Resistance of infection by Plasmodium vivax to chloroquine in Bolivia.

BACKGROUND: Chloroquine (CQ) over three days plus primaquine (PQ) for seven days is the treatment of choice of infections by Plasmodium vivax in Bolivia, where 95% of the cases of malaria are attributed to this species. The aim of this study was to evaluate the therapeutic efficacy of CQ in this setting. METHODS: Patients in the Amazon region of northern Bolivia, were included in the study from May to November 2011 and the therapeutic efficacy of CQ was evaluated over a 28-day follow-up period. Patients with P. vivax mono-infection received 25 mg/Kg body weight of CQ over three days. The concentrations of CQ + desethylchloroquine (DCQ) in blood were determined at days 7 and 28 of follow up; at follow-up and on the day of treatment failure was administered PQ. RESULTS: One hundred patients fulfilled the inclusion criteria, two were lost to follow up and another two were later excluded for protocol violation. Of the 96 patients who completed the follow up 10 showed TF; one presented continued parasitaemia until day 7 of follow up, three on day 21 and six on day 28 of follow up. The geometric mean of CQ + DCQ on day 7 was 321.7 ng/ml (range 197-535 ng/ml). In six patients with TF the CQ + DCQ concentrations in blood on the day of TF were >100 ng/ml. The rate of resistance was 6.5%. CONCLUSION: The present study demonstrates the presence of resistance to CQ in the treatment of malaria by P. vivax in the Amazon region of Bolivia. New clinical trials are needed to establish alternative treatments against these parasites in this region of South America.

Decision trees for the analysis of genes involved in Alzheimer's disease pathology.

BACKGROUND: Alzheimer's disease (AD) is characterized by a gradual loss of memory, orientation, judgement and language. There is still no cure for this disorder. AD pathogenesis remains fairly unknown and its underlying molecular mechanisms are not yet fully understood. Several studies have shown that the abnormal accumulation of beta-amyloid and tau proteins occurs 10 to 20 years before the onset of symptoms of the disease, so it is extremely important to identify changes in the brain before the first symptoms. METHODS: We used decision trees to classify 31 individuals (9 healthy controls and 22 AD patients in three different stages of disease) according to the expression of 69 genes previously reported in a meta-analysis, plus the expression levels of APP, APOE, BACE1, NCSTN, PSEN1, PSEN2 and MAPT. We also included in our analysis the MMSE (Mini-Mental State Examination) scores and number of NFT (neurofibrillary tangles). RESULTS: Results allowed us to generate a model of classification values for different AD stages of severity, according to MMSE scores, and achieve the identification of the expression level of protein tau that may possibly determine the onset (incipient stage) of AD. DISCUSSION: We used decision trees to model the different stages of AD (severe, moderate, incipient and control) based on the meta-analysis of gene expression levels plus MMSE and NFT scores. Both classifiers reported the variable MMSE as most informative, however it we were found that the protein tau also an important role in the onset of AD.

Genomic Differences Associated with Resistance and Virulence in Pseudomonas aeruginosa Isolates from Clinical and Environmental Sites.

Pseudomonas aeruginosa is a pathogen that causes healthcare-associated infections (HAIs) worldwide. It is unclear whether P. aeruginosa isolated from the natural environment has the same pathogenicity and antimicrobial resistance potential as clinical strains. In this study, virulence- and resistance-associated genes were compared in 14 genomic sequences of clinical and environmental isolates of P. aeruginosa using the VFDB, PATRIC, and CARD databases. All isolates were found to share 62% of virulence genes related to adhesion, motility, secretion systems, and quorum sensing and 72.9% of resistance genes related to efflux pumps and membrane permeability. Our results indicate that both types of isolates possess conserved genetic information associated with virulence and resistance mechanisms regardless of the source. However, none of the environmental isolates were associated with high-risk clones (HRCs). These clones (ST235 and ST111) were found only in clinical isolates, which have an impact on human medical epidemiology due to their ability to spread and persist, indicating a correlation between the clinical environment and increased virulence. The genomic variation and antibiotic susceptibility of environmental isolates of P. aeruginosa suggest potential biotechnological applications if obtained from sources that are under surveillance and investigation to limit the emergence and spread of antibiotic resistant strains.

Iadademstat in combination with azacitidine in patients with newly diagnosed acute myeloid leukaemia (ALICE): an open-label, phase 2a dose-finding study.

BACKGROUND: Iadademstat is a potent, selective, oral inhibitor of both the enzymatic and scaffolding activities of the transcriptional repressor lysine-specific demethylase 1 (LSD1; also known as KDM1A) that showed promising early activity and safety in a phase 1 trial and strong preclinical synergy with azacitidine in acute myeloid leukaemia cell lines. Therefore, we aimed to investigate the combination of iadademstat and azacitidine for the treatment of adult patients with newly diagnosed acute myeloid leukaemia. METHODS: The open-label, phase 2a, dose-finding ALICE study was conducted at six hospitals in Spain and enrolled patients aged 18 years or older with newly diagnosed acute myeloid leukaemia not eligible for intensive chemotherapy and an ECOG performance status of 0-2. In the dose escalation portion of the trial, patients received a starting dose of iadademstat at 90 µg/m2 per day (with de-escalation to 60 µg/m2 per day and escalation up to 140 µg/m2 per day) orally, for 5 days on, 2 days off weekly, with azacitidine 75 mg/m2 subcutaneously, for seven of 28 days. The primary objectives were safety (analysed in the safety analysis set; all patients who received at least one dose of study treatment) and establishing the recommended phase 2 dose; secondary objectives included response rates in the efficacy analysis set (all patients who had at least one efficacy assessment). This study is registered on EudraCT (EudraCT 2018-000482-36) and has been completed. FINDINGS: Between Nov 12, 2018, and Sept 30, 2021, 36 patients with newly diagnosed acute myeloid leukaemia were enrolled; the median age was 76 (IQR 74-79) years, all patients were White, 18 (50%) were male, and 18 (50%) were female, and all had intermediate-risk or adverse-risk acute myeloid leukaemia. The median follow-up was 22 (IQR 16-31) months. The most frequent (≥10%) adverse events considered to be related to treatment were decreases in platelet (25 [69%]) and neutrophil (22 [61%]) counts (all grade 3-4) and anaemia (15 [42%]; of which ten [28%] were grade 3-4). Three patients had treatment-related serious adverse events (one fatal grade 5 intracranial haemorrhage, one grade 3 differentiation syndrome, and one grade 3 febrile neutropenia). Based on safety, pharmacokinetic and pharmacodynamic data, and efficacy, the recommended phase 2 dose of iadademstat was 90 µg/m2 per day with azacitidine. 22 (82%; 95% CI 62-94) of 27 patients in the efficacy analysis set had an objective response. 14 (52%) of 27 patients had complete remission or complete remission with incomplete haematological recovery; of these, ten of 11 evaluable for measurable residual disease achieved negativity. In the safety analysis set, 22 (61%) of 36 patients had an objective response. INTERPRETATION: The combination of iadademstat and azacitidine has a manageable safety profile and shows promising responses in patients with newly diagnosed acute myeloid leukaemia, including those with high-risk prognostic factors. FUNDING: Oryzon Genomics and Spain's Ministerio de Ciencia, Innovacion y Universidades (MICIU)-Agencia Estatal de Investigacion (AEI).

Protein body formation in stable transgenic tobacco expressing elastin-like polypeptide and hydrophobin fusion proteins.

BACKGROUND: Plants are recognized as an efficient and inexpensive system to produce valuable recombinant proteins. Two different strategies have been commonly used for the expression of recombinant proteins in plants: transient expression mediated by Agrobacterium; or stable transformation of the plant genome. However, the use of plants as bioreactors still faces two main limitations: low accumulation levels of some recombinant proteins and lack of efficient purification methods. Elastin-like polypeptide (ELP), hydrophobin I (HFBI) and Zera® are three fusion partners found to increase the accumulation levels of recombinant proteins and induce the formation of protein bodies (PBs) in leaves when targeted to the endoplasmic reticulum (ER) in transient expression assays. In this study the effects of ELP and HFBI fusion tags on recombinant protein accumulation levels and PB formation was examined in stable transgenic Nicotiana tabacum. RESULTS: The accumulation of recombinant protein and PB formation was evaluated in two cultivars of Nicotiana tabacum transformed with green fluorescent protein (GFP) fused to ELP or HFBI, both targeted and retrieved to the ER. The ELP and HFBI tags increased the accumulation of the recombinant protein and induced the formation of PBs in leaves of stable transgenic plants from both cultivars. Furthermore, these tags induced the formation of PBs in a concentration-dependent manner, where a specific level of recombinant protein accumulation was required for PBs to appear. Moreover, agro-infiltration of plants accumulating low levels of recombinant protein with p19, a suppressor of post-transcriptional gene silencing (PTGS), increased accumulation levels in four independent transgenic lines, suggesting that PTGS might have caused the low accumulation levels in these plants. CONCLUSION: The use of ELP and HFBI tags as fusion partners in stable transgenic plants of tobacco is feasible and promising. In a constitutive environment, these tags increase the accumulation levels of the recombinant protein and induce the formation of PBs regardless of the cultivar used. However, a specific level of recombinant protein accumulation needs to be reached for PBs to form.

Factors Associated with the Extent of Clinical Attachment Loss in Periodontitis: A Multicenter Cross-Sectional Study.

Periodontitis has significant public health implications, affecting individuals' overall health, well-being, and quality of life. This study aimed to assess the risk factors associated with the extent of clinical attachment loss (CAL) in a population diagnosed with periodontitis. Six hundred and sixty-seven patients with different degrees of CAL (mild, n = 223; moderate, n = 256; and advanced, n = 188) were enrolled. Socio-demographics, lifestyle, microbiological profiles, specific immune response, obesity, and single-nucleotide polymorphism of the IL1 gene were determined. Unconditional logistic regression models were conducted to determine the factors associated with the extent of CAL. Aging, smoking, microbial factors, plaque index, and IgG2 antibodies against Aggregatibacter actinomycetemcomitans were associated with advanced CAL. IgG2 antibodies against A. actinomycetemcomitans (OR 1.50; CI 95% 1.23-1.81), plaque accumulation (OR 2.69; CI 95% 2.20-3.29), Porphyromonas gingivalis (OR 1.93; CI 95% 1.35-2.76), Tanerella forsythia (OR 1.88; CI 95%1.30-2.70), and current smoking (OR 1.94; CI 95% 1.31-2.87) were associated with advanced CAL. Gene IL polymorphisms, obesity, and stress were not associated with the extent of CAL. Aging, plaque accumulation, smoking, and having antibodies against A. actinomycetemcomitans were the most critical factors associated with advanced CAL. In contrast, obesity, stress, and gene polymorphisms were not associated with the extent of CAL.

Molecular characterization of the Plasmodium falciparum k13 gene helix domain in samples from native communities of Condorcanqui, Amazonas, Perú / Caracterización molecular del dominio de la hélice del gen k13 de Plasmodium falciparum en muestras de comunidades nativas de Condorcanqui, Amazonas, Perú.

Introduction. Resistance of Plasmodium falciparum to different antimalarial drugs is an obstacle to disease elimination. The artemisinin-resistant genotype of P. falciparum can be assessed by examining polymorphisms in the helix domain of the Pfk13 gene. The World Health Organization recommends these mutations as molecular markers to detect artemisinin-resistant in countries where P. falciparum malaria is endemic. Objective. To identify artemisinin resistance-related mutations present in the helix domain of the P. falciparum k13 gene. Materials and methods. We collected a total of 51 samples through passive case detection, positive for Plasmodium by microscopy, from six communities in the district of Río Santiago in Condorcanqui, Amazonas. Molecular species confirmation was performed by real-time PCR and Pfk13 helix domain was amplified and sequenced by capillary electrophoresis. The obtained sequences were compared with the wild type 3D7 reference strain. Results. A total of 51 positive samples were confirmed for P. falciparum from the communities of Ayambis, Chapiza, Palometa, Muchinguis, Alianza Progreso and Caterpiza. DNA sequences alignment showed the absence of resistance-associated mutations in the k13 gene of the collected samples. Discussion. The obtained results are consistent with similar studies conducted in other South American countries, including Perú, so these data provide a baseline for artemisinin-resistance molecular surveillance in the Amazon region and reinforce the efficacy of artemisinin-based combination therapy in this area.

Introducción. La resistencia de Plasmodium falciparum a diferentes fármacos antipalúdicos es un obstáculo para eliminar la enfermedad. El genotipo resistente de P. falciparum a la artemisinina puede evaluarse examinando los polimorfismos en el dominio de la hélice del gen Pfk13. La Organización Mundial de la Salud recomienda utilizar estas mutaciones como marcadores moleculares para detectar la resistencia a la artemisinina en países donde la malaria por P. falciparum es endémica. Objetivo. Identificar mutaciones relacionadas con la resistencia a artemisinina presentes en el dominio de la hélice del gen k13 de P. falciparum. Materiales y métodos. Mediante la detección pasiva de casos, se recolectaron 51 muestras positivas por microscopía para Plasmodium, provenientes de seis comunidades del distrito de Río Santiago en Condorcanqui, Amazonas. Se realizó la confirmación molecular de la especie mediante PCR en tiempo real y el dominio de la hélice del gen Pfk13 se amplificó y secuenció por electroforesis capilar. Las secuencias obtenidas se compararon con la cepa de referencia 3D7 de fenotipo silvestre. Resultados. Se confirmó un total de 51 muestras positivas para P. falciparum, provenientes de las comunidades de Ayambis, Chapiza, Palometa, Muchinguis, Alianza Progreso y Caterpiza. Después del alineamiento de las secuencias de ADN, se determinó que las muestras no presentaron mutaciones asociadas con resistencia en el gen K13. Discusión. Los resultados obtenidos son coherentes con estudios similares realizados en otros países de Sudamérica, incluyendo Perú. Estos datos proporcionan una línea base para la vigilancia molecular de resistencia a artemisinina en la región Amazonas y refuerzan la eficacia de la terapia combinada con artemisinina en esta área.

Technological variables predictors of academic stress in nursing students in times of COVID-19. / Variables tecnológicas predictoras del estrés académico en estudiantes de Enfermería en tiempos de COVID-19.

OBJECTIVE: to analyze which technological variables, derived from the use of electronic devices, predict academic stress and its dimensions in Nursing students. METHOD: analytical cross-sectional study carried out with a total of 796 students from six universities in Peru. The SISCO scale was used and four logistic regression models were estimated for the analysis, with selection of variables in stages. RESULTS: among the participants, 87.6% had a high level of academic stress; time using the electronic device, screen brightness, age and sex were associated with academic stress and its three dimensions; the position of using the electronic device was associated with the total scale and the stressors and reactions dimensions. Finally, the distance between the face and the electronic device was associated with the total scale and size of reactions. CONCLUSION: technological variables and sociodemographic characteristics predict academic stress in nursing students. It is suggested to optimize the time of use of computers, regulate the brightness of the screen, avoid sitting in inappropriate positions and pay attention to the distance, in order to reduce academic stress during distance learning.

analizar cuáles son las variables tecnológicas, derivadas del uso de dispositivo electrónico, predicen el estrés académico, y sus dimensiones en estudiantes de enfermería. estudio transversal de tipo analítico, realizado en 796 estudiantes de seis universidades de Perú. Se empleó la escala SISCO y para el análisis se estimaron cuatro modelos de regresión logística, con selección de variables por pasos. entre los participantes, 87,6% presentaron un nivel alto de estrés académico; el tiempo de uso del dispositivo electrónico, el brillo de la pantalla, la edad y el sexo, estuvieron asociados con el estrés académico y sus tres dimensiones; la posición de uso del dispositivo electrónico estuvo asociada con la escala total y con las dimensiones estresores y reacciones. Finalmente, la distancia entre el rostro y el dispositivo electrónico estuvo asociada con la escala total y la dimensión reacciones. las variables tecnológicas y las características sociodemográficas predicen el estrés académico en estudiantes de enfermería. Se sugiere optimizar el tiempo de uso de las computadoras, regular el brillo de la pantalla, evitar sentarse en posiciones inadecuadas y vigilar la distancia, con la finalidad de reducir el estrés académico durante la enseñanza a distancia.

(1) Los estudiantes de enfermería presentan un nivel alto de estrés académico. (2) El tiempo de uso de la computadora es un predictor del estrés académico. (3) El brillo de la pantalla de la computadora es un predictor del estrés académico. (4) Tener entre 30 a 39 años y ser hombre es un factor protector del estrés académico. (5) Estudio realizado en seis universidades peruanas.

analisar quais variáveis tecnológicas, derivadas do uso de dispositivos eletrônicos, predizem o estresse acadêmico e suas dimensões em estudantes de enfermagem. estudo transversal do tipo analítico, realizado em 796 estudantes de seis universidades do Peru. Foi utilizada a escala SISCO e foram estimados quatro modelos de regressão logística para a análise, com seleção das variáveis por etapas. entre os participantes, 87,6% apresentaram alto nível de estresse acadêmico; o tempo de uso do aparelho eletrônico, o brilho da tela, a idade e o sexo foram associados ao estresse acadêmico e suas três dimensões; a posição de uso do aparelho eletrônico foi associada à escala total e às dimensões estressores e reações. Por fim, a distância entre o rosto e o dispositivo eletrônico foi associada à escala total e à dimensão das reações. variáveis tecnológicas e características sociodemográficas predizem estresse acadêmico em estudantes de Enfermagem. Sugere-se otimizar o tempo de uso dos computadores, regular o brilho da tela, evitar sentar-se em posições inadequadas e atentar-se à distância da tela, a fim de diminuir o estresse acadêmico durante o ensino a distância.

Digital Eye Strain among Peruvian Nursing Students: Prevalence and Associated Factors.

There has been a high prevalence of digital eye strain (DES) among students who have received distance-learning lessons due to COVID-19. However, in low- and middle-income countries, there are few studies that have analyzed its associated factors. This study aimed to determine the prevalence of DES and its associated factors among nursing students during COVID-19 distance learning. This was a cross-sectional analytical study conducted between May and June 2021 in six Peruvian universities. The sample comprised 796 nursing students. DES was measured using the Computer Vision Syndrome Questionnaire (CVS-Q). A bivariate logistic regression analysis was performed. DES was found in 87.6% of nursing students. Sitting upright (OR, 0.47; 95% IC, 0.30-0.74), using electronic devices for more than four hours a day (OR, 1.73; 95% IC, 1.02-2.86), not following the 20-20-20 rule (OR, 2.60; 95% IC, 1.25-5.20), having the screen brightness very high (OR, 3.36; 95% IC, 1.23-11.8), and not wearing glasses (OR, 0.59; 95% IC, 0.37-0.93) are factors associated with DES. The prevalence of DES among nursing students is high. Improving the ergonomics of study environments, reducing the time of exposure to electronic devices, adjusting the screen brightness, and taking eye-care measures are key to controlling computer vision syndrome in virtual learning.

Antibacterial and antibiofilm effects of essential oil components, EDTA and HLE disinfectant solution on Enterococcus, Pseudomonas and Staphylococcus sp. multiresistant strains isolated along the meat production chain.

The spread of multidrug resistant (MDR) bacteria and resistance genes along the food chain and the environment has become a global, but silent pandemic. To face this challenge, it is of outmost importance to develop efficient strategies to reduce potential contamination by these agents. In the present study, 30 strains of Enterococcus sp., Staphylococcus sp. and Pseudomonas sp. isolated from various surfaces throughout the meat production chain in a goat and lamb slaughterhouse were characterized as MDR bacteria harboring several antibiotic resistance genes (ARGs). The antimicrobial efficacy of natural essential oil components "EOCs" (carvacrol "CA," cinnamaldehyde "CIN," eugenol "EU," geraniol "GE," limonene "LI" and thymol "TH"), HLE disinfectant solution (3-6% H2O2; 2.2-4.4% lactic acid and 12.5-25 mM EDTA in water) and EDTA was tested against these MDR bacteria. Results showed that Minimum Inhibitory Concentrations (MIC) were compound and strain dependent. In addition, the synergistic effect of these antimicrobials was evaluated at 1/2 MIC. Here our study showed particularly promising results regarding the inhibitory effect at sub-inhibitory concentrations, which were confirmed by the analysis of bacterial growth dynamics over 72 h. Furthermore, the inhibitory effect of EOCs, HLE disinfectant solution and EDTA or their combinations was studied in developing and established biofilms of MDR bacteria obtaining variable results depending on the morphological structure of the tested strain and the phenolic character of the EOCs. Importantly, the combination of EOCs with HLE or EDTA showed particularly positive results given the effective inhibition of biofilm formation. Moreover, the synergistic combinations of EU and HLE/EDTA, TH, CA, GE, LI or CIN + EDTA/HLE caused log reductions in established biofilms of several strains (1-6 log10 CFU) depending on the species and the combination used, with Pseudomonas sp. strains being the most susceptible. Given these results, we propose novel antimicrobial formulations based on the combination of sub-inhibitory concentrations of EOCs and HLE or EDTA as a highly promising alternative to currently used approaches. This novel strategy notably shows great potential to efficiently decrease the emergence and spread of MDR bacteria and ARGs in the food chain and the environment, thus supporting the decrease of resistomes and pathogenesis in clinical and industrial areas while preserving the antibiotic therapeutic action.

[Living in nursing homes. Prognostic factor of mortality in respiratory infections?] / Vivir en residencias de ancianos ¿Factor pronóstico de mortalidad en infecciones respiratorias?

Respiratory infection is one of the most frequent diagnoses associated with high mortality. Living in a nursing home could be a predictive risk factor for mortality. The objective was to study the characteristics of patients with respiratory infection according to whether they came from their home or nursing homes, and to analyze whether their origin is a risk factor for mortality. It was a prospective cohort study, that included 208 patients with respiratory infection admitted to the Internal Medicine Service, that participated in the study. Clinical, analytical, epidemiological, prognostic and therapeutic variables were collected and a multivariate analysis was performed. Patients had an average age of 83 years and 64.9% came from their home. 44.7% had heart failure as a clinical history. Most of patients met criteria of pluripatology, polypharmacy and were moderately dependent according to Barthel's index. Mortality at admission was 16 patients (7.7%), and during the six-month follow-up of 37 patients (17.8%). Those coming from nursing homes had a higher mortality rate, 37%, than those who lived in their own home, 19.3% (p = 0.005). In the multivariate analysis, the prognostic factors for mortality were a higher level of urea at admission (OR = 2.33, IC 95% = 1.06-5.11) and the non-prescription of oxygen at discharge (OR = 2.96, IC 95% = 1.29-6.82). In conclusion, a higher percentage of mortality is observed in patients coming from nursing homes, however further research is needed to clarify whether living in a residence for elderly can be considered an independent risk factor for mortality.

La infección respiratoria es uno de los diagnósticos más frecuentes en el ámbito sanitario asociado a una elevada mortalidad. Residir en una residencia de ancianos podría ser un factor de riesgo predictivo de mortalidad. El objetivo fue estudiar las características de los pacientes con infección respiratoria según procedieran de su domicilio o de residencias de ancianos, y analizar si la procedencia es un factor de riesgo de mortalidad. Se trata de un estudio de cohortes prospectivo. Participaron 208 pacientes con infección respiratoria ingresados en un Servicio de Medicina Interna. Se recogieron variables clínicas, analíticas, epidemiológicas, pronosticas y terapéuticas realizándose un análisis multivariado. Los pacientes tuvieron una edad media 83 años y 135 (64.9%) procedían de su domicilio. El 44.7% presentaban insuficiencia cardiaca como antecedente clínico. La mayoría cumplían criterios de pluripatología, polifarmacia y tenían una dependencia moderada según índice de Barthel. La mortalidad durante el internamiento hospitalario fue de 16 pacientes (7.7%), y durante el seguimiento a seis meses de 37 (17.8%). Los procedentes de residencias de ancianos presentaron una mayor mortalidad, un 37%, que los que vivían en su propio domicilio, un 19,3% (p = 0.005). En el análisis multivariado los factores pronósticos de mortalidad fueron un mayor nivel de urea al ingreso (OR = 2.33, IC 95% = 1.06-5.11) y la no prescripción de oxígeno al alta (OR = 2.96, IC 95% = 1.29-6.82). En conclusión, se observó un mayor porcentaje de mortalidad en los pacientes procedentes de residencias de ancianos, sin embargo, es necesario realizar más investigaciones para clarificar si el residir en un centro geriátrico puede ser considerado un factor de riesgo independiente de mortalidad.

Preclinical studies of efficacy thresholds and tolerability of a clinically ready lentiviral vector for pyruvate kinase deficiency treatment.

Pyruvate kinase deficiency (PKD) is a rare autosomal recessive disorder caused by mutations in the PKLR gene. PKD is characterized by non-spherocytic hemolytic anemia of variable severity and may be fatal in some cases during early childhood. Although not considered the standard of care, allogeneic stem cell transplantation has been shown as a potentially curative treatment, limited by donor availability, toxicity, and incomplete engraftment. Preclinical studies were conducted to define conditions to enable consistent therapeutic reversal, which were based on our previous data on lentiviral gene therapy for PKD. Improvement of erythroid parameters was identified by the presence of 20%-30% healthy donor cells. A minimum vector copy number (VCN) of 0.2-0.3 was required to correct PKD when corrected cells were transplanted in a mouse model for PKD. Biodistribution and pharmacokinetics studies, with the aim of conducting a global gene therapy clinical trial for PKD patients (RP-L301-0119), demonstrated that genetically corrected cells do not confer additional side effects. Moreover, a clinically compatible transduction protocol with mobilized peripheral blood CD34+ cells was optimized, thus facilitating the efficient transduction on human cells capable of repopulating the hematopoiesis of immunodeficient mice. We established conditions for a curative lentiviral vector gene therapy protocol for PKD.

Transcriptomic Profile and Probiotic Properties of Lactiplantibacillus pentosus Pre-adapted to Edible Oils.

In this study, we determined whether pre-adapting Lactiplantibacillus pentosus strains, isolated from Aloreña green table olives, to vegetable-based edible oils improved their robustness and functionality; this may have great importance on their stress response during fermentation, storage, and digestion. Pre-adapting the strains to the corresponding oils significantly increased their probiotic functionality (e.g., auto-aggregation, co-aggregation with pathogens, and mucin adhesion), although results depended on the strain and the oil used for pre-adaptation. As such, we selected olive-adapted (TO) L. pentosus AP2-16, which exhibited improved functionality, and subjected it to transcriptomic profiling with the aim to understand the molecular mechanisms involved in the adaptation and the increased functionality. Global transcriptomic analysis of oil-adapted (olive or almond) and non-adapted (control) L. pentosus AP2-16 realized that 3,259 genes were expressed, with 2,779 mapped to the reference database. Comparative transcriptomic analysis showed that 125 genes (olive vs. control) and 108 genes (olive vs. almond) became significantly differentially expressed. TO L. pentosus AP2-16 responded by rerouting its metabolic pathways to balance energy production and storage, cell growth and survivability, host interactions (glycoconjugates), and other physiological features. As such, the pre-adaptation of lactobacilli with olive oil switches their transcriptional network to regulate robustness and functionality, possibly representing a novel approach toward the design and manufacture of probiotic products with improved stability and functionality.

[Continuous glucose monitoring using the Glucoday system, in children and adolescents who have type one diabetes]. / Determinación continua de glucosa sistema glucoday. En niños adolescentes con diabetes tipo 1.

At present times, Continuous Glucose Monitoring is a recommended method to detect glucemia fluctuations in patients who have diabetes, due to the fine correlation between interstitial glucose and capillary glucemia. The objective of this project is obtain a glucose register during a 48 hour period in a group of Type I diabetes patients who have an irregular metabolic control and to evaluate effectiveness of treatment employed, as well as evaluating compliance of the therapeutic norms established for each patient. At the same time, the authors plan to test the usefulness of a graphical register for diabetic education. After applying an anesthetic cream in the lateral umbilical zone, a subcutaneous catheter connected to a GLUCODAY, Menarini Diagnostics glucose sensor is inserted which, by means of a continuous sequence taking measures in interstitial liquid, registers a value every three minutes for as long as this connection is maintained. After a maximum 48 hour period, data are transferred to a computer and by means of the corresponding computer program, a graphic register for each patient is produced. Informed consent has been obtained from each patient. There were 23 patients in this study group, each diagnosed to have Type I diabetes; eight of these patients, two girls and six boys, were pre-puberty aged while 15, six girls and nine boys, were adolescents. Two of the pre-puberty patients had pathological antecedents, in one case celiac and the other thyroid disease. Two of the puberty aged patients had a history of chronic lymphocytic thyroid disease under opo-therapeutic treatment. Individual analysis of each case permits health professionals to detect a series of facts: it is difficult to comply with glucemic objectives in this group of adolescents having diabetes, with insulin treatment installed and researchers detect postprandial hyper-glucemia which do not appear when using capillary glucemias carried out by habitual methods. Study observations manifest a lack of compliance in indicated agreed upon schedules and researchers detect dietary transgressions. Continuous Glucose Monitoring makes it possible to obtain a graphic which can include those incidences which have occurred, facilitate commenting on the errors detected with adolescent patients and permit proposing a series of therapeutic modifications based on concrete, real data. Continuous Glucose Monitoring promises to be a useful tool to educate patients about diabetes.

Combined inhibition of PIM and CDK4/6 suppresses both mTOR signaling and Rb phosphorylation and potentiates PI3K inhibition in cancer cells.

Aberrant activation of mitogenic signaling pathways in cancer promotes growth and proliferation of cells by activating mTOR and S6 phosphorylation, and D-cyclin kinases and Rb phosphorylation, respectively. Correspondingly, inhibition of phosphorylation of both Rb and S6 is required for robust anti-tumor efficacy of drugs that inhibit cell signaling. The best-established mechanism of mTOR activation in cancer is via PI3K/Akt signaling, but mTOR activity can also be stimulated by CDK4 and PIM kinases. In this study, we show that the CDK4/6 inhibitor abemaciclib inhibits PIM kinase and S6 phosphorylation in cancer cells and concurrent inhibition of PIM, CDK4, and CDK6 suppresses both S6 and Rb phosphorylation. TSC2 or PIK3CA mutations obviate the requirement for PIM kinase and circumvent the inhibition of S6 phosphorylation by abemaciclib. Combination with a PI3K inhibitor restored suppression of S6 phosphorylation and synergized to curtail cell growth. By combining abemaciclib with a PI3K inhibitor, three pathways (Akt, PIM, and CDK4) to mTOR activation are neutralized, suggesting a potential combination strategy for the treatment of PIK3CA-mutant ER+ breast cancer.

[Hospital mortality of community respiratory infections and associated with long-term care facilities: a systematic review]. / Mortalidad hospitalaria de las infecciones respiratorias comunitarias y asociadas a cuidados socio-sanitarios: una revisión sistemática.

BACKGROUND: Respiratory infections are a cause of socio-health concern due to their high mortality and the economic cost. The number of patients from social care centers with respiratory infections requiring hospital admission is increasing in recent decades. The particularities of these patients could influence the evolution of these infections. AIM: To analyze if there are differences respect to mortality between respiratory infections of community origin and those associated with social care centers. METHODS: A systematic review was carried out in three databases: Medline, Web of Science and Scopus. Empirical studies, published between 2000 and 2016, were included. RESULTS: The origin of the patients, age and malnutrition were the factors associated with worse prognosis, together with the presence of cardiac or neurological comorbidity. Mortality was higher in patients from social care centers compared to those who came from their home. CONCLUSION: Health professionals should take into account the origin of the patients in order to give a more personalized care according to the particularities of these patients.

Reflexiones sobre el cuidado ambiental desde la perspectiva de estudiantes universitarios de Enfermería / Reflections on Environmental Care from the Perspective of University Nursing Students

Introducción: Cada día el medio ambiente se ve deteriorado por la contaminación ambiental y el cambio climático, por tanto, es necesario que desde su formación universitaria los futuros enfermeros tomen conciencia ambiental, ayuden a prevenir enfermedades emergentes y se comprometan con el cuidado de su entorno, que le permita un hábitat saludable para todos. Objetivo: Comprender las reflexiones sobre el cuidado ambiental desde la perspectiva de estudiantes universitarios de Enfermería. Métodos: Se realizó una investigación cualitativa descriptiva exploratoria en agosto del 2022. La población fue de 20 estudiantes de Enfermería de la Universidad Nacional "Toribio Rodríguez de Mendoza" de Amazonas en Perú, que cursaron la asignatura de Enfermería en Salud Ambiental, y la muestra fue de 12 estudiantes, obtenida por la técnica de saturación y redundancia. Para recolectar los datos se usó la entrevista semiestructurada a través de la plataforma Zoom, procesadas con el análisis de contenido temático. Resultados: Se obtuvieron cuatro categorías: a) Interés para cuidar el medio ambiente, b) Estrategias para cuidar el medio ambiente a nivel personal y familiar, c) Percepción sobre el cuidado/descuido del medio ambiente en su comunidad, y d) Impacto de la formación profesional para cuidar el medio ambiente. Conclusiones: Los estudiantes de Enfermería son conscientes de la importancia del cuidado del medio ambiente y por ello practican, junto a su familia, acciones que ayudan a mitigar el cambio climático. Se confirma el impacto positivo que tiene la asignatura de Enfermería en salud ambiental, por ello otras escuelas y facultades de Enfermería lo deberían considerar en sus planes curriculares(AU)

Introduction: Every day, the environment becomes much deteriorated by environmental pollution and climate change; therefore, it is necessary that, from their university education, future nurses become environmentally aware, help to prevent emerging diseases and commit themselves to taking care of their environment, allowing a healthy habitat for all. Objective: To understand the reflections on environmental care from the perspective of university Nursing students. Methods: An exploratory descriptive and qualitative research was conducted in August 2022. The population was 20 Nursing students from Universidad Nacional Toribio Rodríguez de Mendoza, of Amazonas in Peru, who studied the subject of Nursing in Environmental Health. The sample, of 12 students, was obtained using the saturation and redundancy technique. To collect the data, a semistructured interview was used through the Zoom platform, processed using thematic content analysis. Results: Four categories were obtained: a) Interest in caring for the environment, b) Strategies to care for the environment at a personal and family level, c) Perception on care/neglect of the environment in their community, and d) Impact of professional training to care for the environment. Conclusions: Nursing students are aware of the importance of caring for the environment; therefore, they carry out, together with their family, actions that help to mitigate climate change. The positive impact of the course Nursing in Environmental Health course is confirmed, and other schools or academic institutions of nursing should consider it for their curricular plans(AU)

Tenofovir-based rescue therapy for advanced liver disease in 6 patients coinfected with HIV and hepatitis B virus and receiving lamivudine.

We summarize the clinical history and laboratory results following the introduction of tenofovir among 6 patients coinfected with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) who presented with severe liver disease while receiving lamivudine-based highly active antiretroviral therapy. In all cases, the introduction of tenofovir led to a sustained undetectable HBV and HIV loads, with marked clinical and laboratory improvement in liver function. We provide supporting evidence for the role of tenofovir in the management of advanced HBV infection in HIV-positive patients after the development of lamivudine resistance.

Pneumocystis jirovecii transmission from immunocompetent carriers to infant.

We report a case of Pneumocystis jirovecii transmission from colonized grandparents to their infant granddaughter. Genotyping of P. jirovecii showed the same genotypes in samples from the infant and her grandparents. These findings support P. jirovecii transmission from immunocompetent carrier adults to a susceptible child.

Caracterización molecular del dominio de la hélice del gen k13 de Plasmodium falciparum en muestras de comunidades nativas de Condorcanqui, Amazonas, Perú / Molecular characterization of the Plasmodium falciparum k13 gene helix domain in samples from native communities of Condorcanqui, Amazonas, Perú

Introducción. La resistencia de Plasmodium falciparum a diferentes fármacos antipalúdicos es un obstáculo para eliminar la enfermedad. El genotipo resistente de P. falciparum a la artemisinina puede evaluarse examinando los polimorfismos en el dominio de la hélice del gen Pfk13. La Organización Mundial de la Salud recomienda utilizar estas mutaciones como marcadores moleculares para detectar la resistencia a la artemisinina en países donde la malaria por P. falciparum es endémica. Objetivo. Identificar mutaciones relacionadas con la resistencia a artemisinina presentes en el dominio de la hélice del gen k13 de P. falciparum. Materiales y métodos. Mediante la detección pasiva de casos, se recolectaron 51 muestras positivas por microscopía para Plasmodium, provenientes de seis comunidades del distrito de Río Santiago en Condorcanqui, Amazonas. Se realizó la confirmación molecular de la especie mediante PCR en tiempo real y el dominio de la hélice del gen Pfk13 se amplificó y secuenció por electroforesis capilar. Las secuencias obtenidas se compararon con la cepa de referencia 3D7 de fenotipo silvestre. Resultados. Se confirmó un total de 51 muestras positivas para P. falciparum, provenientes de las comunidades de Ayambis, Chapiza, Palometa, Muchinguis, Alianza Progreso y Caterpiza. Después del alineamiento de las secuencias de ADN, se determinó que las muestras no presentaron mutaciones asociadas con resistencia en el gen K13. Discusión. Los resultados obtenidos son coherentes con estudios similares realizados en otros países de Sudamérica, incluyendo Perú. Estos datos proporcionan una línea base para la vigilancia molecular de resistencia a artemisinina en la región Amazonas y refuerzan la eficacia de la terapia combinada con artemisinina en esta área.

Introduction. Resistance of Plasmodium falciparum to different antimalarial drugs is an obstacle to disease elimination. The artemisinin-resistant genotype of P. falciparum can be assessed by examining polymorphisms in the helix domain of the Pfk13 gene. The World Health Organization recommends these mutations as molecular markers to detect artemisinin-resistant in countries where P. falciparum malaria is endemic. Objective. To identify artemisinin resistance-related mutations present in the helix domain of the P. falciparum k13 gene. Materials and methods. We collected a total of 51 samples through passive case detection, positive for Plasmodium by microscopy, from six communities in the district of Río Santiago in Condorcanqui, Amazonas. Molecular species confirmation was performed by real-time PCR and Pfk13 helix domain was amplified and sequenced by capillary electrophoresis. The obtained sequences were compared with the wild type 3D7 reference strain. Results. A total of 51 positive samples were confirmed for P. falciparum from the communities of Ayambis, Chapiza, Palometa, Muchinguis, Alianza Progreso and Caterpiza. DNA sequences alignment showed the absence of resistance-associated mutations in the k13 gene of the collected samples. Discussion. The obtained results are consistent with similar studies conducted in other South American countries, including Perú, so these data provide a baseline for artemisinin- resistance molecular surveillance in the Amazon region and reinforce the efficacy of artemisinin-based combination therapy in this area.