Electrochemical degradation of ciprofloxacin through a DoE-driven optimization in a filter-press type reactor under batch recirculation mode.

In this work, the electrochemical degradation of ciprofloxacin (CIP) was studied in a filter-press-type reactor without division in a batch recirculation manner. For this purpose, two boron-doped diamond (BDD) electrodes (as cathode and anode) were employed. Also, the optimal operating conditions were found by response surface methodology (RSM) following a central composite face-centered design with three factors, namely current intensity (i), initial pH (pH0), and initial concentration ([C]0) with two responses, namely remotion efficiency (η) and operating cost. Optimal operating conditions were i = 3 A, pH0 = 8.49, and [C]0 = 33.26 mg L-1 within an electrolysis time of 5 h, leading to a maximum removal efficiency of 93.49% with a minimum operating cost of $0.013 USD L-1. Also, a TOC analysis shows an 80% of mineralization extent with an energy consumption of 5.11 kWh g-1 TOC. Furthermore, the CIP degradation progress was followed by mass spectrometry (LC/MS) and a degradation pathway is proposed.

Metabolomic and Lipidomic Analysis of the Colorectal Adenocarcinoma Cell Line HT29 in Hypoxia and Reoxygenation.

The poor availability of oxygen and nutrients in malignant tumors drives the activation of various molecular responses and metabolic reprogramming in cancer cells. Hypoxic tumor regions often exhibit resistance to chemotherapy and radiotherapy. One approach to enhance cancer therapy is to indirectly increase tumor oxygen availability through targeted metabolic reprogramming. Thus, understanding the underlying metabolic changes occurring during hypoxia and reoxygenation is crucial for improving therapy efficacy. In this study, we utilized the HT29 colorectal adenocarcinoma cell line as a hypoxia-reoxygenation model to investigate central carbon and lipid metabolism. Through quantitative NMR spectroscopy and flow injection analysis - differential mobility spectroscopy-tandem mass spectrometry (FIA-DMS-MS/MS) analysis, we observed alterations in components of mitochondrial metabolism, redox status, specific lipid classes, and structural characteristics of lipids during hypoxia and up to 24 h of reoxygenation. These findings contribute to our understanding of the metabolic changes occurring during reoxygenation and provide the basis for functional studies aimed at metabolic pathways in cancer cells.

Standardizing an Experimental Murine Model of Extraparenchymal Neurocysticercosis That Immunologically Resembles Human Infection.

BACKGROUND: Neurocysticercosis (NCC) is endemic in non-developed regions of the world. Two forms of NCC have been described, for which neurological morbidity depends on the location of the lesion, which can be either within the cerebral parenchyma or in extraparenchymal spaces. The extraparenchymal form (EXP-NCC) is considered the most severe form of NCC. EXP-NCC often requires several cycles of cysticidal treatment and the concomitant use of glucocorticoids to prevent increased inflammation, which could lead to intracranial hypertension and, in rare cases, to death. Thus, the improvement of EXP-NCC treatment is greatly needed. METHODS: An experimental murine model of EXP-NCC, as an adequate model to evaluate new therapeutic approaches, and the parameters that support it are described. EXP-NCC was established by injecting 30 Taenia crassiceps cysticerci, which are less than 0.5 mm in diameter, into the cisterna magna of male and female Wistar rats. RESULTS: Cyst implantation and infection progression were monitored by detecting the HP10 antigen and anti-cysticercal antibodies in the serum and cerebral spinal fluid (CSF) of infected rats and by magnetic resonance imaging. Higher HP10 levels were observed in CSF than in the sera, as in the case of human EXP-NCC. Low cell recruitment levels were observed surrounding established cysticerci in histological analysis, with a modest increase in GFAP and Iba1 expression in the parenchyma of female animals. Low cellularity in CSF and low levels of C-reactive protein are consistent with a weak inflammatory response to this infection. After 150 days of infection, EXP-NCC is accompanied by reduced levels of mononuclear cell proliferation, resembling the human disease. EXP-NCC does not affect the behavior or general status of the rats. CONCLUSIONS: This model will allow the evaluation of new approaches to control neuroinflammation and immunomodulatory treatments to restore and improve the specific anti-cysticercal immunity in EXP-NCC.

Convex optimization for maximizing the degradation efficiency of chloroquine in a flow-by electrochemical reactor.

The degradation efficiency of chloroquine phosphate (CQ), an anti-COVID-19 drug, was investigated in a flow-by electrochemical reactor (FBER) provided with two boron-doped diamond (BDD) electrodes (as cathode and anode) under batch recirculation mode. A central composite rotatable design (CCRD) was run down to model and assess the influence of initial pH in an interval of 3.71 to 11.28, the current density in an interval of 34.32 to 185.68 mA cm-2, and liquid volumetric flow rate in an interval of 0.58 to 1.42 L min-1, and conduct the convex optimization to obtain the maximum degradation efficiency. Experimental results were modeled through a second-order polynomial equation having a determination coefficient (R2) of 0.9705 with a variance coefficient of 1.1%. Optimal operating conditions found (initial pH of 5.38, current density (j) of 34.4 mA cm-2, and liquid flow rate (Q) of 1.42 L min-1) led to a global maximum degradation efficiency, COD removal efficiency, and mineralization efficiency of 89.3, 51.6 and 53.1%, respectively, with an energy consumption of 0.041 kWh L-1 within 9 h of treatment. Additionally, a pseudo-zero-order kinetic model was demonstrated to fit the experimental data and the calculated pseudo-zero-order kinetic constant (kapp) was 13.14 mg L-1 h-1 (2.54 × 10-5 mol dm-3 h-1). Furthermore, the total operating cost was of 0.47 US$ L-1. Finally, this research could be helpful for the treatment of wastewater containing an anti-COVID-19 drug such as CQ. Supplementary Information: The online version contains supplementary material available at 10.1007/s10008-023-05452-7.

A novel scale based on biomarkers associated with COVID-19 severity can predict the need for hospitalization and intensive care, as well as enhanced probabilities for mortality.

Prognostic scales may help to optimize the use of hospital resources, which may be of prime interest in the context of a fast spreading pandemics. Nonetheless, such tools are underdeveloped in the context of COVID-19. In the present article we asked whether accurate prognostic scales could be developed to optimize the use of hospital resources. We retrospectively studied 467 files of hospitalized patients after COVID-19. The odds ratios for 16 different biomarkers were calculated, those that were significantly associated were screened by a Pearson's correlation, and such index was used to establish the mathematical function for each marker. The scales to predict the need for hospitalization, intensive-care requirement and mortality had enhanced sensitivities (0.91 CI 0.87-0.94; 0.96 CI 0.94-0.98; 0.96 CI 0.94-0.98; all with p < 0.0001) and specificities (0.74 CI 0.62-0.83; 0.92 CI 0.87-0.96 and 0.91 CI 0.86-0.94; all with p < 0.0001). Interestingly, when a different population was assayed, these parameters did not change considerably. These results show a novel approach to establish the mathematical function of a marker in the development of highly sensitive prognostic tools, which in this case, may aid in the optimization of hospital resources. An online version of the three algorithms can be found at: http://benepachuca.no-ip.org/covid/index.php.

Pertinencia de los laboratorios de simulación como herramienta de educación avanzada en salud / Relevance of simulation laboratories as a tool for advanced health education

RESUMEN El constante perfeccionamiento del proceso educativo del hombre demanda el enriquecimiento de las prácticas de la educación avanzada. Es preciso efectuar transformaciones en el trabajo educativo, por lo que resulta indispensable que se oriente de forma tal que permita potenciar en cada estudiante aquellos aspectos que le faciliten conocer, de una manera más significativa, el momento histórico en que viven. Los simuladores virtuales, como método de aprendizaje en ciencias médicas, son potenciadores del aprendizaje y ayudan a evadir el obstáculo de horas limitadas en la práctica clínica, grupos numerosos, inconsistencias en la observación de enfermedades de alto riesgo o inusuales. En Cuba, la utilización de estos no ha sido explotada al máximo. Los estudios que han evaluado la efectividad de estos simuladores en la mejoría del desempeño de los profesionales de la salud, han arrojado resultados muy positivos, pero el elevado precio de los simuladores ha constituido la mayor barrera para su completa introducción en Cuba. Este trabajo expresa la posición de los autores sobre la pertinencia de los laboratorios de simulación como herramienta de educación avanzada en salud. El uso de los laboratorios de simulación en la educación médica, es una práctica positiva en el perfeccionamiento de las competencias profesionales y ofrece la seguridad de la atención sanitaria; no es un sustituto de la práctica supervisada en entorno real, sino un complemento deseable para una pericia segura y efectiva que permite desarrollar habilidades, conocimientos y actitudes, es decir, capacidades para su óptimo desempeño.

ABSTRACT The constant improvement of the educational process of man demands the enrichment of the practices of advanced education. It is necessary to carry out transformations in the educational work, so it is essential that it be oriented in such a way that it allows each student to enhance those aspects that make it easier for them to know, in a more significant way, the historical moment in which they live. Virtual simulators, as a learning method in medical sciences, are learning enhancers and help to avoid the obstacle of limited hours in clinical practice, large groups, inconsistencies in the observation of high-risk or unusual diseases. In Cuba, the use of these has not been exploited to the maximum. The studies that have evaluated the effectiveness of these simulators in improving the performance of health professionals have yielded very positive results, but the high price of the simulators has constituted the greatest barrier to their full introduction in Cuba. This work expresses the position of the authors on the relevance of simulation laboratories as a tool for advanced health education. The use of simulation laboratories in medical education is a positive practice in the improvement of professional skills and offers the security of health care, it is not a substitute for supervised practice in a real environment, but a desirable complement to an expertise safe and effective, which allows developing skills, knowledge and attitudes, that is, capacities for optimal performance.

Safety and Long-Term Survival Outcome in Patients With Unresectable Barcelona Clinic Liver Cancer (BCLC) Stages C and D Advanced Hepatocellular Carcinoma Treated With 40 µm Drug-Eluting Bead Transcatheter Arterial Chemoembolization.

Background To evaluate the safety, treatment response, and overall survival (OS) following drug-eluting bead transarterial chemoembolization (DEB-TACE) using doxorubicin-loaded 40 µm microspheres in patients with advanced hepatocellular carcinoma (HCC). Methods This was a single-center retrospective evaluation of patients with unresectable HCC without extrahepatic spread and Barcelona Clinic Liver Cancer (BCLC) stages C and D disease who underwent DEB-TACE between August 2015 and January 2018. Pre-treatment data included demographics, medical history, cancer staging, tumor size, laboratory results, and prior treatments for HCC. Follow-up data included the date of DEB-TACE treatments or microwave ablation (MWA) procedures, laboratory test results, adverse events, treatment response, and the date and cause of death. Results Thirty-two patients met the study inclusion criteria. Eighteen patients (56.3%) underwent a single DEB-TACE and 14 patients (43.8%) had two to five DEB-TACE procedures. Five patients (15.6%) had MWA following initial DEB-TACE. Mild postembolization syndrome occurred in six patients (18.8%) during a 30-day period following initial DEB-TACE. Seven patients (21.9%) experienced worsening ascites, pleural fluid, or encephalopathy during the study observation period. Three patients had moderate to severe worsening liver function tests 90 days post-procedure. Seventeen patients (53.1%) had a complete or partial response and nine patients (28.1%) had disease progression. Median OS was 15.0±14.4 months from the time of initial DEB-TACE, with 63% and 33% of patients still alive at 12 and 24 months. Multivariate analyses identified that Okuda Stage (P=0.03) and Cancer of the Liver Italian Programme (CLIP) score (P=0.05) were significantly associated with overall survival after adjusting for other covariates. There were four HCC-related deaths during the 30-day post-procedure period. Conclusion DEB-TACE with small 40 µm doxorubicin-loaded microspheres is a safe and effective treatment for unresectable patients with BCLC stages C and D advanced HCC. Patients with advanced, high-risk unresectable HCC should be considered for DEB-TACE as opposed to supportive or palliative care alone.

Recent advances in metabolomics analysis for early drug development.

The pharmaceutical industry adapted proteomics and other 'omics technologies for drug research early following their initial introduction. Although metabolomics lacked behind in this development, it has now become an accepted and widely applied approach in early drug development. Over the past few decades, metabolomics has evolved from a pure exploratory tool to a more mature and quantitative biochemical technology. Several metabolomics-based platforms are now applied during the early phases of drug discovery. Metabolomics analysis assists in the definition of the physiological response and target engagement (TE) markers as well as elucidation of the mode of action (MoA) of drug candidates under investigation. In this review, we highlight recent examples and novel developments of metabolomics analyses applied during early drug development.

Metastatic breast cancer masquerading as a pituitary macroadenoma: A case report.

The purpose of this manuscript is to report a case of symptomatic breast cancer metastasis to the pituitary gland, a described yet exceedingly rare phenomenon. A 52-year-old woman with a known history of stage-IV breast cancer treated 3 years prior with chemotherapy presented to the emergency department with 2 weeks of right-sided periorbital headache and 1 week of right-sided ptosis. Magnetic resonance imaging showed a 1.9 cm × 2.8 cm × 2.8 cm mass in the pituitary with mass effect on the right optic chiasm. Endocrine laboratory studies were largely normal, including prolactin, thyroid-stimulating hormone, insulin-like growth factor, and a minimally decreased cortisol. She underwent endoscopic transnasal transsphenoidal resection 4 days later to remove the mass without complication. Postoperative pathologic studies were positive for breast cancer metastasis, and she was subsequently started on adjuvant radiation and oral chemotherapy. While breast cancer metastases to the sella have been described in the literature before, symptomatic spread to the pituitary represents a small percentage of all breast cancer metastases, and we thus feel is worthy of further discussion.

Dentigerous cyst and the importance of early detection. report of a pediatric case.

Dentigerous cysts are a common cystic pathology that develop between the first and third decade of life and are mainly associated with impacted or erupted mandibular third molars followed by maxillary canines and maxillary third molars. These kinds of cysts are the result of the proliferation of enamel epithelium after its formation, the pathogenesis of which is not clear. Few of these cysts have been reported in pediatric patients. The following case report presents the rare occurrence of a dentigerous cyst in a 6-year-old boy and describes the treatment administered.

Los quistes dentígeros son una patología quística común que se desarrolla entre la primera y la tercera década de la vida, y se asocian principalmente con terceros molares mandibulares incluidos o erupcionados, seguidos de caninos superiores y terceros molares superiores. Este tipo de quistes son el resultado de la proliferación del epitelio del esmalte después de su formación, cuya patogenia no está clara. Se han informado pocos de estos quistes en pacientes pediátricos. El siguiente reporte de caso presenta la rara ocurrencia de un quiste dentígero en un niño de 6 años y describe el tratamiento administrado.

A Cysteine-Rich Protein, SpDIR1L, Implicated in S-RNase-Independent Pollen Rejection in the Tomato (Solanum Section Lycopersicon) Clade.

Tomato clade species (Solanum sect. Lycopersicon) display multiple interspecific reproductive barriers (IRBs). Some IRBs conform to the SI x SC rule, which describes unilateral incompatibility (UI) where pollen from SC species is rejected on SI species' pistils, but reciprocal pollinations are successful. However, SC x SC UI also exists, offering opportunities to identify factors that contribute to S-RNase-independent IRBs. For instance, SC Solanum pennellii LA0716 pistils only permit SC Solanum lycopersicum pollen tubes to penetrate to the top third of the pistil, while S. pennellii pollen penetrates to S. lycopersicum ovaries. We identified candidate S. pennellii LA0716 pistil barrier genes based on expression profiles and published results. CRISPR/Cas9 mutants were created in eight candidate genes, and mutants were assessed for changes in S. lycopersicum pollen tube growth. Mutants in a gene designated Defective in Induced Resistance 1-like (SpDIR1L), which encodes a small cysteine-rich protein, permitted S. lycopersicum pollen tubes to grow to the bottom third of the style. We show that SpDIR1L protein accumulation correlates with IRB strength and that species with weak or no IRBs toward S. lycopersicum pollen share a 150 bp deletion in the upstream region of SpDIR1L. These results suggest that SpDIR1L contributes to an S-RNase-independent IRB.

S-RNase Alleles Associated With Self-Compatibility in the Tomato Clade: Structure, Origins, and Expression Plasticity.

The self-incompatibility (SI) system in the Solanaceae is comprised of cytotoxic pistil S-RNases which are countered by S-locus F-box (SLF) resistance factors found in pollen. Under this barrier-resistance architecture, mating system transitions from SI to self-compatibility (SC) typically result from loss-of-function mutations in genes encoding pistil SI factors such as S-RNase. However, the nature of these mutations is often not well characterized. Here we use a combination of S-RNase sequence analysis, transcript profiling, protein expression and reproductive phenotyping to better understand different mechanisms that result in loss of S-RNase function. Our analysis focuses on 12 S-RNase alleles identified in SC species and populations across the tomato clade. In six cases, the reason for gene dysfunction due to mutations is evident. The six other alleles potentially encode functional S-RNase proteins but are typically transcriptionally silenced. We identified three S-RNase alleles which are transcriptionally silenced under some conditions but actively expressed in others. In one case, expression of the S-RNase is associated with SI. In another case, S-RNase expression does not lead to SI, but instead confers a reproductive barrier against pollen tubes from other tomato species. In the third case, expression of S-RNase does not affect self, interspecific or inter-population reproductive barriers. Our results indicate that S-RNase expression is more dynamic than previously thought, and that changes in expression can impact different reproductive barriers within or between natural populations.

Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Spread of self-compatibility constrained by an intrapopulation crossing barrier.

Mating system transitions from self-incompatibility (SI) to self-compatibility (SC) are common in plants. In the absence of high levels of inbreeding depression, SC alleles are predicted to spread due to transmission advantage and reproductive assurance. We characterized mating system and pistil-expressed SI factors in 20 populations of the wild tomato species Solanum habrochaites from the southern half of the species range. We found that a single SI to SC transition is fixed in populations south of the Rio Chillon valley in central Peru. In these populations, SC correlated with the presence of the hab-6 S-haplotype that encodes a low activity S-RNase protein. We identified a single population segregating for SI/SC and hab-6. Intrapopulation crosses showed that hab-6 typically acts in the expected codominant fashion to confer SC. However, we found one specific S-haplotype (hab-10) that consistently rejects pollen of the hab-6 haplotype, and results in SI hab-6/hab-10 heterozygotes. We suggest that the hab-10 haplotype could act as a genetic mechanism to stabilize mixed mating in this population by presenting a disadvantage for the hab-6 haplotype. This barrier may represent a mechanism allowing for the persistence of SI when an SC haplotype appears in or invades a population.

Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

Association between Postmortem Kidney Biopsy Findings and Acute Kidney Injury from Patients with SARS-CoV-2 (COVID-19).

BACKGROUND AND OBJECTIVES: AKI in coronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality. The objective of this study was to identify the kidney histopathologic characteristics of deceased patients with diagnosis of COVID-19 and evaluate the association between biopsy findings and clinical variables, including AKI severity. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Our multicenter, observational study of deceased patients with COVID-19 in three third-level centers in Mexico City evaluated postmortem kidney biopsy by light and electron microscopy analysis in all cases. Descriptive and association statistics were performed between the clinical and histologic variables. RESULTS: A total of 85 patients were included. Median age was 57 (49-66) years, 69% were men, body mass index was 29 (26-35) kg/m2, 51% had history of diabetes, 46% had history of hypertension, 98% received anticoagulation, 66% were on steroids, and 35% received at least one potential nephrotoxic medication. Severe AKI was present in 54% of patients. Biopsy findings included FSGS in 29%, diabetic nephropathy in 27%, and arteriosclerosis in 81%. Acute tubular injury grades 2-3 were observed in 49%. Histopathologic characteristics were not associated with severe AKI; however, pigment casts on the biopsy were associated with significantly lower probability of kidney function recovery (odds ratio, 0.07; 95% confidence interval, 0.01 to 0.77). The use of aminoglycosides/colistin, levels of C-reactive protein and serum albumin, previous use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, antivirals, nonsteroid anti-inflammatory drugs, and anticoagulants were associated with specific histopathologic findings. CONCLUSIONS: A high prevalence of chronic comorbidities was found on kidney biopsies. Nonrecovery from severe AKI was associated with the presence of pigmented casts. Inflammatory markers and medications were associated with specific histopathologic findings in patients dying from COVID-19.

Tumor microenvironment affects exogenous sodium/iodide symporter expression.

For decades, sodium/iodide symporter NIS-mediated iodide uptake has played a crucial role in the radioactive ablation of thyroid cancer cells. NIS-based gene therapy has also become a promising tool for the treatment of tumors of extrathyroidal origin. But its applicability has been hampered by reduced expression of NIS, resulting in a moderated capacity to accumulate 131I and in inefficient ablation. Despite numerous preclinical enhancement strategies, the understanding of NIS expression within tumors remains limited. This study aims at a better understanding of the functional behavior of exogenous NIS expression in the context of malignant solid tumors that are characterized by rapid growth with an insufficient vasculature, leading to hypoxia and quiescence. Using subcutaneous HT29NIS and K7M2NIS tumors, we show that NIS-mediated uptake and NIS expression at the plasma membrane of cancer cells are impaired in the intratumoral regions. For a better understanding of the underlying molecular mechanisms induced by hypoxia and quiescence (separately and in combination), we performed experiments on HT29NIS cancer cells. Hypoxia and quiescence were both found to impair NIS-mediated uptake through mechanisms including NIS mis-localization. Modifications in the expression of proteins and metabolites involved in plasma membrane localization and in energy metabolism were found using untargeted proteomics and metabolomics approaches. In conclusion, our results provide evidence that hypoxia and quiescence impair NIS expression at the plasma membrane, and iodide uptake. Our study also shows that the tumor microenvironment is an important parameter for successful NIS-based cancer treatment.

Detection of Atrial Fibrillation from Single Lead ECG Signal Using Multirate Cosine Filter Bank and Deep Neural Network.

Atrial fibrillation (AF) is a cardiac arrhythmia which is characterized based on the irregsular beating of atria, resulting in, the abnormal atrial patterns that are observed in the electrocardiogram (ECG) signal. The early detection of this pathology is very helpful for minimizing the chances of stroke, other heart-related disorders, and coronary artery diseases. This paper proposes a novel method for the detection of AF pathology based on the analysis of the ECG signal. The method adopts a multi-rate cosine filter bank architecture for the evaluation of coefficients from the ECG signal at different subbands, in turn, the Fractional norm (FN) feature is evaluated from the extracted coefficients at each subband. Then, the AF detection is carried out using a deep learning approach known as the Hierarchical Extreme Learning Machine (H-ELM) from the FN features. The proposed method is evaluated by considering normal and AF pathological ECG signals from public databases. The experimental results reveal that the proposed multi-rate cosine filter bank based on FN features is effective for the detection of AF pathology with an accuracy, sensitivity and specificity values of 99.40%, 98.77%, and 100%, respectively. The performance of the proposed diagnostic features of the ECG signal is compared with other existing features for the detection of AF. The low-frequency subband FN features found to be more significant with a difference of the mean values as 0.69 between normal and AF classes.

A case of envenomation by the false fer-de-lance snake Leptodeira annulata (Linnaeus, 1758) in the department of La Guajira, Colombia. / Un caso de envenenamiento por mordedura de una serpiente falsa cabeza de lanza, Leptodeira annulata (Linnaeus, 1758), en el departamento de La Guajira, Colombia

Envenomations by colubrid snakes in Colombia are poorly known, consequently, the clinical relevance of these species in snakebite accidents has been historically underestimated. Herein, we report the first case of envenomation by opisthoglyphous snakes in Colombia occurred under fieldwork conditions at the municipality of Distracción, in the department of La Guajira. A female biologist was bitten on the index finger knuckle of her right hand when she tried to handle a false fer-de-lance snake (Leptodeira annulata). Ten minutes after the snakebite, the patient started to have symptoms of mild local envenomation such as edema, itching, and pain in the wound. After 40 minutes, the edema reached its maximum extension covering the dorsal surface of the right hand and causing complete loss of mobility. The clinical treatment focused on pain and swelling control. No laboratory tests were performed. The patient showed good progress with the total regression of the edema 120 hours after the snake-bite accident and complete recovery of the movement of the limb in one week. Venomous bites of "non-venomous snakes" (opisthoglyphous colubrid snakes) must be considered as a significant public health problem because patients lose their work capability during hours or even days and they are forced to seek medical assistance to treat the envenomation manifestations.

Los envenenamientos por colúbridos en Colombia son poco conocidos, por lo que la relevancia clínica de estas especies de serpientes en los accidentes ofídicos ha sido históricamente subestimada. Se presenta el primer caso de envenenamiento por una serpiente opistoglifa en Colombia, ocurrido bajo condiciones de trabajo de campo en el municipio de Distracción, departamento de La Guajira. Una bióloga fue mordida en el nudillo del dedo índice de la mano derecha cuando trató de manipular una falsa cabeza de lanza o falsa mapanare (Leptodeira annulata). Diez minutos después de la mordedura de la serpiente, la paciente presentó síntomas de envenenamiento local leve, como edema, picazón y dolor en la herida. Después de 40 minutos, el edema alcanzó su extensión máxima, cubriendo la superficie dorsal de la mano derecha y causando la pérdida completa de la movilidad. El tratamiento clínico se centró en el control del dolor y la inflamación. No se hicieron pruebas de laboratorio. La paciente tuvo una buena evolución, con la regresión total del edema 120 horas después del accidente ofídico y la normalización de los movimientos de la extremidad a la semana. Las mordeduras venenosas de serpientes "no venenosas" (serpientes colúbridas opistoglifas) deben considerarse un problema de salud pública importante, ya que los pacientes pierden la capacidad de trabajo durante horas o días y se ven obligados a buscar asistencia médica para contrarrestar las manifestaciones locales de envenenamiento.

A colorimetric bioassay for quantitation of both basal and insulin-induced glucose consumption in 3T3-L1 adipose cells.

INTRODUCTION: The quantitation of glucose consumption in animal cell cultures is mainly based on the use of radiolabeled or fluorescent analogues, resulting in expensive and tedious procedures, requiring special equipment and, sometimes, with potential health and environmental risks. OBJECTIVES: The objective of this work was to evaluate the application of a blood plasma colorimetric assay to quantify glucose consumption in in vitro cultures of adipose cells. METHODS: We worked with 3T3-L1 adipose cells differentiated by 7-8 days, which were exposed to different initial glucose concentrations (5.5, 2.8 and 1.4 mM) for variable times, either in the absence or the presence of 100 nM insulin. Using a commercial colorimetric glucose assay, extracellular glucose was determined, and glucose uptake was calculated as the difference between the initial and final glucose concentration. RESULTS: The colorimetric assay allowed us to quantify glucose uptake in our cell model, observing a linear response over time (r 2 ≥0.9303) to the different glucose concentrations, both in the basal and insulin-induced condition. The insulin-stimulated glucose consumption was higher than basal consumption at all glucose concentrations evaluated, but significant differences were observed at 120-, 360- and 480-min in glucose 5.5 mM (p ≤ 0.01, n = 5), and 240 min in glucose 1.4 mM (p ≤ 0.01, n = 5). A V max of 4.1 and 5.9 nmol/ml/min (basal and insulin-induced, respectively) and a K m of 1.1 mM (same in basal vs insulin-stimulated) were calculated. The bioassay was also useful in a pharmacological context: in glucose 1.4 mM, glucose consumption showed an effect that depended on insulin concentration, with a calculated EC50 of 18.4 ± 1.1 nM. CONCLUSIONS: A simple and low-cost bioassay is proposed to quantify glucose consumption in 3T3-L1 adipose cells.