Social epidemiology of urban COVID-19 inequalities in Latin America and Canada.

BACKGROUND: The COVID-19 pandemic has spread through pre-existing fault lines in societies, deepening structural barriers faced by precarious workers, low-income populations, and racialized communities in lower income sub-city units. Many studies have quantified the magnitude of inequalities in COVID-19 distribution within cities, but few have taken an international comparative approach to draw inferences on the ways urban epidemics are shaped by social determinants of health. METHODS: Guided by critical epidemiology, this study quantifies sub-city unit-level COVID-19 inequalities across eight of the largest metropolitan areas of Latin America and Canada. Leveraging new open-data sources, we use concentration indices to quantify income- and vulnerability-related inequalities in incidence, test positivity, and deaths over the first 125 weeks of the pandemic between January 2020 and May 2022. RESULTS: Our findings demonstrate that incidence, deaths, and test positivity are all less concentrated in low-income sub-city units than would be expected, with incidence ranging concentration in lower income neighbourhoods in Toronto (CI = -0.07) to concentration in higher income neighbourhoods in Mexico City (CI = 0.33). Drawing on relevant studies and evaluations of data reliability, we conclude that the best available public surveillance data for the largest cities in Latin America are likely not reliable measures of the true COVID-19 disease burden. We also identify recurring trends in the evolution of inequalities across most cities, concluding that higher income sub-city units were frequent early epicentres of COVID-19 transmission across the Latin America and Canada. CONCLUSIONS: Just as critical epidemiology points to individuals biologically embodying the material and social conditions in which we live, it may be just as useful to think of cities reifying their material and social inequities in the form of sub-city unit-level infectious disease inequities. By shifting away from a typical vulnerability-based social determinants of health frame, policymakers could act to redress and reduce externalities stemming from sub-city unit-level income inequality through redistributive and equity-promoting policies to shift the centre of gravity of urban health inequalities before the next infectious disease epidemic occurs.

Altered ubiquitin causes perturbed calcium homeostasis, hyperactivation of calpain, dysregulated differentiation, and cataract.

Although the ocular lens shares many features with other tissues, it is unique in that it retains its cells throughout life, making it ideal for studies of differentiation/development. Precipitation of proteins results in lens opacification, or cataract, the major blinding disease. Lysines on ubiquitin (Ub) determine fates of Ub-protein substrates. Information regarding ubiquitin proteasome systems (UPSs), specifically of K6 in ubiquitin, is undeveloped. We expressed in the lens a mutant Ub containing a K6W substitution (K6W-Ub). Protein profiles of lenses that express wild-type ubiquitin (WT-Ub) or K6W-Ub differ by only ∼2%. Despite these quantitatively minor differences, in K6W-Ub lenses and multiple model systems we observed a fourfold Ca(2+) elevation and hyperactivation of calpain in the core of the lens, as well as calpain-associated fragmentation of critical lens proteins including Filensin, Fodrin, Vimentin, ß-Crystallin, Caprin family member 2, and tudor domain containing 7. Truncations can be cataractogenic. Additionally, we observed accumulation of gap junction Connexin43, and diminished Connexin46 levels in vivo and in vitro. These findings suggest that mutation of Ub K6 alters UPS function, perturbs gap junction function, resulting in Ca(2+) elevation, hyperactivation of calpain, and associated cleavage of substrates, culminating in developmental defects and a cataractous lens. The data show previously unidentified connections between UPS and calpain-based degradative systems and advance our understanding of roles for Ub K6 in eye development. They also inform about new approaches to delay cataract and other protein precipitation diseases.

The effect of glenoid component version and humeral polyethylene liner rotation on subluxation and impingement in reverse shoulder arthroplasty.

BACKGROUND: A previously validated finite element modeling approach was used to determine how changes in glenoid component version and polyethylene liner rotation within the humeral component affect the arm abduction angle at which impingement between the inferior glenoid and the polyethylene liner occurs as well as the amount of subluxation generated by that impingement. MATERIALS AND METHODS: Five glenoid component versions (5° anteversion; neutral; 5°, 10°, and 20° retroversion) and 7 polyethylene liner rotations (20° and 10° anterior; neutral; 10°, 20°, 30°, and 40° posterior) were considered, resulting in 35 different clinically representative models. The humerus was internally and externally rotated and extended and flexed, and the resulting impingement and subluxation were measured. To further analyze more global trends and to identify implantations least prone to subluxation, polyethylene liner rotation was additionally varied in coarser 30° increments across the entire 360° range. RESULTS: All subluxation caused by impingement occurred during external rotation and extension, and external rotation produced nearly 10-fold more subluxation than extension. Neutral glenoid component version was associated with the least amount of subluxation for all polyethylene liner rotations. Posteriorly rotated polyethylene liners, which place the thick inferior region of the component away from the scapula, produced the least amount of subluxation. The 90° and 120° posterior liner rotations produced no subluxation, whereas the 30° and 60° anterior liner rotations produced the greatest amount of subluxation. CONCLUSION: These results indicate that rotating modern radially asymmetric humeral polyethylene liners posteriorly can reduce the risk of subluxation leading to dislocation and increase external rotation range of motion.

Preimplantation genetic testing in assisted reproduction.

In the last years technologies have been developed that allow obtaining genetic information in less time and at lower cost, revolutionizing the genetic diagnosis in reproductive medicine, with availability of genetic tests from conception. High throughput sequencing analyses have increased the ability to detect embryos with genetic diseases, which has contributed to the better selection of embryos for in-vitro fertilization and, therefore, better reproductive outcomes. The preimplantation genetic testing (PGT) includes three subcategories of PGT for aneuploidies (PGT-A), PGT for single gene/monogenic disorders (PGT-M), and PGT for chromosome structural rearrangements (PGT-SR). This review provides an overview of the evolution of preimplantation genetic testing, the advantages and disadvantages of these technologies and their applicability in reproductive medicine as well as a description of the legislation and bioethics aspects. Advances in preimplantation genetic testing are changing clinical practice, posing new challenges for genetic counseling and alternative plausible to substantially reduce the risk of an adverse reproductive outcome related to the transfer of abnormal embryos. Despite the overall important implantation rates achieved following transfer of euploid embryos, PGT-A did not improve overall pregnancy outcomes in all women. There is a definite need for studies to identify the causes of why not all euploid embryos implant. Also, debate continues regarding the accuracy and the safety of this approach, and the currently available evidence is insufficient to support PGT-A in routine clinical practice. The general recommendation is that PGT-A, PGT-M and PGT-SR should be guided according to the antecedents of the couples.

Using the International Pandemic Instrument to Revitalize the Innovation Ecosystem for Antimicrobial R&D.

The inclusion of antimicrobial resistance (AMR) and increased research and development (R&D) capabilities in the most recent outline of the World Health Organization's (WHO's) international pandemic instrument signals an opportunity to reshape pharmaceutical R&D system in favour of antimicrobial product development. This article explains why the current innovation ecosystem has disadvantaged the creation of antimicrobial products for human use. It also highlights how the COVID-19 pandemic experience can inform and stimulate international cooperation to implement innovative R&D incentives to bring new, life-saving antimicrobial products to the market.

Return of Scapulohumeral Rhythm in Patients After Reverse Shoulder Arthroplasty: A Midterm Stereoradiographic Imaging Analysis.

Background: Reverse shoulder arthroplasty (RSA) is associated with high rates of midterm complications including scapular notching, implant wear, and mechanical impingement. Scapulo-humeral rhythm (SHR), described by Codman in the 1920's, is defined as the ratio of glenohumeral motion to scapulothoracic motion. SHR is used as an indicator of shoulder dysfunction, as alterations in SHR can have profound implications on shoulder biomechanics. The determination of SHR can be hindered by soft-tissue motion artifacts and high radiation burdens associated with traditional surface marker or fluoroscopic analysis. EOS low dose stereoradiographic imaging analysis utilizing 3D model construction from a 2D X-ray series may offer an alternative modality for characterizing SHR following RSA. Methods: Patients (n=10) underwent an EOS imaging analysis to determine SHR at six and twelve months post-RSA. Leveraging 3D models of the implants, 2D/3D image registration methods were used to calculate relative glenohumeral and scapulothoracic positioning at 60, 90 and 120° of shoulder elevation. Subject-specific SHR curves were assessed and midterm changes in post-RSA SHR associated with follow-up time and motion phase were evaluated. Pearson correlations assessed associations between patient-specific factors and post-RSA SHR. Results: Mean post-RSA SHR was 0.81:1 across subjects during the entire midterm postoperative period. As a cohort, post-RSA SHR was more variable for 60-90° of shoulder motion. SHR for 90-120° of motion decreased (0.43:1) at twelve months post-RSA. Post-RSA SHR could be categorized using three relative motion curve patterns, and was not strongly associated with demographic factors such as BMI. 50% of subjects demonstrated a different SHR relative motion curve shape at twelve months post-RSA, and SHR during the 90120° of motion was found to generally decrease at twelve months. Conclusion: Midterm post-RSA SHR was successfully evaluated using EOS technology, revealing lower SHR values (i.e., greater scapulothoracic motion) compared to normal values reported in the literature. SHR continued to change for some subjects during the midterm post-RSA period, with the greatest change during 90-120° of shoulder motion. Study findings suggest that future post RSA rehabilitation efforts to address elevated scapulothoracic motion may benefit from being patient-specific in nature and targeting scapular stabilization during 90-120° of shoulder motion. Level of Evidence: IV.

Association between risk polymorphisms for neurodegenerative diseases and cognition in colombian patients with frontotemporal dementia.

Frontotemporal dementia (FTD) is a heterogeneous neurodegenerative disease of presenile onset. A better characterization of neurodegenerative disorders has been sought by using tools such as genome-wide association studies (GWAS), where associations between single nucleotide polymorphisms (SNPs) and cognitive profiles could constitute predictive biomarkers for these diseases. However, in FTD, associations between genotypes and cognitive phenotypes are yet to be explored. Here, we evaluate a possible relationship between genetic variants and some cognitive functions in an FTD population. Methodology: A total of 47 SNPs in genes associated with neurodegenerative diseases were evaluated using the Sequenom MassARRAY platform along with their possible relationship with performance in neuropsychological tests in 105 Colombian patients diagnosed with FTD. Results and discussion: The SNPs rs429358 (APOE), rs1768208 (MOBP), and rs1411478 (STX6), were identified as risk factors for having a low cognitive performance in inhibitory control and phonological verbal fluency. Although the significance level was not enough to reach the corrected alpha for multiple comparison correction, our exploratory data may constitute a starting point for future studies of these SNPs and their relationship with cognitive performance in patients with a probable diagnosis of FTD. Further studies with an expansion of the sample size and a long-term design could help to explore the predictive nature of the potential associations we identified.

Experiences of the Molecular Diagnosis of Fragile X Syndrome in Ecuador.

Fragile X syndrome (FXS) is the most common cause of hereditary intellectual disability and the second most common cause of intellectual disability of genetic etiology. This complex neurodevelopmental disorder is caused by an alteration in the CGG trinucleotide expansion in fragile X mental retardation gene 1 (FMR1) leading to gene silencing and the subsequent loss of its product: fragile X mental retardation protein 1 (FMRP). Molecular diagnosis is based on polymerase chain reaction (PCR) screening followed by Southern blotting (SB) or Triplet primer-PCR (TP-PCR) to determine the number of CGG repeats in the FMR1 gene. We performed, for the first time, screening in 247 Ecuadorian male individuals with clinical criteria to discard FXS. Analysis was carried out by the Genetics Service of the Hospital de Especialidades No. 1 de las Fuerzas Armadas (HE-1), Ecuador. The analysis was performed using endpoint PCR for CGG fragment expansion analysis of the FMR1 gene. Twenty-two affected males were identified as potentially carrying the full mutation in FMR1 and thus diagnosed with FXS that is 8.1% of the sample studied. The average age at diagnosis of the positive cases was 13 years of age, with most cases from the geographical area of Pichincha (63.63%). We confirmed the familial nature of the disease in four cases. The range of CGG variation in the population was 12-43 and followed a modal distribution of 27 repeats. Our results were similar to those reported in the literature; however, since it was not possible to differentiate between premutation and mutation cases, we can only establish a molecular screening approach to identify an expanded CGG repeat, which makes it necessary to generate national strategies to optimize molecular tests and establish proper protocols for the diagnosis, management, and follow-up of patients, families, and communities at risk of presenting FXS.

Analysis of Heritability Across the Clinical Phenotypes of Frontotemporal Dementia and the Frequency of the C9ORF72 in a Colombian Population.

Frontotemporal dementia (FTD) is a highly heritable condition. Up to 40% of FTD is familial and an estimated 15% to 40% is due to single-gene mutations. It has been estimated that the G4C2 hexanucleotide repeat expansions in the C9ORF72 gene can explain up to 37.5% of the familial cases of FTD, especially in populations of Caucasian origin. The purpose of this paper is to evaluate hereditary risk across the clinical phenotypes of FTD and the frequency of the G4C2 expansion in a Colombian cohort diagnosed with FTD. Methods: A total of 132 FTD patients were diagnosed according to established criteria in the behavioral variant FTD, logopenic variant PPA, non-fluent agrammatic PPA, and semantic variant PPA. Hereditary risk across the clinical phenotypes was established in four categories that indicate the pathogenic relationship of the mutation: high, medium, low, and apparently sporadic, based on those proposed by Wood and collaborators. All subjects were also examined for C9ORF72 hexanucleotide expansion (defined as >30 repetitions). Results: There were no significant differences in the demographic characteristics of the patients between the clinical phenotypes of FTD. The higher rate phenotype was bvFTD (62.12%). In accordance with the risk classification, we found that 72 (54.4%) complied with the criteria for the sporadic cases; for the familial cases, 23 (17.4%) fulfilled the high-risk criteria, 23 (17.4%) fulfilled the low risk criteria, and 14 (10.6%) fulfilled the criteria to be classified as subject to medium risk. C9ORF72 expansion frequency was 0.76% (1/132). Conclusion: The FTD heritability presented in this research was very similar to the results reported in the literature. The C9ORF72 expansion frequency was low. Colombia is a triethnic country, with a high frequency of genetic Amerindian markers; this shows consistency with the present results of a low repetition frequency. This study provides an initial report of the frequency for the hexanucleotide repeat expansions in C9ORF72 in patients with FTD in a Colombian population and paves the way for further study of the possible genetic causes of FTD in Colombia.

The Influence of Different Rotator Cuff Deficiencies on Shoulder Stability Following Reverse Shoulder Arthroplasty.

Background: The primary indication for reverse shoulder arthroplasty (RSA) is rotator cuff arthropathy caused by a deficient rotator cuff. Cuff deficiency in patients is highly variable in its distribution and extent, with mechanical implications that may significantly affect post-operative recovery. This study investigated the effects of variable cuff deficiency on the propensity for impingement between the scapula and humeral component and resulting subluxation, the source of two common complications (scapular notching and instability). Methods: Five different finite element models of an RSA were analyzed with varying degrees of rotator cuff deficiency: (1) baseline, with intact subscapularis, infraspinatus and teres minor, (2) no subscapularis, (3) no subscapularis or infraspinatus, (4) no infraspinatus, and (5) no infraspinatus or teres minor. The supraspinatus was not included in any models, as it is absent in rotator cuff arthropathy. Each model was moved through a prescribed arc of 45° internal/ external rotation originating from neutral. Results: Greater rotator cuff deficiency was associated with more impingement and larger magnitudes of subluxation. The largest subluxation (7.5 mm) and highest impingement-related contact stress (479 MPa) was in the model lacking all rotator cuff muscle groups. Posterior subluxation was present in most models lacking the infraspinatus, while anterior subluxation was present in all models lacking the subscapularis. Conclusions: This study helps clarify how different rotator cuff deficiencies influence shoulder stability following RSA and can ultimately help predict which patients may be at greater risk for impingement-related scapular notching and subluxation. Clinical Relevance: Surgeons should carefully consider the nature of the rotator cuff deficiency and its influence on impingement and instability when planning for RSA.Level of Evidence: V.

Características epidemiológicas de la Osteomielitis aguda en niños internados en un hospital infeccioso de referencia

Introducción: La osteomielitis aguda es una infección del hueso que afecta principalmente a los niños y tiene generalmente diseminación hematógena, a veces asociada a un trauma. En la etiología influyen factores, como la edad, el estado inmunológico y las enfermedades concomitantes. En la mayoría de los casos, el principal agente etiológico es Staphylococcus aureus. Es importante el diagnóstico oportuno para evitar secuelas a mediano o largo plazo. Objetivo: Describir las características epidemiológicas de un grupo de pacientes con osteomielitis aguda. Métodos: Se realizó la revisión retrospectiva de los expedientes clínicos de pacientes egresados del servicio de pediatría del Instituto de Medicina Tropical, entre enero de 2016 y diciembre de 2020, con diagnóstico de osteomielitis aguda. Resultados: Los varones con osteomielitis corresponden al 67,8% del total de 59 casos registrados, en cuanto a los signos y síntomas, el dolor, la tumefacción y la impotencia funcional fueron predominantes, la fiebre se documentó en 49 (83,1%) pacientes, se registró antecedentes de cirugía en 37 (62,7%) de los pacientes y complicaciones en 42 (71,2%) de los pacientes, la complicación más frecuente fue osteomielitis crónica El sitio anatómico más frecuente fueron los miembros inferiores. El tratamiento empírico fue realizado con cefalosporinas de 3G en 72,9% de los pacientes, ya sea solo o combinado con clindamicina o vancomicina, un paciente con aislamiento de M. tuberculosis recibió tratamiento HRZE. Se aisló algún germen 44 pacientes (74,5%), el microorganismo predominante fue Staphylococcus aureus en 81,8 %, la mitad (52,3%) correspondieron a SAMR Se encontró una alta resistencia a oxacilina del 55,8% y un solo paciente resistente a clindamicina (2,2%). Conclusión Los hallazgos fueron similares a los reportados en la literatura en cuanto a etiología, sitio anatómico afectado y cobertura antibiótica.

Introduction: Acute osteomyelitis is a bone infection that mainly affects children and generally has hematogenous spread, sometimes associated with trauma. The etiology is influenced by factors such as age, immune status, and comorbidities. In most cases, the main etiologic agent is Staphylococcus aureus. Timely diagnosis is important to avoid sequelae in the medium or long term. Objective: To describe the epidemiological characteristics of a group of patients with acute osteomyelitis. Methods: A retrospective review of the clinical records of patients discharged from the pediatric service of the Institute of Tropical Medicine was carried out between January 2016 and December 2020, with a diagnosis of acute osteomyelitis. Results: Men with osteomyelitis correspond to 67.8% of the total of 59 registered cases, in terms of signs and symptoms, pain, swelling and functional impotence were predominant, fever was documented in 49 (83.1%) patients, a history of surgery was recorded in 37 (62.7%) of the patients and complications in 42 (71.2%) of the patients, the most frequent complication was chronic osteomyelitis The most frequent anatomical site was the lower limbs. Empirical treatment was performed with 3G cephalosporins in 72.9% of the patients, either alone or in combination with clindamycin or vancomycin. One patient with M. tuberculosis isolation received HRZE treatment. Some germ was isolated in 44 patients (74.5%), the predominant microorganism was Staphylococcus aureus in 81.8%, half (52.3%) corresponded to MRSA. A high resistance to oxacillin of 55.8% and a only patient resistant to clindamycin (2.2%). Conclusion The findings were similar to those reported in the literature in terms of etiology, affected anatomical site, and antibiotic coverage.

Ayudas diagnósticas y diagnóstico diferencial de la enfermedad de Pompe / Diagnostic aids and differential diagnosis of Pompe disease

Introducción: La enfermedad de Pompe (EP) o glucogenosis tipo II es una enfermedad autosómica recesiva causada por mutaciones en el gen GAA que codifica para la proteína alfa-1,4-glucosidasa. Su deficiencia lleva a un almacenamiento anormal de glucógeno en los lisosomas de varias células, a través de los diferentes tejidos, lo que causa un compromiso musculoesquelético predominante. Contenidos: Los fenotipos de la enfermedad dependen de las variantes genéticas y de los niveles de la actividad enzimática residual. La enfermedad se presenta como EP de inicio infantil, EP de inicio tardío y EP intermedio, por lo que es de suma importancia su diagnóstico temprano, por medio de estudios moleculares como la secuenciación de Sanger y la secuenciación de nueva generación. Conclusiones: Se ha demostrado, mediante diferentes estudios, que las variaciones genéticas pueden diferir entre etnias, y es importante su caracterización molecular para determinar el tratamiento más adecuado, de acuerdo con el estado del material inmunológico de reacción cruzada (CRIM).

Introduction: Pompe disease (PD) or Glycogenosis Type II is a rare autosomal recessive disease caused by mutations in the GAA gene that codes for the alpha-1,4-glucosidase protein. Its deficiency leads to abnormal glycogen storage in the lysosomes of various cells throughout the different tissues causing a predominant musculoskeletal compromise. Contents: The phenotypes of the disease depend on the genetic variants and the levels of residual enzyme activity, presenting as infantile-onset PD, late-onset PD, and intermediate PD; Therefore, early diagnosis of the disease through molecular studies such as Sanger sequencing and new generation sequencing is of utmost importance. Conclusions: It has been shown through different studies that genetic variations can vary between ethnic groups and the molecular characterization of the variants is important to determine the most appropriate treatment depending on the state of the cross-reactive immunological material (CRIM)

Pioderma gangrenoso en pediatría. a propósito de un caso

RESUMEN El pioderma gangrenoso (PG) es una ulceración cutánea poco común, generalmente idiopática, asociada o no a trastornos sistémicos. La etiopatogenia del PG aún no se conoce bien. Clínicamente se clasifica en tipos ulcerativo, pustular, bulloso y vegetativo. También se han descrito algunas variantes atípicas y raras. El diagnóstico clínico, apoyado en estudios auxiliares (laboratoriales, anatomopatológicos). Se han propuesto algunos criterios para el diagnóstico de PG. El tratamiento consiste principalmente en corticosteroides y agentes inmunosupresores. Caso clínico: adolescente, femenino, sin patología de base, con antecedente de lesión ulcerosa en pierna derecha de 6 meses de evolución, que aumenta de tamaño en el tiempo, consulta en varias oportunidades con tratamientos ambulatorios tórpidos. Ante aparición de fiebre, dolor e impotencia funcional se interna. En el transcurso de la internación presenta rectorragia importante con descenso de Hb. Se realiza colonoscopia de urgencias y se logra unidad diagnóstica egresando con tratamiento apropiado luego de 26 DDI.

ABSTRACT Pyoderma gangrenosum (PG) is an uncommon cutaneous ulceration, usually idiopathic, associated or not with systemic disorders. The etiopathogenesis of PG is still not well understood. Clinically, it is classified into ulcerative, pustular, bullous and vegetative types. Some atypical and rare variants have also been described. The clinical diagnosis, supported by auxiliary studies (laboratorial, anatomopathological). Some criteria have been proposed for the diagnosis of PG. The treatment consists mainly of corticosteroids and immunosuppressive agents. Clinical case: adolescent, female, without basic pathology, with a history of ulcerative lesion in the right leg of 6 months of evolution, which increases in size over time, consulting on several occasions with torpid ambulatory treatments. In the presence of fever, pain and functional impotence is internal. In the course of hospitalization, it presents significant rectorrhagia with a decrease in Hb. An emergency colonoscopy is performed and a diagnostic unit is achieved with appropriate treatment after 26 DDI.

Extractos vegetales de tres especies del género Baccharis inducen la proliferación de células mononucleares humanas / Plant extracts of three species of the genus Baccharis induce human mononuclear cells proliferation

Las plantas de uso en medicina tradicional constituyen una fuente importante de compuestos con actividad inmunomoduladora; entre ellas las especies del género Baccharis, conocidas popularmente como "Jaguareteka´a" en nuestro país, son ampliamente empleadas. En este estudio se evaluó la actividad inmunomoduladora de extractos metanólicos de tres especies del género Baccharis (B. trimera, B. notosergilay B. punctulata) sobre la proliferación de células mononucleares humanas de sangre periférica. Los extractos de las tres especies estudiadas estimularon la proliferación de las células mononucleares. Específicamente, el extracto de B. notosergila estimuló la proliferación celular a todas las concentraciones probadas (5, 10, 25 y 50 µg/mL), mientras que los extractos de B. trimera y B. punctulata mostraron este efecto a 5 y 10 µg/mL. Además, por presentar mayor inducción de la proliferación, se realizó un fraccionamiento con diferentes solventes del extracto metanólico de B. notosergila y B. punctulata. La fracción de acetato de etilo de ambos extractos vegetales aumentó la proliferación celular, sugiriendo que compuestos de polaridad media son los responsables de esta actividad. Estos resultados demuestran que los extractos de B. trimera, B. notosergila y B. punctulata poseen actividad inmunomoduladora sobre células mononucleares humanas y servirán de base a otros estudios para determinar el o los componentes activos de los extractos sobre el sistema inmune(AU)

Plants used in traditional medicine are an important source of compounds with immunomodulatory activity. Species of the genus Baccharis, popularly known as "Jaguareteka'a" in our country, are used in folk medicine for the treatment of liver, gastrointestinal, inflammatory and infectious diseases. In this study, we evaluated the immunomodulatory activity of methanolic extracts of three species of the genus Baccharis (B. trimera, B. notosergila and B. punctulata) on the proliferation of human peripheral blood mononuclear cells. Extracts of the three species studied stimulated the proliferation of mononuclear cells. The extract of B. notosergila stimulated cell proliferation at all concentrations tested, while extracts of B. trimera and B. punctulata stimulated at 5 and 10 µg/mL. In addition, we carried out a separation with different solvents of the methanolic extract of B. notosergila and B. punctulata. The ethyl acetate fraction of both plant extracts induced the proliferation of immune cells. These results show that the extracts of B. trimera, B. notosergila and B. punctulata had immunomodulatory activity on human mononuclear cells. Future work will be required to identify the components responsible for the activity on the immune system(AU)

Glycation-altered proteolysis as a pathobiologic mechanism that links dietary glycemic index, aging, and age-related disease (in nondiabetics).

Epidemiologic studies indicate that the risks for major age-related debilities including coronary heart disease, diabetes, and age-related macular degeneration (AMD) are diminished in people who consume lower glycemic index (GI) diets, but lack of a unifying physiobiochemical mechanism that explains the salutary effect is a barrier to implementing dietary practices that capture the benefits of consuming lower GI diets. We established a simple murine model of age-related retinal lesions that precede AMD (hereafter called AMD-like lesions). We found that consuming a higher GI diet promotes these AMD-like lesions. However, mice that consumed the lower vs. higher GI diet had significantly reduced frequency (P < 0.02) and severity (P < 0.05) of hallmark age-related retinal lesions such as basal deposits. Consuming higher GI diets was associated with > 3 fold higher accumulation of advanced glycation end products (AGEs) in retina, lens, liver, and brain in the age-matched mice, suggesting that higher GI diets induce systemic glycative stress that is etiologic for lesions. Data from live cell and cell-free systems show that the ubiquitin-proteasome system (UPS) and lysosome/autophagy pathway [lysosomal proteolytic system (LPS)] are involved in the degradation of AGEs. Glycatively modified substrates were degraded significantly slower than unmodified substrates by the UPS. Compounding the detriments of glycative stress, AGE modification of ubiquitin and ubiquitin-conjugating enzymes impaired UPS activities. Furthermore, ubiquitin conjugates and AGEs accumulate and are found in lysosomes when cells are glycatively stressed or the UPS or LPS/autophagy are inhibited, indicating that the UPS and LPS interact with one another to degrade AGEs. Together, these data explain why AGEs accumulate as glycative stress increases.

Perturbing the ubiquitin pathway reveals how mitosis is hijacked to denucleate and regulate cell proliferation and differentiation in vivo.

BACKGROUND: The eye lens presents a unique opportunity to explore roles for specific molecules in cell proliferation, differentiation and development because cells remain in place throughout life and, like red blood cells and keratinocytes, they go through the most extreme differentiation, including removal of nuclei and cessation of protein synthesis. Ubiquitination controls many critical cellular processes, most of which require specific lysines on ubiquitin (Ub). Of the 7 lysines (K) least is known about effects of modification of K6. METHODOLOGY AND PRINCIPAL FINDINGS: We replaced K6 with tryptophan (W) because K6 is the most readily modified K and W is the most structurally similar residue to biotin. The backbone of K6W-Ub is indistinguishable from that of Wt-Ub. K6W-Ub is effectively conjugated and deconjugated but the conjugates are not degraded via the ubiquitin proteasome pathways (UPP). Expression of K6W-ubiquitin in the lens and lens cells results in accumulation of intracellular aggregates and also slows cell proliferation and the differentiation program, including expression of lens specific proteins, differentiation of epithelial cells into fibers, achieving proper fiber cell morphology, and removal of nuclei. The latter is critical for transparency, but the mechanism by which cell nuclei are removed has remained an age old enigma. This was also solved by expressing K6W-Ub. p27(kip), a UPP substrate accumulates in lenses which express K6W-Ub. This precludes phosphorylation of nuclear lamin by the mitotic kinase, a prerequisite for disassembly of the nuclear membrane. Thus the nucleus remains intact and DNAseIIß neither gains entry to the nucleus nor degrades the DNA. These results could not be obtained using chemical proteasome inhibitors that cannot be directed to specific tissues. CONCLUSIONS AND SIGNIFICANCE: K6W-Ub provides a novel, genetic means to study functions of the UPP because it can be targeted to specific cells and tissues. A fully functional UPP is required to execute most stages of lens differentiation, specifically removal of cell nuclei. In the absence of a functional UPP, small aggregate prone, cataractous lenses are formed.

Sindrome de Prune Belly: presentación de un caso. Consideraciones sobre diagnóstico ultrasónico y tratamiento / Prune-Belly Syndrome: a case report

Frecuencia: Uno en 50.000 nacimientos. Principales manifestaciones: Agenesia o Atresia de musculatura abdominal; Agenesia o Atresia de uretra; Megavejiga. Etiología: Algunos autores consideran una consecuencia de un defecto mesodérmico primario. Caso clínico: Controles obstétricos normales hasta la semana 16, con diagnóstico ecográfico de Megavejiga. Se realizan punciones con evacuación de orina fetal. Se realiza estudio cromosómico y bioquímico. Consideraciones terapéuticas: 1) Punciones con evacuación de orina para disminuir la presión retrógada del tracto urinario; 2) Derivación de vejiga a líquido amniótico, que trata además el oligoamnios y mejora el desarrollo pulmonar; 3) Corregir las alteraciones morfológicas. Conclusiones: Formar un equipo médico interdisciplinario. Informar a los padres y prevenir que a pesar del tratamiento puede ocurrir fallo renal o pulmonar irreversible. Importancia del diagnóstico ultrasónico precoz.