Enhancing Trypanosomatid Identification and Genotyping with Oxford Nanopore Sequencing: Development and Validation of an 18S rRNA Amplicon-Based Method.

Trypanosomatids, including Trypanosoma and Leishmania species, present significant medical and veterinary challenges, causing substantial economic losses, health complications, and even fatalities. Diagnosing and genotyping these species and their genotypes is often complex, involving multiple steps. This study aimed to develop an amplicon-based sequencing (ABS) method using Oxford Nanopore long-read sequencing to enhance Trypanosomatid detection and genotyping. The 18S rDNA gene was targeted for its inter-species conservation. The Trypanosomatid-ABS method effectively distinguished between 11 Trypanosoma species (including Trypanosoma evansi, Trypanosoma theileri, Trypanosoma vivax, and Trypanosoma rangeli) and 6 Trypanosoma cruzi discrete typing units (TcI to TcVI and TcBat), showing strong concordance with conventional methods (κ index of 0.729, P < 0.001). It detected co-infections between Trypanosomatid genera and T. cruzi, with a limit of detection of one parasite per mL. The method was successfully applied to human, animal, and triatomine samples. Notably, TcI predominated in chronic Chagas samples, whereas TcII and TcIV were found in the acute stage. Triatomine vectors exhibited diverse Trypanosomatid infections, with Triatoma dimidiata mainly infected with TcI and occasional TcBat co-infections, and Rhodnius prolixus showing TcI and TcII infections, along with T. rangeli co-infections and mixed TcII infections. Animals were infected with T. vivax, T. theileri, and T. evansi. The ABS method's high resolution, sensitivity, and accuracy make it a valuable tool for understanding Trypanosomatid dynamics, enhancing disease control strategies, and enabling targeted interventions.

A phased genome assembly of a Colombian Trypanosoma cruzi TcI strain and the evolution of gene families.

Chagas is an endemic disease in tropical regions of Latin America, caused by the parasite Trypanosoma cruzi. High intraspecies variability and genome complexity have been challenges to assemble high quality genomes needed for studies in evolution, population genomics, diagnosis and drug development. Here we present a chromosome-level phased assembly of a TcI T. cruzi strain (Dm25). While 29 chromosomes show a large collinearity with the assembly of the Brazil A4 strain, three chromosomes show both large heterozygosity and large divergence, compared to previous assemblies of TcI T. cruzi strains. Nucleotide and protein evolution statistics indicate that T. cruzi Marinkellei separated before the diversification of T. cruzi in the known DTUs. Interchromosomal paralogs of dispersed gene families and histones appeared before but at the same time have a more strict purifying selection, compared to other repeat families. Previously unreported large tandem arrays of protein kinases and histones were identified in this assembly. Over one million variants obtained from Illumina reads aligned to the primary assembly clearly separate the main DTUs. We expect that this new assembly will be a valuable resource for further studies on evolution and functional genomics of Trypanosomatids.

Vitaminas B neurotrópicas y neuropatía periférica: estado del arte y acuerdo de expertos / Neurotropic B vitamins and peripheral neuropathy: State of the art and agreement of experts

Propósito: La neuropatía periférica tiene un espectro clínico inespecífico y multifactorial, con frecuente subdiagnóstico y terapéutica de eficacia variable. Existe una heterogénea prescripción de vitaminas B, las cuales pueden desempeñar un rol importante en el manejo de diferentes neuropatías; sin embargo, en Colombia no existen guías clínicas al respecto. El propósito de este trabajo es orientar en el reconocimiento temprano de las neuropatías periféricas y generar recomendaciones sobre el uso adecuado de vitaminas B neurotrópicas. Descripción de la metodología: Acuerdo de expertos sobre la neuropatía periférica y el rol terapéutico de las vitaminas B con énfasis en la epidemiología en Colombia, diagnóstico y tratamiento. Contenidos: En Colombia, la prevalencia de neuropatía periférica se estima cercana al 10 %, sin embargo, no hay datos recientes. Dentro de las etiologías más frecuentes se encuentran la neuropatía diabética, infecciosa, inflamatoria, carenciales, toxica y farmacológica. Se recomiendan las siguientes herramientas de tamizaje en población de riesgo: DN4, MNSI, test de monofilamento, test de vibración y valoración de reflejos. Las vitaminas B1, B6 y B12 son seguras, accesibles y pueden ser eficaces en neuropatía periférica, incluso cuando el déficit no ha sido demostrado, pero con requerimientos particulares en su administración conjunta. Conclusiones: Las neuropatías periféricas son un reto diagnóstico y terapéutico que requiere la identificación oportuna para el tratamiento de la etiología subyacente y el control de síntomas. El uso de vitaminas B neurotrópicas es efectivo y seguro en neuropatía periférica carencial, y también parece ser eficaz en el manejo de neuropatías periféricas de diferentes etiologías.

Purpose: Peripheral neuropathy has a nonspecific and multifactorial clinical spectrum, with frequent underdiagnosis and therapeutics of variable efficacy. There is a high but heterogeneous prescription of B vitamins, which can play an important role in the management of different neuropathies; however, in Colombia there are no clinical guidelines in this regard. The purpose of this article is to guide the early recognition of peripheral neuropathy and generate recommendations on the proper use of neurotropic B vitamins. Description of the methodology: Expert agreement on peripheral neuropathy and the therapeutic role of B vitamins with emphasis on epidemiology in Colombia, diagnosis and treatment. Contents: In Colombia, there are no recent data to estimate the prevalence of peripheral neuropathy; the main etiologies are: diabetes mellitus, nutritional deficiencies, herpes zoster and neuropathies due to chemotherapy. Given risk factors in the anamnesis, the use of DN4, MNSI, monofilament test, vibration test and assessment of reflexes is recommended. Vitamins B1, B6, and B12 are safe and can be effective in peripheral neuropathy, even when the deficit has not been demonstrated, but with special requirements in their joint administration. Conclusions: peripheral neuropathies are a diagnostic and therapeutic challenge, and require timely identification, for the treatment of the underlying etiology and symptom control. The use of neurotropic B vitamins is effective and safe in deficient peripheral neuropathy, and also appears to be effective in the management of peripheral neuropathies of different etiologies.

Making Sense of Composite Endpoints in Clinical Research.

Multiple drugs currently used in clinical practice have been approved by regulatory agencies based on studies that utilize composite endpoints. Composite endpoints are appealing because they reduce sample size requirements, follow-up periods, and costs. However, interpreting composite endpoints can be challenging, and their misuse is not uncommon. Incorrect interpretation of composite outcomes can lead to misleading conclusions that impact patient care. To correctly interpret composite outcomes, several important questions should be considered. Are the individual components of the composite outcome equally important to patients? Did the more and less important endpoints occur with similar frequency? Do the component endpoints exhibit similar relative risk reductions? If these questions receive affirmative answers, the use and interpretation of the composite endpoint would be appropriate. However, if any component of the composite endpoint fails to satisfy the aforementioned criteria, interpretation can become difficult, necessitating additional steps. Regulatory agencies acknowledge these challenges and have specific considerations when approving drugs based on studies employing composite endpoints. In conclusion, composite endpoints are valuable tools for evaluating the efficacy and net clinical benefit of interventions; however, cautious interpretation is advised.

Development of Antiepileptic Drugs throughout History: From Serendipity to Artificial Intelligence.

This article provides a comprehensive narrative review of the history of antiepileptic drugs (AEDs) and their development over time. Firstly, it explores the significant role of serendipity in the discovery of essential AEDs that continue to be used today, such as phenobarbital and valproic acid. Subsequently, it delves into the historical progression of crucial preclinical models employed in the development of novel AEDs, including the maximal electroshock stimulation test, pentylenetetrazol-induced test, kindling models, and other animal models. Moving forward, a concise overview of the clinical advancement of major AEDs is provided, highlighting the initial milestones and the subsequent refinement of this process in recent decades, in line with the emergence of evidence-based medicine and the implementation of increasingly rigorous controlled clinical trials. Lastly, the article explores the contributions of artificial intelligence, while also offering recommendations and discussing future perspectives for the development of new AEDs.

Role of Calcium Modulation in the Pathophysiology and Treatment of Alzheimer's Disease.

Alzheimer's disease (AD) is a chronic neurodegenerative disease and the most frequent cause of progressive dementia in senior adults. It is characterized by memory loss and cognitive impairment secondary to cholinergic dysfunction and N-methyl-D-aspartate (NMDA)-mediated neurotoxicity. Intracellular neurofibrillary tangles, extracellular plaques composed of amyloid-ß (Aß), and selective neurodegeneration are the anatomopathological hallmarks of this disease. The dysregulation of calcium may be present in all the stages of AD, and it is associated with other pathophysiological mechanisms, such as mitochondrial failure, oxidative stress, and chronic neuroinflammation. Although the cytosolic calcium alterations in AD are not completely elucidated, some calcium-permeable channels, transporters, pumps, and receptors have been shown to be involved at the neuronal and glial levels. In particular, the relationship between glutamatergic NMDA receptor (NMDAR) activity and amyloidosis has been widely documented. Other pathophysiological mechanisms involved in calcium dyshomeostasis include the activation of L-type voltage-dependent calcium channels, transient receptor potential channels, and ryanodine receptors, among many others. This review aims to update the calcium-dysregulation mechanisms in AD and discuss targets and molecules with therapeutic potential based on their modulation.

Pharmacogenomic profile of actionable molecular variants related to drugs commonly used in anesthesia: WES analysis reveals new mutations.

Background: Genetic interindividual variability is associated with adverse drug reactions (ADRs) and affects the response to common drugs used in anesthesia. Despite their importance, these variants remain largely underexplored in Latin-American countries. This study describes rare and common variants found in genes related to metabolism of analgesic and anaesthetic drug in the Colombian population. Methods: We conducted a study that included 625 Colombian healthy individuals. We generated a subset of 14 genes implicated in metabolic pathways of common medications used in anesthesia and assessed them by whole-exome sequencing (WES). Variants were filtered using two pipelines: A) novel or rare (minor allele frequency-MAF <1%) variants including missense, loss-of-function (LoF, e.g., frameshift, nonsense), and splice site variants with potential deleterious effect and B) clinically validated variants described in the PharmGKB (categories 1, 2 and 3) and/or ClinVar databases. For rare and novel missense variants, we applied an optimized prediction framework (OPF) to assess the functional impact of pharmacogenetic variants. Allelic, genotypic frequencies and Hardy-Weinberg equilibrium were calculated. We compare our allelic frequencies with these from populations described in the gnomAD database. Results: Our study identified 148 molecular variants potentially related to variability in the therapeutic response to 14 drugs commonly used in anesthesiology. 83.1% of them correspond to rare and novel missense variants classified as pathogenic according to the pharmacogenetic optimized prediction framework, 5.4% were loss-of-function (LoF), 2.7% led to potential splicing alterations and 8.8% were assigned as actionable or informative pharmacogenetic variants. Novel variants were confirmed by Sanger sequencing. Allelic frequency comparison showed that the Colombian population has a unique pharmacogenomic profile for anesthesia drugs with some allele frequencies different from other populations. Conclusion: Our results demonstrated high allelic heterogeneity among the analyzed sampled, enriched by rare (91.2%) variants in pharmacogenes related to common drugs used in anesthesia. The clinical implications of these results highlight the importance of implementation of next-generation sequencing data into pharmacogenomic approaches and personalized medicine.

A Latin American consensus meeting on the essentials of mixed pain.

OBJECTIVES: The term "mixed pain" has been established when a mixture of different pain components (e.g. nociceptive, neuropathic, and nociplastic) are present. It has gained more and more acceptance amongst pain experts worldwide, but many questions around the concept of mixed pain are still unsolved. The sensation of pain is very personal. Cultural, social, personal experiences, idiomatic, and taxonomic differences should be taken into account during pain assessment. Therefore, a Latin American consensus committee was formed to further elaborate the essentials of mixed pain, focusing on the specific characteristics of the Latin American population. METHODS: The current approach was based on a systematic literature search and review carried out in Medline. Eight topics about the definition, diagnosis, and treatment of mixed pain were discussed and voted for by a Latin American consensus committee and recommendations were expressed. RESULTS: At the end of the meeting a total of 14 voting sheets were collected. The full consensus was obtained for 21 of 25 recommendations (15 strong agreement and 6 unanimous agreement) formulated for the above described 8 topics (7 of the 8 topics had for all questions at least a strong agreement - 1 topic had no agreement for all 4 questions). CONCLUSION: In a subject as complex as mixed pain, a consensus has been reached among Latin American specialists on points related to the definition and essence of this pain, its diagnosis and treatment. Recommendations for diagnosis and treatment of mixed pain in Latin America were raised.

Definition of self-medication: a scoping review.

Self-medication (SM) is a global and growing phenomenon. It represents a public health problem due to antibiotic resistance, risk of adverse drug reactions, drug-drug interactions, disease masking, and increased morbidity. There is not a consensus on the definition of SM. The definitions found in different studies make it difficult to address this problem from a theoretical perspective and therefore find an adequate solution to this public health problem. The aim of this article is to search the medical literature to characterize the current understanding of SM in the medical community. We conducted a scoping review of definitions of SM by searching on PubMed - Medline, Embase, and LILACS using the following combination of keywords: 'self-prescription' or 'self prescription', 'self-medication' or 'self medication', or 'automedication' and 'definition' or 'explanation'. The search was limited to articles containing the definition of SM, with no limit on language or year. Duplicate studies and those that did not mention the definition of SM were excluded from the final review. A total of 65 studies were included in the final selection. We found a vast heterogeneity in the definition of SM. Most articles based their definition of SM on the process of obtaining the drug, the nonparticipation of a specific health professional, the source of the medication, and the reason for SM. Other interesting concepts such as self-care, nonadherence to a prescription, reuse of stored drugs, and sharing and lending medicines were also considered forms of SM by other authors, however. This study highlights the need to reach a consensus regarding the definition of SM to adequately propose strategies to address this global health problem. This study shows the diverse concepts that need to be included in a future definition of SM. Plain Language Summary: Definition of self-medication: a review with systematic methodology Self-medication (SM) is a global and growing phenomenon that represents a public health problem due to antibiotic resistance, risk of dangerous side effects, interactions between drugs, and disease masking. Currently, there is not a consensus on the definition of SM, which makes it difficult to address this problem and therefore find an adequate solution. Making a standard definition would allow the development of programs focused on addressing drug-related problems associated with self-medication behavior. The purpose of this article is to search the medical literature to define the current understanding of SM in the medical community. We included a total of 65 studies and found a great variance in the definition of SM. Most articles based their definition of SM on the process of obtaining the drug, the nonparticipation of a specific health professional, the source of the medication, and the reason for SM. Other interesting concepts such as self-care, not following a prescription, reuse of stored drugs, and sharing and lending medicines were also considered forms of SM by other authors, however. Furthermore, this study highlights that SM is a wider concept that goes beyond aiming to promote and restore health, as aesthetic and recreational purposes are also reasons for SM that can put individuals at risk and compromise the correct and safe use of medications.

Thermodynamic Analysis of the Solubility of Isoniazid in (PEG 200 + Water) Cosolvent Mixtures from 278.15 K to 318.15 K.

The solubility of drugs in cosolvent systems of pharmaceutical interest is of great importance for understanding and optimizing a large number of processes. Here, we report the solubility of isoniazid in nine (PEG 200 + water) cosolvent mixtures at nine temperatures (278.15, 283.15, 288.15, 293.15, 298.15, 303.15, 308.15, and 318.15 K) determined by UV-vis spectrophotometry. From the solubility data, the thermodynamic solution, mixing, and transfer functions were calculated in addition to performing the enthalpy-entropy compensation analysis. The solubility of isoniazid depends on the concentration of PEG 200 (positive cosolvent effect) and temperature (endothermic process) reaching its maximum solubility in pure PEG 200 at 318.15 K and the lowest solubility in pure water at 278.15 K. The solution process is favored by the solution entropy and according to the enthalpy-entropy compensation analysis it is driven by entropy in mixtures rich in water and by enthalpy in mixtures rich in PEG 200.

Connexins and Pannexins: Important Players in Neurodevelopment, Neurological Diseases, and Potential Therapeutics.

Cell-to-cell communication is essential for proper embryonic development and its dysfunction may lead to disease. Recent research has drawn attention to a new group of molecules called connexins (Cxs) and pannexins (Panxs). Cxs have been described for more than forty years as pivotal regulators of embryogenesis; however, the exact mechanism by which they provide this regulation has not been clearly elucidated. Consequently, Cxs and Panxs have been linked to congenital neurodegenerative diseases such as Charcot-Marie-Tooth disease and, more recently, chronic hemichannel opening has been associated with adult neurodegenerative diseases (e.g., Alzheimer's disease). Cell-to-cell communication via gap junctions formed by hexameric assemblies of Cxs, known as connexons, is believed to be a crucial component in developmental regulation. As for Panxs, despite being topologically similar to Cxs, they predominantly seem to form channels connecting the cytoplasm to the extracellular space and, despite recent research into Panx1 (Pannexin 1) expression in different regions of the brain during the embryonic phase, it has been studied to a lesser degree. When it comes to the nervous system, Cxs and Panxs play an important role in early stages of neuronal development with a wide span of action ranging from cellular migration during early stages to neuronal differentiation and system circuitry formation. In this review, we describe the most recent available evidence regarding the molecular and structural aspects of Cx and Panx channels, their role in neurodevelopment, congenital and adult neurological diseases, and finally propose how pharmacological modulation of these channels could modify the pathogenesis of some diseases.

Immune-related adverse events of biological immunotherapies used in COVID-19.

The use of biological immunotherapeutic drugs is one of the options currently being evaluated and employed to manage COVID-19, specifically monoclonal antibodies, which have shown benefit by regulating the excessive immune response seen in patients with severe infection, known as a cytokine storm. Tocilizumab has received particular importance for this clinical application, as has sarilumab. Both drugs share a substantial similarity in terms of pharmacodynamics, being inhibitors of the interleukin six receptor (IL-6Rα). Furthermore, sotrovimab, a neutralizing anti-SARS CoV-2 antibody, has gained the attention of the scientific community since it has recently been authorized under certain circumstances, positioning itself as a new therapeutic alternative in development. However, despite their clinical benefit, biological immunotherapies have the potential to generate life-threatening immune-related adverse events. Therefore it is essential to review their incidence, mechanism, and risk factors. This review aims to provide a comprehensive understanding of the safety of the biological immunotherapeutic drugs currently recommended for the treatment of COVID-19, provide a review of the known immune-mediated adverse events and explore the potential immune-related mechanisms of other adverse reactions.

Type III Kounis Syndrome Secondary to Ciprofloxacin-Induced Hypersensitivity.

Kounis syndrome (KS) is a rare syndrome characterized by the co-occurrence of acute coronary syndromes in the setting of mast cell and platelet activation in response to hypersensitivity reactions. It can be manifested as coronary vasospasms, acute myocardial infarction, or stent thrombosis triggered by drugs, vaccines, foods, coronary stents, and insect bites. It is a life-threatening condition that needs to be adequately recognized for early diagnosis and appropriate treatment. In this case report, we present a 71-year-old patient with a history of arterial hypertension and non-ST elevation myocardial infarction six months earlier that was treated percutaneously with angioplasty plus stent implantation in the circumflex artery, who subsequently presented to the emergency department due to generalized itching associated with tongue swelling, dyspnea, and chest pain after ingestion of ciprofloxacin for the treatment of a urogenital infection. An electrocardiogram showed ST elevation in II, III, and aVF leads, and positive troponin; thus, a coronary arteriography was performed that showed complete thrombotic stent occlusion in the circumflex artery. Consequently, diagnosis of type 4b inferolateral acute myocardial infarction secondary to ciprofloxacin-triggered type III Kounis syndrome was made. The aim of this report is to understand the relationship between the allergic reaction to ciprofloxacin and the acute coronary syndrome, and to create awareness of the importance of early diagnosis and treatment of this potentially fatal syndrome.

Prescription for COVID-19 by non-medical professionals during the pandemic in Colombia: a cross-sectional study.

Background: The COVID-19 pandemic has led to an increase in the behavior of self-medication (SM). Given the massive release of misleading information during the pandemic, some pharmacies recommend drugs such as ivermectin, azithromycin, and hydroxychloroquine that are not useful for preventing or treating COVID-19 and could expose patients to unnecessary adverse drug reactions (ADRs), drug-drug interactions (DDIs), disease masking, and antibiotic resistance. Rationale: SM with drugs advertised for COVID-19 can have consequences, and people should be aware of approved uses, potential contraindications, and ADRs. Thus, the aim of this study was to know the drug therapies including natural products and homeopathic drugs offered by Colombian pharmaceutical establishments for the prevention and treatment of COVID-19, as well as the information provided on the safe use of the product. Methods: An observational, cross-sectional mystery shopping study was carried out to determine the pharmaceutical alternatives for the management of COVID-19 offered by pharmaceutical establishments (drugstores, pharmacies, homeopathic pharmacies, and nutritional supplements stores) in Colombia, and information related to the safe use of the product. The study included 482 pharmaceutical establishments from 16 Colombian departments. Data collection was done through telephone calls to each of the establishments following an interview protocol pretending to be a patient who presents symptoms related to COVID-19. Results: About 57.3% (276) of the establishments recommended a product for the treatment of COVID-19 infection, 66.6% (321) asked whether the caller had COVID-19 symptoms and what they are, and 44.2% (213) suggested taking a COVID-19 test. Of 59 drugs suggested by pharmacies, the most recommended were azithromycin, ivermectin, acetaminophen, ibuprofen, and ASA (aspirin). From the establishments that recommended a product, dosage was indicated in 85.5% (236) of the pharmaceutical establishments and 14.5% (40) of the establishments reported the most common adverse effects of this substance. About 9.4% (26) of the establishments reported possible interactions of the recommended drugs and substances with food, beverages, or supplements.Conclusion: Pharmaceutical establishments in Colombia seem to have significantly contributed to self-medication for COVID-19 in Colombia during the pandemic. This behavior is inappropriate, since the mild forms of the disease do not have a specific treatment. Plain Language Summary: Self-medication induced by pharmaceutical establishments in Colombia during the COVID-19 pandemic Background: The COVID-19 pandemic has led to an increase in the behavior of self-medication (SM). Given the massive release of misleading information during the pandemic, some pharmacies recommend drugs such as ivermectin, azithromycin, hydroxychloroquine among others, which are not useful for preventing or treating COVID-19 and could expose patients to unnecessary side effects and interactions with other medications. People should be aware of the approved and non-approved uses, and potential side effects of these drugs. Rationale: The aim of this study was to know the drugs, including natural products and homeopathic drugs, offered by Colombian pharmaceutical establishments for the prevention and treatment of COVID-19, as well as the information provided on the safe use of the product. Methods: The study was done using the mystery shopping method, collecting data through telephone calls to each of the establishments by a trained individual pretending to be a patient with COVID-19 symptoms. The study included 482 pharmaceutical establishments from 16 Colombian departments. Results: Of 59 drugs suggested by pharmacies, the most recommended were azithromycin, ivermectin, acetaminophen, ibuprofen, and aspirin. The recommended dose was indicated in 85.5% (236) of the pharmaceutical establishments, and 14.5% (40) of them reported the most common adverse effects of the recommended product. About 9.4% (26) of the establishments reported possible interactions of the recommended drugs and substances with food, beverages, or supplements. Conclusion: The majority of the pharmaceutical establishments included in the study promoted inadequate self-medication for COVID-19 in Colombia during the pandemic.

Therapeutic Drug Monitoring of Antifungal Agents in Critically Ill Patients: Is There a Need for Dose Optimisation?

Invasive fungal infections are an important cause of morbidity and mortality, especially in critically ill patients. Increasing resistance rates and inadequate antifungal exposure have been documented in these patients, due to clinically relevant pharmacokinetic (PK) and pharmacodynamic (PD) alterations, leading to treatment failure. Physiological changes such as third spacing (movement of fluid from the intravascular compartment to the interstitial space), hypoalbuminemia, renal failure and hepatic failure, as well as common interventions in the intensive care unit, such as renal replacement therapy and extracorporeal membrane oxygenation, can lead to these PK and PD alterations. Consequently, a therapeutic target concentration that may be useful for one patient may not be appropriate for another. Regular doses do not take into account the important PK variations in the critically ill, and the need to select an effective dose while minimising toxicity advocates for the use of therapeutic drug monitoring (TDM). This review aims to describe the current evidence regarding optimal PK/PD indices associated with the clinical efficacy of the most commonly used antifungal agents in critically ill patients (azoles, echinocandins, lipid complexes of amphotericin B, and flucytosine), provide a comprehensive understanding of the factors affecting the PK of each agent, document the PK parameters of critically ill patients compared to healthy volunteers, and, finally, make recommendations for therapeutic drug monitoring (TDM) of antifungals in critically ill patients.

Fast and efficient electrochemical thinning of ultra-large supported and free-standing MoS2 layers on gold surfaces.

Molybdenum disulfide (MoS2) is a very promising layered material for electrical, optical, and electrochemical applications because of its unique and outstanding properties. To unlock its full potential, among different preparation routes, electrochemistry has gain interest due to its simple, fast, scalable and simple instrumentation. However, obtaining large-area monolayer MoS2 that will enable the fabrication of novel electronic and electrochemical devices is still challenging. In this work, we reported a simple and fast electrochemical thinning process that results in ultra-large MoS2 down to monolayer on Au surfaces. The high affinity of MoS2 by Au surfaces enables the removal of bulk layers while preserving the first layer attached to the electrode. With a proper choice of the applied potential, more than 90% of the bulk regions can be removed from large-area MoS2 crystals, as confirmed by atomic force microscopy, photoluminescence, and Raman spectroscopy. We further address a set of contributions that are helpful to elucidate the features of MoS2, namely, the hyphenation of electrochemistry and optical microscopy for real-time observation of the thinning process that was revealed to occur from the edges to the center of the flake, an image treatment to estimate the thinning area and thinning rate, and the preparation of free-standing MoS2 layers by electrochemically thinning bulk flakes on microhole-structured Ni/Au meshes.

Estrategia de predicción pacientes con casos de coronavirus; reporte de experiencia Pereira, Risaralda, marzo-abril 2020 / Prediction strategy for patients with coronavirus cases; experience report Pereira, Risaralda, March- April 2020

Resumen Introducción: la infección por COVID 19 corresponde actualmente al evento infeccioso con mayor impacto en salud púbica a nivel mundial, en Colombia, al 30 de abril de 2020 se registraron 6465 casos acumulados, 360 defunciones y 2186 casos recuperados, dado el aumento en los casos reportados mediante los sistemas de vigilancia epidemiológica se precisa de herramientas que faciliten el diagnóstico oportuno y la predicción en el comportamiento de los casos a nivel nacional. Objetivos: proponer un modelo estadístico que permita predecir la probabilidad de cursar con diagnóstico de COVID-19 en la población atendida por sospecha de infección por el mismo en una institución de tercer nivel del municipio de Pereira- Risaralda entre marzo y abril de 2020. Materiales y métodos: se presenta un estudio descriptivo de corte trasversal en el cual se analizaron 82 casos, se realizó un modelo predictivo basado en compuertas lógicas AND y OR, y análisis por estadística descriptiva e inferencial. Resultados: de los 82 registros analizados se encontró una relación hombre: mujer de 1:2; el 6% de los pacientes tuvo alta probabilidad para diagnóstico de COVID 19, el 20% tuvo probabilidad intermedia y el 72% registró baja probabilidad para COVID19, la concordancia del modelo con los resultados de las pruebas fue inferior a 0,5. Conclusiones: el modelo estadístico planteado fue insuficiente para lograr la predicción de la totalidad de los casos de COVID-19 basados en el perfil de riego de la población, se precisan nuevas investigaciones con tamaños de muestra superiores, diseños y análisis distintos. MÉD.UIS.2022;35(1): 57-69.

Abstract Introduction: COVID 19 infection currently corresponds to the infectious event with the greatest impact on public health worldwide, in Colombia, as of April 30, 2020, 6465 accumulated cases, 360 deaths and 2186 recovered cases were registered, given the increase in cases reported through epidemiological surveillance systems, tools are needed to facilitate timely diagnosis and prediction in the behavior of cases at the national level. Objectives: to propose a statistical model that allows predicting the probability of a diagnosis of COVID-19 in the population treated for suspected coronavirus infection in a third-level institution in the population of Pereira-Risaralda between March and April 2020. Materials and methods: a descriptive cross-sectional study is presented, in which 82 cases were analyzed, a predictive model based on AND and OR logic gates, analyzes by descriptive and inferential statistics were performed. Results: of the 82 records analyzed, a male: female ratio of 1: 2 was found; 6% of the patients had a high probability for the diagnosis of COVID 19, 20% had an intermediate probability and 72% had a low probability for COVID19, the agreement of the model with the test results was less than 0.5. Conclusions: the proposed statistical model was insufficient to achieve the prediction of all the cases of COVID-19 based on the irrigation profile of the population. New investigations are required with larger sample sizes associated with longitudinal designs and combined statistical analyzes that allow to refine the proposed model. MÉD.UIS.2022;35(1): 57-69.

Use of extracorporeal membrane oxygenation in non-elective major thoracic surgery for infectious lung abscess.

OBJECTIVES: Extracorporeal membrane oxygenation (ECMO) support for elective cardiothoracic surgery is well established. In contrast, there are not much data regarding the usefulness and outcome of ECMO in non-elective major lung resections for infectious lung abscess. METHODS: All patients undergoing non-elective major lung surgery for infectious lung abscess at 5 centres in Germany, UK and Spain were enrolled in a prospective database. Malignant disorders and intrathoracic complications of other procedures were excluded. RESULTS: There were 127 patients. The median age was 59 years (interquartile range 18.75). The mean Charlson index of comorbidity was 2.83 (standard deviation 2.57). Surgical procedures were lobectomy (89), pneumectomy (20) and segmentectomy (18). ECMO was used for 10 patients (pneumectomy 2, lobectomy 8) and several more received pre-ECMO treatment. Mortality was 17/127. Intraoperatively no ECMO-associated complications were encountered. EMCO [1/10 vs 16/117; odds ratio (OR): 0.70, 95% confidence interval (CI) 0.08-5.91, P = 0.74] and the extent of pulmonary resection were not associated with higher mortality. Preoperative sepsis (OR: 17.84, 95% CI 2.29-139.28, P < 0.01), preoperative air leak (OR: 13.12, 95% CI 4.10-42.07, P < 0.001), acute renal failure (OR: 7.00, 95% CI 2.19-22.43, P < 0.01) and Charlson index of comorbidity ≥3 (OR: 10.83, 95% CI 2.36-49.71, P < 0.01) were associated with significantly higher mortality. CONCLUSIONS: The application of ECMO is widening the possibilities for successful surgical management of infectious, non-malignant lung abscesses. Particularly, patients with marginal functional operability benefit from the availability and readiness to use ECMO. Mortality is determined by the burden of pre-existent comorbidity, severe sepsis and septic shock.

Revisiting Excitotoxicity in Traumatic Brain Injury: From Bench to Bedside.

Traumatic brain injury (TBI) is one of the leading causes of morbidity and mortality. Consequences vary from mild cognitive impairment to death and, no matter the severity of subsequent sequelae, it represents a high burden for affected patients and for the health care system. Brain trauma can cause neuronal death through mechanical forces that disrupt cell architecture, and other secondary consequences through mechanisms such as inflammation, oxidative stress, programmed cell death, and, most importantly, excitotoxicity. This review aims to provide a comprehensive understanding of the many classical and novel pathways implicated in tissue damage following TBI. We summarize the preclinical evidence of potential therapeutic interventions and describe the available clinical evaluation of novel drug targets such as vitamin B12 and ifenprodil, among others.