Revisión sistemática de la literatura de las intervenciones diseñadas para el comportamiento de automedicación no responsable

La automedicación no responsable se ha convertido en un problema de salud pública global en las últimas décadas, por sus consecuencias individuales (por ejemplo, la intoxicación) y colectivas (por ejemplo, la resistencia microbiana a los antibióticos). Las intervenciones orientadas a este comportamiento han sido aisladas y muy diferentes. Aunque se tiene evidencia de que su aplicación puede traer beneficios en diferentes poblaciones, no se halló en la literatura una compilación sistemática de dichas intervenciones. El objetivo de la presente revisión es sistematizar la literatura científica sobre las diferentes alternativas de intervención del comportamiento individual de automedicación no responsable. En cuanto al método, la revisión de literatura involucró la búsqueda sistemática de “automedicación” e “intervención” en las bases de datos académicas internacionales con contenidos de psicología, suscritas por la Biblioteca de la Universidad del Rosario. Como resultado se encontró que las intervenciones orientadas al comportamiento de automedicación no responsable se pueden clasificar en dos grandes grupos: (a) intervenciones regulatorias, con dirección “arriba hacia abajo”, que suponen una acción de los Estados nacionales por medio de sus legislaciones o de entidades internacionales (por ejemplo, Organización Mundial de la Salud); y (b) intervenciones educativas, con dirección “abajo hacia arriba”, que suponen acciones con individuos y comunidades con el fin de enseñar acerca del uso adecuado de los medicamentos. Se concluye acerca de la necesidad de complementar ambos tipos de intervención, los cuales, si bien demuestran resultados positivos, aisladamente son insuficientes para contrarrestar integralmente este fenómeno creciente y complejo.

Incidencia de síndrome de abstinencia secundario a opioides y/o benzodiacepinas en dos unidades de cuidados intensivos pediátricos

• Introducción: El síndrome de abstinencia (SA) es el conjunto de síntomas y signos que se producen al suspender bruscamente la administración de un fármaco una vez se haya establecido dependencia física. • Objetivos: Caracterizar los pacientes que presentan SA secundario a opiodes (OP) y/o benzodiacepinas(BZ) durante la hospitalización en las unidades de cuidados intensivos pediátricos de la Clínica Infantil Colsubsidio (CIC) y Hospital del Niño de Panamá (HDN) del 1 de abril al 30 de septiembre del 2016. • Materiales y métodos: se realizó un estudio descriptivo, longitudinal, prospectivo. Incluimos 189 pacientes en la CIC y 144 pacientes en el HDN. Se utilizó la escala SOPHIA para el diagnóstico de SA, las escalas COMFORT para evaluar la sedación en pacientes ventilados no relajados y la escala FLACC para evaluar la analgesia. Se utilizó software StataV12® para el análisis estadístico. • Resultados: se reportó una incidencia global de SA de 6.1/100 días personas. La incidencia acumulada de SA fue de 56.08% y 29.86% para la CIC y el HDN respectivamente. En la CIC el 69.81% de los pacientes que requirieron infusión de OP y BZ desarrollaron SA. Se reportó una dosis acumulada de fentanyl de 530.34 ± 276.49 mcg/kg. Con respecto al HDN, de los pacientes que recibieron opioides y benzodiacepinas el 53.49 % desarrollaron SA. • Conclusión: El SA secundario a opioides y/o benzodiacepinas es frecuente en nuestras unidades con una incidencia variable, es mayor la presentación del SA al usar ambos fármacos, mayores dosis acumuladas y más días de infusión continua.

The use of expandable megaprostheses for reconstruction of the distal femur in pediatric patients after bone tumor resection

Expandable prostheses are becoming increasingly popular in the reconstruction of children with bone sarcomas of the lower limb. Since the introduction of effective chemotherapy in the treatment of these pathologies, in the 70s, there has been need for new limb salvage techniques. In children, limb salvage of the lower limbs is particularly challenging, not in the last place, because of the loss of growth potential. Therefore, expandable prostheses have been developed. However, the first experiences with these implants were not very successful. High complication rates and unpredictable outcomes raised major concerns on this innovative type of reconstruction. The rarity of the indication is one of the main reasons why there has been a relatively slow learning curve and implant development regarding this type of prosthesis. This PhD thesis, gives an overview of the introduction, the development, the current standards, and the future perspectives of expandable prostheses for the reconstruction of the distal femur in children.

Proton radiotherapy: a therapeutic opportunity for pediatric brain tumor patients

Proton radiation therapy is a form of external radiation that uses charged particles which have distinct physical advantages to deliver the majority of its dose in the target while minimizing the dose of radiation to normal tissues. In children who are particularly susceptible even at low and medium doses of radiation, the significant reduction of integral dose can potentially mitigate the incidence of side effects and improve quality of life. The aim of the first part of the thesis is to describe the physical and radiobiological properties of protons, the Proton Therapy Center of Trento (TCPT) active for clinical purpose since 2014, which use the most recent technique called active pencil beam scanning. The second part of the thesis describes the preliminary clinical results of 23 pediatric patients with central nervous system tumors as well as of two aggressive pediatric meningiomas treated with pencil beam scanning. All the patients were particularly well-suited candidates for proton therapy (PT) for possible benefits in terms of survival and incidence of acute and late side effects. We reported also a multicentric experience of 27 medulloblastoma patients (median age 6 years, M/F ratio 13/14) treated between 2015 and 2020 at TPTC coming from three Pediatric oncology centers: Bologna, Florence, and Ljubljana, with a focus on clinical results and toxicities related to radiotherapy (RT). Proton therapy was associated with mostly mild acute and late adverse effects and no cases of CNS necrosis or high grade of neuroradiological abnormailities. Comparable rates of survival and local control were obtained to those achievable with conventional RT. Finally, we performed a systematic review to specifically address the safety of PT for pediatric CNS patients, late side effects and clinical effectiveness after PT in this patient group.

Phyto-pharmacology of Elettaria cardamomum

Spices are known to add taste, flavor, aroma, color to food. These spices also have been the many traditional medicines in India and elsewhere to provide treatment to various diseases. Elettaria cardamomum is one of the spices used in traditional medicines for several diseases. It is used in treating various gastrointestinal, cardiovascular and neuronal disorders. The inhibitory activity of cardamom extract was studied on human platelets has also been reported. This review aims to highlight the ethno botany, pharmacognostic and pharmacological uses of Elettaria cardamomum. This review will also highlight the patenting trends and the new compositions developed using the actives from Elettaria cardamomum.

Nuclear shape instability caused by lamin A deregulation promotes invasiveness in pediatric bone sarcomas: from nucleo-cytoskeleton dynamics to novel therapeutic opportunities

Osteosarcoma (OS) and Ewing sarcoma (EWS) are the two most frequent primary bone tumors, in which metastases remain the most relevant adverse prognostic factor. Lamin A is the main constituent of the nuclear lamina, with a fundamental role in maintaining the connection between nucleus and cytoskeleton (through LINC complex proteins interactions), and its alterations can be implicated in tumor progression. We investigated how nucleo-cytoskeleton dynamics is influenced by lamin A modulation in OS and EWS, demonstrating that both these cancer models had low levels of lamin A, which are linked to a significantly more marked nuclear misshaping. In our in vitro studies, reduced levels of lamin A promoted migratory abilities in these tumors. Moreover, these findings were corroborated by gene expression analyses on EWS patient samples, showing that LMNA levels were significantly lower in metastatic lesions compared to primary tumors and that patients with low LMNA had a significant worse overall survival. We also found that LMNA expression significantly impaired EWS metastases formation in vivo. We demonstrated that low lamin A expression was linked to a severe mislocalization of LINC complex proteins, thus disrupting nucleo-cytoskeleton interactions, with a corresponding gain in malignant properties, which resulted in increased invasiveness. Lamin A overexpression or its accumulation by a statin-based pharmacological treatment allowed us to reconstitute a functional nucleo-cytoskeleton interplay, which resulted in significant downmodulation of ROCK2 and YAP, two crucial drivers of EWS aggressiveness. Our study demonstrated that lamin A is a favorable mediator of nuclear shape stability in bone sarcomas, and its modulation rescues LINC complex protein localization and regulates mechano-signaling pathways, thus promoting a less aggressive cancer phenotype. We also identified statins, already employed in clinical practice, as a tool capable to increase lamin A levels, and to reconstitute functional nucleo-cytoskeletal dynamics, resulting in reduced cellular migration.

Pedagogy of healthcare interactions. A study on pediatric well-child visits as culture-oriented and culture-making sites

This study investigates interactions between parents and pediatricians during pediatric well-child visits. Despite constituting a pivotal moment for monitoring and evaluating children’s development during the critical ‘first thousand days of life’ and for family support, no study has so far empirically investigated the in vivo realization of pediatrician-parent interactions in the Italian context, especially not from a pedagogical perspective. Filling this gap, the present study draws on a corpus of 23 videorecorded well-child visits involving two pediatricians and twenty-two families with children aged between 0 and 18 months. Combining an ethnographic perspective and conversation analysis theoretical-analytical constructs, the micro-analysis of interactions reveals how well-child visits unfold as culture-oriented and culture-making sites. By zooming into what actually happens during these visits, the analysis shows that there is much more than the “mere” accomplishment of institutionally relevant activities like assessing children’s health or giving parents advice on baby care. Rather, through the interactional ways these institutional tasks are carried out, parents and pediatricians presuppose, ratify, and transmit culturally-informed models of “normal” growth, “healthy” development, “good” caring practices, and “competent” parenting, thereby enacting a pervasive yet unnoticed educational and moral work. Inaugurating a new promising line of inquiry within Italian pedagogical research, this study illuminates how a) pediatricians work as a “social antenna”, bridging families’ private “small cultures” and broader socio-cultural models of children’s well-being and caregiving practices, and b) parents act as agentive, knowledgeable, (communicatively) competent, and caring parents, while also sensitive to the pediatrician’s ultimate epistemic and deontic authority. I argue that a video-based, micro-analysis of interactions represents a heuristically powerful instrument for raising pediatricians’ and parents’ awareness of the educational and moral density of well-child visits. Insights from this study can constitute a valuable empirical resource for underpinning medical and parental training programs aimed at fostering pediatricians’ and parents’ reflexivity.

Modeling of clear cell sarcoma of the kidney of the pediatric age

Clear cell sarcoma of the kidney (CCSK) is the second most common pediatric renal tumor, characterized in 90% of cases by the presence of internal tandem duplications (ITDs) localized at the last exon of BCOR gene. BCOR protein constitute a core component of the non-canonical Polycomb Repressive Complex1 (PRC1.1), which performs a fundamental silencing activity. ITDs in the last BCOR exon at the level of PUFD domain have been identified in many tumor subtypes and could affect PCGF1 binding and the subsequent PRC1.1 activity, although the exact oncogenic mechanism of ITD remains poorly understood. This project has the objective of investigating the molecular mechanisms underlying the oncogenesis of CCSK, approaching the study with different methodologies. A first model in HEK-293 allowed to obtain important informations about BCOR functionality, suggesting that the presence of ITD generates an altered activity which is very different from a loss-of-function. It has also been observed that BCOR function within the PRC1.1 complex varies with different ITDs. Moreover, it allowed the identification of molecular signatures evoked by the presence of BCOR-ITD, including its role in extracellular matrix interactions and invasiveness promotion. The parallel analysis of WTS data from 8 CCSK cases permitted the identification of a peculiar signature for metastatic CCSKs, highlighting a 20-fold overexpression of FGF3. This factor promoted a significant increase in invasive ability in the cellular model. In order to study BCOR-ITD effects over cell stemness and differentiation, an inducible model is being obtained in H1 cells. This way, it will be possible to study the functionality of BCOR-ITD in a context more similar to the origin of CCSKs, evaluating both the specific interactome and phenotypic consequences caused by the mutation.

Framing climate change: a planetary health perspective on the pediatric age

This thesis analyzes an analysis of the risk perception of Italian paediatricians and parents regarding the impact of climate change on pediatric health. The consequences of climate change are now before our eyes; the recent pandemic has highlighted the impact that the destruction of ecosystems and global warming can have on our health. Fragile subjects will pay the most for the consequences of this crisis: children, the elderly, pregnant women. According to the World Health Organization (WHO), 88% of the disease burden linked to climate change falls on children under the age of 5. Climate change poses a challenge of equity not only between different areas of the world but also between generations: the worst consequences will weigh on those who have not caused damage to the ecosystem. This study began by studying the risk perceptions of the two main caregivers who deal with the child's health: parents and paediatricians. The study analyzed a mixed methods approach, exploiting quantitative and qualitative approaches. Two surveys were carried out in collaboration with the Italian Society of Pediatrics (SIP) and AGE, the Italian Parents' Association, using a tool already consolidated in the literature and adapted according to the needs of the thesis. Sixty semi-structured interviews were then conducted with pediatricians of different age groups and different regions of Italy. The collected data were then compared with the literature on the subject, in order to understand differences and similarities. This work is part of a still rather scarce, but growing, field of literature and represents the first study of this type in Italy.

Hemorrhagic Shock Secondary To Button Battery Ingestion.

Button battery ingestion is a frequent pediatric complaint. The serious complications resulting from accidental ingestion have increased significantly over the last two decades due to easy access to gadgets and electronic toys. Over recent years, the increasing use of lithium batteries of diameter 20 mm has brought new challenges, because these are more detrimental to the mucosa, compared with other types, with high morbidity and mortality. The clinical complaints, which are often nonspecific, may lead to delayed diagnosis, thereby increasing the risk of severe complications. A five-year-old boy who had been complaining of abdominal pain for ten days, was brought to the emergency service with a clinical condition of hematemesis that started two hours earlier. On admission, he presented pallor, tachycardia and hypotension. A plain abdominal x-ray produced an image suggestive of a button battery. Digestive endoscopy showed a deep ulcerated lesion in the esophagus without active bleeding. After this procedure, the patient presented profuse hematemesis and severe hypotension, followed by cardiorespiratory arrest, which was reversed. He then underwent emergency exploratory laparotomy and presented a new episode of cardiorespiratory arrest, which he did not survive. The battery was removed through rectal exploration. This case describes a fatal evolution of button battery ingestion with late diagnosis and severe associated injury of the digestive mucosa. A high level of clinical suspicion is essential for preventing this evolution. Preventive strategies are required, as well as health education, with warnings to parents, caregivers and healthcare professionals.

Blockade Of Renin-angiotensin System Prevents Micturition Dysfunction In Renovascular Hypertensive Rats.

Association between hypertension and bladder symptoms has been described. We hypothesized that micturition dysfunction may be associated with renin-angiotensin system (RAS) acting in urethra. The effects of the anti-hypertensive drugs losartan (AT1 antagonist) and captopril (angiotensin-converting enzyme inhibitor) in comparison with atenolol (β1-adrenoceptor antagonist independently of RAS blockade) have been investigated in bladder and urethral dysfunctions during renovascular hypertension in rats. Two kidney-1 clip (2K-1C) rats were treated with losartan (30 mg/kg/day), captopril (50mg/kg/day) or atenolol (90 mg/kg/day) for eight weeks. Cystometric study, bladder and urethra smooth muscle reactivities, measurement of cAMP levels and p38 MAPK phosphorylation in urinary tract were determined. Losartan and captopril markedly reduced blood pressure in 2K-1C rats. The increases in non-voiding contractions, voiding frequency and bladder capacity in 2K-1C rats were prevented by treatments with both drugs. Likewise, losartan and captopril prevented the enhanced bladder contractions to electrical-field stimulation (EFS) and carbachol, along with the impaired relaxations to β-adrenergic-cAMP stimulation. Enhanced neurogenic contractions and impaired nitrergic relaxations were observed in urethra from 2K-1C rats. Angiotensin II also produced greater urethral contractions that were accompanied by higher phosphorylation of p38 MAPK in urethral tissues of 2K-1C rats. Losartan and captopril normalized the urethral dysfunctions in 2K-1C rats. In contrast, atenolol treatment largely reduced the blood pressure in 2K-1C rats but failed to affect the urinary tract smooth muscle dysfunction. The urinary tract smooth muscle dysfunction in 2K-1C rats takes place by local RAS activation irrespective of levels of arterial blood pressure.

15-deoxy-Δ12,14-prostaglandin J2 Reduces Albumin-induced Arthritis In Temporomandibular Joint Of Rats.

The aim of this study was to evaluate the peripheral effect of 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) in albumin-induced arthritis in temporomandibular joint (TMJ) of rats. Antigen-induced arthritis (AIA) was generated in rats with methylated bovine serum albumin (mBSA) diluted in complete Freund׳s adjuvant. Pretreatment with an intra-articular injection of 15d-PGJ2 (100 ng/TMJ) before mBSA intra-articular injection (10 µg/TMJ) (challenge) in immunized rats significantly reduced the albumin-induced arthritis inflammation. The results demonstrated that 15d-PGJ2 was able to inhibit plasma extravasation, leukocyte migration and the release of inflammatory cytokines IL-6, IL-12, IL-18 and the chemokine CINC-1 in the TMJ tissues. In addition, 15d-PGJ2 was able to increase the expression of the anti-adhesive molecule CD55 and the anti-inflammatory cytokine IL-10. Taken together, it is possible to suggest that 15d-PGJ2 inhibit leukocyte infiltration and subsequently inflammatory process, through a shift in the balance of the pro- and anti-adhesive properties. Thus, 15d-PGJ2 might be used as a potential anti-inflammatory drug to treat arthritis-induced inflammation of the temporomandibular joint.

Effect Of Exercise Test On Pulmonary Function Of Obese Adolescents.

to investigate the pulmonary response to exercise of non-morbidly obese adolescents, considering the gender. a prospective cross-sectional study was conducted with 92 adolescents (47 obese and 45 eutrophic), divided in four groups according to obesity and gender. Anthropometric parameters, pulmonary function (spirometry and oxygen saturation [SatO2]), heart rate (HR), blood pressure (BP), respiratory rate (RR), and respiratory muscle strength were measured. Pulmonary function parameters were measured before, during, and after the exercise test. BP and HR were higher in obese individuals during the exercise test (p = 0.0001). SatO2 values decreased during exercise in obese adolescents (p = 0.0001). Obese males had higher levels of maximum inspiratory and expiratory pressures (p = 0.0002) when compared to obese and eutrophic females. Obese males showed lower values of maximum voluntary ventilation, forced vital capacity, and forced expiratory volume in the first second when compared to eutrophic males, before and after exercise (p = 0.0005). Obese females had greater inspiratory capacity compared to eutrophic females (p = 0.0001). Expiratory reserve volume was lower in obese subjects when compared to controls (p ≤ 0,05). obese adolescents presented changes in pulmonary function at rest and these changes remained present during exercise. The spirometric and cardiorespiratory values were different in the four study groups. The present data demonstrated that, in spite of differences in lung growth, the model of fat distribution alters pulmonary function differently in obese female and male adolescents.

The Analgesic Effect Of Dipyrone In Peripheral Tissue Involves Two Different Mechanisms: Neuronal K(atp) Channel Opening And Cb(1) Receptor Activation.

Dipyrone (metamizole) is an analgesic pro-drug used to control moderate pain. It is metabolized in two major bioactive metabolites: 4-methylaminoantipyrine (4-MAA) and 4-aminoantipyrine (4-AA). The aim of this study was to investigate the participation of peripheral CB1 and CB2 cannabinoid receptors activation in the anti-hyperalgesic effect of dipyrone, 4-MAA or 4-AA. PGE2 (100ng/50µL/paw) was locally administered in the hindpaw of male Wistar rats, and the mechanical nociceptive threshold was quantified by electronic von Frey test, before and 3h after its injection. Dipyrone, 4-MAA or 4-AA was administered 30min before the von Frey test. The selective CB1 receptor antagonist AM251, CB2 receptor antagonist AM630, cGMP inhibitor ODQ or KATP channel blocker glibenclamide were administered 30min before dipyrone, 4-MAA or 4-AA. The antisense-ODN against CB1 receptor expression was intrathecally administered once a day during four consecutive days. PGE2-induced mechanical hyperalgesia was inhibited by dipyrone, 4-MAA, and 4-AA in a dose-response manner. AM251 or ODN anti-sense against neuronal CB1 receptor, but not AM630, reversed the anti-hyperalgesic effect mediated by 4-AA, but not by dipyrone or 4-MAA. On the other hand, the anti-hyperalgesic effect of dipyrone or 4-MAA was reversed by glibenclamide or ODQ. These results suggest that the activation of neuronal CB1, but not CB2 receptor, in peripheral tissue is involved in the anti-hyperalgesic effect of 4-aminoantipyrine. In addition, 4-methylaminoantipyrine mediates the anti-hyperalgesic effect by cGMP activation and KATP opening.

The Soluble Guanylyl Cyclase Activator Bay 60-2770 Potently Relaxes The Pulmonary Artery On Congenital Diaphragmatic Hernia Rabbit Model.

Congenital diaphragmatic hernia (CDH) is associated with pulmonary hypertension which is often difficult to manage, and a significant cause of morbidity and mortality. In this study, we have used a rabbit model of CDH to evaluate the effects of BAY 60-2770 on the in vitro reactivity of left pulmonary artery. CDH was performed in New Zealand rabbit fetuses (n = 10 per group) and compared to controls. Measurements of body, total and left lung weights (BW, TLW, LLW) were done. Pulmonary artery rings were pre-contracted with phenylephrine (10 μM), after which cumulative concentration-response curves to glyceryl trinitrate (GTN; NO donor), tadalafil (PDE5 inhibitor) and BAY 60-2770 (sGC activator) were obtained as well as the levels of NO (NO3/NO2). LLW, TLW and LBR were decreased in CDH (p < 0.05). In left pulmonary artery, the potency (pEC50) for GTN was markedly lower in CDH (8.25 ± 0.02 versus 9.27 ± 0.03; p < 0.01). In contrast, the potency for BAY 60-2770 was markedly greater in CDH (11.7 ± 0.03 versus 10.5 ± 0.06; p < 0.01). The NO2/NO3 levels were 62 % higher in CDH (p < 0.05). BAY 60-2770 exhibits a greater potency to relax the pulmonary artery in CDH, indicating a potential use for pulmonary hypertension in this disease.