Cada vez son más graves los problemas derivados de la intoxicación, en todas sus formas. El alcohol, el tabaco y las drogas en general constituyen la fuente principal de este problema, que en algunos lugares del mundo alcanza las dimensiones de una epidemia. Pero además de los productos clásicos de intoxicación, es necesario agregar otras sustancias que, no por ser menos conocidas, necesariamente son inocuas. La generalización del consumo incontrolado y sin prescripción médica de psicofármacos y antibióticos, el nefasto uso de plaguicidas, la ingestión de alimentos aparentemente saludables y la mala administración de productos domésticos e industriales han agravado los perjuicios derivados de estas sustancias.

Abstract: Sexual reproduction depends on the transmission of exactly one copy of each chromosome by the maternal and paternal gametes. This is accomplished during meiosis when diploid progenitors undergo two consecutive rounds of chromosome segregation following a single round of DNA replication. In most organisms, this relies on the establishment of bivalent chromosomes consisting of replicated parental homologues physically linked at sites of meiotic recombination. In female mammals, bivalents are formed during fetal development when the lifetime stock of primordial-stage oocytes is established. However, they are not resolved until shortly before ovulation. Extending this period beyond ~35 years results in a dramatic increase in embryo aneuploidy. Depletion of the lifetime stock of oocytes during ageing culminates in menopause. Our previous studies indicate that Rec8-containing cohesin complexes also become depleted from oocyte chromosomes during female ageing. Consistent with cohesin’s role in maintaining chromosome structure, depletion of Rec8 is associated with destabilisation of bivalents chromosomes. Nevertheless, the mechanisms and timing of cohesin depletion remain unknown. Here, I investigated the possibility that age-related cohesion depletion is a consequence of leaky inhibition of the protease separase, which cleaves Rec8 during anaphase. I found that oocyte-specific deletion of separase did not prevent depletion of oocyte cohesin during female ageing. I, therefore, conclude that age-related depletion occurs by a separaseindependent mechanism. I next investigated the timing, during oogenesis, at which cohesin loss occurs. I found that cohesin is predominantly lost at the primordial stage before oocytes are recruited for growth. In addition, using an oocyte-specific deletion of Pten, I determined that this occurs independently of the decline in the ovarian stock of primordial-stage oocytes. Together, these results indicate that age-related cohesin depletion occurs at the primordial stage by a separase-independent mechanism. Other possible of mechanisms of cohesin depletion include protein damage and/or agerelated deterioration of chromatin structure. From a clinical perspective, my work suggests that “rejuvenation’ of fertility by activating the residual pool of primordial oocytes is unlikely to be successful in older women.

Abstract: Las lesiones cerebrales agudas (LCA) se asocian con altas tasas de mortalidad y malos resultados funcionales a largo plazo. La medición de biomarcadores del líquido cefalorraquídeo ventricular (vLCR) en pacientes con LCA puede ayudar a dilucidar algunas de las vías fisiopatológicas implicadas en el pronóstico de estos pacientes. Primero realizamos una búsqueda sistemática y una revisión descriptiva (Crit Care. 5 de agosto de 2021; 25 (1): 278; DOI: 10.1186/s13054-021-03698-z) donde concluimos que en pacientes con LCA, las concentraciones alteradas de biomarcadores proteicos en el vLCR relacionados con el daño citoesquelético, la inflamación, la apoptosis y el estrés oxidativo pueden predecir peores resultados neurológicos. Debido a estos resultados, realizamos un estudio de observación prospectivo (Neurocrit Care. 2022 Oct;37(2):463-470.doi:10.1007/s12028-022-01507-1.) donde concluimos que la expresión desregulada de la proteína en el vLCR diferenciaba entre LCA y no LCA. Luego realizamos otro estudio (J Neurosurg Anesthesiol. 27 de abril de 2023. doi:10.1097/ANA.0000000000000916.) donde concluimos que la expresión de patrones moleculares asociados al peligro (DAMP) específicos del vLCR se asociaba con un aumento de episodios de hipertensión intracraneal severa y muerte. Por último, en otro estudio observacional (Crit Care. 2023 Jun 24;27(1):249. doi: 10.1186/s13054-023-04538-y.), concluimos que las concentraciones de proteínas del vLCR después de una LCA eran un factor de riesgo para el desarrollo de enfermedades neurodegenerativas crónicas después de una LCA no traumática. Los hallazgos más importantes de esta tesis fueron que la respuesta proteómica después de una LCA es homogénea entre la LCA traumática y no traumática, involucra múltiples proteínas (DAMP) y puede estar asociada con enfermedades neurodegenerativas a largo plazo también en la LCA no traumática.

Background Retinopathy of prematurity is the major cause of blindness in children in Colombia. This cause of childhood blindness is irreversible when stablished, but 100% preventable with the adequate strategies put in place. This raises important questions concerning strategies to reduce the incidence of blindness as a result of ROP, which should ensure that all infants who are at risk of blinding ROP are examined in screening programmes. Aim The aim was to collect data in the neonatal intensive care units. This was used to evaluate the existing human and material resources for preventing, screening and treating ROP and rehabilitation of children suffering from ROP. The data helped to do an analysis of gaps in the service and allowed to present a proposal for a programme to prevent blindness due to ROP in the cities of Manizales, Pereira and Armenia, Colombia. Methods 7 NICUs were visited in the three cities. The study collected quantitative data on neonatal intensive care units, admission and survival of premature babies during 2010, human resources and infrastructure and data on knowledge of the Colombian guidelines on ROP. Results The survival rates vary according to the provider. They are higher in the private sector, and lower in the public sector. Overall, the available data allowed us to estimate that there are approximately 45,000 births per year (2010) in the region (95% occur in hospital) and 1.8% of all the births are less than 2,000g. Therefore, in the region, 810 babies per year weighing less than 2,000g are at risk of developing any type of ROP. The number of places, ventilators and monitors is sufficient. Staffing is adequate in the private NICUs, with a shortage of neonatologists in the public NICUs. The number of nurses monitoring babies is universally adequate, but the lack of knowledge in controlling risk factors of developing ROP such as monitoring oxygen in a constraint. An ROP screening programme is not available in public NICUs and in some of the mixed providers. The Kangaroo Mother programme lack of screening for ROP. Conclusions The unstable health system has allowed (i) unsustainable NICUs and programmes for ROP (ii) If available, programmes running without being monitored or evaluated, and, (iii) no screening in public and some mixed NICUs in Manizales, Pereira and Armenia. (iv) no screening for ROP in the Kangaroo Mother Programe As access and survival rates improve in the NICUS of these cities, ROP is likely to continue to be a significant cause of blindness in the region, despite the progress that has been achieved with the 2010 Colombian guidelines for screening and treating ROP. Recommendations The results suggest that the prevention of blinding ROP is a complex task in Colombia that requires concomitant strategies to be put in place: Firstly, national policies in screening for ROP and oxygen delivery for the babies in the NICUs are needed. Secondly, as a primary preventive strategy, training nurses in the NICUs to control and monitor the delivery of oxygen; as a secondary preventive strategy, ROP programmes offered to the public, mixed, private NICUs and to the Kangaro Mother Programme; as a tertiary strategy, rehabilitation providing a low vision centre for these children Thirdly, running ROP programmes need to be monitored and evaluated.

While working with prison systems, work release programs, mental hospitals, and alternative settings in the public schools, it has become clear to this author that the almost universally accepted idea of rehabilitating criminal offenders is basically false, a myth. The author argues that we need to stop wasting time and money on current forms of rehabilitating criminals and adopt less-traditional methods.

Abstract: OBJECTIVE: To study the severity of symptoms and estimate the prevalence of oral mucosal lesions in a non-referral adult Swedish population, as registered by general dental practitioners. This study also aims to evaluate the possibility of dental practitioners collecting large quantities of reliable and accurate clinical data on oral mucosal lesions. STUDY DESIGN: Data from 6,448 adult Swedish patients were collected by general dental practitioners using a standardized registration method. A correlation analysis between a group with oral mucosal lesions and a control group, with no oral mucosal lesions, was performed for various parameters such as symptoms from the oral mucosa, systemic diseases, medication, allergy history, tobacco habits and the patient's own assessment of their general health. In addition, clinical photos were taken of all oral mucosal lesions in order to determine the degree of agreement between the diagnoses made by general dental practitioners and those made by oral medicine specialists. RESULTS: A total of 950 patients (14.7%) presented with some type of oral mucosal lesion and of these, 141 patients (14.8%) reported subjective symptoms. On a visual analogue scale, 43 patients (4.5%) scored their symptoms <30, 65 patients (6.8%) scored their symptoms ?30, and 28 patients (2.6%) scored their symptoms ?60. The most debilitating condition was aphthous stomatitis and the most common oral mucosal lesion was snuff dipper's lesion (4.8%), followed by lichenoid lesions (2.4%) and geographic tongue (2.2%). There was agreement between the oral medicine specialists and the general practitioners over the diagnosis of oral mucosal lesions on the basis of a clinical photograph in 85% of the cases (n=803). CONCLUSIONS: Nearly 15% of the patients with oral mucosal lesions reported symptoms. General practitioners could contribute significantly to the collection of large quantities of reliable and accurate clinical data, although there is a risk that the prevalence of oral mucosal lesions may be underestimated." Resumen: OBJETIVO: Estudiar la severidad de los síntomas y estimar la prevalencia de lesiones de la mucosa oral en una población de Suecia no referida, y registrada por odontólogos generales. Este estudio también tiene como objetivo evaluar la posibilidad de que odontólogos generales recolecten de forma confiable y precisa grandes cantidades de datos clínicos sobre lesiones de la mucosa oral. DISEÑO DEL ESTUDIO: Datos de 6.448 pacientes adultos suecos fueron recolectados por odontólogos generales usando un método estandarizado de registro. Un análisis de correlación entre un grupo de pacientes con lesiones de la mucosa oral y un grupo control, sin lesiones de la mucosa oral, fue realizado para varios parámetros como síntomas en la mucosa oral, enfermedades sistémicas, medicamentos, alergias, tabaquismo, y la percepción del propio paciente sobre su estado de salud. Además, se tomaron fotos clínicas de todas las lesiones de la mucosa oral con el fin de determinar el grado de concordancia entre los diagnósticos realizados por los odontólogos generales y los especialistas en medicina oral. RESULTADOS: Un total de 950 pacientes (14.7%) presentó algún tipo de lesión de la mucosa oral, y de estos, 141 pacientes (14.8%) reportaron síntomas subjetivos. En una escala analógica visual, 43 pacientes (4.5%) calificaron sus síntomas <30, 65 pacientes (6.8%) calificaron sus síntomas ≥30, y 28 pacientes (2.6%) calificaron sus síntomas ≥60. La condición más debilitante fue la stomatitis aftosa y la lesión más común fue la lesión causada por el tabaco húmedo (4.8%), seguida por reacciones liquenoides (2.4%) y lengua geográfica (2.2%). Basado en las fotografías clínicas, hubo una concordancia en el diagnóstico de lesiones de la mucosa oral entre los especialistas en medicina oral y los odontólogos generales en el 85% de los casos (n=803). CONCLUSION: Aproximadamente el 15% de los pacientes con lesiones de la mucosa oral reportaron síntomas. Los odontólogos generales pueden contribuir significativamente en la recolección confiable y precisa de grandes cantidades de datos clínicos, aunque existe un riego de que la prevalencia de lesiones de la mucosa oral pueda ser subestimada."

Through the financial support from the Open Society Foundations, Dejusticia developed a diagnostic research from eight countries, Argentina, Chile, Colombia, Costa Rica, El Salvador, Guatemala, Panama and Uruguay, regarding the access to palliative care, the institutional development and the guidelines, and the existing barriers of access to opioid medications – used for pain relief. This document is aimed at medical personnel, civil society organizations, policy makers, and any¬one interested in addressing the issue of palliative care from a human rights perspective. Although for years palliative care was confined to a strictly medical analysis, in recent times the international community and United Nations bodies have recognized palliative care as a human rights issue. This document seeks to demonstrate the many linkages between palliative care and human rights in terms of both the conception and the protection of palliative care. We hope this report serves as a useful tool for the medical community, patients, and patients’ fam¬ilies throughout the American continent who seek legal and human rights arguments to facilitate access to more humane end-of-life care, as well as for litigants and human rights activists who wish to protect and guarantee a life without pain for patients, including during their last days of life. Description taken from the introduction Consulte la versión en español en la siguiente URL:

OBJECTIVE: Conditional cash transfer (CCT) programmes provide income to low-income families in return for fulfilling specific behavioural conditions. CCT have been shown to improve child health, but there are few systematic studies of their impact on multiple determinants of child health. We examined the impact of a CCT programme in Colombia on: (i) use of preventive health services; (ii) food consumption and dietary diversity; (iii) mother's knowledge, attitudes and practices about caregiving practices; (iv) maternal employment; and (v) women's empowerment. DESIGN: Secondary analysis of the quasi-experimental evaluation of the Familias en Accion programme. Children and families were assessed in 2002, 2003 and 2005-06. We applied a difference-in-differences approach using logistic or linear regression, separately examining effects for urban and rural areas. SETTING: Colombia. SUBJECTS: Children (n 1450) and their families in thirty-one treatment municipalities were compared with children (n 1851) from sixty-five matched control municipalities. RESULTS: Familias en Accion was associated with a significant increase in the probability of using preventive care services (OR=1·85, 95 % CI 1·03, 3·30) and growth and development check-ups (?=1·36, 95 % CI 0·76, 1·95). It had also a positive impact on dietary diversity and food consumption. No effect was observed on maternal employment, women's empowerment, and knowledge, attitudes and practices about caregiving practices. Overall, Familias en Accion's impact was more marked in rural areas. CONCLUSION: CCT in Colombia increase contact with preventive care services and improve dietary diversity, but they are less effective in influencing mother's employment decisions, empowerment and knowledge of caregiving practices.

Abstract: Antibiotic resistance is driven by selection, but the degree to which a bacterial strain’s evolutionary history shapes the mechanism and strength of resistance remains an open question. Here, we reconstruct the genetic and evolutionary mechanisms of carbapenem resistance in a clinical isolate of Klebsiella quasipneumoniae. A combination of short- and long-read sequencing, machine learning, and genetic and enzymatic analyses established that this carbapenem-resistant strain carries no carbapenemase-encoding genes. Genetic reconstruction of the resistance phenotype confirmed that two distinct genetic loci are necessary in order for the strain to acquire carbapenem resistance. Experimental evolution of the carbapenem-resistant strains in growth conditions without the antibiotic revealed that both loci confer a significant cost and are readily lost by de novo mutations resulting in the rapid evolution of a carbapenem-sensitive phenotype. To explain how carbapenem resistance evolves via multiple, low-fitness single-locus intermediates, we hypothesised that one of these loci had previously conferred adaptation to another antibiotic. Fitness assays in a range of drug concentrations show how selection in the antibiotic ceftazidime can select for one gene (blaDHA-1) potentiating the evolution of carbapenem resistance by a single mutation in a second gene (ompK36). These results show how a patient’s treatment history might shape the evolution of antibiotic resistance and could explain the genetic basis of carbapenem-resistance found in many enteric-pathogens.

Bibliografía: páginas 38-40