Beneath the surface: a case report on nonencapsulated Streptococcus pneumoniae-associated invasive disease in an immunocompromised patient.

Background: Streptococcus pneumoniae, a prominent human pathogen linked to various systemic diseases, includes non-typeable pneumococci marked by the absence of a detectable capsule. However, the majority of invasive infections are attributed to encapsulated strains. This case report details the first documented instance of invasive disease caused by non-typeable S. pneumoniae in Argentina since 2017. Case Presentation: A 19-year-old woman presented with haemorrhagic injuries attributed to chronic oral mucosa irritation. Subsequent hospitalization revealed bone marrow aplasia, leading to antibiotic, antifungal, antiviral, and immunosuppressive treatments, culminating in her discharge. Two weeks later, she was readmitted with sepsis related to a respiratory focus, exhibiting a negative COVID-PCR test. After ten days, ICU admission revealed additional infections: positive COVID-PCR test, fungal sinusitis, and S. pneumoniae bacteremia. Targeted treatments led to improvement, and the patient was subsequently discharged. S pneumoniae characterization: Verification of the capsule's absence utilized traditional methods such as the Quellung reaction, transmission electron microscopy, molecular assays, and Whole Genome Sequencing (WGS). The isolate, identified as ST18335, displayed genetic features and antibiotic resistance patterns, concordant between WGS and the agar dilution method. It demonstrated non-susceptibility to penicillin and cefotaxime, based on meningitis breakpoints, as well as meropenem and cotrimoxazole. Conclusion: This case underscores the clinical significance of non-typeable S. pneumoniae, emphasizing the necessity for a comprehensive approach to identification and characterization. The findings contribute to ongoing discussions regarding the challenges posed by non-typeable strains in vaccine development, understanding clinical impacts, and addressing antibiotic resistance. As the pneumococcal epidemiological landscape evolves, this case serves as a valuable addition to the evolving knowledge surrounding non-typeable S. pneumoniae, highlighting the continued need for surveillance and research in infectious diseases.

Gender-Specific Fine Motor Skill Learning Is Impaired by Myelin-Targeted Neurofibromatosis Type 1 Gene Mutation.

Neurofibromatosis type 1 (NF1) is caused by mutations in the NF1 gene. The clinical presentation of NF1 includes diverse neurological issues in pediatric and adult patients, ranging from learning disabilities, motor skill issues, and attention deficit disorder, to increased risk of depression and dementia. Preclinical research suggests that abnormal neuronal signaling mediates spatial learning and attention issues in NF1; however, drugs that improve phenotypes in models show inconclusive results in clinical trials, highlighting the need for a better understanding of NF1 pathophysiology and broader therapeutic options. Most NF1 patients show abnormalities in their brain white matter (WM) and myelin, and links with NF1 neuropathophysiology have been suggested; however, no current data can clearly support or refute this idea. We reported that myelin-targeted Nf1 mutation impacts oligodendrocyte signaling, myelin ultrastructure, WM connectivity, and sensory-motor behaviors in mice; however, any impact on learning and memory remains unknown. Here, we adapted a voluntary running test-the complex wheel (CW; a wheel with unevenly spaced rungs)-to delineate fine motor skill learning curves following induction of an Nf1 mutation in pre-existing myelinating cells (pNf1 mice). We found that pNf1 mutant females experience delayed or impaired learning in the CW, while proper learning in pNf1 males is predominantly disrupted; these phenotypes add complexity to the gender-dependent learning differences in the mouse strain used. No broad differences in memory of acquired CW skills were detected in any gender, but gene-dose effects were observed at the studied time points. Finally, nitric oxide signaling regulation differentially impacted learning in wild type (WT)/pNf1, male/female mice. Our results provide evidence for fine motor skill learning issues upon induction of an Nf1 mutation in mature myelinating cells. Together with previous connectivity, cellular, and molecular analyses, these results diversify the potential treatments for neurological issues in NF1.

Impact of IKZF1 Deletions in the Prognosis of Childhood Acute Lymphoblastic Leukemia in Argentina.

An association of deletions in the IKZF1 gene (IKZF1del) with poor prognosis in acute lymphoblastic leukemia (ALL) has been demonstrated. Additional deletions in other genes (IKZF1plus) define different IKZF1del subsets. We analyzed the influence of IKZF1del and/or IKZF1plus in the survival of children with ALL. From October 2009 to July 2021, 1055 bone marrow samples from patients with ALL were processed by Multiplex ligation-dependent probe amplification (MLPA). Of them, 28 patients died during induction and 4 were lost-in-follow-up, resulting in an eligible 1023 cases. All patients were treated according to ALLIC-BFM-2009-protocol. Patients were classified into three subsets: IKZF1not-deleted (IKZFF1not-del), IKZF1deleted (IKZF1del) and IKZF1del plus deletion of PAX5, CDKN2A, CDKN2B and/or alterations in CRLF2 with ERG-not-deleted (IKZF1plus). The LFSp and SE were calculated with the Kaplan−Meier calculation and compared with a log-rank test. From the 1023 eligible patients, 835 (81.6%) were defined as IKZF1not-del, 94 (9.2%) as IKZF1del and 94 (9.2%) as IKZF1plus. Of them, 100 (9.8%) corresponded to Standard-Risk (SRG), 629 (61.5%) to Intermediate-Risk (IRG) and 294 (28.7%) to High-Risk (HRG) groups. LFSp(SE) was 7 5(2)% for IKZF1not-del, 51 (6)% for IKZF1del and 48 (6)% for IKZF1plus (p-value < 0.00001). LFSp(SE) according to the risk groups was: in SRG, 91 (4)% for IKZF1not-del, 50 (35)% IKZF1del and 100% IKZF1plus (p-value = ns); in IRG, 77 (2)% IKZF1not-del, 61 (10)% IKZF1del and 54 (7)% IKZF1plus (p-value = 0.0005) and in HRG, 61 (4)% IKZF1not-del, 38 (8)% IKZF1del and 35 (9)% IKZF1plus (p-value = 0.0102). The IKZF1 status defines a population of patients with a poor outcome, mainly in IRG. No differences were observed between IKZF1del versus IKZF1plus. MLPA studies should be incorporated into the risk-group stratification of pediatric ALL.

Análise comparativa dos quadros de ação coletiva das mulheres indígenas / Comparative analysis of case histories of indigenous women as a collective / Análisis comparativo de los marcos de acción colectiva de mujeres indígenas

O objetivo dessa pesquisa é comparar os elementos associados à participação coletiva de mulheres indígenas pertencentes a duas organizações de direitos humanos, Kalli Luz Marina (México) e Federação Regional de Mulheres Asháninkas, Nomatsiguengas e Kakintes da Selva Central (Peru), com base na perspectiva de gênero. Efetuou-se uma análise qualitativa por entrevistas semiestruturadas realizadas com as participantes, além de investigação dos arquivos das organizações. Verificou-se que a organização das mulheres indígenas é motivada pela percepção de injustiça, a capacidade de agência, identidade coletiva e emoções presentes no processo, o que as leva a mobilizar-se e a manter-se em seus grupos, com uma participação ativa, buscando relações de gênero equitativas. As organizações de mulheres nahuas, asháninkas e nomatsiguengas contribuem para a criação de espaços de encontro para seus pares e fornecem elementos relevantes para o desenvolvimento de atividades de gênero culturalmente situadas

The objective of this investigation is to compare the elements associated with the collective participation of indigenous women from two human rights organizations, Kalli Luz Marina (Mexico), and the Regional Federation of Women Asháninkas, Nomatsiguengas and Kakintes, from the Selva Central (Peru), with perspective to gender. Using the Theory of collective action framework, a comparative qualitative analysis was implemented, collecting information through semi-structured interviews of the participants, and organization's archival research. It was found that the organizational process of indigenous women is motivated by the perception of injustice, agency capacity, collective identity and emotions present in the process, which leads them to mobilize and remain in their groups with active participation looking for equal relationships between the genders. Nahua, Asháninka and Nomatsiguenga women organizations contribute to the creation of meeting spaces for their peers and provide relevant elements for the development of culturally situated gender agendas

El objetivo de la investigación es comparar los elementos asociados a la participación colectiva de mujeres indígenas de dos organizaciones de derechos humanos, desde la perspectiva de género. Se efectuó un análisis comparativo de corte cualitativo de los marcos de acción colectiva de mujeres indígenas pertenecientes al Kalli Luz Marina (México) y la Federación Regional de Mujeres Asháninkas, Nomatsiguengas y Kakintes de la Selva Central (Perú), a través de entrevistas semiestructuradas realizadas a las participantes e investigación de archivos de las organizaciones. Se encontró que el proceso organizativo de mujeres nahuas, asháninkas y nomatsiguengas está motivado por la percepción de injusticia, la capacidad de agencia, la identidad colectiva y las emociones presentes en el proceso, que las lleva a movilizarse y mantenerse en sus colectivos con una participación activa, buscando relaciones de género equitativas. Las organizaciones de mujeres indígenas crean espacios de encuentro y desarrollan agendas de género culturalmente situadas