Protein production dynamics and physiological adaptation of recombinant Komagataella phaffii at near-zero growth rates.

BACKGROUND: Specific productivity (qP) in yeast correlates with growth, typically peaking at intermediate or maximum specific growth rates (µ). Understanding the factors limiting productivity at extremely low µ might reveal decoupling strategies, but knowledge of production dynamics and physiology in such conditions is scarce. Retentostats, a type of continuous cultivation, enable the well-controlled transition to near-zero µ through the combined retention of biomass and limited substrate supply. Recombinant Komagataella phaffii (syn Pichia pastoris) secreting a bivalent single domain antibody (VHH) was cultivated in aerobic, glucose-limited retentostats to investigate recombinant protein production dynamics and broaden our understanding of relevant physiological adaptations at near-zero growth conditions. RESULTS: By the end of the retentostat cultivation, doubling times of approx. two months were reached, corresponding to µ = 0.00047 h-1. Despite these extremely slow growth rates, the proportion of viable cells remained high, and de novo synthesis and secretion of the VHH were observed. The average qP at the end of the retentostat was estimated at 0.019 mg g-1 h-1. Transcriptomics indicated that genes involved in protein biosynthesis were only moderately downregulated towards zero growth, while secretory pathway genes were mostly regulated in a manner seemingly detrimental to protein secretion. Adaptation to near-zero growth conditions of recombinant K. phaffii resulted in significant changes in the total protein, RNA, DNA and lipid content, and lipidomics revealed a complex adaptation pattern regarding the lipid class composition. The higher abundance of storage lipids as well as storage carbohydrates indicates that the cells are preparing for long-term survival. CONCLUSIONS: In conclusion, retentostat cultivation proved to be a valuable tool to identify potential engineering targets to decouple growth and protein production and gain important insights into the physiological adaptation of K. phaffii to near-zero growth conditions.

The impact of the COVID-19 pandemic on people living with HIV: a cross-sectional study in Caracas, Venezuela.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has disrupted multiple health services, including human immunodeficiency virus (HIV) testing, care, and treatment services, jeopardizing the achievement of the Joint United Nations Programme on HIV/AIDS 90-90-90 global target. While there are limited studies assessing the impact of the COVID-19 pandemic on people living with HIV (PLHIV) in Latin America, there are none, to our knowledge, in Venezuela. This study aims to assess the impact of the COVID-19 pandemic among PLHIV seen at the outpatient clinic of a reference hospital in Venezuela. METHODS: We conducted a cross-sectional study among PLHIV aged 18 years and over seen at the Infectious Diseases Department of the University Hospital of Caracas, Venezuela between March 2021 and February 2022. RESULTS: A total of 238 PLHIV were included in the study. The median age was 43 (IQR 31-55) years, and the majority were male (68.9%). Most patients (88.2%, n = 210) came for routine check-ups, while 28 (11.3%) were newly diagnosed. The majority of patients (96.1%) were on antiretroviral therapy (ART), but only 67.8% had a viral load test, with almost all (95.6%) being undetectable. Among those who attended regular appointments, 11.9% reported missing at least one medical consultation, and 3.3% reported an interruption in their ART refill. More than half of the patients (55.5%) had received at least one dose of the COVID-19 vaccine, while the rest expressed hesitancy to get vaccinated. Most patients with COVID-19 vaccine hesitancy were male (65.1%), younger than 44 years (57.5%), employed (47.2%), and had been diagnosed with HIV for less than one year (33%). However, no statistically significant differences were found between vaccinated patients and those with COVID-19 vaccine hesitancy. Older age was a risk factor for missing consultations, while not having an alcoholic habit was identified as a protective factor against missing consultations. CONCLUSION: This study found that the COVID-19 pandemic had a limited impact on adherence to medical consultations and interruptions in ART among PLHIV seen at the University Hospital of Caracas, Venezuela.

Understanding the factors associated with COVID-19 vaccine hesitancy in Venezuela.

BACKGROUND: Despite nearly a quarter of Venezuelans remaining unvaccinated against coronavirus disease 2019 (COVID-19), the factors contributing to vaccine hesitancy in the country have not been thoroughly investigated. METHODS: A cross-sectional study was conducted from October 15th to 30th, 2022, using a knowledge, attitudes, and practices (KAP) survey to identify factors associated with COVID-19 vaccine hesitancy. RESULTS: The study analyzed data from 1,930 participants from all 24 states of Venezuela. The majority (93.4%) were vaccinated. The mean age was 40 years, predominantly female (67.3%), and held a university degree (70.6%). The mean KAP score was significantly higher among vaccinated individuals compared to unvaccinated ones (7.79 vs. 3.94 points for knowledge, 40 vs. 24 points for attitudes, and 16 vs. 10 points for practices, all p < 0.001). Increases in the scores for KAP were associated with increased odds of being vaccinated (84.6%, 25.6%, and 33% respectively for each one-point increase, all p < 0.001). Certain demographic factors such as marital status, occupation, religious beliefs, monthly income, and location influence COVID-19 vaccine knowledge. Higher income and certain occupations decrease the odds of low knowledge, while residing in specific states increases it. Attitudes towards the COVID-19 vaccine are influenced by age, health status, vaccination status, and location. Higher income and absence of certain health conditions decrease the odds of negative attitudes. Lastly, age, occupation, monthly income, and location affect vaccine practices. Advanced age and higher income decrease the odds of inappropriate practices, while residing in La Guaira state increases them. CONCLUSION: Factors such as age, education level, occupation, monthly income, and location were found to be associated with knowledge and attitudes towards COVID-19 vaccine among the surveyed Venezuelans.

Plasmodium vivax and SARS-CoV-2 co-infection in Venezuelan pregnant women: a case series.

BACKGROUND: Malaria-endemic areas are not spared from the impact of coronavirus disease 2019 (COVID-19), leading to co-infection scenarios where overlapping symptoms impose serious diagnostic challenges. Current knowledge on Plasmodium spp. and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) co-infection in pregnant women remains limited, especially in Latin America, where Plasmodium vivax infection is highly prevalent. METHODS: This is a case series of five pregnant women with P. vivax and SARS-CoV-2 co-infection hospitalized in two main malaria referral centers of the Capital District and Bolivar state, Venezuela between March 13, 2020 and December 31, 2021. RESULTS: Clinical and laboratory data from five pregnant women with a mean age of 22 years were analyzed; three of them were in the third trimester of pregnancy. Comorbidities included obesity in two cases, hypertension in one, and asthma in one. Three out of five patients had severe to critical COVID-19 disease. Dry cough, fever, chills, and headache were the most frequent symptoms reported. Laboratory analyses showed elevated aspartate/alanine aminotransferase and creatinine levels, thrombocytopenia, and severe anemia as the most relevant abnormalities. The mean period between symptom onset and a positive molecular test for SARS-CoV-2 infection or positive microscopy for Plasmodium spp. was 4.8 ± 2.5 days and 2.8 ± 1.6 days, respectively. The mean hospital stay was 5.4 ± 7 days. Three women recovered and were discharged from the hospital. Two women died, one from cerebral malaria and one from respiratory failure. Three adverse fetal outcomes were registered, two miscarriages and one stillbirth. CONCLUSION: This study documented a predominance of severe/critical COVID-19 disease and a high proportion of adverse maternal-fetal outcomes among pregnant women with malaria and COVID-19 co-infection. More comprehensive prospective cohort studies are warranted to explore the risk factors, management challenges, and clinical outcomes of pregnant women with this co-infection.

A time-series analysis of morbidity and mortality of viral hepatitis in Venezuela, 1990-2016.

BACKGROUND: Viral hepatitis (VH) is a leading contributor to morbidity and mortality worldwide, constituting a public health problem associated with the level of human development. In recent years, Venezuela has experienced a political, social, and economic crisis and has been impacted by natural disasters that have led to the deterioration of sanitary and health infrastructures modifying the determinants of VH. Despite epidemiological studies conducted in specific regions of the country or populations, the national epidemiological behaviour of VH remains unclear. METHODS: This is a time series study involving records of morbidity and mortality by VH in Venezuela reported during the period from 1990 to 2016. The Venezuelan population was taken as the denominator of the morbidity and mortality rates, according to the Venezuelan National Institute of Statistics and the 2016 population projections from the latest census published on the website of the responsible Venezuelan agency. RESULTS: During the study period, 630,502 cases and 4,679 deaths from VH in Venezuela were analysed. Most of the cases (n = 457,278; 72.6%) were classified as unspecific VH (UVH). The deaths were mainly attributed to VHB (n = 1,532; 32.7%), UVH (n = 1,287; 27.5%), and sequelae of VH (n = 977; 20.8%). The mean rates of cases and deaths from VH in the country were 95 ± 40.4 cases per 100,000 inhabitants and 0.7 ± 0.1 deaths per 100,000 inhabitants, respectively, showing a large dispersion that is evident from the calculation of the coefficients of variation. There was document a strong correlation between UVH and VHA cases (0.78, p < 0.01) morbidity rates. VHB mortality rate was very strongly correlated with sequelae of VH (-0.9, p < 0.01). CONCLUSIONS: VH is a major burden of morbidity and mortality in Venezuela with an endemic-epidemic trend and an intermediate prevalence for VHA, VHB, and VHC. Epidemiological information is not published in a timely manner and diagnostic tests are insufficient in primary health services. There is an urgent need to resume epidemiological surveillance of VH and to optimise the classification system for a better understanding of UVH cases and deaths due to sequelae of VHB and VHC.

New daily persistent headache after SARS-CoV-2 infection in Latin America: a cross-sectional study.

BACKGROUND: Persistent headache is a frequent symptom after coronavirus disease 2019 (COVID-19) and there is currently limited knowledge about its clinical spectrum and predisposing factors. A subset of patients may be experiencing new daily persistent headache (NDPH) after COVID-19, which is among the most treatment-refractory primary headache syndromes. METHODS: We conducted a cross-sectional study in Latin America to characterize individuals with persistent headache after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and to identify factors associated with NDPH. Participants over 18 years old who tested positive for SARS-CoV-2 infection and reported persistent headache among their symptoms completed an online survey that included demographics, past medical history, persistent headache clinical characteristics, and COVID-19 vaccination status. Based on participants' responses, NDPH diagnostic criteria were used to group participants into NDPH and non-NDPH groups. Participant data was summarized by descriptive statistics. Student's t and Mann-Whitney U tests were used according to the distribution of quantitative variables. For categorical variables, Pearson's chi-square and Fisher's exact tests were used according to the size of expected frequencies. Binomial logistic regression using the backward stepwise selection method was performed to identify factors associated with NDPH. RESULTS: Four hundred and twenty-one participants from 11 Latin American countries met the inclusion criteria. One in four participants met the NDPH diagnostic criteria. The mean age was 40 years, with most participants being female (82%). Over 90% of the participants reported having had mild/moderate COVID-19. Most participants had a history of headache before developing COVID-19 (58%), mainly migraine type (32%). The most predominant clinical characteristics in the NDPH group were occipital location, severe/unbearable intensity, burning character, and radiating pain (p < 0.05). A higher proportion of anxiety symptoms, sleep problems, myalgia, mental fog, paresthesia, nausea, sweating of the face or forehead, and ageusia or hypogeusia as concomitant symptoms were reported in participants with NDPH (p < 0.05). Palpebral edema as a concomitant symptom during the acute phase of COVID-19, occipital location, and burning character of the headache were risk factors associated with NDPH. CONCLUSION: This is the first study in Latin America that explored the clinical spectrum of NDPH after SARS-CoV-2 infection and its associated factors. Clinical evaluation of COVID-19 patients presenting with persistent headache should take into consideration NDPH.

Posthoc Interpretability of Neural Responses by Grouping Subject Motor Imagery Skills Using CNN-Based Connectivity.

Motor Imagery (MI) refers to imagining the mental representation of motor movements without overt motor activity, enhancing physical action execution and neural plasticity with potential applications in medical and professional fields like rehabilitation and education. Currently, the most promising approach for implementing the MI paradigm is the Brain-Computer Interface (BCI), which uses Electroencephalogram (EEG) sensors to detect brain activity. However, MI-BCI control depends on a synergy between user skills and EEG signal analysis. Thus, decoding brain neural responses recorded by scalp electrodes poses still challenging due to substantial limitations, such as non-stationarity and poor spatial resolution. Also, an estimated third of people need more skills to accurately perform MI tasks, leading to underperforming MI-BCI systems. As a strategy to deal with BCI-Inefficiency, this study identifies subjects with poor motor performance at the early stages of BCI training by assessing and interpreting the neural responses elicited by MI across the evaluated subject set. Using connectivity features extracted from class activation maps, we propose a Convolutional Neural Network-based framework for learning relevant information from high-dimensional dynamical data to distinguish between MI tasks while preserving the post-hoc interpretability of neural responses. Two approaches deal with inter/intra-subject variability of MI EEG data: (a) Extracting functional connectivity from spatiotemporal class activation maps through a novel kernel-based cross-spectral distribution estimator, (b) Clustering the subjects according to their achieved classifier accuracy, aiming to find common and discriminative patterns of motor skills. According to the validation results obtained on a bi-class database, an average accuracy enhancement of 10% is achieved compared to the baseline EEGNet approach, reducing the number of "poor skill" subjects from 40% to 20%. Overall, the proposed method can be used to help explain brain neural responses even in subjects with deficient MI skills, who have neural responses with high variability and poor EEG-BCI performance.

A Novel OpenBCI Framework for EEG-Based Neurophysiological Experiments.

An Open Brain-Computer Interface (OpenBCI) provides unparalleled freedom and flexibility through open-source hardware and firmware at a low-cost implementation. It exploits robust hardware platforms and powerful software development kits to create customized drivers with advanced capabilities. Still, several restrictions may significantly reduce the performance of OpenBCI. These limitations include the need for more effective communication between computers and peripheral devices and more flexibility for fast settings under specific protocols for neurophysiological data. This paper describes a flexible and scalable OpenBCI framework for electroencephalographic (EEG) data experiments using the Cyton acquisition board with updated drivers to maximize the hardware benefits of ADS1299 platforms. The framework handles distributed computing tasks and supports multiple sampling rates, communication protocols, free electrode placement, and single marker synchronization. As a result, the OpenBCI system delivers real-time feedback and controlled execution of EEG-based clinical protocols for implementing the steps of neural recording, decoding, stimulation, and real-time analysis. In addition, the system incorporates automatic background configuration and user-friendly widgets for stimuli delivery. Motor imagery tests the closed-loop BCI designed to enable real-time streaming within the required latency and jitter ranges. Therefore, the presented framework offers a promising solution for tailored neurophysiological data processing.

Combined use of biochar and alternative management systems for imazamox induced pollution control in rice growing environments.

Imazamox (IMZX) is a persistent herbicide having probable risks for non-target organisms in the environment and water contamination. Alternatives to conventional flooding rice production, including biochar amendment, may induce changes in soil properties which can greatly modify the environmental fate of IMZX. This two-year study is the first to evaluate how tillage and irrigation practices, with or without fresh or aged biochar (Bc), that are alternatives to conventional rice production impact IMZX's environmental fate. The treatments were: conventional tillage and flooding irrigation (CTFI), conventional tillage and sprinkler irrigation (CTSI), no-tillage and sprinkler irrigation (NTSI), and the corresponding Bc-amendment treatments (CTFI-Bc, CTSI-Bc, and NTSI-Bc). Fresh and aged Bc amendment decreased IMZX's sorption onto the soil in tillage treatments, with Kf values decreasing 3.7 and 4.2-fold (fresh case) and 1.5 and 2.6-fold (aged case) for CTSI-Bc and CTFI-Bc, respectively. The transition to sprinkler irrigation reduced IMZX persistence. Overall, Bc amendment also reduced chemical persistence with half-life values decreasing 1.6 and 1.5-fold for CTFI and CTSI (fresh year) and 1.1, 1.1, and 1.3-fold for CTFI, CTSI, and NTSI (aged year), respectively. Sprinkler irrigation reduced IMZX leaching by up to a factor of 2.2. The use of Bc as amendment led to a significant decrease in IMZX leaching only under tillage conditions, but notable in particular for the CTFI case where leaching losses were reduced in the fresh year from 80% to 34% and, in the aged year, from 74% to 50%. Hence the change in irrigation from flooding to sprinkler either alone or in combination with the use of Bc (fresh or aged) amendment could be considered an effective way to sharply mitigate IMZX contamination of water in environments where rice is grown, particularly in those managed with tillage.

Understanding the Potential Impact of Different Drug Properties on Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission and Disease Burden: A Modelling Analysis.

BACKGROUND: The public health impact of the coronavirus disease 2019 (COVID-19) pandemic has motivated a rapid search for potential therapeutics, with some key successes. However, the potential impact of different treatments, and consequently research and procurement priorities, have not been clear. METHODS: Using a mathematical model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission, COVID-19 disease and clinical care, we explore the public-health impact of different potential therapeutics, under a range of scenarios varying healthcare capacity, epidemic trajectories; and drug efficacy in the absence of supportive care. RESULTS: The impact of drugs like dexamethasone (delivered to the most critically-ill in hospital and whose therapeutic benefit is expected to depend on the availability of supportive care such as oxygen and mechanical ventilation) is likely to be limited in settings where healthcare capacity is lowest or where uncontrolled epidemics result in hospitals being overwhelmed. As such, it may avert 22% of deaths in high-income countries but only 8% in low-income countries (assuming R = 1.35). Therapeutics for different patient populations (those not in hospital, early in the course of infection) and types of benefit (reducing disease severity or infectiousness, preventing hospitalization) could have much greater benefits, particularly in resource-poor settings facing large epidemics. CONCLUSIONS: Advances in the treatment of COVID-19 to date have been focused on hospitalized-patients and predicated on an assumption of adequate access to supportive care. Therapeutics delivered earlier in the course of infection that reduce the need for healthcare or reduce infectiousness could have significant impact, and research into their efficacy and means of delivery should be a priority.

Remitting neuropsychiatric symptoms in COVID-19 patients: Viral cause or drug effect?

Numerous reports of neuropsychiatric symptoms highlighted the pathologic potential of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its relationship the onset and/or exacerbation of mental disease. However, coronavirus disease 2019 (COVID-19) treatments, themselves, must be considered as potential catalysts for new-onset neuropsychiatric symptoms in COVID-19 patients. To date, immediate and long-term neuropsychiatric complications following SARS-CoV-2 infection are currently unknown. Here we report on five patients with SARS-CoV-2 infection with possible associated neuropsychiatric involvement, following them clinically until resolution of their symptoms. We will also discuss the contributory roles of chloroquine and dexamethasone in these neuropsychiatric presentations.

First wave of COVID-19 in Venezuela: Epidemiological, clinical, and paraclinical characteristics of first cases.

The coronavirus disease 2019 (COVID-19) pandemic has particularly affected countries with weakened health services in Latin America, where proper patient management could be a critical step to address the epidemic. In this study, we aimed to characterize and identify which epidemiological, clinical, and paraclinical risk factors defined COVID-19 infection from the first confirmed cases through the first epidemic wave in Venezuela. A retrospective analysis of consecutive suspected cases of COVID-19 admitted to a sentinel hospital was carried out, including 576 patient cases subsequently confirmed for severe acute respiratory syndrome coronavirus 2 infection. Of these, 162 (28.1%) patients met the definition criteria for severe/critical disease, and 414 (71.2%) were classified as mild/moderate disease. The mean age was 47 (SD 16) years, the majority of which were men (59.5%), and the most frequent comorbidity was arterial hypertension (23.3%). The most common symptoms included fever (88.7%), headache (65.6%), and dry cough (63.9%). Severe/critical disease affected mostly older males with low schooling (p < 0.001). Similarly, higher levels of glycemia, urea, aminotransferases, total bilirubin, lactate dehydrogenase, and erythrocyte sedimentation rate were observed in severe/critical disease patients compared to those with mild/moderate disease. Overall mortality was 7.6% (44/576), with 41.7% (28/68) dying in hospital. We identified risk factors related to COVID-19 infection, which could help healthcare providers take appropriate measures and prevent severe clinical outcomes. Our results suggest that the mortality registered by this disease in Venezuela during the first epidemic wave was underestimated. An increase in fatalities is expected to occur in the coming months unless measures that are more effective are implemented to mitigate the epidemic while the vaccination process is ongoing.

Clinical-epidemiological characteristics and maternal-foetal outcomes in pregnant women hospitalised with COVID-19 in Venezuela: a retrospective study.

BACKGROUND: In low- and middle-income countries, pregnant women and newborns are more vulnerable to adverse outcomes from coronavirus disease 2019 (COVID-19). However, in Venezuela, there are no integrated data in a national surveillance system to identify the clinical-epidemiological characteristics and maternal-foetal outcomes of pregnant women hospitalised with COVID-19. METHODS: A retrospective study was conducted among Venezuelan pregnant women hospitalised with COVID-19 seen at the "Ruiz y Páez" University Hospital Complex and the San Cristobal Central Hospital between June 2020 and September 2021. Information was obtained from physical and digitised clinical records using a purpose-designed proforma to collect epidemiological, clinical, paraclinical, treatment, obstetric and perinatal complications, and maternal-foetal outcomes data. RESULTS: A total of 80 pregnant women with confirmed severe acute respiratory syndrome coronavirus 2 infection were seen within the study period, 59 (73.8%) survived and 21 (26.2%) died. The median (interquartile range) age was 29 (23-33) years, the majority being in the third trimester of pregnancy (81.2%; n = 65). Interestingly, four (5%) pregnant women were co-infected with malaria by Plasmodium vivax and three (3.8%) with syphilis. The most frequent symptoms were fever (75%; n = 60), dry cough (68.8%; n = 55), dyspnoea (55%; n = 44), and headache (53.8%; n = 43). The most frequent maternal complications were anaemia (51.5%; n = 66) and hypertensive disorders of pregnancy (17.5%; n = 14). The most frequent perinatal complications were preterm delivery (39.2%; n = 20/51) and oligohydramnios (31.3%; n = 25). A total of 29 (36.3%) adverse foetal outcomes were documented, 21 stillbirth and eight abortions. CONCLUSION: This is the first study to describe the clinical-epidemiological behaviour of COVID-19 in hospitalised Venezuelan pregnant women. Anaemia, hypertensive disorders of pregnancy, oligohydramnios, and low birth weight were the most frequent maternal-foetal complications in this population of pregnant women.

A Low-Cost Luxometer Benchmark for Solar Illuminance Measurement System Based on the Internet of Things.

Natural illumination has an important place in home automation applications. Among other advantages, it contributes to better visual health, energy savings, and lower CO2 emissions. Therefore, it is important to measure illuminance in the most accurate and cost-effective way. This work compares several low-cost commercial sensors (VEML 7700, TSL2591, and OPT3001) with a professional one (ML-020S-O), all of them installed outdoors. In addition, a platform based on the Internet of Things technology was designed and deployed as a centralized point of data collection and processing. Summer months have been chosen for the comparison. This is the most adverse situation for low-cost sensors since they are designed for indoor use, and their operating range is lower than the maximum reached by sunlight. The solar illuminance was recorded every minute. As expected, the obtained bias depends on the solar height. This can reach 60% in the worst circumstances, although most of the time, its value stays below 40%. The positive side lies in the good precision of the recordings. This systematic deviation makes it susceptible to mathematical correction. Therefore, the incorporation of more sensors and data that can help the global improvement of the precision and accuracy of this low-cost system is left as a future line of improvement.

Malaria in pregnancy complications in Southern Venezuela.

BACKGROUND: Pregnant women are particularly vulnerable to malaria infections, increasing the risk of maternal-fetal complications, mainly in high-endemicity areas. However, few studies of malaria in pregnancy (MiP) have been carried out in Latin America, a region with low endemicity and transmission of both, Plasmodium falciparum and Plasmodium vivax. Despite the high malaria burden in Venezuela in the last years, no recent studies of MiP have been conducted. Hence, epidemiological and clinical characteristics of pregnant women with malaria in southern Venezuela are described herein. METHODS: A retrospective study in pregnant women attending at the "Ruíz y Páez" University Hospital Complex, Bolivar state, Venezuela, was carried out between February and October, 2019. Epidemiological, clinical, and laboratory information was analysed. RESULTS: Thirty-seven out of 52 pregnant women analysed were infected with P. vivax. Age ranged between 15 and 39 years, and adolescent pregnancies were common. Malaria infection was diagnosed mainly during the third trimester of pregnancy (63.4%). The distribution of symptoms and signs as well as clinical laboratory values was similar among Plasmodium spp. Although uncomplicated malaria was most frequent, 30% (13/52) had severe anaemia. A high proportion of studied women (44%) presented at least one complication during the pregnancy or delivery. Spontaneous abortion was recorded in four women, and three fetal deaths were observed. Six women had preterm delivery without any further complication. CONCLUSIONS: A high prevalence of maternal-fetal complications was found in the studied population, highlighting the requirement for a careful medical follow up during the prenatal check-ups, which should include routinary malaria tests. Preventive measures as distribution of insecticide-treated mosquito net for pregnant women at risk should also be implemented. Those measures can help to reduce the negative impact of malaria on the newborn and mother.

The clinical-epidemiological profile of malaria patients from Southern Venezuela, a critical hotspot in Latin America.

BACKGROUND: Venezuela accounted for 55% of the cases and 73% of the malaria deaths in the Americas in 2019. Bolivar state, in the southeast, contributes > 60% of the country's Plasmodium vivax and Plasmodium falciparum cases every year. This study describes the clinical-epidemiological characteristics of clinical malaria patients in this high-transmission area. METHODS: A prospective study was conducted on patients seeking medical attention in three medical centres in the state capital, Ciudad Bolivar, between June and October 2018. Malaria diagnosis was carried out using microscopy following national standards. Malaria-positive patients were examined for clinical symptoms, and haematological tests were performed at the time of diagnosis. Patients were followed up by telephone to evaluate malaria recurrences. RESULTS: Out of 287 patients, 200 (69.7%) were positive for P. vivax, 69 (24%) for P. falciparum, and 18 (6.3%) had mixed (P. vivax/P. falciparum) infections. Patients' median age was 33 years (IQR 20), 168 (69%) were men, and 40% practiced gold mining as the main occupation. Fever (96.5%), chills (91.3%), and headaches (90.6%) were the most frequent symptoms. At least one symptom associated with severe malaria was observed in 69 out of 161 patients with complete clinical evaluation (42.9%). Plasmodium vivax infections were found in 42 out of 69 (60.9%) severe cases; by contrast, P. falciparum and mixed malaria caused 34.8% (24/69) and 4.4% (3/69) of infections, respectively. Two patients died of cerebral malaria. Mean hemoglobin was lower in the patients infected with P. falciparum than those infected with P. vivax. Regardless of the parasite causing the infection, patients presented high levels of total bilirubin, aminotransferases (AST, ALT), and lactate dehydrogenase (LDH). Out of the 142 patients followed up by phone for three months (49.5% of the 287 patients), 35 (24.7%) reported recurrences. CONCLUSIONS: The high malaria prevalence among young male adults practicing gold mining suggests that this occupation is a significant risk factor. The unexpected high prevalence of P. vivax patients with at least one criteria of severe clinical disease is a matter of concern. Whether it is the result of a lack of timely diagnosis and effective treatment should be explored.

Amoebic liver abscess in a COVID-19 patient: a case report.

BACKGROUND: Amoebiasis is a parasitic disease caused by Entamoeba histolytica, which affects people living in low- and middle-income countries and has intestinal and extraintestinal manifestations. To date, knowledge on coronavirus disease 2019 (COVID-19) coinfection with enteric parasites is limited, and E. histolytica coinfection has not been previously described. Here we present the case of a patient with COVID-19 who, during hospitalisation, presented a clinical picture consistent with an amoebic liver abscess (ALA). CASE PRESENTATION: A 54-year-old man, admitted as a suspected case of COVID-19, presented to our hospital with dyspnoea, malaise, fever and hypoxaemia. A nasopharyngeal swab was positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by reverse-transcription polymerase chain reaction. After 7 days, he developed diarrhoea, choluria and dysentery. An abdominal ultrasound showed a lesion compatible with a liver abscess; stool examination revealed E. histolytica trophozoites, and additional serology for E. histolytica was positive. After 12 days of treatment with metronidazole, ceftazidime and nitazoxanide, the patient reported acute abdominal pain, and an ultrasound examination revealed free liquid in the abdominal cavity. An emergency exploratory laparotomy was performed, finding 3000 mL of a thick fluid described as "anchovy paste". Computed tomography scan revealed a second abscess. He ended up receiving 21 days of antibiotic treatment and was discharged with satisfactory improvement. CONCLUSION: Here we present, to the best of our knowledge, the first report of ALA and COVID-19 co-presenting. Based on their pathophysiological similarities, coinfection with SARS-CoV-2 and E. histolytica could change the patient's clinical course; however, larger studies are needed to fully understand the interaction between these pathogens.

Tdnn-Based Engine In-Cylinder Pressure Estimation from Shaft Velocity Spectral Representation.

Pressure is one of the essential variables to give information about engine condition and monitoring. Direct recording of this signal is complex and invasive, while angular velocity can be measured. Nonetheless, the challenge is to predict the cylinder pressure using the shaft kinematics accurately. In this paper, a time-delay neural network (TDNN), interpreted as a finite pulse response (FIR) filter, is proposed to estimate the in-cylinder pressure of a single-cylinder internal combustion engine (ICE) from fluctuations in shaft angular velocity. The experiments are conducted over data obtained from an ICE operating in 12 different states by changing the angular velocity and load. The TDNN's delay is adjusted to get the highest possible correlation-based score. Our methodology can predict pressure with an R2 >0.9, avoiding complicated pre-processing steps.

Random Fourier Features-Based Deep Learning Improvement with Class Activation Interpretability for Nerve Structure Segmentation.

Peripheral nerve blocking (PNB) is a standard procedure to support regional anesthesia. Still, correct localization of the nerve's structure is needed to avoid adverse effects; thereby, ultrasound images are used as an aid approach. In addition, image-based automatic nerve segmentation from deep learning methods has been proposed to mitigate attenuation and speckle noise ultrasonography issues. Notwithstanding, complex architectures highlight the region of interest lacking suitable data interpretability concerning the learned features from raw instances. Here, a kernel-based deep learning enhancement is introduced for nerve structure segmentation. In a nutshell, a random Fourier features-based approach was utilized to complement three well-known semantic segmentation architectures, e.g., fully convolutional network, U-net, and ResUnet. Moreover, two ultrasound image datasets for PNB were tested. Obtained results show that our kernel-based approach provides a better generalization capability from image segmentation-based assessments on different nerve structures. Further, for data interpretability, a semantic segmentation extension of the GradCam++ for class-activation mapping was used to reveal relevant learned features separating between nerve and background. Thus, our proposal favors both straightforward (shallow) and complex architectures (deeper neural networks).

Malaria in Venezuela: changes in the complexity of infection reflects the increment in transmission intensity.

BACKGROUND: Malaria incidence has reached staggering numbers in Venezuela. Commonly, Bolívar State accounted for approximately 70% of the country cases every year. Most cases cluster in the Sifontes municipality, a region characterized by an extractive economy, including gold mining. An increase in migration to Sifontes, driven by gold mining, fueled a malaria spillover to the rest of the country and the region. Here samples collected in 2018 were compared with a previous study of 2003/2004 to describe changes in the parasites population structures and the frequency of point mutations linked to anti-malarial drugs. METHODS: A total of 88 Plasmodium falciparum and 94 Plasmodium vivax isolates were collected in 2018 and compared with samples from 2003/2004 (106 P. falciparum and 104 P. vivax). For P. falciparum, mutations linked to drug resistance (Pfdhfr, Pfdhps, and Pfcrt) and the Pfk13 gene associated with artemisinin delayed parasite clearance, were analysed. To estimate the multiplicity of infection (MOI), and perform P. falciparum and P. vivax population genetic analyses, the parasites were genotyped by using eight standardized microsatellite loci. RESULTS: The P. falciparum parasites are still harbouring drug-resistant mutations in Pfdhfr, Pfdhps, and Pfcrt. However, there was a decrease in the frequency of highly resistant Pfdhps alleles. Mutations associated with artemisinin delayed parasite clearance in the Pfk13 gene were not found. Consistent with the increase in transmission, polyclonal infections raised from 1.9% in 2003/2004 to 39% in 2018 in P. falciparum and from 16.3 to 68% in P. vivax. There is also a decrease in linkage disequilibrium. Bayesian clustering yields two populations linked to the time of sampling, showing that the parasite populations temporarily changed. However, the samples from 2003/2004 and 2018 have several alleles per locus in common without sharing multi-locus genotypes. CONCLUSIONS: The frequency of mutations linked with drug resistance in P. falciparum shows only changes in Pfdhps. Observations presented here are consistent with an increase in transmission from the previously circulating parasites. Following populations longitudinally, using molecular surveillance, provides valuable information in cases such as Venezuela with a fluid malaria situation that is affecting the regional goals toward elimination.