An adenosine derivative promotes mitochondrial supercomplexes reorganization and restoration of mitochondria structure and bioenergetics in a diethylnitrosamine-induced hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) progression is associated with dysfunctional mitochondria and bioenergetics impairment. However, no data about the relationship between mitochondrial supercomplexes (hmwSC) formation and ATP production rates in HCC are available. Our group has developed an adenosine derivative, IFC-305, which improves mitochondrial function, and it has been proposed as a therapeutic candidate for HCC. We aimed to determine the role of IFC-305 on both mitochondrial structure and bioenergetics in a sequential cirrhosis-HCC model in rats. Our results showed that IFC-305 administration decreased the number and size of liver tumors, reduced the expression of tumoral markers, and reestablished the typical architecture of the hepatic parenchyma. The livers of treated rats showed a reduction of mitochondria number, recovery of the mtDNA/nDNA ratio, and mitochondrial length. Also, IFC-305 increased cardiolipin and phosphatidylcholine levels and promoted hmwSC reorganization with changes in the expression levels of hmwSC assembly-related genes. IFC-305 in HCC modified the expression of several genes encoding elements of electron transport chain complexes and increased the ATP levels by recovering the complex I, III, and V activity. We propose that IFC-305 restores the mitochondrial bioenergetics in HCC by normalizing the quantity, morphology, and function of mitochondria, possibly as part of its hepatic restorative effect.

Best practices in phase III clinical trials on DMTs for multiple sclerosis: a systematic analysis and appraisal of published trials.

BACKGROUND: Great advances have been made in the field of multiple sclerosis (MS) therapy due to the publication of numerous randomised clinical trials (RCTs). In this study, we carried out a critical appraisal of phase III RCTs of disease-modifying therapies (DMTs) for MS published after 2010, intending to identify critical areas of improvement. METHODS: We performed a systematic search of published RCTs on MS from January 2010 until December 2021. RCTs were assessed using an ad-hoc tool. This tool was developed based on existing generic methodological instruments and MS-specific guidelines and methodological papers. It included 14 items grouped in 5 domains: methodological quality, adequacy and measurement of outcomes, adverse event reporting, applicability and relevance of results, and transparency and conflict of interest. RESULTS: We identified 31 phase III RCTs. Most of them were fully compliant in terms of sample size (87%), randomisation (68%), blinding (61%), participant selection (68%), adverse event reporting (84%) and clinical relevance (52%). Only a few were compliant in terms of participant description (6%), comparison (42%), attrition bias (26%), adequacy of outcome measures (26%), applicability (23%), transparency (36%) and conflict of interest (6%). None were compliant in terms of analysis and reporting of outcomes. The most common limitations related to the absence of comorbidity data, unjustified use of placebo, inadequacy of outcomes design and absence of protocol and/or prospective registration. CONCLUSIONS: RCTs for DMTs in MS have relevant and frequent limitations. These should be addressed to enhance their quality, transparency and external validity.

Efficacy and Toxicity Evaluation of Bepotastine Besilate 1.5% Preservative-Free Eye Drops Vs Olopatadine Hydrochloride 0.2% Bak-Preserved Eye Drops in Patients with Allergic Conjunctivitis.

Purpose: To study the efficacy and toxic effects of bepotastine besilate 1.5% preservative-free (BB-PF) and olopatadine 0.2% BAK-preserved (OL-BAK) drops on the ocular surface of patients with allergic conjunctivitis. Patients and Methods: Ninety-seven patients with allergic conjunctivitis diagnosis participated in a prospective, multicenter, randomized, double-blind, controlled, parallel-group clinical trial. Patients received either BB-PF (n=48) or OL-BAK (n=49), both administered once daily in the morning. The patients were followed for 60 days. Ocular itching was the primary outcome measure. Secondary outcomes included ocular symptoms, signs, and non-ocular symptoms associated with rhinoconjunctivitis. Conjunctival impression cytology (CIC) was performed to evaluate histopathological changes related to the toxic effects of preservatives. Results: BB-PF treatment was associated with a 1.30 more probability of diminished ocular itching than OL-BAK (odds ratio (OR)=1.30; 95% CI=(0.96-1.7); p=0.086). No statistically significant differences were found between treatments in the resolution of other ocular symptoms or signs, except for tearing, which was superior in the BB-PF (OR=1.37; 95% (1.26-1.47); p<0.0001). BB-PF was superior in terms of the resolution of rhinorrhea (p=0.040) and nasal itching (p=0.037). After 60 days of treatment, the BB-PF group exhibited 2.0 times higher probability of having a lower Nelson scale score compared to the OL-BAK group (OR=2.00; 95% CI=(1.19-3.34); p=0.010). Conclusion: Both medications presented a similar efficacy in terms of the resolution of ocular signs and symptoms associated with ocular conjunctivitis. BB-PF is superior in the resolution of non-ocular symptoms and safer for the ocular surface than OL-BAK.

An adenosine derivative prevents the alterations observed in metabolic syndrome in a rat model induced by a rich high-fat diet and sucrose supplementation.

Metabolic syndrome is a multifactorial disease with high prevalence worldwide. It is related to cardiovascular disease, diabetes, and obesity. Approximately 80% of patients with metabolic syndrome have some degree of fatty liver disease. An adenosine derivative (IFC-305) has been shown to exert protective effects in models of liver damage as well as on elements involved in central metabolism; therefore, here, we evaluated the effect of IFC-305 in an experimental model of metabolic syndrome in rats induced by a high-fat diet and 10% sucrose in drinking water for 18 weeks. We also determined changes in fatty acid uptake in the Huh-7 cell line. In the experimental model, increases in body mass, serum triglycerides and proinflammatory cytokines were induced in rats, and the adenosine derivative significantly prevented these changes. Interestingly, IFC-305 prevented alterations in glucose and insulin tolerance, enabling the regulation of glucose levels in the same way as in the control group. Histologically, the alterations, including mitochondrial morphological changes, observed in response to the high-fat diet were prevented by administration of the adenosine derivative. This compound exerted protective effects against metabolic syndrome, likely due to its action in metabolic regulation, such as in the regulation of glucose blood levels and hepatocyte fatty acid uptake.

Neurotological emergencies: a narrative review.

INTRODUCTION: Vestibular symptoms, including vertigo, dizziness, and gait unsteadiness, are a frequent reason of urgent medical assistance. Their causes are numerous and diverse, including neurological, otorhinolaryngological, and systemic diseases. Therefore, following a systematic approach is essential to differentiate striking but benign conditions from others that can compromise the patient's life. This study is intended to review vestibular disorders from a practical perspective and provide guidance to physicians involved in the emergency care of patients with vestibular symptoms. MATERIALS AND METHODS: A narrative review was performed, revisiting the main causes of vestibular disorders. RESULTS: Based on the speed of onset, duration, and history of similar episodes in the past, vestibular disorders can be categorized into three syndromic entities (acute, recurrent, and chronic vestibular syndromes). The most representative conditions pertaining to each group were reviewed (including their diagnosis and treatment) and a practical algorithm was proposed for their correct management in the acute care setting. CONCLUSIONS: Carrying out a correct categorization of the vestibular disorders is essential to avoid diagnostic pitfalls. This review provides useful tools for clinicians to approach their patients with vestibular symptoms at the emergency room.

Evidence of publication bias in multiple sclerosis clinical trials: a comparative analysis of published and unpublished studies registered in ClinicalTrials.gov.

BACKGROUND: Complete and timely publication of clinical trials ensures that patients and the medical community are fully informed when making treatment decisions. The aim of this study is to assess the publication of phase III and IV clinical trials on multiple sclerosis (MS) drugs that have been carried out between 2010 and 2019 and to identify the factors associated with their publication in peer-reviewed journals. METHODS: An advanced search in ClinicalTrials.gov was performed and consecutive searches in PubMed, EMBASE and Google Scholar were conducted looking for the associated publications of all completed trials. Study design characteristics, results and other relevant information were extracted. Data was analysed following a case-control design. Clinical trials with associated publications in peer-reviewed journals were the cases and unpublished trials were the controls. A multivariate logistic regression analysis was performed to identify factors associated with trial publication. RESULTS: One hundred and fifty clinical trials were included in the analysis. Ninety-six of them (64.0%) were published in peer-reviewed journals. In the multivariate analysis, factors associated with trial publication were a favourable primary outcome (OR 12.49, 95% CI 1.28 to 122.29) and reaching the originally estimated sample size (OR 41.97, 95% CI 1.96 to 900.48), while those associated with a lower odds of publication were having 20% or more patients lost to follow-up (OR 0.03, 95% CI 0.01 to 0.52) and evaluating drugs intended to improve treatment tolerability (OR 0.01, 95% CI 0.00 to 0.74). CONCLUSIONS: Phase III and IV clinical trials on MS drugs are prone to under-reporting and publication bias. Efforts must be made to promote a complete and accurate dissemination of data in MS clinical research.

Cancer-associated spinal cord infarction: A systematic review and analysis of survival predictors.

OBJECTIVE: The association between spinal cord infarction (SCI) and cancer is an infrequent condition but requires an accurate diagnosis to establish the appropriate treatment. Clinical features and prognosis of cancer-associated SCI have never been assessed. The aim of this systematic review is to describe the characteristics and outcomes of patients with cancer-associated SCI. Illustratively, a case of ovarian cancer-related SCI is presented. MATERIAL AND METHODS: Two authors independently analysed three different bibliographic databases looking for cancer-associated SCI case reports and case series. Data regarding age, sex, cardiovascular risk factors (CVRF), history of known cancer, infarction localization, spinal cord syndrome, Zalewski criteria classification, mechanism of ischemia, diagnostic tests, treatment and functional outcome were registered. A statistical analysis was carried out to identify factors related to mortality and survival time. RESULTS: A total of 48 articles met the inclusion criteria and 52 patients were identified. The median age was 62 years. The most frequent neoplasm was intravascular large B-cell lymphoma. The median survival time was 17.4 weeks and the cumulative probability of survival at 12 months was 16.3%. In the group of deceased patients there was a higher proportion of malignant neoplasms than in those who survived (94.7% vs. 5.3%, p < 0.01). There were no statistically significant differences in terms of mortality or survival time depending on age, previously known cancer or CVRF. CONCLUSION: Cancer-associated SCI entails a poor outcome. Mortality is increased in patients with malignant neoplasm. No other prognosis factors could be identified.

An efficient analysis of oblique reflection of airborne ultrasound beams from thin membranes for gas sensing.

The use of the angular spectrum method (ASM) to simulate the reflection of airborne ultrasound beams from a thin membrane separating air from a mixture of air and another gas is examined. The main advantage of this method is its high computing speed and efficiency for practical design calculations, suitable for sensing applications. The implemented ASM code is validated against custom Rayleigh integral code in a pure propagation simulation. In addition, ultrasound beam reflection calculations using ASM with finite element numerical results and experimental measurements are compared, finding good agreement in both cases. Then, ASM is used to estimate the sensitivity of specular reflection signals to variations in the composition of the incidence medium as a function of the angle of incidence. Conditions for which a reflection signal using inexpensive commercial ultrasound emitter/receiver at 40 kHz, in a simple configuration, offer a high enough sensitivity suitable for monitoring air quality indoors are found.

Home-based blood transfusion therapy: A systematic review.

Home care is a healthcare alternative to hospitalisation. Different types of procedures are performed at home care services, such as home transfusion of blood products. However, home blood transfusion is not fully implemented and there is a great lack of knowledge about it. The aims of this study were thus to assess the safety and effectiveness of home blood transfusions and patient acceptance and satisfaction. A systematic literature review was conducted in the main biomedical databases. We included all studies that covered patients who had received a home blood transfusion, regardless of their baseline diagnosis. The literature search yielded 290 studies, 14 of which were included in this study as they met the predefined criteria. The main patient profile of a home-transfusion recipient was a person with anaemia associated with other diseases. Overall incidence of severe adverse events was 0.05%. No studies evaluated the effectiveness of home versus hospital transfusions. One study showed that 51% of patients would be willing to receive home transfusions. Home blood transfusion appears to be a feasible, safe, and well-accepted procedure. Existing studies are of low quality, however, and this is an important limitation when it comes to drawing definitive benefit-risk conclusions.

Clinical and sociodemographic characterization of pregnant women hospitalized with COVID-19.

INTRODUCTION: In pregnant women, a higher risk for developing viral respiratory infections is identified. OBJECTIVE: To analyze sociodemographic characteristics, evolution, clinical manifestations, and complications of pregnant women hospitalized with COVID-19. METHODS: Study conducted at 11 public hospitals; sociodemographic variables, comorbidities, signs and symptoms, laboratory and imaging findings, pregnancy characteristics, treatment and pregnancy outcome were included for analysis. RESULTS: Age ranged between 15 and 40 years; 85.1% were at third trimester of pregnancy, 11.9% at second and 3% at first; 27% had any comorbidity such as obesity, hypertension or asthma; 89.5% had fever, 73.1% cough, 44.8% dyspnea, 43.3% headache and 35.8% myalgia. Diagnoses were mild disease (55.2%), mild pneumonia (26.9%), severe pneumonia (10.4%), severe pneumonia with acute respiratory distress syndrome (4.5%), and severe pneumonia with septic shock (3%); 76.2% had noninvasive oxygen support, and 9%, mechanical ventilation. Pregnancy was interrupted in 53.8%; 95.5% were discharged due to improvement of their condition and 4.5% died. CONCLUSIONS: Age range and symptoms are consistent with those previously reported. Evidence was found of an increase in cesarean section without a clear indication in women with COVID-19.

INTRODUCCIÓN: En las mujeres embarazadas se identifica mayor riesgo de desarrollar infecciones respiratorias virales. OBJETIVO: Analizar características sociodemográficas, evolución, manifestaciones clínicas y complicaciones en mujeres embarazadas con COVID-19 que fueron hospitalizadas. MÉTODOS: Estudio en 11 hospitales públicos; se incluyeron variables sociodemográficas, comorbilidades, síntomas y signos, hallazgos de laboratorio y gabinete, características del embarazo, tratamiento y desenlace de la gestación. RESULTADOS: La edad osciló entre 15 y 40 años; 85.1 % cursaba el tercer trimestre del embarazo, 11.9 % el segundo y 3 % el primero; 27 % presentó alguna comorbilidad como obesidad, hipertensión o asma; 89.5 % presentó fiebre, 73.1 % tos, 44.8 % disnea, 43.3 % cefalea y 35.8 % mialgias. Los diagnósticos fueron enfermedad leve (55.2 %), neumonía leve (26.9 %), neumonía severa (10.4 %), neumonía severa con síndrome de distrés respiratorio agudo (4.5 %) y neumonía severa con choque séptico (3 %); 76.2 % recibió soporte de oxígeno no invasivo y 9 %, ventilación mecánica. Se interrumpió el embarazo en 53.8 %; 95.5 % egresó por mejoría y 4.5 % falleció. CONCLUSIONES: El rango de edad y los síntomas coinciden con los señalados en la literatura especializada. En mujeres con COVID-19 se evidenció el incremento de la operación cesárea sin una indicación clara.

Recreating Tissue Structures Representative of Teratomas In Vitro Using a Combination of 3D Cell Culture Technology and Human Embryonic Stem Cells.

In vitro studies using human embryonic stem cells (hESCs) are a valuable method to study aspects of embryogenesis, avoiding ethical issues when using embryonic materials and species dissimilarities. The xenograft teratoma assay is often traditionally used to establish pluripotency in putative PSC populations, but also has additional applications, including the study of tissue differentiation. The stem cell field has long sought an alternative due to various well-established issues with the in vivo technique, including significant protocol variability and animal usage. We have established a two-step culture method which combines PSC-derived embryoid bodies (EBs) with porous scaffolds to enhance their viability, prolonging the time these structures can be maintained, and therefore, permitting more complex, mature differentiation. Here, we have utilised human embryonic stem cell-derived EBs, demonstrating the formation of tissue rudiments of increasing complexity over time and the ability to manipulate their differentiation through the application of exogenous morphogens to achieve specific lineages. Crucially, these EB-derived tissues are highly reminiscent of xenograft teratoma samples derived from the same cell line. We believe this in vitro approach represents a reproducible, animal-free alternative to the teratoma assay, which can be used to study human tissue development.

Caracterización clínica y sociodemográfica de mujeres embarazadas con COVID-19 hospitalizadas / Clinical and sociodemographic characterization of pregnant women hospitalized with COVID-19

Resumen Introducción: En las mujeres embarazadas se identifica mayor riesgo de desarrollar infecciones respiratorias virales. Objetivo: Analizar características sociodemográficas, evolución, manifestaciones clínicas y complicaciones en mujeres embarazadas con COVID-19 que fueron hospitalizadas. Métodos: Estudio en 11 hospitales públicos; se incluyeron variables sociodemográficas, comorbilidades, síntomas y signos, hallazgos de laboratorio y gabinete, características del embarazo, tratamiento y desenlace de la gestación. Resultados: La edad osciló entre 15 y 40 años; 85.1 % cursaba el tercer trimestre del embarazo, 11.9 % el segundo y 3 % el primero; 27 % presentó alguna comorbilidad como obesidad, hipertensión o asma; 89.5 % presentó fiebre, 73.1 % tos, 44.8 % disnea, 43.3 % cefalea y 35.8 % mialgias. Los diagnósticos fueron enfermedad leve (55.2 %), neumonía leve (26.9 %), neumonía severa (10.4 %), neumonía severa con síndrome de distrés respiratorio agudo (4.5 %) y neumonía severa con choque séptico (3 %); 76.2 % recibió soporte de oxígeno no invasivo y 9 %, ventilación mecánica. Se interrumpió el embarazo en 53.8 %; 95.5 % egresó por mejoría y 4.5 % falleció. Conclusiones: El rango de edad y los síntomas coinciden con los señalados en la literatura especializada. En mujeres con COVID-19 se evidenció el incremento de la operación cesárea sin una indicación clara.

Abstract Introduction: In pregnant women, a higher risk for developing viral respiratory infections is identified. Objective: To analyze sociodemographic characteristics, evolution, clinical manifestations, and complications of pregnant women hospitalized with COVID-19. Methods: Study conducted at 11 public hospitals; sociodemographic variables, comorbidities, signs and symptoms, laboratory and imaging findings, pregnancy characteristics, treatment and pregnancy outcome were included for analysis. Results: Age ranged between 15 and 40 years; 85.1% were at third trimester of pregnancy, 11.9% at second and 3% at first; 27% had any comorbidity such as obesity, hypertension or asthma; 89.5% had fever, 73.1% cough, 44.8% dyspnea, 43.3% headache and 35.8% myalgia. Diagnoses were mild disease (55.2%), mild pneumonia (26.9%), severe pneumonia (10.4%), severe pneumonia with acute respiratory distress syndrome (4.5%), and severe pneumonia with septic shock (3%); 76.2% had noninvasive oxygen support, and 9%, mechanical ventilation. Pregnancy was interrupted in 53.8%; 95.5% were discharged due to improvement of their condition and 4.5% died. Conclusions: Age range and symptoms are consistent with those previously reported. Evidence was found of an increase in cesarean section without a clear indication in women with COVID-19.

Relación de la presión sistólica de la arteria pulmonar medida por ecocardiograma con el tiempo y el tipo de terapia de reemplazo renal / The relationship between systolic pressure of the pulmonary artery measured by echocardiogram and the duration and type of renal replacement therapy

Resumen Introducción: Las alteraciones secundarias a la enfermedad renal crónica (ERC), como inflamación sistémica, anemia y sobrecarga hídrica, son un sustrato importante para el desarrollo de hipertensión arterial pulmonar. Objetivo: Valorar la relación de la presión sistólica de la arteria pulmonar (PSAP) por ecocardiograma con el tiempo y el tipo de terapia de reemplazo renal (TRR) en pacientes con ERC. Método: Estudio observacional, retrospectivo, llevado a cabo en el Hospital de Especialidades del Centro Médico Nacional La Raza, en el que se analizaron medidas de tendencia central y medidas de dispersión. Para comparar porcentajes se utilizó la prueba de χ2 con el programa estadístico SPSS 25. Resultados: Se incluyeron 141 pacientes con ERC en TRR con diálisis peritoneal o hemodiálisis. Se clasificaron de acuerdo con la PSAP en normal (30 pacientes, 21.28%), leve (43 pacientes, 30.5%), moderada (16 pacientes, 12%) y grave (52 pacientes, 36.88%). El tiempo de TRR está relacionado con una PSAP mayor, con 3.53 años en caso de PSAP normal, 5.51 años en caso de PSAP leve, 6.00 años para la PSAP moderada y 6.38 años para la PSAP grave. La PSAP grave se presentó en 13 de 56 pacientes en diálisis peritoneal y en 39 de 85 en hemodiálisis (p = 0.034). Conclusiones: Se encontró que existe relación entre la PSAP con el tiempo y el tipo de sustitución renal en pacientes con ERC.

Abstract Introduction: The disorders secondary to chronic kidney disease (CKD), such as systemic inflammation, anemia, and fluid overload are an important substrate for the development of pulmonary arterial hypertension. Objective: To assess the relationship between pulmonary artery systolic pressure (PASP) on echocardiogram and the duration and type of renal replacement therapy (RRT) in patients with CKD. Method: A retrospective observational study at Hospital de Especialidades del Centro Médico Nacional La Raza. The analysis was performed using measures of central tendency and dispersion. Chi square was used to compare percentages through the SPSS 25 statistical program. Results: A total of 141 patients with CKD on RRT with peritoneal dialysis or hemodialysis were included. They were classified according to PASP as normal (30 patients, 21.28%), mild (43 patients, 30.5%), moderate (16 patients, 12%) and severe (52 patients, 36.88%). The duration of RRT is related to a higher PASP, with 3.53 years for a normal PASP, 5.51 years for mild PASP, 6.00 years for moderate PASP, and 6.38 for those with severe PASP. Severe PASP occurred in 13 of 56 patients on peritoneal dialysis and 39 of 85 patients on hemodialysis (p = 0.034). Conclusions: This study found a relationship between PASP and the duration and type of renal replacement in patients with CKD.

A novel ophthalmic latanoprost 0.005% nanoemulsion: a cytotoxicity study.

BACKGROUND: Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK. METHODS: Two different latanoprost eye drops were used: one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60 min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V-FITC and propidium iodide. RESULTS: The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (p < 0.05 at 15 and 30 min; p < 0.01 at 60 min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe. CONCLUSIONS: The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

Determination of the metabolic pathways for degradation of naphthalene and pyrene in Amycolatopsis sp. Poz14.

Polycyclic aromatic hydrocarbons (PAHs) constitute important soil contaminants derived from petroleum. Poz14 strain can degrade pyrene and naphthalene. Its genome presented 9333 genes, among them those required for PAHs degradation. By phylogenomic analysis, the strain might be assigned to Amycolatopsis nivea. The strain was grown in glucose, pyrene, and naphthalene to compare their proteomes; 180 proteins were detected in total, and 90 of them were exclusives for xenobiotic conditions. Functions enriched with the xenobiotics belonged to transcription, translation, modification of proteins and transport of inorganic ions. Enriched pathways were pentose phosphate, proteasome and RNA degradation; in contrast, in glucose were glycolysis/gluconeogenesis and glyoxylate cycle. Proteins proposed to participate in the upper PAHs degradation were multicomponent oxygenase complexes, Rieske oxygenases, and dioxygenases; in the lower pathways were ortho-cleavage of catechol, phenylacetate, phenylpropionate, benzoate, and anthranilate. The catechol dioxygenase activity was measured and found increased when the strain was grown in naphthalene. Amycolatopsis sp. Poz14 genome and proteome revealed the PAHs degradation pathways and functions helping to contend the effects of such process.

Looking for factors affecting functioning in euthymic patients with bipolar I disorder: the importance of cognitive complaints and BDNF's Val66Met polymorphism.

INTRODUCTION: Functioning in Bipolar Disorder (BD) is affected in a substantial proportion of patients. The impact of demographic, clinical, cognitive, and genetic factors on functioning has been shown individually; however, as a complex phenomenon, a global approach to identify the most relevant as well as possible interactions is needed. METHODS: 102 patients with type I BD in euthymia were invited for evaluation of demographic, clinical, and cognitive characteristics as well as genotype for Val66Met polymorphism of BDNF gene to determine those associated with poor functioning according to the FAST scale cut-off score. Clinical evaluation included assessment of residual affective symptoms and anxiety. Cognitive evaluation included the COBRA scale, verbal memory, and executive functions testing. RESULTS: Residual depressive symptoms, anxiety, cognitive complaints and being a Met carrier were more frequent in the poor functioning group and were entered in a logistic regression model. Being a Met carrier (OR=4.46, CI=1.19-16.67) and cognitive complaints (OR=1.29, CI= 1.13-1.46) were the most important predictors of poor functioning in type I BD. LIMITATIONS: Cross-sectional study, with select population limiting generalizability of findings. CONCLUSIONS: A better understanding of underlying factors affecting cognition, including the possible involvement of BDNF Val66Met polymorphism, its systematic evaluation and a continued search for targeted treatment, along with recognition and attention of residual affective and anxious symptoms might improve psychosocial outcomes such as functioning in this population.

A Tar aspartate receptor and Rubisco-like protein substitute biotin in the growth of rhizobial strains.

Biotin is a key cofactor of metabolic carboxylases, although many rhizobial strains are biotin auxotrophs. When some of these strains were serially subcultured in minimal medium, they showed diminished growth and increased excretion of metabolites. The addition of biotin, or genetic complementation with biotin synthesis genes resulted in full growth of Rhizobium etli CFN42 and Rhizobium phaseoli CIAT652 strains. Half of rhizobial genomes did not show genes for biotin biosynthesis, but three-quarters had genes for biotin transport. Some strains had genes for an avidin homologue (rhizavidin), a protein with high affinity for biotin but an unknown role in bacteria. A CFN42-derived rhizavidin mutant showed a sharper growth decrease in subcultures, revealing a role in biotin storage. In the search of biotin-independent growth of subcultures, CFN42 and CIAT652 strains with excess aeration showed optimal growth, as they also did, unexpectedly, with the addition of aspartic acid analogues α- and N-methyl aspartate. Aspartate analogues can be sensed by the chemotaxis aspartate receptor Tar. A tar homologue was identified and its mutants showed no growth recovery with aspartate analogues, indicating requirement of the Tar receptor in such a phenotype. Additionally, tar mutants did not recover full growth with excess aeration. A Rubisco-like protein was found to be necessary for growth as the corresponding mutants showed no recovery either with high aeration or aspartate analogues; also, diminished carboxylation was observed. Taken together, our results indicate a route of biotin-independent growth in rhizobial strains that included oxygen, a Tar receptor and a previously uncharacterized Rubisco-like protein.

Perspectivas tecnológicas y nutricionales de la quinua (Chenopodium quinoa): un pseudocereal andino funcional / Technological and nutritional perspectives of quinoa (chenopodium quinoa): a functional andean pseudocereal

Fundamentos: La quinua es un pseudocereal andino, de gran importancia para la seguridad alimentaria en Latinoamérica yel mundo. En el presente artículo, se exponen diversos atributos y aplicaciones funcionales, para este producto ancestral. Métodos: Se realizó una revisión general de literatura, siguiendo el protocolo PRISMA, que involucró una investigación cualitativa secundaria de índole teórico. Resultados: La quinua posee un excelente valor nutritivo, albergando proteína de alta calidad, fibra dietética, ácidos grasos insaturados, vitaminas y minerales. Se destacan su potencial antioxidante, hipocolesterolémico, citoprotector y coadyuvante en el tratamiento de la diabetes. Productos como panes, pastas, cereales y embutidos, han sido elaborados con éxito incorporando este insumo. Conclusiones: El uso de los granos y las hojas de la quinua, con otros fines, como la obtención de aceites, separación de saponinas y fabricación de extractos medicinales, cobran gran interés y prominencia en la actualidad. (AU)

Background: Quinoa is an andean pseudocereal, of great importance for food security. In this article, functional applications are exposed for this ancestral product. Methods: A general literature review was carried out, following the PRISMA protocol, which involved a qualitative secondary research, of a theoretical nature.Results: Quinoa has an excellent nutritional value, harboring high quality protein, dietary fiber, unsaturated fattyacids, vitamins and minerals. Its antioxidant, hypocholesterolemic, cytoprotective and coadjuvant potential in the treatment of diabetes, stand out. Products such as breads, pasta, cereals and sausages, have been successfully prepared incorporating quinoa.Conclusions: The use of its grains and leaves for other purposes, such as obtaining oils, separating saponins and manufacturing medicinal extracts, are gaining great interest andprominence. (AU)

Comparison between HET-CAM protocols and a product use clinical study for eye irritation evaluation of personal care products including cosmetics according to their surfactant composition.

The hen's egg test on chorioallantoic membrane (HET-CAM) is one of the most frequently used alternative tests for prediction of ocular irritation of cosmetic products. There are different HET-CAM protocols widely accepted, but there is no information about which of the protocols better correlates with the results obtained in product use clinical study under the conditions of use. Two Fix Time Methods (FTM) -Lüepke and the ICCVAM guideline - and two Reaction Time Methods (RTM) -ECVAM DBALM Prot. No. 47 and No. 96- were employed to test 18 cosmetic products. Simultaneously, they were evaluated by an ophthalmological clinical test. A unified classification system was used, and products were classified into four irritation levels: non-irritant, weak, moderate and severe irritant. The duration of use (rinse-off or leave-on), and the concentration and type of surfactants were taken into account in the analysis. All the products that were classified as non-irritant by any HET-CAM protocols were also safe in the product use clinical study. The product that was found to be non-safe in the product use clinical evaluation was also unsuitable by most of the HET-CAM protocols. These results were employed to develop an algorithm that allows selecting the appropriate HET-CAM protocol for each type of product to be tested.

Genome-wide association study of psychiatric and substance use comorbidity in Mexican individuals.

The combination of substance use and psychiatric disorders is one of the most common comorbidities. The objective of this study was to perform a genome-wide association study of this comorbidity (Com), substance use alone (Subs), and psychiatric symptomatology alone (Psych) in the Mexican population. The study included 3914 individuals of Mexican descent. Genotyping was carried out using the PsychArray microarray and genome-wide correlations were calculated. Genome-wide associations were analyzed using multiple logistic models, polygenic risk scores (PRSs) were evaluated using multinomial models, and vertical pleiotropy was evaluated by generalized summary-data-based Mendelian randomization. Brain DNA methylation quantitative loci (brain meQTL) were also evaluated in the prefrontal cortex. Genome-wide correlation and vertical pleiotropy were found between all traits. No genome-wide association signals were found, but 64 single-nucleotide polymorphism (SNPs) reached nominal associations (p < 5.00e-05). The SNPs associated with each trait were independent, and the individuals with high PRSs had a higher prevalence of tobacco and alcohol use. In the multinomial models all of the PRSs (Subs-PRS, Com-PRS, and Psych-PRS) were associated with all of the traits. Brain meQTL of the Subs-associated SNPs had an effect on the genes enriched in insulin signaling pathway, and that of the Psych-associated SNPs had an effect on the Fc gamma receptor phagocytosis pathway.