Duchenne muscular dystrophy in a developing country: challenges in management and genetic counseling.

BACKGROUND AND OBJECTIVE: Multidisciplinary management of Duchenne Muscular Dystrophy (DMD) has achieved outstanding results in developed nations. We aimed to describe the status of diagnosis and management of DMD in a developing country through the experience of non-profit organizations. METHODS: A Multistate, multiple-source, population-based survey was performed from medical records of 432 patients. Data were retrospectively collected, reviewed and curated by health specialists; including clinical features, age at first symptoms, age at diagnosis, disease progression and management, family history, education, age and cause of death. RESULTS: There is a delay in noticing first symptoms and it did not diminish over the past 20 years. Less than 30% of patients obtained definite diagnosis and most of them are in physiotherapy programs but not under steroid treatment. In our study, family history does not anticipate recognition of symptoms compared to sporadic cases (p = 0.05). Approximately 93.33% of our patients attended to education programs. Mean age at death was 18.94 +/- 6.73 years and the most frequent cause was pneumonia. CONCLUSION: Delayed diagnosis of DMD in Mexico is mainly caused by the late detection of first symptoms. There is no difference in early detection of symptoms between familiar and sporadic cases. Lifespan of patients in our cohort is reduced compared to developed countries. The late diagnosis and low percentage of definite cases may affect patient management and genetic counseling and could also preclude participation of patients into novel clinical trials.

Immunostimulatory nanoparticle incorporating two immune agonists for the treatment of pancreatic tumors.

Pancreatic ductal adenocarcinoma (PDAC) is a highly malignant disease, where even surgical resection and aggressive chemotherapy produce dismal outcomes. Immunotherapy is a promising alternative to conventional treatments, possessing the ability to elicit T cell-mediated killing of tumor cells and prevent disease recurrence. Immunotherapeutic approaches thus far have seen limited success in PDAC due to a poorly immunogenic and exceedingly immunosuppressive tumor microenvironment, which is enriched with dysfunctional and immunosuppressed antigen-presenting cells (APCs). We developed a highly potent immunostimulatory nanoparticle (immuno-NP) to activate and expand APCs in the tumor and induce local secretion of interferon ß (IFNß), which is a pro-inflammatory cytokine that plays a major role in APC recruitment. The effectiveness of the immuno-NP stems from its dual cargo of two synergistic immune modulators consisting of an agonist of the stimulator of interferon genes (STING) pathway and an agonist of the Toll-like receptor 4 (TLR4) pathway. We show the functional synergy of the dual-agonist cargo can be tweaked by adjusting the ratio of the two agonists loaded in the immuno-NP, leading to an increase in IFNß production (11-fold) compared to any single agonist immuno-NP variant. Using the orthotopic murine Panc02 model of PDAC, we show that systemic administration allowed immuno-NPs to deposit into the perivascular regions of the tumor, which coincided with the APC-rich tumor areas leading to predominant uptake of immuno-NPs by APCs. The immuno-NPs were effectively taken up by a significant portion of dendritic cells in the tumor (>56%). This led to a significant expansion of APCs, resulting in an 11.5-fold increase of dendritic cells and infiltration of lymphocytes throughout the pancreatic tumor compared to untreated animals.

[Comparison of surgical techniques for rotator cuff injury: cost-result]. / Comparación de técnicas quirúrgicas para la lesión del manguito de los rotadores: costo-resultado.

INTRODUCTION: Currently, to manage rotator cuff injury (RCI), there is a tendency to replace mini-open (MO) surgery with arthroscopy, but results and costs are controversial. OBJECTIVE: To analyze the cost-result of surgical techniques for RCI. MATERIAL AND METHODS: A partial economic evaluation of cost-result type was performed on 113 patients with RCI surgically operated by mini-open technique (n = 6), or arthroscopy (n = 91), or both (n = 16). Direct costs included: hospital stay, days of work disability, surgery, implants (anchors), medical assessments, laboratory and imaging. One-year shoulder functionality was evaluated with Constant-Murley scale (EscC-M). RESULTS: The MO technique was the most economical (X = $42,950.60 MXN) and the most expensive was the arthroscopy + MO with anchors (X = $89,594.80 MXN); with a non-significant difference in shoulder functionality (EscC-M = 56.33 ± 7.0 vs. 64.25 ± 9.0 points, respectively) (p 0.05; Kruskal-Wallis; post hoc Mann-Whitney). Difference of $46,644.1 MXN between techniques corresponded to 7.92 points. There was a mild relationship between the technique and the functionality of shoulder (rs = 0.26; p = 0.005; Spearman). CONCLUSION: The mini-open technique showed best cost-result, with similar functionality in shoulder to that obtained with the more expensive technique.

INTRODUCCIÓN: Actualmente, para manejar la ruptura del manguito de los rotadores (LMR), se prefiere la artroscopía sobre técnicas abiertas (mini-open [MO]), con resultados y costos controversiales. OBJETIVO: Analizar el costo-resultado de las técnicas quirúrgicas para la LMR. MATERIAL Y MÉTODOS: Se realizó una evaluación económica parcial de tipo costo-resultado a 113 pacientes con LMR intervenidos mediante técnica mini-open (n = 6) o artroscopía (n = 91) o ambas (n = 16). Los costos directos incluyeron: estancia, días de incapacidad laboral, cirugía, implantes (anclas), valoraciones médicas, laboratorio e imagen. Se evaluó la funcionalidad del hombro a un año mediante la escala de Constant-Murley (EscC-M). RESULTADOS: La técnica MO fue la más económica (X = $42,950.60 MXN) y la más costosa fue la artroscopía + MO con anclas (X = $89,594.80 MXN); con una diferencia no significativa en la funcionalidad del hombro (EscC-M = 56.33 ± 7 vs 64.25 ± 9 puntos, respectivamente) (p 0.05; Kruskal-Wallis; post hoc Mann-Whitney). Una diferencia de $46,644.10 MXN entre técnicas correspondió a 7.92 puntos. Hubo relación leve entre la técnica y la funcionalidad del hombro (rs = 0.26; p = 0.005; Spearman). CONCLUSIÓN: La técnica mini-open mostró mejor costo-resultado, con una ganancia en la funcionalidad de hombro similar a la que se obtiene con la técnica más costosa.

[Efficacy of viscosupplementation with high and medium molecular weight hyaluronic acid in patients with symptomatic gonarthrosis grades II-III]. / Eficacia de la viscosuplementación con ácido hialurónico de alto y de mediano peso molecular en pacientes con gonartrosis sintomática grados II-III.

INTRODUCTION: OA is currently the fifth leading cause of adult disability, its prevalence increases from age 40. Viscosupplementation is a treatment for the early stages of knee OA. OBJECTIVE: To compare efficacy and quality of life in patients with symptomatic gonartrosis, treated with high and low molecular weight hyaluronic acid. MATERIAL AND METHODS: Analytical, retrospective, cross-sectional, observational study of clinical records of patients diagnosed with grade II and grade III gonarthrosis, October 2017 to June 2018, treated with viscosupplementation with high molecular weight hyaluronic acid or low molecular weight; WOMAC quality of life and scale were analyzed prior to the first application and tracked at two, four and six months. RESULTS: 194 patients, aged between 30 to 87 years (promedio 61.85; SD = 11.3); 134 women (69.1%), 60 men (30.9%). In both groups the evolution was towards improvement, with a decrease in the WOMAC score, with no significant difference between groups. The WOMAC score had a minimum increase after 6 months of application in both groups, which is interpreted as decreasing the therapeutic effect. Two patients had localized minimal adverse reactions which were resolved with general measures. CONCLUSION: Hyaluronic acid in both presentations, high and low molecular weight, are effective in the treatment of symptomatic goonarthrosis without difference to molecular weight.

INTRODUCCIÓN: La osteoartrosis es actualmente la quinta causa de discapacidad en el adulto. Su prevalencia aumenta a partir de los 40 años. La viscosuplementación es un tratamiento para las etapas iniciales de la osteoartrosis de rodilla. OBJETIVO: Comparar la eficacia y la calidad de vida en pacientes con gonartrosis sintomática tratados con ácido hialurónico de alto y mediano peso molecular. MATERIAL Y MÉTODOS: Estudio analítico, retrospectivo, transversal, observacional de expedientes clínicos de pacientes con diagnóstico de gonartrosis grado II y grado III, de Octubre de 2017 a Junio de 2018, tratados con viscosuplementación con ácido hialurónico de alto o de mediano peso molecular; se analizó la calidad de vida y la escala de WOMAC de manera previa a la primera aplicación y con seguimiento a los dos, cuatro y seis meses. RESULTADOS: 194 pacientes, con edades entre 30 y 87 años (promedio 61.85; DE = 11.3); 134 mujeres (69.1%) y 60 hombres (30.9%). En ambos grupos la evolución fue hacia la mejoría, con disminución en el puntaje WOMAC, sin diferencia significativa entre grupos. El puntaje de WOMAC tuvo un aumento mínimo pasados seis meses de la aplicación en ambos grupos, lo que se interpreta como disminución del efecto terapéutico. Dos pacientes tuvieron reacciones adversas mínimas localizadas, las cuales se resolvieron con medidas generales. CONCLUSIÓN: El ácido hialurónico en ambas presentaciones, de alto y de bajo peso molecular, es efectivo en el tratamiento de la gonartrosis sintomática sin diferencia con el peso molecular.

Treatment of glioblastoma using multicomponent silica nanoparticles.

Glioblastomas (GBMs) remain highly lethal. This partially stems from the presence of brain tumor initiating cells (BTICs), a highly plastic cellular subpopulation that is resistant to current therapies. In addition to resistance, the blood-brain barrier limits the penetration of most drugs into GBMs. To effectively deliver a BTIC-specific inhibitor to brain tumors, we developed a multicomponent nanoparticle, termed Fe@MSN, which contains a mesoporous silica shell and an iron oxide core. Fibronectin-targeting ligands directed the nanoparticle to the near-perivascular areas of GBM. After Fe@MSN particles deposited in the tumor, an external low-power radiofrequency (RF) field triggered rapid drug release due to mechanical tumbling of the particle resulting in penetration of high amounts of drug across the blood-brain tumor interface and widespread drug delivery into the GBM. We loaded the nanoparticle with the drug 1400W, which is a potent inhibitor of the inducible nitric oxide synthase (iNOS). It has been shown that iNOS is preferentially expressed in BTICs and is required for their maintenance. Using the 1400W-loaded Fe@MSN and RF-triggered release, in vivo studies indicated that the treatment disrupted the BTIC population in hypoxic niches, suppressed tumor growth and significantly increased survival in BTIC-derived GBM xenografts.

Delivery of drugs into brain tumors using multicomponent silica nanoparticles.

Glioblastomas are highly lethal cancers defined by resistance to conventional therapies and rapid recurrence. While new brain tumor cell-specific drugs are continuously becoming available, efficient drug delivery to brain tumors remains a limiting factor. We developed a multicomponent nanoparticle, consisting of an iron oxide core and a mesoporous silica shell that can effectively deliver drugs across the blood-brain barrier into glioma cells. When exposed to alternating low-power radiofrequency (RF) fields, the nanoparticle's mechanical tumbling releases the entrapped drug molecules from the pores of the silica shell. After directing the nanoparticle to target the near-perivascular regions and altered endothelium of the brain tumor via fibronectin-targeting ligands, rapid drug release from the nanoparticles is triggered by RF facilitating wide distribution of drug delivery across the blood-brain tumor interface.

Precise targeting of cancer metastasis using multi-ligand nanoparticles incorporating four different ligands.

Metastasis displays a highly heterogeneous cellular population with cancer cells continuously evolving. As a result, a single-ligand nanoparticle cannot account for the continuously changing expression of targetable biomarkers over time and space. To effectively direct nanoparticles to metastasis, we developed a multi-ligand nanoparticle by using four different types of ligands on the same nanoparticle that target biomarkers on the endothelium associated with metastatic disease. These vascular targets included αvß3 integrin, P-selectin, EGFR and fibronectin. Using terminal and in vivo imaging studies, the targeting performance of the multi-ligand nanoparticles was compared to the single-ligand nanoparticle variants. All four single-ligand nanoparticle variants achieved significant targeting of lung metastasis in the 4T1 mouse model of breast cancer metastasis with about 2.5% of the injected dose being deposited into metastasis. A dual-ligand nanoparticle resulted in a nearly 2-fold higher deposition into lung metastases than its single-ligand counterparts. The multi-ligand nanoparticle significantly outperformed its targeting nanoparticle counterparts achieving a deposition of ∼7% of its injected nanoparticles into lung metastases. Using the high sensitivity of radionuclide imaging, PET imaging showed that a multi-ligand nanoparticle labeled with [18F]fluoride was able to precisely target metastatic disease at its very early stage of development in three different animal models of metastatic breast cancer.

One-pot synthesis of nanochain particles for targeting brain tumors.

To synthesize multi-component nanochains, we developed a simple 'one-pot' synthesis, which exhibited high yield and consistency. The nanochains particles consist of parent nanospheres chemically linked into a higher-order, chain-like assembly. The one-pot synthesis is based on the addition of two types of parent nanospheres in terms of their surface chemical functionality (e.g., decorated with PEG-NH2 or PEG-COOH). By reacting the two types of parent nanospheres at a specific ratio (∼2 : 1) for a short period of time (∼30 min) under rigorous stirring, nanochains were formed. For example, we show the synthesis of iron oxide nanochains with lengths of about 125 nm consisting of 3-5 constituting nanospheres. The chain-like shaped nanoparticle possessed a unique ability to target and rapidly deposit on the endothelium of glioma sites via vascular targeting. To target and image invasive brain tumors, we used iron oxide nanochains with the targeting ligand being the fibronectin-targeting peptide CREKA. Overexpression of fibronectin is strongly associated with the perivascular regions of glioblastoma multiforme and plays a critical role in migrating and invasive glioma cells. In mice with invasive glioma tumors, 3.7% of the injected CREKA-targeted nanochains was found in gliomas within 1 h. Notably, the intratumoral deposition of the nanochain was ∼2.6-fold higher than its spherical variant. Using MR imaging, the precise targeting of nanochains to gliomas provided images with the exact topology of the disease including their margin of infiltrating edges and distant invasive sites.

Utilization of byproducts from the tequila industry: part 1: agave bagasse as a raw material for animal feeding and fiberboard production.

Agave bagasse was successfully separated into fractions that were used in sheep feeding trials. Agave bagasse can be substituted for corn stubble in the sheep's diet which resulted in improved weight gain. Agave bagasse was also processed into long and short fiber fractions with a hammermill and fiberboards of medium and high specific gravities being produced. Medium specific gravity agave fiberboards had moisture and mechanical properties comparable to medium specific gravity fiberboards made using aspen fiber. All high specific gravity agave fiberboards made from short or long fibers were stronger in bending than the ANSI standard for hardboards.

Utilization of by-products from the tequila industry. Part 2: Potential value of Agave tequilana Weber azul leaves.

The leaves of the agave plant are left in the field after harvesting the heads for tequila production. Different types of agave leaves were isolated, classified, and their content in the total plant determined. The usable fractions were collected and their properties determined. Of the total wet weight of the agave plant, 54% corresponds to the agave head, 32% corresponds to materials which could be usable for sugar and fiber production which leaves 14% of the wet plant without apparent utility. The fractions with higher total reducing sugars (TRS) content were the fresh fraction of partially dry leaves stuck to the head and the leaf bases with a TRS content of 16.1% and 13.1%, respectively. The highest TRS concentration (16-28%) is in the agave head which is used for tequila production. The leaves are 90-120 cm long and 8-12 cm wide and contain fiber bundles that are 23-52 cm long and 0.6-13 mm wide. The ultimate fiber length is approximately 1.6 mm with an average width of 25 microns. There are several types of leaf fibers that can be utilized depending on what part of the plant they come from and what product is desired. Agave leaf fibers were pulped using a soda pulping process and the pulp was hand formed into test sheets. Test sheets made from pulped agave leaf fibers had a breaking length comparable to paper made from both pine and eucalyptus fibers, but the tear index and burst index were lower than the other two papers.

Eficacia de la viscosuplementación con ácido hialurónico de alto y de mediano peso molecular en pacientes con gonartrosis sintomática grados II-III / Efficacy of viscosupplementation with high and medium molecular weight hyaluronic acid in patients with symptomatic gonarthrosis grades II-III

Resumen: Introducción: La osteoartrosis es actualmente la quinta causa de discapacidad en el adulto. Su prevalencia aumenta a partir de los 40 años. La viscosuplementación es un tratamiento para las etapas iniciales de la osteoartrosis de rodilla. Objetivo: Comparar la eficacia y la calidad de vida en pacientes con gonartrosis sintomática tratados con ácido hialurónico de alto y mediano peso molecular. Material y métodos: Estudio analítico, retrospectivo, transversal, observacional de expedientes clínicos de pacientes con diagnóstico de gonartrosis grado II y grado III, de Octubre de 2017 a Junio de 2018, tratados con viscosuplementación con ácido hialurónico de alto o de mediano peso molecular; se analizó la calidad de vida y la escala de WOMAC de manera previa a la primera aplicación y con seguimiento a los dos, cuatro y seis meses. Resultados: 194 pacientes, con edades entre 30 y 87 años (promedio 61.85; DE = 11.3); 134 mujeres (69.1%) y 60 hombres (30.9%). En ambos grupos la evolución fue hacia la mejoría, con disminución en el puntaje WOMAC, sin diferencia significativa entre grupos. El puntaje de WOMAC tuvo un aumento mínimo pasados seis meses de la aplicación en ambos grupos, lo que se interpreta como disminución del efecto terapéutico. Dos pacientes tuvieron reacciones adversas mínimas localizadas, las cuales se resolvieron con medidas generales. Conclusión: El ácido hialurónico en ambas presentaciones, de alto y de bajo peso molecular, es efectivo en el tratamiento de la gonartrosis sintomática sin diferencia con el peso molecular.

Abstract: Introduction: OA is currently the fifth leading cause of adult disability, its prevalence increases from age 40. Viscosupplementation is a treatment for the early stages of knee OA. Objective: To compare efficacy and quality of life in patients with symptomatic gonartrosis, treated with high and low molecular weight hyaluronic acid. Material and methods: Analytical, retrospective, cross-sectional, observational study of clinical records of patients diagnosed with grade II and grade III gonarthrosis, October 2017 to June 2018, treated with viscosupplementation with high molecular weight hyaluronic acid or low molecular weight; WOMAC quality of life and scale were analyzed prior to the first application and tracked at two, four and six months. Results: 194 patients, aged between 30 to 87 years (promedio 61.85; SD = 11.3); 134 women (69.1%), 60 men (30.9%). In both groups the evolution was towards improvement, with a decrease in the WOMAC score, with no significant difference between groups. The WOMAC score had a minimum increase after 6 months of application in both groups, which is interpreted as decreasing the therapeutic effect. Two patients had localized minimal adverse reactions which were resolved with general measures. Conclusion: Hyaluronic acid in both presentations, high and low molecular weight, are effective in the treatment of symptomatic goonarthrosis without difference to molecular weight.

[Increased stability in osteosynthesis of osteoporotic distal humerus with standard implants]. / Aumento de la estabilidad en la osteosíntesis de húmero distal osteoporótico con implantes convencionales.

UNLABELLED: Surgery has proven to be the treatment of choice for distal humerus fractures if one wants to obtain the best results. However, this involves a high degree of complexity and therefore there are poor results. OBJECTIVE: Is it possible to improve the stability of osteosynthesis for osteoporotic distal humerus fractures using standard plates placed together using a screw 4.5 mm in diameter? MATERIAL AND METHODS: In an eight-month period a total of six female patients with distal humerus fractures underwent surgery at IMSS Trauma Emergencies Hospital. TECHNIQUE: A 1/3 tubular lateral plate was fixed to a reconstruction plate 3.5 mm medially using a 4.5 mm cortical screw going from lateral to medial. ASSESSMENT: The Mayo Scale was used to assess the elbow. RESULTS: Mean follow-up was 23.3 months; three right and three left elbows were operated; mean age of females was 78.83 years; three excellent, one good and two fair results were reported, and no poor results. CONCLUSIONS: It is possible to achieve adequate stability with standard implants; good results are obtained.

Evolution of late-life fecundity in Drosophila melanogaster.

Late-life fecundity has been shown to plateau at late ages in Drosophila analogously to late-life mortality rates. In this study, we test an evolutionary theory of late life based on the declining force of natural selection that can explain the occurrence of these late-life plateaus in Drosophila. We also examine the viability of eggs laid by late-age females and test a population genetic mechanism that may be involved in the evolution of late-life fecundity: antagonistic pleiotropy. Together these experiments demonstrate that (i) fecundity plateaus at late ages, (ii) plateaus evolve according to the age at which the force of natural selection acting on fecundity reaches zero, (iii) eggs laid by females in late life are viable and (iv) antagonistic pleiotropy is involved in the evolution of late-life fecundity. This study further supports the evolutionary theory of late life based on the age-specific force of natural selection.

Rapid assessment of drug consumption at Santa Cruz de la Sierra, Bolivia.

The present paper describes a rapid assessment carried out in 1996 at Santa Cruz de la Sierra, Bolivia, with a view to defining the sociocultural groups at risk and gaining insight, through the comments of those interviewed, into their perceptions of the phenomenon of drug abuse, their reasons for abusing drugs, the drugs most frequently abused and the psychological and social factors involved when they enter, remain in and finally leave drug-abusing circles. By using qualitative methodology and techniques it was possible to gain access to the typical world inhabited by the interviewees, and thus to characterize the subjects of the study in the light of their closest social reference points (family, peer group, education and work). Among the conclusions of the study are the following: drug abuse is a complex and dynamic phenomenon that has occurred throughout the society of Santa Cruz, fostered by cultural and economic factors; there is a need for society, and especially the Government, to devise a specific, focused and diversified range of services, both in prevention and in rehabilitation, with integration and participation being key features of such initiatives; and the mechanisms for controlling the production of drugs and drug trafficking need to be strengthened.

Abdominoplastia: selección de una técnica para la plastia del contorno abdominal / Abdominoplasty: selection of a technique for plasty of the abdominal contour

ES necesario seleccionar técnica apropiada para corregir el contorno abdominal, existen varias técnicas como abdominoplastia clásica, miniabdominoplastia, lipoaspiración, mini tipo abdominoplastia, etcétera. La selección de uno de estos métodos está condicionada a la presencia de ciertos elementos anatómicos del paciente que deben tomarse en consideración

Ingestión de pilas en niños: experiencia preliminar y sugerencias sobre su manejo / Battery ingestion in child: preliminary experience and suggestions on its management

Desde que Jackson en 1937 describieran el manejo de cuerpos extraños en la via aérea superior y esófago, han sido pocos los avances publicados en este aspecto; actualmente el vertiginoso avance tecnológico ha introducido numerosos aparatos electrónicos de uso doméstico que utilizan variedades de baterias (pilas) ya sea tipo botón o cilíndrica. Los niños son especialmente susceptibles a ingerirlas debido a curiosidad natural de esta etapa de la vida y el riesgo es mayor en niños que utilizan audífonos los que necesitan recambio frecuente de baterias y usan la boca como tercera mano en ese momento. El contacto de baterias con la mucosa digestiva rara vez produce intoxicación por metales o necesidad de cirugía, pero puede producir complicaciones serias como perforación, fístulas, estenosis e incluso la muerte. Las comunicaciones de estos accidentes son siempre menores a los de ocurrencia real, calculándose en Chile alrededor de 100 casos anuales con un 25 por ciento de aumento cada año. Debido a la escasa información que se dispone sobre el tema, describimos nuestra experiencia preliminar y recomendaciones respecto del manejo de esta eventualidad

Prescripción y venta de medicamentos importantes sin receta médica en algunas farmacias de la zona / Prescription and sale of important drugs without medical recipe in some drugstore at the zone

Durante Septiembre de 1991, se encuestó una muestra de 400 personas, elegidas aleatoriamente para sexo y edad, las cuales compraron algún medicamento en farmacias de la zona. De las personas encuestadas, sólo un 2 por ciento presentó su receta médica al momento de la compra. En caso de que el medicamento no fuera para el encuestado, los datos obtenidos corresponden al destinatario, como por ejemplo, en el grupo de menores de un año. La distribución de los destinatarios de los medicamentos, comprendió un 67 por ciento al sexo femenino y un 33 por ciento al masculino; en relación a la edad, predominó el grupo de 31-40 años y el de menores de un año, respectivamente. De los productos comprados, predominan los antiinflamatorios no esteroidales (AINE) 32 por ciento, como dipirona e ibuprofeno, seguido de los antibióticos 28 por ciento, como cotrimoxazol, penicilina y ampicilina. El rubro otros (aminofilina, clorpropamida, anovulatorios, etc.) ocupó un papel importante en la compra, con un 32 por ciento