52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16.57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (>65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

Real-world Safety and Efficacy of Risankizumab in Psoriatic Patients: A Multicenter, Retrospective, and Not-interventional Study.

BACKGROUND AND OBJECTIVE: Risankizumab - a humanized monoclonal antibody that targets the p19 subunit of IL-23 - has been recently approved to treat moderate-to-severe plaque psoriasis. Real-world data based on a representative pool of patients are currently lacking. OBJECTIVE: To assess the mid- and long-term safety and efficacy profile of risankizumab in patients with moderate-to-severe psoriasis in the routine clinical practice. METHODS: This was a retrospective and multicenter study of consecutive psoriatic patients on risankizumab from April 2020 through November 2022. The primary endpoint was the number of patients who achieved a 100% improvement in their Psoriasis Area and Severity Index (PASI) (PASI100) on week 52. RESULTS: A total of 510 patients, 198 (38.8%) women and 312 (61.2%) men were included in the study. The mean age was 51.7±14.4 years. A total of 227 (44.5%) study participants were obese (body mass index [BMI] >30kg/m2). The mean baseline PASI score was 11.4±7.2, and the rate of patients who achieved PASI100 on week 52, 67.0%. Throughout the study follow-up, 21%, 50.0%, 59.0%, and 66% of the patients achieved PASI100 on weeks 4, 16, 24, and 40, respectively. The number of patients who achieved a PASI ≤2 was greater in the group with a BMI ≤30kg/m2 on weeks 4 (P=.04), 16 (P=.001), and 52 (P=.002). A statistically significantly greater number of patients achieved PASI100 in the treatment-naïve group on weeks 16 and 52 (P=.001 each, respectively). On week 16 a significantly lower number of participants achieved PASI100 in the group with psoriatic arthropathy (P=.04). Among the overall study sample, 22 (4.3%) patients reported some type of adverse event and 20 (3.9%) discontinued treatment. CONCLUSIONS: Risankizumab proved to be a safe and effective therapy for patients with moderate-to-severe psoriasis in the routine clinical practice.

Congenital and Infantile Hemangiomas: Epidemiological, Clinical, and Treatment Characteristics Based on 3 Years' Experience at a Tertiary Care Hospital - A Retrospective Case Comparison and Review of the Literature. / Características clínico-epidemiológicas y consideraciones terapéuticas de los hemangiomas congénitos e infantiles de un hospital de tercer nivel durante un periodo de 3 años: estudio comparativo y revisión de la literatura.

Distinguishing between congenital and infantile hemangiomas is challenging, but essential for appropriate treatment. The immunohistochemical marker glucose transporter type 1 is helpful, but biopsies are uncommon in this setting. The aim of this retrospective study was to describe and compare epidemiological, clinical, and treatment characteristics of congenital and infantile hemangiomas diagnosed at a tertiary care hospital over 3 years. We studied 107 hemangiomas: 34 congenital hemangiomas (rapidly involuting, partially involuting, and noninvoluting), 70 infantile hemangiomas, and 3 hemangiomas pending classification. Superficial infantile hemangiomas of the head and neck were the most prevalent tumors. Congenital hemangiomas were most often located on the trunk. Studied risk factors were more common in patients with infantile hemangiomas. In this group of patients, treatment response was independent of sex, in vitro fertilization, lesion depth and location, and type of treatment.

[Psychomotor development from 0 to 4 years in indigenous children. A sistematic literature search]. / Desarrollo psicomotor de 0 a 4 años en infancia indígena. Revisión sistemática de la literatura.

INTRODUCTION: The objective of this study was to evaluate published articles regarding the development of indigenous children aged 0 to four years. SUBJECTS AND METHOD: Systematic literature search. Parti cipants: Primary studies with populations of indigenous children aged 0 to four years. Type of studies: Primary studies with qualitative or quantitative methodologies published in the last ten years until November 2015. Databases: MEDLINE, Digital Library of the University of Girona: CERCADOR, EMBASE, Scielo. SEARCH STRATEGY: sensitive and specific. Free terms, MeSH, and Boolean. RESULTS: Nine articles remain for analysis. There are six central subjects related to intracultural patterns of expected development in indigenous childhood: 1) physical, 2) language, 3) socio-cognitive, 4) emo tional, 5) teaching-learning, 6) psychosocial, which reveal the existence of categories of sociocultural and spiritual contents. There is no defined period of time associated with the education. Learning is through observation and participation. Development is understood as a whole, intertwining the social, cultural, natural and spiritual. CONCLUSION: Spirituality and nature are at the center. Time as a goal to gain skills does not have a cultural function to demonstrate the acquisition of the inherent va lues to the culture. To base the assessment of development exclusively on psychomotor development as monitoring guide is insufficient to assess the integrality and complexity of the advances, abilities, and skills of indigenous children.

The microtubular cytoskeleton of olfactory neurons derived from patients with schizophrenia or with bipolar disorder: Implications for biomarker characterization, neuronal physiology and pharmacological screening.

Schizophrenia (SZ) and Bipolar Disorder (BD) are highly inheritable chronic mental disorders with a worldwide prevalence of around 1%. Despite that many efforts had been made to characterize biomarkers in order to allow for biological testing for their diagnoses, these disorders are currently detected and classified only by clinical appraisal based on the Diagnostic and Statistical Manual of Mental Disorders. Olfactory neuroepithelium-derived neuronal precursors have been recently proposed as a model for biomarker characterization. Because of their peripheral localization, they are amenable to collection and suitable for being cultured and propagated in vitro. Olfactory neuroepithelial cells can be obtained by a non-invasive brush-exfoliation technique from neuropsychiatric patients and healthy subjects. Neuronal precursors isolated from these samples undergo in vitro the cytoskeletal reorganization inherent to the neurodevelopment process which has been described as one important feature in the etiology of both diseases. In this paper, we will review the current knowledge on microtubular organization in olfactory neurons of patients with SZ and with BD that may constitute specific cytoskeletal endophenotypes and their relation with alterations in L-type voltage-activated Ca(2+) currents. Finally, the potential usefulness of neuronal precursors for pharmacological screening will be discussed.

Increased levels of adenosine and ecto 5'-nucleotidase (CD73) activity precede renal alterations in experimental diabetic rats.

The pathogenesis of diabetic nephropathy (DN) has not been clearly established, making diagnosis and patient management difficult. Recent studies using experimental diabetic models have implicated adenosine signaling with renal cells dysfunction. Therefore, the study of the biochemical mechanisms that regulate extracellular adenosine availability during DN is of emerging interest. Using streptozotocin-induced diabetic rats we demonstrated that urinary levels of adenosine were early increased. Further analyses showed an increased expression of the ecto 5'-nucleotidase (CD73), which hydrolyzes AMP to adenosine, at the renal proximal tubules and a higher enzymatic activity in tubule extracts. These changes precede the signs of diabetic kidney injury recognized by significant proteinuria, morphological alterations and the presence of the renal fibrosis markers alpha smooth muscle actin and fibronectin, collagen deposits and thickening of the glomerular basement membrane. In the proximal tubule cell line HK2 we identified TGF-ß as a key modulator of CD73 activity. Importantly, the increased activity of CD73 could be screened in urinary sediments from diabetic rats. In conclusion, the increase of CD73 activity is a key component in the production of high levels of adenosine and emerges as a new tool for the early diagnosis of tubular injury in diabetic kidney disease.

Reduction of high-fat diet-induced liver proinflammatory state by eicosapentaenoic acid plus hydroxytyrosol supplementation: involvement of resolvins RvE1/2 and RvD1/2.

High-fat diet (HFD)-fed mice show obesity with development of liver steatosis and a proinflammatory state without establishing an inflammatory reaction. The aim of this work was to assess the hypothesis that eicosapentaenoic acid (EPA) plus hydroxytyrosol (HT) supplementation prevents the inflammatory reaction through enhancement in the hepatic resolvin content in HFD-fed mice. Male C57BL/6J mice were fed an HFD or a control diet and supplemented with EPA (50 mg/kg/day) and HT (5 mg/kg/day) or their respective vehicles for 12 weeks. Measurements include liver levels of EPA, DHA and palmitate (gas chromatography), liver resolvins and triglyceride (TG) and serum aspartate transaminase (AST) (specific kits) and hepatic and serum inflammatory markers (quantitative polymerase chain reaction and enzyme-linked immunosorbent assay). Compared to CD, HFD induced body weight gain, liver steatosis and TG accumulation, with up-regulation of proinflammatory markers in the absence of histological inflammation or serum AST changes; these results were accompanied by higher hepatic levels of resolvins RvE1, RvE2, RvD1 and RvD2, with decreases in EPA and DHA contents. EPA+HT supplementation in HFD feeding synergistically reduced the steatosis score over individual treatments and increased the hepatic levels of EPA, DHA and resolvins, with attenuation of proinflammatory markers. Lack of progression of HFD-induced proinflammatory state into overt inflammation is associated with resolvin up-regulation, which is further increased by EPA+HT supplementation eliciting steatosis attenuation. These findings point to the importance of combined protocols in hepatoprotection due to the involvement of cross-talk mechanisms, which increase effectiveness and diminish dosages, avoiding undesirable effects.

[Self-adjusting monocanalicular intubation for congenital lacrimal obstruction]. / Intubación monocanalicular autoajustable para la obstrucción lagrimal congénita.

OBJECTIVE: To present our work with the Masterka self-adjusting monocanalicular intubation without nasal recuperation in congenital lacrimal obstruction in children over 12-months old. METHODS: A total of 40 children between the ages of one and seven (average age 2.6 years) were consecutively operated on. The Masterka catheter has a flexible metal guide inside the silicone tube that covers it completely. The proximal end is fixed onto the lacrimal punctum by pushing it with a dilator or forceps. Its correct position was monitored and visually checked in real time during surgery in all cases. RESULTS: The average surgery time, excluding anaesthetic, was 1.56min, ranging from 1.05 to 4min. The final success was 97.5%, considering absence of epiphora, disappearance of colouring in lacrimal meniscus, and mucopurulent secretion. The average follow-up time was 15 months (ranging from 7 to 21 months). CONCLUSIONS: Masterka intubation is an effective primary treatment. It is no more difficult than a simple catheter, since the surgical technique is similar, but with better functional results. It avoids the possibility of having to repeat the catheterization and it is easier to carry out than bicanalicular intubation, since there is no need to manipulate repeatedly or use surgical instruments in the inferior meatus, thus simplifying the process.

Electrophysiological effects of opioid receptor selective agonists on guinea-pig papillary muscle.

The cardiac electrophysiological effects of DAMGO, DPDPE and U-50,488H which are selective opioid agonists for mu, delta and kappa receptors, respectively, were studied in the isolated guinea-pig right ventricular papillary muscles. Neither DAMGO (5.10(-6)-5.10(-5)M) nor DPDPE (5.10(-6)-5.10(-5)M) produced any significant effect on the action potential characteristics. However, U.-50,488H (10(-5),5.10(-5) M) caused a concentration-dependent reduction in the maximum rate of depolarization of phase 0 (Vmax) and in the action potential duration measured at 50% repolarization, APD50 and 90% repolarization, APD90. At 5.10(-5) M it also produced a decrease of action potential amplitude (APA). These results suggest that the reported electrophysiological effects of U-50,488H on the cardiac muscle action potential, may be, at least in part, explained by a direct cardiac action.

Cardiac electrophysiological effects of U-50,488H on guinea-pig papillary muscle.

Intracellular microelectrodes were used to study the electrophysiological effects of U-50,488H on guinea-pig papillary muscle. U-50,488H (10(-5) M) caused a significant decrease in the maximum rate of depolarization and a decrease in the action potential duration. At high concentration (5 x 10(-5) M) U-50,488H induced a significant decrease of resting potential, maximum rate of depolarization, action potential amplitude and the action potential duration. The administration of MR-2266 (5 x 10(-7) M) partially antagonized the cardiac electrophysiological effects of U-50,488H. These results suggest that the electrophysiological effects of U-50,488H may be partially due to an interaction with opioid receptors.

Prenatal protein restriction alters synaptic mechanisms of callosal connections in the rat visual cortex.

Mild prenatal protein malnutrition, induced by reduction of the casein content of the maternal diet from 25 to 8%, calorically compensated by the addition of excess carbohydrates, leads to so-called "hidden" malnutrition in the rat. This form of malnutrition results in normal body and brain weights of pups at birth, but in significant alterations of their central nervous system neurochemical profiles. Since severe forms of prenatal malnutrition induce morpho-functional deficits on callosal interhemispheric communication together with brain neurochemical disturbances, we evaluated, in rats born from mothers submitted to an 8% casein diet, the potassium-induced release of [3H]-noradrenaline in visual cortex slices, as well as functional properties of callosal-cortical synapses by determining cerebral cortical excitability to callosal inputs and fatigability and temporal summation of transcallosal evoked responses. Rats born from mothers submitted to a 25% casein diet served as controls. At birth prenatally malnourished pups had significantly higher cortical percent net noradrenaline release (14.79 +/- 1.11) than controls (9.14 +/- 1.26). At 45-50 days of age, rehabilitated previously malnourished rats showed, when compared to controls; (i) significantly reduced percent net noradrenaline release in the visual cortex (4.50 +/- 0.52 vs 11.31 +/- 1.14); (ii) decreased cortical excitability to callosal inputs as revealed by significantly increased chronaxie (607.2 +/- 82.8 microseconds vs 351.3 +/- 47.7 microseconds); (iii) enhanced fatigability of transcallosal evoked responses as revealed by significantly decreased stimulus frequency required to fatigate the responses (4.9 +/- 0.8 Hz vs 9.2 +/- 1.3 Hz); and (iv) decreased ability of callosal-cortical synapses to perform temporal summation, as revealed by significantly reduced percent response increment to double-shock (54.2 +/- 6.2 vs 83.0 +/- 11.0, for a 3.2-ms interstimulus time interval). These changes, resulting from mild prenatal protein restriction, are discussed in relationship to developmental processes leading to the formation of synaptic contacts between callosal axons and their appropriate cortical target during perinatal age.

Intraarticular corticosteroid injections: should we rest the joints?

To prevent damage in injected joints, it has been our policy to rest them for 48 hours. To test this assertion we randomized 30 rheumatoid arthritis (RA) patients (rest, no-rest). Results in 28 patients (63 joints: 27 rest and 36 no-rest) are presented. Joint evaluation was performed at baseline and at 48 hours (pain/tenderness, swelling and range of motion). Two analyses were conducted, the first included all joints, and the second only joint pairs. In both cases measurements at 48 hours were comparable for the rest and no rest group for both upper and lower extremity joints (pain/tenderness/swelling and range of motion). At a later follow up (average 10 months) there were no differences in any of the parameters examined. Our study suggests that rest is not essential for intraarticular corticosteroids to be beneficial, at least in an inpatient setting. The applicability of our data to an outpatient population remains to be determined.

Effects of morphine: an electrophysiological study on guinea-pig papillary muscle.

Intracellular microelectrodes were used to study the electrophysiological effects of morphine on guinea-pig papillary muscle. Morphine (5 x 10(-4) M) caused a significant decrease in the maximum rate of depolarization. At high concentrations (5 x 10(-3) M) morphine induced a decrease in the action potential amplitude and a prolongation of the action potential duration. The administration of naloxone (10(-7) M) partially antagonized the cardiac electrophysiological effects of morphine. These results suggest that the electrophysiological effects of morphine may be due to an interaction with opioid receptors.

Sylvatic focus of American Trypanosomiasis in the State of Morelos, Mexico.

Wild vectors and reservoir hosts of Trypanosoma cruzi were surveyed from February 1993 to June 1994 in Ticumán (18 degrees 46'N, 99 degrees 07'W), Mexico (Deciduous Tropical Forest). Direct faeces examination showed that 87% of Triatoma pallidipennis hosted the parasite; T. cruzi forms were present in cultures inoculated with faeces of fifty 67% triatomine bugs and thirty CD-1 strain mice (10 d old) inoculated (peritoneum) with faeces of positive insects T. cruzi amastigotes were found in heart 67%, kidneys 47%, liver 80%, lungs 50%, oesophagus 60%, skin 23%, spleen 73% and stomach 60%. T. cruzi was isolated by direct blood examination from seven 21% chiropterans and five 38% rodents and T. cruzi forms were present in cultures inoculated with blood of twenty-three 68% chiropterans and seven 54% rodents and T. cruzi amastigotes were seen in the kidneys of one 3% chiropterans and four 31% rodents and only in one Pteronotus parnellii mexicanus, organisms were seen in skin 2%. There was no association between organs and T. cruzi infection (p > 0.05).

Desarrollo psicomotor de 0 a 4 años en infancia indígena: revisión sistemática de la literatura / Psychomotor development from 0 to 4 years in indigenous children: a sistematic literature search

INTRODUCCIÓN: El objetivo de este estudio fue evaluar artículos publicados respecto al desarrollo de niños/niñas de 0 a 4 años en el curso de la infancia indígena. SUJETOS Y MÉTODO: Búsqueda sistemática de la literatura. Participantes: Estudios primarios cuya población correspondiera a niños/as de 0 a 4 años en el curso de la infancia indígena. Tipos de estudios: Se incluyeron aquellos estudios cuyas metodologías fueran cualitativas o cuantitativas publicados en los últimos 10 años hasta noviembre de 2015. Bases de datos: MEDLINE, Biblioteca Digital de la Universidad de Girona: CERCADOR, EMBASE, Scielo. Estrategia de búsqueda: sensible y específica. Términos libres, MeSH, y Boolean. RESULTADOS: Quedan 9 artículos para el análisis. Se presentan 6 temas centrales que se relacionan con patrones intraculturales del desarrollo esperado en la infancia indígena: 1) lo físico; 2) el lenguaje; 3)lo socio-cognitivo; 4) lo emocional; 5) la enseñanza-aprendizaje; 6) lo psicosocial, que permi ten ver la existencia de categorías de contenidos socioculturales y espirituales. No se muestra una temporalidad definida asociada a la formación. El aprendizaje es por observación y participación. El desarrollo es comprendido como un todo, entrelaza lo social, cultural, natural y espiritual. CONCLUSIÓN: La espiritualidad y naturaleza están en el centro. La temporalidad como meta para dominar destrezas no ejerce función cultural para demostrar la adquisición de valores propios de la cultura. Basar la valoración del desarrollo centrándose exclusivamente en el Desarrollo Psicomotor como guía de vigilancia es insuficiente para valorar la integralidad y complejidad de los progresos, habilidades y destrezas de los niños/niñas indígenas.

INTRODUCTION: The objective of this study was to evaluate published articles regarding the development of indigenous children aged 0 to four years. SUBJECTS AND METHOD: Systematic literature search. Participants: Primary studies with populations of indigenous children aged 0 to four years. Type of studies: Primary studies with qualitative or quantitative methodologies published in the last ten years until November 2015. Databases: MEDLINE, Digital Library of the University of Girona: CERCADOR, EMBASE, Scielo. Search strategy: sensitive and specific. Free terms, MeSH, and Boolean. RESULTS: Nine articles remain for analysis. There are six central subjects related to intracultural patterns of expected development in indigenous childhood: 1) physical, 2) language, 3) socio-cognitive, 4) emo tional, 5) teaching-learning, 6) psychosocial, which reveal the existence of categories of sociocultural and spiritual contents. There is no defined period of time associated with the education. Learning is through observation and participation. Development is understood as a whole, intertwining the social, cultural, natural and spiritual. CONCLUSION: Spirituality and nature are at the center. Time as a goal to gain skills does not have a cultural function to demonstrate the acquisition of the inherent va lues to the culture. To base the assessment of development exclusively on psychomotor development as monitoring guide is insufficient to assess the integrality and complexity of the advances, abilities, and skills of indigenous children.

Tumor-intrinsic and tumor-extrinsic factors impacting hsp90- targeted therapy.

In 1994 the first heat shock protein 90 (Hsp90) inhibitor was identified and Hsp90 was reported to be a target for anticancer therapeutics. In the past 18 years there have been 17 distinct Hsp90 inhibitors entered into clinical trial, and the small molecule Hsp90 inhibitors have been highly valuable as probes of the role of Hsp90 and its client proteins in cancer. Although no Hsp90 inhibitor has achieved regulatory approval, recently there has been significant progress in Hsp90 inhibitor clinical development, and in the past year RECIST responses have been documented in HER2-positive breast cancer and EML4-ALK-positive non-small cell lung cancer. All of the clinical Hsp90 inhibitors studied to date are specific in their target, i.e. they bind exclusively to Hsp90 and two related heat shock proteins. However, Hsp90 inhibitors are markedly pleiotropic, causing degradation of over 200 client proteins and impacting critical multiprotein complexes. Furthermore, it has only recently been appreciated that Hsp90 inhibitors can, paradoxically, cause transient activation of the protein kinase clients they are chaperoning, resulting in initiation of signal transduction and significant physiological events in both tumor and tumor microenvironment. An additional area of recent progress in Hsp90 research is in studies of the posttranslational modifications of Hsp90 itself and Hsp90 co-chaperone proteins. Together, a picture is emerging in which the impact of Hsp90 inhibitors is shaped by the tumor intracellular and extracellular milieu, and in which Hsp90 inhibitors impact tumor and host on a microenvironmental and systems level. Here we review the tumor intrinsic and extrinsic factors that impact the efficacy of small molecules engaging the Hsp90 chaperone machine.

Personas en situación de discapacidad visual en relación a las barreras y estrategias que afectan las actividades de la vida diaria instrumentales / Persons with visual impairment in relation with barriers and strategies affecting their performance in instrumentals daily living activities

El objetivo del estudio de metodología cuantitativa fue conocer la información disponible sobre el desempeño en las actividades de la vida diaria instrumentales (AVDI) de las personas en situación de discapacidad visual en relación a las barreras que presentan para su ejecución. Para ello se llevó a cabo una revisión bibliográfica en distintas bases de datos y sitios web y documentos e información disponible en todo tipo de prensa. Las variables utilizadas fueron: actividades de la vida diaria instrumental, discapacidad visual, barreras, edad, año, idioma y país. Del total de la información recopilada, el 32,60 por ciento de las investigaciones tenían relación con la temática a investigar. En su mayoría correspondía a publicaciones del año 2008 con un 17,4 por ciento, siendo con mayor frecuencia documentos en idioma español (78,3 por ciento). En la literatura de Chile se encontró aproximadamente un 21,7% de información. La mayoría de la literatura incluía a todas las personas en situación de discapacidad con un porcentaje de 58,7 por ciento, todas éstas relacionadas con las barreras y AVDI, sin embargo, los documentos abarcaban mayor información sobre las barreras de comunicación (32,6 por ciento) y las AVDI relacionadas con la gestión de comunicación (37 por ciento). En conclusión la información para aquellas actividades como el cuidado de mascotas y crianza de niños y las investigaciones sobre el tema abordado, es insuficiente para así poder implementar estrategias que faciliten la independencia de estas personas.

The aim of this research with quantitative methodology was to know the available information about the performance at instrumental daily life activities of people with visual impairment in relation to the barriers that present to their performance. For this, a bibliographic review was carried out in different databases and websites, documents and information available in all types of press. The variables used were instrumental activities of daily life, visual impairment, barriers, age, year, language and country. The total of the information gathered, 32.60 percent of investigations had related to theme to investigate. The greatest amount of information found corresponded to publications of year 2008 with 17.4 per cent, being more frequently documents of Spanish language (78.3 percent). In the Chilean literature, approximately 21.7 percent of information was found. Most of information included all persons in situations of disability with a percentage of 58.7 percent, all these related to barriers and IADL however, documents included more information on the communication barriers (32.6 percent) and IADL related to the management of communication (37 percent). In conclusion, the information for activities such as pet care, child care and researching on the main theme is insufficient to implement strategies that facilitate the independence of these persons.