Incidence of confusional syndrome (delirium) in a Latin American university hospital.

BACKGROUND: Little is known about the incidence of delirium and its subtypes in patients admitted to different departments of university hospitals in Latin America. OBJECTIVE: To determine the incidence of delirium and the frequency of its subtypes, as well as its associated factors, in patients admitted to different departments of a university hospital in Bogotá, Colombia. METHODS: A cohort of patients over 18 years of age admitted to the internal medicine (IM), geriatrics (GU), general surgery (GSU), orthopaedics (OU) and intensive care unit (ICU) services of a university hospital was followed up between January and June 2018. To detect the presence of delirium, we used the CAM (Confusion Assessment Method) and the CAM-ICU if the patient had decreased communication skills. The delirium subtype was characterised using the RASS (Richmond Agitation and Sedation Scale). Patients were assessed on their admission date and then every two days until discharged from the hospital. Those in whom delirium was identified were referred for specialised intra-institutional interdisciplinary management. RESULTS: A total of 531 patients admitted during the period were assessed. The overall incidence of delirium was 12% (95% CI, 0.3-14.8). They represented 31.8% of patients in the GU, 15.6% in the ICU, 8.7% in IM, 5.1% in the OU, and 3.9% in the GSU. The most frequent clinical display was the mixed subtype, at 60.9%, followed by the normoactive subtype (34.4%) and the hypoactive subtype (4.7%). The factors most associated with delirium were age (adjusted RR = 1.07; 95% CI, 1.05-1.09), the presence of four or more comorbidities (adjusted RR = 2.04; 95% CI, 1.31-3.20), and being a patient in the ICU (adjusted RR = 2.02; 95% CI, 1.22-3.35). CONCLUSIONS: The incidence of delirium is heterogeneous in the different departments of the university hospital. The highest incidence occurred in patients that were admitted to the GU. The mixed subtype was the most frequent one, and the main associated factors were age, the presence of four or more comorbidities, and being an ICU patient.

Study of erythrocyte sedimentation in human blood through the photoacoustic signals analysis.

Introduction: In this study, we utilized the pulsed photoacoustic (PA) technique to analyze globular sedimentation in whole human blood, with a focus on distinguishing between healthy individuals and those with hemolytic anemia. Methods: Blood samples were collected from both healthy individuals (women and men) and those with hemolytic anemia, and temporal and spectral parameters of PA signals were employed for analysis. Results: Significant differences (p < 0.05) were observed in PA metrics between the two groups. The proposed spectral analysis allowed significant differentiation within a 25-minute measurement window. Anemic blood samples exhibited higher erythrocyte sedimentation rate (ESR) values, indicating increased erythrocyte aggregation. Discussion: This study underscores the potential of PA signal analysis in ESR assessment as an efficient method for distinguishing between healthy and anemic blood, surpassing traditional approaches. It represents a promising contribution to the development of precise and sensitive techniques for analyzing human blood samples in clinical settings.

Dynamic modeling of photoacoustic sensor data to classify human blood samples.

The photoacoustic effect is an attractive tool for diagnosis in several biomedical applications. Analyzing photoacoustic signals, however, is challenging to provide qualitative results in an automated way. In this work, we introduce a dynamic modeling scheme of photoacoustic sensor data to classify blood samples according to their physiological status. Thirty-five whole human blood samples were studied with a state-space model estimated by a subspace method. Furthermore, the samples are classified using the model parameters and the linear discriminant analysis algorithm. The classification performance is compared with time- and frequency-domain features and an autoregressive-moving-average model. As a result, the proposed analysis can predict five blood classes: healthy women and men, microcytic and macrocytic anemia, and leukemia. Our findings indicate that the proposed method outperforms conventional signal processing techniques to analyze photoacoustic data for medical diagnosis. Hence, the method is a promising tool in point-of-care devices to detect hematological diseases in clinical scenarios.

What do we know about the function of SARS-CoV-2 proteins?

The COVID-19 pandemic has highlighted the importance in the understanding of the biology of SARS-CoV-2. After more than two years since the first report of COVID-19, it remains crucial to continue studying how SARS-CoV-2 proteins interact with the host metabolism to cause COVID-19. In this review, we summarize the findings regarding the functions of the 16 non-structural, 6 accessory and 4 structural SARS-CoV-2 proteins. We place less emphasis on the spike protein, which has been the subject of several recent reviews. Furthermore, comprehensive reviews about COVID-19 therapeutic have been also published. Therefore, we do not delve into details on these topics; instead we direct the readers to those other reviews. To avoid confusions with what we know about proteins from other coronaviruses, we exclusively report findings that have been experimentally confirmed in SARS-CoV-2. We have identified host mechanisms that appear to be the primary targets of SARS-CoV-2 proteins, including gene expression and immune response pathways such as ribosome translation, JAK/STAT, RIG-1/MDA5 and NF-kß pathways. Additionally, we emphasize the multiple functions exhibited by SARS-CoV-2 proteins, along with the limited information available for some of these proteins. Our aim with this review is to assist researchers and contribute to the ongoing comprehension of SARS-CoV-2's pathogenesis.

Study of Polyvinyl Alcohol Hydrogels Applying Physical-Mechanical Methods and Dynamic Models of Photoacoustic Signals.

This study aims to analyze the physical-mechanical properties and dynamic models of tissue-simulating hydrogels, specifically the photoacoustic (PA) response signals, by varying the concentrations of polyvinyl alcohol (PVA) and molecular weight (MW). A state-space model (SSM) is proposed to study the PVA hydrogels to retrieve the PA-related signal's damping ratio and natural frequency. Nine box-shaped PVA hydrogels containing saline solution were used, with five concentrations of PVA (7, 9, 12, 15, 20%) for MW1 and four for MW2. The results indicated that the concentration of PVA and MW played an important role in the PA wave's amplitude, arrival time, and speed of sound over the hydrogels. The SSM parameters showed that increasing PVA and MW concentrations improved the hydrogels' ability to absorb and transfer energy under the PA effect. These parameters were also found to be correlated with density and modulus of elasticity. Additionally, the concentrations of PVA and MW affected the absorption and optical scattering coefficients. The physical-mechanical properties, including porosity, density, and modulus of elasticity, improved as the concentration of PVA and MW increased. The ultimate goal of this study is to develop hydrogels as phantoms that can be used for tissue simulation and imaging.

Effective Capacitance from Equivalent Electrical Circuit as a Tool for Monitoring Non-Adherent Cell Suspensions at Low Frequencies.

Analyzing the electrical double layer (EDL) in electrical impedance spectroscopy (EIS) measurement at low frequencies remains a challenging task for sensing purposes. In this work, we propose two approaches to deal with the EDL in measuring impedance for particles and non-adherent cells in an electrolytic suspension. The first approach is a simple procedure to compute a normalized electrical impedance spectrum named dispersed medium index (DMi). The second is the EIS modeling through an equivalent electric circuit based on the so-called effective capacitance (Cef), which unifies the EDL phenomena. Firstly, as an experiment under controlled conditions, we examine polymer particles of 6, 15, and 48 µm in diameter suspended in a 0.9% sodium chloride solution. Subsequently, we used K-562 cells and leukocytes suspended in a culture medium (RPMI-1640 supplemented) for a biological assay. As the main result, the DMi is a function of the particle concentration. In addition, it shows a tendency with the particle size; regardless, it is limited to a volume fraction of 0.03 × 10-4 to 58 × 10-4. The DMi is not significantly different between K-562 cells and leukocytes for most concentrations. On the other hand, the Cef exhibits high applicability to retrieve a function that describes the concentration for each particle size, the K-562 cells, and leukocytes. The Cef also shows a tendency with the particle size without limitation within the range tested, and it allows distinction between the K-562 and leukocytes in the 25 cells/µL to 400 cells/µL range. We achieved a simple method for determining an Cef by unifying the parameters of an equivalent electrical circuit from data obtained with a conventional potentiostat. This simple approach is affordable for characterizing the population of non-adherent cells suspended in a cell culture medium.

Loop-mediated isothermal amplification-based electrochemical sensor for detecting SARS-CoV-2 in wastewater samples.

The current pandemic COVID-19 caused by the coronavirus SARS-CoV-2, has generated different economic, social and public health problems. Moreover, wastewater-based epidemiology could be a predictor of the virus rate of spread to alert on new outbreaks. To assist in epidemiological surveillance, this work introduces a simple, low-cost and affordable electrochemical sensor to specifically detect N and ORF1ab genes of the SARS-CoV-2 genome. The proposed sensor works based on screen-printed electrodes acting as a disposable test strip, where the reverse transcription loop-mediated isothermal amplification (RT-LAMP) reaction takes place. Electrochemical detection relies upon methylene blue as a redox intercalator probe, to provide a diffusion-controlled current encoding the presence and concentration of RT-LAMP products, namely amplicons or double-stranded DNA. We test the performance of the sensor by testing real wastewater samples using end-point and time course measurements. Results show the ability of the electrochemical test strip to specifically detect and quantify RT-LAMP amplicons below to ~ 2.5 × 10-6 ng/µL exhibiting high reproducibility. In this sense, our RT-LAMP electrochemical sensor is an attractive, efficient and powerful tool for rapid and reliable wastewater-based epidemiology studies.

Dynamics of SARS-CoV-2 mutations reveals regional-specificity and similar trends of N501 and high-frequency mutation N501Y in different levels of control measures.

Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This disease has spread globally, causing more than 161.5 million cases and 3.3 million deaths to date. Surveillance and monitoring of new mutations in the virus' genome are crucial to our understanding of the adaptation of SARS-CoV-2. Moreover, how the temporal dynamics of these mutations is influenced by control measures and non-pharmaceutical interventions (NPIs) is poorly understood. Using 1,058,020 SARS-CoV-2 from sequenced COVID-19 cases from 98 countries (totaling 714 country-month combinations), we perform a normalization by COVID-19 cases to calculate the relative frequency of SARS-CoV-2 mutations and explore their dynamics over time. We found 115 mutations estimated to be present in more than 3% of global COVID-19 cases and determined three types of mutation dynamics: high-frequency, medium-frequency, and low-frequency. Classification of mutations based on temporal dynamics enable us to examine viral adaptation and evaluate the effects of implemented control measures in virus evolution during the pandemic. We showed that medium-frequency mutations are characterized by high prevalence in specific regions and/or in constant competition with other mutations in several regions. Finally, taking N501Y mutation as representative of high-frequency mutations, we showed that level of control measure stringency negatively correlates with the effective reproduction number of SARS-CoV-2 with high-frequency or not-high-frequency and both follows similar trends in different levels of stringency.

Global Geographic and Temporal Analysis of SARS-CoV-2 Haplotypes Normalized by COVID-19 Cases During the Pandemic.

Since the identification of SARS-CoV-2, a large number of genomes have been sequenced with unprecedented speed around the world. This marks a unique opportunity to analyze virus spreading and evolution in a worldwide context. Currently, there is not a useful haplotype description to help to track important and globally scattered mutations. Also, differences in the number of sequenced genomes between countries and/or months make it difficult to identify the emergence of haplotypes in regions where few genomes are sequenced but a large number of cases are reported. We propose an approach based on the normalization by COVID-19 cases of relative frequencies of mutations using all the available data to identify major haplotypes. Furthermore, we can use a similar normalization approach to tracking the temporal and geographic distribution of haplotypes in the world. Using 171,461 genomes, we identify five major haplotypes or operational taxonomic units (OTUs) based on nine high-frequency mutations. OTU_3 characterized by mutations R203K and G204R is currently the most frequent haplotype circulating in four of the six continents analyzed (South America, North America, Europe, Asia, Africa, and Oceania). On the other hand, during almost all months analyzed, OTU_5 characterized by the mutation T85I in nsp2 is the most frequent in North America. Recently (since September), OTU_2 has been established as the most frequent in Europe. OTU_1, the ancestor haplotype, is near to extinction showed by its low number of isolations since May. Also, we analyzed whether age, gender, or patient status is more related to a specific OTU. We did not find OTU's preference for any age group, gender, or patient status. Finally, we discuss structural and functional hypotheses in the most frequently identified mutations, none of those mutations show a clear effect on the transmissibility or pathogenicity.

Therapeutic dilemma: alcohol withdrawal syndrome and concurrent hepatic encephalopathy. A case report. / Dilema terapéutico: síndrome de abstinencia alcohólica y encefalopatía hepática concurrentes. A propósito de un caso.

Alcohol use disorder is one of the main causes of morbidity and mortality in the world. Alcoholic liver disease is a common complication of this disorder, and hepatic encephalopathy is a serious complication of alcoholic cirrhosis. Precipitating factors may be related to infection, gastrointestinal bleeding, dehydration or the effects of psychotropic drugs (e.g. benzodiazepines and non-benzodiazepine hypnotics). We present a case of the hospital management of a patient with a severe alcohol use disorder, cirrhosis and hepatic encephalopathy who developed alcohol withdrawal symptoms while in hospital, and discuss the complexity of the antagonistic management of a GABAergic delirium characteristic of hepatic encephalopathy in the context of a glutamatergic-noradrenergic delirium due to alcohol withdrawal.

Dilema terapéutico: síndrome de abstinencia alcohólica y encefalopatía hepática concurrentes. A propósito de un caso / Therapeutic dilemma: alcohol withdrawal syndrome and concurrent hepatic encephalopathy. A case report

RESUMEN El trastorno por consumo de alcohol es una de las principales causas de morbimortalidad en el mundo. La enfermedad hepática alcohólica es una complicación común de este trastorno y la encefalopatía hepática es una seria comorbilidad de la cirrosis alcohólica. Los factores precipitantes pueden relacionarse con infección, sangrado gastrointestinal, deshidratación o efectos de psicofármacos (p. ej., benzodiacepinas e hipnóticos no benzodiacepínicos). Se expone un caso del manejo hospitalario de un paciente con un trastorno severo por consumo de alcohol, cirrosis y encefalopatía hepática, quien desarrolla síntomas de abstinencia alcohólica durante su hospitalización y la complejidad del manejo antagónico de un delirium gabaérgico propio de la encefalopatía hepática en el contexto de un delirium glutamatérgico-noradrenérgico por abstinencia alcohólica.

ABSTRACT Alcohol use disorder is one of the main causes of morbidity and mortality in the world. Alcoholic liver disease is a common complication of this disorder, and hepatic encephalopathy is a serious complication of alcoholic cirrhosis. Precipitating factors may be related to infection, gastrointestinal bleeding, dehydration or the effects of psychotropic drugs (e.g. benzodiazepines and non-benzodiazepine hypnotics). We present a case of the hospital management of a patient with a severe alcohol use disorder, cirrhosis and hepatic encephalopathy who developed alcohol withdrawal symptoms while in hospital, and discuss the complexity of the antagonistic management of a GABAergic delirium characteristic of hepatic encephalopathy in the context of a glutamatergic-noradrenergic delirium due to alcohol withdrawal.

Antibody Derived Peptides for Detection of Ebola Virus Glycoprotein.

BACKGROUND: Current Ebola virus (EBOV) detection methods are costly and impractical for epidemic scenarios. Different immune-based assays have been reported for the detection and quantification of Ebola virus (EBOV) proteins. In particular, several monoclonal antibodies (mAbs) have been described that bind the capsid glycoprotein (GP) of EBOV GP. However, the currently available platforms for the design and production of full-length mAbs are cumbersome and costly. The use of antibody fragments, rather than full-length antibodies, might represent a cost-effective alternative for the development of diagnostic and possibly even therapeutic alternatives for EBOV. METHODS/PRINCIPAL FINDINGS: We report the design and expression of three recombinant anti-GP mAb fragments in Escherichia coli cultures. These fragments contained the heavy and light variable portions of the three well-studied anti-GP full-length mAbs 13C6, 13F6, and KZ52, and are consequently named scFv-13C6, scFv-13F6, and Fab-KZ52, respectively. All three fragments exhibited specific anti-GP binding activity in ELISA experiments comparable to that of full-length anti-GP antibodies (i.e., the same order of magnitude) and they are easily and economically produced in bacterial cultures. CONCLUSION/SIGNIFICANCE: Antibody fragments might represent a useful, effective, and low cost alternative to full-length antibodies in Ebola related capture and diagnostics applications.

A baseline process for the production, recovery, and purification of bacterial influenza vaccine candidates.

The current commercial system for influenza vaccine production depends on the culture of virus in embryonated eggs--a strategy that is both costly and poorly scalable. Consequently, a sudden pandemic event with a demand for millions of vaccine doses in a short time could readily overwhelm the available world production capacity. In this communication, we present a process that uses Escherichia coli for scalable production of recombinant vaccine candidates against influenza. A monomeric and a dimeric fragment of hemagglutinin of the influenza A H1N1/2009 virus were successfully expressed in a BL21 (DE3) pLysS variety of C41 E. coli. We present results from batch processes where induction is made with isopropyl thiogalactoside and from fed-batch experiments where expression is induced using lactose/glucose pulses. Concentrations in the range of 1.188-0.605 g/L of recombinant protein were observed in 2-L stirred tank bioreactors. The genetic construct included an N-terminal histidine tag sequence that facilitated recovery, purification, and proper refolding of the vaccine candidate by affinity chromatography in columns loaded with Ni(+2) . The proteins produced by this strategy selectively and specifically recognizes antibodies from patients diagnosed as positive to influenza A H1N1/2009. Overall protein recovery yields between 30.0 and 34.7% were typically observed. Based on these yields, a production of 4.6 × 10(3) doses L(-3) day(-1) is feasible.