Exploring attitudinal barriers to participation in inpatient fall risk assessment using the Theoretical Domains Framework: A survey of providers.

Background and Aims: Lack of provider (physicians and advanced practice providers) participation in fall risk assessment was theorized to be contributing to rising rates of falls with injury at our institution. This project sought to identify if attitudinal barriers to inpatient provider participation in fall risk assessment were similar to those identified in other clinical settings. Methods: Barriers to provider participation in fall risk assessment were identified in the literature. These were mapped to the Theoretical Domains Framework (TDF) domains to assist with interpretation of the data. A 10-item survey using a 5-point Likert scale (strongly agree to strongly disagree) with two open-ended questions was developed using these barriers. The survey was distributed via email to all providers on the Medical Staff in July 2021. Results: The response rate was 9.1% (188/2062). 72.6% (95% confidence interval [CI]: 65.6, 78.5) of providers at our institution did agree that fall risk assessment was within their role and 72% (95% CI: 66.1, 78.5) agreed that assessment can prevent falls. Nearly half felt that they lacked formal training in fall risk assessment (48.1% [95% CI: 41.1, 55.1]) and 52.2% (95% CI: 44.6, 58.6) agreed that other aspects of patient care took priority over falls assessment. These barriers correlated best with the TDF domains of Beliefs about Capabilities and Beliefs about Consequences. Conclusions: Survey results indicate that interventions focused on increasing provider motivation and capability regarding fall risk assessment and helping providers prioritize fall risk assessment are potential targets for future quality improvement projects.

Lorazepam Stimulates IL6 Production and Is Associated with Poor Survival Outcomes in Pancreatic Cancer.

PURPOSE: This research investigates the association between benzodiazepines (BZD) and cancer patient survival outcomes, the pancreatic cancer tumor microenvironment, and cancer-associated fibroblast (CAF) signaling. EXPERIMENTAL DESIGN: Multivariate Cox regression modeling was used to retrospectively measure associations between Roswell Park cancer patient survival outcomes and BZD prescription records. IHC, H&E, Masson's trichrome, RNAscope, and RNA sequencing were used to evaluate the impact of lorazepam (LOR) on the murine PDAC tumor microenvironment. ELISA and qPCR were used to determine the impact of BZDs on IL6 expression or secretion by human-immortalized pancreatic CAFs. PRESTO-Tango assays, reanalysis of PDAC single-cell sequencing/TCGA data sets, and GPR68 CRISPRi knockdown CAFs were used to determine the impact of BZDs on GPR68 signaling. RESULTS: LOR is associated with worse progression-free survival (PFS), whereas alprazolam (ALP) is associated with improved PFS, in pancreatic cancer patients receiving chemotherapy. LOR promotes desmoplasia (fibrosis and extracellular matrix protein deposition), inflammatory signaling, and ischemic necrosis. GPR68 is preferentially expressed on human PDAC CAFs, and n-unsubstituted BZDs, such as LOR, significantly increase IL6 expression and secretion in CAFs in a pH and GPR68-dependent manner. Conversely, ALP and other GPR68 n-substituted BZDs decrease IL6 in human CAFs in a pH and GPR68-independent manner. Across many cancer types, LOR is associated with worse survival outcomes relative to ALP and patients not receiving BZDs. CONCLUSIONS: We demonstrate that LOR stimulates fibrosis and inflammatory signaling, promotes desmoplasia and ischemic necrosis, and is associated with decreased pancreatic cancer patient survival.

NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis.

The sodium-bicarbonate cotransporter (NBCe1) has three primary variants: NBCe1-A, -B and -C. NBCe1-A is expressed in renal proximal tubules in the cortical labyrinth, where it is essential for reclaiming filtered bicarbonate, such that NBCe1-A knockout mice are congenitally acidemic. NBCe1-B and -C variants are expressed in chemosensitive regions of the brainstem, while NBCe1-B is also expressed in renal proximal tubules located in the outer medulla. Although mice lacking NBCe1-B/C (KOb/c) exhibit a normal plasma pH at baseline, the distribution of NBCe1-B/C indicates that these variants could play a role in both the rapid respiratory and slower renal responses to metabolic acidosis (MAc). Therefore, in this study we used an integrative physiologic approach to investigate the response of KOb/c mice to MAc. By means of unanesthetized whole-body plethysmography and blood-gas analysis, we demonstrate that the respiratory response to MAc (increase in minute volume, decrease in pCO2) is impaired in KOb/c mice leading to a greater severity of acidemia after 1 day of MAc. Despite this respiratory impairment, the recovery of plasma pH after 3-days of MAc remained intact in KOb/c mice. Using data gathered from mice housed in metabolic cages we demonstrate a greater elevation of renal ammonium excretion and greater downregulation of the ammonia recycling enzyme glutamine synthetase in KOb/c mice on day 2 of MAc, consistent with greater renal acid-excretion. We conclude that KOb/c mice are ultimately able to defend plasma pH during MAc, but that the integrated response is disturbed such that the burden of work shifts from the respiratory system to the kidneys, delaying the recovery of pH.

The cost of ischaemic stroke in Croatia.

Objective: The aim of this analysis was to estimate 1 year and long-term cost and quality of life of ischaemic stroke patients in Croatia. In addition, we aimed to identify and estimate key categories of costs and outcomes driving the burden of stroke in Croatian healthcare system. Methods: Data were derived from analysis of the RES-Q Registry for Croatia in 2018 and supplemented with clinical expert opinion and relevant medical, clinical and economic literature to estimate the course of the disease and treatment patterns in Croatian healthcare system. The health economic model was comprised of a one-year discrete event simulation (DES) mapping real life patient experience and a 10-year Markov model built on existing literature. Cost and health resources use were obtained using Croatian tariffs. Health utilities were mapped to EQ5D from the Barthel Index utilising previously published studies. Results: The key aspects determining costs and quality of life were rehabilitation, discharge to residential care (currently 13% of patients in Croatia) and recurrent stroke. Total 1 year cost per patient was 18,221 EUR having 0.372 QALYs. Conclusion: Direct costing structure of ischaemic stroke in Croatia is above the value of upper-middle income countries. Our study showed that post stroke rehabilitation seems to be a strong modifier of future post-stroke costs and further research into various models of post-stroke care and rehabilitation could be the answer into more successful rehabilitation that could increase QALY and reduce the economic burden of stroke. Further investment in rehabilitation research and provision might bring promising opportunities to improve long term patient outcomes.

Thoracic point-of-care ultrasound is an accurate diagnostic modality for clinically significant traumatic pneumothorax.

OBJECTIVE: There are conflicting data regarding the accuracy of thoracic point-of-care ultrasound (POCUS) in detecting traumatic pneumothorax (PTX). The purpose of our study was to determine the accuracy of thoracic POCUS performed by emergency physicians for the detection of clinically significant PTX in blunt and penetrating trauma patients. METHODS: We conducted a retrospective institutional review board-approved study of trauma patients 15 years or older presenting to our urban Level I academic trauma center from December 2021 to June 2022. All study patients were imaged with single-view chest radiography (CXR) and thoracic POCUS. The presence or absence of PTX was determined by multidetector computed tomography (CT) or CXR and ultrasound (US) with tube thoracostomy placement. RESULTS: A total of 846 patients were included, with 803 (95%) sustaining blunt trauma. POCUS identified 13/15 clinically significant PTXs (defined as ≥35 mm of pleural separation on a blinded overread or placement of a tube thoracostomy prior to CT) with a sensitivity of 87% (95% confidence interval [CI] 58-97), specificity of 100% (95% CI 99-100), positive predictive value of 81% (95% CI 54%-95%), and negative predictive value of 100% (95% CI 99%-100%). The positive likelihood ratio was 484 and the negative likelihood ratio was 0.1. CXR identified eight (53%) clinically significant PTXs, with a sensitivity of 53% (95% CI 27%-78%) and a specificity of 100%, when correlated with the CT. The most common reason for a missed PTX identified on expert-blinded overread was failure to recognize a lung point sign that was present on US. CONCLUSIONS: Thoracic POCUS accurately identifies the majority of clinically significant PTXs in both blunt and penetrating trauma patients. Common themes for false-negative thoracic US in the expert-blinded overread process identified key gaps in training to inspire US education and medical education research.

Retrospective Review of Multitarget Stool DNA as a Screening Test for Colorectal Cancer.

OBJECTIVES: To review the effectiveness of noninvasive multitarget stool DNA testing as a screening test for colorectal cancer. METHODS: We performed a retrospective review of patients referred to 2 high volume outpatient procedural centers for colonoscopy for positive Cologuard test. Positive findings for colorectal cancer based on pathologic findings and also advanced adenomas were recorded. Positive predictive value (PPV) was assessed. RESULTS: Of the 1585 patients evaluated and referred for colonoscopy from January 1, 2018 to November 1, 2019, for ICD-10 codes R19.5 (other fecal abnormalities) and K92.1 (melena), 84 were referred for a positive Cologuard test. Out of the 84, 6 were excluded based on family history of colon cancer in first degree relative or personal history of inflammatory bowel disease. Of the remaining 78 patients, 1 patient (1.3%) had colorectal cancer and 5 (6.4%) had advanced adenomas (>1 cm size, high grade dysplasia or villous). Postive predictive value for colorectal cancer was 1.3% and for precancerous lesions plus colorectal cancer was 7.7%. A total of 53 (68.0%) patients had either totally normal colonoscopy or hyperplastic polyps. Out of the 78 individuals in our study, 70 (89.7%) had normal findings, hyperplastic polyps, or non-advanced adenomas. CONCLUSIONS: Multitarget stool DNA testing carries an unacceptably low PPV to be utilized as a screening test for colorectal cancer. The study fails to detect both adenomas and colon cancer at a higher rate than screening colonoscopy in selected studies. The advantage of being noninvasive has been noted to increase colorectal cancer screening in otherwise non-compliant Medicare patients.

A Quick Reference Guide for Incidental Findings on Lung Cancer Screening CT Examinations.

PURPOSE: The US Preventive Services Task Force has recommended lung cancer screening (LCS) with low-dose CT (LDCT) in high-risk individuals since 2013. Because LDCT encompasses the lower neck, chest, and upper abdomen, many incidental findings (IFs) are detected. The authors created a quick reference guide to describe common IFs in LCS to assist LCS program navigators and ordering providers in managing the care continuum in LCS. METHODS: The ACR IF white papers were reviewed for findings on LDCT that were age appropriate for LCS. A draft guide was created on the basis of recommendations in the IF white papers, the medical literature, and input from subspecialty content experts. The draft was piloted with LCS program navigators recruited through contacts by the ACR LCS Steering Committee. The navigators completed a survey on overall usefulness, clarity, adequacy of content, and user experience with the guide. RESULTS: Seven anatomic regions including 15 discrete organs with 45 management recommendations were identified as relevant to the age of individuals eligible for LCS. The draft was piloted by 49 LCS program navigators from 32 facilities. The guide was rated as useful and clear by 95% of users. No unexpected or adverse experiences were reported in using the guide. On the basis of feedback, relevant sections were reviewed and edited. CONCLUSIONS: The ACR Lung Cancer Screening CT Incidental Findings Quick Reference Guide outlines the common IFs in LCS and can serve as an easy-to-use resource for ordering providers and LCS program navigators to help guide management.

Distinguishing among HCO 3- , CO 3= , and H + as Substrates of Proteins That Appear To Be "Bicarbonate" Transporters.

BACKGROUND: Differentiating among HCO 3- , CO 3= , and H + movements across membranes has long seemed impossible. We now seek to discriminate unambiguously among three alternate mechanisms: the inward flux of 2 HCO 3- (mechanism 1), the inward flux of 1 CO 3= (mechanism 2), and the CO 2 /HCO 3- -stimulated outward flux of 2 H + (mechanism 3). METHODS: As a test case, we use electrophysiology and heterologous expression in Xenopus oocytes to examine SLC4 family members that appear to transport "bicarbonate" ("HCO 3- "). RESULTS: First, we note that cell-surface carbonic anhydrase should catalyze the forward reaction CO 2 +OH - →HCO 3- if HCO 3- is the substrate; if it is not, the reverse reaction should occur. Monitoring changes in cell-surface pH ( Δ pH S ) with or without cell-surface carbonic anhydrase, we find that the presumed Cl-"HCO 3 " exchanger AE1 (SLC4A1) does indeed transport HCO 3- (mechanism 1) as long supposed, whereas the electrogenic Na/"HCO 3 " cotransporter NBCe1 (SLC4A4) and the electroneutral Na + -driven Cl-"HCO 3 " exchanger NDCBE (SLC4A8) do not. Second, we use mathematical simulations to show that each of the three mechanisms generates unique quantities of H + at the cell surface (measured as Δ pH S ) per charge transported (measured as change in membrane current, ΔIm ). Calibrating ΔpH S /Δ Im in oocytes expressing the H + channel H V 1, we find that our NBCe1 data align closely with predictions of CO 3= transport (mechanism 2), while ruling out HCO 3- (mechanism 1) and CO 2 /HCO 3- -stimulated H + transport (mechanism 3). CONCLUSIONS: Our surface chemistry approach makes it possible for the first time to distinguish among HCO 3- , CO 3= , and H + fluxes, thereby providing insight into molecular actions of clinically relevant acid-base transporters and carbonic-anhydrase inhibitors.

Minimal Aortic Injury Detected on Computed Tomography Angiography during Initial Trauma Imaging: Single Academic Level 1 Trauma Center Experience.

BACKGROUND: Minimal aortic injury (MAI), a subtype of acute traumatic aortic injury, is being increasingly recognized with better imaging techniques. Given conservative management, the role of follow-up imaging albeit important yet has to be defined. METHODS: All trauma chest computed tomography angiographies (CTAs) at our center between January 2012 and January 2019 were retrospectively reviewed for presence of MAI. MAIs were generally reimaged at 24 to 72 hours and then at a 7- and 30-day interval. Follow-up CTAs were reviewed for stability, progression, or resolution of MAI, along with assessment of injury severity scores (ISS) and concomitant injuries, respectively. RESULTS: A total of 17,569 chest CTAs were performed over this period. Incidence of MAI on the initial chest CTA was 113 (0.65%), with 105 patients receiving follow-up CTAs. The first, second, third, and fourth follow-up CTAs were performed at a median of 2, 10, 28, and 261 days, respectively. Forty five (42.9%), 22 (21%), 5 (4.8%), and 1 (1%) of the MAIs were resolved by first, second, third, and fourth follow-up CTAs. Altogether, 21 patients showed stability (mean ISS of 16.6), and 11 demonstrated improvement (mean ISS 25.8) of MAIs. Eight patients had no follow-up CTA (mean ISS 21). No progression to higher-grade injury was observed. Advancing age decreased the odds of MAI resolution on follow-up. A possible trend (p-value 0.22) between increasing ISS and time to resolution of MAIs was noted. CONCLUSION: In our series of acute traumatic MAIs diagnosed on CTA imaging, there was no progression of injuries with conservative management, questioning the necessity of sequential follow-up imaging.

Corneal dystrophy mutations R125H and R804H disable SLC4A11 by altering the extracellular pH dependence of the intracellular pK that governs H+(OH-) transport.

Mutations in the H+(OH-) conductor SLC4A11 result in corneal endothelial dystrophy. In previous studies using mouse Slc4a11, we showed that the pK value that governs the intracellular pH dependence of SLC4A11 (pKi) is influenced by extracellular pH (pHe). We also showed that some mutations result in acidic or alkaline shifts in pKi, indicating that the pH dependence of SLC4A11 is important for physiological function. An R125H mutant, located in the cytosolic amino terminus of SLC4A11, apparently causes a complete loss of function, yet the anion transport inhibitor 4,4'-diisothiocyano-2,2'-stilbenedisulfonic acid (DIDS) can partially rescue SLC4A11/R125H activity. In the present study we set out to determine whether the effect of R125H is explained by an extreme shift in pKi. In Xenopus oocytes, we measured SLC4A11-mediated H+(OH-) conductance while monitoring pHi. We find that 1) the human corneal variant SLC4A11-B has a more acidic pKi than mouse Slc4a11, likely due to the presence of an NH2-terminal appendage; 2) pKi for human SLC4A11 is acid-shifted by raising pHe to 10.00; and 3) R125H and R804H mutants mediate substantial H+(OH-) conductances at pHe = 10.00, with pKi shifted into the wild-type range. These data suggest that the defect in each is a shift in pKi at physiological pHe, brought about by a disconnection in the mechanisms by which pHe influences pKi. Using de novo modeling, we show that R125 is located at the cytosolic dimer interface and suggest that this interface is critical for relaying the influence of pHe on the external face of the transmembrane domain to the intracellular, pKi-determining regions.

Pulmonary barotrauma in COVID-19: A systematic review and meta-analysis.

BACKGROUND: An ever-increasing number of studies have reported an increased incidence of spontaneous pulmonary barotrauma such as pneumothorax, pneumomediastinum, and subcutaneous emphysema in patients with COVID-19. We conducted this systematic review and meta-analysis to assess the value and significance of the available data. METHODS: A thorough systematic search was conducted to identify studies of barotrauma in hospitalized patients with COVID-19. Data analysis of case reports was done using a statistical package for the social sciences (SPSS) version 22, and meta-analysis was performed using CMA-3. RESULTS: We identified a total of 4488 studies after thorough database searching.118 case reports and series, and 15 observational studies were included in the qualitative analysis. Fifteen studies were included in the quantitative analysis. The observational studies reported barotrauma in 4.2% (2.4-7.3%) among hospitalized patients; 15.6% (11-21.8%) among critically ill patients; and 18.4% (13-25.3%) in patients receiving invasive mechanical ventilation, showing a linear relationship of barotrauma with the severity of the disease. In addition, barotrauma was associated with a longer length of hospital stay, more extended ICU stay, and higher in-hospital mortality. Also, a slightly higher odds of barotrauma was seen in COVID-19 ARDS compared with non-COVID-19 ARDS. CONCLUSION: COVID-19 pneumonia is associated with a higher incidence of barotrauma. It presents unique challenges for invasive and non-invasive ventilation management. Further studies are required to unravel the underlying pathophysiology and develop safer management strategies.

The molecular identity of the characean OH- transporter: a candidate related to the SLC4 family of animal pH regulators.

Characeae are closely related to the ancient algal ancestors of all land plants. The long characean cells display a pH banding pattern to facilitate inorganic carbon import in the acid zones for photosynthetic efficiency. The excess OH-, generated in the cytoplasm after CO2 is taken into the chloroplasts, is disposed of in the alkaline band. To identify the transporter responsible, we searched the Chara australis transcriptome for homologues of mouse Slc4a11, which functions as OH-/H+ transporter. We found a single Slc4-like sequence CL5060.2 (named CaSLOT). When CaSLOT was expressed in Xenopus oocytes, an increase in membrane conductance and hyperpolarization of resting potential difference (PD) was observed with external pH increase to 9.5. These features recall the behavior of Slc4a11 in oocytes and are consistent with the action of a pH-dependent OH-/H+ conductance. The large scatter in the data might reflect intrinsic variability of CaSLOT transporter activation, inefficient expression in the oocyte due to evolutionary distance between ancient algae and frogs, or absence of putative activating factor present in Chara cytoplasm. CaSLOT homologues were found in chlorophyte and charophyte algae, but surprisingly not in related charophytes Zygnematophyceae or Coleochaetophyceae.

Revisiting the Role of Ser982 Phosphorylation in Stoichiometry Shift of the Electrogenic Na+/qHCO3- Cotransporter NBCe1.

In most cell types and heterologous expression systems, the electrogenic sodium-bicarbonate cotransporter NBCe1 operates with a 1Na+-2HCO3- stoichiometry that, given typical transmembrane electrochemical gradients, promotes Na+ and HCO3- influx. However, NBCe1 in the kidney mediates HCO3- efflux (HCO3- reabsorption), a direction that has been predicted to be favored only if NBCe1 operates with a 1:3 stoichiometry. The phosphorylation state of Ser982 in the cytosolic carboxy-terminal domain of NBCe1 has been reported to be a key determinant of the transporter stoichiometry, with non-phosphorylated Ser982 favoring a 1:3 stoichiometry. Conversely, phosphoproteomic data from renal cortical preparations have revealed the presence of NBCe1 peptides including phosphoserine982 (pSer982) and/or pSer985 although it was not known what proportion of NBCe1 molecules were phosphorylated. In the present study, we report the generation, characterization, and application of a novel phosphospecific antibody raised against NBCe1/pSer982 and show that, contrary to expectations, Ser982 is more prevalently phosphorylated in murine kidneys (in which NBCe1 mediates HCO3- efflux) than in murine colons (in which NBCe1 mediates HCO3- influx). Using phosphomimetic mutants of murine NBCe1 expressed in Xenopus oocytes, we found no evidence that the phosphorylation state of Ser982 or Ser985 alone influences the transport stoichiometry or conductance. Furthermore, we found that the phosphorylation of NBCe1/Ser982 is enhanced in murine kidneys following a 24 h induction of metabolic acidosis. We conclude that the phosphorylation status of Ser982 is not a key determinant of NBCe1 stoichiometry but correlates with presumed NBCe1 activity.

Flower lose, a cell fitness marker, predicts COVID-19 prognosis.

Risk stratification of COVID-19 patients is essential for pandemic management. Changes in the cell fitness marker, hFwe-Lose, can precede the host immune response to infection, potentially making such a biomarker an earlier triage tool. Here, we evaluate whether hFwe-Lose gene expression can outperform conventional methods in predicting outcomes (e.g., death and hospitalization) in COVID-19 patients. We performed a post-mortem examination of infected lung tissue in deceased COVID-19 patients to determine hFwe-Lose's biological role in acute lung injury. We then performed an observational study (n = 283) to evaluate whether hFwe-Lose expression (in nasopharyngeal samples) could accurately predict hospitalization or death in COVID-19 patients. In COVID-19 patients with acute lung injury, hFwe-Lose is highly expressed in the lower respiratory tract and is co-localized to areas of cell death. In patients presenting in the early phase of COVID-19 illness, hFwe-Lose expression accurately predicts subsequent hospitalization or death with positive predictive values of 87.8-100% and a negative predictive value of 64.1-93.2%. hFwe-Lose outperforms conventional inflammatory biomarkers and patient age and comorbidities, with an area under the receiver operating characteristic curve (AUROC) 0.93-0.97 in predicting hospitalization/death. Specifically, this is significantly higher than the prognostic value of combining biomarkers (serum ferritin, D-dimer, C-reactive protein, and neutrophil-lymphocyte ratio), patient age and comorbidities (AUROC of 0.67-0.92). The cell fitness marker, hFwe-Lose, accurately predicts outcomes in COVID-19 patients. This finding demonstrates how tissue fitness pathways dictate the response to infection and disease and their utility in managing the current COVID-19 pandemic.

Kidney physiology and pathophysiology during heat stress and the modification by exercise, dehydration, heat acclimation and aging.

The kidneys' integrative responses to heat stress aid thermoregulation, cardiovascular control, and water and electrolyte regulation. Recent evidence suggests the kidneys are at increased risk of pathological events during heat stress, namely acute kidney injury (AKI), and that this risk is compounded by dehydration and exercise. This heat stress related AKI is believed to contribute to the epidemic of chronic kidney disease (CKD) occurring in occupational settings. It is estimated that AKI and CKD affect upwards of 45 million individuals in the global workforce. Water and electrolyte disturbances and AKI, both of which are representative of kidney-related pathology, are the two leading causes of hospitalizations during heat waves in older adults. Structural and physiological alterations in aging kidneys likely contribute to this increased risk. With this background, this comprehensive narrative review will provide the first aggregation of research into the integrative physiological response of the kidneys to heat stress. While the focus of this review is on the human kidneys, we will utilize both human and animal data to describe these responses to passive and exercise heat stress, and how they are altered with heat acclimation. Additionally, we will discuss recent studies that indicate an increased risk of AKI due to exercise in the heat. Lastly, we will introduce the emerging public health crisis of older adults during extreme heat events and how the aging kidneys may be more susceptible to injury during heat stress.

The therapeutic importance of acid-base balance.

Baking soda and vinegar have been used as home remedies for generations and today we are only a mouse-click away from claims that baking soda, lemon juice, and apple cider vinegar are miracles cures for everything from cancer to COVID-19. Despite these specious claims, the therapeutic value of controlling acid-base balance is indisputable and is the basis of Food and Drug Administration-approved treatments for constipation, epilepsy, metabolic acidosis, and peptic ulcers. In this narrative review, we present evidence in support of the current and potential therapeutic value of countering local and systemic acid-base imbalances, several of which do in fact involve the administration of baking soda (sodium bicarbonate). Furthermore, we discuss the side effects of pharmaceuticals on acid-base balance as well as the influence of acid-base status on the pharmacokinetic properties of drugs. Our review considers all major organ systems as well as information relevant to several clinical specialties such as anesthesiology, infectious disease, oncology, dentistry, and surgery.