Unmasking crucial residues in adipose triglyceride lipase for coactivation with comparative gene identification-58.

Lipolysis is an essential metabolic process that releases unesterified fatty acids from neutral lipid stores to maintain energy homeostasis in living organisms. Adipose triglyceride lipase (ATGL) plays a key role in intracellular lipolysis and can be coactivated upon interaction with the protein comparative gene identification-58 (CGI-58). The underlying molecular mechanism of ATGL stimulation by CGI-58 is incompletely understood. Based on analysis of evolutionary conservation, we used site directed mutagenesis to study a C-terminally truncated variant and full-length mouse ATGL providing insights in the protein coactivation on a per-residue level. We identified the region from residues N209-N215 in ATGL as essential for coactivation by CGI-58. ATGL variants with amino acids exchanges in this region were still able to hydrolyze triacylglycerol at the basal level and to interact with CGI-58, yet could not be activated by CGI-58. Our studies also demonstrate that full-length mouse ATGL showed higher tolerance to specific single amino acid exchanges in the N209-N215 region upon CGI-58 coactivation compared to C-terminally truncated ATGL variants. The region is either directly involved in protein-protein interaction or essential for conformational changes required in the coactivation process. Three-dimensional models of the ATGL/CGI-58 complex with the artificial intelligence software AlphaFold demonstrated that a large surface area is involved in the protein-protein interaction. Mapping important amino acids for coactivation of both proteins, ATGL and CGI-58, onto the 3D model of the complex locates these essential amino acids at the predicted ATGL/CGI-58 interface thus strongly corroborating the significance of these residues in CGI-58-mediated coactivation of ATGL.

Prevalence of electrocardiographic abnormalities in elite and sub-elite professional athletes / Prevalencia de alteraciones electrocardiográficas en deportistas élite y sub-élite

Objective: The objective of this study is to determine the prevalence of electrocardiographic abnormalities that could endanger the lives of elite and sub-elite professional athletes based on normal, borderline, and abnormal findings described in international recommendations. Material and method: This retrospective observational study was performed only on men elite football players, men elite baseball players, men elite basketball players, and men sub-elite football players (second division, third division, U-15, U-17, and U-20). Data were collected from pre-competition ECGs performed by team-affiliated physicians in the 2012 – 2019 preseasons of active-roster athletes and sub-elite players. The qualitative characteristics of each ECG were analyzed using the international recommendations for electrocardiographic interpretation in athletes to detect accepted training-related ECG findings and findings classified as borderline and abnormal. Results: A total of 716 ECGs were included. Common training-related ECG changes were found in 63.1%; sinus bradycardia was the most prevalent training-related ECG change (47.2%). The prevalence of borderline ECG readings among all the participants was 3.9%; the most frequent change was right axis deviation. The prevalence of abnormal ECG findings overall was 4.2%. Conclusion: Electrocardiographic changes in athletes are frequently seen; however, a constant review of changes within abnormal or borderline parameters is recommended. It is suggested that further research studies should study the electrocardiographic changes in elite and sub-elite athletes and compare these changes considering the biological sex of the athletes to see if there are any differences.(AU)

Objetivo: El objetivo del presente estudio es evaluar la prevalencia de anormalidades electrocardiográficas que puedan poner en peligro la vida de deportistas profesionales élite y sub-élite, a partir de hallazgos normales, limítrofes y anormales en el ECG descritas en consensos internacionales. Material y método: Estudio retrospectivo y observacional donde se analizaron los ECGs de 12 derivaciones en reposo de jugadores de élite de fútbol, béisbol y baloncesto y jugadores sub-élite de fútbol, solamente del género masculino. Los datos se recopilaron de ECGs previos a la competencia realizados por médicos afiliados al equipo en las pretemporadas 2012-2019 en deportistas de la lista activa y jugadores sub-élite. Se utilizaron las recomendaciones internacionales para la interpretación electrocardiográfica de deportistas en las variables cuantitativas para conocer las alteraciones electrocardiográficas aceptadas y evaluar la detección de anormalidades en el trazo para clasificarlas en anormal o en el límite.Resultados: Un total de 716 ECGs fueron incluidos. Se encontraron cambios comunes en el ECG relacionados con el entrenamiento en el 63,1%; la bradicardia sinusal fue el cambio en el ECG relacionado con el entrenamiento más frecuente (47,2%). La prevalencia de lecturas limítrofes de ECG entre todos los participantes fue del 3,9%; el cambio más frecuente fue la desviación del eje a la derecha. La prevalencia de hallazgos ECG anormales en general fue del 4,2%. Conclusiones: Los cambios electrocardiográficos en los deportistas se ven con frecuencia, sin embargo, se recomienda constante revisión de cambios dentro de parámetros anormales o en limitrófes. Se sugiere que estudios de investigación estudien los cambios electrocardiográficos en deportistas élite y sub-élite y que se comparen estos cambios teniendo en cuenta el sexo biológico de los deportistas para ver si existen diferencias.(AU)

The Crystal Structure of Mouse Ces2c, a Potential Ortholog of Human CES2, Shows Structural Similarities in Substrate Regulation and Product Release to Human CES1.

Members of the carboxylesterase 2 (Ces2/CES2) family have been studied intensively with respect to their hydrolytic function on (pro)drugs, whereas their physiological role in lipid and energy metabolism has been realized only within the last few years. Humans have one CES2 gene which is highly expressed in liver, intestine, and kidney. Interestingly, eight homologous Ces2 (Ces2a to Ces2h) genes exist in mice and the individual roles of the corresponding proteins are incompletely understood. Mouse Ces2c (mCes2c) is suggested as potential ortholog of human CES2. Therefore, we aimed at its structural and biophysical characterization. Here, we present the first crystal structure of mCes2c to 2.12 Å resolution. The overall structure of mCes2c resembles that of the human CES1 (hCES1). The core domain adopts an α/ß hydrolase-fold with S230, E347, and H459 forming a catalytic triad. Access to the active site is restricted by the cap, the flexible lid, and the regulatory domain. The conserved gate (M417) and switch (F418) residues might have a function in product release similar as suggested for hCES1. Biophysical characterization confirms that mCes2c is a monomer in solution. Thus, this study broadens our understanding of the mammalian carboxylesterase family and assists in delineating the similarities and differences of the different family members.

Comparison of the effect of whole-body vibration therapy versus conventional therapy on functional balance of patients with Parkinson's disease: adding a mixed group.

OBJECTIVE: Assess the effect of Whole-Body Vibration (WBV) therapy in functional balance status of Parkinson's disease (PD) patients and compare this to conventional and combined therapy. INTRODUCTION: PD patients experience a decreased mobility, inactivity, and loss of independence as consequence of disturbances in gait, posture, and balance. Rehabilitation therapy is a non-pharmacological way of improving functionality. One of the most studied modalities is WBV, with multiple studies showing improvement in motor function. However, results in this manner are inconsistent. METHODS: Forty-five patients were enrolled in a non-randomized controlled trial and divided into three groups. Group 1 received conventional therapy (thermotherapy, stretching, strengthening, coordination and balance). Group 2 received WBV therapy, and group 3 patients underwent a combined therapy protocol. A total of 20 sessions (3 per week) were conducted, assessing Berg Balance Scale (BBS) before initial and after final session. RESULTS: The 3 intervention groups showed significant improvement in BBS scores after concluding the 20-session trial compared to initial assessment. When comparing mean change in BBS score from initial to final assessment, the combined therapy group had a greater increase compared to conventional therapy, but no significant differences were observed comparing to WBV group. Mean change in BBS score showed no significant difference between conventional therapy and WBV therapy group. CONCLUSIONS: WBV therapy is a useful tool as co-adjuvant in conventional therapy. The combination of both therapies is a significant therapeutic alternative for the improvement of functional balance status in PD patients compared to conventional therapy alone.

Relationship between left ventricular hypertrophy and somatotype of high performance athletes using structural equations modeling / Relación entre la hipertrofia ventricular izquierda y el somatotipo en atletas de alto rendimiento utilizando modelamiento de ecuaciones estructurales

Introduction: Sports induce morphological and functional adaptations in the human heart that directly relate to the type, duration and intensity of training and the years of practice. These changes are present in different ways in the electrocardiogram. A high QRS voltage is the most significant finding. Its correlation with left ventricular hypertrophy is low. In this study, the aim was to determine if a relationship exists between electrocardiographic alterations of left ventricular hypertrophy and somatotype in high performance athletes. Methods: A retrospective, cross-sectional, quantitative, multiple correlation, observational and analytical study of a database of 180 resting electrocardiograms and anthropometric evaluations of men's soccer, women's soccer, swimming, cycling, basketball, and tennis athletes was performed. A database containing somatotype and Sokolow-Lyon electrocardiographic voltage criteria was created. Results: The study group was composed of 83.3% men and 16.7% women. Age ranged from 10 to 51 years with a mean of 19.73 ± 5.8. Weight ranged from 35.90 to 122.3 kg with a mean of 66.98 ± 12.67 and height ranged from 143 to 213 cm with a mean of 174.11 ± 10.29 cm. Endomorphy for the entire group ranged from 1.0 to 5.7 with a mean of 2.5 ± 0.9. Mesomorphy ranged from 1.6 to 7.1 with a mean of 4.2 ± 0.95. Ectomorphy ranged from 1.1 to 5.8 with a mean of 2.9 ± 0.96. The structural equation model had a normal multivariable distribution of 3.161, reaching a Pearson of .26 for mesomorphy with a goodness of fit and a variance of 0% for mesomorphy and left ventricular hypertrophy. Conclusion: Based on the findings, we can say that somatotype does not predict left ventricular hypertrophy in high per-formance athletes

Introducción: Los deportes inducen adaptaciones morfológicas y funcionales en el corazón humano directamente relacionadas con el tipo, duración e intensidad del entrenamiento y los años de práctica. Estos cambios se manifiestan de diversas formas en el electrocardiograma. Un alto voltaje del QRS es el hallazgo más significativo. Su correlación con la hipertrofia ventricular izquierda es baja. En este estudio, el objetivo era determinar si existe una relación entre las alteraciones electrocardiográficas de hipertrofia ventricular izquierda y el somatotipo en deportistas de alto rendimiento. Métodos: Se efectuó un estudio transversal, cuantitativo, observacional, analítico retrospectivo de correlación múltiple de una base de datos de 180 electrocardiogramas en reposo y antropometría de atletas de soccer varonil, soccer femenil, natación, basquetbol, ciclismo y tenis. Se creó una base de datos con el somatotipo y los criterios de voltaje electrocardiográfico de Sokolow-Lyon. Resultados: El grupo de estudio estaba compuesto por 83,3% varones y 16,7% mujeres. El rango de edad fue de 10 a 51 años con una media de 19,73 ± 5,8. El peso varió de 35,90 a 122,3 kg con una media de 66,98 ± 12,67 y la estatura varió de 143 a 213 cm con una media de 174,11 ± 10,29 cm. Endomorfia para todo el grupo osciló entre 1,0 y 5,7 con una media de 2,55 ± 0,9. Mesomorfia varió de 1,6 a 7,1 con una media de 4,2 ± 0,95. Ectomorfia varió de 1,1 a 5,8 con una media de 2,9 ± 0,96. El modelo de ecuaciones estructurales tenía una distribución multivariable normal de 3.161, alcanzando un Pearson de 0,26 para mesomorfia con una bondad de ajuste y una varianza de 0% para mesomorfia e hipertrofia ventricular izquierda. Conclusiones: En base a los hallazgos podemos decir que el somatotipo no predice hipertrofia ventricular izquierda en atletas de alto rendimiento

A social health services model to promote active ageing in Mexico: design and evaluation of a pilot programme.

The objective of the study was to design and evaluate a pilot programme aimed at promoting the active ageing of older adults at the Mexican Institute of Social Security. The study was conducted in three stages: (a) design; (b) implementation; and (c) before-after evaluation through analysis of changes in functional status, occupational functioning and health-related quality of life. To overcome the limitations of the study design, we evaluated the effect of 80 per cent adherence to the programme on the outcome variables using the generalised linear regression models (GLM). Two hundred and thirty-nine older adults agreed to participate, of whom 65 per cent completed the programme. Most were women; the average age was 77 years. Adherence to the programme was higher than 75 per cent for the group who completed active ageing services and less than 60 per cent for the drop-out group. Overall, 46 per cent of older adults reached an adherence level of 80 per cent or higher. Adherence was significantly associated with improved quality of life total score (coefficient 2.7, p<0.0001) and occupational functioning total score (coefficient 2.2, p<0.0001). Participation of older adults in an active ageing programme may improve their health-related quality of life and occupational functioning. It is necessary to identify the potential barriers and to implement strategies to improve the recruitment and retention rates during the intervention.

Synthesis and biological evaluation of ( - )-13,14-dihydroxy-8,11,13-podocarpatrien-7-one and derivatives from (+)-manool.

13,14-Dihydroxy-8,11,13-podocarpatrien-7-one (1) and a series of ring C aromatic diterpene derivatives were synthesised from (+)-manool (4) and evaluated for their cytotoxic, leishmanicidal and trypanocidal activities. Our results indicated that compound 1 and other podocarpane-type intermediates are cytotoxic. Cleavage of C6-C7 bond of compound 7 improved cytotoxic activity, indicating that, in particular, the 6,7-seco-podocarpane-type compound 20 might serve as a lead compound for further development.

Facile access to optically active ring C aromatic diterpene derivatives from (+)-manool. first synthesis of 13,14-dihydroxy8,11,13-podocarpatrien-7-one.

14,15,17-Trinorlabdan-8,13-dione 6 was efficiently synthesized via ozonolysis of(+)-manool (4) followed by treatment with aqueous NaOH in the presence of tetra-n-butylammonium bromide as catalyst. This protocol has the advantages of high yield, mild conditions and simple procedure. Utilizing this strategy, the first enantiospecific synthesis of 13,14-dihydroxy-8,11,13-podocarpatrien-7-one (1), a constituent of Taiwania cryptomerioides and Celastrus paniculatus, was achieved starting from (+)-manool (4) after a four-step sequence in 24% overall yield.

[Vaccine against human papilloma virus]. / Vacuna contra el virus del papiloma humano.

Genital human papilloma virus infection (HPV) is the most common sexually transmitted infection worldwide, it is the cause of genital warts, and it is related with cervical cancer, the second most common cause of death from cancer in women in America, and the first in underdeveloped countries, and it is related with penis and prostate cancer in males also, and with anal cancer in both genders. This review examines the most important actual facts about HPV infection, and the new prophylactic vaccines. Two versions of the vaccine had been developed, both target HPV 16 and HPV 18, which involve approximately 70% of cervical cancer. One of them also targets HPV 6 and HPV 11, which account for approximately 90% of external genital warts. Both vaccines have an excellent safety profile, are highly immunogenic, and have atributed complete type specific protection against persistent infection and associated lesions in fully vaccinated girls and young women. The role of men as carriers of HPV as well as vectors for transmission is well documented. Several clinical trials are currently under way to determine the efficacy of vaccinating men. Reducing the cost of vaccination would be a priority for the developing world in order to get a broad target in poor countries.

Enfermedad veno-oclusiva hepática: presentación de un caso / Vend occlusive disease of the liver: presentation a case

La enfermedad oclusiva hepática es una patología poco frecuente con una alta mortalidad y de tratamiento médico quirúrgico, dependiendo de su etiología; con manifestaciones clínicas del dolor abdominal, ascitis y hepatomegalia. Presentamos el caso de una paciente de 34 años, con las manifestaciones clínicas antes descritas, su evolución, exámenes realizados para determinar el sitio de la lesión y su etiología, con la finalidad de distinguir entre síndrome de Budd-Chiari (SBC) y enfermedad veno oclusiva hepática.