Search

We report the p+p and p+d differential cross sections measured in the SeaQuest experiment for J/ψ and ψ(2S) production at [Formula presented] beam energy covering the forward x-Feynman (xF) range of 0.5

Background: Childhood asthma is affected by events and conditions of the school environment. Teachers as de-facto caregivers of children with asthma have a major role to play in ensuring good asthma control in school. This study set out to determine the level of knowledge of school teacher about childhood asthma and factors influencing this knowledge. Methods: Four secondary schools (two private and two public) in Ilesa, South West Nigeria were selected by multistage sampling method. All the teachers in these schools were required to fill a self -administered questionnaire incorporating a validated 40-item asthma knowledge questions. Factors associated with the level of knowledge were determined appropriately. Results: A total of 132 teacher (M: F = 1:2) participated in the study with 85 (64.4%) from private school. The mean (SD) age of the teachers was 38.0 (9.1) years and median (IQR) years in teaching service was 7.0 (5.0 to 15.0) years. Majority (56.1%) of the teachers had university education while only 7 (5.3%) had a post graduate degree. The mean (SD) score of the 40 item questions was 21.5 (7.2) and majority (51.5%) had poor asthma knowledge (score < 22). Poorer knowledge was observed in questions related to the nature and management of childhood asthma than triggers and manifestations. No significant correlation was found between knowledge and age, teaching experience and qualifications (p > 0.05). However, teachers with previous training about childhood asthma had relatively good knowledge about the condition. (p

Evidence for a flavor asymmetry between the ū and d¯ quark distributions in the proton has been found in deep-inelastic scattering and Drell-Yan experiments. The pronounced dependence of this flavor asymmetry on x (fraction of nucleon momentum carried by partons) observed in the Fermilab E866 Drell-Yan experiment suggested a drop of the d¯(x)/ū(x) ratio in the x>0.15 region. We report results from the SeaQuest Fermilab E906 experiment with improved statistical precision for d¯(x)/ū(x) in the large x region up to x=0.45 using the 120 GeV proton beam. Two different methods for extracting the Drell-Yan cross section ratios, σpd/2σpp, from the SeaQuest data give consistent results. The d¯(x)/ū(x) ratios and the d¯(x)-ū(x) differences are deduced from these cross section ratios for 0.13

The level structure of Al36 has been studied via β decay of Mg36 at the Facility for Rare Isotope Beams (FRIB) and the National Superconducting Cyclotron Laboratory (NSCL). A long-lived isomer in Al36 was identified which decays by β to an excited state of Si36. The ground state and the isomeric state of Al36 were found to populate different energy levels of Si36. The results from the two data sets in the present work complement each other. Configuration interaction calculations performed with the FSU shell-model Hamiltonians provide reasonable descriptions to the experimental observations and offer insight into future improvements of the theoretical interpretation.

Introdução: O diagnóstico de deficiência de ferro pode ser particularmente desafiador em pacientes com condições inflamatórias agudas ou crônicas, pois muitos marcadores bioquímicos do metabolismo do ferro, como a ferritina sérica, podem ser influenciados pela reação de fase aguda. Devido a isso, há um crescente interesse na utilização de parâmetros relacionados a eritrócitos e reticulócitos disponíveis em analisadores hematológicos modernos, como o RET-He. Esse parâmetro pode ajudar na detecção precoce de condições clínicas como deficiência de ferro (absoluta ou funcional) e eritropoese ineficaz. Adicionalmente, a aspiração de medula óssea é considerada o padrão-ouro para avaliar as reservas de ferro na medula óssea. Objetivo: Investigar a correlação entre a dosagem de RET-He, o ferro medular e a ferritina sérica em pacientes com análise de ferro medular. Métodos: Foram analisados os dados de 132 pacientes submetidos à pesquisa de ferro medular. Utilizou-se a coloração azul da Prússia (de Perl) para corar a medula óssea. Dentre essas 132 análises, 40 não apresentaram ferro no interstício medular ou havia apenas traços, enquanto 92 mostraram a presença de ferro no interstício medular. Em todos os casos, foi realizada a dosagem do parâmetro RET-He no sangue periférico. Dentre esses 132 pacientes, 47 apresentaram dosagem de ferritina sérica, cujos dados também foram utilizados para análise estatística. Para fins estatísticos, considerou-se os seguintes valores de corte: RET-He (30,1 pg a 38,0 pg); ferritina (homens – 26 a 446 μg/L; mulheres – 15 a 149 μg/L). Resultados: Na análise estatística, observou-se que, entre os pacientes que não apresentaram depósito de ferro ou apresentaram traços no interstício medular, apenas 10 tinham RET-He < 30,1 pg, indicando que 25% dos casos apresentaram correlação direta entre RET-He e ausência de ferro medular. Entre os pacientes com presença de ferro no interstício medular, 15 apresentaram RET-He < 30,1 pg, demonstrando que, nesses casos, houve uma correlação direta entre RET-He e presença de ferro medular em 84% dos casos. A ferritina sérica dosada em 15 pacientes com traços ou ausência de ferro medular estava abaixo do valor de referência em apenas 2 casos, permitindo estabelecer uma correlação entre ausência de ferro medular e ferritina em apenas 13,3% dos casos analisados. Discussão: Os resultados deste estudo mostram uma fraca associação entre a dosagem de RET-He e as reservas de ferro medular, com uma relação entre baixos níveis de RET-He e a ausência de ferro medular identificada em apenas 25% dos casos. Da mesma forma, a conexão entre a ferritina sérica e a ausência de ferro medular foi limitada, com uma correspondência estabelecida em apenas 13,3% dos casos. Conclusão: Esses achados sugerem que tanto o RET-He quanto a ferritina sérica podem ter limitações significativas na detecção precisa da deficiência de ferro medular. Portanto, é recomendável considerar outros métodos diagnósticos ou parâmetros adicionais para uma avaliação mais completa e precisa das reservas de ferro na medula óssea.

Introdução: O linfoma de Hodgkin (LH) é caracterizado pela presença histológica das células de Reed-Sternberg. Sua incidência corresponde a aproximadamente 10% dos linfomas e cerca de 0,6% dos cânceres. O quadro clínico inclui linfonodos aumentados e indolores na região cervical, tóraxsuperior, interior do mediastino, axilas, abdômen e região inguinal. Além disso, os denominados sintomas B podem estar associados como febre, sudorese noturna e emagrecimento. O diagnóstico de LH é realizado por biópsia excisional de linfonodo, sendo a PET/CT considerada padrão-ouro para o estadiamento. Os principais tratamentos para esses pacientes são a quimioterapia e a radioterapia. Outras opções terapêuticas incluem anticorpos monoclonais e o transplante de células tronco hematopoiéticas. Objetivo: Relatar um caso de LH refratário à quimioterapia, mas responsivo ao Nivolumabe. Relato de caso: Paciente de 23 anos, feminino, com quadro de linfonodomegalias em região cervical em 2020, com aumento gradativo em quantidade e tamanho. Ao exame físico, foi possível observar linfonomegalia com múltiplos gânglios móveis, indolores e de consistência fibro-elástica em cadeias ganglionares cervical inferior, supraclavicular e axilar (bulky). Em fevereiro/2021, imuno-histoquímica resultou Linfoma deHodgkin - Esclerose Nodular, CD30+/CD15+/MUM-1+. Em março/2021, relatou perda de 14 kg, sudorese noturna e febre esporádica à noite. Iniciou quimioterapia em abril/2022 e terminou os seis ciclos de ABVD em outubro/2022 sendo a doença refratária. Tentativas de resgate com um ciclo de DHAP (toxicidade renal), dois ciclos de GIV sem resposta satisfatória e então 20 sessões de radioterapia, finalizadas em março/2023 com resposta parcial. Em junho/2023 fez novo PET, que revelou doença em região cervical e axilar, portanto, LH triplo refratário. Iniciado tratamento com Nivolumabe em fevereiro/2024 com resposta clínica completa já no primeiro ciclo e metabólica ao PET após o sexto ciclo. Discussão: O esquema ABVD é o tratamento de primeira linha para o LH, mas cerca de 15% dos pacientes apresentam refratariedade. No caso relatado, a paciente não respondeu ao ABVD, levando a outros esquemas (DHAP, GIV), objetivando um transplante autólogo se responsivo à quimioterapia. Como não houve resposta, foi considerado o uso do anticorpo monoclonal Nivolumabe. O Nivolumabe é uma opção eficaz para pacientes com LH recidivado. Estudos sugerem que sua ativação prolongada ao sistema imunológico contribui para a remissão, mostrando que sua ligação às células T pode persistir por mais de dois meses após uma única dose. No caso da paciente, a resposta positiva ao Nivolumabe pode ser atribuída à essa persistência. Isso reforça estudos que indicam a eficácia do bloqueio de checkpoint anti-PD-1 como uma estratégia potencialmente curativa para pacientes com LH refratário, especialmente em casos com características genéticas que aumentam a expressão dos ligantes do PD-1. Conclusão: O LH apresenta um desafio terapêutico considerável nos casos refratários aos tratamentos convencionais. O caso relatado destaca a importância de alternativas terapêuticas, como o uso do anticorpo monoclonal citado. Mostrou que o inibidor de check point - anti-PD1, Nivolumabe, é uma ótima opção para esses casos refratários.

B-ALL is heterogeneous disease and its classification can be defined by recurrent genetic abnormalities as WHO 5th. Recent gene expression studies have identified genetic drivers that confer distinct prognostic impact, as B-ALL ZNF384-r. We report a case of TAF15::ZNF384 B-ALL recurring 6 years after the 1st diagnosis. 3-year-old boy admitted in 2014 with fever and petechiae. CBC HB 7.9 g/dL WBC 2.9 × 109/L Platelets 30 × 109/L. BMA showed 87% blasts and by flow cytometry (FC) with B-ALL. Cytogenetic analyses (CA):46,XY,t(17;17)(p12;q11)[3]/46,XY[17]. RT-PCR negative for BCR::ABL1 p190 and ETV6::RUNX1. It's collected biospecimens from BMA for further analysis. He's treated as HR-ALL according to “Brazilian Childhood Acute Lymphoblastic Leukemia Treatment Group 2009” protocol and achieved remission by the end of induction. He's out of therapy for 6 years when he presented with 2 weeks of fever. CBC HB 14.9 g/dL WBC 5440 × 109/L Platelet 335 × 109/L with 22% blasts. BMA was performed and through FC was confirmed B-cell ALL and CA was 47,XY,t(17;17)(p12;q11),+21[15]/46,XY[5]. The same translocation from the 1st diagnosis. FISH reveal (ETV6 × 2, RUNX1 × 3)[112/200], (3’IGH × 2, 5’IGH x 1) [109/200], without other changes. He received ALL-REZ BFM 2002 reinduction and as he failure the 1st therapy, he underwent to 2nd reinduction with Mini-CVAD and Blinatumomab as bridge for HSCT. By the end of the 1st cycle MRD was up to 5%. Due to the refractory of the disease, we run NGS using the Oncomine Childhood Cancer Research Assay Panel. He's submitted to a 3rd salvage plan with bortezomib plus chemotherapy. By the end of the 1st cycle MRD was 1%. NGS result showed TAF15::ZNF384 in the biospecimens from the diagnosis and relapse. With this information and in attempt to improve response to reach HSCT, it's proposed hybrid therapeutic with cytarabine, azacytidine and venetoclax. After 1st cycle, BMA demonstrated MRD of 0,02%, achieving better response as he could got to undergo to HSCT. WHO 5th recognizes the importance of genetic information in the evaluation of lymphoid neoplasia, and this harbored spot to incorporate new entities whose recognition is increasing as molecular diagnostic become more available. TAF15::ZNF384 occurs in early common progenitor which may discern into myeloid or lymphoid. Considering the ZNF384-r lineaging plasticity and the highly chemorefractory in our case, it's proposed hybrid treatment associating myeloid scheme as salvage regimen.

A Leucemia Mieloide Aguda (LMA) corresponde a cerca de 15% das neoplasias hematológicas da infância. O diagnóstico, inicialmente baseado em características morfológicas, foi sendo refinado ao longo dos anos com a implementação de novas ferramentas diagnósticas. Objetivos: Caracterizar clínico e laboratorialmente pacientes pediátricos diagnosticados com LMA, correlacionando os achados das diversas ferramentas diagnósticas empregadas. Materiais e métodos: Foi realizado um estudo de coorte retrospectivo com pacientes de 0-18 anos de idade com LMA, diagnosticados e tratados no Hospital de Câncer InfantoJuvenil de Barretos, no período de janeiro de 2002 a junho de 2022. Resultados: Foram incluídos 83 pacientes com mediana de 9,2 anos. Dos achados de hemograma, 36,1% se apresentaram com leucometria acima de 50.000/mm3. Mielograma foi realizado em 97,5% dos pacientes, 98,8% imunofenotipagem por citometria de fluxo, 75,9% citogenética e 74,7% análise molecular. Segundo classificação morfológica adotada (FAB), LMA M2 e M5 (20,5%) foram os subtipos mais frequentes. Dos achados imunofenotípicos, 100% dos pacientes com LMA FAB M1, M2 e M3 tinham MPO+ e nenhum dos pacientes FAB M0; expressão anômala de CD19 foi observado em 37,5% dos pacientes FAB M2 e, destes, 83,3% tinham na pesquisa genética identificação de RUNX1::RUNX1T1 . Todos pacientes com LMA M5, 60% dos pacientes LMA M4 e 77,8% dos FAB M3 tinham CD64+. No que diz respeito à expressão anômala de CD56, mais de 80% dos pacientes com LMA M5 e 75% dos pacientes LMA M4 e M2 tinham mieloblastos CD56+. O antígeno HLA-DR foi negativo na população blástica em 84,6% dos pacientes com diagnóstico de LMA M3; correlacionando com a presença t(15;17) PML::RARA , 80% eram HLA-DR− e 54,5% CD34− A análise citogenética foi alterada em 58,7% e desses 21,6% tinham cariótipo de pior prognóstico. Anormalidades genéticas recorrentes foram observadas em 37,8% pacientes com cariótipo alterado, enquanto 40,5% destes possuíam LMA sem outra especificação. A alteração molecular mais comum foi PML::RARA (18,6%), seguida do rearranjo KMT2A::MLLT3 (15,8%). A pesquisa de mutação dos genes FLT3 , NPM1 e CEBPA foi disponível para 46 pacientes, com 14,9%, 9,5% e 9,1% pacientes positivos, respectivamente. Discussão: A LMA é uma doença heterogênea e sua classificação engloba aspectos clínicos e laboratoriais para definição prognóstica e terapêutica. As características morfológicas, imunofenotípicas, genéticas se correlacionam e muitas vezes os achados iniciais permitem inferir mutação a ser encontrada. É descrito que 20-25% dos pacientes pediátricos tenham alterações genéticas recorrentes. No presente estudo 13,5% possuíam tal alteração, sendo a maioria envolvendo rearranjos do gene KMT2A, compatível com os 10-15% esperado na faixa etária pediátrica. Dos 40% de pacientes com LMA M2 e CD19+, mais de 80% tinha t(8;21), corroborando o que é descrito na literatura. HLA-DR foi negativo em 80% dos casos de LMA com t(15;17) PML::RARA , conforme esperado. Conclusão: Encontrou-se similaridade à literatura quanto a classificação morfológica da LMA, assim como a associação entre perfil morfológico, imunofenotípico e genético de alguns subtipos de LMA.

Introduction: Central nervous system (CNS) involvement is a poor prognostic factor of non-Hodgkin's lymphoma (NHL) in children. Therefore, early diagnosis and treatment of CNS disease is important to improve long-term disease-free survival rates in children. With the continuous progress of science and technology, the methods and technologies used for the diagnosis of CNS disease are constantly improving, from imaging and cerebrospinal fluid (CSF) morphology studies to cerebrospinal fluid CSF flow pattern and genetics studies, and so on. With the continuous progress of diagnosis technology, the clinical staging of patients, which has a vital role in follow-up treatments, has also become more accurate. Most patients with early CNS invasion have no obvious clinical manifestations. Therefore, to improve the diagnostic rate of CNS invasion, flow cytometry (FC) and conventional cytomorphology (CC) of CSF were performed in newly diagnosed NHL patients for the first time of intrathecal chemotherapy. We report the examination findings and flow cytometry (FC) and conventional cytomorphology (CC) of two patients diagnosed with a Burkitt lymphoma and treatment response. Case Report: : Case 1: Adolescent, male, 16 years old, with stage IV Burkitt lymphoma. In first evaluation cerebrospinal fluid, absence of atypical cells in cytological examination, immunophenotyping, presence of 38 cells/mL with immunophenotype: CD10+, CD19+, CD20+, CD38+, CD45+, Kappa+, CD34-, Lambda-. In the second CSF, absence of atypical cells and in the immunophenotyping, absence of monoclonal B lymphoid cells. Currently, the patient is 7 months out of treatment in remission. Case 2: Adolescent, male, 17 years old, with stage IV Burkitt lymphoma; in the first evaluation of the CSF with absence of atypical cells on cytology, on immunophenotyping, presence of 40% of anomalous B cells with immunophenotype: CD10+, CD19+, strong CD20, CD34 weak, CD38 strong. In a second CSF evaluation, the patient presented absence of atypical cells on cytological examination and absence of monoclonal B lymphoid cells. Currently, the patient is undergoing treatment with no evidence of CSF involvement. Conclusion: Central invasion is more common to be found in pediatric NHL patients with bulky disease and/or BM involvement and/or involvement of more than 4 organs. It was also common in the EBV with Burkitt Lymphoma. CSF detection by FC has important clinical significance in the diagnosis of CNS invasion in children with NHL, as it can significantly improve the detection rate of CNS involvement and evaluation during the treatment.

Introduction: Lymphomas are cancers that arise from the white blood cells and have been traditionally divided into two large subtypes: Hodgkin and non-Hodgkin lymphoma. B-cell lymphoma is the most common subtype of non-Hodgkin lymphoma; almost 75% of patients with lymphoma have this variant. Lymphomas can potentially arise from any lymphoid tissue located in the body; however, secondary involvement in the adrenal, pancreas and thyroid is very uncommon. We report the history, examination findings, staging images results of a 17 -year-old adolescent man diagnosed with a Burkitt lymphoma. Case report: Adolescent, male, 17 years old, with the appearance of a subclavicular nodule on the right since November 2023, extending to the axillary region; without presenting fever, weight loss, night sweats, abdominal pain. Admitted to the service in June 2024 with a previous lymph node biopsy result with a reactional appearance. Evolving from April 2024 with a significant increase in the mass, associated with paresthesia of the hand and pain when moving the right upper limb. Chest tomography showed a solid mass in the right axillary region (16.4 × 12.7 × 15.5 cm); with involvement of the axillary and subclavian vessels on the right, maintaining contact with the right lateral and anterior chest wall up to the skin; nodular lesions in the bilateral thyroid parenchyma; lesions compatible with lymphoproliferative disease. Abdominal tomography showed a solid mass in the body of the pancreas (5.8 × 5.2 cm), a solid mass in the topography of the left adrenal gland (10.4 × 6.2 cm), solid nodular lesions in the cortex of the bilateral kidneys (up to 3.2cm on the left); all lesions compatible with metastases. Performed on the lymph node conglomerate that diagnosed Burkitt's lymphoma, the patient concluded the stage without bone marrow involvement but with involvement in the cerebrospinal fluid, defining it as stage IV. Chemotherapy treatment was started with good clinical response and images. Conclusion: Based on this case and a review of the literature, secondary involvement of the adrenal, pancreas and thyroid does not affect the patient's prognosis like involvement of the cerebrospinal fluid or bone marrow. However, this case characterizes an unusual presentation of Burkitt's lymphoma with involvement of three endocrinological organs simultaneously.

A Leucemia Linfoide Aguda (LLA) é a neoplasia mais frequente na faixa etária pediátrica. Fibrose medular é uma alteração estromal que pode ocorrer em medula óssea de forma primária, como na mielofibrose ou associada a outras neoplasias hematológicas. É uma alteração rara nos pacientes com LLA, sendo descrito em torno de 30% das leucemias. Objetivo: Descrever o caso de um paciente que se apresentou com fibrose medular severa ao diagnóstico de LLA, dificultando diagnóstico inicial. Metodologia: descrição de dados clínicos e laboratoriais baseada em revisão de prontuário. Resultados: Paciente masculino, 6 anos de idade, proveniente de Manaus - Amazonas, com antecedente de mal formação em polegares; negou história de neoplasias na família. Deu entrada neste serviço com relato de que há 8 meses da consulta inicial evoluiu com icterícia e palidez na origem, sendo internado para investigação e identificado bicitopenia em hemograma. Tentado mielograma, sem sucesso, e realizado biópsia de medula óssea (BMO) complementar que evidenciou neste momento medula óssea aplasica, com 20% de celularidade e população imatura, fibrose medular grau 3 com hipótese inicial de síndrome mielodisplásica/falência medular congênita; na ocasião recebeu transfusão de hemoderivados e realizado Deb teste, que foi negativo. No período paciente apresentou diversas internações por infecções graves. Devido manutenção dos achados realizada nova avaliação medular que mostrou 100% de celularidade com células de aspecto imaturo, imunohistoquimica compatível com infiltração medular por linfoma/leucemia linfoblástica B. Encaminhado para seguimento neste serviço. Ao exame físico: dismorfismos faciais, emagrecido, com hepatomegalia. Na admissão hemograma com Hb 4,9 g/dL/Ht 13,6%/ VCM 80fL / HCM 29pg / RDW 13,2%, Leucócitos 960/mm3 e Plaquetas 63k/mm3. Avaliação medular hipocelular por diluição com comprometimento de análise e cerca de 5% de blastos; BMO favoreceu diagnóstico de linfoma/leucemia linfoblástica de imunofenótipo B em meio a fibrose reticulínica grau 3. Complementação diagnóstica: cariótipo inconclusivo, painel de translocações negativo e exoma em andamento. Paciente classificado como LLA B, SNC 1, risco intermediário por uso prévio de corticoide, atualmente em quimioterapia na fase de consolidação, respondendo bem ao tratamento. Discussão: A medula óssea é composta por células hematopoiéticas dispostas entre uma matriz extracelular e células estromais, dentre elas os fibroblastos. A fibrose medular é caracterizada por uma desordem arquitetural da medula óssea, gerando prejuízo para a homeostase do ambiente medular. A fibrogênese se dá através da sinalização de fatores de crescimento e citocinas que excitam vias formadoras de fibrose das células tronco mesenquimais na própria medula, culminando com o acúmulo de reticulina, associado ou não ao colágeno. A fibrose medular secundária surge de uma alteração que pode ou não ser clonal. A LLA é uma importante causa de fibrose medular difusa e esta geralmente se resolve com o próprio tratamento da leucemia. Conclusão: A LLA pode se apresentar com fibrose medular e a dificuldade de obtenção de material adequado pode retardar o diagnóstico. É relatado, inclusive, o ressurgimento da fibrose previamente ao aparecimento de blastos na recaída, reforçando a necessidade de um acompanhamento mais minuncioso nestes pacientes.

Introduction: Hodgkin lymphoma (HL), unlike non-Hodgkin lymphoma, rarely involves the central nervous system (CNS). The incidence has been reported as 0.2% to 0.5% of all HL cases, but a recent review of 14 868 patients identified only 2 cases of HL involving the CNS. Consequently, there is no consensus to guide therapeutic decision-making. Involvement of the brain or spinal cord by HL can be primary or, more frequently, secondary to the compromise of adjacent lymph nodes. Lesions are more frequently intraspinal than intracranial. We describe a patient with systemic HL who presented with involvement of the CNS at diagnosis. Case Report: A six year -old female with a history of progressive cervical lymphadenopathy, presented in October 2023 with isolated cervical lymphadenopathy on the right, in addition to fever, pruritus in the upper limbs and night sweats. Initial pediatric evaluation did not conclude that the cause was infectious. In December 2023 cervical lymphadenomeglia increased in size (2x2cm) but in January 2024 with a progressive increase of 3x2 cm in addition to fever, night sweats and worsening itching, a biopsy was performed which defined as Hodgkin's Lymphoma subtype nodular sclerosis. Admitted to our service in March 2024, in addition to enlarged lymph nodes, fever, night sweats and pain in the lower limbs. After 48 hours of admission to this hospital to start the staging, she developed loss of strength in the left lower limbs. She mainly started Dexamethasone 10mg/m2/day and underwent an MRI. Magnetic core scan of the total spine and brain that showed: Solid neoplastic lesion inside the vertebral and sacral canal, from L4 to S3, involving the roots of the cauda equina, infiltrating the neuroforamens L5-S1, S1-S2 and S2-S3 on the left and compressing the corresponding roots. Solid paravertebral neoplastic lesion on the left, infiltrating the spinal canal at the level of T1-T2 and T6-T7 on the left. Diffuse heterogeneous change in the bone marrow signal of the vertebral bodies, which may represent neoplastic involvement. Solid neoplastic lesions with a dural base, one in the left temporal lobe, measuring 4.3 x 3.8 x 1.7 cm and another in the right frontal lobe, measuring 3.9 x 2.3 x 1.7 cm (CC x TT x AP), showing intense homogeneous post-contrast enhancement and diffusion restriction, the latter associated with vasogenic edema in the frontal white matter on the right. These findings may be related to the spread of the underlying neoplastic lesion. PET-CT with 18F-FDG showed - Metabolism in supra and infradiaphragmatic lymphadenopathy, spleen and bones compatible with active lymphoproliferative disease. Twenty-four hours after starting Dexamethasone, the patient experienced improvement in neurological symptoms, then underwent the 1st cycle of chemotherapy with improvement in neurological and systemic symptoms. She showed an excellent response after two cycles and is currently undergoing chemotherapy with no evidence of disease progression. Conclusion: Finally, unusual and aggressive extranodal presentations of HL should alert to the possibility of HIV infection. Whole brain irradiation and systemic chemotherapy remain the treatment of choice for CNS involvement in patients with HL.

Introdução: A Leucemia Mieloide Crônica (LMC) é uma neoplasia mieloproliferativa com incidência de 1-2 casos por 100.000 adultos. A patogênese corresponde à fusão do gene ABL1 no cromossomo 9 com o gene BCR no cromossomo 22, o que resulta na expressão de uma oncoproteína denominada BCR/ABL, que em mais de 95% dos pacientes pode ser visualizada na cariotipagem como um cromossomo 22 encurtado, o cromossomo Filadélfia. O quadro clínico inclui fadiga, perda de peso, dor no quadrante superior esquerdo, anemia e esplenomegalia. O diagnóstico é baseado em aspectos clínicos e exames de sangue, como hemograma, assim como análise citogenética e molecular. Para pacientes com LMC, os inibidores da tirosina quinase (TKIs) são utilizados no tratamento. Objetivo: Relatar um caso de LMC com perda de resposta ao imatinibe associada à mutação E255V. Relato de caso: L.R.V., masculino, 46 anos, iniciou quadro com dores abdominais do lado esquerdo do abdome e perda de peso de 6kg em 1 em agosto/2022. Negava sangramentos, linfonodomegalias, febre ou sudorese noturna. Ao exame físico foi possível observar esplenomegalia. Em agosto/2022 apresentava hematócrito 33,9%, leucócitos 163.000/mm3, plaquetas 650.000/mm3. Mielograma com medula óssea hipercelular nas séries, granulócitos e megacariocítica. Imunofenotipagem com proliferação de células imaturas ou anômalas linfoides T/B/N12. BCR/ABL detectado 53,01%. Fez uso de hydroxiureia por 1 mês e depois imatinibe 400 mg diariamente a partir de dezembro/2022. Exames de março/2023 (3 meses) mostraram hemograma normal e BCR/ABL de 0,1%. Mesmo com boa adesão ao tratamento, em fevereiro/2024, houve incremento do BCR/ABL para 1,9%. Com o aumento do BCR/ABL foi solicitada pesquisa de mutação do gene ABL em dezembro/2023 com resultado de mutação do gene E255V. Como essa mutação parece não responder ao Nilotinibe, optou-se pela mudança para dasatinibe 100 mg/dia em abril/2024. Após três meses de tratamento, redução para 0,005%. Discussão: A mutação do gene E225V ocorre no gene ABL1, que faz parte do cromossomo Filadélfia (Ph), um marcador genético da LMC, desencadeada pelo oncogene BCR-ABL. A presença dessa mutação pode estar associada a uma resistência aos TKIs, que são a principal classe de medicamentos usados no tratamento da LMC, sendo necessário o uso de medicamentos de segunda geração, como o dasatinibe. Estudos in vitro e in vivo demonstram que o medicamento é ativo contra várias mutações da oncoproteína BCR-ABL resistentes ao imatinibe. A resposta à terapia a TKI por meio da relação BCR/ABL é o fator prognóstico mais importante em pacientes com LMC. Mede-se a resposta do paciente no início do tratamento e então depois de 3 meses, 6 meses e 1 ano. O paciente em questão apresentou aumento dessa relação de março de 2023 com 0,1% para 1,9% em fevereiro de 2024, período o qual estava em uso de imatinibe e com a troca para Dasatinibe apresentou resposta entre 4 e 5 log de redução dos transcritos. Conclusão: O caso evidencia a complexidade da LMC com mutação E255V, tratada com dasatinibe após resistência ao imatinibe, destacando a importância das análises genéticas e da adaptação terapêutica individualizada.

Erectile Dysfunction (ED) is a multifactorial disease related to psychosocial determinants and Cardiovascular Disease (CVD). Since Adults with Hemophilia (AwH) may have impaired psychosocial functioning due to the disease and have a high risk of developing CVD, we assumed ED might be prevalent among them. We evaluated perceived ED using a validated self-reported questionnaire in AwH participating in a cross-sectional study to describe CVD and CVD risk factors (HemoCardio Study). Male AwH aged ≥30-years attending a Northeastern Brazilian Hemophilia Treatment Center were invited. Demographic and clinical/therapeutic hemophilia data were collected from medical files. Clinical/therapeutic data about CVD and CVD risk factors were obtained by interview, physical examination, and laboratory tests. Perceived ED was evaluated by the International Index of Erectile Function-Erectile Function Domain (IIEF-6) instrument. Quality of life (QoL) was evaluated by HemoLatin-QoL and EQ-5D. Well-being was evaluated by the Hemophilia Well-Being Index (HWBI). For all questionnaires, higher scores meant better outcomes. A total of 84 AwH was included in the main study. Of the 52 AwH who responded to the IIEF-6, median age was 42.0-years (Interquartile Range [IQR] 36.0‒51.8), 43 (83%) had hemophilia A, and 25 (48%) were severe. Median IIFE-6 was 29.0 (IQR 25.3‒30.0) and 13 (25%) perceived ED. Perceived ED was associated with severe hemophilia (p = 0.025), lower HemoLatin-QoL total score (p = 0.010), and lower EQ-5D index (p = 0.038), but fairly associated with the use of anti-hypertensive (p = 0.043) and antidiabetic (p = 0.049). HWBI did not differ between AwH who perceived or did not ED. IIEF-6 had a positive correlation with the emotional functioning domain of the HemoLatin-QoL (n = 47, ϱ = 0.313, p = 0.032), but not with HemoLatin-QoL total score, EQ-5D index, or HWBI. We could not find associations between CVD or CVD risk factors and perceived ED among AwH. However, perceived ED correlated with QoL.

Objetivos: Descrever um caso de infarto renal secundário a trombose em paciente previamente hígido sem fatores de risco. Material e métodos: Coleta de dados em prontuário e entrevistas com o paciente. Resultados: Homem, 48 anos, procurou pronto atendimento devido quadro de epigastralgia, edema de Membros Inferiores (MMII) e fraqueza, há 1 dia. Em uso diário de cúrcuma, vitamina K2MK7, semente de abóbora, BCAA, maca peruana, vitamina D e melatonina. Antecedente familiar de irmã com artrite reumatóide. Na avaliação clínica, apresentava dor à palpação de epigástrio e hipocôndrio direito, Descompressão Brusca (DB) negativa, edema +/4+ em MMII, bradicardia e hipertensão arterial. Houve melhora parcial da dor com sintomáticos e exames laboratoriais iniciais sem alterações. No dia seguinte, em consulta com cardiologista, apresentava discreto edema bipalpebral, DB positiva e bradicardia, então solicitado Eletrocardiograma (ECG) e Tomografia Computadorizada (TC) de abdome contrastado, que demonstraram, respectivamente, bradicardia sinusal e sinais de pielonefrite aguda à esquerda. Optado por internação, início de antibioticoterapia endovenosa e investigação cardiológica. Para elucidação diagnóstica de isquemia renal, foi solicitado angiotomografia arterial e venosa de abdome e pelve, a qual evidenciou possível área de infarto renal. Com provável diagnóstico, foi proposto iniciar anticoagulação com Enoxaparina 60 mg. Como paciente se mantinha estável hemodinamicamente, sem dor, exames laboratoriais sem alterações, foi preconizado anticoagulação domiciliar. Paciente mantinha-se em bradicardia sinusal pelo ECG, porém, assintomático, com incremento da frequência cardíaca ao conversar e resultado de ecocardiograma transtorácico sem anormalidades. Sem indicação de intervenção, paciente recebeu alta com anticoagulação plena (Rivaroxabana) e orientação para investigação ambulatorial de possíveis causas do evento. Exames para investigação de trombofilias não demonstraram evidência de distúrbios de coagulação. Discussão: As etiologias conhecidas de Oclusão Arterial Aguda (OAA) incluem os estados de hipercoagulabilidade, lesões arteriais, miocardiopatias, entre outras, que na investigação foram descartadas para o quadro clínico apresentado. A trombose de artéria renal sem evidências de fatores causais é uma ocorrência rara. Deve-se considerar, como diferencial, a suplementação de vitamina K2MK7 100 mcg/dia feita por 5 meses consecutivos, sem orientação médica, como agente causal da trombose, visto que a dosagem considerada segura é de 1 mcg/d/kg. Concordantemente com demais casos relatados de infarto renal, o paciente em questão apresentou elevação súbita da pressão arterial, explicada pela ativação do sistema renina-angiotensina-aldosterona na redução da perfusão renal. Além disso, foi observado alteração da função renal com os exames creatinina sérica de 1,17 mg/dL e eGFR 73 mL/min/1,73m2 e 24h após, creatinina sérica 1,28 mg/dL, eGFR 66 mL/min/1,73m2. Conclusão: A OAA é um desafio clínico aqui destacado, pela complexidade diagnóstica frente a uma condição incomum que pode se apresentar em pacientes sem fatores de risco evidentes, mas que requer reconhecimento precoce devido ao risco de insuficiência renal, de modo a considerá-lo como hipótese diferencial prezando pela eficácia do tratamento. Como apresentado, a ocorrência do quadro raro requer investigação adicional para elucidação causal.

A Leucemia Mieloide Aguda (LMA) corresponde a até 50% das mortes relacionadas à leucemia. Embora nas últimas décadas tenha sido observada significativa melhora no prognóstico com avanços no diagnóstico e terapias propostas, em países de renda média a baixa como Brasil a sobrevida de pacientes pediátricos com LMA ainda é de 30-40%. Objetivos: Descrever a sobrevida global e livre de eventos dos pacientes pediátricos diagnosticados com LMA no Hospital Infantojuvenil de Barretos, no período de janeiro de 2002 a junho de 2022. Materiais e métodos: Foi realizado um estudo de coorte retrospectivo. A análise de sobrevida foi estratificada em dois períodos distintos: Entre janeiro/2002 a maio/2013 (tratamento realizado na unidade de adultos do Hospital de Câncer de Barretos); e junho/2013 a junho/2022 (tratamento e suporte realizados na unidade infantil do Hospital). As sobrevidas global (SG) e livre de eventos (SLE) foram avaliadas considerando todos os pacientes LMA, LMA exceto leucemia promielocítica aguda (LPA) e, também, considerando apenas as LPA. Resultados: Foram incluídos 83 pacientes, sendo 25 no primeiro período e 58 no segundo período. Analisando o período de 20 anos, incluindo todos os pacientes pediátricos com LMA, encontrou-se SG de 37,7% e SLE de 35,8%. Excluindo LPA, a SG foi de 31,9% e a SLE foi de 31,2%. Já dentre os pacientes com LPA, a SG foi 64,3%. Ao avaliar a sobrevida nos dois períodos separadamente, a sobrevida global foi de 28% no primeiro período e 41,4% no segundo período. O óbito durante fase de indução chegou a 52,6% no primeiro período, e quase 50% dos pacientes tinham hiperleucocitose; a maioria dos pacientes desse período analisado foram tratados segundo protocolo BFM; 26,5% dos pacientes tiveram recaída de doença. O protocolo brasileiro GELMAI foi implantado recentemente e dos 10 pacientes incluídos não houve nenhum óbito na fase de indução. Quando a sobrevida foi estratificada segundo grupo de risco genético, pacientes de baixo risco tiveram uma sobrevida global de 50%, superior quando comparado aos risco intermediário e alto, com 30 e 28,6% de sobrevida, respectivamente. Discussão: Em nosso serviço, foram observadas taxas elevadas de óbito indutório nos pacientes com LMA. O diagnóstico tardio de muitos pacientes devido a dificuldade em serem referenciados a um centro oncológico, assim como quimioterapia intensiva indutória de protocolos internacionais e cuidado suportivo deficiente podem ser considerados para esse achado. Certamente, o cuidado às crianças realizado por pediatras – oncologistas, intensivistas, equipe multidisciplinar – em hospital pediátrico influenciou na melhora sobrevida global e redução de óbito indutório no serviço a partir de 2013. Conclusão: Pode-se inferir, com os dados obtidos, a importância de um serviço de tratamento especializado em conduzir crianças graves, com suporte necessário e de fácil acesso à disposição, além de profissionais treinados ao atendimento à população pediátrica. A morbimortalidade relacionada ao tratamento, entretanto, permanece um desafio nos países em desenvolvimento, inclusive neste Hospital, com a proposição de tratamentos de intensidade reduzida na indução se monstrando uma realidade fáctivel em países de baixa e média renda como o Brasil.

Introdução: São considerados efeitos adversos das transfusões sanguíneas qualquer intercorrência após a administração de sangue ou hemocomponentes. Essas reações podem ser divididas em imunológicas e não imunológicas e também divididas em agudas, ou seja, nas primeiras 24 horas e tardias após as 24 horas. De forma geral, as reações derivadas de transfusão sanguínea não são comuns em locais especializados visto que há cuidados especiais para evitar tais eventos, como a filtração das bolsas de hemocomponentes e uso de pré-medicação. Objetivos: Avaliar a frequência de reações transfusionais e seus tipos. Material e métodos: Avaliação de prontuários de pacientes submetidos a transfusões de 8/2022 a 7/2023 no Ambulatório de Transfusão do Conjunto Hospitalar de Sorocaba - CHS. Resultados: Foram analisadas 622 transfusões sanguíneas (eventos transfudionais), sendo ao todo 95 pacientes, com 50,52% do sexo masculino e 49,47% do feminino, com média de idade de 58,96 anos Quanto à procedência, 38,94% do municipio de Sorocaba. A doença de base mais prevalente foi o Linfoma Não-Hodgkin (10,52%). Em relação à comorbidades, a maioria dos prontuários estava sem esta informação (49,47%), dificultando a análise desse dado. Foram utilizadas 1477 bolsas nos 622 eventos transfusionais, sendo a maior parte de concentrados de plaquetas (58,56%). Dos 622 eventos avaliados, 613 utilizaram bolsas filtradas e/ou irradiadas e em 9 não havia tal informação. A maioria das transfusões ocorreu após uso de pré-medicação (99,51%), sendo utilizados corticoesteroides, anthistaminicos e diuréticos. Ocorreram 3 reações adversas ao todo, sendo 2 em um mesmo paciente, do sexo masculino (21 anos) e 1 em uma paciente de 60 anos. As reações foram agudas imunológicas. No paciente do sexo masculino, as duas reações apresentaram-se com edema de glote e petéquias, enquanto a paciente do sexo feminino apresentou prurido em membros superiores e inferiores. Discussão: Podemos constatar que as reações adversas às transfusões sanguíneas no ambulatório de transfusão do CHS são extremamente incomuns, 0,48% de reações se considerarmos os eventos transfusionais e ainda menos (0,20%) se considerarmos todas as bolsas transfundidas. Sobre as reações adversas encontradas, todas foram do tipo agudas imunológicas e em transfusões de plaquetas. As 3 reações do tipo aguda imunológica encontradas foram alérgicas e podem ocorrer quando há proteínas estranhas ao paciente, no plasma do doador, causando uma reação do tipo hipersensibilidade tipo II, se revelando clinicamente com lesões urticariformes e prurido, ou ate quadros mais graves como o edema de glote. Além disso, apesar de uma grande variação de faixas etárias, tendo a máxima de 89 e mínima de 18 anos, a idade não pareceu interferir na ocorrência de reações adversas, aasim como o gênero do paciente. Conclusão: As informações coletadas equiparam-se aos dados encontrados na literatura base e referência, na qual afirmam que a filtração das bolsas de hemocomponentes e o uso de pré-medicação como anti-histamínicos e glicocorticoides são importantes para evitar a ocorrência de reações adversas febris nao hemoliticas e alérgicas, respectivamente, assim como diuréticos e um volume e velocidade adequados previnem sobrecarga cardíaca.

Objetivos: Segundo a Pan American Health Organization (PAHO), estima-se que em torno 1.3 bilhão de pessoas vivam com alguma deficiência visual no mundo. No Brasil, o Instituto Brasileiro de Geografia e Estatística (IBGE) aponta que existem mais de 6,5 milhões de pessoas com deficiência visual no Brasil, sendo 500 mil cegas e cerca de 6 milhões com baixa visão. Este estudo explora estratégias realizáveis diante realidade do cuidado farmacêutico para auxiliar na elaboração de documentos voltados para pacientes com deficiência visual, visando melhorar a adesão ao tratamento de medicamentos orais e a orientação no acompanhamento de condições hematológicas. Material e métodos: Realizou-se uma revisão bibliográfica utilizando fontes como, Scielo e Pubmed e descritores: deficiência visual e cuidado farmacêutico, além de diretrizes para a criação de documentos acessíveis, com foco em formatos que atendam às necessidades de pacientes com deficiência visual. Foram avaliados recursos e técnicas para garantir que a informação seja compreensível e utilizável. Resultados: Para orientar eficazmente pacientes com deficiência visual durante o acompanhamento, é crucial desenvolver estratégias específicas que atendam às suas necessidades. Adotar diferentes formatos, como braille, áudio e documentos digitais compatíveis com leitores de tela, assegurando que a informação seja acessível a todos que precisam. Escrever textos claros e bem estruturados, com alto contraste e fontes de tamanho adequado em documentos digitais, garantindo uma apresentação clara e organizada das informações. Usar tecnologias e implementar ferramentas tecnológicas, como aplicativos de leitura de tela e softwares de conversão de texto para áudio, para facilitar o acesso à informação e garantir a autonomia do paciente. Participar e promover capacitações e educar profissionais de saúde sobre a importância da acessibilidade e orientar quanto às melhores práticas na criação de materiais que atendam às necessidades dos pacientes com deficiência visual. Discussão:Existem poucos estudos disponíveis sobre o tema, o que destaca a necessidade de uma investigação mais profunda. É crucial explorar conceitos específicos para profissionais da saúde, como desenvolver materiais educativos que abordem os desafios enfrentados por pacientes com deficiência visual. Além disso, é fundamental criar cursos que ensinem melhores abordagens para lidar com esses pacientes e estabelecer meios eficazes de comunicação entre profissionais e pacientes. Manter-se atualizado sobre as ferramentas que facilitam o dia-a-dia dos pacientes e garantir o acesso a essas ferramentas para pessoas que têm menos informação também são pontos essenciais a serem considerados em especial pacientes oncohematologicos que fazem uso de diversos medicamentos orais e de alto custo. Conclusão: A criação de documentos acessíveis é fundamental para melhorar a adesão e a orientação no acompanhamento de pacientes com deficiência visual em tratamentos oncohematológicos, face a incorporação de novas tecnologias crescentes na hematologia em especial medicamentos orais. A adoção de formatos acessíveis e o uso de tecnologias assistivas são essenciais para garantir que todos os pacientes possam receber e compreender as informações necessárias para um tratamento eficaz e seguro.

Introdução: Os serviços de saúde geram, diariamente, milhares de dados, sendo eles muitas vezes subutilizados devido à sua magnitude ou pela falta de domínio dos profissionais de saúde na análise dos mesmos. A tecnologia da informação vem agregando interdisciplinaridade à saúde, em especial na compilação e análise dos grandes volumes de dados, trazendo subsídios aos profissionais responsáveis pela assistência direta ao paciente bem como aos tomadores de decisão, na entrega de oportunidades estratégicas de negócio. No quesito de planejamento institucional, possibilita a contextualização de comportamentos e visualização de componentes não previstos em indicadores. Objetivos: Abordar o uso da Mineração de Dados como uma estratégia para o cuidado em saúde. Material e métodos: Revisão integrativa na temática nos últimos cinco anos. Resultados: Destaca-se na área de tecnologia da informação a Mineração de Dados, técnica que realiza análise de grande volume de informações através de algoritmos complexos, possibilitando a extração de conexões, associações entre eventos e padrões úteis, produzindo novos conhecimentos que não seriam passíveis de descoberta unicamente através da análise do observador. Atua como norteador de condutas da equipe de saúde e gestores, sejam elas preventivas ou mesmo preditivas. Discussão: Estudos têm demonstrado seu uso para predizer o perfil de pacientes mais propensos a desenvolvimento de doenças, bem como estimar tempo de sobrevida em doentes oncológicos ou mesmo associar características não antes tidas como importantes na caracterização de malignidade do tumor. Conclusão: A possibilidade do uso de novos conhecimentos no cenário oncológico abre a possibilidade de prenunciar contextos, pensar estratégias de monitoramento ativo para grupos de risco, entre outros, impactando diretamente na qualidade de vida, desfecho clínico, bem como proteção da saúde financeira das instituições, que podem planejar e executar ações com base nos conhecimentos apresentados, norteando onde imputar recursos e estratégias. Os profissionais da saúde, juntamente com as equipes da bioinformática e gestores, têm trocado e expandido conhecimentos de forma a fazer um uso mais amplo, oportuno e eficaz desta técnica para prover uma assistência mais qualificada, atrelada a melhores resultados de gestão e cuidado. Faz-se necessário investir tempo e capacitações para que sejam colhidos os frutos da inteligência artificial em prol de um cuidado mais assertivo.

Objectives Methotrexate (MTX) is one of the most commonly used medications to treat rheumatoid arthritis (RA). However, the effect of MTX treatment on cellular immune responses remains incompletely understood. This raises concerns about the vulnerability of these patients to emerging infections and following vaccination.Methods In the current study, we investigated the impact of MTX treatment in patients with immune-mediated inflammatory disease on B and CD4 T cell SARS-CoV-2 vaccination responses. Eighteen patients with RA and two patients with psoriatic arthritis on MTX monotherapy were included, as well as 10 patients with RA without immunosuppressive treatment, and 29 healthy controls. CD4 T and B cell responses were analysed 7 days and 3–6 months after two SARS-CoV-2 messenger RNA vaccinations. High-dimensional flow cytometry analysis was used to analyse fresh whole blood, an activation-induced marker assay to measure antigen-specific CD4 T cells, and spike probes to study antigen-specific B cells.Results Seven days following two SARS-CoV-2 vaccinations, total B and T cell counts were similar between MTX-treated patients and controls. In addition, spike-specific B cell frequencies were unaffected. Remarkably, the frequency of antigen-specific CD4 T cells was reduced in patients using MTX and correlated strongly with anti-RBD IgG antibodies. These results suggest that decreased CD4 T cell activity may result in slower vaccination antibody responses in MTX-treated patients.Conclusion Taken together, MTX treatment reduces vaccine-induced CD4 T cell activation, which correlates with lower antibody responses.Trial registration number NL8900.

Home blood pressure management, including self-monitoring and medication self-titration, is an efficient and cost-effective tool. Although its use is increasing globally, little is known about the feasibility of such interventions in low and middle-income countries. Further, the perspectives and experiences of healthcare providers who play a big role in ensuring the success of home blood pressure management interventions have not been documented. This qualitative study was conducted with a total of 35 healthcare providers (60% female, mean [SD] age = 37.3 [6.9 years] years), through 4 in-depth interviews from Peru, and 8 in-depth interviews and 4 focus groups from Cameroon. Study participants (healthcare providers) include physicians (primary care physicians), specialists (cardiologists and geriatricians), and nurses that were purposively recruited from two hospitals in two of the largest cities in both countries. Results were thematically analyzed by two researchers. Themes derived were related to feasibility and acceptability, and largely reflected providers in both countries endorsing home blood pressure management. Providers' concerns were in three main areas; 1) safety of patients when they self-titrate medications, 2) resources such as healthcare financing, local hospital policies that support communications with patients for home blood pressure management, and 3) sustainability through patient adherence, incorporating home blood pressure management within clinical guidelines and hospital policies, and complementing with continued health education and lifestyle modifications. According to providers, home blood pressure management may be feasible and acceptable if tailored multi-faceted protocols were introduced bearing in mind local contexts.

Jia Shi,1,2,&ast; Meng-Jiao Shao,3,&ast; Miao Yu,1,2 Bao-Peng Tang1,2 1Cardiac Pacing and Physiological Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bao-Peng Tang, Cardiac Pacing and Physiological Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Email tangbaopeng1111@163.comBackground: Inflammation and cardiac fibrosis are important pathogenic drivers of heart failure. The fibrosis-4 index (FIB-4) is associated with a higher degree of fibrosis. The systemic immune inflammation index (SII) is associated with a higher degree of systemic inflammation status. Previous studies have shown that they are associated with a poor prognosis for cardiovascular disease. We sought to investigate the value of FIB-4 combined with the SII as a novel inflammation-fibrosis combined index (IFCI) in predicting left ventricular reverse remodeling (LVRR) and prognosis among reduced ejection fraction heart failure (HFrEF) patients.Methods: A total of 895 patients with HFrEF were continuously recruited. Receiver operating characteristic curves were drawn to assess the abilities of inflammation-fibrosis indicators to predict LVRR. Multivariable Cox regression analysis was used to examine independent predictors of composite cardiac events and all-cause death.Results: After six months of follow-up, 344 (38.4%) patients experienced LVRR. The IFCI had the largest area under the curve (0.835, P < 0.001). In multivariate-adjusted logistic regression analyses, FIB-4, SII, and IFCI were predictive of LVRR (P value < 0.05). The IFCI was associated with a 3.686-fold higher risk of non-LVRR (odds ratio [OR] = 3.686, P < 0.001). Moreover, an increased IFCI predicted a poor prognosis in HFrEF patients. The highest risk of composite cardiac events (hazard ratio [HR] = 2.716, P < 0.001) was observed in the top IFCI-tertile group, and similar results were found regarding independent risk indicators of all-cause death.Conclusion: In summary, this study indicated that increased IFCI at admission offers good predictability regarding non-LVRR and predicts the risk of all-cause mortality or composite cardiovascular events due to HFrEF patients and could be used as a novel marker.Keywords: heart failure, left ventricular reverse remodeling, inflammation-fibrosis combined index, fibrosis-4 index, systemic immune inflammation index, prognosis

Dyah Nindita Carolina,1,2 Mieke Hemiawati Satari,3,&ast; Bambang Pontjo Priosoeryanto,4,&ast; Agus Susanto,1,&ast; Cortino Sukotjo,5,&ast; Rahmana Emran Kartasasmita6,&ast; 1Department of Periodontology, Dental Faculty, Universitas Padjadjaran, Bandung, West Java, Indonesia; 2Doctoral Study Program, Faculty of Medicine, Universitas Padjadjaran, Bandung, West Java, Indonesia; 3Department of Oral Biology, Dental Faculty, Universitas Padjadjaran, Bandung, West Java, Indonesia; 4Division of Veterinary Pathology, School of Veterinary Medicine & Biomedical Sciences, IPB University, Bogor, West Java, Indonesia; 5Department of Restorative Dentistry, College of Dentistry, University of Illinois at Chicago, Chicago, IL, 60612, USA; 6Research Group of Pharmaceutical Chemistry, School of Pharmacy, Institut Teknologi Bandung, Bandung, 40132, Indonesia&ast;These authors contributed equally to this workCorrespondence: Dyah Nindita Carolina, Department of Periodontology, Dental Faculty, Universitas Padjadjaran, Bandung, West Java, 40132, Indonesia, Tel +628156132636, Email dyah.nindita@unpad.ac.idPurpose: The purpose of this study was to synthesize and structurally characterize four ant nest membranes in four different concentrations and determine the best concentration that could potentially be used as an alternative material for the production of new collagen barrier membranes.Materials and Methods: Membranes were created by mixing ant nest extracts at various concentrations of 0.5%, 1%, 1.5%, and 2%, as well as collagen, chitosan, and Polyvinyl Alcohol (PVA) using a film casting. A Universal Testing Machine (UTM) was used to evaluate mechanical properties including elastic modulus, tensile strength, maximum elongation, elongation at break, and maximum force. Water absorption was performed, FTIR was used for functional group identification, and morphology was examined using SEM. Additionally, EDS was used to identify the composition and distribution of elements in membranes. Statistical analysis was conducted using ANOVA (analysis of variance) and post hoc testing with a significance level of p < 0.01 for quantitative data.Results: The results showed that the mechanical properties produced the following mean (standard deviation): elastic modulus 0.87 Mpa (0.11), tensile strength 16.32 N/mm2 (2.46), maximum elongation 4.96% (1.72), elongation at break 5.23% (1.87), and maximum force 22.50 N (5.06). The average water absorption capacity of all four membranes had a p-value < 0.01. FTIR spectrum showed various peaks corresponding to functional groups, while SEM results indicated a homogeneous mixture. EDS analysis confirmed that the addition of ant plant extract at 0.5%, 1%, and 1.5% resulted in the presence of elements C, O, and Ca. Meanwhile, membranes prepared with 2% concentration had a different composition, namely C, O, Ca, and Na.Conclusion: Increasing the concentration of ant nest affects the values of the membrane’s mechanical properties parameters, including the elastic modulus (0.87 Mpa), tensile strength (16.32 N/mm2), maximum elongation (4.96%), elongation at break (5.23%), and maximum force (22.50 N). The average membrane absorption of water (p value < 0.01) was also affected. SEM images showed homogeneous mixing, and membrane EDS results consisted of C, O, and Ca composition. However, there was no effect on FTIR functional groups. The anthill membrane with a 1% concentration has the potential to serve as an alternative membrane in guided tissue regeneration.Keywords: ant nest, carp scales, herbs, chitosan, polyvinyl alcohol, PVA

Abstract Connectome studies have shown how Alzheimer’s disease (AD) disrupts functional and structural connectivity among brain regions. But the molecular basis of such disruptions is less studied, with most genomic/transcriptomic studies performing within-brain-region analyses. To inspect how AD rewires the correlation structure among genes in different brain regions, we performed an Inter-brain-region Differential Correlation (Inter-DC) analysis of RNA-seq data from Mount Sinai Brain Bank on four brain regions (frontal pole, superior temporal gyrus, parahippocampal gyrus and inferior frontal gyrus, comprising 264 AD and 372 control human post-mortem samples). An Inter-DC network was assembled from all pairs of genes across two brain regions that gained (or lost) correlation strength in the AD group relative to controls at FDR 1%. The differentially correlated (DC) genes in this network complemented known differentially expressed genes in AD, and likely reflects cell-intrinsic changes since we adjusted for cell compositional effects. Each brain region used a distinctive set of DC genes when coupling with other regions, with parahippocampal gyrus showing the most rewiring, consistent with its known vulnerability to AD. The Inter-DC network revealed master dysregulation hubs in AD (at genes ZKSCAN1, SLC5A3, RCC1, IL17RB, PLK4, etc.), inter-region gene modules enriched for known AD pathways (synaptic signaling, endocytosis, etc.), and candidate signaling molecules that could mediate region-region communication. The Inter-DC network generated in this study is a valuable resource of gene pairs, pathways and signaling molecules whose inter-brain-region functional coupling is disrupted in AD, thereby offering a new perspective of AD etiology.

Novel word learning refers to the process of learning words. The words are assumed to be acquainted even after a short exposure and this phenomenon is termed as fast mapping. Some proponents believe that the new word learnt as a consequence of new word learning is momentous and the word may not be transferred to the lexicon if the word is not rehearsed and this strategy involving conscious learning is termed as slow mapping. The present study was carried out with the aim of carrying out of error analysis on data involving fast and slow mapping. 20 participants were divided into two sub groups of 10 each. The first method was exposed to lexical method of teaching while the second group was exposed to slow mapping. Participants performed well with slow mapping but the errors were more with this method compared to fast mapping.

Dual-phase xenon time projection chamber (TPC) detectors have demonstratedsuperior search sensitivities to dark matter over a wide range of particlemasses. To extend their sensitivity to include low-mass dark matterinteractions, it is critical to characterize both the light and chargeresponses of liquid xenon to sub-keV nuclear recoils. In this work, we report anew nuclear recoil calibration in the LUX detector $\textit{in situ}$ usingneutron events from a pulsed Adelphi Deuterium-Deuterium neutron generator. Wedemonstrate direct measurements of light and charge yields down to 0.45 keV(1.4 scintillation photons) and 0.27 keV (1.3 ionization electrons),respectively, approaching the physical limit of liquid xenon detectors. Wediscuss the implication of these new measurements on the physics reach ofdual-phase xenon TPCs for nuclear-recoil-based low-mass dark matter detection.

We present the results from combining machine learning with the profile likelihood fit procedure, using data from the Large Underground Xenon (LUX) dark matter experiment. This approach demonstrates reduction in computation time by a factor of 30 when compared with the previous approach, without loss of performance on real data. We establish its flexibility to capture nonlinear correlations between variables (such as smearing in light and charge signals due to position variation) by achieving equal performance using pulse areas with and without position-corrections applied. Its efficiency and scalability furthermore enables searching for dark matter using additional variables without significant computational burden. We demonstrate this by including a light signal pulse shape variable alongside more traditional inputs, such as light and charge signal strengths. This technique can be exploited by future dark matter experiments to make use of additional information, reduce computational resources needed for signal searches and simulations, and make inclusion of physical nuisance parameters in fits tractable.

Industrial tuna and artisanal fisheries targeting multiple species in the eastern Pacific Ocean (EPO) interact with the Critically Endangered East Pacific (EP) leatherback turtle Dermochelys coriacea. In 2021, a revised Inter-American Tropical Tuna Commission (IATTC) resolution on sea turtles aimed to reduce sea turtle bycatch in EPO industrial tuna fisheries and ensure their safe handling and release. A new ecological risk assessment approach—Ecological Assessment for the Sustainable Impacts of Fisheries (EASI-Fish)—was used to assess vulnerability status and to better understand the potential efficacy of 70 scenarios that compared simulated conservation and management measures (CMMs) for EPO industrial (purse-seine and longline) and artisanal (longline and gillnet) fisheries to the status quo in 2019. In 2019, a fishing mortality proxy (F̃2019) and the breeding stock biomass per recruit (BSR2019) exceeded precautionary biological reference points (F80% and BSR80%), classifying the stock as ‘most vulnerable’. Industrial and artisanal longline fisheries had the highest impacts because they had the highest areal overlap with the modelled EP leatherback distribution. Of the 70 CMM scenarios, 42 resulted in significant improvements in vulnerability status (i.e. to ‘least vulnerable’). The use of large circle hooks, finfish bait, and best handling and release practices each decreased vulnerability; however, the most effective scenarios involved using these 3 measures in concert. The benefits predicted from EASI-Fish for CMM scenarios assume full compliance and attaining the modelled levels of efficacy, our modelling provides stakeholders with evidence-based recommendations to address key threats to EP leatherback turtles to improve their conservation status by reducing fishing impacts.

The Eastern Pacific population of leatherback turtles Dermochelys coriacea is Critically Endangered, with incidental capture in coastal and pelagic fisheries as one of the major causes. Given the population’s broad geographic range, status, and extensive overlap with fisheries throughout the region, identifying areas of high importance is essential for effective conservation and management. In this study, we created a machine-learning species distribution model trained with remotely sensed environmental data and fishery-dependent leatherback presence (n = 1088) and absence data (>500000 fishing sets with no turtle observations) from industrial and small-scale fisheries that operated in the eastern Pacific Ocean between 1995 and 2020. The data were obtained through a participatory collaboration between the Inter-American Convention for the Protection and Conservation of Sea Turtles and the Inter-American Tropical Tuna Commission as well as non-governmental organizations to support the quantification of leatherback vulnerability to fisheries bycatch. A daily process was applied to predict the probability of leatherback occurrence as a function of dynamic and static environmental covariates. Coastal areas throughout the region were highlighted as important habitats, particularly highly productive feeding areas over the continental shelf of Ecuador, Peru, and offshore from Chile, and breeding areas off Mexico and Central America. Our model served as the basis to quantify leatherback vulnerability to fisheries bycatch and the potential efficacy of conservation and management measures (Griffiths & Wallace et al. 2024; Endang Species Res 53:295-326). In addition, this approach can provide a modeling framework for other data-limited vulnerable populations and species.

Bronchiectasis denotes fixed and often irreversible dilatation of the bronchial wall caused by persistent inflammation and infection. Children with bronchiectasis in developing countries suffer recurrent hospitalisation and poor quality of life and usually succumb to the condition. These children are poorly recognised, misdiagnosed, and under-reported. We report five cases of computerised tomography-diagnosed paediatric bronchiectasis managed at the Edward Francis Small Teaching Hospital (EFSTH), Banjul, The Gambia. The ages of the children at presentation ranged from 3 to 14 years, and they all had recurrent chest infections. Four out of the five cases had Pulmonary Tuberculosis, among whom two cases had HIV/TB co-infections, and the only non-TB, non-HIV case had features of Down syndrome with congenital heart lesions. All the cases had growth impairment; digital clubbing was observed in four, and low peripheral oxygen saturation in room air in three of the five children. These cases are reported to increase the index of suspicion among clinicians working in resource-limited settings to consider the diagnosis of bronchiectasis in children with recurrent chest infections. Early diagnosis and prompt management, including appropriate follow-up care, will improve the quality of life of these children and ensure better management outcomes.

Background: Anti-retroviral therapy is associated with myriads of side-effects. Central nervous system related side effects are troublesome and mostly self limiting. Working knowledge of these side effects can improve the prescription habits of physicians. The study aimed pattern of central system related adverse drug reactions (ADRs) due to anti-retroviral therapy in HIV infected patients in tertiary care hospitals in North India. Materials and methods: A prospective observational study was conducted and all HIV positive patients, previously registered and new; attending OPD who encountered ADRs were enrolled in our study irrespective of their age and sex. Data was collected using ADR reporting form issued by Indian Pharmacopoeia Commission. Causality assessment was done by using Naranjo’s Probability Scale. Modified Hartwig severity scale was used to evaluate severity, WHO criteria for seriousness and guidelines of council for international organizations of medical sciences to decide the predictability of ADRs. Results: A total of 250 patients encountered various types of ADRs during the study period. Total number of ADRs recorded was 452. Out of total ADRs (n=452) recorded, 20.35% (n=92) were central system related ADRs. Most common central nervous system related ADR was dizziness. Most central nervous system related ADRs were of moderate type and possible in nature on causality assessment. Conclusion: Relatively overweight, older age and baseline CD4 absolute count below 250 cells/mm3, were predictors for central nervous system related side effects due to anti-retroviral therapy in HIV patients. We suggest that more stringent evaluation and monitoring should be carefully done in all HIV/AIDS patients who will receive and on efavirenz based anti-retroviral therapy, especially if they have the above predictors.

Wood-decaying fungi of the class Agaricomycetes (phylum Basidiomycota) are saprotrophs that break down lignocellulose and play an important role in nutrient recycling. They secrete a wide range of extracellular plant cell wall degrading enzymes that break down cellulose, hemicellulose, and lignin, the main building blocks of plant biomass. Although the production of these enzymes is regulated mainly at the transcriptional level, no activating regulators have been identified in any wood-decaying fungus in the class Agaricomycetes. We studied the regulation of cellulase expression in the wood-decaying fungus Schizophyllum commune. Comparative genomics and transcriptomics on two wild isolates revealed a Zn2Cys6-type transcription factor gene (roc1) that was highly upregulated during growth on cellulose, compared to glucose. It is only conserved in the class Agaricomycetes. A roc1 knockout strain showed an inability to grow on medium with cellulose as sole carbon source, and growth on cellobiose and xylan (other components of wood) was inhibited. Growth on non-wood-related carbon sources was not inhibited. Cellulase gene expression and enzyme activity were reduced in the Δroc1 strain. ChIP-Seq identified 1474 binding sites of the Roc1 transcription factor. Promoters of genes involved in lignocellulose degradation were enriched with these binding sites, especially those of LPMO (lytic polysaccharide monooxygenase) CAZymes, indicating that Roc1 directly regulates these genes. A conserved motif was identified as the binding site of Roc1, which was confirmed by a functional promoter analysis. Together, Roc1 is a key regulator of cellulose degradation and the first identified in wood-decaying fungi in the phylum Basidiomycota. IMPORTANCE Wood-degrading fungi in the phylum Basidiomycota play a crucial role in nutrient recycling by breaking down all components of wood. Fungi have evolved transcriptional networks that regulate expression of wood-degrading enzymes, allowing them to prioritize one nutrient source over another. However, to date all these transcription factors have been identified in the phylum Ascomycota, which is only distantly related to the phylum Basidiomycota. Here, we identified the transcription factor Roc1 as a key regulator of cellulose degradation in the mushroom-forming and wood-degrading fungus Schizophyllum commune. Roc1 is highly conserved in the phylum Basidiomycota. Using comparative genomics, transcriptomics, ChIP-Seq and promoter analysis we have identified direct targets of Roc1, as well as other aspects of the transcriptional response to cellulose.

In Fig. 1c of this Article, the x-axis scale was inadvertently duplicated from Fig. 1b. The original Article has been corrected online.

Po upadku ZSSR nastąpiła na Ukrainie prawdziwa eksplozja budownictwa sakralnego. Artykuł, o charakterze przeglądowym, prezentuje czternaście spośród blisko tysiąca cerkwi zbudowanych na Ukrainie w okresie trzydziestolecia od odzyskania niepodległości do agresji rosyjskiej (1991–2022). Kryterium wyboru jest kategoria reprezentatywności, zarówno pod względem jakościowym, formalnym, regionalnym, jak i wyznaniowym (świątynie unickie oraz prawosławne Cerkwi Ukraińskiej i Cerkwi Patriarchatu Moskiewskiego). Przy całym zróżnicowaniu łączy je swoista kanoniczność w podejściu do materii architektonicznej. Opiera się ona zasadniczo na bizantyńskim modelu świątyni krzyżowo-kopułowej, przyjętym na Rusi Kijowskiej. Wybrane przykłady odzwierciedlają zjawisko odwołania do różnych tradycji budowlanych, za którymi kryją się pewne racje ideowe – między swojskością a importem, między ukraińskością a rusofilstwem, między Rusią Kijowską a barokiem, między tradycją a nowoczesnością. Za każdą decyzją wyboru stoi określone przesłanie historyczno-kulturowe, ale także i polityczne. Współczesne ukraińskie cerkwie są nowym wcieleniem, wręcz manifestacją, architecture parlante.

Sea turtles are an iconic group of marine megafauna that have been exposed to multiple anthropogenic threats across their different life stages, especially in the past decades. This has resulted in population declines, and consequently many sea turtle populations are now classified as threatened or endangered globally. Although some populations of sea turtles worldwide are showing early signs of recovery, many still face fundamental threats. This is problematic since sea turtles have important ecological roles. To encourage informed conservation planning and direct future research, we surveyed experts to identify the key contemporary threats (climate change, direct take, fisheries, pollution, disease, predation, and coastal and marine development) faced by sea turtles. Using the survey results and current literature, we also outline knowledge gaps in our understanding of the impact of these threats and how targeted future research, often involving emerging technologies, could close those gaps.

Introduction: Although the prevalence of intercarpal ligament injuries with distal radius fractures ranges from 0.5 to 75 percent, these injuries are often missed by the untrained eye. Currently, wrist arthroscopy is considered gold standard for diagnosis and treatment, but in Indian setting it is an impractical proposition. Scapho-lunate and luno-triquetral injuries can be identified on X rays easily by Gilula’s arc, scapholunate distance and angle, carpal height ratio etc. The aim of this study is to estimate the prevalence of intercarpal ligament injuries in distal radius (DER) fractures and determine their functional outcome at one year. Material and methods: The study was conducted over 18 months at VMMC and Safdarjung Hospital. Patients with distal radius fractures were subjected to wrist X rays in 100% magnification and earlier mentioned parameters were measured. Patients who needed surgery were operated for fracture DER. Immediate post-operative X rays and X rays at 1 year were compared with that of the contralateral wrist. Patients’ clinical outcomes like range of motion, grip strength, quick DASH score and pain on VAS were measured at one year to assess the clinical outcome. Results: The study population was of 103 patients. Prevalence of intercarpal injuries in patients with DER fractures was 11.7%. Out of these 12 patients, 50% had broken Gilula’s arc, 66.6% had increased scapho-lunate distance and 42% had increased scapho-lunate angle. Carpal height ratio was significantly less in patients with intercarpal ligament injuries at one year. Similarly, functional outcome was worse in these patients at one year. Conclusion: Intercarpal injuries are associated with worse outcomes in patients with fracture DER. These injuries can reliably diagnosed on X rays using the parameters mentioned. Since the prevalence is quite high, we should learn to diagnose them early, so that patients can be explained about the prognosis of their injury.

Delineating spatial boundaries that accurately encompass complex, often cryptic, life histories of highly migratory marine megafauna can be a significant conservation challenge. For example, marine turtles range across vast ocean basins and coastal areas, thus complicating the evaluation of relative impacts of multiple overlapping threats and the creation of coherent conservation strategies. To address these challenges, spatially explicit ‘regional management units’ (RMUs) were developed in 2010 for all marine turtle species, globally. RMUs were intended to provide a consistent framework that organizes conspecific assemblages into units above the level of nesting rookeries and genetic stocks, but below the species level, within regional entities that may share demographic trajectories because they experience similar environmental conditions and other factors. From their initial conception, RMUs were intended to be periodically revised using new information about marine turtle distributions, life history, habitat use patterns, and population structure. Here, we describe the process used to update the 2010 RMU framework by incorporating newly published information and inputs from global marine turtle experts who are members of the IUCN Marine Turtle Specialist Group. A total of 48 RMUs for 6 of 7 marine turtle species and 166 distinct genetic stocks for all 7 species are presented herein. The updated RMU framework reflects a significant advance in knowledge of marine turtle biology and biogeography, and it provides improved clarity about the RMU concept and its potential applications. All RMU products have been made open access to support research and conservation initiatives worldwide.

Seda Tural Onur,1 Antonino Natoli,2 Bettina Dreger,2 Sibel Ar&inodot;nç,3 Nurhan Sar&inodot;o&gbreve;lu,4 Mustafa Çörtük,1 Dilek Karado&gbreve;an,5 Abdurrahman &Scedil;enyi&gbreve;it,6 Birsen P&inodot;nar Y&inodot;ld&inodot;z,1 Nurdan Köktürk,7 Serap Argun Bar&inodot;s,8 Sümeyye Kodalak Cengiz,7 Mehmet Polatli9 1Department of Pulmonology, Yedikule Chest Diseases and Thoracic Surgery Education and Research Hospital, University of Health Sciences, Istanbul, Türkiye; 2Scientific and Medical Affairs, Scientific Innovation Office, Grifols, Frankfurt, Deutschland; 3Clinic of Chest Diseases, University of Health Sciences Turkey, S.B.Ü. Süreyyapa&scedil;a Chest Diseases and Thoracic Surgery Training and Research Hospital, &Idot;stanbul, Türkiye; 4Department of Pulmonology, Bal&inodot;kesir University Faculty of Medicine, Pulmonology Clinic, Bal&inodot;kesir, Türkiye; 5Department of Chest Diseases, Recep Tayyip Erdo&gbreve;an University, School of Medicine, Rize, Türkiye; 6Department of Chest Diseases, Dicle University Faculty of Medicine Hospital, Diyarbak&inodot;r, Türkiye; 7Department of Pulmonary Medicine, Gazi University, School of Medicine, Ankara, Türkiye; 8Department of Pulmonary Diseases, Faculty of Medicine, Kocaeli University, Kocaeli, Türkiye; 9Faculty of Medicine, Aydin Adnan Menderes University, Aydin, TürkiyeCorrespondence: Mehmet Polatli, Faculty of Medicine, Aydin Adnan Menderes University, Zafer Mahallesi, Efeler, Aydin, 09100, Türkiye, Email mpolatli09@gmail.comPurpose: Alpha-1 antitrypsin deficiency (AATD) is a rare hereditary condition characterized by decreased serum alpha-1 antitrypsin (AAT) levels. We aim to identify AATD in patients with chronic obstructive pulmonary disease (COPD), bronchiectasis, or asthma and to report the frequency of AAT variants in Turkey.Patients and Methods: This non-interventional, multicenter, prospective study was conducted between October 2021 and June 2022. Adult patients with COPD, bronchiectasis, asthma, liver symptoms, or family members with AATD were included. Demographic and clinical characteristics, pulmonary diagnosis, respiratory symptoms, and AAT serum levels were assessed. Whole blood samples were collected as dried blood spots, and the most common AATD mutations were simultaneously tested by allele-specific genotyping.Results: A total of 1088 patients, mainly diagnosed with COPD (92.7%) and shortness of breath (78.7%), were assessed. Fifty-one (5%) were found to have AATD mutations. Fifteen (29.4%) patients had Pi&ast;S or Pi&ast;Z mutations, whereas 36 (70.6%) patients carried rare alleles Pi&ast;M malton (n=18, 35.3% of mutations), Pi&ast;I (n=8, 16%), Pi&ast;P lowell (n=7, 14%), Pi&ast;M heerlen (n=2, 4%), and Pi&ast;S iiyama (n=1, 2%). The most common heterozygous combinations were Pi&ast;M/Z (n=12, 24%), and Pi&ast;M/M malton (n=11, 22%). Ten patients with severe AATD due to two deficiency alleles were identified, two with the Pi&ast;Z/Z genotype, four with the genotype Pi&ast;M malton/M malton, three with Pi&ast;Z/M malton, and one with Pi&ast;Z/M heerlen.Conclusion: Our results identified AATD mutations as a genetic-based contributor to lung disease in patients with COPD or bronchiectasis and assessed their frequency in a population of Turkish patients.Keywords: alpha-1 antitrypsin deficiency, genotype, diagnosis, chronic obstructive pulmonary disease

Salmonella invades and disrupts gut epithelium integrity, creating an infection-generated electric field that can drive directional migration of macrophages, a process called galvanotaxis. Phagocytosis of bacteria reverses the direction of macrophage galvanotaxis, implicating a bioelectrical mechanism to initiate life-threatening disseminations. The force that drives direction reversal of macrophage galvanotaxis is not understood. One hypothesis is that Salmonella can alter the electrical properties of the macrophages by modifying host cell surface glycan composition, which is supported by the fact that cleavage of surface-exposed sialic acids with a bacterial neuraminidase severely impairs macrophage galvanotaxis, as well as phagocytosis. Here, we utilize N-glycan profiling by nanoLC-chip QTOF mass cytometry to characterize the bacterial neuraminidase-associated compositional shift of the macrophage glycocalyx, which revealed a decrease in sialylated and an increase in fucosylated and high mannose structures. The Salmonella nanH gene, encoding a putative neuraminidase, is required for invasion and internalization in a human colonic epithelial cell infection model. To determine whether NanH is required for the Salmonella infection-dependent direction reversal, we constructed and characterized a nanH deletion mutant and found that NanH is partially required for Salmonella infection in primary murine macrophages. However, compared to wild type Salmonella, infection with the nanH mutant only marginally reduced the cathode-oriented macrophage galvonotaxis, without canceling direction reversal. Together, these findings strongly suggest that while neuraminidase-mediated N-glycan modification impaired both macrophage phagocytosis and galvanotaxis, yet to be defined mechanisms other than NanH may play a more important role in bioelectrical control of macrophage trafficking, which potentially triggers dissemination.

We present the results from combining machine learning with the profilelikelihood fit procedure, using data from the Large Underground Xenon (LUX)dark matter experiment. This approach demonstrates reduction in computationtime by a factor of 30 when compared with the previous approach, without lossof performance on real data. We establish its flexibility to capture non-linearcorrelations between variables (such as smearing in light and charge signalsdue to position variation) by achieving equal performance using pulse areaswith and without position-corrections applied. Its efficiency and scalabilityfurthermore enables searching for dark matter using additional variableswithout significant computational burden. We demonstrate this by including alight signal pulse shape variable alongside more traditional inputs such aslight and charge signal strengths. This technique can be exploited by futuredark matter experiments to make use of additional information, reducecomputational resources needed for signal searches and simulations, and makeinclusion of physical nuisance parameters in fits tractable.

The oxidation of chromium in air at 700 °C was investigated with a focus on point defect behavior and transport during oxide layer growth. A comprehensive set of characterization techniques targeted characteristics of chromium oxide microstructure and chemical composition analysis. TEM showed that the oxide was thicker with longer oxidation times and that, for the thicker oxides, voids formed at the metal/oxide interface. PAS revealed that the longer the oxidation time, there was an overall reduction in vacancy-type defects, though chromium monovacancies were not found in either case. EIS found that the longer oxidized material was more electrochemically stable and that, while all oxides displayed p-type character, the thicker oxide had an overall lower charge carrier density. Together, the results suggest anion oxygen interstitials and chromium vacancy cluster complexes drive transport in an oxidizing environment at this temperature, providing invaluable insight into the mechanisms that regulate corrosion.

Exposure to environmental arsenic is associated with serious of health issues such as cancer, diabetes and developmental delays in infants and children. In human liver, As(III) S-adenosylmethionine methyl transferase (hAS3MT) (EC 2.1.1.137) was proposed to be an detoxification process by methylation of inorganic arsenite into pentavalent methyl MAs(V) and dimethyl arsenite DMAs(V). More recently the first product was shown to be highly toxic and potentially carcinogenic trivalent methylarsenite (MAs(III)). Our studies are designed to elucidate the mechanism of AS3MT and its contribution to arsenic-related diseases. Here, we report the first crystallization and preliminary X-ray diffraction analysis of the human AS3MT enzyme. The crystals belong to the monoclinic P1211 space group with unit cell parameters of a = 135.03 Å, b = 260.44 Å, c = 279.03 Å, α = 90.00°, β = 93.36°, γ = 90.00°.

Jillian Kallman Price,1 Leyla de Avila,1 Maria Stepanova,1– 3 Ali A Weinstein,4 Huong Pham,1 Wisna’odom Keo,1 Andrei Racila,1 Suzannah Gerber,1 Brian P Lam,1– 3 Lynn H Gerber,1,3,&ast; Zobair M Younossi1– 3,&ast; 1Betty and Guy Beatty Center for Integrated Research, Inova Health System, Falls Church, VA, USA; 2Center for Liver Disease, Department of Medicine, Inova Fairfax Medical Campus, Falls Church, VA, USA; 3Inova Medicine, Inova Health System, Falls Church, VA, USA; 4Department of Global and Community Health, George Mason University, Fairfax, VA, USA&ast;These authors contributed equally to this workCorrespondence: Jillian Kallman Price, Research Investigator, Outcomes Research, Beatty Liver and Obesity Research Program, Center for Integrated, Research, Department of Medicine, Inova Health System, Claude Moore Health Education and Research Building, Inova Fairfax Medical Campus, 3300, Gallows Road, Falls Church, VA, 22042, USA, Tel +1-703-776-3032, Fax +1-703- 776-4386, Email Jillian.Price@inova.orgIntroduction: Post-acute SARS-CoV-2 (PASC) symptoms are often persistent, disruptive, and difficult to treat effectively. Fatigue is often among the most frequently reported symptoms and may indicate a more challenging road to recovery.Purpose: To describe the natural history, symptomology, and risk profile of long-term post-acute SARS-CoV-2.Patients and Methods: Participants treated for SARS-CoV-2 within a large, community health system in the US were enrolled prospectively in a longitudinal, observational PASC study examining participants at enrollment and 6 months. Medical history, symptom reporting, validated measures of cognition, and patient-reported outcomes (PROs), were performed for all participants and repeated during study follow-up visits.Results: A total of 323 participants completed baseline evaluations. Sixty one participants indicated clinically significant fatigue (23.1% at baseline); a representative sample of 141 enrollees also completed a baseline Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) in-depth fatigue reporting questionnaire, 37 had severe fatigue. The severely fatigued (FACIT-F ≤ 29.7) were significantly younger, female, had more anxiety and depression, had a higher resting heart rate, reported more sick days, and were less physically active post-COVID. They were more likely to have a diagnosis of chronic kidney disease (13.5% vs 2.9%) but less likely to have a history of cancer (8.1% vs 23.1). Participants who were severely fatigued reported health, diet, weight, and sleep were worse than those not severely fatigued post-COVID (p = 0.02 to 0.0002). Fatigue was significantly correlated with impairment of all PROs administered after COVID-19 infection.Conclusion: Fatigue is a common symptom post-COVID-19 infection and is associated with lower reported well-being and function. Those with severe fatigue tended to be younger and female and have a past medical history of anxiety, depression, kidney disease, and more sedentary lifestyles.Keywords: symptom severity, functional assessment of chronic illness therapy-fatigue, FACIT-F, SARS-CoV-2, COVID-19, recovery

Toni Rahmat Jaelani,1 Kusman Ibrahim,1 Jonny Jonny,2 Sri Hartati Pratiwi,1 Hartiah Haroen,1 Nursiswati Nursiswati,1 Bunga Pinandhita Ramadhani2 1Faculty of Nursing, Padjadjaran University, Bandung, West Java, Indonesia; 2Nephrology Division, Department of Internal Medicine, Gatot Soebroto Indonesia Army Central Hospital, Jakarta, IndonesiaCorrespondence: Toni Rahmat Jaelani, Faculty of Nursing, Padjadjaran University, Jalan Ir. Soekarno Km. 21 Jatinangor, Sumedang, West Java, 45363, Indonesia, Tel +62-813-2211-0115, Fax +62-022-7795596, Email toni15003@mail.unpad.ac.idBackground: Peritoneal dialysis (PD) training is essential to ensure patient independence and prevent life-threatening complications, such as peritonitis. The International Society for Peritoneal Dialysis (ISPD) recommends that every PD unit worldwide implement local PD training programs with the goal of improving self-care capabilities. This scoping review aims to give an overview of recent literature and recommendations on PD training programs aiming to improve the quality of care and outcomes for PD patients.Methods: The literature search was conducted using the PC (Population, Concept) approach. The population of interest in this study is PD patients, and the study concept is the PD training program. Several databases were used to conduct the literature search, including PubMed, Science Direct, and CINAHL. The search process began from July 2022 until January 2023. The inclusion criteria for the search included research articles and recommendations.Results: The search yielded 22 articles recommending training programs lasting from 5– 8 days, with 1– 3-hour sessions and a nurse-to-patient ratio of 1:1. A cumulative training time of 15 hours or more is recommended to enhance patient independence and reduce peritonitis rates. Home-based or in-unit PD training, conducted by experienced nurses using adult learning strategies, has shown significant value in improving self-care and preventing peritonitis. Evaluating training outcomes should encompass knowledge, skills, and attitudes, and the impact on peritonitis rates. Training programs should be flexible and consider physiological and psychosocial barriers to achieving the best results.Conclusion: There are a variety of strategies for dialysis training concerning duration, session length, patient-to-trainer ratio, timing, methods, location, compliance, and the need for retraining. More evidence is needed to assess the impact of PD patient training programs on self-care capabilities and peritonitis incidence. Future studies should investigate the effects of training programs on compliance, self-efficacy, and patient and nurse perspectives.Keywords: training program, peritoneal dialysis, chronic kidney disease, patient education, nursing

Background: Hypotension following spinal anesthesia (SA) in lower segment cesarean section can be deleterious to the parturient and to fetus. Ketamine acts by stimulating the cardiovascular system leading to high blood pressure and increase in heart rate (HR) and cardiac output. Aims and Objectives: This study aimed to assess the efficacy of 15 mg of prophylactic intravenous ketamine in elective cesarean section for prevention of hypotension after SA. Materials and Methods: This double-blinded randomized controlled study was conducted on 98 participating parturients who were American Society of Anesthesiologists term pregnant women. The parturients were randomly divided into two groups (n=49 in each). All the parturients received SA. Ketamine group - Group K received 15 mg of ketamine IV bolus in 3 mL saline and control group - Group C received the same volume of normal saline IV bolus. HR and systolic blood pressure (SBP) were recorded at baseline at 5, 10, 15, and 20 min after the injection and then every 15 min till the end of the operation. Incidences of hypotension were recorded. The total number dose of ephedrine used, APGAR score, and Visual Analog Scale scores were recorded. The Ramsay Sedation Score was also recorded at baseline, then 5, 10, 15, 30, and 45 min after injection, and then at the end of the operation. Results: This study showed a statistically significant increase in the incidence of hypotension and higher use of intravenous ephedrine 6 mg boluses in the control group when compared to the ketamine group. Forty-two parturients in the control group developed hypotension compared to 23 parturients in the ketamine group with P