Transition-Metal-Catalyzed Transformations for the Synthesis of Marine Drugs.

Transition metal catalysis has contributed to the discovery of novel methodologies and the preparation of natural products, as well as new chances to increase the chemical space in drug discovery programs. In the case of marine drugs, this strategy has been used to achieve selective, sustainable and efficient transformations, which cannot be obtained otherwise. In this perspective, we aim to showcase how a variety of transition metals have provided fruitful couplings in a wide variety of marine drug-like scaffolds over the past few years, by accelerating the production of these valuable molecules.

Identification of Olives Using In-Field Hyperspectral Imaging with Lightweight Models.

During the growing season, olives progress through nine different phenological stages, starting with bud development and ending with senescence. During their lifespan, olives undergo changes in their external color and chemical properties. To tackle these properties, we used hyperspectral imaging during the growing season of the olives. The objective of this study was to develop a lightweight model capable of identifying olives in the hyperspectral images using their spectral information. To achieve this goal, we utilized the hyperspectral imaging of olives while they were still on the tree and conducted this process throughout the entire growing season directly in the field without artificial light sources. The images were taken on-site every week from 9:00 to 11:00 a.m. UTC to avoid light saturation and glitters. The data were analyzed using training and testing classifiers, including Decision Tree, Logistic Regression, Random Forest, and Support Vector Machine on labeled datasets. The Logistic Regression model showed the best balance between classification success rate, size, and inference time, achieving a 98% F1-score with less than 1 KB in parameters. A reduction in size was achieved by analyzing the wavelengths that were critical in the decision making, reducing the dimensionality of the hypercube. So, with this novel model, olives in a hyperspectral image can be identified during the season, providing data to enhance a farmer's decision-making process through further automatic applications.

Acute hepatitis secondary to febuxostat.

Febuxostat is a drug from the group of xanthine dehydrogenase inhibitors and is used in the treatment of hyperuricemia and gouty arthritis. However, it is not free of adverse effects, including alteration of liver profile tests. This is why we must pay attention to this type of adverse events in case it is necessary to suspend treatment. We present a clinical case of acute hepatitis secondary to Febuxostat.

Continuous Flow Chemistry: A Novel Technology for the Synthesis of Marine Drugs.

In this perspective, we showcase the benefits of continuous flow chemistry and photochemistry and how these valuable tools have contributed to the synthesis of organic scaffolds from the marine environment. These technologies have not only facilitated previously described synthetic pathways, but also opened new opportunities in the preparation of novel organic molecules with remarkable pharmacological properties which can be used in drug discovery programs.

High cobalamin levels as a five-year risk predictor for developing hematological cancer.

BACKGROUND: A high cobalamin level has been related to non-malignant diseases (mainly liver diseases, alcoholism, and renal diseases) and cancer (hematological malignancies and solid cancers such as liver and stomach cancer). However, a previous high level of cobalamin and the implications in the possible development of cancer is still unclear. The main aim of this study was to describe if a previous high cobalamin level is a determinant in the future development of cancer in five years of follow-up. The secondary objective was to determine any differences between cancer groups. METHODS: A retrospective study was performed. Two databases were employed. The first one included all patients who had a determination of cobalamin in a routine blood test during the year 2010 (a total of 44,166 patients). The second one showed every patient who was admitted to the reference hospital, Hospital Clinico Universitario de Valladolid, during the following five years. Finally, a number of 6710 patients was included. Both databases belong to the medical records of the Hospital Data Surveillance System and are completely validated. Multivariate logistic regression analyses were employed to evaluate the association between cobalamin levels and the appearance of cancer (total and in each subgroup). All analyses were performed using IBM SPSS 24 software (IBM Corp., Armonk, NY, USA). RESULTS: The sample studied showed a clear association between the risk of hematological cancer and a previous high Cbl level. This relationship was higher among patients with the highest levels (over 779 pmol/L), showing almost two times more risk for development of hematological malignance within 5 years in the multivariate analysis (OR: 1.975, 95% CI: 1.056-3.697, P=0.033). Hematological malignancies were mostly diagnosed within the first three years (86.6%), showing a similar percentage in those three years. There was no association between this previous level and the development of any other type of cancer. CONCLUSIONS: Our study shows that a high cobalamin plasma level (hypervitaminosis) is associated with the development of hematologic cancer within five years after the measurement. The clinical implication of these findings, together with the clinical suspicion, reinforces the necessity of carrying out specific screening hematological tests in patients with not justified elevated plasma cobalamin levels. New prospective and multicenter studies are necessary to validate these results.

DRESS syndrome secondary to carbamazepine.

DRESS syndrome is a multisystem disorder that appears in the context of an adverse drug reaction, characterized by fever, rash and peripheral eosinophilia with involvement of other organs such as the liver. The typical liver involvement is acute toxic hepatitis (DILI), showing improvement and a tendency to resolution when corticotherapy is started. We must not forget this manifestation in the clinical context of a DRESS syndrome.

Adrenal insufficiency and hepatic cirrhosis: a relationship to discover.

Liver cirrhosis is an entity that predisposes to adrenal insufficiency. Adequate screening for this condition in patients with liver cirrhosis, since several studies have shown increased survival with the use of corticosteroids in cirrhotic patients with septic shock, it seems reasonable to identify patients with adrenal insufficiency in the context of liver cirrhosis and individualize your treatment.

Cefditoren-induced hepatitis.

There are many daily antibiotic prescriptions, especially beta-lactams in trivial infections such as cystitis in young women. Many of these drugs carry an implicit probability of producing hepatotoxicity, manifested by a nonspecific general picture and elevated analytical transaminases. We must take it into account when making the differential diagnosis in the hepatotoxicity study and suspend it as soon as we recognize it.

Design and Evaluation of a Heterogeneous Lightweight Blockchain-Based Marketplace.

The proposal of this paper is to introduce a low-level blockchain marketplace, which is a blockchain where participants could share its power generation and demand. To achieve this implementation in a secure way for each actor in the network, we proposed to deploy it over efficient and generic low-performance devices. Thus, they are installed as IoT devices, registering measurements each fifteen minutes, and also acting as blockchain nodes for the marketplace. Nevertheless, it is necessary that blockchain is lightweight, so it is implemented as a specific consensus protocol that allows each node to have enough time and computer requirements to act both as an IoT device and a blockchain node. This marketplace will be ruled by Smart Contracts deployed inside the blockchain. With them, it is possible to make registers for power generation and demand. This low-level marketplace could be connected to other services to execute matching algorithms from the data stored in the blockchain. Finally, a real test-bed implementation of the marketplace was tested, to confirm that it is technically feasible.

Coding Variation and Adherence to Methodological Standards in Cardiac Research Using the National Inpatient Sample.

Background: Code selection is crucial to the accuracy and reproducibility of studies using administrative data, however a comprehensive assessment of coding trends for major cardiac diagnoses and procedures is lacking. We aimed to evaluate trends in administrative code utilization for major cardiac diagnoses and procedures, and adherence to required methodological practices in cardiac research using the National Inpatient Sample (NIS). Methods: In this observational study of 445 articles, ICD-9-CM codes corresponding to acute myocardial infarction (AMI), heart failure, atrial fibrillation, percutaneous coronary intervention, and coronary artery bypass grafting were collected and analyzed. The NIS was used to compare the number of hospitalizations between the most frequently encountered AMI case definitions. Key elements were abstracted from each article to evaluate adherence to required methodological practices. Results: Variation in code utilization was observed for each diagnosis and procedure assessed, and the number of unique case definitions published per year increased throughout the study period (P < 0.001), driven largely by the significant increase in articles per year (P < 0.001). Off-target codes were observed in 39 (8.8%) studies. Upon reintroduction into the NIS for 2008-2012, the most commonly encountered case definitions for AMI were found to yield significantly different estimates of AMI hospitalizations and hospitalization trends over time. Three hundred and ninety-nine articles (84%) did not adhere to one or more required research practices. Overall adherence was superior for publications in higher-impact journals (P = 0.002). Conclusions: Substantial variation in code selection exists for major cardiac diagnoses and procedures, and non-adherence to methodological standards is widespread. These data have important implications for the accuracy and generalizability of analyses using the NIS.

Association Between Preexisting Versus Newly Identified Atrial Fibrillation and Outcomes of Patients With Acute Pulmonary Embolism.

Background Atrial fibrillation (AF) may exist before or occur early in the course of pulmonary embolism (PE). We determined the PE outcomes based on the presence and timing of AF. Methods and Results Using the data from a multicenter PE registry, we identified 3 groups: (1) those with preexisting AF, (2) patients with new AF within 2 days from acute PE (incident AF), and (3) patients without AF. We assessed the 90-day and 1-year risk of mortality and stroke in patients with AF, compared with those without AF (reference group). Among 16 497 patients with PE, 792 had preexisting AF. These patients had increased odds of 90-day all-cause (odds ratio [OR], 2.81; 95% CI, 2.33-3.38) and PE-related mortality (OR, 2.38; 95% CI, 1.37-4.14) and increased 1-year hazard for ischemic stroke (hazard ratio, 5.48; 95% CI, 3.10-9.69) compared with those without AF. After multivariable adjustment, preexisting AF was associated with significantly increased odds of all-cause mortality (OR, 1.91; 95% CI, 1.57-2.32) but not PE-related mortality (OR, 1.50; 95% CI, 0.85-2.66). Among 16 497 patients with PE, 445 developed new incident AF within 2 days of acute PE. Incident AF was associated with increased odds of 90-day all-cause (OR, 2.28; 95% CI, 1.75-2.97) and PE-related (OR, 3.64; 95% CI, 2.01-6.59) mortality but not stroke. Findings were similar in multivariable analyses. Conclusions In patients with acute symptomatic PE, both preexisting AF and incident AF predict adverse clinical outcomes. The type of adverse outcomes may differ depending on the timing of AF onset.

Meta-analysis of intravascular volume expansion strategies to prevent contrast-associated acute kidney injury following invasive angiography.

OBJECTIVE: To perform a detailed analysis of published data regarding intravascular volume expansion to prevent contrast-associated acute kidney injury (CA-AKI) and to determine if an ideal dose of IV fluids can be recommended. BACKGROUND: Administration of contrast media during invasive angiography is associated with CA-AKI. Intravascular volume expansion is the most effective intervention to prevent CA-AKI, yet evidenced based protocols are lacking. METHODS: Literature review and meta-analysis of randomized controlled trials (RCT) of patients receiving IV volume expansion as prophylaxis for CA-AKI was performed. Normal saline, Lactated Ringer's and sodium bicarbonate were included. The primary outcome was incidence of CA-AKI. RESULTS: 37 RCTs studying 12,166 patients were included. Mean age was 67 ± 5 years, 70% of the patients were male. 68% had chronic kidney disease, 41% diabetes, and 30% heart failure. The incidence of CA-AKI was 9.5% (95% CI: 8-12%). IV expansion versus no volume administration was associated with a lower risk of CA-AKI (RR:0.62; 95% CI: 0.49-0.77, p < .001). Intensive IV volume expansion was associated with a reduced risk of CA-AKI(RR: 0.66; 95%CI: 0.52-0.85, p < .01). The intensive IV volume expansion arm received significantly more fluids than the standard protocols: 1,574(1,123 - 1,913) ml versus 849(558-1,067) ml (p = .03) without significant difference in the duration of infusion (median of 12 vs. 17 hr, p = .1) or pulmonary edema (1.7% vs 1.3%, p = .7). CONCLUSIONS: Despite high variability in protocols used, IV volume expansion is effective in preventing CA-AKI. Intensive IVF expansion (median 1.6 L over 17 hr) was associated with decreased risk of CA-AKI.

Microwave-assisted functionalization of carbon nanohorns with oligothiophene units with SERS activity.

Carbon nanohorns have been functionalized with oligothiophene units via the 1,3-dipolar cycloaddition reaction under microwave irradiation and solvent-free conditions. A dramatic Raman enhancement was found for one of the synthesized derivatives. Experimental and in silico studies helped to understand the enhancement, attributed to the modification of electromagnetic fields upon functionalization at the tip of the nanostructures.

COVID-19 and the cardiovascular system: A review of current data, summary of best practices, outline of controversies, and illustrative case reports.

As the severe acute respiratory syndrome coronavirus 2 virus pandemic continues to grow globally, an association is apparent between patients with underlying cardiovascular disease comorbidities and the risk of developing severe COVID-19. Furthermore, there are potential cardiac manifestations of severe acute respiratory syndrome coronavirus 2 including myocyte injury, ventricular dysfunction, coagulopathy, and electrophysiologic abnormalities. Balancing management of the infection and treatment of underlying cardiovascular disease requires further study. Addressing the increasing reports of health care worker exposure and deaths remains paramount. This review summarizes the most contemporary literature on the relationship of the cardiovascular system and COVID-19 and society statements with relevance to protection of health care workers, and provides illustrative case reports in this context.

Programme for Harmonization to the International Scale in Latin America for BCR-ABL1 quantification in CML patients: findings and recommendations.

Objectives The quantitation of BCR-ABL1 mRNA is mandatory for chronic myeloid leukemia (CML) patients, and RT-qPCR is the most extensively used method in testing laboratories worldwide. Nevertheless, substantial variation in RT-qPCR results makes inter-laboratory comparability hard. To facilitate inter-laboratory comparative assessment, an international scale (IS) for BCR-ABL1 was proposed. Methods The laboratory-specific conversion factor (CF) to the IS can be derived from the World Health Organization (WHO) genetic reference panel; however, this material is limited to the manufacturers to produce and calibrate secondary reference reagents. Therefore, we developed secondary reference calibrators, as lyophilized cellular material, aligned to the IS. Our purpose was both to re-evaluate the CF in 18 previously harmonized laboratories and to propagate the IS to new laboratories. Results Our field trial including 30 laboratories across Latin America showed that, after correction of raw BCR-ABL1/ABL1 ratios using CF, the relative mean bias was significantly reduced. We also performed a follow-up of participating laboratories by annually revalidating the process; our results support the need for continuous revalidation of CFs. All participating laboratories also received a calibrator to determine the limit of quantification (LOQ); 90% of them could reproducibly detect BCR-ABL1, indicating that these laboratories can report a consistent deep molecular response. In addition, aiming to investigate the variability of BCR-ABL1 measurements across different RNA inputs, we calculated PCR efficiency for each individual assay by using different amounts of RNA. Conclusions In conclusion, for the first time in Latin America, we have successfully organized a harmonization platform for BCR-ABL1 measurement that could be of immediate clinical benefit for monitoring the molecular response of patients in low-resource regions.