Red blood cell flickering activity locally controlled by holographic optical tweezers.

Red blood cells possess a singular mechanobiology, enabling efficient navigation through capillaries smaller than their own size. Their plasma membrane exhibits non-equilibrium shape fluctuation, often reported as enhanced flickering activity. Such active membrane motion is propelled by motor proteins that mediate interactions between the spectrin skeleton and the lipid bilayer. However, modulating the flickering in living red blood cells without permanently altering their mechanical properties represents a significant challenge. In this study, we developed holographic optical tweezers to generate a force field distributed along the equatorial membrane contour of individual red blood cells. In free-standing red blood cells, we observed heterogeneous flickering activity, attributed to localized membrane kickers. By employing holographic optical forces, these active kickers can be selectively halted under minimal invasion. Our findings shed light on the dynamics of membrane flickering and established a manipulation tool that could open new avenues for investigating mechanotransduction processes in living cells.

Advancements in dementia research, diagnostics, and care in Latin America: Highlights from the 2023 Alzheimer's Association International conference satellite symposium in Mexico City.

INTRODUCTION: While Latin America (LatAm) is facing an increasing burden of dementia due to the rapid aging of the population, it remains underrepresented in dementia research, diagnostics, and care. METHODS: In 2023, the Alzheimer's Association hosted its eighth satellite symposium in Mexico, highlighting emerging dementia research, priorities, and challenges within LatAm. RESULTS: Significant initiatives in the region, including intracountry support, showcased their efforts in fostering national and international collaborations; genetic studies unveiled the unique genetic admixture in LatAm; researchers conducting emerging clinical trials discussed ongoing culturally specific interventions; and the urgent need to harmonize practices and studies, improve diagnosis and care, and use affordable biomarkers in the region was highlighted. DISCUSSION: The myriad of topics discussed at the 2023 AAIC satellite symposium highlighted the growing research efforts in LatAm, providing valuable insights into dementia biology, genetics, epidemiology, treatment, and care.

A Comparative Analysis of Three Online Drug-Drug Interaction Checkers: A Short Communication

ABSTRACT Objective: To assess the agreement among three different online drug-drug interaction (DDI) checkers for the detection of psychotropic drug interactions among dental patients in the state of Minas Gerais, Brazil. Material and Methods: Between January and December 2017, a cross-sectional study was conducted in Minas Gerais with data on pharmaceutical claims of psychotropic drugs prescribed by dental practitioners. Data from the Pharmaceutical Management System provided the drug dispensing history of the patients, allowing the identification of those on concomitant medication use. The occurrence of DDI was determined by entering the name of the drugs taken by each patient into Merative Micromedex®, Medscape®, and DrugBank. The degree of agreement among the three DDI online checkers was analyzed using the Fleiss' kappa test. Results: Overall, 797 dental patients were found to be taking some psychotropic medication with other drugs simultaneously. The number of patients with DDI varied according to Micromedex® (n= 366), Medscape® (n= 473), and DrugBank (n= 736). The agreement between the DDI checkers was poor (Fleiss' kappa: 0.165; p<0.001). Conclusion: The online DDI checkers assessed in this study showed variations in their ability to detect interactions and poor agreement among them.

[The 5-5-2 criteria for biliary cannulation and post endoscopic retrograde cholangiopancreatography complications: Experience in a reference hospital, Peru]. / Criterios 5-5-2 de canulación biliar y complicaciones post colangiopancreatografía retrógrada endoscópica: Experiencia en un hospital de referencia, Perú.

The European Society for Gastrointestinal Endoscopy (ESGE) defines "difficult biliary cannulation" by the presence of one or more of the following: more than 5 contacts with the papilla, more than 5 minutes attempting to cannulate, or inadvertent cannulation of the pancreatic duct in 2 or more times (5-5-2 criteria), recommending these cut-off points to perform advanced cannulation techniques in order to reduce the rate of post-ERCP adverse events. Our objective was to evaluate the performance of the 5-5-2 criteria and their association with post-ERCP complications in a reference hospital in Peru. We performed a prospective analytical case-control study and 120 patients who underwent ERCP were enrolled. The case group included 30 patients who met at least one of the 5-5-2 criteria and the control group included 90 patients without any of these criteria. The ERCP- related complications in both groups and their association with each of the 5-5-2 criteria were compared. The ERCP-related complications that occurred were post-ERCP pancreatitis (6.6% in the case group vs. 3.3% in the control group), bleeding (3.3% controls vs. 0% cases) and perforation (1.1% controls vs. 0% cases); no statistically significant differences were observed. The criterion of 2 or more unintended cannulations to the pancreatic duct showed a significant association (OR= 10.29, CI: 1.47-71.98; p= 0.005) with the incidence of post-ERCP pancreatitis. The criteria 5 minutes and 5 attempts were not associated with post-ERCP complications. In conclusion, among 5-5-2 criteria only the unintended cannulation of 2 or more times into the pancreatic duct was associated with an increased risk of post-ERC pancreatitis. The time and number of attempts criteria could be cautiously expanded without increasing the rate of post-ERCP complications.

Social network interventions to reduce race disparities in living kidney donation: Design and rationale of the friends and family of kidney transplant patients study (FFKTPS).

INTRODUCTION: Racial/ethnic disparities in living donor kidney transplantation (LDKT) are a persistent challenge. Although nearly all directed donations are from members of patients' social networks, little is known about which social network members take steps toward living kidney donation, which do not, and what mechanisms contribute to racial/ethnic LDKT disparities. METHODS: We describe the design and rationale of the Friends and Family of Kidney Transplant Patients Study, a factorial experimental fielding two interventions designed to promote LKD discussions. Participants are kidney transplant candidates at two centers who are interviewed and delivered an intervention by trained center research coordinators. The search intervention advises patients on which social network members are most likely to be LKD contraindication-free; the script intervention advises patients on how to initiate effective LKD discussions. Participants are randomized into four conditions: no intervention, search only, script only, or both search and script. Patients also complete a survey and optionally provide social network member contact information so they can be surveyed directly. This study will seek to enroll 200 transplant candidates. The primary outcome is LDKT receipt. Secondary outcomes include live donor screening and medical evaluations and outcomes. Tertiary outcomes include LDKT self-efficacy, concerns, knowledge, and willingness, measured before and after the interventions. CONCLUSION: This study will assess the effectiveness of two interventions to promote LKD and ameliorate Black-White disparities. It will also collect unprecedented information on transplant candidates' social network members, enabling future work to address network member structural barriers to LKD.

Stereoselective synthesis of highly substituted 1-isomorphans (1-azabicyclo[3.3.1]nonanes).

We describe the first enantioselective synthesis of highly functionalized 1-azabicyclo[3.3.1]nonanes (1-IM). The 1-IM scaffold is present in natural products and drugs and is an isomer of the morphan moiety. The proposed methodology is based on an organocatalytic Michael addition of N-protected piperidine ketoesters to nitroalkenes and an intramolecular nitro-Mannich reaction as key transformations. The 1-IMs feature 6 contiguous stereocenters, substituents at positions 2 and 4, and nitro, ester, and hydroxyl functional groups at positions 3, 5, and 6 respectively. The synthesis is straightforward, highly stereoselective (up to 98% ee, >99 : 1 d.r.), with overall yields of up to 83% and requires only two purification steps.

Criterios 5-5-2 de canulación biliar y complicaciones post colangiopancreatografía retrógrada endoscópica: Experiencia en un hospital de referencia, Perú

La Sociedad Europea de Endoscopia Gastrointestinal (ESGE) define "canulación difícil" como aquella en la que se realizan más de 5 intentos, se exceden 5 minutos, o se produce canulación inadvertida del conducto pancreático 2 o más veces (criterios 5-5-2), recomendando estos puntos de corte para realizar técnicas avanzadas de canulación y disminuir la tasa de eventos adversos post CPRE. Nuestro objetivo fue evaluar el rendimiento de los criterios 5-5-2 y su asociación con complicaciones post CPRE en un hospital de referencia de Perú. Realizamos un estudio analítico prospectivo de casos y controles en el que se incluyó 120 pacientes a los que se realizó CPRE. El grupo casos estuvo formado por 30 pacientes que cumplieron al menos uno de los criterios 5-5-2 y el grupo controles por 90 pacientes sin ninguno de estos criterios. Se comparó el desarrollo de complicaciones en cada grupo y su asociación con cada uno de los criterios 5-5-2. Las complicaciones presentadas fueron: pancreatitis post CPRE (6,6% en el grupo casos vs 3,3% en el grupo controles), sangrado (3,3% controles vs 0% casos) y perforación (1,1% controles vs 0 % casos); sin observar diferencia estadísticamente significativa. El criterio de 2 o más ingresos inadvertidos al conducto pancreático presentó asociación significativa (OR= 10,29, IC: 1,47-71,98; p= 0,005) con el desarrollo de pancreatitis post CPRE. Los criterios 5 minutos y 5 intentos no se asociaron a complicaciones post CPRE. En conclusión, el más relevante de los criterios 5-5-2 fue el ingreso inadvertido al conducto pancreático en 2 o más ocasiones, mostrando asociación por sí solo con pancreatitis post CPRE. Los criterios tiempo y número de intentos podrían ampliarse con cautela sin aumentar la tasa de complicaciones post CPRE.

The European Society for Gastrointestinal Endoscopy (ESGE) defines "difficult biliary cannulation" by the presence of one or more of the following: more than 5 contacts with the papilla, more than 5 minutes attempting to cannulate, or inadvertent cannulation of the pancreatic duct in 2 or more times (5-5-2 criteria), recommending these cut-off points to perform advanced cannulation techniques in order to reduce the rate of post-ERCP adverse events. Our objective was to evaluate the performance of the 5-5-2 criteria and their association with post-ERCP complications in a reference hospital in Peru. We performed a prospective analytical case-control study and 120 patients who underwent ERCP were enrolled. The case group included 30 patients who met at least one of the 5-5-2 criteria and the control group included 90 patients without any of these criteria. The ERCP- related complications in both groups and their association with each of the 5-5-2 criteria were compared. The ERCP-related complications that occurred were post-ERCP pancreatitis (6.6% in the case group vs. 3.3% in the control group), bleeding (3.3% controls vs. 0% cases) and perforation (1.1% controls vs. 0% cases); no statistically significant differences were observed. The criterion of 2 or more unintended cannulations to the pancreatic duct showed a significant association (OR= 10.29, CI: 1.47-71.98; p= 0.005) with the incidence of post-ERCP pancreatitis. The criteria 5 minutes and 5 attempts were not associated with post-ERCP complications. In conclusion, among 5-5-2 criteria only the unintended cannulation of 2 or more times into the pancreatic duct was associated with an increased risk of post-ERC pancreatitis. The time and number of attempts criteria could be cautiously expanded without increasing the rate of post-ERCP complications.

High prevalence of potential psychotropic drugs interactions among Brazilian dental patients.

OBJECTIVE: To determine the prevalence of potential drug-drug interactions involving psychotropics prescribed by dentists, and dispensed by the public healthcare system, as well as to describe the severity and level of evidence of those interactions in the state of Minas Gerais, Brazil. MATERIALS AND METHODS: We conducted data analysis from pharmaceutical claims in which dental patients received systemic psychotropics in 2017. Data from the Pharmaceutical Management System provided the drug dispensing history of the patients, allowing the identification of those on concomitant medication use. The outcome was the occurrence of potential drug-drug interactions, which were detected according to IBM Micromedex®. Independent variables were the patient's sex, age, and the number of drugs used. Descriptive statistics was performed using SPSS v. 26. RESULTS: Overall, 1480 individuals were prescribed psychotropic drugs. The prevalence of potential drug-drug interactions was 24.8% (n = 366). The total of 648 interactions was observed and, most of which were of major severity (n = 438, 67.6%). Most interactions occurred in female individuals (n = 235; 64.2%), with 46.0 (±17.3) years-old, concurrently taking 3.7 (±1.9) drugs. CONCLUSION: A substantial proportion of dental patients presented potential drug-drug interactions, mostly of major severity, which might be life-threatening.

Comparing the transcriptome of developing native and iPSC-derived mouse retinae by single cell RNA sequencing.

We report the generation and analysis of single-cell RNA-Seq data (> 38,000 cells) from mouse native retinae and induced pluripotent stem cell (iPSC)-derived retinal organoids at four matched stages of development spanning the emergence of the major retinal cell types. We combine information from temporal sampling, visualization of 3D UMAP manifolds, pseudo-time and RNA velocity analyses, to show that iPSC-derived 3D retinal organoids broadly recapitulate the native developmental trajectories. However, we observe relaxation of spatial and temporal transcriptome control, premature emergence and dominance of photoreceptor precursor cells, and susceptibility of dynamically regulated pathways and transcription factors to culture conditions in retinal organoids. We demonstrate that genes causing human retinopathies are enriched in cell-type specifying genes and identify a subset of disease-causing genes with expression profiles that are highly conserved between human retinae and murine retinal organoids. This study provides a resource to the community that will be useful to assess and further improve protocols for ex vivo recapitulation and study of retinal development.

Erythroid SLC7A5/SLC3A2 amino acid carrier controls red blood cell size and maturation.

Inhibition of the heterodimeric amino acid carrier SLC7A5/SLC3A2 (LAT1/CD98) has been widely studied in tumor biology but its role in physiological conditions remains largely unknown. Here we show that the SLC7A5/SLC3A2 heterodimer is constitutively present at different stages of erythroid differentiation but absent in mature erythrocytes. Administration of erythropoietin (EPO) further induces SLC7A5/SLC3A2 expression in circulating reticulocytes, as it also occurs in anemic conditions. Although Slc7a5 gene inactivation in the erythrocyte lineage does not compromise the total number of circulating red blood cells (RBCs), their size and hemoglobin content are significantly reduced accompanied by a diminished erythroblast mTORC1 activity. Furthermore circulating Slc7a5-deficient reticulocytes are characterized by lower transferrin receptor (CD71) expression as well as mitochondrial activity, suggesting a premature transition to mature RBCs. These data reveal that SLC7A5/SLC3A2 ensures adequate maturation of reticulocytes as well as the proper size and hemoglobin content of circulating RBCs.

Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages.

A colloidal synthesis' proof-of-concept based on the Bligh-Dyer emulsion inversion method was designed for integrating into lipid nanoparticles (LNPs) cell-permeating DNA antisense oligonucleotides (ASOs), also known as GapmeRs (GRs), for mRNA interference. The GR@LNPs were formulated to target brain border-associated macrophages (BAMs) as a central nervous system (CNS) therapy platform for silencing neuroinflammation-related genes. We specifically aim at inhibiting the expression of the gene encoding for lipocalin-type prostaglandin D synthase (L-PGDS), an anti-inflammatory enzyme expressed in BAMs, whose level of expression is altered in neuropsychopathologies such as depression and schizophrenia. The GR@LNPs are expected to demonstrate a bio-orthogonal genetic activity reacting with L-PGDS gene transcripts inside the living system without interfering with other genetic or biochemical circuitries. To facilitate selective BAM phagocytosis and avoid subsidiary absorption by other cells, they were functionalized with a mannosylated lipid as a specific MAN ligand for the mannose receptor presented by the macrophage surface. The GR@LNPs showed a high GR-packing density in a compact multilamellar configuration as structurally characterized by light scattering, zeta potential, and transmission electronic microscopy. As a preliminary biological evaluation of the mannosylated GR@LNP nanovectors into specifically targeted BAMs, we detected in vivo gene interference after brain delivery by intracerebroventricular injection (ICV) in Wistar rats subjected to gene therapy protocol. The results pave the way towards novel gene therapy platforms for advanced treatment of neuroinflammation-related pathologies with ASO@LNP nanovectors.

Características morfológicas de la papila duodenal y su relación con complicaciones poscolangiopancreatografía retrógrada endoscópica en un hospital de Perú / Morphological Characteristics of the Duodenal Papilla and its Association with Complications Post-Endoscopic Retrograde Cholangiopancreatography (ERCP) in a Peruvian Hospital

Resumen Introducción: existen diversos factores de riesgo para presentar complicaciones poscolangiopancreatografía retrógrada endoscópica (CPRE), uno de los recientemente estudiados es la morfología de la papila duodenal. Objetivos: evaluar la asociación entre las características morfológicas de la papila duodenal y las complicaciones pos-CPRE en pacientes atendidos en el servicio de gastroenterología de un hospital de referencia de Perú. Métodos: estudio prospectivo y analítico que incluyó a 138 pacientes en los que se realizó CPRE, estableciendo relación entre el tipo de papila duodenal según la clasificación endoscópica propuesta por Haraldsson y colaboradores, y las complicaciones pos-CPRE de hasta 1 mes de seguimiento. Resultados: se incluyeron 138 pacientes, 93 mujeres (68,42 %) y 45 varones (31,58 %), con una edad promedio de 51,46 años. El tipo 1 se asoció con menor dificultad en la canulación con un odds ratio (OR): 0,42 (intervalo de confianza [IC]: 0,20-0,88). El tipo 4 presentó significativamente mayor tiempo de canulación (6,83 minutos). La tasa de pancreatitis pos-CPRE fue de 2,9 %; de sangrado, 1,45 %, y de perforación, 0,72 %. La perforación presentó asociación estadísticamente significativa con el tipo de papila (p = 0,009). El tipo 2 presentó mayores tasas de pancreatitis (9,09 %) y perforación (9,09 %) pos-CPRE. Conclusión: el tipo de papila duodenal se asocia significativamente con perforación pos-CPRE. El tipo 2 presentó tasas más altas de complicaciones.

Abstract Introduction: several risk factors exist for complications post-endoscopic retrograde cholangiopancreatography (ERCP), and the morphology of the duodenal papilla is among those recently studied. Objectives: to evaluate the association between the morphological characteristics of the duodenal papilla and post-ERCP complications in patients seen in the gastroenterology unit of a Peruvian referral hospital. Methods: a prospective and analytical study including 138 patients who underwent ERCP, establishing a relationship between the type of duodenal papilla according to the endoscopic classification proposed by Haraldsson et al. and post-ERCP complications for up to 1 month of follow-up. Results: one hundred thirty-eight patients were included, 93 were females (68.42%), and 45 were males (31.58%), with 51.46 years of mean age. Type 1 was associated with less difficulty in cannulation, with an odds ratio (OR): 0.42 (confidence interval [CI]: 0.20-0.88). Type 4 had a significantly longer cannulation time (6.83 minutes). The post-ERCP ratio for pancreatitis was 2.9%; bleeding, 1.45%, and perforation, 0.72%. The perforation showed a statistically significant association with papilla type (p = 0.009). Type 2 showed higher rates of pancreatitis (9.09%) and post-ERCP perforation (9.09%). Conclusion: the duodenal papilla type is significantly associated with post-ERCP perforation. Type 2 showed higher complication rates.

Análisis retrospectivo de un protozoo emergente en México: Blastocystis spp

Blastocystis spp. es el protista intracelular que en los últimos años ha infectado a más de mil millones de personas a nivel mundial. Sin embargo, el aumento en la prevalencia en México y su potencial patógeno son inciertos, por lo que este microorganismo aún se encuentra bajo investigación. Principalmente a nivel pediátrico, la blastocistosis es estudiada con mayor atención, debido a que destaca sobre otros agentes en diversos estudios realizados mundialmente y en México. El objetivo de este trabajo fue mediante revisión bibliográfica, evidenciar la frecuencia y su transición parasitaria como el agente más prevalente en la actualidad, pese a que no se asocia a sintomatología clínica.

Blastocystis spp. is the intracellular protist that in recent years has infected more than a billion people worldwide. However, the increase in prevalence in Mexico and its pathogenic potential are uncertain, so this microorganism is still under investigation. Mainly at the pediatric level, blastocystosis is studied with greater attention, due to the fact that it stands out over other agents in various studies carried out worldwide and in Mexico. The objective of this work was to show the frequency and its parasitic transition as the most prevalent agent today through a bibliographic review, despite the fact that it is not associated with clinical symptoms.

Biosafety in Dental Health Care During the COVID-19 Pandemic: A Longitudinal Study.

Background: The coronavirus disease 2019 (COVID-19) pandemic had quite an impact on dental health care. Concerns about the risk of SARS-CoV-2 transmission through contaminant fluids and droplet formation during several dental procedures highly impacted dental health care, drastically reducing the number of dental practices worldwide. To monitor SARS-CoV-2 contamination in dental clinics, a longitudinal study was carried out during the return of dental practice at university. Methods: Dental health care professionals [(DHCPs); teachers, undergraduate dental students, and dental assistants] and patients were screened for SARS-CoV-2 RNA in a dental school clinic environment from 11th January to 12th March 2021 (9 weeks). Serological testing was performed on DHCPs in two-time points. Additionally, samples with low Ct values were sequenced to identify the circulating SARS-CoV-2 variant and possible transmission clusters. Results: We found a low number of dental staff (5.8%), patients (0.9%), and environment sites (0.8%) positive for SARS-CoV-2. Most positive cases had asymptomatic to mild symptoms, and two asymptomatic DHCPs presented prolonged infection. In the first week after previous exposure to COVID-19, 16.2% of DHCPs had IgM or IgG antibodies against SARS-CoV-2, and 1/3 of them had undetected antibodies in the last weeks. The variant zeta (P.2) could be detected. No cross-infection was observed between participants. Conclusion: Our study suggests that dental practice can be safely executed when adequate control measures and biosafety protocols are applied. DHCP and patient testing, patient telemonitoring, proper use of personal protection equipment, and sanitization of surfaces are essential to avoid SARS-CoV-2 cross-infection in dental practice.

Association between Stress at Work and Temporomandibular Disorders: A Systematic Review.

Temporomandibular disorders (TMD) have been traditionally associated with psychosocial factors; however, occupational stress as a factor related to TMD has not been adequately assessed in the literature. The aim was to investigate the association between stress at work and TMD on adult paid workers. An electronic search included PubMed, Scopus, Web of Science, Embase, and LILACS databases. Manual searches in the included articles' reference and gray literature were performed. There were no restrictions regarding language or publication period. The inclusion criteria comprised observational studies with paid workers of any category, of both sexes, above 18 years old, assessing occupational stress/stress or distress and TMD as diagnosis or isolated signs and symptoms. Methodological quality was evaluated using Joanna Briggs tools. We narratively assessed the evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach. We collected 12 studies. 50% reported a positive association between stress and TMD diagnostic across various job categories. On the other hand, TMJ sounds (a TMD sign) and work stress were associated only in a musicians' population. However, the shortage of eligible articles and the methodological limitations provided a very low certainty of the evidence; only 4 of the studies used validated tools for both stress and TMD (2 reporting positive association). The association between stress and TMD is inconclusive by the available data. In the future, we expect more robust epidemiologic studies addressing these relevant aspects.

Moulding hydrodynamic 2D-crystals upon parametric Faraday waves in shear-functionalized water surfaces.

Faraday waves, or surface waves oscillating at half of the natural frequency when a liquid is vertically vibrated, are archetypes of ordering transitions on liquid surfaces. Although unbounded Faraday waves patterns sustained upon bulk frictional stresses have been reported in highly viscous fluids, the role of surface rigidity has not been investigated so far. Here, we demonstrate that dynamically frozen Faraday waves-that we call 2D-hydrodynamic crystals-do appear as ordered patterns of nonlinear gravity-capillary modes in water surfaces functionalized with soluble (bio)surfactants endowing in-plane shear stiffness. The phase coherence in conjunction with the increased surface rigidity bears the Faraday waves ordering transition, upon which the hydrodynamic crystals were reversibly molded under parametric control of their degree of order, unit cell size and symmetry. The hydrodynamic crystals here discovered could be exploited in touchless strategies of soft matter and biological scaffolding ameliorated under external control of Faraday waves coherence.

Significancia clínica de la presencia de granulomas en enfermedad de Crohn / Clinical significance of the presence of granulomas in Crohn's disease

RESUMEN Los granulomas epitelioides son hallazgos característicos de un grupo de pacientes con enfermedad de Crohn (EC), pero su significancia con respecto a la severidad y progresión de la enfermedad es aún incierta. Objetivo: Evaluar las características clínicas de los pacientes con EC en relación a la presencia o no de granulomas en los hallazgos histológicos. Materiales y métodos: Estudio observacional, descriptivo, retrospectivo en pacientes con diagnóstico de EC desde enero 2004 a diciembre 2019 en el servicio de gastroenterología del Hospital Nacional Guillermo Almenara Irigoyen, Lima-Perú. Resultados: Se incluyó 55 pacientes con media de edad de 56 ± 8,2 años. La mediana de tiempo de enfermedad fue de 16 meses. Tener dos o más recaídas al año (p<0,001; OR= 9,75), edad menor a 30 años (p<0,001; OR=3,57) y un CDAI moderado a severo (≥220 puntos, OR= 11,4; p<0,008) se asoció significativamente con la presencia de granulomas. La actividad endoscópica severa (p<0,003; OR= 9,91) y el fenotipo estenosante-penetrante (p<0,001; OR= 22,1) también mostraron asociación con la presencia de granulomas. El grupo de granulomas presentó mayor probabilidad de uso de corticoides (p<0,024; OR= 3,92) e inmunomodulador (p<0,001; OR= 7,10) además de necesidad de cirugía de resección intestinal (p< 0,027; OR: 5,07). Conclusiones: La presencia de granulomas en EC podría asociarse a mayor severidad clínica, endoscópica, requerimiento de terapia inmunosupresora y mayor necesidad de resección intestinal.

ABSTRACT Epithelioid granuloma is a characteristic histological feature of Crohn's disease (CD), but their significance with respect to the severity and progression of the disease is still uncertain. Objective: To evaluate the clinical characteristics of CD patients in relation to the presence or not of granulomas in histological findings. Materials and methods: An observational, descriptive, retrospective study in patients diagnosed with CD from January 2004 to December 2019 in the gastroenterology department of the Guillermo Almenara Irigoyen National Hospital, Lima-Peru. Results: 55 patients were included. Average age of 56 ± 8.2 years. The median time of disease was 16 months. Have two or more relapses per year (p<0.001; OR=9.75), age less than 30 years (p<0.001; OR=3.57) and a moderate to severe CDAI (≥220 points, OR=11.4, p <0.008) was significantly associated with the presence of granulomas. Severe endoscopic activity (p <0.003; OR=9.91) and the stenosing-penetrating phenotype (p<0.001; OR=22.1) also showed association with the presence of granulomas. The group of granulomas had a higher probability of corticosteroid use (p <0.024; OR=3.92) and immunomodulator (p <0.001; OR=7.10), besides the need for intestinal resection surgery (p<0.027; OR=5.07). Conclusions: The presence of granulomas in CD may be associated with increased clinical severity, endoscopic severity, immunosuppressive therapy requirement and undergo for intestinal resection.

Multiple particle tracking analysis in isolated nuclei reveals the mechanical phenotype of leukemia cells.

The nucleus is fundamentally composed by lamina and nuclear membranes that enclose the chromatin, nucleoskeletal components and suspending nucleoplasm. The functional connections of this network integrate external stimuli into cell signals, including physical forces to mechanical responses of the nucleus. Canonically, the morphological characteristics of the nucleus, as shape and size, have served for pathologists to stratify and diagnose cancer patients; however, novel biophysical techniques must exploit physical parameters to improve cancer diagnosis. By using multiple particle tracking (MPT) technique on chromatin granules, we designed a SURF (Speeded Up Robust Features)-based algorithm to study the mechanical properties of isolated nuclei and in living cells. We have determined the apparent shear stiffness, viscosity and optical density of the nucleus, and how the chromatin structure influences on these biophysical values. Moreover, we used our MPT-SURF analysis to study the apparent mechanical properties of isolated nuclei from patients of acute lymphoblastic leukemia. We found that leukemia cells exhibited mechanical differences compared to normal lymphocytes. Interestingly, isolated nuclei from high-risk leukemia cells showed increased viscosity than their counterparts from normal lymphocytes, whilst nuclei from relapsed-patient's cells presented higher density than those from normal lymphocytes or standard- and high-risk leukemia cells. Taken together, here we presented how MPT-SURF analysis of nuclear chromatin granules defines nuclear mechanical phenotypic features, which might be clinically relevant.

Efectos del entrenamiento físico en pacientes con hipotiroidismo subclínico: una revisión sistemática / Effects of physical training in patients with subclinical hypothyroidism: a systematic review

OBJETIVO: revisar la bibliografía disponible sobre los efectos del entrenamiento en pacientes con hipotiroidismo subclínico. MATERIAL Y MÉTODOS: se realizó una revisión de las bases de datos PubMed, Scopus y Springer incluyendo artículos originales publicados desde el 01 enero del 2009 hasta 11 de junio de 2019 en los que se intervino de forma aguda o prolongada con entrenamiento en pacientes con hipotiroidismo subclínico. Los conectores utilizados fueron AND y OR junto con las palabras claves hypothyroidism, exercise, effect, thyroid hormone, training, subclinical hypothyroidism, underactive thyroid, aerobic training, anaerobic training, resistance training, strength training. Las palabras claves debían encontrarse en los títulos y resumen. Se evaluó en dos fases la elegibilidad de los artículos según: título, idioma, año de publicación y el análisis de texto completo. RESULTADOS: 8 de las 17 publicaciones encontradas en la búsqueda cumplieron con los criterios de inclusión. En estos se reportó una mejora en la calidad de vida y capacidad física posterior a la aplicación de un programa de entrenamiento mientras que ante un ejercicio físico agudo se observó una cinética cardiorrespiratoria más lenta en pacientes con HSC. CONCLUSIONES: el entrenamiento físico produce mejoras en la calidad de vida y capacidad aeróbica. Se requiere de más investigación en el área.

OBJECTIVE: the aim of this article was to perform a systematic review investigating the effects of training in patients with subclinical hypothyroidism (HSC). MATERIAL AND METHODS: PubMed, Scopus and Springer databases were searched. Original articles published between January 01, 2009 -June 11, 2019 in which acute exercise or prolonged training programs applied to patients with HSC were included. The search was made using AND & OR boolean operators and the following key words: hypothyroidism, exercise, effect, thyroid hormone, training, subclinical hypothyroidism, underactive thyroid, aerobic training, anaerobic training, resistance training, strength training, were required to be found in titles or abstract for the first eligibility phase, while the second phase consisted in article analysis. RESULTS: eight studies met the inclusion criteria. Improves in quality of life, and physical fitness were found as effect of a training program while kinematic cardiorespiratory acute response to exercise was found to be slower in patients with HSC. CONCLUSIONS: physical training improves quality of life and aerobic capacity in patients with subclinical hypothyroidism. More investigation in this area is needed.

[Clinical significance of the presence of granulomas in Crohn's disease]. / Significancia clínica de la presencia de granulomas en enfermedad de Crohn.

Epithelioid granuloma is a characteristic histological feature of Crohn's disease (CD), but their significance with respect to the severity and progression of the disease is still uncertain. OBJECTIVE: To evaluate the clinical characteristics of CD patients in relation to the presence or not of granulomas in histological findings. MATERIALS AND METHODS: An observational, descriptive, retrospective study in patients diagnosed with CD from January 2004 to December 2019 in the gastroenterology department of the Guillermo Almenara Irigoyen National Hospital, Lima-Peru. RESULTS: 55 patients were included. Average age of 56 ± 8.2 years. The median time of disease was 16 months. Have two or more relapses per year (p<0.001; OR=9.75), age less than 30 years (p<0.001; OR=3.57) and a moderate to severe CDAI (≥220 points, OR=11.4, p <0.008) was significantly associated with the presence of granulomas. Severe endoscopic activity (p <0.003; OR=9.91) and the stenosing-penetrating phenotype (p<0.001; OR=22.1) also showed association with the presence of granulomas. The group of granulomas had a higher probability of corticosteroid use (p <0.024; OR=3.92) and immunomodulator (p <0.001; OR=7.10), besides the need for intestinal resection surgery (p<0.027; OR=5.07). CONCLUSIONS: The presence of granulomas in CD may be associated with increased clinical severity, endoscopic severity, immunosuppressive therapy requirement and undergo for intestinal resection.