Enhanced clinical decisions for management of benign prostatic hyperplasia using patient-reported outcomes: protocol for a prospective observational study.

BACKGROUND: Lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) significantly impact quality of life among older men. Despite the prevalent use of the American Urological Association Symptom Index (AUA-SI) for BPH, this measure overlooks key symptoms such as pain and incontinence, underscoring the need for more comprehensive patient-reported outcome (PRO) tools. This study aims to integrate enhanced PROs into routine clinical practice to better capture the spectrum of LUTS, thereby improving clinical outcomes and patient care. METHODS: This prospective observational study will recruit men with LUTS secondary to BPH aged ≥ 50 years from urology clinics. Participants will be stratified into medical and surgical management groups, with PRO assessments scheduled at regular intervals to monitor LUTS and other health outcomes. The study will employ the LURN Symptom Index (SI)-29 alongside the traditional AUA-SI and other non-urologic PROs to evaluate a broad range of symptoms. Data on comorbidities, symptom severity, and treatment efficacy will be collected through a combination of electronic health records and PROs. Analyses will focus on the predictive power of these tools in relation to symptom trajectories and treatment responses. Aims are to: (1) integrate routine clinical tests with PRO assessment to enhance screening, diagnosis, and management of patients with BPH; (2) examine psychometric properties of the LURN SIs, including test-retest reliability and establishment of clinically meaningful differences; and (3) create care-coordination recommendations to facilitate management of persistent symptoms and common comorbidities measured by PROs. DISCUSSION: By employing comprehensive PRO measures, this study expects to refine symptom assessment and enhance treatment monitoring, potentially leading to improved personalized care strategies. The integration of these tools into clinical settings could revolutionize the management of LUTS/BPH by providing more nuanced insights into patient experiences and outcomes. The findings could have significant implications for clinical practices, potentially leading to updates in clinical guidelines and better health management strategies for men with LUTS/BPH. TRIAL REGISTRATION: This study is registered in ClinicalTrials.gov (NCT05898932).

Structural and biochemical investigations of a HEAT-repeat protein involved in the cytosolic iron-sulfur cluster assembly pathway.

Iron-sulfur clusters are essential for life and defects in their biosynthesis lead to human diseases. The mechanism of cluster assembly and delivery to cytosolic and nuclear client proteins via the cytosolic iron-sulfur cluster assembly (CIA) pathway is not well understood. Here we report cryo-EM structures of the HEAT-repeat protein Met18 from Saccharomyces cerevisiae, a key component of the CIA targeting complex (CTC) that identifies cytosolic and nuclear client proteins and delivers a mature iron-sulfur cluster. We find that in the absence of other CTC proteins, Met18 adopts tetrameric and hexameric states. Using mass photometry and negative stain EM, we show that upon the addition of Cia2, these higher order oligomeric states of Met18 disassemble. We also use pulldown assays to identify residues of critical importance for Cia2 binding and recognition of the Leu1 client, many of which are buried when Met18 oligomerizes. Our structures show conformations of Met18 that have not been previously observed in any Met18 homolog, lending support to the idea that a highly flexible Met18 may be key to how the CTC is able to deliver iron-sulfur clusters to client proteins of various sizes and shapes, i.e. Met18 conforms to the dimensions needed.

Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide.

The eukaryotic cytosolic Fe-S protein assembly (CIA) machinery inserts iron-sulfur (Fe-S) clusters into cytosolic and nuclear proteins. In the final maturation step, the Fe-S cluster is transferred to the apo-proteins by the CIA-targeting complex (CTC). However, the molecular recognition determinants of client proteins are unknown. We show that a conserved [LIM]-[DES]-[WF]-COO- tripeptide is present at the C-terminus of more than a quarter of clients or their adaptors. When present, this targeting complex recognition (TCR) motif is necessary and sufficient for binding to the CTC in vitro and for directing Fe-S cluster delivery in vivo. Remarkably, fusion of this TCR signal enables engineering of cluster maturation on a nonnative protein via recruitment of the CIA machinery. Our study advances our understanding of Fe-S protein maturation and paves the way for bioengineering novel pathways containing Fe-S enzymes.

Cytosolic iron-sulfur protein assembly system identifies clients by a C-terminal tripeptide.

The eukaryotic cytosolic Fe-S protein assembly (CIA) machinery inserts iron-sulfur (Fe-S) clusters into cytosolic and nuclear proteins. In the final maturation step, the Fe-S cluster is transferred to the apo-proteins by the CIA-targeting complex (CTC). However, the molecular recognition determinants of client proteins are unknown. We show that a conserved [LIM]-[DES]-[WF]-COO- tripeptide present at the C-terminus of clients is necessary and sufficient for binding to the CTC in vitro and directing Fe-S cluster delivery in vivo. Remarkably, fusion of this TCR (target complex recognition) signal enables engineering of cluster maturation on a non-native protein via recruitment of the CIA machinery. Our study significantly advances our understanding of Fe-S protein maturation and paves the way for bioengineering applications.

Incidencia de Delírium en una población de adultos mayores de 65 años hospitalizados en un centro de referencia del Nororiente Colombiano / Incidence of Delírium in a population of hospitalized adults over 65 years old in a reference center of Colombian northeast

Resumen Introducción: El delírium es un síndrome neuropsiquiátrico de etiología multifactorial que se presenta de forma frecuente en el adulto mayor hospitalizado. En Santander no hay estudios que describan su incidencia y factores epidemiológicos asociados. Objetivo: Evaluar la incidencia de delírium, características clínicas según el tipo, mortalidad a 30 días de hospitalización y complicaciones asociadas al delírium, en pacientes adultos mayores de 65 años hospitalizados en un departamento del nororiente colombiano. Materiales y métodos: Se incluyeron pacientes ≥ 65 años hospitalizados en sala general de la Clínica FOSCAL. Se excluyeron pacientes con delírium al ingreso, hospitalizados en unidad de cuidado crítico, intubación orotraqueal, Glasgow <8/15 y con limitación para evaluar el delírium de forma adecuada. Resultados: De 492 pacientes hospitalizados con edad promedio de 75 años, la incidencia acumulada fue de 9,3%; con mayor porcentaje en mujeres (63%) y en ≥ 85 años (31,5%). Se evidenció una asociación con mayor estancia hospitalaria (11.0 vs 7.1 días, p <0.05), un mayor deterioro funcional evaluado por escala Barthel y riesgo de mortalidad (HR:2.9 IC95%: 2.1-3.4). El sexo masculino, el estado cognitivo normal, índice de Barthel ≥ 60 y estado nutricional normal fueron factores protectores. Conclusiones: La incidencia de delirium en la población del oriente colombiano tuvo una incidencia similar que a nivel mundial. Se asoció con mayor estancia hospitalaria, declinación funcional y mortalidad. Aplicando escalas de tamizado cognitivo, funcional y nutricional se podrían identificar los pacientes con mayor vulnerabilidad para desarrollo de delirium. MÉD.UIS.2021;34(1):9-17.

Abstract Introduction: Delirium is a neuropsychiatric syndrome of multifactorial etiology that occurs frequently in hospitalized older adults. There are no studies describing the incidence of delirium in Santander and its associated epidemiological factors. Objective: To assess the incidence of delirium, clinical characteristics according to type, mortality after 30 days of hospitalization and complications associated with delirium, in adult patients over 65 years hospitalized in a department in Colombian northeast. Materials and Methods: We included all hospitalized patients ≥ 65 years. We excluded patients with delirium on admission, those hospitalized in intensive care unit, with orotracheal intubation, Glasgow < 8/15, or with factors limiting the ability to assess delirium. Results: 492 hospitalized patients with an average age of 75 years were analyzed. The cumulative incidence of delirium was 9.3%. Of these patients there was a higher percentage of women (63%) and adults ≥ 85 years (31.5%). The greatest association was related to longer hospital stay (11.0 vs 7.1 days, p <0.05), functional impairment evaluated by Barthel scale, and increased risk of mortality (HR:2.9 IC95%: 2.1-3.4). Male sex, normal cognitive status, Barthel index ≥ 60 and normal nutritional status were protective factors. Conclusions: The incidence of delirium in the population of eastern Colombia was similar to the incidence worldwide. Delirium was associated with longer hospital stay, functional decline, and mortality. Applying cognitive, functional, and nutritional screening scales, it would be possible to identify patients with greater vulnerability to delirium development. MÉD.UIS.2021;34(1):9-17.

Parálisis facial en enfermedad de Lyme. Caso clínico de paciente pediátrico / Facial paralysis secondary to Lyme disease. Pediatric case report

Se presenta el caso de un paciente de 23 meses de edad que desarrolló parálisis facial unilateral secundaria a Enfermedad de Lyme sin síntomas otológicos previos. El caso se presentó en Colombia, considerada un área no endémica.

The paper presents the case of a 23 months old child who developed an unilateral facial paralysis secondary to Lyme Disease without previous otologic symptoms. Colombia is not considered an endemic area.

The Drosophila Werner exonuclease participates in an exonuclease-independent response to replication stress.

Members of the RecQ family of helicases are known for their roles in DNA repair, replication, and recombination. Mutations in the human RecQ helicases, WRN and BLM, cause Werner and Bloom syndromes, which are diseases characterized by genome instability and an increased risk of cancer. While WRN contains both a helicase and an exonuclease domain, the Drosophila melanogaster homolog, WRNexo, contains only the exonuclease domain. Therefore the Drosophila model system provides a unique opportunity to study the exonuclease functions of WRN separate from the helicase. We created a null allele of WRNexo via imprecise P-element excision. The null WRNexo mutants are not sensitive to double-strand break-inducing reagents, suggesting that the exonuclease does not play a key role in homologous recombination-mediated repair of DSBs. However, WRNexo mutant embryos have a reduced hatching frequency and larvae are sensitive to the replication fork-stalling reagent, hydroxyurea (HU), suggesting that WRNexo is important in responding to replication stress. The role of WRNexo in the HU-induced stress response is independent of Rad51. Interestingly, the hatching defect and HU sensitivity of WRNexo mutants do not occur in flies containing an exonuclease-dead copy of WRNexo, suggesting that the role of WRNexo in replication is independent of exonuclease activity. Additionally, WRNexo and Blm mutants exhibit similar sensitivity to HU and synthetic lethality in combination with mutations in structure-selective endonucleases. We propose that WRNexo and BLM interact to promote fork reversal following replication fork stalling and in their absence regressed forks are restarted through a Rad51-mediated process.

Lepra laríngea / Laryngeal leprosy

La lepra, o enfermedad de Hansen, es una afección causada por el Mycobacterium leprae, cuyas manifestaciones clínicas varían entre dos polos, lepromatoso y tuberculoide, pudiéndose encontrar en toda la extensión corporal, incluyendo la larínge. La entidad es rara, pero en Colombia existen focos reconocidos, y dentro de la evaluación de pacientes con lesiones granulomatosas o síntomas laríngeos, con nexos epidemiológicos, debe sospecharse y diagnosticarse apropiadamente, para evitar secuelas irreversibles. Presentamos el caso de un paciente de 28 años con cuadro de disfonía, voz apagada y disnea progresiva, asociado a manifestaciones nasales y cutáneas de tres años de evolución, correspondientes a infección por Mycobacterium leprae...

Leprosy or Hansen’s Disease is a condition caused by Mycobacterium leprae, which clinical presentations may vary between two poles: lepromatous and tuberculoid, compromising several systems including the larynx. Leprosy is a very rare disease but in Colombia there are known places where the condition is often found, leading to the necessity of suspicion and diagnosis in patients with granulomatous lesions or laryngeal symptoms with a positive epidemiological bind, to avoid future irreversible sequels. We present a 28 years-old patient with dysphonia, muffled voice and progressive dyspnea, associated with nasal and cutaneous manifestations over 3 years, corresponding to Mycobacterium leprae infection...