Clinical and Patient Reported Outcomes of an Optimized Trifocal Intraocular Lens.

Background/Objectives: To evaluate the clinical and patient-reported outcomes (PROMs) obtained with an optimized version of a previously investigated trifocal IOL. Methods: Prospective non-comparative single-center study enrolling 29 patients (55-71 years) undergoing bilateral cataract surgery with implantation of the trifocal diffractive IOL Liberty 677CMY (Medicontur Medical Engineering Ltd., Zsámbék, Hungary). Visual and refractive outcomes as well as PROMs were evaluated during a 3-month follow-up: measurement of uncorrected and corrected distance (UDVA, CDVA), intermediate (UIVA, DCIVA) and near visual acuities (UNVA, DCNVA), defocus curve, patient satisfaction, photic phenomena perception, spectacle independence, and difficulty in performing some vision-related activities. Results: A total of 100%, 92%, and 80% of patients achieved a postoperative binocular UDVA, UIVA, and UNVA of 20/25 or better, respectively. Likewise, 100%, 80%, and 84% of patients achieved a postoperative binocular CDVA, DCIVA, and DCNVA of 20/25 or better, respectively. In the defocus curve, all mean visual acuity values were better than 0.15 logMAR for all defocus levels. A total of 95.8%, 95.8%, and 91.7% of patients referred to be satisfied with their distance, intermediate, and near visual vision, respectively. Mean overall Catquest Rasch calibrated score was -3.12 ± 0.98. Most of the patients were spectacle independent: far (95.8%), intermediate (95.8%) or near vision (91.7%). No bothersome or minimal to moderately bothersome halo, starburst, and glare was perceived by 83.3%, 83.4%, and 83.3% of patients, respectively. Conclusions: The trifocal IOL evaluated provides a visual acuity improvement, with high levels of spectacle independence, patient satisfaction, and perceived visual quality associated.

Atorvastatin Effect on Aortic Dilatation and Valvular Calcification Progression in Bicuspid Aortic Valve (BICATOR): A Randomized Clinical Trial.

BACKGROUND: Ascending aorta dilation and aortic valve degeneration are common complications in patients with bicuspid aortic valve. Several retrospective studies have suggested the benefit of statins in reducing these complications. This study aimed to determine whether atorvastatin treatment is effective in reducing the growth of aortic diameters in bicuspid aortic valve and if it slows the progression of valve calcification. METHODS: In a randomized clinical trial, 220 patients with bicuspid aortic valve (43 women; 46±13 years of age) were included and treated with either 20 mg of atorvastatin per day or placebo for 3 years. Inclusion criteria were ≥18 years of age, nonsevere valvular dysfunction, nonsevere valve calcification, and ascending aorta diameter ≤50 mm. Computed tomography and echocardiography studies were performed at baseline and after 3 years of treatment. RESULTS: During follow-up, 28 patients (12.7%) discontinued medical treatment (15 on atorvastatin and 13 taking placebo). Thus, 192 patients completed the 36 months of treatment. Low-density lipoprotein cholesterol levels decreased significantly in the atorvastatin group (median [interquartile range], -30 mg/dL [-51.65 to -1.75 mg/dL] versus 6 mg/dL [-4, 22.5 mg/dL]; P<0.001). The maximum ascending aorta diameter increased with no differences between groups: 0.65 mm (95% CI, 0.45-0.85) in the atorvastatin group and 0.74 mm (95% CI, 0.45-1.04) in the placebo group (P=0.613). Similarly, no significant differences were found for the progression of the aortic valve calcium score (P=0.167) or valvular dysfunction. CONCLUSIONS: Among patients with bicuspid aortic valve without severe valvular dysfunction, atorvastatin treatment was not effective in reducing the progression of ascending aorta dilation and aortic valve calcification during 3 years of treatment despite a significant reduction in low-density lipoprotein cholesterol levels. REGISTRATION: URL: https://www.clinicaltrialsregister.eu; Unique identifier: 2015-001808-57. URL: https://www.clinicaltrials.gov; Unique identifier: NCT02679261.

Fallo en la regulación de la fertilidad posparto en mujeres en vulnerabilidad social en Colombia / Failured to regulate postpartum fertility in vulnerable women in Colombia

Objetivo: Evaluar la prevalencia de fallo en la regulación de la fertilidad posparto y la asociación con otros factores en un municipio colombiano (2017). Método: Estudio observacional de corte transversal con 148 mujeres. Se aplicó un muestreo no aleatorio para incluir mujeres que hubieran tenido un parto en los últimos 5 años. Se calcularon la prevalencia y las razones de prevalencia. Se exploró la asociación con la prueba χ2 o la prueba exacta de Fisher bajo una significancia estadística de 0,05. Resultados: Se encontró una prevalencia de fallo de la regulación de la fertilidad posparto del 40,5%. La prevalencia se asoció con ejercer oficios del hogar, tener uno o dos hijos, no planificar o no acceder a métodos de planificación y haber tenido un embarazo con periodo intergenésico menor de 2 años (p < 0,05). Conclusiones: Es necesario implementar estrategias para identificar barreras de acceso a la planificación, impactando en el espaciamiento entre embarazos y el acceso a los servicios. Lo anterior para generar múltiples beneficios para la madre, su hijo/a, el sistema de salud y la sociedad.

Objective: To evaluate the prevalence of regulated postpartum fertility failure and possible associated factors in a Colombian municipality (2017). Method: Cross-sectional observational study of 148 women. A non-random sampling method was used to include women who had given birth to a child in the last five years. Prevalence and prevalence ratios were calculated. Associations were examined at 0.05 statistical significance using χ2 test or Fishers exact test. Results: The prevalence of postpartum fertility failure was found to be 40.5%. The prevalence was associated with household work, having one or two children, not planning, or not having access to planning methods, and having a pregnancy with an interval between pregnancies of less than 2 years (p < 0.05). Conclusions: It is necessary to implement strategies to identify barriers to access to planning, which have an impact on the spacing between pregnancies and access to services. This will have multiple benefits for mother, child, health system and society.

Multiple minute digitate hyperkeratosis: 10 years from Caccetta's algorithm. A case report and narrative review.

To date, the clinical appearance and histological features of multiple minute digitate hyperkeratosis have been well characterized. However, there is no consensus on its treatment. After a comprehensive search of the databases MEDLINE, EMBASE, Web of Science, and the Cochrane Library and Database of Systematic Reviews, we have summarized the available clinical evidence regarding the therapeutic approaches already reported for this entity since its first description in 1967. Additional publications were identified within the references of retrieved papers. Sixty-five articles have been revised, resulting in a total of 73 compatible cases. The histopathological features and different classifications used through history have also been considered, updating and completing the available knowledge. Ultimately, we propose topical treatment with 5 % 5-fluorouracil formulated with 10 % salicylic acid as a potential treatment that has been used successfully in a 51-year-old woman at our facility. Further research in form of prospective or comparative studies is encouraged for a better conceptualization of the therapeutics of this disease.

Upregulation of Heat-Shock Protein (hsp)-27 in a Patient with Heterozygous SPG11 c.1951C>T and SYNJ1 c.2614G>T Mutations Causing Clinical Spastic Paraplegia.

We report a 49-year-old patient suffering from spastic paraplegia with a novel heterozygous mutation and analyzed the levels of heat shock proteins (hsp)-27, dopamine (DA), and its metabolites in their cerebrospinal fluid (CSF). The hsp27 protein concentration in the patient's CSF was assayed by an ELISA kit, while DA levels and its metabolites in the CSF, 3,4-dihydroxyphenylacetic acid (DOPAC), Cys-DA, and Cys-DOPA were measured by HPLC. Whole exome sequencing demonstrated SPG-11 c.1951C>T and novel SYNJ1 c.2614G>T mutations, both heterozygous recessive. The patient's DA and DOPAC levels in their CSF were significantly decreased (53.0 ± 6.92 and 473.3 ± 72.19, p < 0.05, respectively) while no differences were found in their Cys-DA. Nonetheless, Cys-DA/DOPAC ratio (0.213 ± 0.024, p < 0.05) and hsp27 levels (1073.0 ± 136.4, p < 0.05) were significantly higher. To the best of our knowledge, the c.2614G>T SYNJ1 mutation has not been previously reported. Our patient does not produce fully functional spatacsin and synaptojanin-1 proteins. In this line, our results showed decreased DA and DOPAC levels in the patient's CSF, indicating loss of DAergic neurons. Many factors have been described as being responsible for the increased cys-DA/DOPAC ratio, such as MAO inhibition and decreased antioxidant activity in DAergic neurons which would increase catecholquinones and consequently cysteinyl-catechols. In conclusion, haploinsufficiency of spatacsin and synaptojanin-1 proteins might be the underlying cause of neurodegeneration produced by protein trafficking defects, DA vesicle trafficking/recycling processes, autophagy dysfunction, and cell death leading to hsp27 upregulation as a cellular mechanism of protection and/or to balance impaired protein trafficking.

Amiloidosis traqueobronquial en contexto de enfermedad sistémica / Tracheobronchial Amyloidosis in the Context of Systemic Disease

Siglos después de la detección de material amiloide como depósitos extracelulares, encontramos en la bibliografía diversas clasificaciones. En cuanto a la afección torácica, se reconocen cuatro tipos; el traqueobronquial es el menos frecuente. Presentamos el caso de un paciente masculino de 32 años sin antecedentes, que consulta por disfonía de 3 años, al que se le constata una lesión nodular en la pared posterior de la tráquea. Se realiza una biopsia por fibrobroncoscopia, cuyo resultado indica la presencia de amiloidosis traqueobronquial. Se realiza quimioterapia y se valora la realización de una resección quirúrgica según respuesta al tratamiento. La amiloidosis pulmonar asociada con amiloidosis sistémica generalmente se presenta como un patrón intersticial difuso. Las formas traqueobronquial y parenquimatosa nodular no son frecuentes y se manifiestan con síntomas obstructivos. El diagnóstico definitivo se logra mediante biopsia. Disponemos de diversas opciones terapéuticas, como la quimioterapia, el trasplante autólogo de médula ósea y, para pacientes con síntomas obstructivos, se recomienda la resección endoscópica y colocación de stent(AU)

Centuries after the detection of amyloid material as extracellular deposits, we find various classifications in the literature. Regarding thoracic involvement, four types are recognized, with the tracheobronchial type being the least common. We present the case of a 32-year-old male patient with no previous medical record, who sought medical attention due to a 3-year history of dysphonia. A nodular lesion was found in the posterior wall of the trachea. A biopsy was performed through fiberoptic bronchoscopy, and the result indicated the presence of tracheobronchial amyloidosis. Chemotherapy was administered, and the possibility of surgical resection was evaluated basing on treatment response. Pulmonary amyloidosis associated with systemic amyloidosis typically presents as a diffuse interstitial pattern. Tracheobronchial and nodular parenchymal forms are uncommon and manifest with obstructive symptoms. A definitive diagnosis was achieved through biopsy. There are various therapeutic options available, such as chemotherapy, autologous bone marrow transplantation, and for patients with obstructive symptoms, endoscopic resection and stent placement are recommended(AU)

Determining the need for a thoracoscopic approach to treat a giant hiatal hernia when abdominal access is poor.

BACKGROUND: Giant hernias present a significant challenge for digestive surgeons. The approach taken (laparoscopic vs thoracoscopic) depends largely on the preferences and skills of each surgeon, although in most cases today the laparoscopic approach is preferred. AIM: To determine whether patients presenting inadequate laparoscopic access to the intrathoracic hernial sac obtain poorer postoperative results than those with no such problem, in order to assess the need for a thoracoscopic approach. METHODS: For the retrospective series of patients treated in our hospital for hiatal hernia (n = 112), we calculated the laparoscopic field of view and the working area accessible to surgical instruments, by means of preoperative imaging tests, to assess the likely outcome for cases inaccessible to laparoscopy. RESULTS: Patients with giant hiatal hernias for whom a preoperative calculation suggested that the laparoscopic route would not access all areas of the intrathoracic sac presented higher rates of perioperative complications and recurrence during follow-up than those for whom laparoscopy was unimpeded. The difference was statistically significant. Moreover, the insertion of mesh did not improve results for the non-accessible group. CONCLUSION: For patients with giant hiatal hernias, it is essential to conduct a preoperative evaluation of the angle of vision and the working area for surgery. When parts of the intrathoracic sac are inaccessible laparoscopically, the thoracoscopic approach should be considered.

Case report: Endovascular embolization of a cerebral pseudoaneurysm caused by SARS-CoV2 infection.

Background: Severe COVID-19 has been shown to produce convulsions, encephalitis, Guillain-Barré syndrome, or cerebrovascular disease. However, only 4 case reports described subarachnoid or brain hemorrhage caused by ruptured cerebral aneurysms or pseudoaneurysms in patients with COVID-19. Cerebral pseudoaneurysms represent <1% of all intracranial aneurysms and have been related to radiation therapy, vasculitis, rupture of true saccular aneurysms, arteriovenous malformations, and infections by bacteria and viruses, such as Epstein-Bar and Herpes virus. Case presentation: A 28-year-old Caucasian woman, with no medical history of interest and completely vaccinated against SARS-CoV-2, was admitted to Neurology due to progressive tetraparesis with areflexia, a cough, and a fever of 38°C. SARS-CoV2 PCR was positive while lumbar puncture, blood tests, and electromyogram showed criteria for Guillain-Barré syndrome. Despite the treatment, the patient developed dyspnea and tetraplegia requiring invasive mechanical ventilation. There was motor neurological improvement but a decreased level of consciousness was observed on day 13. A brain CT scan demonstrated an acute haematoma and cerebral arteriography showed a 4-mm pseudoaneurysm located in a branch of the left middle cerebral artery. Given the high risk of rebleeding, endovascular treatment was decided upon. Therefore, complete embolization of the pseudoaneurysm was carried out by using the synthetic glue N-butyl-cyanocrylate. Two days later, the patient was clinically and neurologically recovered and was discharged. Lastly, a new angiography showed no evidence of the pseudoaneurysm 3-weeks later. Conclusions: We report, for the first time, a patient suffering a severe immune reaction caused by SARS-CoV2 infection and developing a cerebral pseudoaneurysm treated with endovascular embolization without complications.

Estudio fitoquimico, actividad antioxidante y toxicidad sobre Artemia salina de los extractos de las hojas de Justicia secunda Vahl. (Acanthaceae), recolectada en Merida-Venezuela

Objetivos: realizar el estudio fitoquímico cualitativo para determinar la actividad antioxidante y toxicidad sobre Artemia salina de los extractos de las hojas de Justicia secunda Vahl, recolectada en Mérida, Venezuela. Metodología: el tamizaje fitoquímico de los extractos de las hojas de Justicia secunda Vahl. (Acanthaceae) se realizó a través de pruebas químicas específicas y permitió determinar la presencia de este-roles en el extracto hexanoico; esteroles y compuestos fenólicos en el diclorometanoico; alcaloides, esteroles y compuestos fenólicos en el extracto etanólico. La actividad antioxidante de los extractos de J. secunda fue evaluada usando el método de la capacidad secuestrante de radicales libres de 2,2-difenil-1-picrilhidrazilo (DPPH») mediante espectrofotometría UV-visible a una longitud de onda de 517 nm, con ácido ascórbico como control positivo (176 µg/rnL). Resultados: los extractos diclorometanoico y etanólico mostraron actividad antioxidante, con un porcentaje de inhibición superior a 50 a 4 mg/mL y a una concentración de 0,75 mg/mL un porcentaje de inhibición de 27,7 y 53,0; IC50 de 1,85 mg/mL y 0,69 mg/mL, respectivamente. En cuanto a la toxicidad sobre A. salina, del extracto etanólico mostró una DL50 entre 919,32 y 3781,9 ppm y es relativamente inocuo, según la clasificación CYTED. Conclusión: en general, los resultados obtenidos sugieren que los extractos de las hojas de J. secunda Vahl, podrían ser una alternativa en la formulación de fármacos, debido a su potencial como antioxidante y su baja toxicidad.

SUMMARY Aims: To carry out the qualitative phytochemical study to determine the antioxidant activity and toxicity on Artemia salina of the extracts of the leaves of Justicia secunda Vahl, collected in Mérida, Venezuela. Methodology: Phytochemical screening of extracts from the aerial parts of Justicia secunda Vahl. (Acanthaceae) was carried out through specific chemical tests that allowed the presence of sterols in the hexanoic extract to be determined; sterols and phenolic compounds in the dichloromethane and alkaloids, sterols and phenolic compounds in the ethanolic extract. The antioxidant activity of extracts from the aerial parts of J. secunda was evaluated by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH•) radical scavenging method, using spectrophotometry UV-Visible at a wavelength of 517 nm, with ascorbic acid as control (176 µg/mL). Results: The dichloromethane and ethanolic extracts showed anti-oxidant activity, with an inhibition percentage higher than 50 to 4 mg/mL and at a concentration of 0.75 mg / mL, percentage of 27.7 and 53.0; IC50 of 1.85 mg/mL and 0.69 mg/mL, respectively. Regarding toxicity on A. salina, the ethanolic extract showed an LD50 between 919.32 and 3781.9 ppm, it was relatively harmless, according to the CYTED classification. Conclusion: Overall, the results obtained suggest that the extracts of the aerial parts of J. secunda Vahl, could be an alternative for future drug formulation since it has potent antioxidant activity and low toxicity.

Objetivo: realizar o estudo fitoquímico qualitativo para determinar a atividade antioxidante e toxicidade sobre Artemia salina dos extratos das folhas de Justicia secunda Vahl, coletadas em Mérida, Venezuela. Metodologia: triagem fitoquímica de extratos das partes aéreas de Justicia secunda Vahl. (Acanthaceae) foi realizado por meio de testes químicos específicos e permitiu determinar a presença de esteróis no extrato hexanoico; esteróis e compostos fenólicos no diclorometano e alcalóides, esteróis e compostos fenólicos no extrato etanólico. A atividade antioxidante de extratos das partes aéreas de J. secunda foi avaliada pelo método de sequestro do radical 1,1-difenil-2-picrilhidrazil (DPPH»), por espectrofotometria UV-Visível no comprimento de onda de 517 nm, com ácido ascórbico como controle (176 µg/mL). Resultados: os extratos diclorometano e etanólico apresentaram atividade antioxidante, com percentual de inibição superior a 50 a 4 mg/mL e na concentração de 0,75 mg/ mL, percentagem de 27,7 e 53,0; IC50 de 1,85 mg/mL e 0,69 mg/mL, respectivamente. Em relação à toxicidade sobre A. salina, o extrato etanólico apresentou DL50 entre 919,32 e 3781,9 ppm, sendo relativamente inofensivo, segundo a classificação CYTED. Conclusão: de maneira geral, os resultados obtidos sugerem que os extratos das partes aéreas de J. secunda Vahl, podem ser uma alternativa para futura formulação de fármacos por apresentarem potente atividade antioxidante e baixa toxicidade.

Case Report: Identification of a Heterozygous XPA c.553C>T Mutation Causing Neurological Impairment in a Case of Xeroderma Pigmentosum Complementation Group A.

We aimed to determine if an adolescent patient presenting with neurological impairment has xeroderma pigmentosum (XP). For this purpose, whole-exome sequencing was performed to assess mutations in XP genes. Dermal fibroblasts were established from a skin biopsy and XPA expression determined by immunoblotting. Nucleotide excision repair (NER) capacity was measured by detection of unscheduled DNA synthesis (UDS) in UVC-irradiated patient fibroblasts. Genetic analysis revealed two recessive mutations in XPA, one known c.682C>T, p.Arg228Ter, and the other c.553C>T, p.Gln185Ter, only two cases were reported. XPA protein was virtually undetectable in lysates from patient-derived fibroblast. The patient had significantly lower UV-induced UDS (3.03 ± 1.95%, p < 0.0001) compared with healthy controls (C5RO = 100 ± 12.2; C1UMN = 118 ± 5.87), indicating significant NER impairment. In conclusion, measurement of NER capacity is beneficial for the diagnosis of XP and in understanding the functional impact of novel mutations in XP genes. Our findings highlight the importance of neurologists considering XP in their differential diagnosis when evaluating patients with atypical neurodegeneration.

Dysregulation of Components of the Inflammasome Machinery After Bariatric Surgery: Novel Targets for a Chronic Disease.

BACKGROUND: Obesity is a metabolic chronic disease with important associated morbidities and mortality. Bariatric surgery is the most effective treatment for maintaining long-term weight loss in severe obesity and, consequently, for decreasing obesity-related complications, including chronic inflammation. AIM: To explore changes in components of the inflammasome machinery after bariatric surgery and their relation with clinical/biochemical parameters at baseline and 6 months after bariatric surgery. PATIENTS AND METHODS: Twenty-two patients with morbid-obesity that underwent bariatric surgery (sleeve gastrectomy and Roux-en-Y gastric bypass) were included. Epidemiological/clinical/anthropometric/biochemical evaluation was performed at baseline and 6 months after bariatric surgery. Inflammasome components and inflammatory-associated factors [nucleotide-binding oligomerization domain-like receptors (NLRs), inflammasome activation components, cytokines and inflammation/apoptosis-related components, and cell-cycle and DNA-damage regulators) were evaluated in peripheral blood mononuclear cells (PBMCs) at baseline and 6 months after bariatric surgery. Clinical molecular correlations/associations were analyzed. Functional parameters (lipid accumulation/viability/apoptosis) were analyzed in response to specific inflammasome components silencing in liver HepG2 cells). RESULTS: A profound dysregulation of inflammasome components after bariatric surgery was found, especially in NLRs and cell-cycle and DNA damage regulators. Several components were associated with baseline metabolic comorbidities including type 2 diabetes (C-C motif chemokine ligand 2/C-X-C motif chemokine receptor 1/sirtuin 1), hypertension (absent in melanoma 2/ASC/purinergic receptor P2X 7), and dyslipidemia [C-X-C motif chemokine ligand 3 (CXCL3)/NLR family pyrin domain containing (NLRP) 7) and displayed changes in their molecular profile 6 months after bariatric surgery. The gene expression fingerprint of certain factors NLR family CARD domain containing 4 (NLRC4)/NLRP12/CXCL3)/C-C motif chemokine ligand 8/toll-like receptor 4) accurately differentiated pre- and postoperative PBMCs. Most changes were independent of the performed surgical technique. Silencing of NLRC4/NLRP12 resulted in altered lipid accumulation, apoptosis rate, and cell viability in HepG2 cells. CONCLUSION: Bariatric surgery induces a profound alteration in the gene expression pattern of components of the inflammasome machinery in PBMCs. Expression and changes of certain inflammasome components are associated to baseline metabolic comorbidities, including type 2 diabetes, and may be related to the improvement and reversion of some obesity-related comorbidities after bariatric surgery.

Factores asociados a la decisión paterna sobre el retorno a clases presenciales en Colombia durante la pandemia COVID-19 / Associated factors with the paternal decision on the return to face-to-face classes in Colombia during the COVID-19 pandemic

Resumen Introducción: La pandemia por SARS-CoV-2 generó el cierre de los colegios y el inicio de la educación virtual, como medida para disminuir la propagación del virus. Rápidamente, se planteó el regreso a los colegios; sin embargo, es probable que exista un rechazo de los padres por el regreso a clases de forma presencial o mediante alternancia. Por esta razón, se evaluaron los factores asociados a esta oposición. Material y métodos: Se realizó un estudio analítico de corte transversal mediante una encuesta, dirigida a padres que acuden a consultorios con sus hijos en varias ciudades de Colombia. Se determinó el porcentaje de padres que deseaban mantener la escolarización mediante la virtualidad y los factores asociados que motivan a no aceptar el pronto retorno a clases presenciales. Se realizó un análisis de regresión binomial para estimar razones de prevalencia (RP), ajustado a la edad de los padres, tomando como variable dependiente la aceptación de la virtualidad como estrategia para no regresar a los colegios, y se determinaron los factores de mayor importancia en la no aceptación del retorno a clases. Resultados: El 81,06 % de los padres no acepta el retorno a clase de forma presencial. El principal factor asociados a esta decisión fue que alguno de los padres presentara alguna comorbilidad, principalmente, hipertensión y obesidad. Tener hijos mayores de 10 años (RP: 2,64: IC 95 %: 1,48-4,72), convivir con personas mayores de 70 años (RP: 2,2; IC 95 %; 1,46-3,29) y conocer alguna persona fallecida por COVID-19 (RP: 1,86; IC 95 %: 1,42-2,44) también fueron asociadas a no aceptar el retorno a clase presencial. Conclusiones: Existe una clara tendencia a mantener la virtualidad como opción educativa en Colombia para el no regreso a clases presenciales en población de estrato medio y alto. Los factores asociados sugieren una forma de protección familiar. Esta evidencia debe considerarse específica para el periodo de recolección de datos y el grupo incluido en el estudio. Se requieren estudios en los estratos socioeconómicos más bajos, donde se supone ocurren más efectos adversos asociados al no retorno a clases presenciales.

Abstract Introduction: The SARS-CoV-2 pandemic led to the closure of schools and the beginning of virtual education, as a measure to reduce the spread of the virus. Shortly after, there was a planned return to in-person learning, however, there existed the possibility of parents rejecting the notion of returning to in-person learning or a hybrid model of in-person and online learning, there is likely a rejection of parents to return to classes in person. For this reason, the factors possibly associated with this opposition were evaluated. Material and methods: A cross-sectional analytical study was carried out through an online survey aimed at parents who attend private clinics with their children, in several cities of Colombia. The percentage of parents who wished to maintain their children's schooling through virtuality and the factors associated with not accepting the prompt return to face-to-face classes were determined. A binomial regression analysis, to estimate Prevalence Ratios (PR), adjusted for the age of the parents was carried out, taking as a dependent variable the acceptance of virtuality as a strategy for not returning to school and the most important factors in the non-acceptance of returning to school were determined. Results: 81.06% of the parents did not accept the return to class in person. The main factors associated with this decision were that one of the parents had some comorbidity, mainly hypertension and obesity. Having children older than 10 years (PR: 2.64; 95% CI: 1.48-4.72), living with people older than 70 years (PR: 2.2; 95% CI;1.46-3.29), and knowing someone who died from COVID-19 (PR: 1.86; 95% CI 1.42- 2.44) were associated with not accepting the return to face classes. Conclusions: There is a clear tendency to maintain virtuality as an educational option in Colombia for not returning to face-to-face classes in the middle and upper stratum population. Associated factors suggest a form of family protection. This evidence should be considered specific for the data collection period and the group included in the study. Studies are required in the lowest socioeconomic strata, where it is assumed that there are more adverse effects associated with not returning to face-to-face classes.

Switching from clozapine to paliperidone palmitate-3-monthly improved obesity, hyperglycemia and dyslipidemia lowering antipsychotic dose equivalents in a treatment-resistant schizophrenia cohort.

Clozapine, an antipsychotic developed in 1958, is considered the gold standard and the treatment of choice in treatment-resistant schizophrenia despite its side effects and despite 40-70% of these patients not responding to clozapine. In the last decade, new antipsychotics, such as paliperidone palmitate (PP), have emerged as well as its long acting-injectable (LAI) formulations, available as PP-1-monthly (PP1M) and the newest PP-3-montlhy (PP3M). Despite paliperidone having shown a similar efficacy as others antipsychotics for the treatment of schizophrenia, and that PP3M has been shown to reduce relapses compared to oral formulations, no study has been carried out in treatment-resistant schizophrenia. The aim of our study was to carry out an exploratory evaluation of endocrine and hepatic profiles as well as the concomitant treatments associated to PP3M vs. clozapine, the gold standard, in patients with treatment-resistant schizophrenia. We designed a retrospective study. A total number of 33 patients previously diagnosed as schizophrenics treatment-resistant, who were prescribed clozapine followed by PP1M and PP3M when available, were selected. Demographic data, BMI, hepatic enzymes (glutamic oxaloacetic transaminase, glutamate-pyruvate transaminase and gamma-glutamyl transferase (GGT)], thyroid function (thyroid stimulating hormone), blood platelets and both white and red blood cells as well as the use of concomitant antipsychotics, benzodiazepines and biperiden were compared under treatment with clozapine and PP3M. Antipsychotics and benzodiazepines dosages were compared using by the defined daily dose (DDD) method and haloperidol or diazepam dose equivalents. All statistical analyses were performed using the paired Student t-test for repeated measures. Our data showed that patients under treatment with PP3M showed a significant decrease in BMI (P < 0.01), glucose (P < 0.01), cholesterol (P < 0.05) and triglycerides (P < 0.01) when compared with basal values under treatment with clozapine. Hepatic cholestasis enzyme, GGT, were significantly elevated (P < 0.05) under treatment with clozapine when compared to PP3M. Switching clozapine to PP3M led to a significant lower pharmacological exposure to antipsychotics, by both the DDD (P < 0.05) and haloperidol dose equivalents (P < 0.001) methods without increasing the dose of benzodiazepines while biperiden was more used under PP3M. Finally, antipsychotic monotherapy was higher and less polypharmacy was used with PP3M. In conclusion, our findings suggest that switching clozapine to PP3M improved endocrine and hepatic profile with a lower total exposure to antipsychotics. More studies are needed to truly establish the role of PP3M in treatment-resistant schizophrenia and should be compared against clozapine by using clinical trials.

Methamphetamine withdrawal induces activation of CRF neurons in the brain stress system in parallel with an increased activity of cardiac sympathetic pathways.

Methamphetamine (METH) addiction is a major public health problem in some countries. There is evidence to suggest that METH use is associated with increased risk of developing cardiovascular problems. Here, we investigated the effects of chronic METH administration and withdrawal on the activation of the brain stress system and cardiac sympathetic pathways. Mice were treated with METH (2 mg/kg, i.p.) for 10 days and left to spontaneous withdraw for 7 days. The number of corticotrophin-releasing factor (CRF), c-Fos, and CRF/c-Fos neurons was measured by immunohistochemistry in the paraventricular nucleus of the hypothalamus (PVN) and the oval region of the bed nucleus of stria terminalis (ovBNST), two regions associated with cardiac sympathetic control. In parallel, levels of catechol-o-methyl-transferase (COMT), tyrosine hydroxylase (TH), and heat shock protein 27 (Hsp27) were measured in the heart. In the brain, chronic-METH treatment enhanced the number of c-Fos neurons and the CRF neurons with c-Fos signal (CRF+/c-Fos+) in PVN and ovBNST. METH withdrawal increased the number of CRF+ neurons. In the heart, METH administration induced an increase in soluble (S)-COMT and membrane-bound (MB)-COMT without changes in phospho (p)-TH, Hsp27, or pHsp27. Similarly, METH withdrawal increased the expression of S- and MB-COMT. In contrast to chronic treatment, METH withdrawal enhanced levels of (p)TH and (p)Hsp27 in the heart. Overall, our results demonstrate that chronic METH administration and withdrawal activate the brain CRF systems associated with the heart sympathetic control and point towards a METH withdrawal induced activation of sympathetic pathways in the heart. Our findings provide further insight in the mechanism underlining the cardiovascular risk associated with METH use and proposes targets for its treatment.

Iron-Catalyzed Hydroborylative Cyclization of 1,6-Enynes.

We report first Fe-catalyzed hydroborylative cyclization reaction. The process provides one C-C and one C-B bond in a single operation and shows a wide scope, allowing the formation of carbo- and heterocycles containing a homoallylic boryl unit that can be further functionalized. The reaction takes place in smooth conditions, with inexpensive catalytic system and full atom economy since HBpin is the borylation agent, in contrast to our previously reported Pd-catalyzed reaction. Both aryl and alkyl substituted alkynes are reactive, revealing a wide reaction scope. Mechanistic studies suggest the intermediacy of FeII -hydride active catalyst capable to react with the alkyne group prior to alkene insertion, and computational studies suggest the occurrence of barrierless σ-bond metathesis involving HBpin and Fe-C bonds along the catalytic cycle.

Anatomical and clinical predictors of valve dysfunction and aortic dilation in bicuspid aortic valve disease.

OBJECTIVE: Bicuspid aortic valve (BAV) is associated with early valvular dysfunction and proximal aorta dilation with high heterogeneity. This study aimed to assess the determinants of these complications. METHODS: Eight hundred and fifty-two consecutive adults diagnosed of BAV referred from cardiac outpatient clinics to eight echocardiographic laboratories of tertiary hospitals were prospectively recruited. Exclusion criteria were aortic coarctation, other congenital disorders or intervention. BAV morphotype, significant valve dysfunction and aorta dilation (≥2 Z-score) at sinuses and ascending aorta were established. RESULTS: Three BAV morphotypes were identified: right-left coronary cusp fusion (RL) in 72.9%, right-non-coronary (RN) in 24.1% and left-non-coronary (LN) in 3.0%. BAV without raphe was observed in 18.3%. Multivariate analysis showed aortic regurgitation (23%) to be related to male sex (OR: 2.80, p<0.0001) and valve prolapse (OR: 5.16, p<0.0001), and aortic stenosis (22%) to BAV-RN (OR: 2.09, p<0.001), the presence of raphe (OR: 2.75, p<0.001), age (OR: 1.03; p<0.001), dyslipidaemia (OR: 1.77, p<0.01) and smoking (OR: 1.63, p<0.05). Ascending aorta was dilated in 76% without differences among morphotypes and associated with significant valvular dysfunction. By contrast, aortic root was dilated in 34% and related to male sex and aortic regurgitation but was less frequent in aortic stenosis and BAV-RN. CONCLUSIONS: Normofunctional valves are more prevalent in BAV without raphe. Aortic stenosis is more frequent in BAV-RN and associated with some cardiovascular risk factors, whereas aortic regurgitation (AR) is associated with male sex and sigmoid prolapse. Although ascending aorta is the most commonly dilated segment, aortic root dilation is present in one-third of patients and associated with AR. Remarkably, BAV-RL increases the risk for dilation of the proximal aorta, whereas BAV-RN spares this area.

Empirical comparison of reduced representation bisulfite sequencing and Infinium BeadChip reproducibility and coverage of DNA methylation in humans.

We empirically examined the strengths and weaknesses of two human genome-wide DNA methylation platforms: rapid multiplexed reduced representation bisulfite sequencing and Illumina's Infinium BeadChip. Rapid multiplexed reduced representation bisulfite sequencing required less input DNA, offered more flexibility in coverage, and interrogated more CpG loci at a higher regional density. The Infinium covered slightly more protein coding, cancer-associated and mitochondrial-related genes, both platforms covered all known imprinting clusters, and rapid multiplexed reduced representation bisulfite sequencing covered more microRNA genes than the HumanMethylation450, but fewer than the MethylationEPIC. Rapid multiplexed reduced representation bisulfite sequencing did not always interrogate exactly the same CpG loci, but genomic tiling improved overlap between different libraries. Reproducibility of rapid multiplexed reduced representation bisulfite sequencing and concordance between the platforms increased with CpG density. Only rapid multiplexed reduced representation bisulfite sequencing could genotype samples and measure allele-specific methylation, and we confirmed that Infinium measurements are influenced by nearby single-nucleotide polymorphisms. The respective strengths and weaknesses of these two genome-wide DNA methylation platforms need to be considered when conducting human epigenetic studies.