Real-world effectiveness of the heterologous SOBERANA-02 and SOBERANA-Plus vaccine scheme in 2-11 years-old children during the SARS-CoV-2 Omicron wave in Cuba: a longitudinal case-population study.

Background: Increased pediatric COVID-19 occurrence due to the SARS-CoV-2 Omicron variant has raised concerns about the effectiveness of existing vaccines. The protection provided by the SOBERANA-02-Plus vaccination scheme against this variant has not yet been studied. We aimed to evaluate the scheme's effectiveness against symptomatic Omicron infection and severe disease in children. Methods: In September 2021, Cuba implemented a mass pediatric immunization with the heterologous SOBERANA-02-Plus scheme: 2 doses of conjugated SOBERANA-02 followed by a heterologous SOBERANA-Plus dose. By December, before the Omicron outbreak, 95.4% of 2-18 years-old had been fully immunized. During the entire Omicron wave, we conducted a nationwide longitudinal post-vaccination case-population study to evaluate the real-world effectiveness of the SOBERANA-02-Plus scheme against symptomatic infection and severe disease in children without previous SARS-CoV-2 infection. The identification of COVID-19 cases relied on surveillance through first line services, which refer clinical suspects to pediatric hospitals where they are diagnosed based on a positive RT-PCR test. We defined the Incidence Rate ratio (IRR) as IRvaccinated age group/IRunvaccinated 1-year-old and calculated vaccine effectiveness as VE = (1-IRR)∗100%. 24 months of age being the 'eligible for vaccination' cut-off, we used a regression discontinuity approach to estimate effectiveness by contrasting incidence in all unvaccinated 1-year-old versus vaccinated 2-years-old. Estimates in the vaccinated 3-11 years-old are reported from a descriptive perspective. Findings: We included 1,098,817 fully vaccinated 2-11 years-old and 98,342 not vaccinated 1-year-old children. During the 24-week Omicron wave, there were 7003/26,241,176 person-weeks symptomatic COVID-19 infections in the vaccinated group (38.2 per 105 person-weeks in 2-years-old and 25.5 per 105 person-weeks in 3-11 years-old) against 3577/2,312,273 (154.7 per 105 person-weeks) in the unvaccinated group. The observed overall vaccine effectiveness against symptomatic infection was 75.3% (95% CI, 73.5-77.0%) in 2-years-old children, and 83.5% (95% CI, 82.8-84.2%) in 3-11 years-old. It was somewhat lower during Omicron BA.1 then during Omicron BA.2 variant circulation, which took place 1-3 and 4-6 months after the end of the vaccination campaign. The effectiveness against severe symptomatic disease was 100.0% (95% CI not estimated) and 94.6% (95% CI, 82.0-98.6%) in the respective age groups. No child death from COVID-19 was observed. Interpretation: Immunization of 2-11 years-old with the SOBERANA-02-Plus scheme provided strong protection against symptomatic and severe disease caused by the Omicron variant, which was sustained during the six months post-vaccination follow-up. Our results contrast with the observations in previous real-world vaccine effectiveness studies in children, which might be explained by the type of immunity a conjugated protein-based vaccine induces and the vaccination strategy used. Funding: National Fund for Science and Technology (FONCI-CITMA-Cuba).

Panapophenanthrin, a Rare Oligocyclic Diterpene from Panus strigellus.

During the course of our search for biologically active secondary metabolites from fungal cultures, a new oligocyclic diterpenoidal derivative, panapophenanthrin (1), was isolated from Panus strigellus. In addition, two known metabolites, panepophenanthrin (2) and dihydrohypnophilin (3), were also obtained. The chemical structures of the isolated compounds were elucidated based on extensive 1D and 2D NMR spectral analyses together with high-resolution electrospray ionization mass spectrometry (HR-ESI-MS). The absolute configuration was determined through TDDFT-ECD calculations. All of the compounds were assessed for their antimicrobial and cytotoxic activities. Compounds 1 and 3 showed moderate to weak activities in the performed antimicrobial assays, while compound 1 exhibited potent cytotoxic activity against the mammalian cell lines mouse fibroblast (L929) and human endocervical adenocarcinoma (KB3.1).

CSF1R-related Adult-onset Leukoencephalopathy: The First Reported Case in Spain.

Colony-stimulating factor 1 receptor-related adult-onset leukoencephalopathy is a primary microgliopathy characterized by a complex phenotype, which can be easily misdiagnosed with other leukoencephalopathy and neurodegenerative diseases such as frontotemporal dementia. It is estimated to be the most common adult-onset leukodystrophy. Here, we report the case of a 67-year-old man with a history of progressive impairment of behavioral and cognitive functions, including apathy, inhibition, tendency to mutism, and deficits in complex planning skills. Neurological examination revealed pyramidalism in the lower limbs. Brain imaging showed symmetrical confluent frontal leukoencephalopathy, bilateral frontal calcifications, and thinning of the corpus callosum. The diagnosis was confirmed by the identification of a heterozygous pathogenic variant in the colony-stimulating factor 1 receptor. As far as we know, this is the first documented case in Spain. In this paper, we aim to expand on clinical features and underline the importance of brain imaging for the diagnosis of an entity that we consider to be underdiagnosed.

Familia y Escuela. Perspectivas transformacionales en el acompañamiento afectivo y sexual / Family and School. Transformational perspectives in emotional and sexual accompaniment

Familia y escuela son instituciones primarias de la sociedad que convergen en la construcción de las bases del carácter y las pautas de comportamiento; por ello, se espera que en estas inicien los acompañamientos al desarrollo afectivo-sexual, mediante el reconocimiento del derecho a la libertad y la autonomía de los niños, niñas y adolescentes. Este artículo tuvo como objetivo analizar la transformación de las perspectivas sobre el acompañamiento afectivo-sexual de la familia y la escuela. Se llevó a cabo una revisión documental de textos académicos que tratan a la familia y la escuela como escenarios de formación afectivo-sexual. Se encontró que las perspectivas del acompañamiento afectivo-sexual son muy diversas, en ocasiones se abordan con fines informativos y, otras, como un elemento importante para la formación de seres sociales. Se concluyó que familia y escuela son aptas para ofrecer acompañamiento afectivo-sexual, por lo cual es importante que su labor sea colaborativa y en pro de la libertad y autonomía de los niños, niñas y adolescentes.

Family and school are the primary institutions of society, which converge in the construction of the foundations of character and behavior patterns; For this reason, it is there that support for affective-sexual development is expected to begin, by recognizing the right to freedom and autonomy of children and adolescents. This article aimed to analyze how the perspectives on the affective-sexual accompaniment of the family and the school have been transformed. A documentary review of academic texts that treat the family and the school as scenarios of affective-sexual formation was carried out. It was found that the perspectives of affective-sexual accompaniment are very diverse, sometimes it is addressed for informational purposes and, others, as an important element for the formation of social beings. It was concluded that family and school are suitable to offer affective-sexual accompaniment, for which it is important that their work is collaborative and in favor of the freedom and autonomy of children and adolescents.

Population Pharmacokinetics of Intra-articular and Intravenous Administration of Tranexamic Acid in Patients Undergoing Total Knee Replacement.

BACKGROUND: Tranexamic acid (TXA), an antifibrinolytic drug, is usually administered intravenously; however, intra-articular administration has recently been proven to be as effective as intravenous administration. Limited information regarding the pharmacokinetics (PK) of TXA after intra-articular administration has been reported. AIMS: The aim of this study was to develop a population PK model of TXA administered as a single intra-articular dose and as two intravenous doses, and to study the sources of interindividual variability (IIV) in the PK processes of TXA. The developed model was used to simulate PK profiles of TXA at different dosage regimens and in patients with renal impairment. METHODS: Patients who underwent primary unilateral total knee replacement (TKR) received 1 g/10 mL (concentration of 100 mg/mL) of TXA applied directly to the surgical field before wound closure, or 2 g (two doses of 1 g) of intravenous TXA. A population PK model was developed using a nonlinear mixed-effects approach and sources of IIV, such as sex, age, body weight, height, body mass index (BMI), preoperative haemoglobin, preoperative haematocrit, and creatinine clearance. RESULTS: Twenty-four patients were included, 12 in each group. Twenty patients were female, mean age (standard deviation) was 73.7 years (5.6). The disposition of TXA was best described as a two-compartment model with clearance dependent on creatinine clearance. Bootstrap results indicated that the model was stable and robust. The estimated bioavailability for intra-articular administration was 81%. Simulations indicated that 100% of patients would have plasma concentrations associated with partial fibrinolysis at 8 h post-administration with the dosages and routes of administration used in the present study. Intra-articular administration would produce complete inhibition of fibrinolysis in only 12% of patients compared with 72.5% with intravenous administration. No adverse events were reported. CONCLUSIONS: This population PK model demonstrated that a single dose of high-concentration, low-volume intra-articular TXA can achieve antifibrinolytic plasma concentrations of the drug for 8 h, providing both local and systemic effects in patients undergoing TKR. TXA administration to the surgical field could be an alternative to the intravenous; route for patients undergoing TKR; however, clinical studies are needed to assess the toxic local effects of TXA. TRIAL REGISTRATION: Spanish Clinical Studies Registry Number: 2017-004059-22. Date of registration: 12 April 2018.

Transcriptomic analyses of cacao flavonoids produced in photobioreactors.

BACKGROUND: Theobroma cacao is a major source of flavonoids such as catechins and their monomers proanthocyanidins (PAs), widely studied for their potential benefits in cardiovascular diseases. Light has been shown to promote plant secondary metabolite production in vitro. In this study, cacao cells cultured in 7.5 L stirred tank photobioreactors (STPs) were exposed to a change of white to blue LED lights for 28 days (d). RESULTS: Transcriptomic analyses were performed in three time points comparing changing expression patterns, after cell exposure to white light (d0-VS-d14), after a shift from white to blue light (d14-VS-d15), and after an extended period of blue light for the following 15 days (d15-VS-d28). Under white light, there was enrichment in metabolic pathways associated with cell growth (carbon, glycolysis, and amino acid biosynthesis) accompanied by a significant increase in the PAs content. In the shift to blue light, further increase in PAs content was observed concomitantly with the significant expression of TWO-COMPONENT RESPONSE REGULATOR genes involved in the early stress responses via circadian clock and hormone pathways. Under blue light exposure, we observed a depletion of PAs content associated with ROS-mediated stress pathways. CONCLUSIONS: Light effects on large-scale cell cultures in photobioreactors are complex and pleiotropic; however, we have been able to identify key regulatory players upstream cacao flavonoid biosynthesis in STPs, including TWO-COMPONENT SYSTEM and ROS-signaling genes. The crosstalk between flavonoid biosynthesis and regulatory networks led to understand the dynamics of flavonoid production and degradation in response to light-driven ROS signals. This can be used to optimize the time, and the yield of in vitro targeted metabolites in large-scale culture systems.

Mortality in Children Treated With Maintenance Peritoneal Dialysis: Findings From the International Pediatric Peritoneal Dialysis Network Registry.

RATIONALE & OBJECTIVE: Research on pediatric kidney replacement therapy (KRT) has primarily focused on Europe and North America. In this study, we describe the mortality risk of children treated with maintenance peritoneal dialysis (MPD) in different parts of the world and characterize the associated demographic and macroeconomic factors. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Patients younger than 19 years at inclusion into the International Pediatric Peritoneal Dialysis Network registry, who initiated MPD between 1996 and 2017. EXPOSURE: Region as primary exposure (Asia, Western Europe, Eastern Europe, Latin America, North America, and Oceania). Other demographic, clinical, and macroeconomic (4 income groups based on gross national income) factors also were studied. OUTCOME: All-cause MPD mortality. ANALYTICAL APPROACH: Patients were observed for 3 years, and the mortality rates in different regions and income groups were calculated. Cause-specific hazards models with random effects were fit to calculate the proportional change in variance for factors that could explain variation in mortality rates. RESULTS: A total of 2,956 patients with a median age of 7.8 years at the start of KRT were included. After 3 years, the overall probability of death was 5%, ranging from 2% in North America to 9% in Eastern Europe. Mortality rates were higher in low-income countries than in high-income countries. Income category explained 50.1% of the variance in mortality risk between regions. Other explanatory factors included peritoneal dialysis modality at start (22.5%) and body mass index (11.1%). LIMITATIONS: The interpretation of interregional survival differences as found in this study may be hampered by selection bias. CONCLUSIONS: This study shows that the overall 3-year patient survival on pediatric MPD is high, and that country income is associated with patient survival.

Elevated [CO2] benefits coffee growth and photosynthetic performance regardless of light availability.

Despite being evolved in shaded environments, most coffee (Coffea arabica L.) is cultivated worldwide under sparse shade or at full sunlight. Coffee is ranked as greatly responsive to climate change (CC), and shading has been considered an important management strategy for mitigating the harmful CC outcomes on the crop. However, there is no information on the effects of enhanced [CO2] (eCa) on coffee performance in response to light availability. Here, we examined how carbon assimilation and use are affected by eCa in combination with contrasting light levels. For that, greenhouse-grown plants were submitted to varying light levels (16 or 7.5 mol photons m-2 day-1) and [CO2] (ca. 380 or 740 µmol mol-1 air) over six months. We demonstrated that both high light and eCa improved growth and photosynthetic performance, independently. Despite marginal alterations in biomass partitioning, some allometric changes, such as higher root biomass-to-total leaf area and lower leaf area ratio under the combination of eCa and high light were found. Stimulation of photosynthetic rates by eCa occurred with no direct effect on stomatal and mesophyll conductances, and no signs of photosynthetic down-regulation were found irrespective of treatments. Particularly at high light, eCa led to decreases in both photorespiration rates and oxidative pressure. Overall, our novel findings suggest that eCa could tandemly act with shading to mitigate the harmful CC effects on coffee sustainability.

Detección prospectiva espacio-temporal de conglomerados de COVID-19 en Cuba

RESUMEN Introducción: Durante enfermedades infecciosas emergentes en curso como la COVID-19, la vigilancia espacio-temporal es fundamental para identificar áreas prioritarias para intervenciones específicas, diferenciar intensidad diagnóstica y asignación de recursos. Objetivo: Modelar la evolución del riesgo relativo de presentación de casos de COVID-19 e identificar conglomerados en municipios donde la enfermedad se mantuvo en el periodo posterior al descenso de la curva epidémica en Cuba. Métodos: El periodo mencionado comprendió entre el 26/05/2020 hasta el 4/09/2020. Se realizaron corridas cíclicas del modelo prospectivo espacio-temporal de Poisson, con incrementos progresivos de 14 días, mediante la aplicación SaTScan™ 9.6. Resultados: Se identificaron 15 conglomerados significativos (p ≤ 0,0001) cuya extensión involucró desde uno hasta trece municipios, con distribución en seis provincias (Pinar del Río, Artemisa, La Habana, Mayabeque, Matanzas, Villa Clara y Ciego de Ávila). En los conglomerados todos los municipios mostraron riesgo relativo alto, entre ellos, La Palma en la provincia de Pinar del Río y Ciego de Ávila en la provincia del mismo nombre, con los valores más altos, 119,95 y 121,04, respectivamente. Conclusión: El modelo empleado pudo identificar los conglomerados en territorios con significativa probabilidad de ocurrencia de COVID-19, así como periodos de evolución del riesgo relativo. Además, reconoce los municipios que merecen prioridad para intensificar en ellos intervenciones de contención y control sanitario y evitar la reemergencia de la enfermedad con mayor dispersión espacial.

ABSTRACT Introduction: During the occurrence of ongoing emerging infectious diseases such as COVID-19, spatiotemporal surveillance is crucial to identify priority areas for specific interventions, differentiate diagnostic intensity and assign resources. Objective: To model the evolution of the relative risk of presentation of COVID-19 cases and to identify clusters in municipalities where the disease remains at the stage following the descent of the epidemic curve in Cuba. Methods: The period mentioned was from 26/05/2020 to 4/09/2020. Cyclic runs of Poisson's prospective spatiotemporal model were performed, with progressive 14-day increases, using the software SaTScan™ 9.6. Results: A total 15 significant clusters were identified (p ≤ 0.0001) extending over one to thirteen municipalities and distributed in six provinces (Pinar del Río, Artemisa, Havana, Mayabeque, Matanzas, Villa Clara and Ciego de Ávila). In the clusters, all municipalities showed a high relative risk among them, La Palma in Pinar del Rio province and Ciego de Avila in the province of the same name, with the highest values, 119.95 and 121.04, respectively. Conclusion: The model was able to identify territories with a significant likelihood of COVID-19 occurrence, as well as periods in the evolution of relative risk. It also showed that surveillance and early warning strategies may facilitate prioritization of health control and containment interventions aimed at preventing the reemergence of the disease with greater spatial coverage.

Tocilizumab in giant cell arteritis: differences between the GiACTA trial and a multicentre series of patients from the clinical practice.

OBJECTIVES: A potential point of concern among clinicians is whether results derived from the clinical trials can be reasonably applied or generalised to a definable group of patients seen in real world. It can be the case of the GiACTA study that is a phase III randomised controlled trial of tocilizumab (TCZ) in giant cell arteritis (GCA). To address this question, we compared the clinical features and the responses to TCZ from the GiACTA trial patients with those from a series of GCA seen in the daily clinical practice. METHODS: Comparative study of clinical features between patients from the GiACTA trial (overall n=251) and those from a multicentre series of real-world GCA patients undergoing TCZ therapy (n=134). The diagnosis of GCA in the GiACTA trial was established by the ACR modified criteria whereas in the series of real-world patients it was made by using the ACR criteria, a positive biopsy of temporal artery or the presence of imaging techniques consistent with large-vessel vasculitis in individuals who presented cranial symptoms of GCA. GiACTA trial patients received subcutaneous TCZ (162 mg every 1 or 2 weeks) whereas those from the clinical practice series were treated using standard IV dose (8 mg/kg/month) or subcutaneous (162 mg/week). RESULTS: Real-life patients undergoing TCZ were older with longer disease duration and higher values of ESR and had received conventional immunosuppressive therapy (mainly methotrexate) more commonly than those included in the GiACTA trial. Despite clinical differences, TCZ was equally effective in both GiACTA trial and clinical practice patients. However, serious infections were more commonly observed in GCA patients recruited from the clinical practice. CONCLUSIONS: Despite clinical differences with patients recruited in clinical trials, data from real-life patients confirm the efficacy of TCZ in GCA.

Tocilizumab in giant cell arteritis. Observational, open-label multicenter study of 134 patients in clinical practice.

OBJECTIVE: Tocilizumab (TCZ) has shown efficacy in clinical trials on giant cell arteritis (GCA). Real-world data are scarce. Our objective was to assess efficacy and safety of TCZ in unselected patients with GCA in clinical practice Methods: Observational, open-label multicenter study from 40 national referral centers of GCA patients treated with TCZ due to inefficacy or adverse events of previous therapy. Outcomes variables were improvement of clinical features, acute phase reactants, glucocorticoid-sparing effect, prolonged remission and relapses. A comparative study was performed: (a) TCZ route (SC vs. IV); (b) GCA duration (≤6 vs. >6 months); (c) serious infections (with or without); (d) ≤15 vs. >15 mg/day at TCZ onset. RESULTS: 134 patients; mean age, 73.0 ± 8.8 years. TCZ was started after a median [IQR] time from GCA diagnosis of 13.5 [5.0-33.5] months. Ninety-eight (73.1%) patients had received immunosuppressive agents. After 1 month of TCZ 93.9% experienced clinical improvement. Reduction of CRP from 1.7 [0.4-3.2] to 0.11 [0.05-0.5] mg/dL (p < 0.0001), ESR from 33 [14.5-61] to 6 [2-12] mm/1st hour (p < 0.0001) and decrease in patients with anemia from 16.4% to 3.8% (p < 0.0001) were observed. Regardless of administration route or disease duration, clinical improvement leading to remission at 6, 12, 18, 24 months was observed in 55.5%, 70.4%, 69.2% and 90% of patients. Most relevant adverse side-effect was serious infections (10.6/100 patients-year), associated with higher doses of prednisone during the first three months of therapy. CONCLUSION: In clinical practice, TCZ yields a rapid and maintained improvement of refractory GCA. Serious infections appear to be higher than in clinical trials.

Transcriptomic analyses of cacao cell suspensions in light and dark provide target genes for controlled flavonoid production.

Catechins, including catechin (C) and epicatechin (E), are the main type of flavonoids in cacao seeds. They play important roles in plant defense and have been associated with human health benefits. Although flavonoid biosynthesis has been extensively studied using in vitro and in vivo models, the regulatory mechanisms controlling their accumulation under light/dark conditions remain poorly understood. To identify differences in flavonoid biosynthesis (particularly catechins) under different light treatments, we used cacao cell suspensions exposed to white-blue light and darkness during 14 days. RNA-Seq was applied to evaluate differential gene expression. Our results indicate that light can effectively regulate flavonoid profiles, inducing a faster accumulation of phenolic compounds and shifting E/C ratios, in particular as a response to switching from white to blue light. The results demonstrated that HY5, MYB12, ANR and LAR were differentially regulated under light/dark conditions and could be targeted by overexpression aiming to improve catechin synthesis in cell cultures. In conclusion, our RNA-Seq analysis of cacao cells cultured under different light conditions provides a platform to dissect key aspects into the genetic regulatory network of flavonoids. These light-responsive candidate genes can be used further to modulate the flavonoid production in in vitro systems with value-added characteristics.

Surface temperature of ewes during estrous cycle measured by infrared thermography.

The use of infrared thermography has not been used previously to assist sheep reproduction. The aim of this study was evaluate the viability of infrared thermography to identify body surface temperature patterns during ewes' estrous cycle. The estrous cycles of 20 Santa Ines ewes were synchronized through hormone treatment (progesterone implant). The ewes were submitted to measurements of body temperature (rectal and vaginal) with a digital thermometer and surface temperature of the anus, vulva, muzzle, left ear and left eye by infrared thermography. Temperature and humidity of the environment and wet-bulb globe temperature (WBGT) were measured. After the progesterone implant's removal, the follicular dynamic was evaluated daily during five days with ultrasound. The estrous cycle was separated into six phases to facilitate interpretation of the differences in body temperatures in each period. Phase 1 was the period before estrous synchronization, phase 2 was the beginning of estrous synchronization, phase 3 was the intermediate period and end of synchronization, phase 4 was the period of estrus manifestations, phase 5 was the ovulation period, and phase 6 was the post-ovulatory period. There was a difference among phases for all body regions evaluated (P < 0.05). All temperatures were higher in the ovulation phase. The rectal and vaginal temperatures measured by digital thermometer were lower during the diestrus period and increased during and after ovulation. The surface temperature of the vulva, measured by thermography, was higher from the estrus phase (4) to the ovulation and post-ovulation phases (5 and 6). The surface temperature of the muzzle was higher from the ovulation phase (5) to the post-ovulation phase (6), showing potential to detect ovulation. The thermography was efficient to detect small temperature variations during different phases of the estrous cycle, allowing the identification of different phases of the cycle in Santa Ines ewes.

Extraction and identification of endopeptidases in convection dried papaya and pineapple residues: A methodological approach for application to higher scale.

The use of agro-industrial waste for application in the obtention of products with high added value has become a trend in recent years, especially in tropical countries whose main economic sector is agricultural exports. In the present study, an applicable method to food industry of extracting proteolytic enzymes from dryed papaya and pineapple residues by convection was developed. Different to other scientific reports the heat treatment at 40 °C of waste residues, to reach 20% moisture, allowed an increase in total soluble protein content and did not alter the proteolytic activity of the extracts when phosphate buffer pH 7.0 was used as solvent. In the residues evaluated as candidates for the extraction of endopeptidases, we observed that green dried papaya peel and dried pineapple core, had higher activity values (914.34 ±â€¯25.47 U/mg and 2152.36 ±â€¯75.99 U/mg, respectively). These results, combined with one-dimensional electrophoresis and protein identification methods by MALDI TOF-TOF, showed the presence of signal peptides characteristic of papain, bromelain and other endopeptidases previously reported in extracts of fresh papaya and pineapple residues. These findings show that the drying of the residues by convection does not alter neither the activity nor the structure of the proteolytic enzymes. Finally, it is confirmed that the use of 20% ammonium sulfate as a precipitating agent allows to reach an efficiency of 74% in different work scales the use of purification and identification protocols in a more adaptable way, making them the most promising waste in Colombia, due to its potential for the production of bromelain on a larger scale.

A rational approach for the improvement of biomass production and lipid profile in cacao cell suspensions.

Cocoa butter (CB) is produced in the seeds of Theobroma cacao representing 50% of its dry weight. The lipid composition plays an important role in the physicochemical, rheological, and sensory properties of the CB, making this fat a valuable resource for the production of chocolates, cosmetics, and pharmaceuticals. In this paper, are described experimental strategies used for a rational improvement of biomass production and fatty acids in cacao cell suspension cultures. First, the lipid profile in four cacao varieties is characterized, and then, one variety is selected to induce cell suspensions using a direct method without previous establishment of a callus phase. To improve growth and total fat production in cell suspension cultures, modified DKW media and newly designed media culture, based on the mineral concentrations of cacao seeds (cacao biomass production, "CBP"), are analyzed and compared. In addition, the effect of acetate in the lipid profile of cell suspensions is evaluated. Ultrastructural histological analysis of lipid vesicles in cacao seeds and cell suspensions is also performed. The results will show that it is feasible to establish cacao suspensions without the calli step and increase the biomass production by selecting a suitable cacao variety and tissue and also applying a new culture media formulation. In addition, it is possible to synthesize fatty acids in cell cultures and modify the lipid profile adding a precursor of the novo biosynthesis of fatty acids such as the acetate. Transmission electronic microscopy examinations and differential interference contrast microscopy analysis will demonstrate that lipid vesicles are the main reserve substance in both cacao seeds and cell suspensions.

Comportamiento del grado de dependencia en pacientes geriátricos, Hospital Psiquiátrico de La Habana 2015 / Behavior of the degree of dependence in geriatric patients, Havana Psychiatric Hospital 2015

Introducción: El envejecimiento en Cuba constituye el principal problema demográfico y las Actividades de la Vida Diaria, constituyen el indicador más importante para medir el funcionamiento en el anciano. Objetivo: Determinar el grado de dependencia en la actividad básica de la vida diaria en pacientes geriátricos del Hospital Psiquiátrico de La Habana, octubre 2015. Métodos: Se realizó un estudio descriptivo de corte transversal en 81 pacientes geriátricos con trastornos mentales. Las variables usadas fueron: edad, sexo, grado de dependencia a través del índice de Barthel, causas asociadas a la discapacidad. Resultados: La cantidad de pacientes geriátricos con discapacidad del sexo femenino fueron 48 con un 59.2 por ciento y 33 masculino para el 40.7 por ciento. El grupo de 60-74 años es la que arrojó mayores resultado con 51 pacientes para un 63 por ciento. Las causas de las discapacidades más elevadas fueron las fracturas con un 43.2 por ciento y las afecciones ortopédicas con un 26.0 por ciento, en las féminas. En las AVD los pacientes se comportaron más independientes en: comer, vestirse y menos independientes y necesitando ayuda en: deambular, arreglarse, bañarse. Conclusiones: El índice de Barthel es un instrumento muy valioso para medir las AVD en pacientes geriátricos con trastornos mentales porque permite determinar el grado de dependencia del paciente(AU)

Introduction: Aging in Cuba is the main demographic problem and Activities of Daily Life, are the most important indicator to measure performance in the elderly. Objective: To determine the degree of dependence in basic activities of daily life in geriatric patients in the Havana Psychiatric Hospital, in October 2015. Methods: A descriptive cross-sectional study was conducted in 81 elderly patients with mental disorders. The variables used were: age, sex, degree of dependence through Barthel index causes associated with disability. Results: The number of elderly persons with disabilities were 48 females for a 59.2 percent and 33 malesfor a 40.7 percent. The group of 60-74 years was the one that had the greatest result with 51 patients for a 63 percent. The causes of the highest disabilities were fractures with 43.2 percent and orthopedic conditions with 26.0 percent in females. In ADL patients behaved more independent in eating, dressing and less independent and needing help: wandering, grooming and bathing(AU)

SQSTM1 splice site mutation in distal myopathy with rimmed vacuoles.

OBJECTIVE: To identify the genetic etiology and characterize the clinicopathologic features of a novel distal myopathy. METHODS: We performed whole-exome sequencing on a family with an autosomal dominant distal myopathy and targeted exome sequencing in 1 patient with sporadic distal myopathy, both with rimmed vacuolar pathology. We also evaluated the pathogenicity of identified mutations using immunohistochemistry, Western blot analysis, and expression studies. RESULTS: Sequencing identified a likely pathogenic c.1165+1 G>A splice donor variant in SQSTM1 in the affected members of 1 family and in an unrelated patient with sporadic distal myopathy. Affected patients had late-onset distal lower extremity weakness, myopathic features on EMG, and muscle pathology demonstrating rimmed vacuoles with both TAR DNA-binding protein 43 and SQSTM1 inclusions. The c.1165+1 G>A SQSTM1 variant results in the expression of 2 alternatively spliced SQSTM1 proteins: 1 lacking the C-terminal PEST2 domain and another lacking the C-terminal ubiquitin-associated (UBA) domain, both of which have distinct patterns of cellular and skeletal muscle localization. CONCLUSIONS: SQSTM1 is an autophagic adaptor that shuttles aggregated and ubiquitinated proteins to the autophagosome for degradation via its C-terminal UBA domain. Similar to mutations in VCP, dominantly inherited mutations in SQSTM1 are now associated with rimmed vacuolar myopathy, Paget disease of bone, amyotrophic lateral sclerosis, and frontotemporal dementia. Our data further suggest a pathogenic connection between the disparate phenotypes.

Efficient gene targeting in a Candida guilliermondii non-homologous end-joining pathway-deficient strain.

The yeast, Candida guilliermondii, has been widely studied due to its biotechnological interest as well as its biological control potential. It integrates foreign DNA predominantly via ectopic events, likely through the well-known non-homologous end-joining (NHEJ) pathway involving the Ku70p/Ku80p heterodimer, Lig4p, Nej1p and Lif1p. This phenomenon remains highly deleterious for targeted gene knock-out strategies that require the homologous recombination process. Here, we have constructed a ku70 mutant strain derived from the ATCC 6260 reference strain of C. guilliermondii. Following a series of disruption attempts of various genes (FCY1, ADE2 and TRP5), using several previously described dominant selectable markers (URA5, SAT-1 and HPH#), we demonstrated that the efficiencies of homologous gene targeting in such a NHEJ-deficient strain was very high compared to the wild type strain. The C. guilliermondii ku70 deficient mutant thus represents a powerful recipient strain to knock-out genes efficiently in this yeast.