Unfavorable hydroxychloroquine COVID-19 research associated with authors having a history of political party donations.

We explored the degree to which political bias in medicine and study authors could explain the stark variation in Hydroxychloroquine (HCQ)/Chloroquine (CQ) study favorability in the US compared to the rest of the world. COVID-19/SARS-CoV-2 preprint and published papers between January 1, 2020-July 26, 2020 with Hydroxychloroquine and/or Chloroquine; 267 met study criteria, 68 from the US. A control subset was selected. HCQ/CQ study result favorability (favorable, unfavorable, or neutral) was noted. First and last main authors of each US study were entered into FollowTheMoney.org Website, extracting any history of political party donation. Of all US studies (68 total), 39/68 (57.4%) were unfavorable, with only 7/68 (10.3%) of US studies yielding favorable results-compared to 199 non-US studies, 66/199 (33.2%) unfavorable, 69/199 (34.7%) favorable, and 64/199 (32.2%) neutral. Studies with at least one US main author were 20.4% (SE 0.053, P < 0.05) more likely to report unfavorable results than non-US studies. US Studies with at least one main author donating to any political party were 25.6% (SE 0.085, P < 0.01) more likely to have unfavorable results. US studies with at least one author donating to the Democratic party were 20.4% (SE 0.045, P < 0.05) more likely to have unfavorable results. US authors were more likely to publish studies with medically harmful conclusions than non-US authors. Cardiology-specific HCQ/CQ studies were 44.2% more likely to yield harmful conclusions (P < 0.01). Inaccurate propagation of HCQ/CQ cardiac adverse effects with individual scientific author political bias has contributed to unfavorable US HCQ/CQ publication patterns and political polarization of the medications.

Jaundice and Elevated Beta-Human Chorionic Gonadotropin in a Female: Duodenal Choriocarcinoma, Not Pregnancy.

A 29-year-old woman with developmental delay presented with 2.5 weeks of jaundice of the skin with accompanying microcytic anemia (hemoglobin 6.8 g/dL, mean corpuscular volume 70.5 fL), elevated liver enzymes (aspartate aminotransferase 77 U/L, alanine aminotransferase 95 U/L, alkaline phosphatase 362 U/L), total bilirubin (9.5 mg/dL; 4.4 mg/dL direct), lipase (325 U/L), and cancer antigen 19-9 (68 U/mL). The patient had no prior gastrointestinal or liver disease. CT of the chest/abdomen/pelvis found a large lobulated non-fully obstructing mass in the second and third part of the duodenum, with endoscopic biopsies yielding an invasive, well-differentiated adenocarcinoma positive for cytoplasmic-stained cells to antibody to beta-human chorionic gonadotropin (hCG) antigen, suggesting a duodenal choriocarcinoma. Treatment included biliary drainage with a percutaneous transhepatic catheter and folinic acid, fluorouracil, and oxaliplatin (FOLFOX) chemotherapy, but a repeat CT scan five months later revealed an increase in tumor size and invasion; the patient died shortly thereafter. Beta-hCG-secreting choriocarcinomas are rare, rapidly growing, highly invasive malignant tumors and are uncommonly present at extragonadal sites.

Evolution of near-ground optical turbulence over concrete runway throughout multiple days in summer and winter.

Experimental data are presented that demonstrate the evolution of the anisotropy/isotropy of atmospheric statistics throughout the course of four days (two winter, two summer) near the ground over a concrete runway in Florida. In late January and early February of 2017, a 532 nm near-plane-wave beam was propagated 1 and 2 km at a height of 2 m above the runway, and irradiance fluctuations were captured on a CCD array. In August of 2017, a 532 nm Gaussian beam was propagated 100 m at a height of near 2 m, and fluctuation data were captured on a CCD array. Winter data were processed to calculate the covariance of intensity and summer data processed to calculate the scintillation index. The resulting contours indicated a consistent pattern of anisotropy early in the day, evolving into isotropy midday, and returning to anisotropy in late afternoon. Accompanying atmospheric and wind data are presented throughout the measurement days.

Physician Body Mass Index and Bias Toward Obesity Documentation Patterns.

BACKGROUND: Many healthcare professionals consider obese individuals to be unmotivated and to lack the willpower to follow through with weight-loss plans. This attitude may result in less effort put into diagnosing, documenting, and treating obesity. Our aim was to assess documentation patterns of obesity and hypertension overall, by primary care specialty, and in relation to provider body mass index (BMI). METHODS: Twenty-two physicians from one outpatient community practice were included: 10 internal medicine and 12 family practice practitioners. We conducted a retrospective review of medical records from a 1-year period to determine provider documentation of obesity and hypertension. RESULTS: A total of 3,275 obese patients were under the care of 6 physicians with normal BMI, yielding an obesity documentation rate of 23.2%. The 10 overweight physicians had 6,218 obese patients and a documentation rate of 33.5%. The 6 obese physicians had 4,014 patients with obesity and a documentation rate of 21.7%. Obesity documentation rates differed between nonobese physicians (BMI 20-29.9 kg/m2) (30.0%) and obese (BMI ≥30 kg/m2) physicians (21.7%) (P<0.001). We found no difference (P=0.132) between documentation rates of normal-weight BMI physicians and obese physicians. The overall documentation rate of obesity (27.5%) was significantly different than the overall documentation rate of hypertension (83.3%) (P<0.001). CONCLUSION: In our study, nonobese physicians were more likely to document obesity, and documentation of obesity lagged significantly in comparison to hypertension. Addressing weight loss in obese patients starts at the provider level. Steps include documenting obesity on the problem list and providing weight-loss advice during each patient encounter.

Embedded pork bone causing esophageal perforation and an esophagus-innominate artery fistula.

Chronically embedded foreign bodies can lead to perforations, mediastinitis, and abscess, amongst a host of other complications. A 20-year-old mentally challenged female presented with "something stuck in her throat," severe dysphagia, and recurrent vomiting. Initial imaging was unremarkable; however, subsequent imaging and esophagogastroduodenoscopy two weeks later revealed an embedded pork bone. Surgery was performed to remove the bone and fix the subsequent esophageal perforation and esophagus-innominate artery fistula. This case helps reinforce the urgency in removing an ingested foreign body and the ramifications that may arise with chronically embedded foreign bodies.

Reversible voltammograms and a Pourbaix diagram for a protein tyrosine radical.

Reversible voltammograms and a voltammetry half-wave potential versus solution pH diagram are described for a protein tyrosine radical. This work required a de novo designed tyrosine-radical protein displaying a unique combination of structural and electrochemical properties. The α(3)Y protein is structurally stable across a broad pH range. The redox-active tyrosine Y32 resides in a desolvated and well-structured environment. Y32 gives rise to reversible square-wave and differential pulse voltammograms at alkaline pH. The formal potential of the Y32-O(•)/Y32-OH redox couple is determined to 918 ± 2 mV versus the normal hydrogen electrode at pH 8.40 ± 0.01. The observation that Y32 gives rise to fully reversible voltammograms translates into an estimated lifetime of ≥30 ms for the Y32-O(•) state. This illustrates the range of tyrosine-radical stabilization that a structured protein can offer. Y32 gives rise to quasireversible square-wave and differential pulse voltammograms at acidic pH. These voltammograms represent the Y32 species at the upper edge of the quasirevesible range. The square-wave net potential closely approximates the formal potential of the Y32-O(•)/Y32-OH redox couple to 1,070 ± 1 mV versus the normal hydrogen electrode at pH 5.52 ± 0.01. The differential pulse voltammetry half-wave potential of the Y32-O(•)/Y32-OH redox pair is measured between pH 4.7 and 9.0. These results are described and analyzed.

Electrochemical and structural properties of a protein system designed to generate tyrosine Pourbaix diagrams.

This report describes a model protein specifically tailored to electrochemically study the reduction potential of protein tyrosine radicals as a function of pH. The model system is based on the 67-residue α(3)Y three-helix bundle. α(3)Y contains a single buried tyrosine at position 32 and displays structural properties inherent to a protein. The present report presents differential pulse voltammograms obtained from α(3)Y at both acidic (pH 5.6) and alkaline (pH 8.3) conditions. The observed Faradaic response is uniquely associated with Y32, as shown by site-directed mutagenesis. This is the first time voltammetry is successfully applied to detect a redox-active tyrosine residing in a structured protein environment. Tyrosine is a proton-coupled electron-transfer cofactor making voltammetry-based pH titrations a central experimental approach. A second set of experiments was performed to demonstrate that pH-dependent studies can be conducted on the redox-active tyrosine without introducing large-scale structural changes in the protein scaffold. α(3)Y was re-engineered with the specific aim to place the imidazole group of a histidine close to the Y32 phenol ring. α(3)Y-K29H and α(3)Y-K36H each contain a histidine residue whose protonation perturbs the fluorescence of Y32. We show that these variants are stable and well-folded proteins whose helical content, tertiary structure, solution aggregation state, and solvent-sequestered position of Y32 remain pH insensitive across a range of at least 3-4 pH units. These results confirm that the local environment of Y32 can be altered and the resulting radical site studied by voltammetry over a broad pH range without interference from long-range structural effects.

Exploring amino-acid radical chemistry: protein engineering and de novo design.

Amino-acid radical enzymes are often highly complex structures containing multiple protein subunits and cofactors. These properties have in many cases hampered the detailed characterization of their amino-acid redox cofactors. To address this problem, a range of approaches has recently been developed in which a common strategy is to reduce the complexity of the radical-containing system. This work will be reviewed and it includes the light-induced generation of aromatic radicals in small-molecule and peptide systems. Natural redox proteins, including the blue copper protein azurin and a bacterial photosynthetic reaction center, have been engineered to introduce amino-acid radical chemistry. The redesign strategies to achieve this remarkable change in the properties of these proteins will be described. An additional approach to gain insights into the properties of amino-acid radicals is to synthesize de novo designed model proteins in which the redox chemistry of these species can be studied. Here we describe the design, synthesis and characteristics of monomeric three-helix bundle and four-helix bundle proteins designed to study the redox chemistry of tryptophan and tyrosine. This work demonstrates that de novo protein design combined with structural, electrochemical and quantum chemical analyses can provide detailed information on how the protein matrix tunes the thermodynamic properties of tryptophan.