EMERGE: Evaluating the value of Measuring Random Plasma Glucose Values for Managing Hyperglycemia in the Inpatient Setting.

IMPORTANCE: A diagnosis of diabetes is considered when a patient has hyperglycemia with a random plasma glucose ≥200 mg/dL. However, in the inpatient setting, hyperglycemia is frequently non-specific, especially among patients who are acutely unwell. As a result, patients with transient hyperglycemia may be incorrectly labeled as having diabetes, leading to unnecessary treatment, and potential harm. DESIGN, SETTING, AND PARTICIPANTS: We conducted a multicenter cohort study of patients hospitalized at six hospitals in Ontario, Canada, and identified those with a glucose value ≥200 mg/dL (including standing measurements and randomly drawn). We validated a definition for diabetes using manual chart review that included physician notes, pharmacy notes, home medications, and hemoglobin A1C. Among patients with a glucose value ≥200 mg/dL (11.1 mmol/L), we identified patients without diabetes who received a diabetes medication, and the number who experienced hypoglycemia during the same admission. MAIN OUTCOMES AND MEASURES: To determine the diagnostic value of using random blood glucose to diagnose diabetes in the inpatient setting, and its impact on patient outcomes. RESULTS: We identified 328,786 hospitalizations from hospital between 2010 and 2020. A blood glucose value of ≥200 mg/dL (11.1 mmol/L) had a positive predictive value of 68% and a negative predictive value of 90% for a diagnosis of diabetes. Of the 76,967 patients with an elevated glucose value reported, 16,787 (21.8%) did not have diabetes, and of these, 5375 (32%) received a diabetes medication. Hypoglycemia was frequently reported among the 5375 patients that received a diabetes medication, with 1406 (26.2%) experiencing hypoglycemia and 405 (7.5%) experiencing severe hypoglycemia. CONCLUSIONS AND RELEVANCE: Hyperglycemia in hospital is common but does not necessarily indicate a patient has diabetes. Furthermore, it can lead to treatment with diabetes medications with potential harm. Our findings highlight that clinicians should be cautious when responding to elevated random plasma glucose tests in the inpatient setting.

Press Releases of Drug-Related Randomized Trial Results Prior to Publication in High-Impact Journals: an Observational Study.

IMPORTANCE: Results from high-profile randomized controlled trials (RCTs) are routinely reported through press release months prior to peer-reviewed publication. There are potential benefits to press releases (e.g., knowledge dissemination, ensuring regulatory compliance), but also potential drawbacks (e.g., selective reporting, positive "spin"). OBJECTIVE: To characterize the practice of press release predating the publication of a drug-related RCT in a peer-reviewed journal ("preemptive press release"), including factors associated with this practice. DESIGN, SETTING, AND PARTICIPANTS: We systematically reviewed all RCTs of medications published between 2015 and 2019 in the New England Journal of Medicine (NEJM), Journal of the American Medical Association (JAMA), and Lancet. Press releases were identified using a systematic search of the grey literature (e.g., press release databases, study sponsor websites). An RCT was considered to have a preemptive press release if the press release was published at least three months (90 days) prior to the date of publication in a peer-reviewed journal. MAIN OUTCOMES AND MEASURES: Presence of preemptive press release, defined as a press-release at least 90 days prior to the date of publication in a peer-reviewed journal. As secondary measures for dissemination, we also assessed citation count and Altmetric score. RESULTS: We identified 988 RCTs, of which 172 (17%) had a press release published at least 90 days before the date of peer-reviewed publication. Press releases were published a median of 246 days (interquartile range [IQR] 169-366 days) before publication in a peer-reviewed journal. In the multivariable logistic regression model, the strongest predictor of having a preemptive press release was funding by a pharmaceutical company (odds ratio 13, 95% CI 7, 25). Approximately 85% of RCTs with preemptive press releases had a positive primary outcome and, concordantly, 81% of the corresponding press releases had a positive headline. Multivariable regression models identified studies with a preemptive press release had a similar Altmetric score (median - 15, 95% CI - 33, 12) and higher median citation count (median 22 [95% CI 10 to 33] compared to studies without a preemptive press release. CONCLUSIONS AND RELEVANCE: Preemptive press releases were common, most often issued for trials funded by a pharmaceutical company, and typically preceded publication in a peer-reviewed journal by approximately eight months.

Does a deep learning inventory predict knowledge transfer? Linking student perceptions to transfer outcomes.

Students are often encouraged to learn 'deeply' by abstracting generalizable principles from course content rather than memorizing details. So widespread is this perspective that Likert-style inventories are now routinely administered to students to quantify how much a given course or curriculum evokes deep learning. The predictive validity of these inventories, however, has been criticized based on sparse empirical support and ambiguity in what specific outcome measures indicate whether deep learning has occurred. Here we further tested the predictive validity of a prevalent deep learning inventory, the Revised Two-Factor Study Process Questionnaire, by selectively analyzing outcome measures that reflect a major goal of medical education-i.e., knowledge transfer. Students from two undergraduate health sciences courses completed the deep learning inventory before their course's final exam. Shortly after, a random subset of students rated how much each final exam item aligned with three task demands associated with transfer: (1) application of general principles, (2) integration of multiple ideas or examples, and (3) contextual novelty. We then used these ratings from students to examine performance on a subset of exam items that were collectively perceived to demand transfer. Despite good reliability, the resulting transfer outcomes were not substantively predicted by the deep learning inventory. These findings challenge the validity of this tool and others like it.

Larvicidal activity of green synthesized iron oxide nanoparticles using Grevillea robusta Cunn. leaf extract against vector mosquitoes and their characterization.

Extensive fumigation of synthetic pesticides to control the mosquito vector during each post-monsoon season in Pakistan significantly enhanced the environmental contamination and extinction of beneficial insects from the urban ecosystems. In this context, the present study examined the larvicidal efficacy of green synthesized iron nanoparticles (IONPs), using an aqueous leaf extract of Grevillea robusta against the early 2nd and 4th instar larvae of Aedes aegypti and Anopheles stephensi in Pakistan. The prepared IONPs were characterized by UV-Vis spectrum, FTIR, X-ray diffraction, scanning electron microscopy, and energy-dispersive diffraction. Larvicidal bioassay was conducted at various concentrations (80, 160, 240, 320, and 400 ppm) of IONPs prepared from leaf extract of G. robusta, and readings were taken-every 12 h for two consecutive days. In vitro, larvicidal assay, G. robusta leaf extract IONPs exhibited high mortalities of 64-96% (LC50 = 259.07 ppm; LC90 = 443.92 ppm) for the second instar and 65-98% (LC50 = 238.05 ppm; LC90 = 433.93 ppm) for the fourth instar of Ae. aegypti, while in the case of An. stephensi 56-84% (LC50 = 297.96 ppm; LC90 = 528.69 ppm) for the second and 56-88% (LC50 = 292.72 ppm; LC90 = 514.00 ppm) mortality for fourth larvae at 12-48 h post-exposure times were observed respectively. Significant (p < 0.05) dose-dependent and exposure time-dependent trends were observed among the 2nd and 4th larvalinstar of An. stephensi and Ae. aegypti. However, both species showed similar response and observed no significant (p > 0.05) difference in percentage mortality between the vector mosquitoes An. stephensi and Ae. aegypti. Overall, this study demonstrates that the larvicidal efficacy of green synthesized IONPs at low concentrations can be an ideal eco-friendly and cost-effective biocontrol of vector mosquitoes' larvae of An. stephensi and Ae. aegypti.

Interrupting reactivation of immunologic memory diverts the allergic response and prevents anaphylaxis.

BACKGROUND: IgE production against innocuous food antigens can result in anaphylaxis, a severe life-threatening consequence of allergic reactions. The maintenance of IgE immunity is primarily facilitated by IgG+ memory B cells, as IgE+ memory B cells and IgE+ plasma cells are extremely scarce and short-lived, respectively. OBJECTIVE: Our aim was to investigate the critical requirements for an IgE recall response in peanut allergy. METHODS: We used a novel human PBMC culture platform, a mouse model of peanut allergy, and various experimental readouts to assess the IgE recall response in the presence and absence of IL-4Rα blockade. RESULTS: In human PBMCs, we have demonstrated that blockade of IL-4/IL-13 signaling aborted IgE production after activation of a recall response and skewed the cytokine response away from a dominant type 2 signature. TH2A cells, identified by single-cell RNA sequencing, expanded with peanut stimulation and maintained their pathogenic phenotype in spite of IL-4Rα blockade. In mice with allergy, anti-IL-4Rα provided long-lasting suppression of the IgE recall response beyond antibody treatment and fully protected against anaphylaxis. CONCLUSION: The findings reported here advance our understanding of events mediating the regeneration of IgE in food allergy.

The Potentially Recommended Pharmacotherapy for COVID-19.

CONTEXT: A completely unique coronavirus (2019-nCoV), formally referred to as severe acute respiratory syndrome (SARS-CoV-2), appeared in China. SARS-CoV-2 is an etiological mediator of coronavirus 2 (COVID-19), characterized by pneumonic contagion in human beings. In spite of forceful suppression, this virus has spread worldwide. No specific drugs have been approved by the FDA for treating COVID-19 patients. OBJECTIVE: The study intended to examine the data from studies on clinical management of COVID-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data, and PubMed. The search terms were treatment of the novel coronavirus, management of nCoV-19, chloroquine, and hydroxychloroquine. SETTING: The study took place in the main library of the University of Sargodha in Sargodha, Pakistan. RESULTS: The study identified 42 unique studies that had reported and confirmed over 1500 cases of nCoV-19 by April 21, 2020. The studies found that clinical management, for patients who presented with symptoms, included supportive care and control measures that comprised mechanical ventilator support and supplementary oxygen. CONCLUSIONS: There have been intensive attempts to explore drug therapy for the prophylaxis and treatment of SARS-CoV-2 infection during this COVID-19 pandemic. Several drugs have been identified which including remdesivir, two antimalarials (chloroquine and hydroxychloroquine) and immunosuppressive agents. The effects of most drug interventions are currently highly uncertain and several drugs and vaccines are under trail for the effective treatment of COVID-19 virus, until an effective treatment will discover social distancing and physical hygiene should be practiced strictly.

Biochemical Dynamics and Clinical Features of Novel Corona Virus (2019-nCoV).

CONTEXT: The novel Corona Virus (nCoV-19) was initially reported in Wuhan, China during December 2019, and later people with nCoV-19 were identified in different parts of the world. Infected people had shown symptoms resembling pneumonia, but about 50% of patients were asymptomatic. OBJECTIVE: The study intended to examine the data from studies on nCoV-19. DESIGN: The research team performed a literature review, searching relevant literature databases. The sources of data included bioRxiv, medRxiv, Google Scholar, Embase, PsychINFO, WanFang Data and PubMed. The search terms were novel Corona Virus, and nCoV-19 structure. SETTING: The study took place in the main library of the University of Sargodha, Sargodha, Pakistan. RESULTS: The study identified 22 studies that had reported and confirmed over 2000 cases of nCoV-19 by January 26, 2020. The studies found that the virus was transmitted through respiratory droplets. The virus has two serotypes, OC43 and 229E. CONCLUSIONS: No specific curative therapy is available for CoVid-19. However, certain precautionary measures may potentially reduce the transmission, including washing hands, using sanitizers frequently, avoiding public gatherings, and quarantining or isolating patients. This virus has spread globally and immunocompromised individuals, and especially older individuals, are at significant risk. Community and healthcare professionals have a positive role to play in controlling the spread of the disease.

Experimental Determination of Zinc Isotope Fractionation in Complexes with the Phytosiderophore 2'-Deoxymugeneic Acid (DMA) and Its Structural Analogues, and Implications for Plant Uptake Mechanisms.

The stable isotope signatures of zinc and other metals are increasingly used to study plant and soil processes. Complexation with phytosiderophores is a key reaction and understanding the controls of isotope fractionation is central to such studies. Here, we investigated isotope fractionation during complexation of Zn2+ with the phytosiderophore 2'-deoxymugeneic acid (DMA), and with three commercially available structural analogues of DMA: EDTA, TmDTA, and CyDTA. We used ion exchange chromatography to separate free and complexed zinc, and identified appropriate cation exchange resins for the individual systems. These were Chelex-100 for EDTA and CyDTA, Amberlite CG50 for TmDTA and Amberlite IR120 for DMA. With all the ligands we found preferential partitioning of isotopically heavy zinc in the complexed form, and the extent of fractionation was independent of the Zn:ligand ratio used, indicating isotopic equilibrium and that the results were not significantly affected by artifacts during separation. The fractionations (in ‰) were +0.33 ± 0.07 (1σ, n = 3), + 0.45 ± 0.02 (1σ, n = 2), + 0.62 ± 0.05 (1σ, n = 3) and +0.30 ± 0.07 (1σ, n = 4) for EDTA, TmDTA, CyDTA, and DMA, respectively. Despite the similarity in Zn-coordinating donor groups, the fractionation factors are significantly different and extent of fractionation seems proportional to the complexation stability constant. The extent of fractionation with DMA agreed with observed fractionations in zinc uptake by paddy rice in field experiments, supporting the possible involvement of DMA in zinc uptake by rice.

Does this patient have Clostridioides difficile infection? A systematic review and meta-analysis.

BACKGROUND: The clinical features and predictors of Clostridioides difficile infection overlap with many conditions. OBJECTIVES: We performed a systematic review to evaluate the diagnostic utility of clinical features (clinical examination, risk factors, laboratory tests, and radiographic findings) associated with C. difficile. METHODS: Systematic review and meta-analysis of diagnostic features for C. difficile. DATA SOURCES: MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched up to September 2021. STUDY ELIGIBILITY CRITERIA: Studies that reported clinical features of C. difficile, a valid reference standard test for confirming diagnosis of C. difficile, and a comparison among patients with a positive and negative test result. PARTICIPANTS: Adult and paediatric patients across diverse clinical settings. OUTCOMES: Sensitivity, specificity, likelihood ratios. REFERENCE STANDARD: Stool nucleic acid amplification tests, enzyme immunoassays, cell cytotoxicity assay, and stool toxigenic culture. ASSESSMENT OF RISK OF BIAS: Rational Clinical Examination Series and Quality Assessment of Diagnostic Accuracy Studies-2. METHODS OF DATA SYNTHESIS: Univariate and bivariate analyses. RESULTS: We screened 11 231 articles of which 40 were included, enabling the evaluation of 66 features for their diagnostic utility for C. difficile (10 clinical examination findings, 4 laboratory tests, 10 radiographic findings, prior exposure to 13 antibiotic types, and 29 clinical risk factors). Of the ten features identified on clinical examination, none were significantly clinically associated with increased likelihood of C. difficile infection. Some features that increased likelihood of C. difficile infection were stool leukocytes (LR+ 5.31, 95% CI 3.29-8.56) and hospital admission in the prior 3 months (LR+ 2.14, 95% CI 1.48-3.11). Several radiographic findings also strongly increased the likelihood of C. difficile infection like ascites (LR+ 2.91, 95% CI 1.89-4.49). DISCUSSION: There is limited utility of bedside clinical examination alone in detecting C. difficile infection. Accurate diagnosis of C. difficile infection requires thoughtful clinical assessment for interpretation of microbiologic testing in all suspected cases.

Pathogenetic Mechanisms of Liver-Associated Injuries, Management, and Current Challenges in COVID-19 Patients.

The global outbreak of COVID-19 possesses serious challenges and adverse impacts for patients with progression of chronic liver disease and has become a major threat to public health. COVID-19 patients have a high risk of lung injury and multiorgan dysfunction that remains a major challenge to hepatology. COVID-19 patients and those with liver injury exhibit clinical manifestations, including elevation in ALT, AST, GGT, bilirubin, TNF-α, and IL-6 and reduction in the levels of CD4 and CD8. Liver injury in COVID-19 patients is induced through multiple factors, including a direct attack of SARS-CoV-2 on liver hepatocytes, hypoxia reperfusion dysfunction, cytokine release syndrome, drug-induced hepatotoxicity caused by lopinavir and ritonavir, immune-mediated inflammation, renin-angiotensin system, and coagulopathy. Cellular and molecular mechanisms underlying liver dysfunction are not fully understood in severe COVID-19 attacks. High mortality and the development of chronic liver diseases such as cirrhosis, alcoholic liver disease, autoimmune hepatitis, nonalcoholic fatty liver disease, and hepatocellular carcinoma are also associated with patients with liver damage. COVID-19 patients with preexisting or developing liver disease should be managed. They often need hospitalization and medication, especially in conjunction with liver transplants. In the present review, we highlight the attack of SARS-CoV-2 on liver hepatocytes by exploring the cellular and molecular events underlying the pathophysiological mechanisms in COVID-19 patients with liver injury. We also discuss the development of chronic liver diseases during the progression of SARS-CoV-2 replication. Lastly, we explore management principles in COVID-19 patients with liver injury and liver transplantation.

Impact of presentation at conference with timed release of academic publication.

Fast-tracking publication of original research to coincide with a conference presentation ("coordinated publication") is a mechanism of rapidly disseminating new data. How often this occurs, whether its frequency is changing, and the impact of this approach on information dissemination, is unknown. Our objective was to describe the characteristics of coordinated publications, how the practice has changed over time, and evaluate its potential impact on dissemination of study results. We conducted a cross-sectional study of randomized controlled trials published in NEJM, Lancet, and JAMA between January 1, 2015, and December 31, 2019. Among the 1533 included randomized controlled trials, 502 (33%) had coordinated publications. Coordinated publications increased from 30% [n = 94] in 2015 to 37% [n = 136] in 2019. Coordinated publications were more likely to be unblinded (61% [n = 305] vs. 52% [n = 532]) and more likely to be funded by industry (50% [n = 249] vs. 30% [n = 311]). The strongest predictor of a coordinated publication was cardiovascular disease subspecialty (OR = 3.96, 95% CI [2.95, 5.36]). The median number of citations (188 vs. 98) and the median Altmetric score (318 vs. 182) were higher for coordinated publications than non-coordinated publications. These differences persisted in a multivariable regression model. Coordinated publication is increasingly common. While coordinated publications may generate greater attention, they were observed to be more likely to be unblinded and more likely to be funded by industry, raising questions about the value and intentions of such promotion.

Biological control potential of entomopathogenic fungal strains against peach Fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae).

The peachfruit fly, Bactrocera zonata (Saunders) is a polyphagous pest in nature, belonging to order, Diptera and their respective family is Tephritidae. It mostly feeds on different crops, vegetables and fruits. Different traditional chemical insecticides have been used to control this notorious pest. Excessive consumption of pesticides has become a major threat to the fresh fruits trade since many importing countries refused to accept the shipments due to public health and environmental concerns. There is a growing trend to control these pests using the most effective biological control methods and other preventive measures have been adopted for reducing their attacks. Fungal agents have been used as biological agents to manage the attack of different insects pest through biological means. The present study was conducted to assess the virulence of three entomopathogenic fungi, Metarhizium anisopliae, Beauveria bassiana and Verticillium lecanii, against Bactrocera zonata stages under different laboratory conditions. The results showed that B. bassiana and M. anisopliae were more effective in pathogenicity and potentially kill at all stages of B. zonata as compared to V. lecanii. The highest mortality rate for the third larval instar and the pupal stage were recorded after exposure to the 1 × 1010 conidia/ml concentrations, B. bassiana, with 68.67% and 89.67%, respectively. Adult B. zonata flies were the most susceptible to all entomopathogenic fungi. However, M. anisopliae was more virulent against B. zonata adult flies than B. bassiana and V. lecanii at 1 × 1010 conidial concentration. Therefore, the entomopathogenic fungi B. bassiana and M. anisopliae can be used as an cost effective bio-insecticide in the integrated pest management programs to control B. zonata. This study will be helpful to overcome this pest through biological control means.

Fungal Proteases as Emerging Biocatalysts to Meet the Current Challenges and Recent Developments in Biomedical Therapies: An Updated Review.

With the increasing world population, demand for industrialization has also increased to fulfill humans' living standards. Fungi are considered a source of essential constituents to produce the biocatalytic enzymes, including amylases, proteases, lipases, and cellulases that contain broad-spectrum industrial and emerging applications. The present review discussed the origin, nature, mechanism of action, emerging aspects of genetic engineering for designing novel proteases, genome editing of fungal strains through CRISPR technology, present challenges and future recommendations of fungal proteases. The emerging evidence revealed that fungal proteases show a protective role to many environmental exposures and discovered that an imbalance of protease inhibitors and proteases in the epithelial barriers leads to the protection of chronic eosinophilic airway inflammation. Moreover, mitoproteases recently were found to execute intense proteolytic processes that are crucial for mitochondrial integrity and homeostasis function, including mitochondrial biogenesis, protein synthesis, and apoptosis. The emerging evidence revealed that CRISPR/Cas9 technology had been successfully developed in various filamentous fungi and higher fungi for editing of specific genes. In addition to medical importance, fungal proteases are extensively used in different industries such as foods to prepare butter, fruits, juices, and cheese, and to increase their shelf life. It is concluded that hydrolysis of proteins in industries is one of the most significant applications of fungal enzymes that led to massive usage of proteomics.

Effects of Perioperative Cannabis Use on Bariatric Surgical Outcomes: a Systematic Review.

PURPOSE: While cannabis is the most commonly used non-prescription drug in the USA and has established effects on weight, its implication for bariatric surgery has not been formally evaluated. We aimed to review the current literature on perioperative cannabis use in patients undergoing bariatric surgery. MATERIALS AND METHODS: Our systematic search of MEDLINE and Embase until March 2020 returned 169 citations. Screening and abstraction of results were performed in duplicate, and qualitative synthesis of the data was performed. Primary outcomes were cannabis use characteristics, weight loss outcomes, and 30-day postoperative morbidity. Study quality was assessed through the MINORS risk-of-bias tool. RESULTS: Six observational studies with a total of 1167 patients (78.6% female, median follow-up 12 months [3-38.4 months]) were included. A total of 9.9% of patients (n = 116/1167) used cannabis in the perioperative period. Compared with non-users, 1-year weight loss was significantly higher in a study evaluating 8 preoperative cannabis users (n = 8/239, p = 0.002); however, there were no differences in single-study data on 90-day total weight loss (n = 434, p = 0.89) nor 2-year excess BMI loss (n = 146, p = 0.631). There was no difference in 30-day minor (RR 0.91, 95%CI 0.49-1.71, p = 0.77) or major morbidity (RR 0.75, 95%CI 0.31-1.79; p = 0.50). CONCLUSION: There are only uncontrolled studies to date on cannabis use in bariatric surgery. While these have reported conflicting effects on weight loss and no effect on morbidity to date, validation in randomized trials is required to facilitate evidence-based recommendations.