Induction of Monoterpenoid Oxindole Alkaloids Production and Related Biosynthetic Gene Expression in Response to Signaling Molecules in Hamelia patens Plant Cultures.

Hamelia patens (Rubiaceae), known as firebush, is a source of bioactive monoterpenoid oxindole alkaloids (MOAs) derived from monoterpenoid indole alkaloids (MIAs). With the aim of understanding the regulation of the biosynthesis of these specialized metabolites, micropropagated plants were elicited with jasmonic acid (JA) and salicylic acid (SA). The MOA production and MIA biosynthetic-related gene expression were evaluated over time. The production of MOAs was increased compared to the control up to 2-fold (41.3 mg g DW-1) at 72 h in JA-elicited plants and 2.5-fold (42.4 mg g DW-1) at 120 h in plants elicited with SA. The increment concurs with the increase in the expression levels of the genes HpaLAMT, HpaTDC, HpaSTR, HpaNPF2.9, HpaTHAS1, and HpaTHAS2. Interestingly, it was found that HpaSGD was downregulated in both treatments after 24 h but in the SA treatment at 120 h only was upregulated to 8-fold compared to the control. In this work, we present the results of MOA production in H. patens and discuss how JA and SA might be regulating the central biosynthetic steps that involve HpaSGD and HpaTHAS genes.

Applicability and usefulness of pupillometry in the study of lexical access. A scoping review of primary research.

Pupil dilation has been associated with the effort required to perform various cognitive tasks. At the lexical level, some studies suggest that this neurophysiological measure would provide objective, real-time information during word processing and lexical access. However, due to the scarcity and incipient advancement of this line of research, its applicability, use, and sensitivity are not entirely clear. This scoping review aims to determine the applicability and usefulness of pupillometry in the study of lexical access by providing an up-to-date overview of research in this area. Following the PRISMA protocol, 16 articles were included in this review. The results show that pupillometry is a highly applicable, useful, and sensitive method for assessing lexical skills of word recognition, word retrieval, and semantic activation. Moreover, it easily fits into traditional research paradigms and methods in the field. Because it is a non-invasive, objective, and automated procedure, it can be applied to any population or age group. However, the emerging development of this specific area of research and the methodological diversity observed in the included studies do not yet allow for definitive conclusions in this area, which in turn does not allow for meta-analyses or fully conclusive statements about what the pupil response actually reflects when processing words. Standardized pupillary recording and analysis methods need to be defined to generate more accurate, replicable research designs with more reliable results to strengthen this line of research.

The Relationship Between Anti-SSA-52 and Interstitial Lung Disease.

OBJECTIVE: The aims of this study were to assess whether a relationship between anti-SSA-52 and interstitial lung disease (ILD) can be further defined, and to enhance screening, detection, and potentially guide treatment. METHODS: A historical cohort study of 201 patients was conducted at a single tertiary care center between January 1, 2016 and December 31, 2020. All included patients were anti-SSA-52 antibody positive. Chart review was performed for laboratory values, symptoms, pulmonary function tests, treatment, and imaging. Chest computed tomographies were reviewed by chest radiologists. RESULTS: Among anti-SSA-52 antibody-positive patients, ILD was found in 125 (62.2%) compared with 76 (37.8%) with no ILD (p = 0.001). For those with ILD, 78 (62.4%) were diagnosed with connective tissue disease (CTD)-associated ILD, 28 (22.4%) were diagnosed ILD only, and 19 (15.2%) met the criteria for interstitial pneumonia with autoimmune features. In patients with CTD-ILD, 18 (23.0%) had their ILD diagnosis made over 6 months before a CTD diagnosis, and an additional 43 (55.1%) had their ILD and CTD diagnosed within 6 months of each other (p < 0.001). Common computed tomography patterns were nonspecific interstitial pneumonia/organizing pneumonia overlap in 44 (35.2%), 25 (20.0%) nonspecific interstitial pneumonia, and 15 (12%) usual interstitial pneumonia. Twenty-eight (35.9%) had antisynthetase syndrome, followed by 16 (20.5%) with dermatomyositis, 10 (12.8%) with CTD overlap, and 6 (7.7%) with systemic scleroderma. CONCLUSIONS: There was a significant association between anti-SSA-52 antibodies and ILD across a wide spectrum of rheumatological diagnoses. A significant portion of patients were diagnosed with ILD either at the same time or before their CTD diagnosis. Further study will be needed to assess effective treatment and response.

Word or pseudoword? The lexicality effect in naming and lexical decision tasks during advanced aging.

Although there is evidence that recognizing pseudowords is more difficult than recognizing words during childhood, adulthood, and early old age (60-75 years), it is not yet clear what happens during advanced aging or the fourth age, a stage when the decline of fluid intelligence strongly affects processing speed, but a good performance of crystallized intelligence is described through an increase in vocabulary and knowledge. The objective of this study was to determine the lexicality effect in advanced aging, specifically exploring how the ability to recognize words and pseudowords (ortho-phonologically plausible for Spanish) is affected during the third and fourth-ages. The lexicality effect was measured using naming and lexical decision tasks. Response time and accuracy were compared between a fourth-age group (80+ years) and two third-age groups (60-69 and 70-79 years) through linear regression models. The results showed that, in general, the fourth-age group had longer response times and reduced accuracy when recognizing words and pseudowords. Moreover, they showed a significant lexicality effect (which increases from the third- age onwards), reflected in higher costs during pseudoword recognition, especially when the task required more cognitive effort (lexical decision task). These results were consistent with the impact of the deterioration of fluid intelligence on the speed of lexical recognition and with the better performance that crystallized intelligence can generate on accuracy, especially in the early stages of old age. Additionally, this study supports the fact that pseudoword recognition resists cognitive decline, as accentuated deterioration is visualized only after 80 years.

CNS Efficacy of Osimertinib With or Without Chemotherapy in Epidermal Growth Factor Receptor-Mutated Advanced Non-Small-Cell Lung Cancer.

PURPOSE: We report CNS efficacy of first-line osimertinib plus chemotherapy versus osimertinib monotherapy in patients with epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) from the phase III FLAURA2 study according to baseline CNS metastasis status. METHODS: Patients were randomly assigned to osimertinib plus platinum-pemetrexed (combination) or osimertinib monotherapy until disease progression or discontinuation. Brain scans were performed in all patients at baseline and progression and at scheduled assessments until progression for patients with baseline CNS metastases; scans were assessed by neuroradiologist CNS blinded independent central review (BICR). RESULTS: On the basis of baseline CNS BICR, 118 of 279 (combination) and 104 of 278 (monotherapy) randomly assigned patients had ≥one measurable and/or nonmeasurable CNS lesion and were included in the CNS full analysis set (cFAS); 40 of 118 and 38 of 104 had ≥one measurable target CNS lesion and were included in the post hoc CNS evaluable-for-response set (cEFR). In the cFAS, the hazard ratio (HR) for CNS progression or death was 0.58 (95% CI, 0.33 to 1.01). In patients without baseline CNS metastases, the HR for CNS progression or death was 0.67 (95% CI, 0.43 to 1.04). In the cFAS, CNS objective response rates (ORRs; 95% CI) were 73% (combination; 64 to 81) versus 69% (monotherapy; 59 to 78); 59% versus 43% had CNS complete response (CR). In the cEFR, CNS ORRs (95% CI) were 88% (73 to 96) versus 87% (72 to 96); 48% versus 16% had CNS CR. CONCLUSION: Osimertinib plus platinum-pemetrexed demonstrated improved CNS efficacy compared with osimertinib monotherapy, including delaying CNS progression, irrespective of baseline CNS metastasis status. These data support this combination as a new first-line treatment for patients with EGFR-mutated advanced NSCLC, including those with CNS metastases.

Thoracic Complications of Liver-Directed Therapy and Interventions.

ABSTRACT: Liver-directed percutaneous and endovascular therapies are effective methods to diagnose and treat various hepatic disorders and malignancies. Because of the close anatomic proximity of the liver to the right hemidiaphragm, pleura, and lung bases, complications can arise involving these structures. Although they are rare, awareness of intrathoracic complications associated with liver-directed therapies and their imaging features will ensure timely detection and management. We aim to review the clinical and imaging features of thoracic complications related to liver-directed therapy and interventions.

New species of Demidospermus (Monogenoidea: Dactylogyridae) from the gills of Pseudoplatystoma punctifer (Siluriformes: Pimelodidae) collected in the Peruvian Amazonia.

Pseudoplatystoma punctifer is a catfish species that occupies the first place in the statistics of fishing landings in the region of Loreto, being of economic importance in the Peruvian Amazonia. As an initiative to know the parasites present in the gills of P. punctifer from the Peruvian Amazonia, a study was carried out with fish collected in the Belén Market, in Loreto-Peru. Specimens were provided between June and October 2018 from local fishermen from the Belén Market, in Loreto-Peru and samples were processed and analyzed in the "Laboratorio de Parasitología y Sanidad Acuícola" from the "Instituto de Investigaciones de la Amazonía Peruana" (IIAP) in Iquitos, Loreto-Peru. The analyzes of the gills revealed the presence of two new species of Monogenoidea: Demidospermus aureagarciae n. sp. and D. doncellae n. sp. These species are unique among congeners by the morphology of the copulatory complex and vagina. Demidospermus aureagarciae n. sp presents a male copulatory organ as a coiled tube, with a complete counterclockwise ring, with dilated base with a developed sclerotized margin, from which a flap projects; a concave accessory piece, with a tapered and curved distal part and a saculiform vaginal vestibule, connected to the vaginal canal. Demidospermus doncellae n. sp. presents a copulatory complex that is an elongated coiled tube, with approximately three clockwise rings, with dilated base with a developed sclerotized margin, from which a flap projects; an accessory piece sheath like, and a sclerotized vagina with dextral position, with saclike vaginal vestibule, connected to an elongated canal.

The willingness to forgive among the Wayuu and among people from other indigenous communities in Colombia

Introduction/Objectives: Willingness to forgive has been studied in different situations, however, there are no published studies in Colombia with indigenous populations and taking into account their worldview. The present research was aimed at examining the willingness to forgive of people from various ethnic minorities in Colombia such as the Embera, Nasa, Pijao and Kaamash-Hu communities and focusing in particular on the Wayuu community. Method: An experimental design was used and a cluster analysis was performed. The sample was composed of 159 indigenous adults (30% male) between the ages of 18 and 76, who were shown a series of scenarios describing a common situation in which an orchard was damaged by domestic animals belonging to a neighbour. Three factors were manipulated in the scenario: the severity of the damage, the level of carelessness of the animals' owner, and the animals' owner's explanations and apologetic behaviour. Results: Cluster analysis yielded five qualitatively different positions: Never forgive under any circumstances (6% of the sample, primarily participants from the Embera community), Depends on apology and neglect (15%), Depends on apology, consequences, and neglect (30%, primarily participants from the Kaamash-Hu community), and Almost always forgive (36%, primarily people from the Wayuu community). Conclusion: Thus, there is a convergence between the results of this study and the anthropological observations of the participating ethnic communities. Forgiveness is closely linked to the cosmovision of each indigenous group.

Introducción/Objetivos: La voluntad de perdonar ha sido estudiada en diferentes situaciones, sin embargo, no existen estudios publicados en Colombia con población indígena y teniendo en cuenta su cosmovisión. La presente investigación tuvo como objetivo examinar la voluntad a perdonar de personas de diversas minorías étnicas en Colombia como la comunidad Embera, Nasa, Pijao, Kaamash-Hu y centrándose en particular en la comunidad Wayuu. Método: Se presentaron una serie de escenarios a una muestra de 159 adultos indígenas (30% hombres) de entre 18 y 76 años. Dichos escenarios describían una situación común en la que una huerta era dañada por animales domésticos de un vecino. Se manipularon tres factores en cada escenario: la gravedad del daño, el nivel de descuido del dueño de los animales y, las explicaciones y el comportamiento de disculpa del dueño de los animales. Resultados: El análisis de clústeres arrojó cinco posiciones cualitativamente diferentes: Nunca perdona bajo ninguna circunstancia (6% de la muestra, principalmente participantes de la comunidad Embera), Depende de las disculpas y del descuido (15%), Depende de las disculpas, las consecuencias y el descuido (30%, principalmente participantes de la comunidad Kaamash-Hu), y Casi siempre perdona (36%, principalmente personas de la comunidad Wayuu). Conclusiones: Por tanto, existe una convergencia entre los resultados de este estudio y las observaciones antropológicas que condujeron a la decisión de la Unesco de considerar el sistema de justicia restaurativa de la comunidad Wayuu como un patrimonio inalterable.

Coffee Colored Serum, Adverse Reaction of Eltrombopag.

Serum index and macroscopic characteristics of samples can give valuable information and should be interpreted as a result. Following centrifugation of the sample, on gross inspection it was observed that the serum had a brown color. After ruling out the main causes that can cause a brown coloration, such as intravascular hemolysis or high concentrations of methemoglobin, it was noted that the patient was receiving a high-dose of Eltrombopag therapy. Eltrombopag is a non-peptide thrombopoietin receptor agonist approved for the treatment of severe aplastic anemia (SAA). The drug in solution has a brown color and at high concentrations it is capable of changing the color of the serum and may have different effects in different assays of laboratory. This article describes the case of a patient with brown serum due to the consumption of high doses of Eltrombopag that started to cause cutaneous hyperpigmentation.

Gibberellin and miRNA156-targeted SlSBP genes synergistically regulate tomato floral meristem determinacy and ovary patterning.

Many developmental processes associated with fruit development occur at the floral meristem (FM). Age-regulated microRNA156 (miR156) and gibberellins (GAs) interact to control flowering time, but their interplay in subsequent stages of reproductive development is poorly understood. Here, in tomato (Solanum lycopersicum), we show that GA and miR156-targeted SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE (SPL or SBP) genes interact in the tomato FM and ovary patterning. High GA responses or overexpression of miR156 (156OE), which leads to low expression levels of miR156-silenced SBP genes, resulted in enlarged FMs, ovary indeterminacy and fruits with increased locule number. Conversely, low GA responses reduced indeterminacy and locule number, and overexpression of a S. lycopersicum (Sl)SBP15 allele that is miR156 resistant (rSBP15) reduced FM size and locule number. GA responses were partially required for the defects observed in 156OE and rSBP15 fruits. Transcriptome analysis and genetic interactions revealed shared and divergent functions of miR156-targeted SlSBP genes, PROCERA/DELLA and the classical WUSCHEL/CLAVATA pathway, which has been previously associated with meristem size and determinacy. Our findings reveal that the miR156/SlSBP/GA regulatory module is deployed differently depending on developmental stage and create novel opportunities to fine-tune aspects of fruit development that have been important for tomato domestication.

Condylar femoral arthroplasty with bone cement as a salvage measure in open fracture with articular bone defect in a young patient.

Open fractures often require complex treatments, especially those with joint involvement or critical bone defects. Managing both combined injuries present even greater challenges and is not without complications. We present the case of a young patient with an open fracture of the femoral condyle and loss of bone stock in the articular surface. In this case, a combined osteosynthesis approach was employed, utilizing cannulated screws and a femoral condyle arthroplasty with bone cement as a salvage measure, allowing a favorable clinical and functional outcome at the 3-year follow-up. This technique serves as a simple, reproducible, and cost-effective alternative for transient or potentially definitive management in such cases.

Sub-lineage B.1.6 of hMPXV in a global context: Phylogeny and epidemiology.

During the 2022 COVID-19 pandemic, monkeypox emerged as a significant threat to global health. The virus responsible for the disease, the human monkeypox virus (hMPXV), underwent various genetic changes, resulting in the emergence of over a dozen distinct lineages, which could be identified by only a small number of unique mutations. As of January 25, 2023, genomic information of hMPXV generated had reached 4632 accessions in the GISAID database. In this study, we aimed to investigate the epidemiological and phylogenetic characteristics of the B.1.6 sub-lineage of hMPXV in Peru, compared with other circulating sub-lineages during the global outbreak. The B.1.6 sub-lineage, characterized by the 111029G>A mutation, was estimated to have emerged in June 2022 and was found mainly in Peru. Most cases (95.8%) were men with an average age of 33 years, and nearly half of the patients had HIV, of whom only 77.35% received antiretroviral therapy. Our findings revealed that the B.1.6, B.1.4, and B.1.2 sub-lineages were well represented and had a higher number of mutations despite having the lowest media substitution rates per site per year. Moreover, it was estimated that B.1.2 and B.1.4 appeared in February 2022 and were the first two sub-lineages to emerge. A mutation profile was also obtained for each sub-lineage, reflecting that several mutations had a pattern similar to the characteristic mutation. This study provides the first estimation of the substitution rate and ancestry of each monkeypox sub-lineage belonging to the 2022 outbreak. Based on our findings, continued genomic surveillance of monkeypox is necessary to understand better and track the evolution of the virus.

Lexical Access Restrictions after the Age of 80.

BACKGROUND: During the fourth age (80+ years), cognitive difficulties increase. Although language seems to resist the advancement of age, an older person without pathological developments in cognition may exhibit deficits in lexical access. This study examines the restrictions on lexical access in people aged 80 and older in word recognition and retrieval modalities through four lexical tasks. METHOD: The effect of aging on response time and accuracy was measured using recognition (lexical decision/naming/priming) and retrieval (picture naming) tasks. A fourth age group (>80) and two third age groups (60-69/70-79) were compared according to lexical access modality and type of task employed through linear regression models. RESULTS: People aged 80 and older exhibit a strong lexical access constraint, as they are slower and less accurate in recognizing and retrieving words than both third age groups. These restrictions are more profound for the word retrieval modality, especially in the picture naming task. CONCLUSION: Impaired fluid intelligence and internode transmission deficits during advanced aging could further reduce the ability to recognize and/or retrieve words, having an impact on access speed and accuracy. Furthermore, the idea that crystallized intelligence could strengthen the accuracy of lexical access during aging is supported, specifically in word recognition modality.

Clinical and Endoscopic Characterization of Gastrointestinal Kaposi's Sarcoma in an Institution in Southwestern Colombia between 2011 and 2020

Kaposi's sarcoma is an angioproliferative neoplasm associated with the human herpesvirus 8. According to the clinical characteristics and the degree of immunosuppression, there are four epidemiological forms: classic, endemic, iatrogenic, and epidemic. The latter is associated with acquired immunodeficiency syndrome (AIDS) and 40% GI involvement. There is little epidemiological, clinical, and endoscopic evidence of the disease. This study sought to characterize this condition in a Colombian population and compare the findings with publications from other countries. One hundred thirty-five records of patients who consulted between 2011 and 2020 for Kaposi's sarcoma were reviewed, of which 24 had GI involvement. Epidemiological, clinical, endoscopic, and treatment characteristics were obtained. Twenty-two patients were men. There were 21 patients infected with human immunodeficiency virus (HIV; 87.5%) and 19 receiving antiretroviral therapy (90%); 33.3% had HIV viral load > 100,000 copies/mL. The CD4+ count was <50 cells/µL in 28.6% of cases, between 50 and 100 cells/µL in 19.0%, and between 100 and 200 cells/µL in 14.4%. The rate of infection by other opportunistic infections was 41.7%. There were GI symptoms in 33% of the patients, and the most frequent were hematochezia, abdominal pain, nausea, and diarrhea. Most had concomitant skin lesions (70.8%). GI lesions were located mainly in the oropharynx (41.7%), stomach (20.8%), and colon (16.7%). The most common endoscopic finding was maculopapular erythema. This article provided insight into the local epidemiology of gastrointestinal Kaposi's sarcoma. In contrast to studies in other populations, GI symptoms were more frequent in this one, and there was a difference in endoscopic findings. Studies with larger populations are needed.

El sarcoma de Kaposi es una neoplasia angioproliferativa asociada al virus del herpes humano 8. Según las características clínicas y el grado de inmunosupresión, son cuatro las formas epidemiológicas: clásica, endémica, iatrogénica y epidémica, esta última asociada al síndrome de inmunodeficiencia adquirida (SIDA) y con un 40% de compromiso gastrointestinal. Existe escasa evidencia epidemiológica, clínica y endoscópica de la enfermedad. Este estudio buscó caracterizar esta condición en una población colombiana y contrastar los hallazgos con publicaciones de otros países. Se revisaron 135 registros de pacientes que consultaron entre el 2011 y 2020 por sarcoma de Kaposi, de los cuales 24 tenían compromiso gastrointestinal. Se obtuvieron características epidemiológicas, clínicas, endoscópicas y tratamientos. Veintidós pacientes eran hombres. Hubo 21 pacientes infectados por virus de la inmunodeficiencia humana (VIH; 87,5%) y 19 recibían terapia antirretroviral (90%). El 33,3% tenía carga viral VIH > 100 000 copias/mL. El recuento de CD4+ fue < 50 cel/µL en el 28,6% de los casos, entre 50 y 100 cel/µL en el 19,0%, y entre 100 y 200 cel/µL en el 14,4%. La tasa de infecciones por otros oportunistas fue de 41,7%. Hubo síntomas gastrointestinales en el 33% de los pacientes y los más frecuentes fueron hematoquecia, dolor abdominal, náuseas y diarrea. La mayoría tuvo lesiones cutáneas concomitantes (70,8%). Las lesiones gastrointestinales se localizaron principalmente en la orofaringe (41,7%), estómago (20,8%) y colon (16,7%). El hallazgo endoscópico más común fue eritema maculopapular. Este artículo mostró una visión de la epidemiología local del sarcoma de Kaposi gastrointestinal. En contraste con estudios en otras poblaciones, en este, los síntomas gastrointestinales fueron más frecuentes y hubo diferencia en los hallazgos endoscópicos. Son necesarios estudios con poblaciones más grandes.

Tofacitinib en el tratamiento de la colitis ulcerosa moderada a grave en Colombia: experiencia en mundo real / Tofacitinib in the treatment of moderate to severe ulcerative colitis in Colombia: Real world experience

Introducción: No hay estudios sobre eficacia de tofacitinib para colitis ulcerosa (CU) en Latinoamérica. Se plantea como objetivo describir la eficacia y seguridad, en mundo real, de pacientes con CU moderada-grave tratados con tofacitinib en nuestro medio. Materiales y métodos: Estudio observacional descriptivo multicéntrico, en pacientes con CU que recibieron tratamiento con tofacitinib en fase de inducción por 8 semanas y luego, terapia de mantenimiento, entre junio de 2019 y junio de 2022. Resultados: Treinta y cuatro pacientes adultos, 50% mujeres, edad media 38,1 (rango 22-72) años. El 76,5% presentó pancolitis y el 20,6% colitis izquierda; el 79,4% fallo a inhibidores del factor de necrosis tumoral (anti-TNF) y el 35,3% a vedolizumab; el 14,7% era naïve a terapia biológica; el 23,5% presentó previamente manifestaciones extraintestinales. Durante la inducción, el 58,8% de los pacientes alcanzaron remisión clínica, bioquímica y endoscópica. En el mantenimiento, el 76,9% de los pacientes a las 26 semanas, y el 66,6% a las 52 semanas, presentaron remisión clínica; 8 pacientes presentaron eventos adversos, ninguno cardiovascular ni tromboembólico. El 44,1% fueron dependientes de esteroides, y el 23,5% requirieron esteroides como terapia de rescate. El 38,3% requirió aumento de tofacitinib a 10mg cada 12h durante el mantenimiento. En el 17,6% se suspendió tofacitinib por ausencia de eficacia. Se incluyeron 3 pacientes en edad pediátrica, femeninas, edad media 15,3 (rango 14-17) años, 2/3 con pancolitis y 1/3 con colitis izquierda, todas con exposición previa a terapia biológica, quienes presentaron remisión clínica, biológica y endoscópica en la inducción. Conclusiones: En este primer estudio latinoamericano con tofacitinib en CU se demuestra eficacia y seguridad en el tratamiento de nuestros pacientes con actividad moderada a grave.(AU)

Introduction: There are no studies on efficacy of tofacitinib for ulcerative colitis (UC) in Latin America. The aim of this study was to describe the efficacy and safety, in the real world, of patients with moderate-severe UC treated with tofacitinib in our setting. Materials and methods: Multicenter descriptive observational study, in patients with UC who received treatment with tofacitinib in induction phase for 8 weeks and then, maintenance therapy, between June 2019 and June 2022. Results: Thirty-four adult patients, 50% female, mean age 38.1 (range 22–72) years. 76.5% pancolitis, and 20.6% left colitis. 79.4% failure to tumor necrosis factor inhibitors (anti-TNFs), and 35.3% to vedolizumab. 14.7% naïve to biologic therapy. 23.5% had previous extraintestinal manifestations. During induction, 58.8% of patients achieved clinical, biochemical and endoscopic remission. During maintenance, 76.9% of patients at 26 weeks and 66.6% at 52 weeks presented clinical remission. Eight patients presented adverse events, none of them cardiovascular or thromboembolic. 44.1% were steroid-dependent, and 23.5% required steroids as rescue therapy. 38.3% required an increase in tofacitinib to 10mg every 12h during maintenance. In 17.6% tofacitinib was discontinued due to lack of efficacy. We included three pediatric-aged female patients, mean age 15.3 (range 14–17) years, 2/3 with pancolitis and 1/3 with left colitis, all with prior exposure to biologic therapy, who had clinical, biologic and endoscopic remission at induction. Conclusions: In this first Latin American study with tofacitinib in UC, efficacy and safety are demonstrated in the treatment of our patients with moderate to severe activity.(AU)

Bempegaldesleukin Plus Nivolumab in Untreated Advanced Melanoma: The Open-Label, Phase III PIVOT IO 001 Trial Results.

PURPOSE: Despite marked advances in the treatment of unresectable or metastatic melanoma, the need for novel therapies remains. Bempegaldesleukin (BEMPEG), a pegylated interleukin-2 (IL-2) cytokine prodrug, demonstrated efficacy in the phase II PIVOT-02 trial. PIVOT IO 001 (ClinicalTrials.gov identifier: NCT03635983) is a phase III, randomized, open-label study that builds on the PIVOT-02 results in first-line melanoma. METHODS: Patients with previously untreated, unresectable, or metastatic melanoma were randomly assigned 1:1 to receive BEMPEG plus nivolumab (NIVO) or NIVO monotherapy. Primary end points were objective response rate (ORR) and progression-free survival (PFS) by blinded independent central review and overall survival (OS). Secondary and exploratory end points included additional efficacy measures, safety, and pharmacokinetics (PKs) and pharmacodynamics analyses. RESULTS: In 783 patients (n = 391, BEMPEG plus NIVO; n = 392, NIVO monotherapy), the median follow-up was 11.6 months in the intent-to-treat population. The ORR with BEMPEG plus NIVO was 27.7% versus 36.0% with NIVO (two-sided P = .0311). The median PFS with BEMPEG plus NIVO was 4.17 months (95% CI, 3.52 to 5.55) versus 4.99 months (95% CI, 4.14 to 7.82) with NIVO (hazard ratio [HR], 1.09; 97% CI, 0.88 to 1.35; P = .3988). The median OS was 29.67 months (95% CI, 22.14 to not reached [NR]) with BEMPEG plus NIVO versus 28.88 months (95% CI, 21.32 to NR) with NIVO (HR, 0.94; 99.929% CI, 0.59 to 1.48; P = .6361). Grade 3-4 treatment-related adverse events (AEs) and serious AE rates were higher with the combination (21.7% and 10.1%, respectively) versus NIVO (11.5% and 5.5%, respectively). BEMPEG PK exposure and absolute lymphocyte count changes after BEMPEG plus NIVO were comparable between PIVOT IO 001 and PIVOT-02. CONCLUSION: The PIVOT IO 001 study did not meet its primary end points of ORR, PFS, and OS. Increased toxicity was observed with BEMPEG plus NIVO versus NIVO.

Epidemiology and Genetic Diversity of Hepatitis B Virus and Hepatitis Delta Virus Infection in Indigenous Communities in Colombia.

Despite the universal vaccination program, there are still regions and territories with a high prevalence of Hepatitis B Virus infection (HBV), such as the Amazon basin, where several indigenous communities live. Additionally, Hepatitis Delta Virus (HDV) is a defective that requires the hepatitis B surface antigen (HBsAg) for the assembly and release of de novo viral particles. Therefore, hepatitis D could be the result of HBV/HDV coinfection or HDV superinfection in individuals with chronic hepatitis B. Among the high prevalence HDV populations are indigenous communities of America. This study aims to describe and characterize the frequency of HBV and HDV infection, viral genotypes and HBV immune escape mutants in indigenous populations from different regions of Colombia. The diagnosis of hepatitis B and hepatitis D was confirmed by serological markers. Moreover, the HBV and HDV genome were amplified by PCR and RT-PCR, respectively, and, subsequently, the phylogenetic analysis was performed. We characterized 47 cases of chronic hepatitis B, 1 case of reactivation and 2 cases of occult hepatitis B infection (OBI). Furthermore, a high prevalence of HDV infection was identified in the study population (29.33%, 22/75) and the circulation of several HBV genotypes and subgenotypes (F1b, F3, F4, and D). Interestingly, this is the first report of the HDV genotype I circulation in this country. These findings demonstrated that HBV and HDV infections are still public health problems in indigenous communities in Colombia.

Tuning the conductance of carbon rings with impurities and electric fields.

We explore two mechanisms to tune the electronic conductance of carbon atom rings, namely, substitutional impurities and in-plane external electric fields. First-principles calculations and a tight-binding approach are used to model the systems. Two bond configurations are studied, cumulenic and polyynic, which can be relevant depending on the number of carbon atoms in the ring. We find that both impurity substitution and electric field mechanisms allow for modifying the electronic spectrum and transport characteristics. Interestingly, cumulenic and polyynic carbon rings present a different response to these perturbations, which can also be a way to elucidate the bond nature of these structures.