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Pressure overload of the heart is characterized by concentric hypertrophy and interstitial fibrosis. Cardiac fibroblasts (CFs) in the ventricular wall become activated during injury and synthesize and compact the extracellular matrix, which causes interstitial fibrosis and stiffening of the ventricular heart walls. Talin1 (Tln1) and Talin2 (Tln2) are mechanosensitive proteins that participate in focal adhesion transmission of signals from the extracellular environment to the actin cytoskeleton of CFs. The aim of the present study was to determine whether the removal of Tln1 and Tln2 from CFs would reduce interstitial fibrosis and cardiac hypertrophy. Twelve-week-old male and female Tln2-null (Tln2(−/−)) and Tln2-null, CF-specific Tln1 knockout (Tln2(−/−);Tln1(CF−/−)) mice were given angiotensin-II (ANG II) (1.5 mg/kg/day) or saline through osmotic pumps for 8 wk. Cardiomyocyte area and measures of heart thickness were increased in the male ANG II-infused Tln2(−/−);Tln1(CF−/−) mice, whereas there was no increase in interstitial fibrosis. Systolic blood pressure was increased in the female Tln2(−/−);Tln1(CF−/−) mice after ANG II infusion compared with the Tln2(−/−) mice. However, there was no increase in cardiac hypertrophy in the Tln2(−/−);Tln1(CF−/−) mice, which was seen in the Tln2(−/−) mice. Collectively, these data indicate that in male mice, the absence of Tln1 and Tln2 in CFs leads to cardiomyocyte hypertrophy in response to ANG II, whereas it results in a hypertrophy-resistant phenotype in female mice. These findings have important implications for the role of mechanosensitive proteins in CFs and their impact on cardiomyocyte function in the pathogenesis of hypertension and cardiac hypertrophy. NEW & NOTEWORTHY The role of talins has been previously studied in cardiomyocytes; however, these mechanotransductive proteins that are members of the focal adhesion complex have not been examined in cardiac fibroblasts previously. We hypothesized that loss of talins in cardiac fibroblasts would reduce interstitial fibrosis in the heart with a pressure overload model. However, we found that although loss of talins did not alter fibrosis, it did result in cardiomyocyte and ventricular hypertrophy.

The role of extracorporeal membrane oxygenation (ECMO) for patients with refractory respiratory failure due to coronavirus 2019 (COVID-19) is still unclear even now over a year into the pandemic. ECMO is becoming more commonplace even at smaller community hospitals. While the advantages of venovenous (VV) ECMO in acute respiratory distress syndrome (ARDS) from COVID-19 have not been fully determined, we believe the benefits outweighed the risks in our patient population. Here we describe all patients who underwent VV ECMO at our center.All patients placed on ECMO at our center since the beginning of the pandemic, May 5, 2020, until February 20, 2021 were included in our study. All patients placed on ECMO during the time period described above were followed until discharge or death. The primary endpoint was in-hospital death. Secondary outcomes included discharge disposition, that is, whether patients were sent to a long-term acute care center (LTAC), inpatient rehabilitation, or went directly home.A total of 41 patients were placed on VV ECMO for refractory acute respiratory failure. Survival to discharge, the primary end point, was 63.4% (26/41). Inpatient mortality was 36.6% (15/41).We show here that a successful high-volume VV ECMO program for ARDS is achievable at even a medium-size community hospital. We think our success can be replicated by most small- and medium-size community hospitals with cardiothoracic surgery programs and intensivist teams.

Summary Still’s disease, the paradigm of autoinflammation-cum-autoimmunity, predisposes for a cytokine storm with excessive T lymphocyte activation upon viral infection. Loss of function of the purine nucleoside enzyme FAMIN is the sole known cause for monogenic Still’s disease. Here we discovered that a FAMIN-enabled purine metabolon in dendritic cells (DCs) restrains CD4+ and CD8+ T cell priming. DCs with absent FAMIN activity prime for enhanced antigen-specific cytotoxicity, IFNγ secretion, and T cell expansion, resulting in excessive influenza A virus-specific responses. Enhanced priming is already manifest with hypomorphic FAMIN-I254V, for which ∼6% of mankind is homozygous. FAMIN controls membrane trafficking and restrains antigen presentation in an NADH/NAD+-dependent manner by balancing flux through adenine-guanine nucleotide interconversion cycles. FAMIN additionally converts hypoxanthine into inosine, which DCs release to dampen T cell activation. Compromised FAMIN consequently enhances immunosurveillance of syngeneic tumors. FAMIN is a biochemical checkpoint that protects against excessive antiviral T cell responses, autoimmunity, and autoinflammation., Graphical abstract, Highlights • A FAMIN-enabled purine metabolon in dendritic cells restrains T cell priming • FAMIN prevents cytoplasmic NADH/NAD+ reductive stress that enhances priming • Inosine generated from hypoxanthine by FAMIN inhibits T cell priming • FAMIN ameliorates immunopathology in influenza but dampens tumor surveillance, Saveljeva et al. identify a biochemical mechanism in dendritic cells that restrains T cell priming and prevents immunopathology but dampens tumor surveillance. FAMIN enables a purine nucleotide cycle, which prevents cytoplasmic NADH/NAD+ reductive stress that augments antigen presentation, and it generates inosine, which inhibits T cell activation.

Pulmonary arterial hypertension (PAH) is a fatal vasculopathy that ultimately leads to elevated pulmonary pressure and death by right ventricular (RV) failure, which occurs in part due to decreased fatty acid oxidation and cytotoxic lipid accumulation. In this study, we tested the hypothesis that decreased fatty acid oxidation and increased lipid accumulation in the failing RV is driven, in part, by a relative carnitine deficiency. We then tested whether supplementation of l-carnitine can reverse lipotoxic RV failure through augmentation of fatty acid oxidation. In vivo in transgenic mice harboring a human BMPR2 mutation, l-carnitine supplementation reversed RV failure by increasing RV cardiac output, improving RV ejection fraction, and decreasing RV lipid accumulation through increased PPARγ expression and augmented fatty acid oxidation of long chain fatty acids. These findings were confirmed in a second model of pulmonary artery banding-induced RV dysfunction. In vitro, l-carnitine supplementation selectively increased fatty acid oxidation in mitochondria and decreased lipid accumulation through a Cpt1-dependent pathway. l-Carnitine supplementation improves right ventricular contractility in the stressed RV through augmentation of fatty acid oxidation and decreases lipid accumulation. Correction of carnitine deficiency through l-carnitine supplementation in PAH may reverse RV failure.

For almost 60 years, electret microphones have been the preferred sensors for applications in communications, mainly because the microphones are linear over a broad frequency range and rather simple to manufacture. Because the electret microphone can be mass produced with only slight differences in phase and frequency response, multiple units can be combined to form a variety of directional arrays ranging from second-order unidirectional to two-dimensional arrays for focusing on a specific area. While electret microphones and arrays have similar utility for monitoring lung and heart sounds from the body, the body sounds captured can be easily corrupted by noise external to the body. Advanced signal processing techniques can mitigate contributions from airborne noise but are computationally intensive. By modifying the acoustic impedance of the electret microphone’s diaphragm to match that of the body, we are able to capture high-fidelity heart and lung sounds without corruption from airborne noise. This redesign of the original electret microphone could provide a method to continuously monitor lung and heart sounds from a subject regardless of their surrounding noise environment.

Ubiquitin related modifier 1 (Urm1) is a unique eukaryotic member of the ubiquitin-fold (UbF) protein family and conserved from yeast to humans. Urm1 is dual-functional, acting both as a sulfur carrier for thiolation of tRNA anticodons and as a protein modifier in a lysine-directed Ub-like conjugation also known as urmylation. Although Urm1 conjugation coincides with oxidative stress and targets proteins like 2-Cys peroxiredoxins from yeast (Ahp1) and fly (Prx5), it was unclear how urmylation proceeds molecularly and whether it is affected by the activity of these antioxidant enzymes. An in-depth study of Ahp1 urmylation in yeast from our laboratory (Brachmann et al., 2020) uncovered that promiscuous lysine target sites and specific redox requirements determine the Urm1 acceptor activity of the peroxiredoxin. The results clearly show that the dimer interface and the 2-Cys based redox-active centers of Ahp1 are affecting the Urm1 conjugation reaction. Together with in vivo assays demonstrating that high organic peroxide concentrations can prevent Ahp1 from being urmylated, Brachmann et al. provide insights into a potential link between Urm1 utilization and oxidant defense of cells. Here, we highlight these major findings and discuss wider implications with regards to an emerging link between Urm1 conjugation and redox biology. Moreover, from these studies we propose to redefine our perspective on Urm1 and the molecular nature of urmylation, a post-translational conjugation that may not be that ubiquitin-like after all.

Despite growing interest in edible seaweeds, there is limited information on seaweed chemical contaminant levels in the Salish Sea. Without this knowledge, health-based consumption advisories can not be determined for consumers that include Tribes and First Nations, Asian and Pacific Islander community members, and recreational harvesters. We measured contaminant concentrations in edible seaweeds (Fucus distichus, F. spiralis, and Nereocystis luetkeana) from 43 locations in the Salish Sea. Metals were analyzed in all samples, and 94 persistent organic pollutants (POPs) (i.e. 40 PCBs, 15 PBDEs, 17 PCDD/Fs, and 22 organochlorine pesticides) and 51 PAHs were analyzed in Fucus spp. We compared concentrations of contaminants to human health-based screening levels calculated from the USEPA and to international limits. We then worked with six focal contaminants that either exceeded screening levels or international limits (Cd, total Hg, Pb, benzo[a]pyrene [BaP], and PCBs) or are of regional interest (total As). USEPA cancer-based screening levels were exceeded in 30 samples for the PCBs and two samples for BaP. Cadmium concentrations did not exceed the USEPA noncancer-based screening level but did exceed international limits at all sites. Lead exceeded international limits at three sites. Because there are no screening levels for total Hg and total As, and to be conservative, we made comparisons to methyl Hg and inorganic As screening levels. All samples were below the methyl Hg and above the inorganic As screening levels. Without knowledge of the As speciation, we cannot assess the health risk associated with the As. While seaweed was the focus, we did not consider contaminant exposure from consuming other foods. Other chemicals, such as contaminants of emerging concern (e.g., PFAS, pharmaceuticals and personal care products), should also be considered. Additionally, although we focused on toxicological aspects, there are cultural and health benefits of seaweed use that may affect consumer choice.

SUMMARYPost-traumatic stress disorder (PTSD) is a common trauma and stressor-related disorder. Trauma-focused psychotherapies and selective serotonin reuptake inhibitors represent current state of the art treatment for PTSD, with current evidence favouring psychotherapy as first-line treatment. Much room remains for development of more effective therapeutics. This article give a brief update on diagnosis and treatment of PTSD.

OBJECTIVERathke’s cleft cysts (RCCs) are benign lesions of the sella turcica that usually come to neurosurgical attention due to compression of the optic apparatus (OA) and headaches. Treatment options for these lesions include observation, aspiration of cyst contents, or open resection of the cyst with the cyst wall. All of these options involve the potential for cyst recurrence or enlargement. In this study the authors report on a potential new therapeutic option for RCCs, i.e., stereotactic radiosurgery (SRS).METHODSA retrospective review was conducted of 5 patients with histologically confirmed, multiply recurrent RCCs who were treated with single-fraction SRS at a tertiary referral academic medical center.RESULTSThe total cohort consisted of 5 female patients with an average age of 31.8 years. The most common presenting symptom was headache followed by blurry vision. The symptoms were present on average for 7 months before intervention. The median number of surgeries prior to radiosurgery was 2. The average volume of lesion treated was 0.34 cm3. The median SRS dose was 12.5 Gy prescribed to the 50% isodose line with an average prescription coverage of 96.6%. The median dose to the OA was 5 Gy. At last follow-up, 3 of 5 cysts had completely regressed, 1 had regressed by more than 50% but was still present, and 1 was stable, with an overall mean follow-up duration of 34.2 months. There were no neurological, endocrinological, or visual complications attributable to SRS during the follow-up period.CONCLUSIONSRCCs can be a challenging clinical entity to treat, especially when they are multiply recurrent. In patients with an average of 2 previous surgeries for resection, a single SRS session prevented recurrence universally, with an average follow-up of almost 3 years. These results indicate that further investigation of the treatment of RCCs with SRS is indicated.

Mutations in VHL, which encodes von Hippel-Lindau tumor suppressor (VHL), are associated with divergent diseases. We describe a patient with marked erythrocytosis and prominent mitochondrial alterations associated with a severe germline VHL deficiency due to homozygosity for a novel synonymous mutation (c.222C→A, p.V74V). The condition is characterized by early systemic onset and differs from Chuvash polycythemia (c.598C→T) in that it is associated with a strongly reduced growth rate, persistent hypoglycemia, and limited exercise capacity. We report changes in gene expression that reprogram carbohydrate and lipid metabolism, impair muscle mitochondrial respiratory function, and uncouple oxygen consumption from ATP production. Moreover, we identified unusual intermitochondrial connecting ducts. Our findings add unexpected information on the importance of the VHL-hypoxia-inducible factor (HIF) axis to human phenotypes. (Funded by Associazione Italiana Ricerca sul Cancro and others.).

The authors report the case of a 30-year-old female patient with suspected Cushing’s disease with an anatomical variation of hypoplastic inferior petrosal sinuses and nearly exclusive anterior drainage from the cavernous sinus, who underwent external jugular venous blood sampling with successful disease confirmation and microadenoma localization. The patient presented with signs and symptoms consistent with Cushing’s syndrome, but with discordant preliminary diagnostic testing. She underwent attempted bilateral inferior petrosal sinus sampling; however, she had hypoplastic inferior petrosal sinuses bilaterally and predominantly anterior drainage from the cavernous sinus into the external jugular circulation. Given this finding, the decision was made to proceed with external jugular venous access and sampling in addition to internal jugular venous sampling. A positive adrenocorticotropic hormone (ACTH) response to corticotropin-releasing factor was obtained in the right external jugular vein alone, suggesting a right-sided pituitary microadenoma as the cause of her Cushing’s disease. The patient subsequently underwent a transsphenoidal hypophysectomy that confirmed the presence of a right-sided ACTH-secreting microadenoma, which was successfully resected. She was hypocortisolemic on discharge and has had no signs of recurrence or relapse at 6 months postoperation.

This paper estimates the impact of racially diverse peers on white males’ subsequent behavior toward minorities. To overcome selection bias, we exploit data from the US Air Force Academy where students are randomly assigned to autonomous peer groups. A randomly assigned increase in freshman black peer ability causes white men to more frequently choose a black roommate in their sophomore year, after reassignment to a new peer group with a different set of black peers. We also find increased exposure to black students from the middle and top of the high school performance distribution, but not the bottom, increases future interactions. (JEL I23, J15)

In the framework of immunity testing, there has been recently a great interest to determine the maximum field distribution in a nested reverberation chamber, the inner cavity being considered as the equipment under test (EUT). The generalized extreme value distribution is a generalization of three asymptotic distributions that does not require knowledge of the field sample parent distribution in comparison with traditional method. It can therefore be applied in situations when the parent distribution is unknown, such as when an EUT is reverberant or is operating in the undermoded regime. In this paper, we present an experimental validation of the maximum statistical distribution of the internal field samples inside different nested cavity configurations. The Anderson–Darling test is applied to verify if a dataset is collected from a single statistical population inside the EUT with different stirring scenarios and two different EUT aperture dimensions. Parametric and nonparametric estimation are then used to model and to verify the results. The parametric and nonparametric distributions show good agreement for all test configurations considered, extending earlier works which considered reverberation-chamber fields themselves with no EUT included or did not include EUT internal stirring.

The effects of frequency stirring on the statistics of the currents induced on an equipment-under-test (EUT) placed in a reverberation chamber field are analyzed. A reciprocal approach that relates the received currents in a susceptibility test to the free-space input impedance presented by the EUT when excited at the test point is used. An analytical expression is then derived to give the distribution functions of the induced currents under frequency stirring that accounts for the frequency dependence of the EUT radiation characteristics. A numerical study of shielding-box EUTs with coupling apertures shows that the changes in the EUT test-port input impedance with frequency yield non-Rayleigh current statistics when frequency stirring is used. It is unlikely that a single distribution family with a limited number of parameters can be fit to the current statistics with EUTs of arbitrary volume, coupling aperture, and measurement probe configurations.

Background Radiation therapy for malignant head and neck cancers includes a risk for off-target effects to bony structures, posing a risk for osteoradionecrosis (ORN). Patients in whom ORN develops can also harbor concomitant osteomyelitis and reduced healing capacity, making for a particularly challenging entity to treat. Hyperbaric oxygen therapy (HBO) has been shown to be effective in the treatment of mandibular ORN in the otolaryngology literature; yet, few reports exist detailing its utility when treating ORN of the craniocervical junction. Herein, we report 2 cases of ORN of the craniocervical junction who received both neoadjuvant and adjuvant HBO in combination with posterior spinal fusion. Case Description Two patients with craniocervical junction ORN were treated with HBO delivered over 20 sessions before and after surgery in 90-minute treatments to 2.5 atmospheres of pressure. The patients underwent posterior occipital–cervical fusions with an average operative time of 301 (±21.5) minutes with 250 (±150) mL of blood loss. Both patients stayed in the hospital for 5 days, with no periprocedural complications. Outcomes included a 30% improvement of global assessment of function on follow-up EuroQol 5-Dimension Questionnaire. Postoperative imaging demonstrated solid bony fusion, and both patients returned to full work duty. Conclusions ORN is a difficult-to-treat radiation complication in head and neck cancers. Few reports exist detailing treatment options for ORN of the craniocervical junction in conjunction with surgical stabilization. We report 2 successful cases of HBO-assisted treatment of ORN and highlight the important role HBO can play in promoting bony fusion in these at-risk patients.

We used manually spawned, field-deployed embryos of a common marine fish species, Pacific herring (Clupea pallasii), to evaluate accumulation of polycyclic aromatic hydrocarbons (PAHs) associated with an incomplete creosote-treated piling (CTP) removal project. Embryos near undisturbed 100-year-old CTPs (before removal) accumulated higher PAHs and exhibited higher cyp1a gene expression than embryos from reference areas. Embryos incubated close to CTP debris after CTP removal showed PAHs 90 times higher than reference areas up to a year after CTP removal. cyp1a fold-induction correlated with total embryo PAHs in all three years. Patterns of individual PAH chemicals differed slightly between embryos, wood sampled from CTPs, and passive samplers. This study illustrates the importance of using appropriate techniques and procedures to remove CTPs in aquatic environments to prevent release of toxic chemicals. Of particular concern is that incomplete CTP removal could expose sensitive life stages of fishes to chemicals that may reduce their survival.

You wake up one morning to discover that your child is ill: His forehead feels hot to the touch, and his rapid breathing has a wheezing sound. You live in Malawi, where your health care options are few. When the local clinic opens, you wait for your turn with the solitary clinic worker. She's not a doctor, but she's been trained to identify and handle routine problems.

Background Spinal anesthesia (SA) is routinely used in obstetrics and orthopedic surgery but has not been widely adopted in lumbar spine surgery (LSS). One perceived barrier is the learning curve for the neurosurgical and anesthesia team associated with managing a patient in the prone position under SA. Methods A retrospective cohort of 34 LSS cases under SA at our institution was examined. Operative time, corrected operative time per level, and complications were analyzed. The learning curve was assessed using a curve-fit regression analysis. Results Of patients, 62% were female, with mean (SD) age and body mass index of 60.7 (10.8) years and 29.9 (4.6) kg/m2, respectively. The mean (SD) for each time segment was operating room arrival to incision 35.7 (8.1) minutes, total surgical time 100.4 (35.8) minutes, and procedure finish to operating room exit 3.4 (2.5) minutes. When the times were normalized to procedure type and analyzed sequentially, the mean (SD) slope of all trendlines was 0.003 (0.005) with correlation coefficients of R2 = 0.0002–0.01, indicating no appreciable learning curve. Normalized postanesthesia care unit time was significantly shorter for overnight stay versus same-day discharge (0.64 vs. 1.36, P = 0.0005). Conclusions Our data demonstrate the lack of a learning curve when SA is implemented in LSS cases by an anesthetic team already familiar with SA techniques for other procedures. Importantly, the surgical team was already familiar with the minimally invasive surgery approaches used in conjunction with SA. This study highlights that the barriers to transitioning to SA for LSS may be fewer than perceived.

Extrahepatic tissues which oxidise ketone bodies also have the capacity to accumulate them under particular conditions. We hypothesised that acetyl-coenzyme A (acetyl-CoA) accumulation and altered redox status during low-flow ischaemia would support ketone body production in the heart. Combining a Langendorff heart model of low-flow ischaemia/reperfusion with liquid chromatography coupled tandem mass spectrometry (LC-MS/MS), we show that β-hydroxybutyrate (β-OHB) accumulated in the ischaemic heart to 23.9 nmol/gww and was secreted into the coronary effluent. Sodium oxamate, a lactate dehydrogenase (LDH) inhibitor, increased ischaemic β-OHB levels 5.3-fold and slowed contractile recovery. Inhibition of β-hydroxy-β-methylglutaryl (HMG)-CoA synthase (HMGCS2) with hymeglusin lowered ischaemic β-OHB accumulation by 40%, despite increased flux through succinyl-CoA-3-oxaloacid CoA transferase (SCOT), resulting in greater contractile recovery. Hymeglusin also protected cardiac mitochondrial respiratory capacity during ischaemia/reperfusion. In conclusion, net ketone generation occurs in the heart under conditions of low-flow ischaemia. The process is driven by flux through both HMGCS2 and SCOT, and impacts on cardiac functional recovery from ischaemia/reperfusion.

Data supporting "β-Hydroxybutyrate Accumulates in the Rat Heart during Low-Flow Ischaemia with Implications for Functional Recovery". See README file for description.

In the space community, there is increasing interest in adaption and augmentation of launch fairing thermal-acoustic blankets, to also control electromagnetic environment threats. This paper reports on the development of simulation methods to both optimize blanket materials for RF absorption and to provide quantitative guidance on their minimal spatial deployment inside the fairing. A stochastic power-balance model with multiple connected sub-cavities is used to map the reverberant electric field in the fairing when RF absorbing blankets are applied only locally – ie only partial coverage of the fairing wall. The sub-cavity Q factors resulting from different RF absorption blanket materials is calculated from published reflection loss data and a field incidence correction factor. Comparison with model-scale test data verified that the model correctly predicts the attenuation of different absorber materials, the spatial distribution of the field and the improvement in shielding effectiveness.

The electric field levels established at various points within a modeled rocket fairing under different excitations are measured. Both interior sources placed within different fairing sub cavities and exterior excitation was used. The effect of the addition of different absorbers on the electric field level in different sub cavities was investigated as well. The shielding effectiveness of the fairing within the different fairing sub cavities was considered. The relation between the total surface of absorber and the electric field level studied. In addition, the electric field level excited inside the fairing under external illumination was numerically simulated. The laboratory measurements were verified through comparison with the simulation results.

A launch vehicle payload fairing scale model has been designed, fabricated, and tested to investigate the reverberant electromagnetic fields within launch vehicle fairings. The fairing scale model uses a mechanical stirrer to attain statistically uniform fields within the fairing cavity. A removable payload model and payload adapter model are included in the fairing to study the interactions of fields with these structures. The layering of the fairing walls, use of shielding gaskets, and field probes to measure the cavity fields are described. The quality factor is measured when the fairing cavity is empty and when the surrogate payload and payload adapter models are added. The quality factor of the empty fairing measured from about 32 dB at 1 GHz to 41 dB at 6 GHz. The Q values dropped approximately 2 dB across the band when the payload and payload adapter models were placed in the fairing cavity. Measurements of Q at different probe positions within the fairing yielded similar results.

Electronic stethoscopes offer several advantages over conventional acoustic stethoscopes, including noise reduction, increased amplification, and ability to store and transmit sounds. However, the acoustical characteristics of electronic and acoustic stethoscopes can differ significantly, introducing a barrier for clinicians to transition to electronic stethoscopes. This work proposes a method to process lung sounds recorded by an electronic stethoscope, such that the sounds are perceived to have been captured by an acoustic stethoscope. The proposed method calculates an electronic-to-acoustic stethoscope filter by measuring the difference between the average frequency responses of an acoustic and an electronic stethoscope to multiple lung sounds. To validate the method, a change detection experiment was conducted with 51 medical professionals to compare filtered electronic, unfiltered electronic, and acoustic stethoscope lung sounds. Participants were asked to detect when transitions occurred in sounds comprising several sections of the three types of recordings. Transitions between the filtered electronic and acoustic stethoscope sections were detected, on average, by chance (sensitivity index equal to zero) and also detected significantly less than transitions between the unfiltered electronic and acoustic stethoscope sections (p < 0.01), demonstrating the effectiveness of the method to filter electronic stethoscopes to mimic an acoustic stethoscope. This processing could incentivize clinicians to adopt electronic stethoscopes by providing a means to shift between the sound characteristics of acoustic and electronic stethoscopes in a single device, allowing for a faster transition to new technology and greater appreciation for the electronic sound quality.

During disasters, the roles of physicians, nurses, and ancillary medical staff are defined by their individual certifications, whereas the roles of medical students remain less clear. Medical students are unlicensed physicians-in-training, with variable degrees of skill and knowledge, and thus, their involvement in disaster response has historically varied. In light of the coronavirus disease 2019 pandemic, many junior students were asked to remove themselves from the hospital setting, whereas some senior students graduated early to join the physician workforce. In this article, the authors will examine the psychosocial benefits and consequences of medical student involvement in prior disasters and developing attitudes in light of the coronavirus disease 2019 pandemic. We conclude by offering our thoughts on medical student involvement in future disasters.

Background Numerous pathologies result in multiple-organ failure, which is thought to be a direct consequence of compromised cellular bioenergetic status. Neither the nature of this phenotype nor its relevance to survival are well understood, limiting the efficacy of modern life-support. Methods To explore the hypothesis that survival from critical illness relates to changes in cellular bioenergetics, we combined assessment of mitochondrial respiration with metabolomic, lipidomic and redox profiling in skeletal muscle and blood, at multiple timepoints, in 21 critically ill patients and 12 reference patients. Results We demonstrate an end-organ cellular phenotype in critical illness, characterized by preserved total energetic capacity, greater coupling efficiency and selectively lower capacity for complex I and fatty acid oxidation (FAO)-supported respiration in skeletal muscle, compared to health. In survivors, complex I capacity at 48 h was 27% lower than in non-survivors (p = 0.01), but tended to increase by day 7, with no such recovery observed in non-survivors. By day 7, survivors’ FAO enzyme activity was double that of non-survivors (p = 0.048), in whom plasma triacylglycerol accumulated. Increases in both cellular oxidative stress and reductive drive were evident in early critical illness compared to health. Initially, non-survivors demonstrated greater plasma total antioxidant capacity but ultimately higher lipid peroxidation compared to survivors. These alterations were mirrored by greater levels of circulating total free thiol and nitrosated species, consistent with greater reductive stress and vascular inflammation, in non-survivors compared to survivors. In contrast, no clear differences in systemic inflammatory markers were observed between the two groups. Conclusion Critical illness is associated with rapid, specific and coordinated alterations in the cellular respiratory machinery, intermediary metabolism and redox response, with different trajectories in survivors and non-survivors. Unravelling the cellular and molecular foundation of human resilience may enable the development of more effective life-support strategies., Graphical abstract Image 1

Background Incidental durotomy, a known complication of spinal surgery, can lead to persistent cerebrospinal fluid leak and pseudomeningocele if unrecognized or incompletely repaired. We describe the use of ultrasound to visualize the site of durotomy, observe the aspiration of the pseudomeningocele, and guide the precise application of an ultrasound-guided epidural blood patch (US-EBP), under direct visualization in real time. Methods A retrospective review was performed to determine demographic, procedural, and outcome characteristics for patients who underwent US-EBP for symptomatic postoperative pseudomeningocele. Results Overall, 48 patients who underwent 49 unique episodes of care were included. The average age and body mass index were 60.5 (±12.6) years and 27.8 (±4.50) kg/m2, respectively. The most frequent index operation was laminectomy (24.5%), and 36.7% of surgeries were revision operations. Durotomy was intended or recognized in 73.4% of cases, and the median time from surgery to symptom development was 7 (interquartile range 4–16) days. A total of 61 US-EBPs were performed, with 51.0% of patients experiencing resolution of their symptoms after the first US-EBP. An additional 20.4% were successful with multiple US-EBP attempts. Complications occurred in 14.3% of cases, and the median clinical follow-up was 4.3 (interquartile range 2.4–14.5) months. Conclusions This manuscript represents the largest series in the literature describing US-EBP for the treatment of postoperative pseudomeningocele. The success rate suggests that routine utilization of US-guided EBP may allow for targeted treatment of pseudomeningoceles, without the prolonged hospitalization associated with lumbar drains or the risks of general anesthesia and impaired wound healing associated with surgical revision.