Nanotechnology-Driven Cell-Based Therapies in Regenerative Medicine.

The administration of cells as therapeutic agents has emerged as a novel approach to complement the use of small molecule drugs and other biologics for the treatment of numerous conditions. Although the use of cells for structural and/or functional tissue repair and regeneration provides new avenues to address increasingly complex disease processes, it also faces numerous challenges related to efficacy, safety, and translational potential. Recent advances in nanotechnology-driven cell therapies have the potential to overcome many of these issues through precise modulation of cellular behavior. Here, we describe several approaches that illustrate the use of different nanotechnologies for the optimization of cell therapies and discuss some of the obstacles that need to be overcome to allow for the widespread implementation of nanotechnology-based cell therapies in regenerative medicine.

Sleeve gastrectomy for idiopathic acute gastric dilatation with transmural necrosis.

Acute gastric dilatation (AGD) is usually related to eating disorders, postoperative status and mechanical obstruction of the duodenum. When intragastric pressure is augmented, it can lead to alteration of blood flow and result in transmural necrosis. However, there are very few reports on idiopathic AGD and so here we describe the case of a 26-year-old woman diagnosed with AGD without any apparent cause. Conservative treatment was initially conducted, but because of the persistence of dilatation, presence of gastric ulcer and gastric pneumatosis, a surgical approach was necessary. During surgery, gastric necrosis was observed in the greater curvature. A sleeve gastrectomy was conducted from the angle of His to the antrum. No complications were present during the postoperative course. Oeso-gastro-duodenal barium study showed no signs of gastric emptying and psychiatric evaluation ruled out any eating disorder.

Non-viral reprogramming of human nucleus pulposus cells with FOXF1 via extracellular vesicle delivery: an in vitro and in vivo study.

Intervertebral disc (IVD) degeneration is characterized by decreased cellularity and proteoglycan synthesis and increased inflammation, catabolism, and neural/vascular ingrowth. Regenerative methods for IVD degeneration are largely cell-therapy-based or involve viral vectors, which are associated with mutagenesis and undesired immune responses. The present study used bulk electroporation and engineered extracellular vesicles (EVs) to deliver forkhead-box F1 (FOXF1) mRNA to degenerate human nucleus pulposus (NP) cells as a minimally invasive therapeutic strategy for IVD regeneration. Bulk electroporation was used to investigate FOXF1 effects on human NP cells during a 4-week culture in 3D agarose constructs. Engineered EV delivery of FOXF1 into human IVD cells in monolayer was determined, with subsequent in vivo validation in a pilot mouse IVD puncture model. FOXF1 transfection significantly altered gene expression by upregulating healthy NP markers [FOXF1, keratin 19 (KRT19)], decreasing inflammatory cytokines [interleukin (IL)-1ß, -6], catabolic enzymes [metalloproteinase 13 (MMP13)] and nerve growth factor (NGF), with significant increases in glycosaminoglycan accumulation in human NP cells. Engineered EVs loaded with FOXF1 demonstrated successful encapsulation of FOXF1 cargo and effective uptake by human NP cells cultured in monolayer. Injection of FOXF1-loaded EVs into the mouse IVD in vivo resulted in a significant upregulation of FOXF1 and Brachyury, compared to controls at 7 d post-injection, with no evidence of cytotoxicity. This is the first study to demonstrate non-viral delivery of FOXF1 and reprogramming of human NP cells in vitro and mouse IVD cells in vivo. This strategy represents a non-addictive approach for treating IVD degeneration and associated back pain.

[Analysis of the demand for detection of SARSCoV-2 in a health area of Spain]. / Análisis de la demanda de detección de SARS-CoV-2 en un área de salud de España.

OBJECTIVE: Since the discovery of the SARS-CoV-2 virus, the polymerase chain reaction technique (RT-PCR) has become the fundamental method for diagnosing the disease in its acute phase. The objective is to describe the demand-based series of RT-PCR determinations received at a Microbiology Service at a third-level reference hospital for a health area for three months spanning from the onset of the epidemic by SARS-CoV-2. METHODS: A retrospective analysis of the total of the RT-PCR requested in the Microbiology Service analyzed from 02/25/2020 to 05/26/2020 (90 days) has been carried out. They have been grouped by epidemiological weeks and by the petitioner service. A descriptive analysis was carried out by age, gender and number of requests for each patient. In the tests carried out, a confidence level of 95% (p <0.05) was considered significant. RESULTS: A total of 27,106 requests was received corresponding to 22,037 patients. Median age 53.7 (RIC 40.9-71.7) years, women: 61.3%. Proportion of patients with any positive RT-PCR: 14%. Of the total requests for RT-PCR, positive 3,710. Week 13 had the highest diagnosis performance (39.0%). The primary care has been the service thar has made the most requests (15,953). Patients with 3 or more RT-PCR: 565, of them, 19 patients had a positive result after previously having a negative one. CONCLUSIONS: Requests have been increasing depending on the evolution of the epidemic. The RT-PCR has a high diagnostic performance in the phases of highest contagiousness and / or transmissibility of the virus.

Diagnosis of Sarcopenia in Long-Term Care Homes for the Elderly: the Sensitivity and Specificity of Two Simplified Algorithms with Respect to the EWGSOP Consensus.

OBJECTIVE: To analyze the prevalence of sarcopenia in elderly care homes using the algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP) and to evaluate the applicability, sensitivity, and specificity of two simplified algorithms that do not include gait speed measurement. DESIGN: Cross-sectional study. SETTING: Long-term care homes. PARTICIPANTS: 249 residents (187 females and 62 males) with a mean age of 84.9 ± 6.7 years (range, 70-106 yrs). MEASUREMENTS: Cognitive impairment was evaluated with the Pfeiffer test, functional capacity with the Barthel index, walking ability by the Functional Ambulation Classification, muscle mass by bioelectrical impedance analysis, muscle strength by handgrip dynamometry and, gait speed over a distance of 4 m. Sarcopenia was assessed using the EWGSOP-recommended algorithm and two simplified algorithms (A and B). Algorithms A and B were validated with respect to the EWGSOP algorithm using the MacNemar test and obtaining the sensitivity and specificity, kappa coefficient, and area under the receiver operating characteristic curve (AUC). RESULTS: Total or severe dependence was recorded in 67% of the 249 residents, severe or moderate cognitive impairment in 64%, inability to walk in 49%, and capacity to walk only with the aid of an ambulator or two people in 21%. The prevalence of sarcopenia was 63.0% by the EWGSOP algorithm, 62.9% by algorithm A and 63.2% by algorithm B (P = 1.000); 143 participants were diagnosed with sarcopenia by all three methods (P =1.000, K = 1.000). CONCLUSION: Further studies that include residents with functional and/or cognitive impairment are required to validate these results, comparing the diagnostic performance of the EGWSOP algorithm with that of the simplified algorithms validated in the present report.

Flow of colloidal suspensions through small orifices.

In this work, we numerically study a dense colloidal suspension flowing through a small outlet driven by a pressure drop using lattice-Boltzmann methods. This system shows intermittent flow regimes that precede clogging events. Several pieces of evidence suggest that the temperature controls the dynamic state of the system when the driving force and the aperture size are fixed. When the temperature is low, the suspension's flow can be interrupted during long time periods, which can be even two orders of magnitude larger than the system's characteristic time (Stokes). We also find that strong thermal noise does not allow the formation of stable aggregate structures avoiding extreme clogging events, but, at the same time, it randomizes the particle trajectories and disturbs the advective particle flow through the aperture. Moreover, examining the particle velocity statistics, we obtain that in the plane normal to the pressure drop the colloids always move as free particles regardless of the temperature value. In the pressure drop direction, at high temperature the colloids experience a simple balance between advective and diffusive transport, but at low temperature the nature of the flow is much more complex, correlating with the occurrence of very long clogging events.

Relación entre la infección por el virus del papiloma humano y Chlamydia trachomatis / Relationship between human papillomavirus infection and Chlamydia trachomatis

La infección persistente por el virus del papiloma humano (VPH) es un requisito necesario pero no suficiente para el desarrollo del cáncer de cuello uterino (CCU), puesto que solo una baja proporción de las pacientes infectadas desarrolla una lesión intraepitelial cervical o un CCU. Esto hace pensar que son necesarios algunos cofactores que favorezcan dicha progresión. Según varios estudios, la infección por Chlamydia trachomatis (CT) es más prevalente en las pacientes con infección por VPH y parece que puede influir en la progresión de las lesiones epiteliales producidas por el VPH, relacionándose así de forma indirecta con el CCU. El cribado de la infección por CT y el correcto tratamiento de los casos permitiría evitar las consecuencias derivadas de la propia infección (salpingitis, EIP, esterilidad…) y la influencia que ejerce en el desarrollo del cáncer de cérvix

Human papillomavirus (HPV) infection is required but not sufficient to develop cervical cancer, since only a small proportion of HPV-infected women develop cervical intraepithelial lesions or cancer. This leads to the conclusion that other factors are required to facilitate disease progression. According to several studies, Chlamydia trachomatis (CT) infection is more prevalent in HPV-infected women and seems to contribute to the progression of HPV-related epithelial lesions. It is therefore indirectly related to cervical cancer. CT infection screening and the proper treatment of this condition could avoid the consequences of this genital infection (salpingitis, pelvic inflammatory disease, infertility, etc.) and its impact on developing cervical cancer

Complete laparoscopic excision of a giant retroperitoneal paraganglioma.

Paragangliomas (or 'extra-adrenal phaeochromocytomas') are rare tumours arising from neural crest cells. They occur most commonly in the abdomen along the paraspinal sympathetic ganglion. The malignancy rate can be up to 35% and surgical resection is the recommended treatment. While laparoscopic excision of phaeochromocytomas is now well established, the overall number of cases of paragangliomas reported is much smaller owing to their rarity (even more so for giant paragangliomas of ≥8cm) and controversy remains over the completeness of excision. Furthermore, the risk of malignancy and recurrence rate are higher in paragangliomas, with incomplete excision giving rise to recurrent endocrinopathy and carcinomatosis. We report the case of a 26-year-old woman who underwent laparoscopic excision of an 8.2cm functioning paraganglioma. Complete resection of the tumour was achieved and the patient's symptoms resolved. Twelve months later, she remains well with no evidence of recurrence.

Visualización por resonancia magnética del drenaje venoso en las masas pélvicas: una ayuda para filiar su origen / MRI visualization of venous drainage helps determine the origin of pelvic masses

Objetivo Evaluar la utilidad de la detección en la resonancia magnética (RM) de un pedículo vascular ovárico y de la presencia de vasos prominentes entre el útero y las tumoraciones de gran tamaño como signos para filiar el origen de las masas en el ovario o el útero, respectivamente. Material y métodos Se revisan los estudios de RM de 80 pacientes con masas pélvicas >7cm y confirmadas histológicamente. Se valoró la presencia de venas gonadales que drenaran las tumoraciones y la presencia de vasos interpuestos entre la superficie de la lesión y el útero. Resultados Se detectaron venas gonadales que drenaban las masas pélvicas en 36 de las 43 tumoraciones de origen ovárico (84%), mientras que en 30 de las 37 tumoraciones de origen uterino se demostraron vasos interpuestos entre ellas y el útero (81%). La sensibilidad, especificidad, valores predictivos positivo y negativo de los signos de presencia de vasos gonadales drenando la lesión fueron del 84, 95, 95 y 83% para masas ováricas, y del 81, 91, 88 y 85% para los vasos interpuestos entre el útero y la masa en los miomas subserosos, respectivamente. ConclusiónLa valoración del drenaje venoso de tumoraciones pélvicas resulta de gran utilidad cuando el origen de las tumoraciones no resulta fácil de establecer (AU)

Objective To evaluate the usefulness of detecting at MRI an ovarian vascular pedicle or prominent vessels between the uterus and large tumors for determining whether masses originate in the ovary or uterus. Material and methods We reviewed MRI studies from 80 patients with histologically confirmed pelvic masses greater than 7cm in diameter. We evaluated the presence of gonadal veins draining the tumors and the presence of vessels between the surface of the lesion and the uterus. ResultsWe detected gonadal veins draining the pelvic masses in 36 of the 43 tumors originating in the ovaries (84%); we detected vessels between the uterus and the pelvic mass in 30 of the 37 tumors that originated in the uterus (81%). The sensitivity, specificity, and positive and negative predictive values for the presence of gonadal veins draining the lesion were 84%, 95%, 95%, and 83%, respectively, for ovarian masses, and 81%, 91%, 88%, and 85%, respectively, for vessels between the uterus and the mass in subserous myomas. Conclusion Evaluating the venous drainage of pelvic tumors is very useful in cases in which it is not easy to establish the origin of the tumor (AU)

[MRI visualization of venous drainage helps determine the origin of pelvic masses.]. / Visualización por resonancia magnética del drenaje venoso en las masas pélvicas: una ayuda para filiar su origen.

OBJECTIVE: To evaluate the usefulness of detecting at MRI an ovarian vascular pedicle or prominent vessels between the uterus and large tumors for determining whether masses originate in the ovary or uterus. MATERIAL AND METHODS: We reviewed MRI studies from 80 patients with histologically confirmed pelvic masses greater than 7cm in diameter. We evaluated the presence of gonadal veins draining the tumors and the presence of vessels between the surface of the lesion and the uterus. RESULTS: We detected gonadal veins draining the pelvic masses in 36 of the 43 tumors originating in the ovaries (84%); we detected vessels between the uterus and the pelvic mass in 30 of the 37 tumors that originated in the uterus (81%). The sensitivity, specificity, and positive and negative predictive values for the presence of gonadal veins draining the lesion were 84%, 95%, 95%, and 83%, respectively, for ovarian masses, and 81%, 91%, 88%, and 85%, respectively, for vessels between the uterus and the mass in subserous myomas. CONCLUSION: Evaluating the venous drainage of pelvic tumors is very useful in cases in which it is not easy to establish the origin of the tumor.

Acalculous cholecystitis in a patient with Plasmodium falciparum infection after a trip to the Dominican Republic.

Acalculous cholecystitis has been associated with several infectious agents, but its relation with Plasmodium falciparum infection has not been clearly defined. This is the first case of acalculous cholecystitis produced by Plasmodium falciparum infection that is directly documented and should be included among the differential diagnoses of acalculous cholecystitis.

[Application of the motor unit number estimation (MUNE-Poisson) statistical technique in patients with neurogenic processes]. / Aplicación en pacientes con procesos neurogénicos de la técnica estadística de estimación del número de unidades motoras (MUNE-Poisson).

INTRODUCTION: Little research has been conducted on applying the statistical estimation of the number of motor units (the MUNE statistic) in the diagnosis of neurogenic processes. AIMS: To determine the sensitivity of this test in patients with different neurogenic processes and to disseminate and clarify its basic methodological aspects. SUBJECTS AND METHODS: Both the conventional calculation and the modified version of the MUNE-Poisson put forward by Shefner et al (MUNEm) were used to carry out unilateral studies of the extensor digitorum brevis muscle in 82 patients who had previously been clinically and electromyographically diagnosed with sensory-motor axonal polyneuropathy (36 cases), unilateral L5 radiculopathy (26 patients) and second motor neuron disease (20 cases). RESULTS: Overall sensitivity of the two methods was 81.7% and 82.9%, respectively, with no significant differences between them. Similarly, the sensitivity of the MUNE studies does not differ statistically according to the diagnosis. Patients who had a compound muscle action potential (CMAP) with a reduced amplitude displayed significantly higher sensitivity in MUNE studies (94.8%) than those who exhibited a normal CMAP (69.7%) (p < 0.001). CONCLUSIONS: Although routine use of the MUNE statistical method is unnecessary in daily practice, it should be considered for use in processes in which conventional muscle electromyography, especially involving distal ones, offers doubtful results or the aim is to follow the progression of certain neurogenic processes.

Aplicación en pacientes con procesos neurogénicos de la técnica estadística de estimación del número de unidades motoras (MUNE-Poisson) / Application of the motor unit number estimation (mune-poisson) statistical technique in patients with neurogenic processes

Introducción. Existe poca experiencia sobre la aplicación de la estimación estadística del número de unidades motoras (MUNE estadístico) en el diagnóstico de procesos neurogénicos. Objetivos. Determinar la sensibilidad de dicho test en pacientes con distintos procesos neurogénicos y difundir y aclarar los aspectos metodológicos fundamentales de aquél. Sujetos y métodos. Se ha estudiado mediante MUNE-Poisson, utilizando el calculo convencional y el modificado propuesto por Shefner et al (MUNEm), unilateralmente el músculo extensor digitorum brevis de 82 pacientes previamente diagnosticados clínica y electromiográficamente de polineuropatía axonal sensitivomotora (36 casos), radiculopatía L5 unilateral (26 pacientes) y enfermedad de la segunda motoneurona (20 casos). Resultados. La sensibilidad global de ambos métodos ha sido de 81,7 y 82,9%, respectivamente, sin diferencias significativas entre ellos. La sensibilidad de los estudios MUNE tampoco es estadísticamente diferente según el diagnóstico. Los pacientes que presentaron amplitud del potencial muscular compuesto (CMAP) reducida en amplitud mostraron significativamente mayor sensibilidad en los estudios MUNE (94,8%) que los que exhibieron un CMAP normal (69,7%) (p < 0,001). Conclusión. Aunque es innecesario utilizar rutinariamente en la práctica diaria el método MUNE estadístico, sí se debe considerar su empleo en procesos en los que la electromiografía convencional de músculos, sobre todo distales, presenta resultados dudosos, o se pretende seguir la evolución de ciertos procesos neurogénicos

Introduction. Little research has been conducted on applying the statistical estimation of the number of motor units (the MUNE statistic) in the diagnosis of neurogenic processes. Aims. To determine the sensitivity of this test in patients with different neurogenic processes and to disseminate and clarify its basic methodological aspects. Subjects and methods. Both the conventional calculation and the modified version of the MUNE-Poisson put forward by Shefner et al (MUNEm) were used to carry out unilateral studies of the extensor digitorum brevis muscle in 82 patients who had previously been clinically and electromyographically diagnosed with sensory-motor axonal polyneuropathy (36 cases), unilateral L5 radiculopathy (26 patients) and second motor neuron disease (20 cases). Results. Overall sensitivity of the two methods was 81.7% and 82.9%, respectively, with no significant differences between them. Similarly, the sensitivity of the MUNE studies does not differ statistically according to the diagnosis. Patients who had a compound muscle action potential (CMAP) with a reduced amplitude displayed significantly higher sensitivity in MUNE studies (94.8%) than those who exhibited a normal CMAP (69.7%) (p < 0.001). Conclusions. Although routine use of the MUNE statistical method is unnecessary in daily practice, it should be considered for use in processes in which conventional muscle electromyography, especially involving distal ones, offers doubtful results or the aim is to follow the progression of certain neurogenic processes

Evolución de la capacidad funcional en ancianos institucionalizados tras una intervención nutricional / Evolution of functional capacity in elderly before nutritional intervention

Este trabajo forma parte de un amplio estudio, realizado con el propósito de conocer la influencia del enriquecimiento en calcio de la dieta, a partir de la utilización de leche semidesnatada enriquecida en calcio, sobre la calidad de vida y el estado óseo de una población mayor institucionalizada, que participa en un programa de intervención nutricional de 18 meses de duración. El objetivo de este trabajo es conocer la evolución de la capacidad funcional, física y mental, de dicha población. Se estableció un grupo control, cuya ingesta media de calcio fue de 921ñ128 mg/día y un grupo problema con una dieta similar pero con un aporte mayor de calcio, 1.056ñ 256 mg/día, por la incorporación de leche enriquecida en este mineral. La capacidad física se evaluó mediante el Indice de Katz, que mide el grado de independencia para la realización de las actividades básicas de la vida diaria (ABVD). Para la valoración de la capacidad mental se utilizó la Escala de Cruz Roja. Al inicio del estudio, los resultados de la valoración de capacidad funcional, tanto física como mental, fueron bastante similares en los dos grupos. Tras la intervención nutricional, se observó que la pérdida de capacidad física fue significativamente menor en el grupo problema que en el control (P<0,05), ya que el 91,8 por ciento de los individuos del grupo problema no desciende de categoría, frente al 74,6 por ciento del control. La pérdida de capacidad mental ha sido considerable en ambos grupos, aunque sin diferencias significativas entre ellos. (AU)

Evolución de salud percibida durante una intervención nutricional en una población anciana institucionalizada / Health evolution perceived during a nutritional intervention in an elderly population institucionalized

El objetivo de este estudio es conocer la evolución de la autopercepción de salud de una población anciana institucionalizada, que participa en un programa de intervención nutricional de 18 meses de duración, cuya finalidad es estudiar la influencia del enriquecimiento en calcio de la dieta sobre el estado óseo de esta población. Se estableción un grupo control, cuya ingesta media de calcio fue de 921 +/- 128 mg/día, y un grupo problema con una dieta similar pero con un aporte mayor de calcio, 1056 +/- 256 mg/día, por la incorporación de leche enriquecida en este mineral. Las cuestines planteadas a los ancianos, al inicio y al final de la intervención, fueron: 1: ¿Se siente limitado en su movilidad? 2: ¿Considera su fuerza muscular normal para su edad?; 3: ¿Tiene dolores "de huesos"?. Los resultados obtenidos indican que la autopercepción de salud de la población anciana estudiada es independiente de la edad, y mejor en los hombres que en las mujeres. Tras la intervención mutricional, se observó que la salud percibida disminuyó menos en el grupo problema que en el control, por lo que al final del estudio, en el grupo problema la autopercepción de salud ósea era mejor que en el grupo control. No obstante, son necesarios estudios más amplios que permitan confirmar estos resultados (AU)

[Nutritional state of iron in the institutionalized aged: study of intake and hematological indices]. / Estado nutricional en hierro en ancianos institucionalizados: estudio de la ingesta e índices hematológicos.

In this study we determined the nutritional state of iron in 93 elderly people who were institutionalized in Granada, by means of a determination of their ingested iron, as well as the determination of the serum iron, hematologic parameters (hemoglobin and hematocrit), and the corpuscular indexes (mean corpuscular volume and mean corpuscular hemoglobin). The elderly people had an iron intake that was considered to be adequate (10.2 +/- 2.1 mg/day), and this is not related to the hematological parameters studied. 4% of the men, and 22% of the women showed hemoglobin values that were considered to be low.

Body composition in institutionalized elderly people in Granada (Spain). Relation with other nutritional parameters.

Anthropometric characteristics and body composition were assessed in a group of 93 institutionalized elderly people, mean age 80.9 +/- 7.6 years, in Granada (Spain). The body composition was measured by the bioelectrical impedance technique. The influence of dietary energy intake, lifestyle, physical activity and health data were studied. Forty-five per cent of the women and 17% of the men were obese (BMI > 30 kg/m2) and 78% of the women and 54% of the men were overweight (BMI > 25 kg/m2). Only 12% of men and 4% of women suffered from undernutrition (BMI < 20 kg/m2). No significant correlations (P > 0.05) were found between BMI or body fat percentage and energy intake. Lifestyle and health data do not affect the BMI or body composition, but a significant negative correlation (P < 0.05) was found between the physical handicap level and the energy intake in all the sample (r = -0.26) and in the women (r = -0.16).

Serum concentration and dietary intake of Zn in healthy institutionalized elderly subjects.

We determined the serum concentrations and dietary intake of zinc, as indicators of Zn status, in 44 healthy institutionalized elderly subjects in Granada (Spain) (mean age 81.4 +/- 7.9 years). Determination of Zn in serum was carried out by electrothermal atomic absorption spectrophotometry. Serum samples had a mean Zn concentration of 10.49 +/- 3.5 mumol/1. No significant differences were found in the serum levels of Zn as regards the sex of the subjects. However, concerning Zn intake, determined by a 7-day weighted food record, a significant statistical difference (P < 0.001) was found between men and women, with mean values of 10.01 +/- 1.76 mg/day and 7.33 +/- 1.33 mg/day, respectively. Application of regression analysis to the serum concentration of Zn and other nutritional parameters shows a statistically significant correlation (P < 0.05) between serum levels of Zn and the body mass index. The lack of statistical correlation between the serum concentration of zinc and its intake indicates that this index cannot be used as an indicator of zinc status in the elderly.