Acute taurine reduced alcohol intake and preference in alcohol-experienced, but not in alcohol-näive rats by central mechanisms.

Taurine is a non-essential ß sulfonated amino acid involved in a plethora of biological functions in the mammalian central nervous system. Taurine is easily accessible in energy drinks for human consumption. Previous preclinical and clinical reports suggest that acute systemic administration of taurine could inhibit some of the behavioral and metabolic effects of alcohol use disorder. Overall, both in rodent and human studies, acute taurine administration reduced voluntary alcohol intake. This study aimed to assess the pharmacological effects of taurine (intracerebroventricular; i.c.v.) on ethanol intake/preference of rats either control (i.e., alcohol naïve) or forced ethanol intake (since juvenile age with a chronic intermittent access model). In addition, to explore anxiety-like behavior (through defensive burying behavior test) as pharmacological control of taurine. We found that acute (i.c.v.) taurine reduced alcohol consumption, i.e., taurine significantly decreased both alcohol intake and preference in adult male Wistar rats. Moreover, taurine elicits an anxiolytic-like effect in all administered groups independently of previous alcohol exposure.

Molecular characterization of Sarcoptes scabiei causing severe mange in two Andean foxes (Lycalopex culpaeus) from Peru.

Cases of sarcoptic mange in the wildlife population have been increasing around the world in recent years. In this study, we report the first case of severe sarcoptic mange in two Andean foxes (Lycalopex culpaeus) and molecularly analyze the collected mites. The National Forestry and Wildlife Service of Lima, Peru, found an adult male Andean fox in the province of Callao in August 2022. The veterinarians decided to euthanize the fox due to the severity of the mange. In August 2023, an adult male Andean fox was found dead in the province of Huaral by veterinarians. Both foxes were sent to the veterinary school in Lima for necropsy. Skin samples from different body zones were digested in buffer lysis, and mites were detected in the tissue samples. A morphological diagnosis identified the mites as Sarcoptes scabiei. The mites from both foxes had the same nuclear (ITS2) and mitochondrial (cox1) genetic marker sequences as the S. scabiei sequences from dogs, vicunas, Andean foxes, and water buffalos recorded in GenBank. Unlike ITS2, phylogenetic analysis of S. scabiei cox1 showed host-related nucleotide sequence polymorphisms. Future molecular studies of S. scabiei from different hosts and localities will be necessary to better understand the transmission of this disease in Andean foxes.

Molecular survey of hemoplasmas in asymptomatic vicunas (Vicugna vicugna) from the Pampa Galeras Bárbara D'Achille National Reserve in Peru.

Hemotrophic mycoplasmas (hemoplasmas) are epierythrocytic bacteria that infect wild and domestic animals, and can cause anemia in some of them. They are considered emerging and zoonotic pathogens, causing serious health problems in wildlife. Candidatus Mycoplasma haemolamae is the only species of hemoplasma that infects domestic South American camelids (alpacas and llamas), with limited studies in wild camelids. Therefore, the objective of this study was to determine the prevalence of Candidatus M. haemolamae in vicunas (Vicugna vicugna) from the Pampa Galeras National Reserve, located in the Ayacucho region of Peru, using molecular diagnosis. For this, blood samples from 79 vicunas were collected, which were molecularly analyzed by partially amplifying the 16S ribosomal RNA gene of Mycoplasma sp. Fourteen vicunas (17.7 %) were positive for the molecular diagnosis of Mycoplasma sp. All PCR-positive products were sequenced and showed more than 99 % identity with Candidatus M. haemolamae. Statistical analysis showed that tick-infested vicunas had 6.10 odds of presenting Candidatus M. haemolamae compared with tick-free vicunas. Sex and age were not associated with Candidatus M. haemolamae infections. This is the first report of hemoplasmas in vicunas, a wild South American camelid, demonstrating that the pathogen can have both a domestic and a wild life cycle. Future studies are necessary to know the current situation of this pathogen in domestic and wild camelids from other locations in Peru.

Stress, a Brief Update.

Stress is fundamental for health and adaptation; it is an evolutionarily conserved response that involves several systems in the organism. The study of the stress response could be traced back to the end of the nineteenth century with George Beard's or Claude Bernard's work and, from that moment on, several studies that have allowed the elucidation of its neurobiology and the consequences of suffering from it were consolidated. In this theoretical review, we discuss the most relevant researches to our knowledge on the study of stress response, from the concept of stress, its neurobiology, the hormonal response during stress, as well as its regulation, the effects of acute and chronic stress, stress from cognition, the different stress responses during life, as well as its relationship with different psychiatric disorders. Taken together, the reviewed research updates the classic perspective on stress, increasing the factors that should be considered in research to explore the effects of stress on health.

El estrés es fundamental para la salud y la adaptación; es una respuesta conservada evolutivamente que implica a varios sistemas del organismo. El estudio de la respuesta de estrés se remonta a finales del siglo xix con los trabajos de George Beard o Claude Bernard y a partir de ese momento se consolidaron diversos estudios que han permitido dilucidar su neurobiología y las consecuencias de padecerlo. En esta revisión teórica, abordamos lo más relevante para nuestro conocimiento sobre el estudio de la respuesta de estrés, desde el concepto de estrés, su neurobiología, la respuesta hormonal durante el estrés, así como su regulación, los efectos del estrés agudo y crónico, el estrés desde la cognición, las diferentes respuestas de estrés a lo largo de la vida, además de su relación con diferentes trastornos psiquiátricos. En conjunto, las investigaciones revisadas actualizan la perspectiva clásica sobre el estrés, incrementando los factores que deben tenerse en cuenta en la investigación para explorar los efectos del estrés sobre la salud.

Use of a microgravity analog to explore the effects of simulated microgravity on the development of Escherichia coli K12 biofilms.

The rapid development of space technologies and the increase of human presence in space has brought the discussion of the effects of microgravity on cells into the undergraduate classroom. This paper proposes an idea to simulate microgravity on a bacterial culture, suitable for an introductory microbiology laboratory. For this purpose, we show the use of a 2D clinostat designed for microbial studies, along with traditional microbiology techniques such as optical density, plate counts, and biofilm biomass measurement to test the effect of simulated microgravity on the growth of Escherichia coli K12. This exercise aims to facilitate further discussions on the effects of microgravity on bacteria growth and communication, as well as the use of technology to simulate space and predict physiological changes in cells.

Assessment of the elastic stiffness of human cardiac fibres after an apical infarction using finite element simulation.

Several research works in the literature have focused on understanding the post-infarction ventricular remodelling phenomenon, but few works have considered the evaluation of the elastic behaviour of the cardiac tissue after a myocardial infarction. This paper presents an investigation focused on predicting the elastic performance of the human heart after a left ventricular apical infarction. The aim is to understand the elastic alterations of the cardiac fibres at different periods after an apical infarct. For this purpose, a hybrid method based on pressure and volume measurements of the left ventricle (LV) at different periods of ventricular remodelling, and the Finite Element Method (FEM), is developed. In addition, several performance indexes are defined to evaluate the heart performance during the ventricular remodelling process. The results show that during the first 2 weeks after a heart infarction, the cardiac fibres must support a much higher structural overload than during normal conditions. This structural overload is proportional to the aneurysm size but diminishes with the time, together with a significant reduction of the ventricular pumping capacity.

Pharmacologic hyperreactivity of kappa opioid receptors in periaqueductal gray matter during alcohol withdrawal syndrome in rats.

BACKGROUND: Periaqueductal gray matter (PAG) is a brain region rich in kappa-opioid receptors (KOR). KOR in PAG mediates behavioral responses related to pain integration, and panic response, among others. Its participation in the addiction phenomena has been poorly studied. Hence, this preliminary study explored the pharmacological effects of KOR stimulation/blockade in dorsal-PAG (D-PAG) during alcohol withdrawal on anxiety-type behaviors and alcohol intake/preference. METHODS: Juvenile male Wistar rats were unexposed (A-naïve group) or exposed to alcohol for 5 weeks and then restricted (A-withdrawal group). Posteriorly, animals received intra D-PAG injections of vehicle (10% DMSO), salvinorin A (SAL-A; a selective KOR agonist), or 2-Methyl-N-((2'-(pyrrolidin-1-ylsulfonyl)biphenyl-4-yl)methyl)propan-1-amine (PF-04455242; a highly selective KOR-antagonist). Subsequently, the defensive burying behavior (DBB) and alcohol intake/preference paradigms were evaluated. RESULTS: SAL-A markedly increased burying time, the height of bedding, and alcohol consumption/preference in A-withdrawal, while slightly increased the height of bedding in A-näive rats. PF-04455242 decreased both burying and immobility duration, whereas increases latency to burying, frequency of rearing, and the number of stretches attempts with no action on alcohol intake/preference in A-withdrawal rats. CONCLUSIONS: In general, stimulation/blockade of KOR in A-withdrawal animals exert higher responses compared to A-naïve ones. SAL-A produced anxiety-like behaviors and increased alcohol consumption/preference, especially/solely in the alcohol-withdrawal condition, while PF-04455242 augmented exploration with no effects on alcohol intake/preference. Our findings suggest a possible pharmacologic hyperreactivity of the KOR in PAG during alcohol withdrawal.

Development of a new low-cost computer vision system for human gait analysis: A case study.

Today, human gait analysis is commonly used for clinical diagnosis, rehabilitation and performance improvement in sports. However, although previous research works in the literature address the use of motion capture systems by means of optoelectronic sensors, Inertial Measurement Units (IMUs) and depth cameras, few of them discuss their conception, guidelines and algorithms for measuring and calculating gait metrics. Moreover, commercially available motion capture systems, although efficient, are cost restrictive for most of the low-income institutions. In this research work, a new computer vision-based system (CVS) for gait analysis is developed and proposed. The aim is to close the gap found in the literature about the design and development of such systems by providing the requirements, considerations, algorithms and methodologies used to develop a gait analysis system with acceptable precision and accuracy, and at low cost. For this purpose, a linear computer vision method based on the non-homogeneous solution of the calibration matrix was used. The spatio-temporal and angular gait parameters were implemented in the proposed system, and compared with those reported in the literature. The denoising of the spatial gait trajectories and the strategies to detect gait events, are also presented and discussed. The results have shown that the proposed system is satisfactory for human gait analysis in terms of precision, computational performance and low cost.

Exposure to anandamide on young rats causes deficits in learning, temporal perception and induces changes in NMDA receptor expression.

Human use of marijuana at an early age has been reported to lead to cognitive impairment. However, researchers have not yet clearly determined whether this impairment is due to marijuana-induced alterations in the developing nervous system and whether this deficit persists into adulthood after marijuana use has ceased. We administered anandamide to developing rats to assess the effect of cannabinoids on development. We subsequently evaluated learning and performance on a temporal bisection task in adulthood and assessed the expression of genes encoding principal subunits of NMDA receptors (Grin1, Grin2A, and Grin2B) in the hippocampus and prefrontal cortex. Rats in two age groups, namely, 21-day-old and 150-day-old rats, received intraperitoneal injections of anandamide or the vehicle for 14 days. Both groups performed a temporal bisection test, which included listening to tones of different durations and classifying them as short or long. The expression of the Grin1, Grin2A and Grin2B mRNAs was evaluated using quantitative PCR in both age groups after extracting mRNA from the hippocampus and prefrontal cortex. We observed a learning impairment in the temporal bisection task (p < 0.05) and changes in the response latency (p < 0.05) in rats that received anandamide. Furthermore, these rats exhibited decreased expression of Grin2b (p = 0.001) compared to those that received the vehicle. In human subjects, the use of cannabinoids during development induces a long-term deficit, but this deficit is not observed in subjects who use cannabinoids in adulthood. Rats treated with anandamide earlier in development took longer to learn the task, suggesting that anandamide exerts a harmful effect on cognition in developing rats. Administration of anandamide during early stages of development induced deficits in learning and other cognitive processes that depend on an adequate estimation of time. The cognitive demands of the environment must be considered when evaluating the cognitive effects of cannabinoids on developing or mature brains. High cognitive demands might induce differential expression of NMDA receptors that improves cognitive capacity, overcoming altered glutamatergic function.

Novel object recognition in Octopus maya.

The Novel Object Recognition task (NOR) is widely used to study vertebrates' memory. It has been proposed as an adequate model for studying memory in different taxonomic groups, allowing similar and comparable results. Although in cephalopods, several research reports could indicate that they recognize objects in their environment, it has not been tested as an experimental paradigm that allows studying different memory phases. This study shows that two-month-old and older Octopus maya subjects can differentiate between a new object and a known one, but one-month-old subjects cannot. Furthermore, we observed that octopuses use vision and tactile exploration of new objects to achieve object recognition, while familiar objects only need to be explored visually. To our knowledge, this is the first time showing an invertebrate performing the NOR task similarly to how it is performed in vertebrates. These results establish a guide to studying object recognition memory in octopuses and the ontological development of that memory.

Defensive and Emotional Behavior Modulation by Serotonin in the Periaqueductal Gray.

Serotonin 5-hydroxytryptamine (5-HT) is a key neurotransmitter for the modulation and/or regulation of numerous physiological processes and psychiatric disorders (e.g., behaviors related to anxiety, pain, aggressiveness, etc.). The periaqueductal gray matter (PAG) is considered an integrating center for active and passive defensive behaviors, and electrical stimulation of this area has been shown to evoke behavioral responses of panic, fight-flight, freezing, among others. The serotonergic activity in PAG is influenced by the activation of other brain areas such as the medial hypothalamus, paraventricular nucleus of the hypothalamus, amygdala, dorsal raphe nucleus, and ventrolateral orbital cortex. In addition, activation of other receptors within PAG (i.e., CB1, Oxytocin, µ-opioid receptor (MOR), and γ-aminobutyric acid (GABAA)) promotes serotonin release. Therefore, this review aims to document evidence suggesting that the PAG-evoked behavioral responses of anxiety, panic, fear, analgesia, and aggression are influenced by the activation of 5-HT1A and 5-HT2A/C receptors and their participation in the treatment of various mental disorders.

Phenotypic and transcriptional changes in Escherichia coli K12 in response to simulated microgravity on the EagleStat, a new 2D microgravity analog for bacterial studies.

Understanding the impacts of microgravity on bacteria is vital for successful long duration space missions. In this environment, bacteria have been shown to become more virulent, more resistant to antibiotics and to regulate biofilm formation. Since the study of these phenomena under true microgravity is cost- and time challenging, the use of ground-based analogs might allow researchers to test hypotheses before planning and executing experiments in the space environment. We designed and developed a 2D clinostat with capabilities robust enough for bacterial studies to allow for multiple simultaneous replicates of treatment and control conditions, thus permitting the generation of growth curves, in a single run. We used computational fluid dynamics (CFD), biofilm growth measurement and differential gene expression analysis on Escherichia coli cultures grown to late exponential phase (24 h) to validate the system's ability to simulate microgravity conditions. The CFD model with a rotational speed of 8 rpm projected cells growing homogeneously distributed along the tube, while the static condition showed the accumulation of the cells at the bottom of the container. These results were empirically validated with cultures on nutrient broth. Additionally, crystal violet assays showed that higher biofilm biomass grew on the internal walls of the gravity control tubes, compared to the simulated microgravity treatment. In contrast, when cells from both treatments were grown under standard conditions, those exposed to simulated microgravity formed significantly more biofilms than their gravity counterparts. Consistent with this result, transcriptome analysis showed the upregulation of several gene families related to biofilm formation and development such as cells adhesion, aggregation and regulation of cell motility, which provides a potential transcriptional explanation for the differential phenotype observed. Our results show that when operated under parameters for simulated microgravity, our 2D clinostat creates conditions that maintain a proportion of the cells in a constant free-falling state, consistent with the effect of microgravity. Also, the high-throughput nature of our instrument facilitates, significantly, bacterial experiments that require multiple sampling timepoints and small working volumes, making this new instrument extremely efficient.

Sarcoptic mange outbreaks in vicuñas (Cetartiodactyla: Camelidae): A scoping review and future prospects.

Sarcoptic mange is considered an emerging disease-causing countless epizootics and significantly affecting wild mammals worldwide. The vicuña (Vicugna vicugna) is a medium-sized South American wild camelid inhabiting Andean ecosystems, where several populations are live-sheared by Andean peasant communities as a way of providing an economic income to the people while promoting vicuña conservation. Institutions and scientists have shown concern for the impact and extent of sarcoptic mange in several vicuña populations across their range, as well as the lack of consistent knowledge about this disease in the species. Here, we perform a review about sarcoptic mange distribution throughout the vicuña's native range, evidence of effects of age and sex, the modes of transmission and the veterinary treatments employed. The review retrieved a few scientific papers, but found several reports and academic studies mostly considered as 'grey literature'. Mange was recorded across the entire native vicuña range (Argentina, Bolivia, Chile and Peru). Mange prevalence varied across vicuña studies (up to 60% prevalence in some populations) and severely affected a number of populations, being an important source of mortality. Mange was reported as more frequent in adults than in offspring. The modes of mange transmission remain unclear, although direct transmission between infected and healthy animals seems to be the most likely, including the transmission between domestic camelids and vicuñas. Regarding the treatments employed, ivermectin was the most frequently used. We further identified several gaps in knowledge and point to future research lines, which seek to promote both species conservation and the maintenance of live-shearing vicuñas under sustainable approaches in low-income Andean peasant communities.

Chinese hamster V79 cells' dependence on background ionizing radiation for optimal growth.

The study of depriving cells from background ionizing radiation for the past decades has provided valuable insights into its role in cellular homeostasis control. To explore the existence of such response in eukaryotic cells, we grew Chinese hamster (Cricetulus griseus) V79 cells for 23 days using three different dose rates: 0.91 (below background), 35 (surface control) and 72 nGy h-1 (underground KCl-amended control). We did not observe a significant difference in cell number during the course of the experiment. However, cells grown at below background showed significantly lower viability compared to those grown at both control levels after 5 days of incubation and lasted, intermittently, for up to 21 days. We also observed a clear differentiation between the underground and the surface controls that could be explained by the variety of radiation sources present during cell growth under unshielded conditions. To explore the molecular mechanisms for these responses we performed transcriptome analysis on samples collected on days 2 and 5, but only samples from day 5 resulted in significant regulation. Gene enrichment analysis revealed two control-dependent general transcriptional responses. When compared the underground-KCl control, below-background cells showed the upregulation of processes intended for the response to drugs, metals and mechanical stimuli. In comparison, the response relative to the surface control was characterized by the upregulation of responses to organic substances and abiotic stimuli involved in the regulation of signaling, as well as to cell proliferation and homeostatic control of the number of cell processes.

Towards implementing an antibiotic stewardship programme (ASP) in Ecuador: evaluating antibiotic consumption and the impact of an ASP in a tertiary hospital according to World Health Organization (WHO) recommendations.

OBJECTIVES: Ecuador is a lower-to-middle-income country not yet adherent to World Health Organization (WHO) antibiotic stewardship strategies, and data regarding basic metrics are still lacking. METHODS: We conducted a retrospective study of an antibiotic stewardship programme (ASP) consisting of restrictive measures on carbapenem dispensing pending required pre-authorisation and expert audit. We evaluated antibiotic consumption and its relationship to carbapenem resistance at a 610-bed, tertiary-level hospital in Quito, Ecuador. We used prescription data from 2010-2017 and converted them into defined daily doses (DDD). We then correlated these findings with the nature of service provided and antibiotic resistance data from the microbiology laboratory. We used descriptive statistics and interrupted time series (ITS) analysis. RESULTS: Throughout the study period, we analysed 16 984 355 prescriptions of 8 191 418.57 g of antibiotics (5 760 479.37 DDD). The in-hospital mean antibiotic prescription rate was 148.8 ± 14.8 DDD/100 occupied bed-days and 293.5 ± 65.3 DDD/100 occupied bed-days in the ICU. First-, second- and third-line antibiotic consumption was 38%, 52% and 10%, respectively. Our hospital data showed a high rate of antibiotic prescription in all hospital areas, mainly broad-spectrum antibiotics. Regarding the ASP introduced in 2016, ITS analysis showed a change in the outcome level immediately following the introduction for imipenem [-3.97; 95% confidence interval (CI) -5.31 to -2.61] but not for meropenem (0.66; 95% CI -0.37 to 1.71). CONCLUSION: Although our institution's ASP was successful in reducing imipenem consumption, a more embracing plan is required for further interventions to avoid unexpected effects.

Coccidiosis in clinically asymptomatic alpaca (Vicugna pacos) crias from the Peruvian Andes.

Parasites of the genus Eimeria are involved in the neonatal diarrhea complex of alpaca (Vicugna pacos) crias, and infection by Eimeria is commonly known as coccidiosis. There are limited reports of these protozoa in clinically asymptomatic crias. In this study, fecal samples from 78 clinically asymptomatic alpaca crias were analyzed to evaluate the prevalence, parasitological load, and diversity of Eimeria species. This study was conducted in the Quenamari community located in the Peruvian Andes (Marangani, Cuzco) at 4500 m above sea level. All fecal samples were examined for parasites using the quantitative McMaster and modified Stoll techniques. Microscopic examination showed the presence of Eimeria oocysts in 68 out of the 78 samples (87.18%). Among the 78 samples we found E. lamae in 67 (85.90%), E. punoensis in 49 (62.82%), E. alpacae in 42 (53.85%), E. macusaniensis in 32 (41.03%), and E. ivitaensis in four (5.13%). Regarding parasitized crias, overall there was a mean parasitological load of 43,920 oocysts per gram of feces (OPG). Eimeria lamae had the highest parasitological load (mean 206,600 OPG). These findings could be due to environmental contamination with oocysts of different Eimeria species. Additional research is needed to determine if this burden of coccidiosis could produce subclinical impacts to the health of alpaca crias.

Differentiated thyroid cancer clinical trends in Quito, Ecuador / Tendencias clínicas del cáncer diferenciado de tiroides en Quito, Ecuador

Introduction.Thyroid cancer is currently the first most common cancer in women in Ecuador. This study aimed to assess the changes in clinical presentation and diagnosis of differentiated thyroid cancer at a third level hospital in Quito, Ecuador.Methods and Materials.This is a retrospective case series performed in three consecutive periods from 1990 to 2019 at a tertiary level hospital, in Quito, Ecuador. The clinical records of 875 patients who had been diagnosed and surgically treated for differentiated thyroid cancer were reviewed. Demographic, clinical, imaging, and pathological data were collected and analyzed.Results. Significant trends toward older age, higher educational level, less palpable primary tumors, less palpable neck nodes, less distant metastases, more ultrasound, tomography and cytology exams, smaller primary tumors, more stage I patients, and more histological variant description, were found. Introduction.Thyroid cancer is currently the first most common cancer in women in Ecuador. This study aimed to assess the changes in clinical presentation and diagnosis of differentiated thyroid cancer at a third level hospital in Quito, Ecuador.Methods and Materials.This is a retrospective case series performed in three consecutive periods from 1990 to 2019 at a tertiary level hospital, in Quito, Ecuador. The clinical records of 875 patients who had been diagnosed and surgically treated for differentiated thyroid cancer were reviewed. Demographic, clinical, imaging, and pathological data were collected and analyzed.Results. Significant trends toward older age, higher educational level, less palpable primary tumors, less palpable neck nodes, less distant metastases, more ultrasound, tomography and cytology exams, smaller primary tumors, more stage I patients, and more histological variant description, were found.

Introducción. El cáncer de tiroides es actualmente el cáncer más frecuente en la mujer en Ecuador. El presente estudio ha tenido como objetivo evaluar los cambios en la presentación clínica y el diagnóstico del cáncer diferenciado de tiroides en un hospital de tercer nivel de Quito, Ecuador. Material y Métodos. El presente es un estudio retrospectivo de casos realizado en tres períodos consecutivos desde 1990 a 2019 en un hospital del tercer nivel en Quito, Ecuador. Los expedientes clínicos de 875 pacientes tratados quirúrgicamente por un cáncer diferenciado de tiroides fueron revisados. Los datos demográficos, clínicos, de imagen y patología fueron extraídos y analizados. Resultados. Se encontraron tendencias significativas hacia una edad más avanzada, nivel educativo más alto, menos tumores palpables, menos adenopatías regionales palpables, menos metástasis a distancia, más exámenes de ultrasonido y tomografía, más estudios de citología, más tumores pequeños y pacientes con estadío I y más descripciones de las variantes histológicas. Conclusiones. El cáncer de tiroides no sólo que ha aumentado continuamente en su frecuencia en los años recientes, sino que la presentación clínica, el manejo diagnóstico y terapéutico ha cambiado significativamente en las tres últimas décadas.

Deinococcus radiodurans UWO298 Dependence on Background Radiation for Optimal Growth.

Ionizing radiation is a major environmental variable for cells on Earth, and so organisms have adapted to either prevent or to repair damages caused by it, primarily from the appearance and accumulation of reactive oxygen species (ROS). In this study, we measured the differential gene expression in Deinococcus radiodurans UWO298 cultures deprived of background ionizing radiation (IR) while growing 605 m underground at the Waste Isolation Pilot Plant (WIPP), reducing the dose rate from 72.1 to 0.9 nGy h-1 from control to treatment, respectively. This reduction in IR dose rate delayed the entry into the exponential phase of the IR-shielded cultures, resulting in a lower biomass accumulation for the duration of the experiment. The RNASeq-based transcriptome analysis showed the differential expression of 0.2 and 2.7% of the D. radiodurans genome after 24 and 34 h of growth in liquid culture, respectively. Gene expression regulation after 34 h was characterized by the downregulation of genes involved in folding newly synthesized and denatured/misfolded proteins, in the assimilation of nitrogen for amino acid synthesis and in the control of copper transport and homeostasis to prevent oxidative stress. We also observed the upregulation of genes coding for proteins with transport and cell wall assembly roles. These results show that D. radiodurans is sensitive to the absence of background levels of ionizing radiation and suggest that its transcriptional response is insufficient to maintain optimal growth.

Improvement in quality of life with sacubitril/ /valsartan in cardiac resynchronization non-responders: The RESINA (RESynchronization plus an Inhibitor of Neprilysin/Angiotensin) registry.

BACKGROUND: Clinical management of cardiac resynchronization therapy (CRT) non-responders is difficult, and their prognosis is poor. The aim of the present study was to evaluate whether treatment with sacubitril/valsartan can improve quality of life (QoL) parameters in these patients. METHODS: Thirty five non-responders to CRT were included (75 ± 7 years, 28% females, mean left ventricular ejection fraction 28 ± 8%, 54% non-ischemic cardiomyopathy) with maximally optimized drug therapy and New York Heart Association class II-III. They were all on angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers and were switched to sacubitril/valsartan. One week before and 6 months after initiation of the therapy they completed both the Minnesota Living with Heart Failure (MLWHF) and the 12-item Kansas City Cardiomyopathy Questionnaires (KCCQ-12). The primary outcome was the effect of sacubitril/valsartan on the physical, clinical, social and emotional QoL parameters and number of hospitalizations. RESULTS: The mean total scores of both questionnaires improved from baseline to the follow-up visit at 6-months (KCCQ-12 40 ± 10 to 47 ± 10; p < 0.001; MLWHF 40 ± 15 to 29 ± 15; p < 0.001). The best results were seen in the KCCQ-12 total symptom domains (77% improvement), the MLWHF physical domain (81% improvement), and the MLWHF emotional domain (71% improvement). Two patients died during follow-up. The mean number of hospitalizations reduced significantly (1 ± 0.6 vs. 0.5 ± 0.8; p = 0.003) CONCLUSIONS: In CRT non-responders, sacubitril/valsartan significantly improved overall QoL, physical limitations and emotional domains and reduced the number of hospitalizations.

Prevalence and molecular characterization of Sarcoptes scabiei from vicuñas (Vicugna vicugna) from Southern Peruvian Andes.

Sarcoptic mange is a disease caused by an infectious parasite in the vicuñas (Vicugna vicugna) from South America. Although molecular studies have provided much information about the epidemiology of this disease, this information is still unknown in vicuñas. This study determined the prevalence and molecular characterization of Sarcoptes scabiei from vicuñas from Southern Peruvian Andes. During the 2018 shearing season, 181 vicuñas were clinically evaluated for lesions compatible with mange. Sarcoptes scabiei was detected in 35 (19.3%) vicuñas, and 50 mites from 25 vicuñas were selected for molecular analyses of the mitochondrial (cox1) and nuclear (ITS2) genetic markers. Molecular analyses of the cox1 and ITS2 sequences showed an identity of 94­99% and 99.8­100% with previous S. scabiei sequences registered in the GenBank, respectively. Sequence polymorphisms were more evident in the ITS2 than in the cox1, but only the cox1 had an association with the host. Phylogenetic analysis of S. scabiei cox1 sequences from vicuñas showed a cluster with S. scabiei cox1 sequences from canids, suggesting that the origin of S. scabiei from vicuña is associated with canid mites. This research is the first molecular analysis of S. scabiei from vicuñas. Future molecular studies will be necessary to determine the species variety, geographic segregation and host­parasite adaptation for this vicuña's mite.