hnRNPM protects against the dsRNA-mediated interferon response by repressing LINE-associated cryptic splicing.

RNA splicing is pivotal in post-transcriptional gene regulation, yet the exponential expansion of intron length in humans poses a challenge for accurate splicing. Here, we identify hnRNPM as an essential RNA-binding protein that suppresses cryptic splicing through binding to deep introns, maintaining human transcriptome integrity. Long interspersed nuclear elements (LINEs) in introns harbor numerous pseudo splice sites. hnRNPM preferentially binds at intronic LINEs to repress pseudo splice site usage for cryptic splicing. Remarkably, cryptic exons can generate long dsRNAs through base-pairing of inverted ALU transposable elements interspersed among LINEs and consequently trigger an interferon response, a well-known antiviral defense mechanism. Significantly, hnRNPM-deficient tumors show upregulated interferon-associated pathways and elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity by repressing cryptic splicing and suggest that targeting hnRNPM in tumors may be used to trigger an inflammatory immune response, thereby boosting cancer surveillance.

Cytochrome c levels affect the TOR pathway to regulate growth and metabolism under energy-deficient conditions.

Mitochondrial function is essential for plant growth, but the mechanisms involved in adjusting growth and metabolism to changes in mitochondrial energy production are not fully understood. We studied plants with reduced expression of CYTC-1, one of two genes encoding the respiratory chain component cytochrome c (CYTc) in Arabidopsis, to understand how mitochondria communicate their status to coordinate metabolism and growth. Plants with CYTc deficiency show decreased mitochondrial membrane potential and lower ATP content, even when carbon sources are present. They also exhibit higher free amino acid content, induced autophagy, and increased resistance to nutritional stress caused by prolonged darkness, similar to plants with triggered starvation signals. CYTc deficiency affects target of rapamycin (TOR)-pathway activation, reducing S6 kinase (S6K) and RPS6A phosphorylation, as well as total S6K protein levels due to increased protein degradation via proteasome and autophagy. TOR overexpression restores growth and other parameters affected in cytc-1 mutants, even if mitochondrial membrane potential and ATP levels remain low. We propose that CYTc-deficient plants coordinate their metabolism and energy availability by reducing TOR-pathway activation as a preventive signal to adjust growth in anticipation of energy exhaustion, thus providing a mechanism by which changes in mitochondrial activity are transduced to the rest of the cell.

Functional analysis of CTLA4 promoter variant and its possible implication in colorectal cancer immunotherapy.

Background: Colorectal cancer (CRC) is a prevalent cancer, ranking as the third most common. Recent advances in our understanding of the molecular causes of this disease have highlighted the crucial role of tumor immune evasion in its initiation and progression. CTLA4, a receptor that acts as a negative regulator of T cell responses, plays a pivotal role in this process, and genetic variations in CTLA4 have been linked to CRC susceptibility, prognosis, and response to therapy. Methods: We conducted a case-control study involving 98 CRC patients and 424 controls. We genotyped the CTLA4 c.-319C > T variant (rs5742909) and performed an association analysis by comparing allele frequencies between the patients and controls. To assess the potential functional impact of this variant, we first performed an In Silico analysis of transcription factor binding sites using Genomatix. Finally, to validate our findings, we conducted a luciferase reporter gene assay using different cell lines and an electrophoretic mobility shift assay (EMSA). Results: The case-control association analysis revealed a significant association between CTLA4 c.-319C > T and CRC susceptibility (p = 0.023; OR 1.89; 95% CI = 1.11-3.23). Genomatix analysis identified LEF1 and TCF7 transcription factors as specific binders to CTLA4 c.-319C. The reporter gene assay demonstrated notable differences in luciferase activity between the c.-319 C and T alleles in COS-7, HCT116, and Jurkat cell lines. EMSA analysis showed differences in TCF7 interaction with the CTLA4 C and T alleles. Conclusion: CTLA4 c.-319C > T is associated with CRC susceptibility. Based on our functional validation results, we proposed that CTLA4 c.-319C > T alters gene expression at the transcriptional level, triggering a stronger negative regulation of T-cells and immune tumoral evasion.

Minireview: functional roles of tissue kallikrein, kinins, and kallikrein-related peptidases in lung cancer.

Despite campaigns and improvements in detection and treatment, lung cancer continues to increase worldwide and represents a major public health problem. One approach to treating patients suffering from lung cancer is to target surface receptors overexpressed on tumor cells, such as GPCR-family kinin receptors, and proteases that control tumor progression, such as kallikrein-related peptidases (KLKs). These proteases have been visualized in recent years due to their contribution to the progression of cancers, such as prostate and ovarian cancer, facilitating the invasive and metastatic capacity of tumor cells in these tissues. In fact, KLK3 is the specific prostate antigen, the only tissue-specific biomarker used to diagnose this malignancy. In lung cancer to date, evidence indicates that KLK5, KLK6, KLK8, KLK11, and KLK14 are the major peptidases regulated and involved in its progression. The expression levels of KLKs in this neoplasm are modulated by the secretome of the different cell types present in the tumor microenvironment, the cancer subtype and the tumor stage, among others. Considering the multiple functions of kinin receptors and KLKs, this review highlights their roles, even considering the SARS-CoV-2 effects. Since lung cancer is often diagnosed in advanced stages, our efforts should focus on early diagnosis, validating for example specific KLKs, especially in high-risk populations such as smokers and people exposed to carcinogenic fumes, oil fields, and contaminated workplaces, unexplored fields to investigate. Furthermore, their modulation could be considered as a promising approach in lung cancer therapeutics.

Effect of paediatric early warning systems (PEWS) implementation on clinical deterioration event mortality among children with cancer in resource-limited hospitals in Latin America: a prospective, multicentre cohort study.

BACKGROUND: Paediatric early warning systems (PEWS) aid in the early identification of clinical deterioration events in children admitted to hospital. We aimed to investigate the effect of PEWS implementation on mortality due to clinical deterioration in children with cancer in 32 resource-limited hospitals across Latin America. METHODS: Proyecto Escala de Valoración de Alerta Temprana (Proyecto EVAT) is a quality improvement collaborative to implement PEWS in hospitals providing childhood cancer care. In this prospective, multicentre cohort study, centres joining Proyecto EVAT and completing PEWS implementation between April 1, 2017, and May 31, 2021, prospectively tracked clinical deterioration events and monthly inpatient-days in children admitted to hospital with cancer. De-identified registry data reported between April 17, 2017, and Nov 30, 2021, from all hospitals were included in analyses; children with limitations on escalation of care were excluded. The primary outcome was clinical deterioration event mortality. Incidence rate ratios (IRRs) were used to compare clinical deterioration event mortality before and after PEWS implementation; multivariable analyses assessed the correlation between clinical deterioration event mortality and centre characteristics. FINDINGS: Between April 1, 2017, and May 31, 2021, 32 paediatric oncology centres from 11 countries in Latin America successfully implemented PEWS through Proyecto EVAT; these centres documented 2020 clinical deterioration events in 1651 patients over 556 400 inpatient-days. Overall clinical deterioration event mortality was 32·9% (664 of 2020 events). The median age of patients with clinical deterioration events was 8·5 years (IQR 3·9-13·2), and 1095 (54·2%) of 2020 clinical deterioration events were reported in male patients; data on race or ethnicity were not collected. Data were reported per centre for a median of 12 months (IQR 10-13) before PEWS implementation and 18 months (16-18) after PEWS implementation. The mortality rate due to a clinical deterioration event was 1·33 events per 1000 patient-days before PEWS implementation and 1·09 events per 1000 patient-days after PEWS implementation (IRR 0·82 [95% CI 0·69-0·97]; p=0·021). In the multivariable analysis of centre characteristics, higher clinical deterioration event mortality rates before PEWS implementation (IRR 1·32 [95% CI 1·22-1·43]; p<0·0001), being a teaching hospital (1·18 [1·09-1·27]; p<0·0001), not having a separate paediatric haematology-oncology unit (1·38 [1·21-1·57]; p<0·0001), and having fewer PEWS omissions (0·95 [0·92-0·99]; p=0·0091) were associated with a greater reduction in clinical deterioration event mortality after PEWS implementation; no association was found with country income level (IRR 0·86 [95% CI 0·68-1·09]; p=0·22) or clinical deterioration event rates before PEWS implementation (1·04 [0·97-1·12]; p=0·29). INTERPRETATION: PEWS implementation was associated with reduced clinical deterioration event mortality in paediatric patients with cancer across 32 resource-limited hospitals in Latin America. These data support the use of PEWS as an effective evidence-based intervention to reduce disparities in global survival for children with cancer. FUNDING: American Lebanese Syrian Associated Charities, US National Institutes of Health, and Conquer Cancer Foundation. TRANSLATIONS: For the Spanish and Portuguese translations of the abstract see Supplementary Materials section.

Loss-of-function mutations in WRKY22 and WRKY25 impair stomatal-mediated immunity and PTI and ETI responses against Pseudomonas syringae pv. tomato.

Plants defend themselves against pathogens using a two-layered immune system. The first response, pattern-triggered immunity (PTI), is activated upon recognition of microbe-associated molecular patterns (MAMPs). Virulent bacteria such as Pseudomonas syringae pv. tomato (Pst), deliver effector proteins into the plant cell to promote susceptibility. However, some plants possess resistance (R) proteins that recognize specific effectors leading to the activation of the second response, effector-triggered immunity (ETI). Resistant tomatoes such as Río Grande-PtoR recognize two Pst effectors (AvrPto and AvrPtoB) through the host Pto/Prf complex and activate ETI. We previously showed that the transcription factors (TF) WRKY22 and WRKY25 are positive regulators of plant immunity against bacterial and potentially non-bacterial pathogens in Nicotiana benthamiana. Here, the CRISPR-Cas9 technique was used to develop three knockout tomato lines for either one or both TFs. The single and double mutants were all compromised in Pto/Prf-mediated ETI and had a weaker PTI response. The stomata apertures in all of the mutant lines did not respond to darkness or challenge with Pst DC3000. The WRKY22 and WRKY25 proteins both localize in the nucleus, but we found no evidence of a physical interaction between them. The WRKY22 TF was found to be involved in the transcriptional regulation of WRKY25, supporting the idea that they are not functionally redundant. Together, our results indicate that both WRKY TFs play a role in modulating stomata and are positive regulators of plant immunity in tomato.

LINE-associated cryptic splicing induces dsRNA-mediated interferon response and tumor immunity.

RNA splicing plays a critical role in post-transcriptional gene regulation. Exponential expansion of intron length poses a challenge for accurate splicing. Little is known about how cells prevent inadvertent and often deleterious expression of intronic elements due to cryptic splicing. In this study, we identify hnRNPM as an essential RNA binding protein that suppresses cryptic splicing through binding to deep introns, preserving transcriptome integrity. Long interspersed nuclear elements (LINEs) harbor large amounts of pseudo splice sites in introns. hnRNPM preferentially binds at intronic LINEs and represses LINE-containing pseudo splice site usage for cryptic splicing. Remarkably, a subgroup of the cryptic exons can form long dsRNAs through base-pairing of inverted Alu transposable elements scattered in between LINEs and trigger interferon immune response, a well-known antiviral defense mechanism. Notably, these interferon-associated pathways are found to be upregulated in hnRNPM-deficient tumors, which also exhibit elevated immune cell infiltration. These findings unveil hnRNPM as a guardian of transcriptome integrity. Targeting hnRNPM in tumors may be used to trigger an inflammatory immune response thereby boosting cancer surveillance.

Expression and distribution of kallikrein-related peptidases 5, 7, 8 and 10 in normal apocrine gland of canine skin / Expresión y distribución de péptidos relacionados con la calicreína 5, 7, 8 y 10 en glándula apocrina normal de piel canina

SUMMARY: Apocrine glands are sweat glands that are located in the skin of the dog. Anal sac apocrine, circunanal apocrine, and mammary glands are considered modified apocrine structures, and there are about nine possible types of neoplasms and other tumors in the apocrine glands of the dog and cat, including cysts, adenoma, carcinoma, and adenocarcinoma. Thus, it is important to provide new markers to characterize these glands to improve the histopathological diagnosis. In this article, we describe the distribution of kallikrein- related peptidases 5, 7, 8, and 10 in the normal apocrine glands of the dog's skin. These proteases have been shown to play a fundamental role in the homeostasis of the human skin barrier but have been scarcely studied in canine skin.

Las glándulas apocrinas son glándulas sudoríparas que se encuentran en la piel del perro. Las glándulas apocrinas del saco anal, apocrinas circunanales y mamarias se consideran estructuras apocrinas modificadas, y existen alrededor de nueve tipos posibles de neoplasias y otros tumores en las glándulas apocrinas del perro y el gato, incluidos quistes, adenoma, carcinoma y adenocarcinoma. Por lo tanto, es importante proporcionar nuevos marcadores para caracterizar estas glándulas para mejorar el diagnóstico histopatológico. En este artículo, describimos la distribución de las peptidasas 5, 7, 8 y 10 relacionadas con la calicreína en las glándulas apocrinas normales de la piel del perro. Se ha demostrado que estas proteasas desempeñan un papel fundamental en la homeostasis de la barrera de la piel humana, pero apenas se han estudiado en la piel canina.

Recursos educativos digitales como herramientas de apoyo para la enseñanza de patología general en cursos de pregrado del área de la salud / Digital educational resources as support tools for teaching general pathology in undergraduate health courses

Los recursos educativos digitales se han transformado en un importante material de apoyo al proceso de enseñanza- aprendizaje, especialmente durante la pandemia por COVID-19. Estos corresponden a recursos de autoaprendizaje, generalmente en línea y de dominio público cuya disponibilidad inmediata a todo tipo de dispositivos electrónicos permite una rápida interacción del estudiante con materiales didácticos programados. El objetivo de este estudio fue evaluar el grado de satisfacción de cinco recursos educativos digitales, desarrollados como herramientas de apoyo para la enseñanza de la patología general, en estudiantes de carreras de pregrado del área de la salud de la Universidad Austral de Chile. Estudio descriptivo y exploratorio. Se desarrollaron cinco recursos educativos digitales donde se visualizan imágenes microscópicas correspondientes a procesos patológicos ocurridos en diferentes tejidos. Estos recursos fueron alojados en repositorios de la universidad y se encuentran actualmente disponibles en el canal de YouTube. Para conocer el grado de satisfacción, en sus aspectos pedagógicos y técnicos, se realizó una encuesta digital, anónima y voluntaria a estudiantes que cursaron asignaturas de patología, la que contempló cuatro dominios con sus respectivas preguntas: forma; control de usuario; contenido educativo y valoración global. El 94 % de los estudiantes calificaron el recurso de excelente o muy bueno y todos los dominios obtuvieron sobre el 80 % de satisfacción. Los contenidos representan lo que el recurso dice ofrecer, ayuda a resolver dudas y facilita la comprensión de la materia. El tamaño y color del texto es el adecuado y las imágenes presentan una excelente calidad y resolución. Los recursos cumplen con una alta calidad técnica y pedagógica, que asegura un gran potencial de uso para la enseñanza de la patología general, guiar el trabajo autónomo del estudiante y las actividades prácticas con el microscopio.

SUMMARY: Digital educational resources have become an important material to support the teaching-learning process, especially during the COVID-19 pandemic. These correspond to self-learning resources, generally online and the public domain, whose immediate availability to all types of electronic devices allows for rapid learner interaction with programmed didactic materials. The public domain and its immediate availability to all types of electronic devices allows a quick interaction of the student with self-explanatory didactic materials. The objective of this study was to evaluate the degree of satisfaction of five digital educational resources, developed as support tools for the teaching of general pathology, in undergraduate students of the health area of the Universidad Austral de Chile. Descriptive and exploratory study. Five digital educational resources have been developed where microscopic images corresponding to pathological processes occurring in different tissues are visualized these resources were hosted in university repositories and uploaded to the YouTube channel. To determine the degree of satisfaction, in their pedagogical and technical aspects, an anonymous and voluntary digital survey was carried out among students taking pathology courses, which included four domains with their respective questions: form; user control; educational content and overall assessment. The 94 % of the students evaluated the resource as excellent or very good and all domains obtained over 80 % satisfaction. The contents represent what the resource says it offers, helps to resolve doubts and facilitates the understanding of the subject. The size and color of the text is adequate, and the images present excellent quality and resolution. The resources developed offer a high technical and pedagogical quality, which guarantees a great potential for use in the teaching of general pathology, guiding the student's autonomous work and practical activities with the microscope.

Post-polypectomy syndrome-a rare complication in colonoscopy procedures: a case report.

Post-polypectomy syndrome (PPS) is a complication that may arise after some colonoscopy procedures that require electrocoagulation, due to a transmural burn, which irritates the serous membrane. Its clinical presentation is similar to the one of intestinal perforation, but it has a favorable prognosis, and does not require surgical treatment. We report the case of a 55-year-old woman diagnosed with a polyp in the ascending colon, who was admitted for an endoscopic resection. After the procedure, she complained of nausea, emesis and abdominal pain in the right iliac fossa. She was transferred to the emergency department. An abdominal tomography showed cecal wall thickening without pneumoperitoneum. Therefore, the diagnosis of PPS was made and was managed with bowel rest, parenteral fluids and antibiotics, with full recovery. Despite of its low incidence, it is important to suspect this syndrome to avoid unnecessary surgical treatment and initiate medical management right away.

Regulation of Anthocyanin Biosynthesis by Drought and UV-B Radiation in Wild Tomato (Solanum peruvianum) Fruit.

Anthocyanins are plant pigments derived from the phenylpropanoid pathway which are produced in many different species, contributing to defense against stresses by their antioxidant properties. Cultivated tomatoes cannot synthesize flavonoids; however, wild tomatoes such as Solanum chilense and Solanum lycopersicoides have anthocyanin pigmented skin. Other wild tomato species such as Solanum peruvianum have been poorly studied concerning anthocyanin accumulation in the fruit. This research is the first to address the regulation of anthocyanin biosynthesis mediated by drought stress and light radiation in S. peruvianum fruit. Transcript accumulation of SpAN2, encoding for a key MYB type transcription factor for the regulation of anthocyanin biosynthesis, was induced in the fruit of plants exposed to drought treatment. In addition, fruit peel accumulates a greater anthocyanin content in water deficit-treated plants. The expression of SpAN2 was also regulated according to sunlight exposure, reaching a higher expression during maximal daily UV radiation and under controlled UV-B treatments. Similar results were observed for the expression of the late flavonoid biosynthetic gene dihydroflavonol 4-reductase (SpDFR). These results suggest that SpAN2 and SpDFR are involved in anthocyanin biosynthesis under drought stress and UV radiation in S. peruvianum.

Absceso hepático por Enterobius vermicularis como diagnóstico diferencial de metástasis hepática en cáncer colorrectal, reporte de caso / Liver Abscess Caused by Enterobius vermicularis as a Differential Diagnosis for Liver Metastasis in Colorectal Cancer, Case Report

Resumen Introducción: el cáncer colorrectal es la cuarta causa de mortalidad asociada con cáncer en el mundo. La identificación de las metástasis de este tumor en el momento prequirúrgico es cada vez más frecuente por los estudios imagenológicos con los que se cuenta en la actualidad. Presentamos el caso de una paciente con infección por Enterobius vermicularis que simula la presencia de metástasis hepáticas. Presentación del caso: se presenta el caso de una paciente femenina proveniente del área rural, con dolor abdominal de 1 año de evolución asociado con hemorragia de vías digestivas bajas y pérdida de peso. Las imágenes y estudios endoscópicos muestran una lesión tumoral en el colon sigmoide con biopsias que reportan adenocarcinoma de colon sigmoides, además de lesiones hepáticas sugestivas de malignidad. Se llevó a resección anterior de recto y sigmoides con anastomosis alta y toma de biopsias hepáticas, que descartaron la malignidad e informaron la presencia de infección hepática por E. vermicularis. Discusión: La infección por E. vermicularis a nivel hepático presentada en el caso es poco frecuente, dicha infección puede simular la presencia de metástasis hepáticas, por lo cual debe tenerse en cuenta como diagnóstico diferencial de enfermedad metastásica de cáncer colorrectal.

Abstract Introduction: colorectal cancer is the fourth leading cause of cancer-related mortality worldwide. The identification of the metastases of this tumor in the preoperative stage is increasingly frequent due to the imaging studies currently available. We present the case of a patient with an infection caused by Enterobius vermicularis that simulates the presence of liver metastases. Case presentation: a female patient from a rural area showing a one-year abdominal pain evolution associated with lower gastrointestinal tract bleeding and weight loss. Endoscopic imaging and studies displayed a tumor lesion in the sigmoid colon, with biopsies reporting sigmoid colon adenocarcinoma and liver lesions suggesting malignancy. Anterior resection of the rectum and sigmoid was performed with high anastomosis and liver biopsies, which ruled out malignancy and reported the presence of liver infection by E. vermicularis. Discussion: in this case, the hepatic E. vermicularis infection was rare. This infection can simulate the presence of liver metastases; therefore, it should be considered a differential diagnosis of metastatic colorectal cancer.

The family of kallikrein-related peptidases and kinin peptides as modulators of epidermal homeostasis.

The epidermis is the outermost skin layer and is part of one of the largest organs in the body; it is supported by the dermis, a network of fibrils, blood vessels, pilosebaceous units, sweat glands, nerves, and cells. The skin as a whole is a protective shield against numerous noxious agents, including microorganisms and chemical and physical factors. These functions rely on the activity of multiple growth factors, peptide hormones, proteases, and specific signaling pathways that are triggered by the activation of distinct types of receptors sited in the cell membranes of the various cell types present in the skin. The human kallikrein family comprises a large group of 15 serine proteases synthesized and secreted by different types of epithelial cells throughout the body, including the skin. At this site, they initiate a proteolytic cascade that generates the active forms of the proteases, some of which regulate skin desquamation, activation of cytokines, and antimicrobial peptides. Kinin peptides are formed by the action of plasma and tissue kallikreins on kininogens, two plasma proteins produced in the liver and other organs. Although kinins are well known for their proinflammatory abilities, in the skin they are also considered important modulators of keratinocyte differentiation. In this review, we summarize the contributions of the kallikreins and kallikrein-related peptidases family and those of kinins and their receptors in skin homeostasis, with special emphasis on their pathophysiological role.

Anal canal lymphoma: Case report and literature review / Linfoma de canal anal, reporte de caso y revisión de la literatura

Abstract Introduction: Primary tumors of the anal canal other than carcinomas are rare entities; among them, anal canal lymphomas are extremely unusual and pose both a diagnostic and therapeutic challenge for the coloproctologist. Case presentation: A male patient with positive human immunodeficiency virus (HIV) with proctalgia and mass sensation at the perianal level. A concentric thickening of the walls of the lower rectum was documented by magnetic resonance imaging, with colonoscopy and biopsies with histopathology compatible with plasmablastic lymphoma. Therefore, a diverting colostomy was performed and, subsequently, the hematology service indicated chemotherapy with the EPOCH scheme. Discussion: Lymphoma of the anus represents 0.2 % of anorectal tumors, most of these are non-Hodgkin's lymphomas; Hodgkin's disease at the anorectal level is even rarer. The population with the highest risk of this entity is HIV-positive patients, such as the patient in this case, although other associated factors are described in the literature.

Resumen Introducción: los tumores primarios del canal anal diferentes a carcinomas son entidades poco frecuentes; dentro de estos, los linfomas del canal anal son extremadamente raros y generan un reto tanto diagnóstico como terapéutico para el coloproctólogo. Presentación de caso: se presenta a continuación un caso clínico de un paciente con virus de inmunodeficiencia humana (VIH) positivo con proctalgia y sensación de masa a nivel perianal, se documentó por resonancia magnética un engrosamiento concéntrico de las paredes del recto inferior, con realización de colonoscopia y biopsias con histopatología compatible con linfoma plasmablástico, por lo que se realizó una colostomía derivativa y, posteriormente, se indicó por el servicio de hematología una quimioterapia con esquema EPOCH. Discusión: el linfoma de ano representa el 0,2 % de los tumores anorrectales, la mayoría de estos corresponde a linfomas no Hodgkin, y es aún más rara la enfermedad de Hodgkin a nivel anorrectal. La población con mayor riesgo de presentar esta entidad es los pacientes con VIH positivo, como el paciente descrito en el caso, aunque existen otros factores asociados descritos en la literatura.

Tracheal stenosis as a complication of prolonged intubation in coronavirus disease 2019 (COVID-19) patients: a Peruvian cohort.

Background: Tracheal stenosis (TS) is associated with prolonged intubation and inflammation due to coronavirus disease 2019 (COVID-19) infection. Because of the COVID-19 pandemic, longer times of mechanical ventilation have been required, and different tracheostomies beyond 10 to 12 days have been made. All of these have increased the number of cases and complexity of tracheal pathology in patients with severe COVID-19 infection. Methods: A retrospective, chart review, from patients who were managed in the Service of Thoracic Surgery of Guillermo Almenara Irigoyen National Hospital, Lima, Peru, with a diagnosis of TS, tracheo-esophageal fistula and tracheomalacia between June 2020 until May 2021. Results: Sixty-three patients were diagnosed with TS because of prolonged intubation due to COVID-19 infection. Mean hospitalization time in the intensive care unit (ICU) was 30 days. Mean mechanical ventilation time was 25 days. The most frequent anatomical localization of TS was upper and middle third (55.6%), upper third (44.4%). Fifty-three patients (84.1%) had TS between 1-4 cm, and ten patients (15.9%) had TS longer than 4 cm. Most patients with TS were classified with Cotton-Myer grade III (88.9%). Conclusions: We report a retrospective study of 63 patients with a diagnosis of TS, in whom corrective surgery was performed: cervical tracheoplasty, Montgomery T tube, or tracheostomy.

Cell-in-cell phenomenon in urinary sediment: a case report.

The internalization of apoptotic cells by non-phagocytic cells has been observed in different tissues and could be an important mechanism for the elimination of dying cells. Here, we describe a probable event of phagocytosis of apoptotic cells mediated by urothelial cells in urinary sediment. A 90-years-old male patient was admitted unconscious to the hospital, visible signs included: pale skin and dry mucous membranes, presumptively diagnosed as dehydration. Blood test revealed anaemia (haemoglobin 130 g/L) and hyperglycaemia (glucose 7.8 mmol/L), urinalysis showed a picture of urinary tract infection (leukocyturia and bacteriuria). The microscopic analysis of urinary sediment revealed the presence of urothelial cells and leukocytes internalized in urothelial cells. Anti-CD68 (membrane marker of macrophages) was tested by immunocytochemistry and a negative result was observed. Based on the findings phagocytosis of apoptotic cells mediated by urothelial cells was identified. This phenomenon can be observed in urinary sediment and should not be confused with a neoplastic process since it is a physiological event of cell elimination.

Structure, function, and evolution of plant ADP-glucose pyrophosphorylase.

KEY MESSAGE: This review outlines research performed in the last two decades on the structural, kinetic, regulatory and evolutionary aspects of ADP-glucose pyrophosphorylase, the regulatory enzyme for starch biosynthesis. ADP-glucose pyrophosphorylase (ADP-Glc PPase) catalyzes the first committed step in the pathway of glycogen and starch synthesis in bacteria and plants, respectively. Plant ADP-Glc PPase is a heterotetramer allosterically regulated by metabolites and post-translational modifications. In this review, we focus on the three-dimensional structure of the plant enzyme, the amino acids that bind the regulatory molecules, and the regions involved in transmitting the allosteric signal to the catalytic site. We provide a model for the evolution of the small and large subunits, which produce heterotetramers with distinct catalytic and regulatory properties. Additionally, we review the various post-translational modifications observed in ADP-Glc PPases from different species and tissues. Finally, we discuss the subcellular localization of the enzyme found in grain endosperm from grasses, such as maize and rice. Overall, this work brings together research performed in the last two decades to better understand the multiple mechanisms involved in the regulation of ADP-Glc PPase. The rational modification of this enzyme could improve the yield and resilience of economically important crops, which is particularly important in the current scenario of climate change and food shortage.

The ADP-glucose pyrophosphorylase from Melainabacteria: a comparative study between photosynthetic and non-photosynthetic bacterial sources.

Until recently, the cyanobacterial phylum only included oxygenic photosynthesizer members. The discovery of Melainabacteria as a group of supposed non-photosynthetic cyanobacteria asked to revisit such scenario. From metagenomic data, we were able to identify sequences encoding putative ADP-glucose pyrophosphorylases (ADP-GlcPPase) from free-living and intestinal Melainabacteria. The respective genes were de novo synthesized and over-expressed in Escherichia coli. The purified recombinant proteins from both Melainabacteria species were active as ADP-GlcPPases, exhibiting Vmax values of 2.3 (free-living) and 7.1 U/mg (intestinal). The enzymes showed similar S0.5 values (∼0.3 mM) for ATP, while the one from the intestinal source exhibited a 6-fold higher affinity toward glucose-1P. Both recombinant ADP-GlcPPases were sensitive to glucose-6P activation (A0.5 ∼0.3 mM) and Pi and ADP inhibition (I0.5 between 0.2 and 3 mM). Interestingly, the enzymes from Melainabacteria were insensitive to 3-phosphoglycerate, which is the principal activator of ADP-GlcPPases from photosynthetic cyanobacteria. As far as we know, this is the first biochemical characterization of an active enzyme from Melainabacteria. This work contributes to a better understanding of the evolution of allosteric regulation in the ADP-GlcPPase family, which is critical for synthesizing the main reserve polysaccharide in prokaryotes (glycogen) and plants (starch). In addition, our results offer further information to discussions regarding the phylogenetic position of Melainabacteria.

Competencia para el cuidado y soporte social percibido en cuidadores de personas con enfermedad cerebrovascular / Competence for care and perceived social support in caregivers of people with cerebrovascular disease

Resumen Las enfermedades cerebrovasculares son una de las principales causas de mortalidad, morbilidad y discapacidad en el mundo según la Organización Mundial de la Salud, al igual que para América Latina y Colombia, generando una gran carga de tipo económica y social para los sistemas de salud, para las personas y familias que lo padecen, los cuales no se encuentran preparados para la atención de este fenómeno. Objetivo Determinar la relación entre soporte social percibido y competencia para el cuidado en el hogar de cuidadores familiares de personas con enfermedad cerebrovascular. Diseño Estudio descriptivo con abordaje cuantitativo y correlacional. La población estuvo constituida por los cuidadores familiares de personas con enfermedad cerebrovascular internados en el Hospital Universitario San José de Popayán. Se utilizó la ficha de caracterización de la diada cuidador-persona con enfermedad crónica GCPC-UN-D1, el cuestionario MOS de apoyo social percibido y la escala de competencia para el cuidado en el hogar. Se realizó análisis descriptivo de las características de la población de estudio, para determinar la correlación entre variables, se acudió al coeficiente de correlación estadístico de Spearman. Resultados Predominan cuidadores del género femenino, con niveles medios de escolaridad. Se evidencia relación estadísticamente significativa entre la competencia para el cuidado en el hogar y el soporte social percibido. Conclusiones Se requiere consolidar intervenciones de soporte social y competencia para el cuidado que disminuyan la carga para el cuidado en los cuidadores familiares.

Abstract Chronic diseases are the main cause of mortality, morbidity and disability in the world according to the World Health Organization, as well as for Latin America and Colombia, generating a great economic and social burden for health systems, for people and families that suffer from it, which are not prepared for the attention of this phenomenon. Objective To determine the relationship between perceived social support and competence for care in the home of family caregivers of people with cerebrovascular disease. Design Descriptive study with quantitative and correlational approach. Population The eligible population is constituted by the family caregivers of people with cerebrovascular disease admitted to the San José de Popayán University Hospital. Collection of information It will be carried out through the approach of family caregivers of people with cerebrovascular disease hospitalized in the San José de Popayán. Instruments Characterization sheet of the caregiver dyad-person with chronic disease GCPC-UN-D1, MOS questionnaire of perceived social support, Competence for home care. A descriptive analysis of the characteristics of the study population will be carried out, in order to determine the correlation between variables, the Spearman statistical correlation coefficient was to used. Results Female caregivers predominate, with average levels of schooling. There is a statistically significant relationship between the competence for home care and the perceived social support. Conclusions It is necessary to consolidate interventions of social support and competence for care that reduce the burden for the care of family caregivers.