High TGM1 Allelic Heterogeneity causing Lamellar ichthyosis in a small geographic area in South Mexico: Another Example of the "Réunion Paradox".

Lamellar ichthyosis (LI) is an autosomal recessive congenital ichthyosis characterized by generalized dry skin and severe scaling. It is caused by biallelic mutations in the TGM1 gene, however molecular data from non-Caucasian populations are limited. Results of genetic-molecular analysis of a group of LI pedigrees originating from two close small populations from south Mexico are presented. LI affected individuals belonging to 9 apparently unrelated families were studied. Exome sequencing or Sanger sequencing in probands from each family was carried out. Furthermore, DNA from 294 unaffected subjects from one of the communities were Sanger sequenced to determine the carrier frequency of the c.427C > T TGM1 variant. Five different TGM1 pathogenic variants, either in homozygous or in compound heterozygous state, were demonstrated in affected subjects. The two most common variants were c.427C > T (p.Arg143Cys) and c.1159+1G > T. A novel c.1645+1G > T TGM1 pathogenic allele was recognized. Carrier frequency analysis identified a total of 23 individuals heterozygous for the c.427C > T variant, predicting a prevalence of 78 carriers per 1000 inhabitants in the community. A high TGM1 allelic heterogeneity with 5 different LI-causing alleles in a limited geographic area was demonstrated. While the occurrence of homozygosity for a founder mutation is expected in small populations with high frequency of a particular autosomal recessive disorder, the occurrence of multiple pathogenic alleles has been previously described, a situation known as the Reúnion paradox. Our results expand the current knowledge of the mutational spectrum of TGM1-linked LI.

Highly asymmetrical distribution of muscle wasting correlates to the heteroplasmy in a patient carrying a large-scale mitochondrial DNA deletion: a novel pathophysiological mechanism for explaining asymmetry in mitochondrial myopathies.

Mitochondrial diseases are a heterogeneous group of pathologies, caused by missense mutations, sporadic large-scale deletions of mitochondrial DNA (mtDNA) or mutations of nuclear maintenance genes. We report the case of a patient in whom extended muscle pathology, biochemical and genetic mtDNA analyses have proven to be essential to elucidate a unique asymmetrical myopathic presentation. From the age of 34 years on, the patient has presented with oculomotor disorders, right facial peripheral palsy and predominantly left upper limb muscle weakness and atrophy. By contrast, he displayed no motor weakness on the right hemi-body, and no sensory symptoms, cerebellar syndrome, hypoacusis, or parkinsonism. Cardiac function was normal. CK levels were elevated (671 UI/L). Electroneuromyography (ENMG) and muscle MRI showed diffuse myogenic alterations, more pronounced on the left side muscles. Biopsy of the left deltoid muscle showed multiple mitochondrial defects, whereas in the right deltoid, mitochondrial defects were much less marked. Extended mitochondrial biochemical and molecular workup revealed a unique mtDNA deletion, with a 63.4% heteroplasmy load in the left deltoid, versus 8.1% in the right one. This case demonstrates that, in mitochondrial myopathies, heteroplasmy levels may drastically vary for the same type of muscle, rising the hypothesis of a new pathophysiological mechanism explaining asymmetry in hereditary myopathies.

Systemic infusion of exogenous ghrelin in male broiler chickens (Gallus gallus domesticus). The effect of pulse frequency, doses, and ghrelin forms on feed intake, average daily gain, corticosterone, and growth hormone concentrations.

There is limited information on the effect of exogenous ghrelin infusion on feed intake (FI) in chickens. Therefore, male broilers were used in 3 factorial experiments to determine the relationships between doses (0, 1, or 4 nM; Dose), frequency (once every two h; 2 h), once every 4th h (4 h) or continuous infusion, and ghrelin forms including acylated-ghrelin (AG) and desacylated-ghrelin (DAG) on FI, ADG, and concentrations of corticosterone and Growth Hormone (GH). Treatments were delivered via a jugular cannula, using programmable pumps for 11 consecutive days. FI and ADG were recorded, and plasma was collected. Data were analyzed using a factorial design. In Experiment 1 the effect of AG pulse frequency and doses were evaluated. There was a linear decrease in FI (P = 0.002) and a linear increase in corticosterone (P = 0.033) and GH (P = 0.011) concentrations when AG was infused. However, ADG decreased with doses (P = 0.011) only when AG was given at 2 h. In Experiment 2 the effect of ghrelin forms and doses given at 2 h was evaluated. There was a linear decrease in FI when AG was infused and a linear increase in FI when DAG was infused (P < 0.05). Birds infused with DAG gained more weight than those infused with AG. There was a linear increase in corticosterone and GH concentrations only when AG was infused (P < 0.01). In Experiment 3 the effect of continuous infusion of 2 doses (0 and 1 nM) of AG and DAG were evaluated. There was a linear decrease in FI and ADG when AG (P < 0.001) was infused and a linear increase in FI and ADG when DAG was infused (P < 0.05). There was an increase in corticosterone concentrations only when AG was infused (P = 0.022). However, GH concentrations were not affected by treatments. We concluded that AG and DAG pulse frequency and doses had a differential effect on FI, ADG, corticosterone, and GH concentrations in broiler chickens.

Future care for long-term cancer survivors: towards a new model

PurposeThe increase in the prevalence "long-term cancer survivor” (LCS) patients is expected to increase the cost of LCS care. The aim of this study was to obtain information that would allow to optimise the current model of health management in Spain to adapt it to one of efficient LCS patient care.MethodsThis qualitative study was carried out using Delphi methodology. An advisory committee defined the criteria for participation, select the panel of experts, prepare the questionnaire, interpret the results and draft the final report.Results232 people took part in the study (48 oncologists). Absolute consensus was reached in three of the proposed sections: oncological epidemiology, training of health professionals and ICT functions.ConclusionThe role of primary care in the clinical management of LCS patients needs to be upgraded, coordination with the oncologist and hospital care is essential. The funding model needs to be adapted to determine the funding conditions for new drugs and technologies.

Future care for long-term cancer survivors: towards a new model.

PURPOSE: The increase in the prevalence "long-term cancer survivor" (LCS) patients is expected to increase the cost of LCS care. The aim of this study was to obtain information that would allow to optimise the current model of health management in Spain to adapt it to one of efficient LCS patient care. METHODS: This qualitative study was carried out using Delphi methodology. An advisory committee defined the criteria for participation, select the panel of experts, prepare the questionnaire, interpret the results and draft the final report. RESULTS: 232 people took part in the study (48 oncologists). Absolute consensus was reached in three of the proposed sections: oncological epidemiology, training of health professionals and ICT functions. CONCLUSION: The role of primary care in the clinical management of LCS patients needs to be upgraded, coordination with the oncologist and hospital care is essential. The funding model needs to be adapted to determine the funding conditions for new drugs and technologies.

Factores motivacionales y de autoconcepto implicados en la predicción del rendimiento académico en Educación Secundaria / Motivational and self-concept factors implicated in academic performance at Secondary School

El objetivo del presente estudio fue evaluar el papel de la motivación y del autoconcepto en el rendimiento académico de estudiantes de Educación Secundaria Obligatoria (ESO). Los resultados mostraron que la autoeficacia académica per-cibida, las atribuciones del éxito a la capacidad, y el autoconcepto académico predijeron mayores niveles de rendimiento académico. Por otro lado, la motivación de evitación de fracaso, las atribuciones del éxito a la suerte y del fracaso a la dificultad de la tarea predijeron un peor rendimiento académico. Las atribuciones internas del éxito académico (capa-cidad y esfuerzo), y las atribuciones internas y estables del fracaso (capacidad), predijeron mayores y menores niveles de expediente académico, respectivamente, indirectamente a través de su influencia sobre el autoconcepto académico. Nuestros resultados muestran la importancia del papel del estilo atribucional en el desarrollo del autoconcepto y su influencia en el rendimiento académico en alumnos de Educación Secundaria (AU)

The aim of the present study was to evaluate the role of motivational factors and self-concept in predicting aca-demic performance at the end of academic year in secondary school students. Results showed that perceived academic self-efficacy, attributions of academic success to one’s ability, and academic self-concept were predictive of higher levels of academic sucsess. In contrast, motivation to avoid failure, attributions of academic success to good luck, and attributions of failure to task difficulties predicted lower levels of academic success. Results also showed that attributions of academic success to one’s ability and effort, and attributions of failure to one’s ability were indirectly predictive of higher and lower academic performance, respectively, via their influence in academic self-concept. Our results point out the importance of attributional styles in the development of self-concept and their influence in academic performance in secondary school students (AU)

Analysis of outcomes of emergency general and gastrointestinal surgery during the COVID-19 pandemic.

BACKGROUND: Few surgical studies have provided adjusted comparative postoperative outcome data among contemporary patients with and without COVID-19 infection and patients treated before the pandemic. The aim of this study was to determine the impact of performing emergency surgery in patients with concomitant COVID-19 infection. METHODS: Patients who underwent emergency general and gastrointestinal surgery from March to June 2020, and from March to June 2019 in 25 Spanish hospitals were included in a retrospective study (COVID-CIR). The main outcome was 30-day mortality. Secondary outcomes included postoperative complications and failure to rescue (mortality among patients who developed complications). Propensity score-matched comparisons were performed between patients who were positive and those who were negative for COVID-19; and between COVID-19-negative cohorts before and during the pandemic. RESULTS: Some 5307 patients were included in the study (183 COVID-19-positive and 2132 COVID-19-negative during pandemic; 2992 treated before pandemic). During the pandemic, patients with COVID-19 infection had greater 30-day mortality than those without (12.6 versus 4.6 per cent), but this difference was not statistically significant after propensity score matching (odds ratio (OR) 1.58, 95 per cent c.i. 0.88 to 2.74). Those positive for COVID-19 had more complications (41.5 versus 23.9 per cent; OR 1.61, 1.11 to 2.33) and a higher likelihood of failure to rescue (30.3 versus 19.3 per cent; OR 1.10, 0.57 to 2.12). Patients who were negative for COVID-19 during the pandemic had similar rates of 30-day mortality (4.6 versus 3.2 per cent; OR 1.35, 0.98 to 1.86) and complications (23.9 versus 25.2 per cent; OR 0.89, 0.77 to 1.02), but a greater likelihood of failure to rescue (19.3 versus 12.9 per cent; OR 1.56, 95 per cent 1.10 to 2.19) than prepandemic controls. CONCLUSION: Patients with COVID-19 infection undergoing emergency general and gastrointestinal surgery had worse postoperative outcomes than contemporary patients without COVID-19. COVID-19-negative patients operated on during the COVID-19 pandemic had a likelihood of greater failure-to-rescue than prepandemic controls.

Capromorelin, a ghrelin receptor agonist, increases feed intake and body weight gain in broiler chickens (Gallus gallus domesticus).

Ghrelin is a hormone that induces orexigenic effects in mammals. However, in avian species, there is scant and conflictive results on the effect of ghrelin on feed intake (FI). Therefore, we evaluated the effect of a ghrelin receptor agonist (capromorelin) on FI, ADG, water intake (WI), animal behavior and concentrations of ghrelin, glucose, growth hormone (GH) and insulin in broiler chickens. One-day-old male broilers were reared as recommended by the industry. At 4 wk of age (experimental day 0; D0), birds were blocked by weight and randomly assigned to 3 treatments in 2 identical trials. Control birds received a vehicle control solution containing 0 mg/kgBW/d of capromorelin. Birds in treatments 2 and 3 received capromorelin at target doses of 6 or 12 mg/kgBW/d of capromorelin (n = 27). FI and WI were measured 3 times a day at 0700 h (Period 1; P1), 1200 h (P2) and 1700 h (P3), while BW was recorded daily. Blood samples were collected on D-1 and D5. Bird behavior (pecking, sitting and standing) was evaluated for 9 h on D2. Data were analyzed using a randomized complete block design with repeated measures over time. Orthogonal polynomial contrasts were used to determine linear and quadratic effects of increasing levels of capromorelin. Polynomial contrasts showed that capromorelin doses linearly increased FI (P = 0.002) and ADG (P = 0.019). There were no treatment, day or treatment x d interactions on glucose, ghrelin and GH concentrations. However, there was a treatment x d interaction (P = 0.041) on insulin concentrations. Concentrations of insulin were higher on D5 for the 0 and 12 mg/kgBW/d treatments as compared with D-1. Polynomial contrasts showed that capromorelin doses linearly increased number of pecks/h (P = 0.018). Per hour FI and WI was higher during P1 (i.e., 0700-1200) as compared to P2 and P3 (P < 0.001). Our observations suggest that capromorelin linearly increases feed intake; thus, the same effect of that reported in mammalian species.

The electronic nose as a rule-out test for tuberculosis in an indigenous population.

INTRODUCTION: To end the tuberculosis (TB) epidemic, efficient diagnostic tools are needed. In a previous calibration study, a portable 'point of care' electronic nose device (AeonoseTM ) proved to be a promising tool in a hospital setting. We evaluated this technology to detect TB in an indigenous population in Paraguay. METHODS: A total of 131 participants were enrolled. eNose results were compared with anamnesis, physical examinations, chest radiography and mycobacterial cultures in individuals with signs and symptoms compatible with TB. The eNose analysis was performed in two stages: first, the training with a combination of a previous study population plus 47 participants from the new cohort (total n = 153), and second, the 'blind prediction' of 84 participants. RESULTS: 21% of all participants (n = 131) showed symptoms and/or chest radiography abnormalities suspicious of TB. No sputum samples resulted culture positive for Mycobacterium tuberculosis complex. Only one patient had a positive smell print analysis. In the training model, the specificity was 92% (95% confidence interval (CI): 85%-96%) and the negative predictive value (NPV) was 95%. In the blind prediction model, the specificity and the NPV were 99% (95% CI: 93%-99%) and 100%, respectively. Although the sensitivity and positive predictive value of the eNose could not be assessed in this cohort due to the small sample size, no active TB cases were found during a one year of follow-up period. CONCLUSION: The eNose showed promising specificity and negative predictive value and might therefore be developed as a rule-out test for TB in vulnerable populations.

Clinical correlations and long-term follow-up in 100 patients with sarcoglycanopathies.

BACKGROUND AND PURPOSE: To describe a large series of patients with α, ß, and γ sarcoglycanopathies (LGMD-R3, R4, and R5) and study phenotypic correlations and disease progression. METHODS: A multicentric retrospective study in four centers in the Paris area collecting neuromuscular, respiratory, cardiac, histologic, and genetic data. The primary outcome of progression was age of loss of ambulation (LoA); disease severity was established according to LoA before or after 18 years of age. Time-to-event analysis was performed. RESULTS: One hundred patients (54 γ-SG; 41 α-SG; 5 ß-SG) from 80 families were included. The γ-SG patients had earlier disease onset than α-SG patients (5.5 vs. 8 years; p = 0.022) and ß-SG patients (24.4 years). Axial muscle weakness and joint contractures were frequent and exercise intolerance was observed. At mean follow-up of 22.9 years, 65.3% of patients were wheelchair-bound (66.7% α-SG, 67.3% γ-SG, 40% ß-SG). Dilated cardiomyopathy occurred in all sarcoglycanopathy subtypes, especially in γ-SG patients (p = 0.01). Thirty patients were ventilated and six died. Absent sarcoglycan protein expression on muscle biopsy and younger age at onset were associated with earlier time to LoA (p = 0.021 and p = 0.002). Age at onset was an independent predictor of both severity and time to LoA (p = 0.0004 and p = 0.009). The α-SG patients showed genetic heterogeneity, whereas >90% of γ-SG patients carried the homozygous c.525delT frameshift variant. Five new mutations were identified. CONCLUSIONS: This large multicentric series delineates the clinical spectrum of patients with sarcoglycanopathies. Age at disease onset is an independent predictor of severity of disease and LoA, and should be taken into account in future clinical trials.

Bevacizumab dose adjustment to improve clinical outcomes of glioblastoma.

BACKGROUND: Glioblastoma (GBM) is one of the most aggressive and vascularized brain tumors in adults, with a median survival of 20.9 months. In newly diagnosed and recurrent GBM, bevacizumab demonstrated an increase in progression-free survival, but not in overall survival. METHODS: We conducted an in silico analysis of VEGF expression, in a cohort of 1082 glioma patients. Then, to determine whether appropriate bevacizumab dose adjustment could increase the anti-angiogenic response, we used in vitro and in vivo GBM models. Additionally, we analyzed VEGFA expression in tissue, serum, and plasma in a cohort of GBM patients before and during bevacizumab treatment. RESULTS: We identified that 20% of primary GBM did not express VEGFA suggesting that these patients would probably not respond to bevacizumab therapy as we proved in vitro and in vivo. We found that a specific dose of bevacizumab calculated based on VEGFA expression levels increases the response to treatment in cell culture and serum samples from mice bearing GBM tumors. Additionally, in a cohort of GBM patients, we observed a correlation of VEGFA levels in serum, but not in plasma, with bevacizumab treatment performance. CONCLUSIONS: Our data suggest that bevacizumab dose adjustment could improve clinical outcomes in Glioblastoma treatment.

Preoperative giant sacrococcygeal teratoma embolization in a newborn - A case report and a review. / Embolización preoperatoria de teratoma sacrococcigéo gigante en un recién nacido. Reporte de un caso y revisión.

Sacrococcygeal teratoma (SCT) is the most frequent congenital germ cell tumor. Patients have a higher risk of perinatal complications and death, with bleeding and cardiac decompensation being the most common causes of neonatal mortality. This is the case of a 35-week preterm newborn with a large SCT diagnosed at ultrasound screening in the second trimester. Preoperative selective embolization of the middle sacral artery and total surgical resection were performed postnatally with minimal blood loss. The patient was discharged at 25 days of life with a normal physical examination. Selective embolization prior to giant SCT resection is feasible and appears as a safe and useful technique in the control of perioperative bleeding.

El teratoma sacrococcígeo (TSC) es el tumor congénito de células germinales más frecuente. Los pacientes afectados tienen un mayor riesgo de complicaciones perinatales y muerte, siendo la hemorragia y la descompensación cardiaca las causas más comunes de mortalidad neonatal. Presentamos el caso de un recién nacido pretérmino de 35 semanas con un TSC de gran tamaño diagnosticado por ecografía en el segundo trimestre. La embolización selectiva preoperatoria de la arteria sacra media y la resección quirúrgica total postnatal se realizaron con una mínima pérdida de sangre. El paciente fue dado de alta a los 25 días de vida con un examen físico normal. La embolización selectiva antes de la cirugía de resección del TSC gigante es factible y aparece como una técnica segura y útil en el control del sangrado perioperatorio.

Embolización preoperatoria de teratoma sacrococcígeo gigante en un recién nacido. Reporte de un caso y revisión / Preoperative giant sacrococcygeal teratoma embolization in a newborn - A case report and a review

El teratoma sacrococcígeo (TSC) es el tumor congénito de células germinales más frecuente. Los pacientes afectados tienen un mayor riesgo de complicaciones perinatales y muerte, siendo la hemorragia y la descompensación cardiaca las causas más comunes de mortalidad neonatal. Presentamos el caso de un recién nacido pretérmino de 35 semanas con un TSC de gran tamaño diagnosticado por ecografía en el segundo trimestre. La embolización selectiva preoperatoria de la arteria sacra media y la resección quirúrgica total postnatal se realizaron con una mínima pérdida de sangre. El paciente fue dado de alta a los 25 días de vida con un examen físico normal. La embolización selectiva antes de la cirugía de resección del TSC gigante es factible y aparece como una técnica segura y útil en el control del sangrado perioperatorio

Sacrococcygeal teratoma (SCT) is the most frequent congenital germ cell tumor. Patients have a higher risk of perinatal complications and death, with bleeding and cardiac decompensation being the most common causes of neonatal mortality.This is the case of a 35-week preterm newborn with a large SCT diagnosed at ultrasound screening in the second trimester. Preoperative selective embolization of the middle sacral artery and total surgical resection were performed postnatally with minimal blood loss. The patient was discharged at 25 days of life with a normal physical examination. Selective embolization prior to giant SCT resection is feasible and appears as a safe and useful technique in the control of perioperative bleeding

Vivencias del ejercicio libre de la profesión en enfermeras que emplean terapias complementarias / Experiences of the free exercise of the profession in nurses who use complementary therapies

INTRODUCCIÓN: Actualmente enfermeras con posgrados y estudios en terapias complementarias, incursionan en el ejercicio libre de la profesión, al interior de consultorios propios, con la experiencia de varios años en funciones clínicas y utilización de terapias como: Acupuntura, Homeopatía, Masajes, entre otras, permiten resultados exitosos en usuarios que presentan procesos de enfermedades comunes, así como acciones sinérgicas cuando se combinan con terapias farmacológicas y quirúrgicas convencionales. METODOLOGÍA: Estudio de investigación cualitativo, descriptivo con enfoque fenomenológico, las informantes fueron 4 enfermeras residentes de la Ciudad de México y Estado de Hidalgo que utilizan terapias complementarias en ejercicio libre de la profesión, en consultorio privado, con un tiempo de trabajo mayor de tres años. Se estableció el consentimiento informado para obtener los permisos de grabar las entrevistas a profundidad. Con el método de análisis de datos de Sousa Minayo. RESULTADOS: Se describen 3 categorías con sus respectivas subcategorías las cuales representan: 1. Intencionalidad de sanar mediante terapias complementarias 2. Percepción del ejercicio libre de Enfermería 3. Inicios para la apertura del consultorio. CONCLUSIONES: Las licenciadas en Enfermería están asumiendo roles de liderazgo al llevar acabo el ejercicio libre de la profesión ya que se requiere capacitación y preparación para cumplir con la responsabilidad de tomar decisiones, esta autonomía implica un juicio crítico basado en conocimientos previos y la posibilidad de aplicar conocimientos generados a través de la investigación en la práctica para lograr un cambio en el cuidado a los usuarios, familias y comunidad por medio de la utilización de terapias complementarias.

INTRODUCTION: Currently nurses with postgraduate degrees and studies in complementary therapies, enter into the free exercise of the profession, inside their own offices, with the experience of several years in clinical functions and the use of therapies such as: Acupuncture, Homeopathy, Massages, Neural Therapy among others, they allow successful results in users who present common disease processes, as well as synergistic actions when combined with conventional pharmacological and surgical therapies. METHODOLOGY: Qualitative, descriptive research study with a phenomenological approach, the informants were 4 resident nurses from Mexico City and the State of Hidalgo who used complementary therapies in free practice of the profession, in their private office, with a working time of more than three years. Informed consent was established to obtain permission to record the interviews in depth. With the Sousa Minayo data analysis method. RESULTS: 3 categories are described with their respective subcategories which represent: 1. Intentionality to heal through complementary therapies 2. Perception of free exercise by Nursing 3. Beginnings for opening the office. CONCLUSIONS: Nursing graduates are assuming leadership roles by carrying out the free exercise of the profession since training and preparation are required to fulfill the responsibility of making decisions, this autonomy implies a critical judgment based on previous knowledge and the possibility of apply knowledge generated through research in practice to achieve a change in care for users, families and the community through the use of complementary therapies.

Dilated cardiomyopathy and limb-girdle muscular dystrophy-dystroglycanopathy due to novel pathogenic variants in the DPM3 gene.

Deficiency of Dolichol-P-mannose synthase subunit 3 (DPM3) affects the N-glycosylation and O-mannosylation pathways that are respectively involved in congenital disorders of glycosylation (CDG) and alpha-dystroglycanopathies. Herein, we describe novel pathogenic variants in the DPM3 gene in two unrelated male patients. They developed dilated cardiomyopathy in their late teens, limb-girdle muscular dystrophy - one patient in childhood and the other in adulthood. In both patients, next generation sequencing found in the DPM3 gene a heterozygous deletion and a heterozygous pathogenic missense mutation in exon 2 (c.41T>C, p.Leu14Pro). Electrophoresis of serum transferrin found an abnormal N-glycosylation profile suggestive of CDG type 1 (decreased tetrasialotransferrin, increased disialo- and asialotransferrin). Only two cases of DPM3 gene mutations with limb-girdle muscular dystrophy-dystroglycanopathy have been reported previously. The present study highlights several aspects related to DPM3 gene mutations such as mild to moderately severe limb-girdle muscular dystrophy, dilated cardiomyopathy, and abnormal N-glycosylation profile suggestive of CDG type 1.