Dispelling myths and misconceptions about the treatment of acute hyperkalemia.

Hyperkalemia represents a widespread and potentially lethal condition that affects millions of people across their lives. Despite the prevalence and severity of the condition, there are no consensus guidelines on the treatment of hyperkalemia or even a standard definition. Herein, we provide a succinct review of what we believe to be the most significant misconceptions encountered in the emergency care of hyperkalemia, examine current available literature, and discuss practical points on several modalities of hyperkalemia treatment. Additionally, we review the pathophysiology of the electrocardiographic effects of hyperkalemia and how intravenous calcium preparations can antagonize these effects. We conclude each section with recommendations to aid emergency physicians in making safe and efficacious choices for the treatment of acute hyperkalemia.

Identifying metabolites by integrating metabolome databases with mass spectrometry cheminformatics.

Novel metabolites distinct from canonical pathways can be identified through the integration of three cheminformatics tools: BinVestigate, which queries the BinBase gas chromatography-mass spectrometry (GC-MS) metabolome database to match unknowns with biological metadata across over 110,000 samples; MS-DIAL 2.0, a software tool for chromatographic deconvolution of high-resolution GC-MS or liquid chromatography-mass spectrometry (LC-MS); and MS-FINDER 2.0, a structure-elucidation program that uses a combination of 14 metabolome databases in addition to an enzyme promiscuity library. We showcase our workflow by annotating N-methyl-uridine monophosphate (UMP), lysomonogalactosyl-monopalmitin, N-methylalanine, and two propofol derivatives.

Analysis of absolute lymphocyte count in patients with COVID-19.

INTRODUCTION: Symptoms of COVID-19 vary in severity and presentation. When admitting patients to the hospital, it is desirable to isolate patients with COVID-19 from those without the disease. However, reliably identifying patients with COVID-19 in the emergency department before hospital admission is often limited by the speed and availability of testing. Previous studies determined a low lymphocyte count is commonly found in patients with COVID-19. We sought to explore the sensitivity of absolute lymphocyte count in patients presenting to the emergency department requiring subsequent hospitalization who were found to have COVID-19. METHODS: A retrospective chart review was performed on 312 patients with laboratory-confirmed COVID-19 who were admitted to the hospital from the emergency department. The absolute lymphocyte count for these patients was used to calculate sensitivities at various cut-off values. The relationships between absolute lymphocyte count and variables, including age, sex, need for intubation, and mortality, were also explored. RESULTS: Cut-off values for absolute lymphocyte count ranged from 1.1 K/uL to 2.0 K/uL, with sensitivities of 72% and 94%, respectively. Additionally, lower mean absolute lymphocyte counts were identified in males, patients who required intubation, and patients who died. CONCLUSION: Knowing the sensitivity of absolute lymphocyte count in patients with COVID-19 may help identify patients who are unlikely to have the disease. Additionally, absolute lymphocyte count can be used as a marker of disease severity in patients with COVID-19.

The Changing Climate: Managing Health Impacts.

Concentrations of greenhouse gases continue to accumulate in the atmosphere at increasing rates, heating the Earth's surface and destabilizing climate. Health impacts from climate change may include increased morbidity and mortality from worsening cardiopulmonary health, worsening allergies, and greater risk of infectious disease and mental illness, including anxiety, depression, and posttraumatic stress disorder from extreme weather events. Family physicians should advise patients to minimize exposure to air pollution, which is potentiated by rising temperatures. Use of self-monitoring devices, tracking local weather information, and awareness of events such as wildfires can alert patients to poor ambient air quality. Vulnerable individuals should avoid intense outdoor exercise and stay indoors or wear protective N95 masks when air quality is in the harmful range. Physicians can teach patients to recognize early symptoms of heat illness and advise adequate hydration and cooling on hot days. Physicians should become aware of the signs and symptoms of vectorborne illnesses to ensure early treatment and limit spread. Physicians should be aware of the climate and health benefits of active transport and plant-based diets when counseling their patients. Physicians can have a positive impact on climate change awareness and policy by incorporating counseling, public health precepts, and advocacy into their practice.

Characterization, comparison, and optimization of lattice light sheets.

Lattice light sheet microscopy excels at the noninvasive imaging of three-dimensional (3D) dynamic processes at high spatiotemporal resolution within cells and developing embryos. Recently, several papers have called into question the performance of lattice light sheets relative to the Gaussian sheets most common in light sheet microscopy. Here, we undertake a theoretical and experimental analysis of various forms of light sheet microscopy, which demonstrates and explains why lattice light sheets provide substantial improvements in resolution and photobleaching reduction. The analysis provides a procedure to select the correct light sheet for a desired experiment and specifies the processing that maximizes the use of all fluorescence generated within the light sheet excitation envelope for optimal resolution while minimizing image artifacts and photodamage. We also introduce a new type of "harmonic balanced" lattice light sheet that improves performance at all spatial frequencies within its 3D resolution limits and maintains this performance over lengthened propagation distances allowing for expanded fields of view.

A Comparison of Intubation and Airway Complications Between COVID-19 and Non-COVID-19 Critically Ill Subjects.

Introduction The number of subjects infected with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) throughout the western hemisphere increased exponentially in the later months of 2020. With this increase in infection, the number of subjects requiring advanced ventilatory support increased concomitantly. We decided to compare the survival rates between coronavirus disease 2019 (COVID-19) subjects versus non-COVID-19 subjects undergoing intubation in the intensive care unit (ICU). We hypothesized that COVID-19 subjects would have lower rates of survival post-intubation. Methods We screened all subjects admitted to the adult critical care unit between January 2020 and June 2020 to determine if they met the inclusion criteria. These subjects were required to be spontaneously ventilating upon admission and eventually required intubation. Subjects were selected from our electronic health record (EHR) system EPIC© (Epic Systems, Verona, WI) through a retrospective ICU admission analysis. We identified and included 267 non-COVID-19 subjects and 56 COVID-19 subjects. Our primary outcome of interest was intubation-related mortality. We defined intubation mortality as unexpected death (within 48 hours of intubation). Our secondary outcomes were the length of stay in the ICU, length of time requiring ventilator support, and proportion of subjects requiring tracheostomy placement. Results Compared to non-coronavirus disease (COVID) subjects, COVID subjects were more likely to be intubated for acute respiratory distress. COVID subjects had longer stays in the ICU and longer ventilator duration than non-COVID subjects. COVID-positive subjects had a decreased hazard ratio for mortality (HR = 0.42, 95% CI: 0.20-0.87, P < 0.05) and increased chances of survival compared to non-COVID subjects. Conclusions We showed the rates of intubation survival were no different between the COVID and non-COVID groups. We attribute this finding to intubation preparation, a multidisciplinary team approach, and having the most experienced provider lead the intubation process.

Assortative flocking in crossbills and implications for ecological speciation.

How reproductive isolation is related to divergent natural selection is a central question in speciation. Here, we focus on several ecologically specialized taxa or 'call types' of red crossbills (Loxia curvirostra complex), one of the few groups of birds providing much evidence for ecological speciation. Call types differ in bill sizes and feeding capabilities, and also differ in vocalizations, such that contact calls provide information on crossbill phenotype. We found that two call types of red crossbills were more likely to approach playbacks of their own call type than those of heterotypics, and that their propensity to approach heterotypics decreased with increasing divergence in bill size. Although call similarity also decreased with increasing divergence in bill size, comparisons of responses to familiar versus unfamiliar call types indicate that the decrease in the propensity to approach heterotypics with increasing divergence in bill size was a learned response, and not a by-product of calls diverging pleiotropically as bill size diverged. Because crossbills choose mates while in flocks, assortative flocking could lead indirectly to assortative mating as a by-product. These patterns of association therefore provide a mechanism by which increasing divergent selection can lead to increasing reproductive isolation.

Cutaneous vasomotor responses in boys and men.

Few studies have investigated skin blood flow in children and age-related differences in the underlying mechanisms. We examined mechanisms of skin blood flow responses to local heating, postocclusive reactive hyperaemia (PORH), and isometric handgrip exercise in adult and prepubescent males, hypothesizing that skin blood flow responses would be greater in children compared with adults. We measured skin blood flow in 12 boys (age, 9 ± 1 years) and 12 men (age, 21 ± 1 years) using laser-Doppler flowmetry at rest, in response to 3-min PORH, 2-min isometric handgrip exercise, and local skin heating to 39 °C (submaximal) and 44 °C (maximal). Using wavelet analysis we assessed endothelial, neural, and myogenic activities. At rest and in response to local heating to 39 °C, children had higher skin blood flow and endothelial activity compared with men (d ≥ 1.1, p < 0.001) and similar neurogenic and myogenic activities (d < 0.2, p > 0.05). Maximal responses to 44 °C local skin heating, PORH, and isometric handgrip exercise did not differ between boys and men (all d ≤ 0.2, p > 0.05). During PORH children demonstrated greater endothelial activity compared with men (d ≥ 0.6, p < 0.05); in contrast, men had higher neurogenic activity (d = 1.0, p < 0.01). During isometric handgrip exercise there were no differences in endothelial, neurogenic, and myogenic activities (d < 0.2, p > 0.3), with boys and men demonstrating similar increases in endothelial activity and decreases in myogenic activity (d ≥ 0.8, p < 0.05). These data suggest that boys experience greater levels of skin blood flow at rest and in response to submaximal local heating compared with men, while maximal responses appear to be similar. Additionally, endothelial mediators seem to contribute more to vasodilatation in boys than in men.

PARP1 is required for preserving telomeric integrity but is dispensable for A-NHEJ.

Poly-ADP ribose polymerase 1 (PARP1) is clinically important because of its synthetic lethality with breast cancer allele 1 and 2 mutations, which are causative for inherited breast and ovarian cancers. Biochemically, PARP1 is a single-stranded DNA break repair protein that is needed for preserving genomic integrity. In addition, PARP1 has been implicated in a veritable plethora of additional cellular pathways and thus its precise contribution(s) to human biology has remained obscure. To help address this deficiency, we utilized gene editing to construct genetically-null PARP1 human cancer cells. We found a minor role for PARP1 in an alternative form of DNA double-strand break (DSB) repair, but only when these cells were deficient for the classical form of DSB repair. Despite being proficient for DSB repair, however, cell cycle progression defects and elevated endogenous DNA damage signaling were observed. These deficiencies were instead linked to telomere defects, where PARP1 -/- cells had short telomeres that co-localized with markers of endogenous DNA damage and were compromised in their ability to escape a telomere-driven crisis. Our data suggest that while PARP1 does not participate significantly in DNA DSB repair itself, it does prevent the incidence of telomeric DSBs, which, in turn, can drive genomic instability.

The lymphoid cell surface receptor NTB-A: a novel monoclonal antibody target for leukaemia and lymphoma therapeutics.

NTB-A is a CD2-related cell surface protein expressed primarily on lymphoid cells including B-lymphocytes from chronic lymphocytic leukaemia (CLL) and lymphoma patients. We have generated a series of monoclonal antibodies (mAbs) against NTB-A and assessed their therapeutic potential for CLL. Selective mAbs to NTB-A were further tested in functional complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicty (ADCC) assays in cell lines and B lymphocytes freshly isolated from CLL patients. While lower levels of NTB-A were detected in T and natural killer (NK) cells, CDC activity was demonstrated primarily in B cells isolated from CLL patients and B lymphoma cell lines. Knockdown of NTB-A by small interfering RNA in target cells results in lower cytotoxicity, demonstrating the specificity of the mAbs. Furthermore, anti NTB-A mAbs demonstrated anti-tumour activity against CA46 human lymphoma xenografts in nude mice and against systemically disseminated Raji human lymphoma cells in severe combined immunodeficient mice. Taken together, these results demonstrate NTB-A as a potential new target for immunotherapy of leukaemia and lymphomas.