Recent advances in photoaffinity labeling strategies to capture Glycan-Protein interactions.

Glycans decorate all cells and are critical mediators of cellular processes through recognition by glycan-binding proteins (GBPs). While targeting glycan-protein interactions has great therapeutic potential, these interactions are challenging to study as they are generally transient and exhibit low binding affinities. Glycan-based photo-crosslinkable probes have enabled covalent capture and identification of unknown GBP receptors and glycoconjugate ligands. Here, we review recent progress in photo-crosslinking approaches targeting glycan-mediated interactions. We discuss two prominent emerging strategies: 1) development of photo-crosslinkable oligosaccharide ligands to identify GBP receptors; and 2) cell-surface glyco-engineering to identify glycoconjugate ligands of GBPs. Overall, photoaffinity labeling affords valuable insights into complex glycan-protein networks and is poised to help elucidate the glycan-protein interactome, providing novel targets for therapeutic intervention.

External beam radiation therapy for recurrent or residual thyroid cancer: What is the best treatment time and the best candidate for long-term local disease control?

INTRODUCTION: Cervical disease control might be challenging in advanced thyroid cancer (DTC). Indications for cervical external beam radiation therapy (EBRT) are controversial. PURPOSE: To identify clinical and molecular factors associated with control of cervical disease with EBRT. METHODS: Retrospective evaluation and molecular analysis of the primary tumor DTC patients who underwent cervical EBRT between 1995 and 2022 was performed. RESULTS: Eighty adults, median age of 61 years, were included. T4 disease was present in 43.7%, lymph node involvement in 42.5%, and distant metastasis in 47.5%. Those with cervical progression were older (62.5 vs. 57.3, p = 0.04) with more nodes affected (12.1 vs. 2.8, p = 0.04) and had EBRT performed later following surgery (76.6 vs. 64 months, p = 0.05). EBRT associated with multikinase inhibitors showed longer overall survival than EBRT alone (64.3 vs. 37.9, p = 0.018) and better local disease control. Performing EBRT before radioiodine (RAI) was associated with longer cervical progression-free survival (CPFS) than was RAI before (67.5 vs. 34.5, p < 0.01). EBRT ≥2 years after surgery was associated with worse CPFS (4.9 vs. 34, p = 0.04). The most common molecular alterations were ERBB2, BRAF, FAT1, RET and ROS1 and TERT mutation was predictive of worse disease control after EBRT (p = 0.04). CONCLUSION: Younger patients, with fewer affected nodes and treated earlier after surgery had better cervical disease control. Combination of EBRT with MKI improved OS. TERT mutation might indicate worse responders to EBRT; however, further studies are necessary to clarify the role of molecular testing in selecting candidates for cervical EBRT.

Glyco-Engineering Cell Surfaces by Exo-Enzymatic Installation of GlcNAz and LacNAz Motifs.

Exo-enzymatic glyco-engineering of cell-surface glycoconjugates enables the selective display of well-defined glyco-motifs bearing bioorthogonal functional groups, which can be used to study glycans and their interactions with glycan-binding proteins. In recent years, strategies to edit cellular glycans by installing monosaccharides and their derivatives using glycosyltransferase enzymes have rapidly expanded. However, analogous methods to introduce chemical reporter-functionalized type 2 LacNAc motifs have not been reported. Herein, we report the chemo-enzymatic synthesis of unnatural UDP-GlcNAc and UDP-GalNAc nucleotide-sugars bearing azide, alkyne, and diazirine functionalities on the C2-acetamido group using the mutant uridylyltransferase AGX1F383A. The unnatural UDP-GlcNAc derivatives were examined as substrates for the human GlcNAc-transferase B3GNT2, where it was found that modified donors were tolerated for transfer, albeit to a lesser extent than the natural UDP-GlcNAc substrate. When the GlcNAc derivatives were examined as acceptor substrates for the human Gal-transferase B4GalT1, all derivatives were well tolerated and the enzyme could successfully form derivatized LacNAcs. B3GNT2 was also used to exo-enzymatically install GlcNAc and unnatural GlcNAc derivatives on cell-surface glycans. GlcNAc- or GlcNAz-engineered cells were further extended by B4GalT1 and UDP-Gal, producing LacNAc- or LacNAz-engineered cells. Our proof-of-concept glyco-engineering labeling strategy is amenable to different cell types and our work expands the exo-enzymatic glycan editing toolbox to selectively introduce unnatural type 2 LacNAc motifs.

Glycosyltransferases as versatile tools to study the biology of glycans.

All cells are decorated with complex carbohydrate structures called glycans that serve as ligands for glycan-binding proteins (GBPs) to mediate a wide range of biological processes. Understanding the specific functions of glycans is key to advancing an understanding of human health and disease. However, the lack of convenient and accessible tools to study glycan-based interactions has been a defining challenge in glycobiology. Thus, the development of chemical and biochemical strategies to address these limitations has been a rapidly growing area of research. In this review, we describe the use of glycosyltransferases (GTs) as versatile tools to facilitate a greater understanding of the biological roles of glycans. We highlight key examples of how GTs have streamlined the preparation of well-defined complex glycan structures through chemoenzymatic synthesis, with an emphasis on synthetic strategies allowing for site- and branch-specific display of glyco-epitopes. We also describe how GTs have facilitated expansion of glyco-engineering strategies, on both glycoproteins and cell surfaces. Coupled with advancements in bioorthogonal chemistry, GTs have enabled selective glyco-epitope editing of glycoproteins and cells, selective glycan subclass labeling, and the introduction of novel biomolecule functionalities onto cells, including defined oligosaccharides, antibodies, and other proteins. Collectively, these approaches have contributed great insight into the fundamental biological roles of glycans and are enabling their application in drug development and cellular therapies, leaving the field poised for rapid expansion.

An outbreak of trichophytic tinea capitis in a group of schoolchildren in a rural area of the department of Cauca, Colombia / Brote de tinea capitis tricofítica en un grupo de niños escolares en un área rural del departamento del Cauca, Colombia

Introduction. Tinea capitis is a mycosis of keratinized tissue, which affects the scalp and may cause alopecia, pruritus, and desquamation. This type of mycosis is more frequent in school-age children, and it may represent a public health problem; the main etiological agents reported for Colombia are zoophilic dermatophytes. Objective. To characterize an outbreak of Tinea capitis in 32 children from a rural school in the department of Cauca. Materials and methods. We conducted an epidemiological field study using a structured survey to characterize sociodemographic aspects and predisposing factors for this mycosis. We collected samples of affected scalp scales and hair for mycological studies. The children and the general population received recommendations, about these mycoses' prevention, from Cauca's health authorities and the local hospital. The parents verbally approved the informed consent. Results. The etiological agent isolated in 63% of the collected samples was Trichophyton tonsurans, an anthropophilic dermatophyte, and the main predisposing factor was sharing razors (87.5%). Conclusions. Ideally, mycological studies define the etiological agent to propose therapeutics and recommendations in agreement with management guidelines. Implementation of multidisciplinary measures to control the outbreak and educate the population is required.

Introducción. La tiña de la cabeza es una micosis que se presenta en el tejido queratinizado, afecta al cuero cabelludo y puede causar alopecia, prurito y descamación. Este tipo de micosis es más frecuente en niños de edad escolar, por lo que puede desencadenar un problema de salud pública. En Colombia, los principales agentes etiológicos reportados son los dermatofitos zoofílicos. Objetivo. En el presente estudio se buscó caracterizar un brote de tinea capitis en 32 niños de un colegio de la zona rural del departamento del Cauca. Materiales y métodos. Se llevó a cabo una investigación epidemiológica de campo en la que se aplicó una encuesta estructurada para caracterizar aspectos sociodemográficos y factores predisponentes para su ocurrencia. Se recolectaron muestras de escamas de cuero cabelludo y cabellos afectados para estudios micológicos. Finalmente, por medio de la Secretaría Departamental del Cauca y del hospital local, se manejó el brote de tinea capitis y se hicieron recomendaciones a los niños, los padres de familia y la población en general para prevenir estas micosis. Este estudio contó con el consentimiento informado verbal por parte de los padres de familia y los niños. Resultados. El agente etiológico aislado en el 63 % de las muestras recolectadas fue Trichophyton tonsurans y el principal factor predisponente para esta micosis fue compartir máquinas rasuradoras (87,5 %). El agente etiológico de este brote de tinea capitis no inflamatoria fue un dermatofito antropofílico.

The relevance of clinical and epidemiological correlation in the early diagnosis of histoplasmosis: report of two clinical cases in Popayán, Colombia / La importancia de la correlación clínico-epidemiológica en el diagnóstico temprano de la histoplasmosis: reporte de dos casos clínicos en Popayán, Colombia

Histoplasmosis is an endemic mycosis in Colombia. Here we present two cases in the Cauca department, to indicate the clinical impact of histoplasmosis delayed diagnosis and treatment when its epidemiology is unknown. Informed consent was requested to review patients' medical records and case report publication. The first case was a patient diagnosed with human immunodeficiency virus and generalized presence of skin lesions. Initially, these lesions were diagnosed as herpes, but a postmortem diagnosis confirmed histoplasmosis through fungal cultures of tissues from the skin lesions. The second case is an immunocompetent patient with pulmonary symptoms diagnosed and treated for tuberculosis. However, given the lack of improvement and considering the bat cave entrance history, the patient was treated for possible pulmonary histoplasmosis with an adequate response. We made a review of laboratory tests and histoplasmosis epidemiological data relevant to health professionals. We concluded that health institutions must provide rapid tests, such as antigen ones, to adequately diagnose and treat this mycosis; and also take corrective measures to minimize exposure to Histoplasma.

La histoplasmosis es una micosis endémica en Colombia. Se presentan dos casos del departamento del Cauca, para mostrar el impacto clínico que conlleva un retraso en su diagnóstico y tratamiento. Se obtuvo el consentimiento informado para revisar las historias clínicas de los pacientes y publicar los casos. El primer caso se trata de un paciente con infección por el virus de inmunodeficiencia humana (Human Immunodeficiency Virus, HIV), quien presentaba lesiones cutáneas generalizadas atribuidas inicialmente al virus del herpes; post mortem y mediante el cultivo para hongos de muestras de las lesiones dérmicas, se confirmó el diagnóstico de histoplasmosis. El segundo caso es un paciente inmunocompetente con sintomatología pulmonar, a quien se le diagnosticó tuberculosis clínicamente y se le instauró tratamiento; sin embargo, ante la nula mejoría y teniendo en cuenta el antecedente de ingreso a una cueva de murciélagos, se enfocó como una posible histoplasmosis pulmonar y se obtuvo mejoría con el tratamiento. Se revisó la literatura sobre las pruebas de laboratorio y los datos epidemiológicos de histoplasmosis que deben considerar los profesionales de la salud. Se concluyó que las instituciones de salud deben disponer de pruebas rápidas (por ejemplo, antigénicas) para el diagnóstico y tratamiento adecuado de esta micosis, además de adoptar los correctivos necesarios para minimizar la exposición a Histoplasma.

Brote de tinea capitis tricofítica en un grupo de niños escolares en un área rural del departamento del Cauca, Colombia / An outbreak of trichophytic tinea capitis in a group of schoolchildren in a rural area of the department of Cauca, Colombia

Introducción. La tiña de la cabeza es una micosis que se presenta en el tejido queratinizado, afecta al cuero cabelludo y puede causar alopecia, prurito y descamación. Este tipo de micosis es más frecuente en niños de edad escolar, por lo que puede desencadenar un problema de salud pública. En Colombia, los principales agentes etiológicos reportados son los dermatofitos zoofílicos. Objetivo. En el presente estudio se buscó caracterizar un brote de tinea capitis en 32 niños de un colegio de la zona rural del departamento del Cauca. Materiales y métodos. Se llevó a cabo una investigación epidemiológica de campo en la que se aplicó una encuesta estructurada para caracterizar aspectos sociodemográficos y factores predisponentes para su ocurrencia. Se recolectaron muestras de escamas de cuero cabelludo y cabellos afectados para estudios micológicos. Finalmente, por medio de la Secretaría Departamental del Cauca y del hospital local, se manejó el brote de tinea capitis y se hicieron recomendaciones a los niños, los padres de familia y la población en general para prevenir estas micosis. Este estudio contó con el consentimiento informado verbal por parte de los padres de familia y los niños. Resultados. El agente etiológico aislado en el 63 % de las muestras recolectadas fue Trichophyton tonsurans y el principal factor predisponente para esta micosis fue compartir máquinas rasuradoras (87,5 %). El agente etiológico de este brote de tinea capitis no inflamatoria fue un dermatofito antropofílico. Conclusión. Idealmente, se deben practicar los estudios micológicos con el fin de establecer el agente etiológico y, así, plantear las terapéuticas y recomendaciones según las guías de manejo. Además, se debe realizar un trabajo multidisciplinario para el control del brote y la educación de la población respecto a esta micosis.

Introduction. Tinea capitis is a mycosis of keratinized tissue, which affects the scalp and may cause alopecia, pruritus, and desquamation. This type of mycosis is more frequent in school-age children, and it may represent a public health problem; the main etiological agents reported for Colombia are zoophilic dermatophytes. Objective. To characterize an outbreak of Tinea capitis in 32 children from a rural school in the department of Cauca. Materials and methods. We conducted an epidemiological field study using a structured survey to characterize sociodemographic aspects and predisposing factors for this mycosis. We collected samples of affected scalp scales and hair for mycological studies. The children and the general population received recommendations, about these mycoses' prevention, from Cauca's health authorities and the local hospital. The parents verbally approved the informed consent. Results. The etiological agent isolated in 63% of the collected samples was Trichophyton tonsurans, an anthropophilic dermatophyte, and the main predisposing factor was sharing razors (87.5%). Conclusions. Ideally, mycological studies define the etiological agent to propose therapeutics and recommendations in agreement with management guidelines. Implementation of multidisciplinary measures to control the outbreak and educate the population is required.

La importancia de la correlación clínico- epidemiológica en el diagnóstico temprano de la histoplasmosis: reporte de dos casos clínicos en Popayán, Colombia / The relevance of clinical and epidemiological correlation in the early diagnosis of histoplasmosis: report of two clinical cases in Popayán, Colombia

La histoplasmosis es una micosis endémica en Colombia. Se presentan dos casos del departamento del Cauca, para mostrar el impacto clínico que conlleva un retraso en su diagnóstico y tratamiento. Se obtuvo el consentimiento informado para revisar las historias clínicas de los pacientes y publicar los casos. El primer caso se trata de un paciente con infección por el virus de inmunodeficiencia humana (Human Immunodeficiency Virus, HIV), quien presentaba lesiones cutáneas generalizadas atribuidas inicialmente al virus del herpes; post mortem y mediante el cultivo para hongos de muestras de las lesiones dérmicas, se confirmó el diagnóstico de histoplasmosis. El segundo caso es un paciente inmunocompetente con sintomatología pulmonar, a quien se le diagnosticó tuberculosis clínicamente y se le instauró tratamiento; sin embargo, ante la nula mejoría y teniendo en cuenta el antecedente de ingreso a una cueva de murciélagos, se enfocó como una posible histoplasmosis pulmonar y se obtuvo mejoría con el tratamiento. Se revisó la literatura sobre las pruebas de laboratorio y los datos epidemiológicos de histoplasmosis que deben considerar los profesionales de la salud. Se concluyó que las instituciones de salud deben disponer de pruebas rápidas (por ejemplo, antigénicas) para el diagnóstico y tratamiento adecuado de esta micosis, además de adoptar los correctivos necesarios para minimizar la exposición a Histoplasma.

Histoplasmosis is an endemic mycosis in Colombia. Here we present two cases in the Cauca department, to indicate the clinical impact of histoplasmosis delayed diagnosis and treatment when its epidemiology is unknown. Informed consent was requested to review patients' medical records and case report publication. The first case was a patient diagnosed with human immunodeficiency virus and generalized presence of skin lesions. Initially, these lesions were diagnosed as herpes, but a postmortem diagnosis confirmed histoplasmosis through fungal cultures of tissues from the skin lesions. The second case is an immunocompetent patient with pulmonary symptoms diagnosed and treated for tuberculosis. However, given the lack of improvement and considering the bat cave entrance history, the patient was treated for possible pulmonary histoplasmosis with an adequate response. We made a review of laboratory tests and histoplasmosis epidemiological data relevant to health professionals. We concluded that health institutions must provide rapid tests, such as antigen ones, to adequately diagnose and treat this mycosis; and also take corrective measures to minimize exposure to Histoplasma.

COVID-19 vaccination rate and willingness of an additional dose among inflammatory bowel disease patients receiving biologic therapy: Fearless and with desire / Tasa de vacunación y aceptación de la dosis adicional de la vacuna frente al COVID-19 en los pacientes con enfermedad inflamatoria intestinal que reciben terapia biológica: sin miedo y con ganas

Background: Vaccination against COVID-19 prevents its severe forms and associated mortality and offers a promising action to control this pandemic. In September 2021, an additional dose of vaccine was approved in patients with immunosuppression including IBD patients on biologic agents. We evaluated the vaccination rate and additional dose willingness in this group of at risk patients. Methods: A single-center, cross-sectional study was performed among IBD patients on biologic agents and eligible for an additional dose of the COVID-19 vaccine. IBD clinical characteristics and type of vaccine and date of administration were checked in medical records. Acceptance was evaluated after telephone or face-to-face surveys in IBD patients. Results: Out of a total of 344 patients, 269 patients (46.1% male; mean age 47±16 years; Crohn's disease 73.6%) were included. Only 15 (5.6%) patients refused the COVID-19 vaccine mainly (40%) for conviction (COVID-19 pandemic denial). 33.3% would re-consider after discussing with their doctor and/or receiving information on the adverse effects of the vaccine. Previous to the additional dose, the COVID-19 vaccination was present in 94.4% of patients (n=254). Adverse effects occurred in 53.9% of the cases, mainly pain in the arm (40%). Up to 94.1% of the patients agreed to an additional dose and 79.4% had already received the additional dose at the final time of the assessment. Conclusions: IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. Physicians in charge of IBD units should provide information and confidence in the use of the vaccine in these IBD patients.(AU)

Antecedentes: La vacunación frente al COVID-19 constituye una acción prometedora para controlar esta pandemia. En septiembre de 2021, se aprobó una dosis adicional de vacuna en pacientes con inmunosupresión, incluidos los pacientes con enfermedad inflamatoria intestinal (EII) que reciben agentes biológicos. En este estudio se evaluó la tasa de vacunación y la disposición de recibir la dosis adicional de vacuna en este grupo de pacientes de riesgo. Métodos: Se realizó un estudio transversal unicéntrico con pacientes afectos de EII con tratamiento biológico y elegibles para una dosis adicional de la vacuna COVID-19. Se evaluó la aceptación y los efectos adversos de la vacuna mediante encuesta telefónica o presencial y se recopiló en las historias clínicas las características de la EII, el tipo de vacuna recibida y la fecha de administración. Resultados: De un total de 344 pacientes, 269 (46,1% varones; edad media 47±16 años; enfermedad de Crohn n=198) fueron incluidos. Solo 15 (5,6%) pacientes rechazaron la vacuna frente al COVID-19, el 40% por convicción (negación de la pandemia COVID-19). Antes de la dosis adicional, la vacuna COVID-19 se había administrado en el 94,4% de los pacientes (n=254). En el 53,9% de los casos presentaron efectos adversos, principalmente dolor en el brazo (40%). Hasta el 94,1% de los pacientes refería la aceptación de una dosis adicional de la vacuna y el 79,1% ya había recibido esta dosis adicional en el momento de la evaluación final. Conclusiones: Los pacientes con EII que reciben agentes biológicos aceptan la vacuna frente al COVID-19, así como una dosis adicional si se les recomienda. Los médicos responsables de las unidades de EII deben proporcionar información y confianza en el uso de la vacuna en estos pacientes.(AU)

Neutrophil-to-lymphocyte ratio as an independent factor for worse prognosis in radioiodine refractory thyroid cancer patients.

PURPOSE: This study aimed to evaluate neutrophil to lymphocyte ratio (NLR) as a laboratory biomarker in radioactive iodine-refractory (RAIR) locally advanced and/or metastatic differentiated thyroid cancer (DTC) and determine its correlation with overall survival (OS). METHODS: We retrospectively included 172 patients with locally advanced and/or metastatic RAIR DTC admitted between 1993 and 2021 at INCA. Age at diagnosis, histology, presence of distant metastasis (DM), DM site, neutrophil-to- lymphocyte ratio (NLR), imaging studies such as PET/CT results, progression free survival (PFS) and overall survival (OS) data were analyzed. NLR was calculated at the time of locally advanced and/or metastatic disease diagnosis and the cutoff value was 3. Survival curves were established using the Kaplan-Meier method. The confidence interval is 95%, and a p-value of less than 0.05 was considered statistically significant RESULTS: Out of 172 patients, 106 were locally advanced, and 150 presented DM at some point during follow-up. Regarding NLR data, 35 had NLR over 3 and 137 had NLR under 3. Higher NLR at was associated with shorter OS (6 vs. 10; p = 0.05) and with highest SUV on FDG PET-CT (15.9 vs. 7.7, p = 0.013). We found no association between higher NLR and age at diagnosis, DM or final status. CONCLUSION: NLR higher than 3 at the time of locally advanced and/or metastatic disease diagnosis is an independent fator for shorter OS in RAIR DTC patients. Noteworthy higher NLR was also associated with highest SUV on FDG PET-CT in this population.

Molecular Sensitization Enabled High Performance Organic Metal Halide Hybrid Scintillator.

Scintillators, one of the essential components in medical imaging and security checking devices, rely heavily on rare-earth-containing inorganic materials. Here, a new type of organic-inorganic hybrid scintillators containing earth abundant elements that can be prepared via low-temperature processes is reported. With room temperature co-crystallization of an aggregation-induced emission (AIE) organic halide, 4-(4-(diphenylamino) phenyl)-1-(propyl)-pyrindin-1ium bromide (TPA-PBr), and a metal halide, zinc bromide (ZnBr2 ), a zero-dimensional (0D) organic metal halide hybrid (TPA-P)2 ZnBr4 with a yellowish-green emission peaked at 550 nm has been developed. In this hybrid material, dramatically enhanced X-ray scintillation of TPA-P+ is achieved via the sensitization by ZnBr4 2- . The absolute light yield (14,700 ± 800 Photons/MeV) of (TPA-P)2 ZnBr4 is found to be higher than that of anthracene (≈13,500 Photons/MeV), a well-known organic scintillator, while its X-ray absorption is comparable to those of inorganic scintillators. With TPA-P+ as an emitting center, short photoluminescence and radioluminescence decay lifetimes of 3.56 and 9.96 ns have been achieved. Taking the advantages of high X-ray absorption of metal halides and efficient radioluminescence with short decay lifetimes of organic cations, the material design paves a new pathway to address the issues of low X-ray absorption of organic scintillators and long decay lifetimes of inorganic scintillators simultaneously.

COVID-19 vaccination rate and willingness of an additional dose among inflammatory bowel disease patients receiving biologic therapy: Fearless and with desire.

Effective vaccines against the SARS-CoV-2 are already available and offer a promising action to control the COVID-19 pandemic. IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. BACKGROUND: Vaccination against COVID-19 prevents its severe forms and associated mortality and offers a promising action to control this pandemic. In September 2021, an additional dose of vaccine was approved in patients with immunosuppression including IBD patients on biologic agents. We evaluated the vaccination rate and additional dose willingness in this group of at risk patients. METHODS: A single-center, cross-sectional study was performed among IBD patients on biologic agents and eligible for an additional dose of the COVID-19 vaccine. IBD clinical characteristics and type of vaccine and date of administration were checked in medical records. Acceptance was evaluated after telephone or face-to-face surveys in IBD patients. RESULTS: Out of a total of 344 patients, 269 patients (46.1% male; mean age 47±16 years; Crohn's disease 73.6%) were included. Only 15 (5.6%) patients refused the COVID-19 vaccine mainly (40%) for conviction (COVID-19 pandemic denial). 33.3% would re-consider after discussing with their doctor and/or receiving information on the adverse effects of the vaccine. Previous to the additional dose, the COVID-19 vaccination was present in 94.4% of patients (n=254). Adverse effects occurred in 53.9% of the cases, mainly pain in the arm (40%). Up to 94.1% of the patients agreed to an additional dose and 79.4% had already received the additional dose at the final time of the assessment. CONCLUSIONS: IBD patients on biological agents accept the vaccine as well as an additional dose if recommended. Physicians in charge of IBD units should provide information and confidence in the use of the vaccine in these IBD patients.

Efficient Red Light Emitting Diodes Based on a Zero-Dimensional Organic Antimony Halide Hybrid.

Zero-dimensional (0D) organic metal halide hybrids (OMHHs) have recently emerged as a new class of light emitting materials with exceptional color tunability. While near-unity photoluminescence quantum efficiencies (PLQEs) are routinely obtained for a large number of 0D OMHHs, it remains challenging to apply them as emitter for electrically driven light emitting diodes (LEDs), largely due to the low conductivity of wide bandgap organic cations. Here, the development of a new OMHH, triphenyl(9-phenyl-9H-carbazol-3-yl) phosphonium antimony bromide (TPPcarzSbBr4 ), as emitter for efficient LEDs, which consists of semiconducting organic cations (TPPcarz+ ) and light emitting antimony bromide anions (Sb2 Br8 2- ), is reported. By replacing one of the phenyl groups in a well-known tetraphenylphosphonium cation (TPP+ ) with an electroactive phenylcarbazole group, a semiconducting TPPcarz+ cation is developed for the preparation of red emitting 0D TPPcarzSbBr4 single crystals with a high PLQE of 93.8%. With solution processed TPPcarzSbBr4 thin films (PLQE of 86.1%) as light emitting layer, red LEDs are fabricated to exhibit an external quantum efficiency (EQE) of 5.12%, a peak luminance of 5957 cd m-2 , and a current efficiency of 14.2 cd A-1 , which are the best values reported to date for electroluminescence devices based on 0D OMHHs.

FoxO1 is required for high glucose-dependent cardiac fibroblasts into myofibroblast phenoconversion.

In the normal heart, cardiac fibroblasts (CFs) maintain extracellular matrix (ECM) homeostasis, whereas in pathological conditions, such as diabetes mellitus (DM), CFs converse into cardiac myofibroblasts (CMFs) and this CFs phenoconversion increase the synthesis and secretion of ECM proteins, promoting cardiac fibrosis and heart dysfunction. High glucose (HG) conditions increase TGF-ß1 expression and FoxO1 activity, whereas FoxO1 is crucial to CFs phenoconversion induced by TGF-ß1. In addition, FoxO1 increases CTGF expression, whereas CTGF plays an active role in the fibrotic process induced by hyperglycemia. However, the role of FoxO1 and CTGF in CFs phenoconversion induced by HG is not clear. In this study, we investigated the effects of FoxO1 pharmacological inhibition on CFs phenoconversion in both in vitro and ex vivo models of DM. Our results demonstrate that HG induces CFs phenoconversion and FoxO1 activation. Moreover, AS1842856, a pharmacological inhibitor of FoxO1 activity, prevents CFs phenoconversion and CTGF expression increase induced by HG, whereas these results were corroborated by FoxO1 silencing. Additionally, K252a, a pharmacological blocker of CTGF receptor, prevents HG-induced CFs phenoconversion, which was corroborated with CTGF expression knockdown. Furthermore, through CFs isolation from heart of diabetic rats, we showed that hyperglycemia induces FoxO1 activation, the increase of CTGF expression and CFs phenoconversion, whereas the FoxO1 activity inhibition reverses the effects induced by hyperglycemia on CFs. Altogether, our results demonstrate that FoxO1 and CTGF are necessary for CFs phenoconversion induced by HG and suggest that both proteins are likely to become a potential targeted drug for fibrotic response induced by hyperglycemic conditions.

Attitudes of Costa Rican individuals towards donation of personal genetic data for research.

Aim: We explore attitudes from the public in Costa Rica regarding willingness to donate DNA data for research. Materials & methods: A total of 224 Costa Rican individuals answered the anonymous online survey 'Your DNA, Your Say'. It covers attitudes toward DNA and medical data donation, trust in research professionals and concerns about consequences of reidentification. Results & conclusion: Most individuals (89%) are willing to donate their information for research purposes. When confronted with different potential uses of their data, participants are significantly less likely to donate data to for-profit researchers (34% willingness to donate). The most frequently cited concerns regarding donation of genetic data relate to possible discrimination by health/life insurance companies and employers. For the participants in the survey, the most trusted professionals are their own medical doctor and nonprofit researchers from their country. This is the first study regarding attitudes toward genetic data donation in Costa Rica.

SARS coronavirus protein nsp1 disrupts localization of Nup93 from the nuclear pore complex.

Severe acute respiratory syndrome coronavirus nonstructural protein 1 (nsp1) is a key factor in virus-induced down-regulation of host gene expression. In infected cells, nsp1 engages in a multipronged mechanism to inhibit host gene expression by binding to the 40S ribosome to block the assembly of translationally competent ribosome, and then inducing endonucleolytic cleavage and the degradation of host mRNAs. Here, we report a previously undetected mechanism by which nsp1 exploits the nuclear pore complex and disrupts the nuclear-cytoplasmic transport of biomolecules. We identified members of the nuclear pore complex from the nsp1-associated protein assembly and found that the expression of nsp1 in HEK cells disrupts Nup93 localization around the nuclear envelope without triggering proteolytic degradation, while the nuclear lamina remains unperturbed. Consistent with its role in host shutoff, nsp1 alters the nuclear-cytoplasmic distribution of an RNA binding protein, nucleolin. Our results suggest that nsp1, alone, can regulate multiple steps of gene expression including nuclear-cytoplasmic transport.

Nivel de ruido ambiental en 2 unidades de cuidados críticos de un centro de tercer nivel de atención / Environmental noise levels in 2 intensive care units in a tertiary care centre

Resumen Introducción: La Organización Mundial de la Salud establece como nivel máximo de ruido 40 decibelios (dB) para una unidad de cuidados críticos. El objetivo de este estudio fue comparar la intensidad del nivel de ruido ambiental en 2 unidades de cuidados críticos de un hospital de tercer nivel de atención. Métodos: En un diseño observacional, descriptivo y transversal se comparó el nivel máximo de ruido dentro de la unidad de cuidados intensivos metabólicos y coronarios con un medidor digital. La medición en 4 puntos diferentes de cada habitación con intervalos de 5 min durante un período de 60 min se llevó a cabo a las 7:30, 14:30 y 20:30. El promedio de las observaciones se comparó con estadística descriptiva y U de Mann-Whitney. Un análisis con la prueba de Kruskal-Wallis se realizó para comparar los promedios de ruido en las diferentes lecturas. Resultados: Se observó que el ruido en la unidad de cuidados intensivos tuvo un promedio de 64.77 ± 3.33 dB (p = 0.08); algo similar sucedió en la unidad de cuidados intensivos metabólicos coronarios con un promedio de 60.20 ± 1.58 dB (p = 0.129). El 25% o más de las mediciones superaron hasta por 20 puntos lo recomendado por la Organización Mundial de la Salud. Conclusiones: El nivel de ruido que se encontró en las unidades de cuidados intensivos estudiadas sobrepasan el nivel máximo recomendado para un hospital. Es necesario diseñar y aplicar acciones para una mayor participación del personal de salud en la disminución del ruido ambiental.

Abstract Introduction: The World Health Organisation (WHO) has established a maximum noise level of 40 decibels (dB) for an intensive care unit. The aim of this study was to compare the noise levels in 2 different intensive care units at a tertiary care centre. Methods: Using a cross-sectional design study, an analysis was made of the maximum noise level was within the intensive coronary care unit and intensive care unit using a digital meter. A measurement was made in 4 different points of each room, with 5 minute intervals, for a period of 60 minutes 7:30, 14:30, and 20:30. The means of the observations were compared with descriptive statistics and Mann-Whitney U. An analysis with Kruskal-Wallis test was performed to the mean noise level. Results: The noise observed in the intensive care unit had a mean of 64.77 ± 3.33 dB (P = .08), which was similar to that in the intensive coronary care unit, with a mean of 60.20 ± 1.58 dB (P = .129). Around 25% or more of the measurements exceeded the level recommended by the WHO by up to 20 points. Conclusions: Noise levels measured in intensive care wards exceed the maximum recommended level for a hospital. It is necessary to design and implement actions for greater participation of health personnel in the reduction of environmental noise.