocytosis in adults: developing new thresholds for blood smear review by pathologists.

BACKGROUND: Peripheral smear review is a critical, but labor intensive adjunct for evaluation of lymphocytosis. Standard practice based on consensus guidelines is to review cases with absolute lymphocyte count (ALC) >5×109/L. We hypothesize that identifying cases for review by applying appropriately adjusted ALC and age discriminators will decrease laboratory workload without compromising patient care. METHODS: 1170 complete blood counts with ALCs >5×109/L analyzed in the core laboratory during a 2-year period were included. Patients were categorized into diagnostic groups based on follow-up criteria. A total of 402 patients with new onset lymphocytosis who met criteria for reactive lymphocytosis (82%) or lymphoproliferative disorder (18%) were used to establish optimal ALC and age thresholds from receiver operating characteristic (ROC) curve analysis. RESULTS: ALC as a discriminator for neoplastic lymphocytosis had an ROC area under the curve (AUC) of 0.732. Selecting cases with ALC >10×109/L enriched the proportion of neoplastic cases in the review pool (90% specificity); however, many cases with ALC below this threshold were also neoplastic (52% sensitivity). For cases with ALC between 5 and 10×109/L, age as a discriminator had an ROC AUC of 0.886. Selecting patients >50 years old in this group for review captured the neoplastic cases while excluding the reactive cases (93% sensitivity, 62% specificity). When applied to a validation cohort, the predictive performance of the thresholds was maintained while reducing smears reviewed by 50%. CONCLUSIONS: We show that modifying the standard 5×109/L ALC smear review threshold through retrospective analysis of institutional data can reduce laboratory workload without compromising quality.

The Legionella IcmSW complex directly interacts with DotL to mediate translocation of adaptor-dependent substrates.

Legionella pneumophila is a Gram-negative bacterium that replicates within human alveolar macrophages by evasion of the host endocytic pathway through the formation of a replicative vacuole. Generation of this vacuole is dependent upon the secretion of over 275 effector proteins into the host cell via the Dot/Icm type IVB secretion system (T4SS). The type IV coupling protein (T4CP) subcomplex, consisting of DotL, DotM, DotN, IcmS and IcmW, was recently defined. DotL is proposed to be the T4CP of the L. pneumophila T4SS based on its homology to known T4CPs, which function as inner-membrane receptors for substrates. As a result, DotL is hypothesized to play an integral role(s) in the L. pneumophila T4SS for the engagement and translocation of substrates. To elucidate this role, a genetic approach was taken to screen for dotL mutants that were unable to survive inside host cells. One mutant, dotLY725Stop, did not interact with the type IV adaptor proteins IcmS/IcmW (IcmSW) leading to the identification of an IcmSW-binding domain on DotL. Interestingly, the dotLY725Stop mutant was competent for export of one class of secreted effectors, the IcmSW-independent substrates, but exhibited a specific defect in secretion of IcmSW-dependent substrates. This differential secretion illustrates that DotL requires a direct interaction with the type IV adaptor proteins for the secretion of a major class of substrates. Thus, by identifying a new target for IcmSW, we have discovered that the type IV adaptors perform an additional role in the export of substrates by the L. pneumophila Dot/Icm T4SS.