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Elicitation of CD4 IFN-gamma T cell responses to Mycobacterium tuberculosis (MTB) is a rational vaccine strategy to prevent clinical tuberculosis. Diagnosis of MTB infection is based on T-cell immune memory to MTB antigens. The MTB proteome contains over four thousand open reading frames (ORFs). We conducted a pilot antigen identification study using 164 MTB proteins and MTB-specific T-cells expanded in vitro from 12 persons with latent MTB infection. Enrichment of MTB-reactive T-cells from PBMC used cell sorting or an alternate system compatible with limited resources. MTB proteins were used as single antigens or combinatorial matrices in proliferation and cytokine secretion readouts. Overall, our study found that 44 MTB proteins were antigenic, including 27 not previously characterized as CD4 T-cell antigens. Antigen truncation, peptide, NTM homology, and HLA class II tetramer studies confirmed malate synthase G (encoded by gene Rv1837) as a CD4 T-cell antigen. This simple, scalable system has potential utility for the identification of candidate MTB vaccine and biomarker antigens.

Background Prehospital triage scores aim to identify large vessel occlusions (LVOs) in the field; however, their real‐world performance and accuracy across a 24‐hour period remains unknown. In this study, we compare the positive predictive value of the prehospital Rapid Arterial occlusion Evaluation (RACE) score for the detection of LVO during working hours and nonworking hours. Methods We performed a retrospective review of all patients presenting with a RACE score of ≥5 at one comprehensive and one thrombectomy‐capable hospital between July 2015 and December 2019. Patients were dichotomized to those presenting during “working hours” (7:00 am to 6:00 pm on weekdays) or “nonworking hours” (6:01 pm to 6:59 am on weekdays or anytime during weekends). The primary outcome was diagnosis of LVO. Secondary outcomes included diagnosis of acute neurovascular syndromes, door‐to‐treatment time metrics, and a modified Rankin Scale of ≤2 in those undergoing mechanical thrombectomy. Results Of the 701 patients with RACE score ≥5, 687 patients were included (355 nonworking hours and 332 working‐hours cohorts). Mean age was 71 and 72 years in the nonworking hours and working hours groups, respectively (P=0.13). Median National Institutes of Health Stroke Scale and baseline demographics were comparable between the 2 groups. There was no significant difference in the diagnosis of LVO (36.3% versus 34.6%; P=0.69) or final discharge diagnosis. The positive predictive value of the RACE score for the detection of an acute neurovascular syndrome (transient ischemic attack and stroke) was improved during nonworking hours (76.3% versus 67.8%; P=0.01). In patients undergoing mechanical thrombectomy, rates of good clinical outcome were similar (44.7% versus 48%; P=0.76), despite the shorter door‐to‐groin‐puncture and revascularization times during working hours. Conclusions The RACE score shows a consistent positive predictive value in determining LVO during working and nonworking hours. However, it is more accurate in determining acute neurovascular syndromes during nonworking hours, which is driven by a decrease in stroke mimics during this time.

Background: Neurointerventional procedures in acute ischemic stroke often require immediate antiplatelet therapy in the cases of acute stenting and occasionally re-occluding vessels. Intravenous cangrelor is a P2Y12 receptor antagonist with short onset and quick offset. The study objective was to evaluate the safety and efficacy of intravenous cangrelor in patients with acute ischemic stroke requiring urgent antiplatelet effect.Methods: Patients who received intravenous cangrelor intra-procedurally during acute ischemic stroke treatment were identified from a prospectively collected database. Cangrelor was administered as a bolus of 15 mcg/kg, followed by an infusion rate of 2 mcg/kg/min. A historical control group consisting of anterior circulation tandem occlusions was used to compare to patients with similar lesions who received intravenous cangrelor. Outcomes of interest included in-stent thrombosis, thromboembolic complications, intracranial hemorrhage, and functional outcomes at 90 days.Results: Twelve patients received intravenous cangrelor for acute ischemic stroke between October 2018 and April 2020 at a comprehensive stroke center. Eleven patients had intra or extracranial stenting performed, which included two posterior circulation lesions. No cases of symptomatic intracranial hemorrhage were reported. At 90 day follow-up, two patients had died and 10 had a good functional outcome. Patients with anterior circulation tandem occlusions who received cangrelor and those who received dual antiplatelets orally had similar radiographic and clinical outcomes.Conclusion: Low dose intravenous cangrelor is similar in safety and efficacy to oral antiplatelets in acute ischemic stroke in a small case series. Larger prospective studies on the efficacy, safety, and effect on procedure times of intravenous cangrelor in neurointervention are warranted.

Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation increased the QT-interval at RR-intervals that were ≥130 ms. Inducing the deletion of Bmal1 in the cardiomyocytes of mice with or without the ΔKPQ-Scn5a mutation also increased the day/night rhythm-adjusted mean in the RR-interval, but it did not change the period, phase or amplitude. Compared to mice without the ΔKPQ-Scn5a mutation, mice with the ΔKPQ-Scn5a mutation had reduced heart rate variability (HRV) during the peak of the day/night rhythm in the RR-interval. Inducing the deletion of Bmal1 in cardiomyocytes did not affect HRV in mice without the ΔKPQ-Scn5a mutation, but it did increase HRV in mice with the ΔKPQ-Scn5a mutation. The data demonstrate that deleting Bmal1 in cardiomyocytes exacerbates QT- and RR-interval prolongation in mice with the ΔKPQ-Scn5a mutation.

Trauma is currently the leading cause of death in the age group 15 to 44 years globally, with road trauma now representing the sixth leading cause of death worldwide. We present a case of a young male, who was brought to the apex trauma centre of the province with a metallic roadside guardrail impaled in his neck up to his oral cavity, which had to be cut to transport him to the hospital. A meticulous local exploration resulted in the successful removal of the spiked guardrail, with no damage to critical structures. We discuss the paradigm changes in and the expertise required for the management of such penetrating neck injuries (PNIs). For family physicians, this case represents one of the wide variety of cases they will be called to help upon and administer prehospital care. Thus, utilization of principles of basic life support, recognition of the severity of road trauma cases, and ensuring urgency of referral by general practitioners are all critical.

ImportanceElectromechanical reshaping (EMR) is a low-cost, needle-based, and simple means to shape cartilage tissue without the use of scalpels, sutures, or heat that can potentially be used in an outpatient setting to perform otoplasty.ObjectivesTo demonstrate that EMR can alter the shape of intact pinnae in an in vivo animal model and to show that the amount of shape change and the limited cell injury are proportional to the dosimetry.Design, setting, and specimensIn an academic research setting, intact ears of 18 New Zealand white rabbits underwent EMR using 6 different dosimetry parameters (4 V for 5 minutes, 4 V for 4 minutes, 5 V for 3 minutes, 5 V for 4 minutes, 6 V for 2 minutes, and 6 V for 3 minutes). A custom acrylic jig with 2 rows of platinum needle electrodes was used to bend ears at the middle of the pinna and to perform EMR. Treatment was repeated twice per pinna, in proximal and distal locations. Control pinnae were not subjected to current application when being bent and perforated within the jig. Pinnae were splinted for 3 months along the region of the bend using soft silicon sheeting and a cotton bolster.Main outcomes and measuresThe ears were harvested the day after splints were removed and before euthanasia. Photographs of ears were obtained, and bend angles were measured. Tissue was sectioned for histologic examination and confocal microscopy to assess changes to microscopic structure and cellular viability.ResultsTreated pinnae were bent more and retained shape better than control pinnae. The mean (SD) bend angles in the 7 dosimetry groups were 55° (35°) for the control, 60° (15°) for 4 V for 4 minutes, 118° (15°) for 4 V for 5 minutes, 88° (26°) for 5 V for 3 minutes, 80° (17°) for 5 V for 4 minutes, 117° (21°) for 6 V for 2 minutes, and 125° (18°) for 6 V for 3 minutes. Shape change was proportional to electrical charge transfer, which increased with voltage and application time. Hematoxylin-eosin staining of the pinnae identified localized areas of cell injury and fibrosis in the cartilage and in the surrounding soft tissue where the needle electrodes were inserted. This circumferential zone of injury (range, 1.5-2.5 mm) corresponded to dead cells on cell viability assay, and the diameter of this region increased with total electrical charge transfer to a maximum of 2.5 mm at 6 V for 3 minutes.Conclusions and relevanceElectromechanical reshaping produced shape change in intact pinnae of rabbits in this expanded in vivo study. A short application of 4 to 6 V can achieve adequate reshaping of the pinnae. Tissue injury around the electrodes increases with the amount of total current transferred into the tissue and is modest in spatial distribution. This study is a critical step toward evaluation of EMR in clinical trials.Level of evidenceNA.

ImportanceElectromechanical reshaping (EMR) is a low-cost, needle-based, and simple means to shape cartilage tissue without the use of scalpels, sutures, or heat that can potentially be used in an outpatient setting to perform otoplasty.ObjectivesTo demonstrate that EMR can alter the shape of intact pinnae in an in vivo animal model and to show that the amount of shape change and the limited cell injury are proportional to the dosimetry.Design, setting, and specimensIn an academic research setting, intact ears of 18 New Zealand white rabbits underwent EMR using 6 different dosimetry parameters (4 V for 5 minutes, 4 V for 4 minutes, 5 V for 3 minutes, 5 V for 4 minutes, 6 V for 2 minutes, and 6 V for 3 minutes). A custom acrylic jig with 2 rows of platinum needle electrodes was used to bend ears at the middle of the pinna and to perform EMR. Treatment was repeated twice per pinna, in proximal and distal locations. Control pinnae were not subjected to current application when being bent and perforated within the jig. Pinnae were splinted for 3 months along the region of the bend using soft silicon sheeting and a cotton bolster.Main outcomes and measuresThe ears were harvested the day after splints were removed and before euthanasia. Photographs of ears were obtained, and bend angles were measured. Tissue was sectioned for histologic examination and confocal microscopy to assess changes to microscopic structure and cellular viability.ResultsTreated pinnae were bent more and retained shape better than control pinnae. The mean (SD) bend angles in the 7 dosimetry groups were 55° (35°) for the control, 60° (15°) for 4 V for 4 minutes, 118° (15°) for 4 V for 5 minutes, 88° (26°) for 5 V for 3 minutes, 80° (17°) for 5 V for 4 minutes, 117° (21°) for 6 V for 2 minutes, and 125° (18°) for 6 V for 3 minutes. Shape change was proportional to electrical charge transfer, which increased with voltage and application time. Hematoxylin-eosin staining of the pinnae identified localized areas of cell injury and fibrosis in the cartilage and in the surrounding soft tissue where the needle electrodes were inserted. This circumferential zone of injury (range, 1.5-2.5 mm) corresponded to dead cells on cell viability assay, and the diameter of this region increased with total electrical charge transfer to a maximum of 2.5 mm at 6 V for 3 minutes.Conclusions and relevanceElectromechanical reshaping produced shape change in intact pinnae of rabbits in this expanded in vivo study. A short application of 4 to 6 V can achieve adequate reshaping of the pinnae. Tissue injury around the electrodes increases with the amount of total current transferred into the tissue and is modest in spatial distribution. This study is a critical step toward evaluation of EMR in clinical trials.Level of evidenceNA.

While most friction burns are adequately managed in an outpatient setting, many may require hospital admission, operative excision, and extended care. To this day, there is a wide variance in friction burn management. Our goal is to review the etiology, management, and outcomes of such burns warranting hospitalization. We conducted a retrospective review of all friction burns admitted to a single, American Burn Association-verified burn center from January 1, 2016 to December 31, 2020. A total of 28 (34%) patients required surgery for their friction burns and 15 (18%) ultimately required a split-thickness skin graft. The mean number of operations was 2.4 (95% CI 1.6-3.1). Overall, the operative group was younger (29.9 vs 38.3 years, P =.026), more likely to have a concomitant traumatic brain injury (25% vs 7%, P =.027), and had a longer hospital length of stay (17.5 vs 3.9 days, P <.001). Both groups had a similar overall TBSA (8.5% vs 10.0%, P =.35), but the operative group had a larger surface area comprised of third-degree burns (3.05% vs 0.2%, P <.001). Overall, friction burns resulting in hospital admission are associated with high-energy traumatic mechanisms and concomitant injuries. Patients who need operative intervention for their burns typically require multiple procedures often culminating in a split-thickness skin graft. While non-operative management of friction burns with topical agents has been found to be successful, patients with higher injury severity scores should be monitored very closely as they may require surgical excision. [ABSTRACT FROM AUTHOR]

Objective: Telestroke (TS) service has been shown to improve stroke diagnosis timing and accuracy, facilitate treatment decisions, and decrease interfacility transfers. Expanding TS service to inpatient units at the community hospital provides an opportunity to follow up on stroke patients and optimize medical management. This study examines the outcome of expanding TS coverage from acute emergency room triage to incorporate inpatient consultation. Methods: We studied the effect of expanding TS to inpatient consultation service at 19 regional hospitals affiliated with Promedica Stroke Network. We analyzed data pre‐ and post‐TS expansion. We reviewed changes in TS utilization, admission rate, thrombolytic therapy, patient transfer rate, and diagnosis accuracy. Results: Between January 2018 and June 2022, a total of 9,756 patients were evaluated in our stroke network (4,705 in pre‐ and 5,051 in the post‐TS expansion). In the post‐TS expansion period, stroke patients' admission at the spoke hospital increased from 18/month to 40/month, and for TIA from 11/month to 16/month. TS cart use increased from 12% to 35.2%. Patient transfers to hub hospital decreased by 31%. TS service expansion did not affect intravenous thrombolytic therapy rate or door‐to‐needle time. There was no difference in length of stay or readmission rate, and the patients at the spoke hospitals had a higher rate of home discharge 57.38% compared with 52.58% at hub hospital. Interpretation: Telestroke service expansion to inpatient units helped decrease transfers and retain patients in their communities, increased stroke and TIA diagnosis accuracy, and did not compromise patients' hospitalization or outcome. ANN NEUROL 2024;95:576–582 [ABSTRACT FROM AUTHOR]

Seth Hayes,1 Rebecca Miller,1 Ambrish Patel,2,3 Dmitry Tumin,1,2 Hina Walia,1 Mohammed Hakim,1 Faizaan Syed,1 Joseph D Tobias1,2,41Department of Anesthesiology and Pain Medicine, Nationwide Children’s Hospital, Columbus, OH 43205, USA; 2Department of Pediatrics, The Ohio State University, Columbus, OH 43210, USA; 3Division of Pediatric Critical Care, Nationwide Children’s Hospital, Columbus, OH 43205, USA; 4Department of Anesthesiology and Pain Medicine, The Ohio State University, Columbus, OH 43210, USACorrespondence: Seth HayesDepartment of Anesthesiology and Pain Medicine, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USATel +1 614 722 4200Fax +1 614 722 4203Email seth.hayes@nationwidechildrens.orgPurpose: To compare invasive blood pressure (IBP) readings obtained from an arterial cannula with non-invasive blood pressure (NIBP) measurements from oscillometric cuffs on the upper and lower extremities of infants and children under general anesthesia.Patients and methods: Patients under 10 years of age were enrolled in our study if they were to receive general anesthesia with planned placement of a radial arterial cannula. At 5 mins intervals, IBP was measured using a fluid-coupled pressure transducer and NIBP was measured with two oscillometers with appropriately sized cuffs placed on the upper arm and lower leg, for 10 readings per patient.Results: The study enrolled 18 boys and 12 girls, ranging in age from 0 to 8 years. Across 300 data points, the absolute difference between the arm and invasive mean arterial pressure (MAP) measurements was 7±7 mmHg (range: 0–52 mmHg). The absolute difference between the leg and invasive MAP measurements was 8±8 mmHg (range: 0–52 mmHg). Although both non-invasive measurement sites demonstrated frequent deviation from invasive measurement, large deviations were more common when BP was measured at the leg (81 of 298 observations (27%) deviating by >10 mmHg) compared to the arm (60 of 300 observations (20%) deviating by >10 mmHg).Conclusion: The frequency of clinically significant NIBP deviation in children under general anesthesia supports the importance of IBP monitoring when hemodynamic fluctuations are likely and would be particularly detrimental. NIBP measured at the lower leg is more likely to result in clinically significant deviation from invasively measured MAP than NIBP values obtained from an upper arm.Keywords: invasive blood pressure, non-invasive blood pressure, blood pressure cuff

Abstract Ce-doped LaMnO3 perovskite ceramics (La1−xCexMnO3) were synthesized by sol-gel based co-precipitation method and tested for the oxidation of benzyl alcohol using molecular oxygen. Benzyl alcohol conversion of ca. 25–42% was achieved with benzaldehyde as the main product. X-ray diffraction (XRD), thermogravimetric analysis (TGA), BET surface area, transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), temperature-programmed reduction (H2-TPR), temperature-programmed oxidation (O2-TPO), FT-IR and UV-vis spectroscopic techniques were used to examine the physiochemical properties. XRD analysis demonstrates the single phase crystalline high purity of the perovskite. The Ce-doped LaMnO3 perovskite demonstrated reducibility at low-temperature and higher mobility of surface O2-ion than their respective un-doped perovskite. The substitution of Ce3+ ion into the perovskite matrix improve the surface redox properties, which strongly influenced the catalytic activity of the material. The LaMnO3 perovskite exhibited considerable activity to benzyl alcohol oxidation but suffered a slow deactivation with time-on-stream. Nevertheless, the insertion of the A site metal cation with a trivalent Ce3+ metal cation led to an enhanced in catalytic performance because of atomic-scale interactions between the A and B active site. La0.95Ce0.05MnO3 catalyst demonstrated the excellent catalytic activity with a selectivity of 99% at 120 °C.

Sepsis continues to produce widespread inflammation, illness, and death, prompting intensive research aimed at uncovering causes and therapies. In this article, we focus on ghrelin, an endogenous peptide with promise as a potent anti-inflammatory agent. Ghrelin was discovered, tracked, and isolated from stomach cells based on its ability to stimulate release of growth hormone. It also stimulates appetite and is shown to be anti-inflammatory in a wide range of tissues. The anti-inflammatory effects mediated by ghrelin are a result of both the stimulation of anti-inflammatory processes and an inhibition of pro-inflammatory forces. Anti-inflammatory processes are promoted in a broad range of tissues including the hypothalamus and vagus nerve as well as in a broad range of immune cells. Aged rodents have reduced levels of growth hormone (GH) and diminished immune responses; ghrelin administration boosts GH levels and immune response. The anti-inflammatory functions of ghrelin, well displayed in preclinical animal models of sepsis, are just being charted in patients, with expectations that ghrelin and growth hormone might improve outcomes in patients with sepsis.

Background. The association between economic status and kidney disease is incompletely explored even in countries with higher economy (HE); the situation is complex in lower economies (LE) of South Asia and Southeast Asia (SA and SEA). Methods. Fifteen countries of SA and SEA categorized as HE and LE, represented by the representatives of the national nephrology societies, participated in this questionnaire and interview-based assessment of the impact of economic status on renal care. Results. Average incidence and prevalence of end-stage kidney disease (ESKD) per million population (pmp) are 1.8 times and 3.3 times higher in HE. Hemodialysis is the main renal replacement therapy (RRT) (HE-68%, LE-63%). Funding of dialysis in HE is mainly by state (65%) or insurance bodies (30%); out of pocket expenses (OOPE) are high in LE (41%). Highest cost for hemodialysis is in Brunei and Singapore, and lowest in Myanmar and Nepal. Median number of dialysis machines/1000 ESKD population is 110 in HE and 53 in LE. Average number of machines/dialysis units in HE is 2.7 times higher than LE. The HE countries have 9 times more dialysis centers pmp (median HE-17, LE-02) and 16 times more nephrologist density (median HE-14.8 ppm, LE-0.94 ppm). Dialysis sessions >2/week is frequently followed in HE (84%) and 10% in all the HE countries except Taiwan, 10%–20% in the majority of LE countries. Conclusion. Economic disparity in SA and SEA is reflected by poor dialysis infrastructure and penetration, inadequate manpower, higher OOPE, higher dialysis dropout rates, and lesser renal transplantations in LE countries. Utility of RRT can be improved by state funding and better insurance coverage.

In the published publication [...]

ObjectiveTo report the first successful study to date of in vivo electromechanical reshaping of ear cartilage in a rabbit model.MethodsEars of New Zealand white rabbits were reshaped using percutaneous needle electrode electromechanical reshaping (5 V for 4 minutes) and were then bolstered for 4 weeks. Ten ears were treated, with 2 undergoing sham procedures and serving as controls. The treatment was performed using a platinum array of electrodes consisting of 4 parallel rows of needles inserted across the region of flexures in the ear. After 4 weeks, the animals were killed, and the ears were photographed and sectioned for conventional light microscopy and confocal microscopy (live-dead fluorescent assays).ResultsSignificant shape change was noted in all the treated ears (mean, 102.4°; range, 87°-122°). Control ears showed minimal shape retention (mean, 14.5°; range, 4°-25°). Epidermis and adnexal structures were preserved in reshaped ears, and neochondrogenesis was noted in all the specimens. Confocal microscopy demonstrated a localized zone of nonviable chondrocytes (