Hypernatremia in Hyperglycemia: Clinical Features and Relationship to Fractional Changes in Body Water and Monovalent Cations during Its Development.

In hyperglycemia, the serum sodium concentration ([Na]S) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na]S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na]S, which results in a [Na]S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ([Glu]S) and [Na]S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu]S and [Na]S, those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

Abiraterone-Associated Mineralocorticoid Excess: A Case Report.

Abiraterone acetate causes an adrenocorticotropic hormone (ACTH)-mediated mineralocorticoid excess. We present a 77-year-old man with prostate adenocarcinoma who developed signs and symptoms of mineralocorticoid excess while on abiraterone and discuss its pathophysiology and treatment options. The patient developed hypokalemia, metabolic alkalosis, and hypertension, indicative of increased mineralocorticoid activity, confirmed by elevated ACTH, corticosterone, and deoxycorticosterone levels. Abiraterone inhibits cytochrome P450c17 (CYP17A1), thus inhibiting testosterone and cortisol synthesis. Diminished cortisol synthesis, in turn, leads to excessive mineralocorticoid precursor production mediated by ACTH, leading to enhanced sodium absorption and potassium excretion. Abiraterone is often prescribed with low-dose prednisone to suppress ACTH; however, this strategy may not provide physiological glucocorticoid levels, resulting in ACTH-mediated mineralocorticoid excess in some patients. High-dose steroids or mineralocorticoid antagonists may activate mutant androgen receptors in prostate cancer tissue; therefore, amiloride is suggested for managing residual mineralocorticoid activity. This case highlights the importance of being vigilant for the signs and symptoms of mineralocorticoid excess in patients on abiraterone.

Continuous manufacturing of highly stable lead halide perovskite nanocrystals via a dual-reactor strategy.

Lead halide perovskite nanocrystals possess incredible potential as next generation emitters due to their stellar set of optoelectronic properties. Unfortunately, their instability towards many ambient conditions and reliance on batch processing hinder their widespread utilities. Herein, we address both challenges by continuously synthesizing highly stable perovskite nanocrystals via integrating star-like block copolymer nanoreactors into a house-built flow reactor. Perovskite nanocrystals manufactured in this strategy display significantly enhanced colloidal, UV, and thermal stabilities over those synthesized with conventional ligands. Such scaling up of highly stable perovskite nanocrystals represents an important step towards their eventual use in many practical applications in optoelectronic materials and devices.

The onset of rare earth metallosis begins with renal gadolinium-rich nanoparticles from magnetic resonance imaging contrast agent exposure.

The leitmotifs of magnetic resonance imaging (MRI) contrast agent-induced complications range from acute kidney injury, symptoms associated with gadolinium exposure (SAGE)/gadolinium deposition disease, potentially fatal gadolinium encephalopathy, and irreversible systemic fibrosis. Gadolinium is the active ingredient of these contrast agents, a non-physiologic lanthanide metal. The mechanisms of MRI contrast agent-induced diseases are unknown. Mice were treated with a MRI contrast agent. Human kidney tissues from contrast-naïve and MRI contrast agent-treated patients were obtained and analyzed. Kidneys (human and mouse) were assessed with transmission electron microscopy and scanning transmission electron microscopy with X-ray energy-dispersive spectroscopy. MRI contrast agent treatment resulted in unilamellar vesicles and mitochondriopathy in renal epithelium. Electron-dense intracellular precipitates and the outer rim of lipid droplets were rich in gadolinium and phosphorus. We conclude that MRI contrast agents are not physiologically inert. The long-term safety of these synthetic metal-ligand complexes, especially with repeated use, should be studied further.

Hypertonic Saline Infusion for Hyponatremia: Limitations of the Adrogué-Madias and Other Formulas.

Hypertonic saline infusion is used to correct hyponatremia with severe symptoms. The selection of the volume of infused hypertonic saline ( VInf ) should address prevention of overcorrection or undercorrection. Several formulas computing this VInf have been proposed. The limitations common to these formulas consist of (1) failure to include potential determinants of change in serum sodium concentration ([ Na ]) including exchanges between osmotically active and inactive sodium compartments, changes in hydrogen binding of body water to hydrophilic compounds, and genetic influences and (2) inaccurate estimates of baseline body water entered in any formula and of gains or losses of water, sodium, and potassium during treatment entered in formulas that account for such gains or losses. In addition, computing VInf from the Adrogué-Madias formula by a calculation assuming a linear relation between VInf and increase in [ Na ] is a source of errors because the relation between these two variables was proven to be curvilinear. However, these errors were shown to be negligible by a comparison of estimates of VInf by the Adrogué-Madias formula and by a formula using the same determinants of the change in [ Na ] and the curvilinear relation between this change and VInf . Regardless of the method used to correct hyponatremia, monitoring [ Na ] and changes in external balances of water, sodium, and potassium during treatment remain imperative.

Effect of vaccination on the case fatality rate for COVID-19 infections 2020-2021: multivariate modelling of data from the US Department of Veterans Affairs.

OBJECTIVES: To evaluate the benefits of vaccination on the case fatality rate (CFR) for COVID-19 infections. DESIGN, SETTING AND PARTICIPANTS: The US Department of Veterans Affairs has 130 medical centres. We created multivariate models from these data-339 772 patients with COVID-19-as of 30 September 2021. OUTCOME MEASURES: The primary outcome for all models was death within 60 days of the diagnosis. Logistic regression was used to derive adjusted ORs for vaccination and infection with Delta versus earlier variants. Models were adjusted for confounding factors, including demographics, comorbidity indices and novel parameters representing prior diagnoses, vital signs/baseline laboratory tests and outpatient treatments. Patients with a Delta infection were divided into eight cohorts based on the time from vaccination to diagnosis. A common model was used to estimate the odds of death associated with vaccination for each cohort relative to that of unvaccinated patients. RESULTS: 9.1% of subjects were vaccinated. 21.5% had the Delta variant. 18 120 patients (5.33%) died within 60 days of their diagnoses. The adjusted OR for a Delta infection was 1.87±0.05, which corresponds to a relative risk (RR) of 1.78. The overall adjusted OR for prior vaccination was 0.280±0.011 corresponding to an RR of 0.291. Raw CFR rose steadily after 10-14 weeks. The OR for vaccination remained stable for 10-34 weeks. CONCLUSIONS: Our CFR model controls for the severity of confounding factors and priority of vaccination, rather than solely using the presence of comorbidities. Our results confirm that Delta was more lethal than earlier variants and that vaccination is an effective means of preventing death. After adjusting for major selection biases, we found no evidence that the benefits of vaccination on CFR declined over 34 weeks. We suggest that this model can be used to evaluate vaccines designed for emerging variants.

Gadolinium Deposition Disease: A Case Report and the Prevalence of Enhanced MRI Procedures Within the Veterans Health Administration.

Background: Gadolinium (Gd) usage in the Veterans Health Administration is increasing and patients with renal disease are frequently exposed. Gd is not entirely eliminated within 24 hours after administration, which may pose long-term adverse effects. Case Presentation: A Vietnam-era veteran aged > 70 years presented for evaluation of Gd-based contrast agent-induced chronic multisymptom illness. In the course of his routine clinical care, he was exposed to repeated Gd-enhanced magnetic resonance imaging studies. After his second Gd-based contrast agent exposure, he noted rash, pain, headaches, and hoarseness. Years after the exposure to the contrast agents, he continued to have detectable Gd in urine and serum. Conclusions: Practitioners should be aware of long-term intracellular Gd retention (including the brain) as patients increasingly turn to consultants with concerns about Gd deposition disease. Data from patient advocates demonstrate that Gd is eliminated in intermediate and long phases, which may represent a multicompartment model. The commercialization of Gd use in imaging studies is outpacing the science addressing the long-term consequences of harboring this alien, toxic, nonphysiologic rare earth metal.

Dysnatremia in Gastrointestinal Disorders.

The primary solute of the milieu intérieur is sodium and accompanying anions. The solvent is water. The kidneys acutely regulate homeostasis in filtration, secretion, and resorption of electrolytes, non-electrolytes, and minerals while balancing water retention and clearance. The gastrointestinal absorptive and secretory functions enable food digestion and water absorption needed to sustain life. Gastrointestinal perturbations including vomiting and diarrhea can lead to significant volume and electrolyte losses, overwhelming the renal homeostatic compensatory mechanisms. Dysnatremia, potassium and acid-base disturbances can result from gastrointestinal pathophysiologic processes. Understanding the renal and gastrointestinal contributions to homeostatis are important for the clinical evaluation of perturbed volume disturbances.

FASCIOLOIDES MAGNA IN FREE-RANGING ROCKY MOUNTAIN BIGHORN SHEEP (OVIS CANADENSIS).

From February to May 2021, four nonmigratory rams from the Radium-Stoddart bighorn sheep (BHS; Ovis canadensis) herd in the Rocky Mountains of southeastern British Columbia, Canada, died from infection with the giant liver fluke, Fascioloides magna. Affected animals were emaciated, weak, and lethargic or were found dead. Gross lesions, histopathology, and parasite burdens were consistent with those reported in experimentally infected BHS, domestic sheep, and other aberrant hosts. Although BHS range does not typically overlap with fluke-contaminated aquatic habitats, the change in migratory behavior recently observed in some Radium-Stoddart rams may have exposed the affected animals to F. magna. We describe clinical signs and gross and histopathologic findings of hepatobiliary trematodiasis associated with F. magna in free-ranging BHS. From experimental data and our findings, giant liver fluke is pathogenic and is a threat to the conservation of the Radium-Stoddart BHS herd and other BHS herds in endemic F. magna regions.

The ABR 2021 Radiation Oncology Remote Examinations: Development, Administration, and Implications for the Future.

With the onset of the global coronavirus disease 2019 pandemic in early 2020, it became apparent that routine administration of the ABR Qualifying and Certifying Exams would be disrupted. Initial intent for postponement was later altered to a recognition that replacement of the existing delivery methodologies was essential. Herein, the authors describe the conceptualization, development, administration, and future implications of the new remote examination delivery platforms.

Host and geographic differences in prevalence and diversity of gastrointestinal helminths of foxes (Vulpes vulpes), coyotes (Canis latrans) and wolves (Canis lupus) in Québec, Canada.

Wild canids are hosts to a wide range of parasites and can play a role in transmission of zoonoses. As many parasites are transmitted through food webs, and wild canids are at high trophic levels, parasite prevalence and diversity in wild canids can serve as excellent indicators of ecosystem health. Our main objectives were to update knowledge on the composition of gastrointestinal helminths in wild canids from Québec, Canada, and to describe differences in parasite prevalence and diversity among canid species and regions. Hunters and trappers provided whole carcasses of red foxes (Vulpes vulpes) (N = 176), and intestinal tracts of coyotes (Canis latrans) (N = 77) and gray wolves (Canis lupus) (N = 23) harvested for non-research purposes over the winter of 2016-2017. A modified Stoll's centrifugation sucrose flotation on feces of 250 wild canids was used, and eggs of one family and eight genera of parasitic helminths were recovered: diphyllobothriids, Taenia/Echinococcus spp., Capillaria spp., Toxascaris sp., Toxocara sp., Trichuris sp., Uncinaria sp., and Metorchis sp. Adult Taenia spp. cestodes were recovered from 61 of 276 (22%) canids. Six different species (T. hydatigena, T. twitchelli, T. crassiceps, T. polyacantha, T. krabbei, and T. pisiformis-"like") were differentiated based on DNA sequenced from 65 individual adult cestodes using primers for the nicotinamide adenosine dinucleotide dehydrogenase subunit 1 (ND1) and cytochrome c oxidase subunit 1 (CO1) mitochondrial DNA loci. Alaria sp. trematodes infected 89 of 276 canids (32%). A subset were identified as A. americana at the CO1 locus. The marine trematode Cryptocotyle lingua was reported for the first time in foxes in the province of Québec. These results help us understand more fully the predator-prey relationships within this group of canids. This baseline data in regional parasite prevalence and intensity is critical in order to detect future changes following ecological disturbances due to climate and landscape alterations.

Continuous production of ultrathin organic-inorganic Ruddlesden-Popper perovskite nanoplatelets via a flow reactor.

Because of their enhanced quantum confinement, colloidal two-dimensional Ruddlesden-Popper (RP) perovskite nanosheets with a general formula L2[ABX3]n-1BX4 stand as a promising narrow-wavelength blue-emitting nanomaterial. Despite ample studies on batch synthesis, for RP perovskites to be broadly applied, continuous synthetic routes are needed. Herein, we design and optimize a flow reactor to continuously produce high-quality n = 1 RP perovskite nanoplatelets. The effects of antisolvent composition, reactor tube length, precursor solution injection rate, and antisolvent injection rate on the morphology and optical properties of the nanoplatelets are systematically examined. Our investigation suggests that flow reactors can be employed to synthesize high-quality L2PbX4 perovskite nanoplatelets (i.e., n = 1) at rates greater than 8 times that of batch synthesis. Mass-produced perovskite nanoplatelets promise a variety of potential applications in optoelectronics, including light emitting diodes, photodetectors, and solar cells.

Copro-polymerase chain reaction has higher sensitivity compared to centrifugal fecal flotation in the diagnosis of taeniid cestodes, especially Echinococcus spp, in canids.

Prompt and reliable diagnostic tests for taeniid infection in canids are important due to the risk of zoonoses like Echinococcus spp. Current diagnostic methods relying on fecal flotation lack sensitivity and specificity, but this has rarely been quantified due to the challenges in performing adult cestode recovery (the gold standard) in domestic dogs (Canis familiaris). Therefore, we recovered adult Taenia and Echinococcus spp. from intestines, as well as fecal/intestinal material from 484 wild canids trapped for fur in two Canadian provinces (276 foxes - primarily Vulpes vulpes, coyotes - Canis latrans, and wolves - Canis lupus in Québec and 208 coyotes in Saskatchewan). The performances of a newly developed coproPCR for tapeworm DNA detection in dogs, and centrifugal fecal flotation using Sheather's solution, were evaluated against adult cestode recovery. Overall, adult taeniid cestode prevalence (Taenia and/or Echinococcus) was 28 % (95 % CI: 23-33 %) in Québec (62 % (CI: 51-73%) of 74 coyotes, 65 % (CI: 44-82) of 23 wolves, and 11 % (CI: 7-16%) of 179 foxes) and 79 % (CI: 73-84%) of 208 coyotes in Saskatchewan. In Québec, E. canadensis and Taenia spp. were detected in coyotes and wolves, and foxes were only infected with Taenia spp., whereas Saskatchewan coyotes were predominantly infected with E. multilocularis (at significantly higher prevalence, but not intensity, than coyotes in Québec). Compared with centrifugal fecal flotation, the new coproPCR had at least double the sensitivity (58 % vs 23 % in QC coyotes, 57 % vs 23 % in QC wolves, 24 % vs 0% in QC foxes, and 80 % vs 25 % in SK coyotes). Notably, no taeniid eggs were detected on flotations from foxes infected with Taenia spp., and the new coproPCR had highest sensitivity in Saskatchewan coyotes, which were predominantly infected with E. multilocularis. CoproPCR has promising prospects for use in Veterinary clinics and diagnostic laboratories to detect taeniid cestode infections because of its higher sensitivity than faecal flotation methods. This is particularly important for zoonotic Echinococcus spp. where, from a public health perspective, false negatives are a much greater concern than false positives.

Overlapping roles of NADPH oxidase 4 for diabetic and gadolinium-based contrast agent-induced systemic fibrosis.

Dozens of millions of people are exposed to gadolinium-based contrast agents annually for enhanced magnetic resonance imaging. Gadolinium-based contrast agents are known nephrotoxins and can trigger the potentially fatal condition of systemic fibrosis. Risk factors are practically entirely undefined. We examined the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Age- and weight-matched mice were randomized to experimental diabetes (streptozotocin) and control groups followed by systemic gadolinium-based contrast agent treatment. Nox4-deficient mice were randomized to experimental diabetes and gadolinium-based contrast agent treatment. Skin fibrosis and cellular infiltration were apparent in both gadolinium-based contrast agent-treated and experimental diabetes groups. Similarly, both groups demonstrated renal pathologies with evidence of reactive oxygen species generation. Deletion of Nox4 abrogated both skin and renal pathology, whether from diabetes or gadolinium-based contrast agent treatment. These discoveries demonstrate the importance of Nox4 in gadolinium-based contrast agent- and diabetes-induced fibrosis.NEW & NOTEWORTHY A mouse model of gadolinium-based contrast agent- and diabetes-induced fibrosis was used to demonstrate the role of NADPH oxidase 4 (Nox4) in gadolinium-induced systemic disease. Using these models, we established the role of Nox4 as a mediator of reactive oxygen species generation and subsequent skin and kidney fibrosis. These novel findings have defined Nox-4-mediated mechanisms by which gadolinium-based contrast agents induce systemic diseases.

Rosuvastatin-Induced Rhabdomyolysis, Pancreatitis, Transaminitis, and Acute Kidney Injury.

Changing medications within a drug class requires considering the indication and dosage, possible adverse effects, and drug-drug interactions.

Hiding in plain sight: discovery and phylogeography of a cryptic species of Trichinella (Nematoda: Trichinellidae) in wolverine (Gulo gulo).

Understanding parasite diversity and distribution is essential in managing the potential impact of parasitic diseases in animals and people. Imperfect diagnostic methods, however, may conceal cryptic species. Here, we report the discovery and phylogeography of a previously unrecognized species of Trichinella in wolverine (Gulo gulo) from northwestern Canada that was indistinguishable from T. nativa using the standard multiplex PCR assay based on the expansion segment 5 (ESV) of ribosomal DNA. The novel genotype, designated as T13, was discovered when sequencing the mitochondrial genome. Phylogenetic analyses of the mitochondrial genome and of 15 concatenated single copy orthologs of nuclear DNA indicated a common ancestor for the encapsulated clade is shared by a subclade containing Trichinella spiralis and Trichinella nelsoni, and a subclade containing T13 and remaining taxa: T12 + (T2 + T6) + [(T5 + T9) + (T3 + T8)]. Of 95 individual hosts from 12 species of mammalian carnivores from northwestern Canada from which larvae were identified as T. nativa on multiplex PCR, only wolverines were infected with T13 (14 of 42 individuals). These infections were single or mixed with T. nativa and/or T6. Visual examination and motility testing confirmed that T13 is encapsulated and likely freeze-tolerant. We developed a new Polymerase Chain Reaction-Restriction Fragment Length Polymorphism which unequivocally distinguishes between T13 and T. nativa. We propose Trichinella chanchalensis n. sp. for T13, based on significant genetic divergence from other species of Trichinella and broad-based sampling of the Trichinella genome. Exploration of Alaskan and Siberian isolates may contribute to further resolution of a phylogeographically complex history for species of Trichinella across Beringia, including Trichinella chanchalensis n. sp. (T13).

Not playing by the rules: Unusual patterns in the epidemiology of parasites in a natural population of feral horses (Equus caballus) on Sable Island, Canada.

Sable Island, Nova Scotia, Canada hosts one of few natural populations of feral horses (Equus caballus) never exposed to anthelmintics. Coproculture revealed cyathostomes, Strongylus equinus, S. edentatus, and S. vulgaris, with S. equinus (unusually) dominating in adult horses and cyathostomes dominating in young horses (<3 years of age). We examined 35 horses found dead in the springs of 2017 and 2018, as well as fecal samples from live horses in spring (n = 45) and summer 2018 (n = 236) using McMaster fecal flotation and Baermann larval sedimentation on fresh samples, and modified Wisconsin flotation and sucrose gradient immunofluorescent assay for Giardia and Cryptosporidium on frozen samples. Mean strongyle fecal egg counts were 666 eggs per gram (EPG) in dead horses, 689 EPG in live horses in spring, and 1105 EPG in summer; domestic horses are usually treated at counts exceeding 200 EPG. Adult horses (unusually) had patent infections with the lungworm Dictyocaulus arnfieldi and ascarids (Parascaris spp.), and in spring, dead horses had 5 times higher odds of having patent ascarid infections than live horses, likely due to malnutrition and corresponding immunodeficiency. Fecal prevalence and intensity of D. arnfieldi and Parascaris spp. were significantly higher in young horses, and in spring versus summer. A higher proportion of fecal samples were positive for strongyle and ascarid eggs using a centrifugal flotation technique on previously frozen feces, as compared to a passive flotation method on fresh feces. Eggs of the tapeworm Paranoplocephala mamillana were present in fecal samples from 28% of live, and 42% of dead, horses in spring. This research represents several new geographic records (S. edentatus, D. arnfieldi, and Eimeria leuckarti), provides insight into unusual patterns of parasite epidemiology in a nutrition-limited environment, and has conservation and biosecurity implications for this unique equine population, as well as for parasite management in domestic horses.

Dialysis-associated hyperglycemia: manifestations and treatment.

PURPOSE: Dialysis-associated hyperglycemia (DAH), is associated with a distinct fluid and electrolyte pathophysiology. The purpose of this report was to review the pathophysiology and provide treatment guidelines for DAH. METHODS: Review of published reports on DAH. Synthesis of guidelines based on these reports. RESULTS: The following fluid and solute abnormalities have been identified in DAH: (a) hypoglycemia: this is a frequent complication of insulin treatment and its prevention requires special attention. (b) Elevated serum tonicity. The degree of hypertonicity in DAH is lower than in similar levels of hyperglycemia in patients with preserved renal function. Typically, correction of hyperglycemia with insulin corrects the hypertonicity of DAH. (c) Extracellular volume abnormalities ranging from pulmonary edema associated with osmotic fluid shift from the intracellular into the extracellular compartment as a consequence of gain in extracellular solute (glucose) to hypovolemia from osmotic diuresis in patients with residual renal function or from fluid losses through extrarenal routes. Correction of DAH by insulin infusion reverses the osmotic fluid transfer between the intracellular and extracellular compartments and corrects the pulmonary edema, but can worsen the manifestations of hypovolemia, which require saline infusion. (d) A variety of acid-base disorders including ketoacidosis correctable with insulin infusion and no other interventions. (e) Hyperkalemia, which is frequent in DAH and is more severe when ketoacidosis is also present. Insulin infusion corrects the hyperkalemia. Extreme hyperkalemia at presentation or hypokalemia developing during insulin infusion require additional measures. CONCLUSIONS: In DAH, insulin infusion is the primary management strategy and corrects the fluid and electrolyte abnormalities. Patients treated for DAH should be monitored for the development of hypoglycemia or fluid and electrolyte abnormalities that may require additional treatments.