Probing the optical properties and toxicological profile of zinc tungstate nanorods.

Zinc tungstate is a semiconductor known for its favorable photocatalytic, photoluminescence, and scintillation properties, coupled with its relatively low cost, reduced toxicity, and high stability in biological and catalytic environments. In particular, zinc tungstate evinces scintillation properties, namely the ability to emit visible light upon absorption of energetic radiation such as x rays, which has led to applications not only as radiation detectors but also for biomedical applications involving the delivery of optical light to deep tissue, such as photodynamic therapy and optogenetics. Here, we report on the synthesis of zinc tungstate nanorods generated via an optimized but facile method, which allows for synthetic control over the aspect ratio of the as-synthesized anisotropic motifs via rational variation of the solution pH. We investigate the effect of aspect ratio on their resulting photoluminescent and radioluminescent properties. We further demonstrate the potential of these zinc tungstate nanorods for biomedical applications, such as photodynamic therapy for cancer treatment, by analyzing their toxicological profile within cell lines and neurons.

Investigation of the photoluminescent properties, scintillation behaviour and toxicological profile of various magnesium tungstate nanoscale motifs.

We have synthesized several morphologies and crystal structures of MgWO4 using a one-pot hydrothermal method, producing not only monoclinic stars and large nanoparticles but also triclinic wool balls and sub-10 nm nanoparticles. Herein we describe the importance of reaction parameters in demonstrating morphology control of as-prepared MgWO4. Moreover, we correlate structure and composition with the resulting photoluminescence and radioluminescence properties. Specifically, triclinic-phase samples yielded a photoluminescence emission of 421 nm, whereas monoclinic-phase materials gave rise to an emission maximum of 515 nm. The corresponding radioluminescence data were characterized by a broad emission peak, located at 500 nm for all samples. Annealing the wool balls and sub-10 nm particles to transform the crystal structure from a triclinic to a monoclinic phase yielded a radioluminescence (RL) emission signal that was two orders of magnitude greater than that of their unannealed counterparts. Finally, to confirm the practical utility of these materials for biomedical applications, a series of sub-10 nm particles, including as-prepared and annealed samples, were functionalized with biocompatible PEG molecules, and subsequently were found to be readily taken up by various cell lines as well as primary cultured hippocampal neurons with low levels of toxicity, thereby highlighting for the first time the potential of this particular class of metal oxides as viable and readily generated platforms for a range of biomedical applications.

A Tale of Two Twins: Discordant Presentation of COVID-19 in Identical Twins.

Coronavirus disease 2019 (COVID-19) is a highly contagious viral illness caused by the RNA virus Coronaviridae subtype severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Rapid infection caused by this virus became overwhelming and resulted in millions of deaths worldwide. The effects of smoking have been heavily studied and lead to increased occurrence of COVID-19 viral infections and mortality. The phenomenon of cytokine storm has been shown as one of the leading factors of mortality. However, the question remains as to what factors, either genetic or environmental, ultimately lead to the increased incidence of cytokine storms compared to others. We present a case of two cohabitating, 57-year-old, male, identical twins (Twin A and Twin B) who contracted SARS-CoV-2 simultaneously. Both Twin A and Twin B had similar medical histories, except for Twin A being a former smoker while Twin B a current smoker. While both twins presented with cough and shortness of breath, Twin A also presented with hypoxia, leukocytosis, evidence of acute kidney injury, and transaminitis while Twin B presented normoxic with solely tachycardia. Due to his presentation and vital signs, Twin B received Bamlanivimab but developed hypoxia during the infusion. Both twins were subsequently initiated on Remdesivir, dexamethasone, and supplemental oxygen daily. After completion of treatment courses, both twins had improvement in their laboratory values and were subsequently discharged with supplemental oxygen to be further weaned in the outpatient setting. Due to the twins' cohabitation, contracting SARS-CoV-2 simultaneously, and similar medical history, we highlight the potential mechanism of nicotine's chemical ability to blunt the subsequent inflammatory process of COVID-19. Despite nicotine's potential ability to dampen cytokine storms, smoking has well-documented adverse effects and we, like many experts, entirely discourage it. However, given the rare situation of identical twins contracting SARS-CoV-2, we can extrapolate information regarding the effects of the virus without obfuscation from genetic and environmental factors to identify areas of research for new therapies.

Directed mechanisms for apical dendrite development during neuronal polarization.

The development of the dendrite and the axon during neuronal polarization underlies the directed flow of information in the brain. Seminal studies on axon development have dominated the mechanistic analysis of neuronal polarization. These studies, many originating from examinations in cultured hippocampal and cortical neurons in vitro, have established a prevalent view that axon formation precedes and is necessary for neuronal polarization. There is also in vivo evidence supporting this view. Nevertheless, the establishment of bipolar polarity, the leading edge, and apical dendrite development in pyramidal neurons in vivo occur when axon formation is prevented. Furthermore, recent mounting evidence suggest that directed mechanisms might mediate bipolar polarity/leading process and subsequent apical dendrite development. In the presence of spatially directed extracellular cues in the developing brain, these events may operate independently of axon forming events. In this perspective we summarize evidence in support of these evolving views in neuronal polarization and highlight recent findings on dedicated mechanisms acting in apical dendrite development.

New-Onset Heart Failure in the Setting of T4-Conversion Disorder.

Thyroid hormone is essential in accomplishing the appropriate metabolism of the body. Achieving euthyroidism is of importance due to the deadly ramifications of being hypothyroid, such as multiple organ failure, profound decrease in mentation and even death. We present a case of an 80-year-old female with a history of hypertension, coronary artery disease, chronic kidney disease, hypothyroidism due to total thyroidectomy, and a cerebral vascular accident who presented with slurred speech, decreased appetite, dizziness and lethargy with new-onset weakness. She was adherent to all her medications. Her labs were significant for elevated thyroid-stimulating hormone, elevated free thyroxine, and low total triiodothyronine. Brain MRI revealed no acute pathology. She was given her home dose of Levothyroxine and was admitted to the telemetry unit for evaluation of her symptoms and abnormal thyroid panel. During her hospital course, she was found to have an abnormal rhythm and worsening lethargy. Subsequent electrocardiogram and laboratory values revealed new T-wave inversions and elevated troponin. An echocardiogram revealed a new severely reduced left ventricular function with severe global hypokinesis of the left ventricle and an ejection fraction of 30%. It was only after initiating combination therapy of levothyroxine and liothyronine that her symptoms and abnormal cardiac rhythm resolved. With this careful titration of the patient's medication, we concluded that combination therapy was essential to the patient being euthyroid. This phenomenon was also cited in multiple literature, which warrants an investigation of a certain population's inability to convert T4 to T3. By sharing this case, we aim to aid providers with their differential diagnoses and bring to light a potential area of further investigation. Ultimately, by optimizing and tailoring these medications, we hope to improve their quality of life.

Semaphorin3A/PlexinA3 association with the Scribble scaffold for cGMP increase is required for apical dendrite development.

The development of the apical dendrite from the leading process of the bipolar pyramidal neuron might be directed by spatially organized extrinsic cues acting on localized intrinsic determinants. The extracellular cues regulating apical dendrite polarization remain elusive. We show that leading process and apical dendrite development are directed by class III Semaphorins and mediated by a localized cGMP-synthesizing complex. The scaffolding protein Scribble that associates with the cGMP-synthesizing enzyme soluble guanylate cyclase (sGC) also associates with the Semaphorin3A (Sema3A) co-receptor PlexinA3. Deletion or knockdown of PlexinA3 and Sema3A or disruption of PlexinA3-Scribble association prevents Sema3A-mediated cGMP increase and causes defects in apical dendrite development. These manipulations also impair bipolar polarity and leading process establishment. Local cGMP elevation or sGC expression rescues the effects of PlexinA3 knockdown or PlexinA3-Scribble complex disruption. During neuronal polarization, leading process and apical dendrite development are directed by a scaffold that links Semaphorin cue to cGMP increase.

Using Artificial Neural Networks to Model Errors in Biochemical Manipulation of DNA Molecules.

In recent years, the non-biological applications of DNA molecules have made considerable progress; most of these applications were performed in vitro, involving biochemical operations such as synthesis, amplification and sequencing. Because errors may occur with specific sequence patterns or experimental instruments, these biochemical operations are not completely reliable. Modeling errors in these biochemical procedures is an interesting research topic. For example, researchers have proposed several methods to avoid the known vulnerable sequence patterns in the study of storing binary information in DNA molecules. However, there are few end-to-end methods to evaluate these biochemical errors with regard to the DNA sequences. In this article, based on the data generated by a DNA storage research, we use artificial neural networks to predict whether a DNA sequence tends to cause errors in biochemical operations. Through comparative experiments and hyperparameter optimization, we analyze the known and potential problems in the research process. As a result, an end-to-end method to model the biochemical errors of DNA molecules in vitro through a computer system is proposed.

A Localized Scaffold for cGMP Increase Is Required for Apical Dendrite Development.

Studies in cultured neurons have established that axon specification instructs neuronal polarization and is necessary for dendrite development. However, dendrite formation in vivo occurs when axon formation is prevented. The mechanisms promoting dendrite development remain elusive. We find that apical dendrite development is directed by a localized cyclic guanosine monophosphate (cGMP)-synthesizing complex. We show that the scaffolding protein Scribble associates with cGMP-synthesizing enzymes soluble-guanylate-cyclase (sGC) and neuronal nitric oxide synthase (nNOS). The Scribble scaffold is preferentially localized to and mediates cGMP increase in dendrites. These events are regulated by kinesin KifC2. Knockdown of Scribble, sGC-ß1, or KifC2 or disrupting their associations prevents cGMP increase in dendrites and causes severe defects in apical dendrite development. Local cGMP elevation or sGC expression rescues the effects of Scribble knockdown on dendrite development, indicating that Scribble is an upstream regulator of cGMP. During neuronal polarization, dendrite development is directed by the Scribble scaffold that might link extracellular cues to localized cGMP increase.

Machine Learning Models Improve the Diagnostic Yield of Peripheral Blood Flow Cytometry.

OBJECTIVES: Peripheral blood flow cytometry (PBFC) is useful for evaluating circulating hematologic malignancies (HM) but has limited diagnostic value for screening. We used machine learning to evaluate whether clinical history and CBC/differential parameters could improve PBFC utilization. METHODS: PBFC cases with concurrent/recent CBC/differential were split into training (n = 626) and test (n = 159) cohorts. We classified PBFC results with abnormal blast/lymphoid populations as positive and used two models to predict results. RESULTS: Positive PBFC results were seen in 58% and 21% of training cases with and without prior HM (P < .001). % neutrophils, absolute lymphocyte count, and % blasts/other cells differed significantly between positive and negative PBFC groups (areas under the curve [AUC] > 0.7). Among test cases, a decision tree model achieved 98% sensitivity and 65% specificity (AUC = 0.906). A logistic regression model achieved 100% sensitivity and 54% specificity (AUC = 0.919). CONCLUSIONS: We outline machine learning-based triaging strategies to decrease unnecessary utilization of PBFC by 35% to 40%.

Characterization of disinfection byproduct formation and associated changes to dissolved organic matter during solar photolysis of free available chlorine.

Solar irradiation of chlorine-containing waters enhances inactivation of chlorine-resistant pathogens (e.g., Cryptosporidium oocysts), through in situ formation of ozone, hydroxyl radical, and other reactive species during photolysis of free available chlorine (FAC) at UVB-UVA wavelengths of solar light (290-400 nm). However, corresponding effects on regulated disinfection byproduct (DBP) formation and associated dissolved organic matter (DOM) properties remain unclear. In this work, when compared to dark chlorination, sunlight-driven FAC photolysis over a range of conditions was found to yield higher DBP levels, depletion of DOM chromophores and fluorophores, preferential removal of phenolic groups versus carboxylic acid groups, and degradation of larger humic substances to smaller molecular weight compounds. Control experiments showed that increased DBP levels were not due to direct DOM photolysis and subsequent dark reactions with FAC, but to co-exposure of DOM to FAC and reactive species (e.g., O3, HO•, Cl•, Cl2•-, ClO•) generated by FAC photolysis. Because solar chlorine photolysis can enable inactivation of chlorine-resistant pathogens at far lower CTFAC values than chlorination alone, the increases in DBP formation inherent to this approach can likely be offset to some extent by the ability to operate at significantly decreased CTFAC. Nonetheless, these findings demonstrate that applications of solar chlorine photolysis will require careful attention to potential impacts on DBP formation.

Morphologists overestimate the nuclear-to-cytoplasmic ratio.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) has defined nuclear-to-cytoplasmic (N:C) ratio cutoff values for several of its risk-stratified diagnostic categories. However, because pathologists are not trained to recognize strict N:C ratio cutoff values, a previously designed survey was used to determine whether pathologists could accurately identify N:C ratios according to TPS standards. METHODS: Participants were instructed to estimate the N:C ratio of ideal (line drawing) and real (cell photograph) images presented via an online survey. Actual N:C ratios ranged from 0.3 to 0.8, and 3 answer choices were available: < 0.5, ≥ 0.5 and <0.7, and ≥0.7. The resulting data were analyzed to determine the accuracy and performance of the subgroups. RESULTS: A total of 137 individuals completed the survey. Approximately 24.1% were cytopathologists, 18.2% were pathologists without formal cytopathology training, 18.2% were cytotechnologists, 24.1% were pathology residents, and 15.3% were nonmorphologists. Overall, 70.0%, 67.6%, and 93.3% of responses, respectively, were correct for images with an N:C ratio of < 0.5, ≥0.5 and < 0.7, and ≥0.7. For images with an actual N:C ratio < 0.5 and ≥0.5 and < 0.7, 30.0% and 25.0% of responses, respectively, overestimated the N:C ratio. Furthermore, for images with an N:C ratio of 0.4 and 0.6, > 40.0% of responses overestimated the N:C ratio. As a whole, morphologists were significantly more accurate than nonmorphologists (P = .030). CONCLUSIONS: Morphologists tended to overestimate the N:C ratio, particularly at ratios close to TPS-recommended cutoff values. Additional training regarding N:C ratio estimation may help pathologists to adapt to this new system. Cancer Cytopathol 2016;124:669-77. © 2016 American Cancer Society.

Residents managed trauma adequately using their own radiological interpretation as compared with "nighthawk" radiologists.

OBJECTIVE: To determine whether senior surgical residents can independently interpret radiologic studies for the trauma patients under their care. METHOD: Five senior surgical residents (PGY-4 and -5) participated in this prospective study. The residents independently read trauma films as part of the emergency assessment, documenting their interpretations to be compared with the reports by nighthawk radiologists. RESULTS: During a period of 4 months, 426 films of 124 trauma patients admitted to a Level II trauma center were read by one of the five senior surgical residents, and by nighthawk radiologists. Approximately 22% of these were penetrating injuries and the remainder blunt trauma. Residents identified 127 injuries versus 128 injuries identified by the radiologists, with 99.2% agreement. The residents missed two injuries, while the radiologists missed one. CONCLUSIONS: Senior surgical residents can independently and accurately interpret the trauma radiology studies, a skill essential for time-critical decision making.