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Background: Previous phase 3 studies showed that the AS01E-adjuvanted respiratory syncytial virus (RSV) prefusion F protein-based vaccine for older adults (RSVPreF3 OA) is well tolerated and efficacious in preventing RSV-associated lower respiratory tract disease in adults ≥ 60 years of age. This study evaluated lot-to-lot immunogenicity consistency, reactogenicity, and safety of three RSVPreF3 OA lots. Methods: This phase 3, multicenter, double-blind study randomized (1:1:1) participants ≥ 60 years of age to receive one of three RSVPreF3 OA lots. Serum RSVPreF3-binding immunoglobulin G (IgG) concentration was assessed at baseline and 30 days post-vaccination. Lot-to-lot consistency was demonstrated if the two-sided 95 % confidence intervals (CIs) of the RSVPreF3-binding IgG geometric mean concentration (GMC) ratios between each lot pair at 30 days post-vaccination were within 0.67 and 1.50. Solicited adverse events (AEs) within four days, unsolicited AEs within 30 days, and serious AEs (SAEs) and potential immune-mediated diseases within six months post-vaccination were recorded. Results: A total of 757 participants received RSVPreF3 OA, of whom 708 were included in the per-protocol set (234, 237, and 237 participants for each lot). Lot-to-lot consistency was demonstrated: GMC ratios were 1.06 (95 % CI: 0.94–1.21), 0.92 (0.81–1.04), and 0.87 (0.77–0.99) between the lot pairs (lot 1/2; 1/3; 2/3). For the three lots, the RSVPreF3-binding IgG concentration increased 11.84-, 11.29-, and 12.46-fold post-vaccination compared to baseline. The reporting rates of solicited and unsolicited AEs, SAEs, and potential immune-mediated diseases were balanced between lots. Twenty-one participants reported SAEs; one of these–a case of atrial fibrillation–was considered by the investigator as vaccine-related. SAEs with a fatal outcome were reported for four participants, none of which were considered by the investigator as vaccine-related. Conclusion: This study demonstrated lot-to-lot immunogenicity consistency of three RSVPreF3 OA vaccine lots and indicated that the vaccine had an acceptable safety profile.ClinicalTrials.gov: NCT05059301.

Purpose: We report a patient who initially visited the ophthalmology clinic for a vision loss diagnosed with Erdheim-Chester Disease (ECD). Observations: ECD is a rare non-Langerhans cell histiocytosis characterized by multisystemic organ involvement and poor prognosis. Our patient had complete vision loss due to prominent orbital involvement before any systemic symptoms appeared. This case demonstrates variable clinical manifestations of ECD. Conclusions and importance: Painless bilateral proptosis with poor response to steroid treatment should prompt consideration for ECD and systemic evaluation. In addition, in the absence of typical clinical manifestations, a thorough evaluation of the biopsy can be crucial for an accurate diagnosis.

We present a case of a 65-year-old male who previously underwent left axillofemoral bypass, left carotid stenting, and right iliac stenting followed by ascending and hemiarch repair for type A aortic dissection, complicated by left external iliac artery occlusion. He presented to our center with a symptomatic 8.5 cm post-dissection extent II thoracoabdominal aortic aneurysm. A staged repair was performed to decrease spinal cord ischemia. The first stage employed the novel use of a jump graft from the left axillary-femoral bypass to the left internal iliac artery to restore pelvic circulation, combined with zone 2 thoracic branched endoprosthesis (TBE). The second stage included thoracic endovascular repair (TEVAR) extension and 3-vessel custom-modified fenestrated/branched endovascular repair (FBEVAR).

Background and purpose: Despite the superior dose conformity of proton therapy, the dose distribution is sensitive to daily anatomical changes, which can affect treatment accuracy. This study evaluated the dose recalculation accuracy of two synthetic computed tomography (sCT) generation algorithms in a commercial treatment planning system. Materials and methods: The evaluation was conducted for head-and-neck, thorax-and-abdomen, and pelvis sites treated with proton therapy. Thirty patients with two cone-beam computed tomography (CBCT) scans each were selected. The sCT images were generated from CBCT scans using two algorithms, Corrected CBCT (corrCBCT) and Virtual CT (vCT). Dose recalculations were performed based on these images for comparison with “ground truth” deformed CTs. Results: The choice of algorithm influenced dose recalculation accuracy, particularly in high dose regions. For head-and-neck cases, the corrCBCT method showed closer agreement with the “ground truth”, while for thorax-and-abdomen and pelvis cases, the vCT algorithm yielded better results (mean percentage dose discrepancy of 0.6 %, 1.3 % and 0.5 % for the three sites, respectively, in the high dose region). Head-and-neck and pelvis cases exhibited excellent agreement in high dose regions (2 %/2 mm gamma passing rate >98 %), while thorax-and-abdomen cases exhibited the largest differences, suggesting caution in sCT algorithm usage for this site. Significant systematic differences were observed in the clinical target volume and organ-at-risk doses in head-and-neck and pelvis cases, highlighting the importance of using the correct algorithm. Conclusions: This study provided treatment site-specific recommendations for sCT algorithm selection in proton therapy. The findings offered insights for proton beam centers implementing adaptive radiotherapy workflows.

Rationale & Objective: In the wake of the coronavirus disease 2019 (COVID-19) pandemic, the United States federal government expanded originating telemedicine sites to include outpatient dialysis units. For the first time, nephrology practitioners across the United States could replace face-to-face visits with telemedicine for patients receiving in-center hemodialysis. This study describes patients’ perspectives on the use of telemedicine during in-center hemodialysis. Study Design: A qualitative study. Setting & Participants: Thirty-two patients from underserved populations (older, less educated, unemployed, persons of color) receiving in-center hemodialysis who used telemedicine with their nephrologist during the COVID-19 pandemic. Analytical Approach: Telephone semistructured interviews were conducted in English or Spanish. Transcripts were thematically analyzed. Results: We identified 6 themes with subthemes: adapting to telemedicine (gaining familiarity and confidence, overcoming and resolving technical difficulties, and relying on staff for communication); ensuring availability of the physician (enabling an immediate response to urgent medical needs, providing peace of mind, addressing patient needs adequately, and enhanced attention and contact from physicians); safeguarding against infection (limiting COVID-19 exposures and decreasing use); straining communication and physical interactions (loss of personalized touch, limited physical examination, and unable to reapproach physicians about forgotten issues); maintaining privacy (enhancing privacy and projecting voice enables others to hear); and supporting confidence in telemedicine (requiring established rapport with physicians, clinical stabilty of health, and ability to have in-person visits when necessary). Limitations: Interviews were conducted later in the pandemic when some nephrology care providers were using telemedicine infrequently. Conclusions: Patients receiving in-center hemodialysis adapted to telemedicine visits by their nephrologists in the context of the COVID-19 pandemic and observed its benefits. However, further considerations regarding communication, privacy, and physical assessments are necessary. Integrating telemedicine into future in-center hemodialysis care using a hybrid approach could potentially build trust, optimize communication, and augment care. Plain-Language Summary: This study describes patients’ perspectives on the use of telemedicine while receiving in-center hemodialysis during the coronavirus disease 2019 (COVID-19) pandemic. Data are derived from semistructured interviews with thirty-two patients from underserved populations (older, less educated, unemployed, persons of color). We identified 6 major themes including adapting to telemedicine, ensuring availability of the physicians, safeguarding against infection, straining communication and physical interactions, maintaining privacy, and supporting confidence in telemedicine. These findings suggest that patients receiving in-center hemodialysis adapted to telemedicine visits by their nephrologists in the context of the COVID-19 pandemic and observed its benefits. However, further considerations regarding communication, privacy, and physical assessments are necessary. Integrating telemedicine into future in-center hemodialysis care using a hybrid approach could potentially build trust, optimize communication, and augment care.

Manufacturing of adeno-associated viruses (AAV) for gene and cell therapy applications has increased significantly and spurred development of improved mammalian and insect cell-based production systems. We developed a baculovirus-based insect cell production system—the SGMO Helper—with a novel gene architecture and greater flexibility to modulate the expression level and content of individual Rep and Cap proteins. In addition, we incorporated modifications to the AAV6 capsid sequence that improves yield, capsid integrity, and potency. Production of recombinant AAV 6 (rAAV6) using the SGMO Helper had improved yields compared to the Bac-RepCap helper from the Kotin lab. SGMO Helper-derived rAAV6 is resistant to a previously described proteolytic cleavage unique to baculovirus-insect cell production systems and has improved capsid ratios and potency, in vitro and in vivo, compared with rAAV6 produced using Bac-RepCap. Next-generation sequencing sequence analysis demonstrated that the SGMO Helper is stable over six serial passages and rAAV6 capsids contain comparable amounts of non-vector genome DNA as rAAV6 produced using Bac-RepCap. AAV production using the SGMO Helper is scalable using bioreactors and has improved yield, capsid ratio, and in vitro potency. Our studies demonstrate that the SGMO Helper is an improved platform for AAV manufacturing to enable delivery of cutting-edge gene and cell therapies.

Chillies are members of the genus Capsicum L. (family Solanaceae). They are native to Central and South America and consist of approximately 35 species [1,2]. Among these, five species (C. annuum L., C. baccatum L., C. chinense Jacq., C. frutescens L., and C. pubescens Ruiz & Pav.) have been domesticated and are mainly cultivated for consumption as vegetables and spices. Of the domesticated chillies, C. annuum is commercially cultivated worldwide, while C. frutescens and C. chinense are mainly cultivated in American, Asian, and African countries [3]. We compared the diversity of microbiota in various compartments of farm-cultivated (FC) and home-planted (HP) chilli plants (Capsicum frutescens). Targeted 16S rRNA gene (V5-V6 region) was sequenced using the Illumina NovaSeq 6000 platform. Proteobacteria, Actinobacteriota, Acidobacteriota, Gemmatimonadota, Bacteroidota, and Firmicutes were present in all compartments of both the FC and HP plants. Proteobacteria (or Pseudomonadota) was the predominant phylum in all the compartments of both HP and FC plants, while Actinobacteriota (or Actinomycetota) was the second most abundant phylum. Most plant compartments (leaves, fruits and roots) exhibited a higher relative abundance of Proteobacteria compared to the soil samples. With few exceptions, the soil compartments (bulk and rhizospheric soils) displayed a higher relative abundance of the phyla Myxococcota, Acidobacteriota, Gemmatimonadota, Bacteroidota, Nitrospirota, Verrucomicrobiota, and Firmicutes than the plant compartments. Diversity indices revealed that the bacterial community in chili plants clustered based on both compartment and cultivation area.

Rationale & Objective: Because of coronavirus disease 2019 (COVID-19), the US government issued emergency waivers in March 2020 that removed regulatory barriers around the use of telemedicine. For the first time, nephrologists were reimbursed for telemedicine care delivered during in-center hemodialysis. We examined the use of telemedicine for in-center hemodialysis during the first 16 months of the pandemic. Study Design: We ascertained telemedicine modifiers on nephrologist claims. We used multivariable regression to examine time trends and patient, dialysis facility, and geographic correlates of telemedicine use. We also examined whether the estimated effects of predictors of telemedicine use changed over time. Setting & Participants: US Medicare beneficiaries receiving in-center hemodialysis between March 1, 2020, and June 30, 2021. Exposures: Patient, geographic, and dialysis facility characteristics. Outcomes: The use of telehealth for in-center hemodialysis care. Analytic Approach: Retrospective cohort analysis. Results: Among 267,434 Medicare beneficiaries identified, the reported use of telemedicine peaked at 9% of patient-months in April 2020 and declined to 2% of patient-months by June 2021. Telemedicine use varied geographically and was more common in areas that were remote and socioeconomically disadvantaged. Patients were more likely to receive care by telemedicine in areas with higher incidence of COVID-19, although the predictive value of COVID-19 diminished later in the pandemic. Patients were more likely to receive care using telemedicine if they were at facilities with more staff, and the use of telemedicine varied by facility ownership type. Limitations: Limited reporting of telemedicine on claims could lead to underestimation of its use. Reported telemedicine use was higher in an analysis designed to address this limitation by focusing on patients whose physicians used telemedicine at least once during the pandemic. Conclusions: Some US nephrologists continued to use telemedicine for in-center hemodialysis throughout the pandemic, even as the association between COVID-19 incidence and telemedicine use diminished over time. These findings highlight unique challenges and opportunities to the future use of telemedicine in dialysis care. Plain-Language Summary: Emergency waivers issued during the coronavirus disease 2019 pandemic enabled reimbursement to US nephrologists for telemedicine care delivered during in-center hemodialysis. Using modifiers from Medicare claims, we examined telemedicine use in the first 16 months of the pandemic. Reported telemedicine use peaked early in the pandemic and declined subsequently. Telemedicine use was more common in areas that were remote and socioeconomically disadvantaged and at facilities with more staff. Telemedicine use also varied by facility ownership type. Some nephrologists continued to use telemedicine for in-center hemodialysis throughout the pandemic, even as the association between coronavirus disease 2019 incidence and telemedicine use diminished over time. These findings highlight unique challenges and opportunities to the future use of telemedicine in dialysis care.

Objective: To determine the feasibility of a self-directed training protocol to promote actual arm use in everyday life. The secondary aim was to explore the initial efficacy on upper extremity (UE) outcome measures. Design: Feasibility study using multiple methods. Setting: Home and outpatient research lab. Participants: Fifteen adults (6 women, 9 men, mean age=53.08 years) with chronic stroke living in the community. There was wide range of UE functional levels, ranging from dependent stabilizer (limited function) to functional assist (high function). Intervention: Use My Arm-Remote protocol. Phase 1 consisted of clinician training on motivational interviewing (MI). Phase 2 consisted of MI sessions with participants to determine participant generated goals, training activities, and training schedules. Phase 3 consisted of UE task-oriented training (60 minutes/day, 5 days/week, for 4 weeks). Participants received daily surveys through an app to monitor arm training behavior and weekly virtual check-ins with clinicians to problem-solve challenges and adjust treatment plans. Outcome Measures: Primary outcome measures were feasibility domains after intervention, measured by quantitative study data and qualitative semi-structured interviews. Secondary outcomes included the Canadian Occupational Performance Measure (COPM), Motor Activity Log (MAL), Fugl-Meyer Assessment (FMA), and accelerometry-based duration of use metric measured at baseline, discharge, and 4-week follow-up. Results: The UMA-R was feasible in the following domains: recruitment rate, retention rate, intervention acceptance, intervention delivery, adherence frequency, and safety. Adherence to duration of daily practice did not meet our criteria. Improvements in UE outcomes were achieved at discharge and maintained at follow-up as measured by COPM-Performance subscale (F[1.42, 19.83]=17.72, P

Summary: Blood-borne pathogens can cause systemic inflammatory response syndrome (SIRS) followed by protracted, potentially lethal immunosuppression. The mechanisms responsible for impaired immunity post-SIRS remain unclear. We show that SIRS triggered by pathogen mimics or malaria infection leads to functional paralysis of conventional dendritic cells (cDCs). Paralysis affects several generations of cDCs and impairs immunity for 3–4 weeks. Paralyzed cDCs display distinct transcriptomic and phenotypic signatures and show impaired capacity to capture and present antigens in vivo. They also display altered cytokine production patterns upon stimulation. The paralysis program is not initiated in the bone marrow but during final cDC differentiation in peripheral tissues under the influence of local secondary signals that persist after resolution of SIRS. Vaccination with monoclonal antibodies that target cDC receptors or blockade of transforming growth factor β partially overcomes paralysis and immunosuppression. This work provides insights into the mechanisms of paralysis and describes strategies to restore immunocompetence post-SIRS.

Purpose: To evaluate the biomechanical effects of acellular human dermal allograft tuberoplasty (AHDAT) in a cadaveric model of an irreparable supraspinatus + anterior one-half infraspinatus (stage III) rotator cuff tear. Methods: Eight cadaveric shoulders were tested at 20°, 40°, and 60° of glenohumeral abduction (AB) and 0°, 30°, 60°, and 90° of external rotation (ER). Superior humeral translation, acromiohumeral distance, and subacromial contact were quantified for 4 conditions: (1) intact, (2) stage III tear (entire supraspinatus and anterior one-half infraspinatus), (3) single-layer AHDAT, and (4) double-layer AHDAT. Results: Stage III tear significantly increased superior translation at 20° and 40° AB and all ER angles and at 60° AB/60° ER (P ≤ .045 vs intact). Compared to the stage III tear, the single-layer AHDAT significantly decreased superior translation at 60° AB/60° ER (P = .003), whereas the double-layer AHDAT significantly decreased superior translation at 40° and 60° AB at all ER angles except 60° AB/0° ER (P ≤ .028). The stage III tear significantly decreased acromiohumeral distance at 20° AB (P ≤ .003); both grafts increased acromiohumeral distance to intact levels (P ≥ .055 vs intact). Stage III tear increased subacromial contact pressure at 20° and 40° AB/0° and 30° ER and at 60° AB/30° and 60° ER (P ≤ .034). Both AHDAT groups decreased contact pressure at 40° AB/30° and 60° ER back to intact, whereas the double-layer AHDAT also decreased contact pressure at 20° AB/0° and 60° ER and 60° AB/30° ER (P ≥ .051 vs intact). Conclusions: Both single- and double-layer grafts for AHDAT improved superior translation, subacromial contact characteristics, and acromiohumeral distance after a stage III rotator cuff tear, with varying effectiveness due to the position-dependent nature of greater tuberosity to acromial contact with abduction. Clinical Relevance: The best treatment for massive or irreparable rotator cuff tears is a matter of concern. The results of this study will help determine whether an acellular human dermal allograft tuberoplasty is a potential treatment option worthy of further investigation.

Background and purpose: High-density dental fillings pose a non-negligible impact on head and neck cancer treatment. For proton therapy, stopping power ratio (SPR) prediction will be significantly impaired by the associated image artifacts. Dose perturbation is also inevitable, compromising the treatment plan quality. While plenty of work has been done on metal or amalgam fillings, none has touched on composite resin (CR) and glass ionomer cement (GIC) which have seen an increasing usage. Hence, this work aims to provide a detailed characterisation of SPR and dose perturbation in proton therapy caused by CR and GIC. Materials and methods: Four types of fillings were used: CR, Fuji Bulk (FB), Fuji II (FII) and Fuji IX (FIX). The latter three belong to GIC category. Measured SPR were compared with SPR predicted using single-energy computed tomography (SECT) and dual-energy computed tomography (DECT). Dose perturbation of proton beams with lower- and higher-energy levels was also quantified using Gafchromic films. Results: The measured SPR for CR, FB, FII and FIX were 1.68, 1.77, 1.77 and 1.76, respectively. Overall, DECT could predict SPR better than SECT. The lowest percentage error achieved by DECT was 19.7 %, demonstrating the challenge in estimating SPR, even for fillings with relatively lower densities. For both proton beam energies and all four fillings of about 4.5 mm thickness, the maximum dose perturbation was 3 %. Conclusion: This study showed that dose perturbation by CR and GIC was comparatively small. We have measured and recommended the SPR values for overriding the fillings in TPS.

Introduction: In the United States (US), prophylactic treatment with the antiemetic trimethobenzamide has been used before initiating apomorphine therapy. However, US trimethobenzamide stores have been depleted, leaving uncertainty regarding whether antiemetic pretreatment is needed. Methods: This modified Delphi panel aimed to inform circumstances when apomorphine is initiated without antiemetic pretreatment. During Round 1, a panel of 9 US movement disorder specialists rated the appropriateness of prescribing apomorphine therapy with and without antiemetic pretreatment across 192 patient scenarios and were able to review their scores in relation to other scores. During the Round 2, consensus was defined for each scenario as either strong (>75 % agreement) or moderate (66 % agreement). Results: There was strong consensus on 118 of 192 scenario’s (97 as appropriate and 21 as inappropriate), moderate consensus on 29 scenarios, some agreement on 32 scenarios, and lack of agreement on 13 scenarios. In the absence of an antiemetic, there was strong consensus that titration schedules should be flexible and based on dose response. However, the group only reached moderate consensus on the speed of titration, highlighting the need for more systematic information on this area. In the presence of an antiemetic, panelists considered usual initial dosing and flexible titration to be appropriate in most scenarios except for when the patient is already experiencing dopaminergic adverse events. Conclusions: Experts generally reached consensus that apomorphine can usually be prescribed without antiemetic pretreatment. Recommendations described here reflect the areas of greatest agreement among a panel of experts based on current available evidence.

Summary: Glioblastoma (GBM) is the most common lethal primary brain cancer in adults. Despite treatment regimens including surgical resection, radiotherapy, and temozolomide (TMZ) chemotherapy, growth of residual tumor leads to therapy resistance and death. At recurrence, a quarter to a third of all gliomas have hypermutated genomes, with mutational burdens orders of magnitude greater than in normal tissue. Here, we quantified the mutational landscape progression in a patient’s primary and recurrent GBM, and we uncovered Cas9-targetable repeat elements. We show that CRISPR-mediated targeting of highly repetitive loci enables rapid elimination of GBM cells, an approach we term “genome shredding.” Importantly, in the patient’s recurrent GBM, we identified unique repeat sequences with TMZ mutational signature and demonstrated that their CRISPR targeting enables cancer-specific cell ablation. “Cancer shredding” leverages the non-coding genome and therapy-induced mutational signatures for targeted GBM cell depletion and provides an innovative paradigm to develop treatments for hypermutated glioma.

Ganglioneuromas are benign tumors arising from the neural crest. Histologically, they are composed of mature Schwann cells and ganglion cells admixed with fibrous tissue. While they frequently are seen in the abdomen and mediastinum, rare reports have highlighted their occurrences in the genitourinary system. The only prior reported prostatic ganglioneuroma arose in a patient with a history of neurofibromatosis type 1. In this report, we highlight the first reported prostatic ganglioneuroma without a known genetic linkage.

Objetivos: Relatar o caso de um paciente portador de Doença de Castleman variante hialino-vascular do tipo multicêntrico. Material e métodos: Trata-se de um estudo descritivo e observacional, com análise do prontuário do paciente. Relato do caso: Paciente B.P.G, sexo masculino, 17 anos, procedente do Marajó, interior do Pará, internado no hospital em julho de 2020 com quadro de febre elevada, sudorese noturna, leucocitose, algumas vezes acompanhada de calafrios e tremores desde junho, levado a UTI onde solicitou-se exames como tomografia computadorizada de abdome, observando linfonodomegalias esparsos pelo retroperitônio e mesentério. Solicitado a biópsia de linfonodo inguinal direito, o qual era compatível com processo linfoproliferativo de padrão hialino-vascular, PET-CT com achados de linfonodomegalias nas axilas e em cadeias inguinais bilaterais, e imuno-histoquímica do linfonodo inguinal direito sugestivo de Doença de Castleman com padrão hialino-vascular. B.P.G iniciou terapia com corticoides em doses prolongadas o qual gerou desaparecimento das manifestações clínicas e buscou por acompanhamento clínico em abril de 2021, negando a presença dos sintomas anteriores e tendo ao exame físico apenas a presença de linfonodo palpável nas regiões axilares bilaterais. Obteve melhora laboratorial, com redução dos leucócitos que antes estavam elevados. Foi afastado síndrome de poems e visualizado em um novo PET-CT que a doença está em progressão, pois achados compatíveis com infiltração tímica de 6 cm. Em virtude da pandemia optou-se por continuar utilizando o corticoide dexametasona 40 mg, porém explicando ao acompanhante que em breve se iniciará a terapia padrão com o siltuximabe. Discussão: A DC é uma doença hematológica rara e acomete predominantemente idosos, portanto contrariando a faixa etária epidemiológica da doença, este caso se torna desafiador por ser tratar de um adolescente de 17 anos o qual tem uma longa expectativa de vida e apresenta impacto da qualidade de vida quando está sem medicação. Vale ressaltar que o paciente do caso está sob uso de corticosteroides o qual reduziu bruscamente sua sintomatologia, porém ainda não está utilizando o tratamento padrão com siltuximabe pela situação da pandemia e pelo fato do paciente ser do interior e precisar ser acompanhado de perto com exames laboratoriais durante as 3 primeiras semanas. Conclusão: A raridade da Doença de Castleman torna o relato de cada caso diagnosticado de extrema importância para difusão das dificuldades encontradas não só inerentes ao diagnóstico, mas também como peculiaridades de cada região do Brasil, especialmente na região Norte como o estado do Pará com dimensões continentais, onde uma parte da população vive às margens dos rios tendo os barcos como meio de transporte. A decisão da instituição de um tratamento nem sempre é possível seguir exclusivamente o que a comunidade cientifica orienta, mas por vezes nos resta escolher caminhos pautados em mundo de vida real, como a decisão tomada de se tentar um curso de corticoide para se postergar o início de siltuximabe em um contexto possível para o paciente.

Objetivos: Relatar o caso de uma paciente com dificuldade diagnóstica da Síndrome de Sézary (SS). Material e métodos: Estudo descritivo e observacional, com análise do prontuário da paciente. Relato do caso: Paciente C.L.S.S, sexo feminino, 71 anos, procurou atendimento médico com queixa de prurido corporal intenso e linfocitose persistente desde 2020, meio a pandemia, em que buscou por opinião de diversos especialistas como alergista, dermatologista, reumatologista e infectologista, sem elucidação diagnóstica. Encaminhada ao serviço de hematologia em outubro de 2022, onde relatou apenas o prurido corporal, negando os sintomas B. De comorbidades prévias, relatou apenas depressão e doença de Alzheimer, utilizando como medicações contínuas: Sertralina 50 mg/dia e Rivastigmina 3 mg/dia. Ao exame físico, detectou-se a presença de linfonodomegalias de 2 cm em cadeia cervical profunda e de 3 cm em região axilar bilateralmente. Exames laboratoriais com leucocitose a custas de linfócitos (leucócitos: 11.840; segmentados: 3446; linfócitos: 7672). Sem outras alterações no hemograma. Sorologias negativas para HTLV, hepatite b, hepatite C e HIV. Imunofenotipagem com presença de linfócitos T CD4-positivo: 57% (7.073), tendo perfil anômalo, caracterizado pela expressão dos antígenos CD3 de membrana e CD5, CD2 parcial, em associação com perda anômala dos antígenos de PAN-T CD7 e CD26. Os linfócitos T anômalos apresentaram restrição clonal, com ausência de expressão de antígeno TRBC1 (região constante 1 da cadeia beta do receptor de células T). Dentre as neoplasias maduras, a perda da expressão do CD7 ocorre mais frequentemente na SS. Realizada biópsia de pele que não concluíram a presença do linfoma. No PET-CT evidenciou-se linfonodos hipercaptantes na cadeia axilar bilateral, de morfologia anatômica inespecífica, sugerindo apenas processo inflamatório. Diagnosticada com SS ou linfoma cutâneo T em fase leucêmica, conforme imunofenotipagem, com estadiamento IVA1. Caso discutido com experts na área de hematologia e dermatologia e optado por iniciar terapia local com fototerapia com raios UVB- NB associado a terapia sistêmica com alfa-peginterferona-2ª(Pegasys 180 mg), semanalmente de forma continua até toxicidade ou progressão de doença. Atualmente, em 8°ciclo de Pagasys, com melhora clínica, laboratorial e encontrando-se assintomática. Discussão: A SS é um raro linfoma de células T, muitas vezes subdiagnosticado. O caso relatado demonstra a dificuldade e demora no diagnóstico da paciente, principalmente em um contexto de pandemia. Trata-se de uma doença rara com prognóstico grave, dessa forma, a intervenção precoce se faz de suma importância para impedir a progressão da doença. Após a realização da imunofenotipagem, iniciou-se as terapias tópicas e sistêmicas, com alívio sintomático e retardo na progressão da doença. Conclusão: A Síndrome de Sézary é rara e apresenta um prognóstico diferente para cada paciente. Por tratar-se de uma doença rara com interface com mais de uma especialidade médica, por muitas vezes ela é subdiagnosticada ou detectada apenas em estágios avançados. Sendo assim, o caso demonstra a dificuldade diagnóstica, em um contexto de pandemia, havendo a demora de 2 anos para o diagnóstico. Diante disso, faz-se necessário o conhecimento da patologia para o diagnóstico adequado e precoce, investigação correta e tratamento para aumentar a qualidade de vida desses pacientes, além do alívio dos sintomas e de evitar o avanço da doença.

Objetivo: Descrever a experiência de organizar a III Jornada de Hematologia e Hemoterapia em Belém do Pará. Relato da experiência: Promover um evento de cunho cientifico sempre é necessário para atualizações na especialidade, sendo assim surgiu a necessidade de organizar um evento que abordasse a Hematologia e Hemoterapia, e abrangesse profissionais da área da saúde, incluindo médicos, enfermeiros, técnicos de enfermagem e acadêmicos das áreas da saúde. A III Jornada de Hematologia e Hemoterapia contou com submissão e apresentação de trabalhos científicos, sendo esses selecionados se relevantes para a comunidade cientifica. Além do mais, a programação incluiu diversos assuntos importantes, como: manejo da anemia na jornada do paciente, Patient Blood Management (PBM), tromboelastometria, tromboelastograma na cirurgia, tipagem ABO, orientações para demandas imunohematológicas das agências transfusionais e captação de doadores.O intuito principal era difundir conhecimentos e novas atualizações sobre a área da Hematologia, com isso o Hospital das Clínicas Gaspar Viana (HCGV) promoveu o evento em conjunto com a Liga Acadêmica de Hematologia do Pará (LAHEPA). O evento ocorreu no mês de Junho, com 2 dias seguidos de evento, e contando com a participação de palestrantes renomados de outros estados. Destarte, a jornada proporcionou uma boa interação entre acadêmicos e profissionais da área da saúde. Discussão: Entende-se que atualizações são mais que necessárias em qualquer área, principalmente naquelas relacionadas a saúde, pois protocolos mudam com frequência, novas drogas surgem, além de novos estudos sobre a especialidade. Sendo assim, analisou-se a necessidade de promover e organizar um evento que atualizasse profissionais e acadêmicos sobre a Hematologia e Hemoterapia, incluindo os temas mais diversos da especialidade. Com isso, recrutou-se a liga acadêmica para auxiliar no processo de organização, pois um dos seus pilares principais é aproximar os acadêmicos de suas temáticas de interesse e promover maior visualização dos cenários reais. Dessa maneira, o evento foi promovido e elogiado pelos participantes pela amplitude dos assuntos debatidos. Conclusão: Diante do exposto, é essencial a promoção de eventos que atualizem frequentemente médicos, enfermeiros e técnicos de enfermagem à respeito de mudanças nas mais diversas áreas. A partir disso, a III Jornada de Hematolgia e Hemoterapia ampliou debates sobre anemias, tromboelastometria e mais temáticas, com o apoio da liga acadêmica e das médicas hematologistas do hospital que proporcionou o evento. surgem e tem por objetivo promover um contato maior dos participantes com a temática. Com isso, conclui-se a importância de aulas para profissionais da área da saúde como forma de incentivo para a busca de atualizações, e o evento promovido atuou justamente nesse objetivo de atualização e integração entre médicos, enfermeiros e acadêmicos da área da saúde.

Objetivos: Relatar a experiência da implementação da grade de onco-hematologia em uma liga de oncologia. Relato de experiência: Ligas acadêmicas são de extrema relevância aos estudantes de medicina, pois por meio dela amplia-se a visão de assuntos, como também proporciona um maior contato com a realidade da área através das práticas. Sendo assim, para o funcionamento ideal de todos os pilares dentre da liga, faz-se necessário a organização de um cronograma da gestão anual por meio dos diretores desta. Dessa forma, a Liga Acadêmica de Oncologia do Pará (LAOPA) na gestão de Setembro de 2021 a Outubro de 2022, desempenhou diversas atividades, mas de inovador houve a implementação de uma grade de onco-hematologia, não tão visualizada anteriormente. Com isso, a primeira aula inaugural da liga, para recepção dos novos ligantes contou com uma aula sobre “panorama geral da onco-hematologia”, ministrada por uma hematologista. Além disso, posteriormente ministrou-se uma aula sobre mieloma múltiplo. Concomitantemente ocorria estágios extracurriculares voluntários na especialidade de onco-hematologia em uma clínica, visualizando a rotina dos hematologistas, as doenças mais comuns e seus principais tratamentos. Além do mais, aulas sobre doação de sangue foi ministrada, e campanhas internas para doação de sangue foram iniciadas, estimulando os participantes da liga a se tornarem doadores. Ademais, na finalização da gestão, realizou-se um congresso aberto para os interessados de fora da liga, onde se abordaria temáticas importantes, e 2 das 5 palestras eram sobre Leucemias e outra sobre linfomas. Diante do exposto, deu-se uma atenção redobrada a área, jamais abordada amplamente em gestões passadas. Discussão: Entende-se que o papel das ligas acadêmicas são de suma importância para o maior contato com áreas não tão observadas durante a faculdade de medicina, sendo assim, a implementação de uma grade/módulo de onco-hematologia proporcionou o aprendizado continuo com essa especialidade nova para os ligantes que nunca tinham tido contato. Por isso, a diretoria selecionou temas mais que necessários para serem abordados além da busca pelo estágio na área, proporcionando experiências únicas e construtivas na área. Conclusão: Diante do exposto, observa-se apenas vantagens positividades da participação em ligas acadêmicas e da implementação de uma grade de onco-hematologia nela, pois assim, a temática passa a se tornar foco de palestras, estágios e ações de extensão. Muitos avanços foram obtidos na gestão de 2021 a 2022 na LAOPA, e um deles foi o feedback positivo por parte dos ligantes ao conhecerem temáticas jamais estudadas e vistas anteriormente. A experiência só foi obtida por meio do comprometimento dos diretores e presidentes da liga em organizarem um calendário para as atividades além de colocarem em prática suas idealizações envolvendo a especialidade citada.

Objetivos: Descrever o intuito e a experiência de organizar o I Simpósio de Onco-hematologia que ocorreu de forma online. Relato da experiência: O evento de cunho acadêmico foi idealizado pelos diretores da Liga Acadêmica de Oncologia do Pará (LAOPA) ao perceberem que havia uma precariedade de debate sobre a temática nas faculdades de medicina. Buscou-se assim parceria com a Liga Acadêmica de Hematologia (LAHEPA), a qual se interessou pelo propósito de difundir os conhecimentos sobre os assuntos da onco-hematologia. Sendo assim, selecionou-se temáticas importantes e profissionais competentes na área, divulgando o evento nas redes sociais das ligas. Como obtiveram uma grande demanda de inscrição, totalizando em 300 acadêmicos de medicina e de outras áreas do Brasil, optou-se por fazer o evento de forma online, em 2 dias, em live remota do Youtube, para assim sanar as dúvidas eprorcionar maior interação entre os médicos e os interessados pelos assuntos. O primeiro dia de evento contou com aula sobre linfoma de hodgkin e mieloma múltiplo. Já o segundo dia contou com aula sobre linfoma não Hodgkin e hemoterapia dos pacientes oncológicos. Nos momentos finais, pós palestras, as médicas hematologistas se disponibilizaram de sanar as dúvidas postadas no chat do Youtube. Houve bastante interação e interesse por parte dos acadêmicos, além da disposição das médicas de respondê-los. Dessa forma, o evento proporcionou boa interação entre acadêmicos e médicos, além de um amplo debate de uma temática não explorada nas faculdades, gerando assim interesse nos participantes. Discussão: Sabe-se que os aprendizados são obtidos por meio do aprofundamento dos assuntos e visualização deles na prática, seja na medicina ou em outra área da saúde. Porém a Onco-hematologia não faz parte da grade curricular da maioria das faculdades de medicina, fazendo com que muitos estudantes desconheçam pontos importantes sobre o diagnóstico das doenças onco-hematológicas. Com isso, as ligas acadêmicas tem por objetivo de aproximar os acadêmicos de tais especialidades e promover maior visualização do cenário. Sendo assim, foi promovido esse evento, o qual unia a especialidade de ambas as ligas, aproximando não só os ligantes da temática, como também alunos do Brasil inteiro que demonstraram interesse pelo assunto. Conclusão: Diante disso, é de suma importância os conhecimentos de onco-hematologia para os futuros profissionais médicos e não médicos, tornando de fundamental importância maiores debates sobre a temática, já que nas faculdades médicas o assunto não é explorado. A partir disso as ligas surgem e tem por objetivo promover um contato maior dos participantes com a temática. E assim foi feito com a parceria da Liga Acadêmica de Oncologia do Pará (LAOPA) com a Liga Acadêmica de Hematologia (LAHEPA), as quais promoveram a I Jornada de Onco-hematologia, que teve grande número de inscrições, além de elogios pela temática explorada. Conclui-se assim a importância do debate acerca das patologias onco-hematológica para a boa formação dos futuros profissionais que exercerão não somente a medicina.

Objetivo: Descrever a importância dos estágios extracurriculares na área de onco-hematologia. Relato da experiência: Compreende-se que a grade curricular do curso de medicina é bem ampla, com isso, as experiências proporcionadas englobam diversas especialidades, porém o contato contínuo acaba sendo prejudicado pelas poucas semanas em cada área. Dessa forma, o contato com a hematologia dura cerca de 1 mês e meio, tornando assim uma quebra da continuidade do aprendizado. Diante disso, surgiu a necessidade de buscar por um estágio extracurricular prolongado que proporcionasse um maior contato com as diversas doenças onco-hematológicas, além de proporcionar experiências e conhecimentos para o futuro profissional. Buscou-se meios para conseguir o estágio com um profissional competente na área, sendo assim a liga acadêmica de oncologia, interviu e proporcionou o rodízio voluntário e extracurricular na especialidade buscada. Tal experiência foi guiada por médicos hematologistas de um centro de referência ao tratamento em oncologia em Belém do Pará e a partir disso, acompanhou-se a rotina e os atendimentos desses profissionais, de maneira semanal e contínua por 3 meses, com intuito de adquirir conhecimentos na área e ampliar os aprendizados voltados a subárea da onco-hematologia. Destarte, os profissionais repassaram suas experiências a respeito das neoplasias do sangue e rotinas corriqueiras da hematologia, além da explicação da fisiopatologia, quadro clínico, semiologia e tratamento das doenças. Diante do exposto, a prática nessa área forneceu substratos diferenciados aos que o estágio obrigatório do internato proporcionou, obtendo assim um grande crescimento na área visualizada. Discussão: Estágios extracurriculares são mais que necessários na trajetória acadêmica dos estudantes, proporcionando experiências novas aos acadêmicos de medicina, principalmente envolvendo assuntos que não são abordados amplamente e aprofundados, ou então que o contato na faculdade tenha sido corrido e breve. Por isso, a inserção destes, cada vez mais precoce, proporciona aprendizados impares a respeito das leucemias, linfomas, síndromes raras, somado a doenças hematológicas, como anemias, trombocitopenias e entre outras patologias que serão relevantes para o futuro profissional daqueles que exercerão a medicina, seja como médicos generalistas ou então especialistas na área. Conclusão: Conclui-se que é de extrema relevância o contato com especialidades não visualizadas de forma ampla na faculdade, e a busca se dá por meio da forma ativa, seja por meio das ligas acadêmicas que visem colocar os acadêmicos em cenários reais de prática ou pelo contato com instituições e hospitais que apresentem a modalidade de estágios extracurriculares voluntários para os discentes. Nesse caso, destacam-se apenas pontos positivos com a experiência do rodízio em onco-hematologia, destacando principalmente a observação das doenças mais incidentes naquele meio, além do seu manejo e suas repercussões. Academicamente, essa oportunidade soma de forma construtiva e instrutiva para o futuro dos profissionais médicos que exercerão tanto a medicina como generalistas, quanto para aqueles que farão demais especialidades.

Summary: SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) causing COVID-19 (coronavirus disease 2019) poses a greater health risk to immunocompromized individuals including people living with HIV (PLWH). However, most studies on PLWH have been conducted in higher-income countries. We investigated the post-vaccination antibody responses of PLWH in Rwanda by collecting peripheral blood from participants after receiving a second or third COVID-19 vaccine. Virus-binding antibodies as well as antibody neutralization ability against all major SARS-CoV-2 variants of concern were analyzed. We found that people with high HIV viral loads and two COVID-19 vaccine doses had lower levels of binding antibodies that were less virus neutralizing and less cross-reactive compared to control groups. A third vaccination increased neutralizing antibody titers. Our data suggest that people with high HIV viral loads require a third dose of vaccine to neutralize SARS-CoV-2 virus and new variants as they emerge.

The R47H variant of triggering receptor expressed on myeloid cells 2 (TREM2) increases the risk of Alzheimer's disease (AD). To investigate potential mechanisms, we analyzed knockin mice expressing human TREM2-R47H from one mutant mouse Trem2 allele. TREM2-R47H mice showed increased seizure activity in response to an acute excitotoxin challenge, compared to wildtype controls or knockin mice expressing the common variant of human TREM2. TREM2-R47H also increased spontaneous thalamocortical epileptiform activity in App knockin mice expressing amyloid precursor proteins bearing autosomal dominant AD mutations and a humanized amyloid-β sequence. In mice with or without such App modifications, TREM2-R47H increased the density of putative synapses in cortical regions without amyloid plaques. TREM2-R47H did not affect synaptic density in hippocampal regions with or without plaques. We conclude that TREM2-R47H increases AD-related network hyperexcitability and that it may do so, at least in part, by causing an imbalance in synaptic densities across brain regions.

Summary: Background: Screening for colorectal cancer (CRC) decreases cancer burden through removal of precancerous lesions and early detection of cancer. The COVID-19 pandemic has disrupted organised CRC screening programs worldwide, with some programs completely suspending screening and others experiencing significant decreases in participation and diagnostic follow-up. This study estimated the global impact of screening disruptions on CRC outcomes, and potential effects of catch-up screening. Methods: Organised screening programs were identified in 29 countries, and data on participation rates and COVID-related changes to screening in 2020 were extracted where available. Four independent microsimulation models (ASCCA, MISCAN-Colon, OncoSim, and Policy1-Bowel) were used to estimate the long-term impact on CRC cases and deaths, based on decreases to screening participation in 2020. For countries where 2020 participation data were not available, changes to screening were approximated based on excess mortality rates. Catch-up strategies involving additional screening in 2021 were also simulated. Findings: In countries for which direct data were available, organised CRC screening volumes at a country level decreased by an estimated 1.3–40.5% in 2020. Globally, it is estimated that COVID-related screening decreases led to a deficit of 7.4 million fewer faecal screens performed in 2020. In the absence of any organised catch-up screening, this would lead to an estimated 13,000 additional CRC cases and 7,900 deaths globally from 2020 to 2050; 79% of the additional cases and 85% of additional deaths could have been prevented with catch-up screening, respectively. Interpretation: COVID-19-related disruptions to screening will cause excess CRC cases and deaths, but appropriately implemented catch-up screening could have reduced the burden by over 80%. Careful management of any disruption is key to improving the resilience of colorectal cancer screening programs. Funding: The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Cancer Council New South Wales, Health Canada, and Dutch National Institute for Public Health and Environment.

The effects of multiple stressors (salinity, temperature, nutrient and light availability or human activities) on the abundance of FIB (Escherichia coli and Enterobacteriaceae) were studied in nine lakes on the southern Baltic coast. Monitoring also included physicochemical factors and land use in the catchment. The results showed that FIB is a natural component of microbial community in coastal lakes, with its abundance varying temporally and spatially. The key factors predicting the abundance of E. coli and Enterobacteriaceae are the availability of ammonia nitrogen and water temperature. Regardless of the degree of connection with the sea, the sanitary condition of coastal lakes deteriorates during the summer months. Although agricultural use and residential development do not significantly affect fecal bacteria counts (PLS-R model), human pressure on the sanitary condition of lakes increases seasonally and is limited to the vicinity of tourist sites. The degree of contact with seawater regulates the size of the microbial community, but is not a factor that directly affects the presence of E. coli in the microbial community in coastal lakes. Monitoring the sanitary conditions of these ecosystems using sensitive, rapid survey methods based on hydrochemical and microbiological inventories, supported by GIS, is important for public health.

Objective: A novel transdermal arterial gasotransmitter sensor (TAGS) has been tested as a diagnostic tool for lower limb microvascular disease in individuals with and without diabetes mellitus (DM). Methods: The TAGS system noninvasively measures hydrogen sulfide (H2S) emitted from the skin. Measurements were made on the forearm and lower limbs of individuals from three cohorts, including subjects with DM and chronic limb-threatening ischemia, to evaluate skin microvascular integrity. These measurements were compared with diagnosis of peripheral artery disease (PAD) using the standard approach of the toe brachial index. Other measures of vascular health were made in some subjects including fasting blood glucose, hemoglobin A1c, plasma lipids, blood pressure, estimated glomerular filtration, and body mass index. Results: The leg:arm ratio of H2S emissions correlated with risk factors for microvascular disease (ie, high-density lipoprotein levels, estimated glomerular filtration rate, systolic blood pressure, and hemoglobin A1c). The ratios were significantly lower in symptomatic DM subjects being treated for chronic limb-threatening ischemia (n = 8, 0.48 ± 0.21) compared with healthy controls (n = 5, 1.08 ± 0.30; P = .0001) and with asymptomatic DM subjects (n = 4, 0.79 ± 0.08; P = .0086). The asymptomatic DM group ratios were also significantly lower than the healthy controls (P = .0194). Using ratios of leg:arm transdermal H2S measurement (17 subjects, 34 ratios), the overall accuracy to identify limbs with severe PAD had an area under the curve of the receiver operating curve of 0.93. Conclusions: Ratios of transdermal H2S measurements are lower in legs with impaired microvascular function, and the decrease in ratio precedes clinically apparent severe microvascular disease and diabetic ulcers. The TAGS instrument is a novel, sensitive tool that may aid in the early detection and monitoring of PAD complications and efforts for limb salvage.

Background: Half of all stroke survivors experience hemiparesis on the contralateral side, resulting in chronic upper extremity (UE) impairment. Remote rehabilitation is a promising approach to optimize the gains made in the clinic to maximize function and promote UE use at home. This paper describes the study protocol for a remote home-based UE self-training program. Design: This was a feasibility study that used a convergent mixed methods approach. Methods: We collected data on 15 community-dwelling individuals with UE hemiparesis after stroke. The study used motivational interviewing (MI) and ecological momentary assessments (EMA) to maximize engagement in a 4-week personalized UE self-training program. The study consisted of three phases: 1) training in MI for the interventionists 2) creating customized treatment plans using shared decision making, and 3) four weeks of UE self-training. Measures and analysis: To evaluate feasibility, we will summarize recruitment and retention rates, intervention delivery, acceptance, adherence, and safety. Quantitative UE outcomes will measure change in UE status after the intervention (Fugl-Meyer Assessment, Motor Activity Log, Canadian Occupational Performance Measure, and bilateral magnitude ratio). Qualitative data (1:1 semi-structured interviews) will capture participants’ perceptions and experience with the intervention. Quantitative and qualitative data will be integrated to gain a deeper understanding of the facilitators and barriers for engagement and adherence to UE self-training. Conclusion: The results of this study will advance the scientific knowledge for use of MI and EMA as methods for enhancing adherence and engagement in UE self-training in stroke rehabilitation. The ultimate impact of this research will be to improve UE recovery for individuals with stroke transitioning back into community. Clinical trials registration: NCT05032638.

Summary: mRNA vaccines are effective in preventing severe COVID-19, but breakthrough infections, emerging variants, and waning immunity warrant the use of boosters. Although mRNA boosters are being implemented, the extent to which pre-existing immunity influences the efficacy of boosters remains unclear. In a cohort of individuals primed with the mRNA-1273 or BNT162b2 vaccines, we report that lower antibody levels before boost are associated with higher fold-increase in antibody levels after boost, suggesting that pre-existing antibody modulates the immunogenicity of mRNA vaccines. Our studies in mice show that pre-existing antibodies accelerate the clearance of vaccine antigen via Fc-dependent mechanisms, limiting the amount of antigen available to prime B cell responses after mRNA boosters. These data demonstrate a “tug of war” between pre-existing antibody responses and de novo B cell responses following mRNA vaccination, and they suggest that transient downmodulation of antibody effector function may improve the efficacy of mRNA boosters.

Objective: Lateral flow assays (LFA) are sensitive for detecting antibodies to SARS-CoV-2 proteins within weeks after infection. This study tested samples from immunocompetent adults, and those receiving treatments for chronic inflammatory diseases (CID), before and after mRNA SARS-CoV-2 vaccination. Methods: We compared results obtained with the COVIBLOCK Covid-19 LFA to those obtained by anti-spike (S) ELISA. Results: The LFA detected anti-S antibodies in 29 of 29 (100%) of the immunocompetent and 110 of 126 (87.3%) of the CID participants after vaccination. Semiquantitative LFA scores were statistically significantly lower in samples from immunosuppressed participants, and were significantly correlated with anti-S antibody levels measured by ELISA. Conclusions: This simple LFA test is a practical alternative to laboratory-based assays for detecting anti-S antibodies after infection or vaccination. This type of test may be most useful for testing people in outpatient or resource-limited settings.

Coxiella burnetii, the causative organism of Q fever, has been increasingly reported to be associated with infections of abdominal aortic aneurysms and endovascular stent grafts. We have added to the current literature by presenting a case of the surgical management of chronic Q fever that had infected a prior aortic endovascular stent graft placed for a contained rupture of an infrarenal aortic aneurysm in a 68-year-old woman. We presented our case of the surgical management of the excision and explantation of the infected aorta and stent graft, with reconstruction of the aorta using a cryopreserved aortic graft and visceral artery pump perfusion.

This study investigates freeze-dried okra seed flour (OSF) as a functional ingredient to attenuate postprandial blood glucose rise by creating lower glycemic index (GI) rice noodles. Secondary objectives are postprandial gut hormone responses, noodle satiety, and sensory evaluation. Twenty healthy individuals consumed control rice noodle (CON), 10 % okra seed fortified noodle (OKN), 20 % OKN and glucose reference drinks on separate visits. 20 % OKN significantly lowered the postprandial glucose and insulin peaks compared to CON. Compared to CON, there was a 20-point reduction of GI value for 20 % OKN to 64. All noodles produced similar responses in postprandial ghrelin and glucagon-like peptide-1 (GLP-1). OKN were found to be more satiating than control noodles given the same amount of available carbohydrates. Sensory evaluation revealed that OSF can be added to noodle to create sensorially acceptable products, though ratings for sensory characteristics decreased with increased fortification.

Background: Spontaneous beta activity in the primary motor cortices has been shown to increase in amplitude with advancing age, and that such increases are tightly coupled to stronger motor-related beta oscillations during movement planning. However, the relationship between these age-related changes in spontaneous beta in the motor cortices, local cortical thickness, and overall motor function remains unclear. Methods: We collected resting-state magnetoencephalography (MEG), high-resolution structural MRI, and motor function scores using a neuropsychological battery from 126 healthy adults (56 female; age range = 22–72 years). MEG data were source-imaged and a whole-brain vertex-wise regression model was used to assess age-related differences in spontaneous beta power across the cortex. Cortical thickness was computed from the structural MRI data and local beta power and cortical thickness values were extracted from the sensorimotor cortices. To determine the unique contribution of age, spontaneous beta power, and cortical thickness to the prediction of motor function, a hierarchical regression approach was used. Results: There was an increase in spontaneous beta power with age across the cortex, with the strongest increase being centered on the sensorimotor cortices. Sensorimotor cortical thickness was not related to spontaneous beta power, above and beyond age. Interestingly, both cortical thickness and spontaneous beta power in sensorimotor regions each uniquely contributed to the prediction of motor function when controlling for age. Discussion: This multimodal study showed that cortical thickness and spontaneous beta activity in the sensorimotor cortices have dissociable contributions to motor function across the adult lifespan. These findings highlight the complexity of interactions between structure and function and the importance of understanding these interactions in order to advance our understanding of healthy aging and disease.

Background: COVID-19 has become a global pandemic. It has affected patients the world over, and when minimally symptomatic, it can be an incidental finding in trauma patients. It may also make the diagnosis of other rare conditions more difficult due to clinical finding superimposition. Case presentation: A 23-year-old male was transferred to our Trauma Center in hemorrhagic shock after sustaining multiple gunshot wounds in the upper back. Imaging showed a retained projectile in the right pharyngeal area, a right upper lobe contusion, and a right hemopneumothorax; with additional infiltrates on both lungs suggestive of atelectasis. After intubation, a propofol infusion was started for sedation. Shortly thereafter worsening acidosis, refractory hypoxia, and hypotension with additional laboratory anomalies ensued, as the PCR screening for SARS-CoV-2 returned positive. The clinical findings suggested COVID-19 pneumonia with possible superimposed Propofol Infusion Syndrome. The drug was stopped, and the symptoms improved. Conclusion: A high index of suspicion is necessary to manage unusual pathologies and difficult differential diagnoses, and this is especially true during the ongoing pandemic.

Inhibitors of dopamine transporters (DAT), norepinephrine transporters (NET) and serotonin transporters (SERT) are effective treatments for neuropsychiatric diseases. Dasotraline [(1R,4 S)− 4-(3,4-dichlorophenyl)− 1,2,3,4-tetrahydro-1-naphthalenamine, also known as SEP-225289) was evaluated for its inhibitory potency at DAT, NET and SERT using in vitro and in vivo assays. In vitro radiometric functional uptake studies showed preferential inhibition by dasotraline of hDAT (IC50 =3 nM) and hNET (IC50 =4 nM relative to hSERT(IC50 =15 nM). In mouse ex vivo occupancy studies, dasotraline demonstrated total plasma concentration-dependent occupancy at DAT, NET and SERT. Determination of the TO50 (50% transporter occupancy) were 32, 109 and 276 ng/ml, respectively. In SPECT imaging studies in baboons, dasotraline (0.2 mg/kg iv) displaced radiotracer binding to DAT by 87% but only 20% at NET and SERT. Rat microdialysis studies were performed in prefrontal cortex and striatum. Dasotraline produced sustained (>4 h) increases in dopamine and norepinephrine concentrations. Dasotraline was also more potent at increasing synaptic dopamine in the striatum, and norepinephrine in the prefrontal cortex than serotonin in these regions. In summary, dasotraline preferentially inhibits DAT and NET relative to SERT. Together, the occupancy and neurochemical profile of dasotraline provide a mechanistic basis for the treatment of diseases that have an underlying causality involving dopamine and norepinephrine dysfunction.

The WEPPcloud interface is a new online decision-support tool for the Water Erosion Prediction Project (WEPP) model that facilitates data preparation and model runs, and summarizes model outputs into tables and maps that are easily interpretable by users. The interface can be used by land and water managers in the United States, Europe, and Australia interested in simulating streamflow, sediment and pollutant loads from both undisturbed and disturbed (e.g. post-wildfire or post-treatment such as thinning or prescribed fires) forested watersheds. This article contains full hydrologic model runs for 28 forested watersheds in the U.S. Pacific Northwest with the WEPPcloud online interface. It also includes links to repositories with the individual model runs, a table containing default model parameters for disturbed conditions, and figures with model outputs as compared to observed data. The data in the repositories include all the raw data input and output from the model as well as the processed data, which can be accessed through tables and shapefiles to provide additional insights into the model outputs. Lastly, the article describes how the data are organized and the content of each folder containing the data. These model runs are useful for anyone interested in modeling forested watersheds with the WEPPcloud interface.

Next-generation high frequency, high power density, and high operating temperature electrical machines require superior materials which possess an attractive combination of structural as well as functional properties. Development of such new materials by conventional methods is very slow, expensive, and restricted to a few compositions. Hence, we addressed this challenge by the accelerated assessment of multiple properties of a range of Fe-Co-Ni based material compositions. We utilized the magnetron co-sputtering method to prepare compositionally modulated ternary Fe-Co-Ni thin film alloy (TFA) libraries. The structural, electrical, magnetic, and mechanical properties of these libraries were assessed. The structure and properties were found to vary over a wide range with composition and thin film processing parameters. The Fe-Co-Ni TFA library prepared at a substrate temperature of 500 °C exhibited a good combination of multiple properties. The specific alloy composition Ni54.9Co33.1Fe12 was found to possess an attractive blend of properties. Thus, a rapid property assessment of TFA libraries of a wide range of compositions and processing conditions was successfully used to identify a novel specific composition and processing protocol which exhibited an attractive mix of properties.

Purpose: Primary care physicians (PCP) are at a high risk of contracting COVID-19 as they manage patients with fever or respiratory symptoms, but it is intuitive that private and public practice PCPs may face different challenges during this pandemic. This study compared work- and non-work-related concerns, COVID-19’s impact on personal and professional lives, and perceived pandemic preparedness between private and public PCPs in Singapore. Methods: 216 PCPs who were a registered member of either the National University Polyclinics, National University Health System Primary Care Network or College of Family Physicians Singapore, participated in this online cross-sectional study. The data collection period lasted from 6th March 2020 to 29th March 2020. Results: A final sample of 172 questionnaires were analysed. Private PCPs tended to be older and more experienced. Perceived COVID-19 exposure and overall preparedness was high in both groups. More private PCPs perceived their exposure risk as unacceptable, aOR = 3.96 (1.07, 14.62); that they should not be caring for COVID-19 patients, aOR = 3.55 (1.23, 10.24); and perceived more stigma against their loved ones, aOR = 4.27 (1.74, 10.44). Private PCPs felt less well-trained, aOR = 0.05 (0.01, 0.23); and supported, aOR = 0.14 (0.03, 0.63). Conclusions: Private PCPs are more likely to be self-employed or work in smaller practices where COVID-19 infection could mean loss of livelihood. As a healthcare system without primary care is crippled in its ability to manage outbreaks, authorities should respond appropriately to the needs of their general practitioners and family physicians.

Purpose: Relative biological effectiveness (RBE) uncertainties have been a concern for treatment planning in proton therapy, particularly for treatment sites that are near organs at risk (OARs). In such a clinical situation, the utilization of variable RBE models is preferred over constant RBE model of 1.1. The problem, however, lies in the exact choice of RBE model, especially when current RBE models are plagued with a host of uncertainties. This paper aims to determine the influence of RBE models on treatment planning, specifically to improve the understanding of the influence of the RBE models with regard to the passing and failing of treatment plans. This can be achieved by studying the RBE-weighted dose uncertainties across RBE models for OARs in cases where the target volume overlaps the OARs. Multi-field optimization (MFO) and single-field optimization (SFO) plans were compared in order to recommend which technique was more effective in eliminating the variations between RBE models. Methods: Fifteen brain tumor patients were selected based on their profile where their target volume overlaps with both the brain stem and the optic chiasm. In this study, 6 RBE models were analyzed to determine the RBE-weighted dose uncertainties. Both MFO and SFO planning techniques were adopted for the treatment planning of each patient. RBE-weighted dose uncertainties in the OARs are calculated assuming (αβ)x of 3 Gy and 8 Gy. Statistical analysis was used to ascertain the differences in RBE-weighted dose uncertainties between MFO and SFO planning. Additionally, further investigation of the linear energy transfer (LET) distribution was conducted to determine the relationship between LET distribution and RBE-weighted dose uncertainties. Results: The results showed no strong indication on which planning technique would be the best for achieving treatment planning constraints. MFO and SFO showed significant differences (P

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) in silico, which suppressed SARS-CoV-2 replication in vitro. In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers (P

Abstract: The highly selective BCL2 inhibitor venetoclax achieves deep responses in patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL), including undetectable minimal residual disease (uMRD). We retrospectively reviewed 62 patients with CLL treated with venetoclax to investigate the performance of peripheral blood (PB) compared with bone marrow (BM) assessment of MRD; the kinetics, clinicopathological associations, and longer-term outcomes of uMRD attainment and recrudescence; and the ability of venetoclax dose escalation to deepen responses. Among 16 patients who achieved PB uMRD and had contemporaneous BM assessments, 13 (81%) had confirmed BM uMRD, and patients with PB uMRD had outcomes at least as favorable as those with BM uMRD for time to progression, overall survival, and MRD recrudescence. Excluding 2 patients lacking earlier assessment, the median time to PB uMRD was 18 (range, 5-26) months, with 90% of instances achieved by 24 months. There was no new PB uMRD attainment after 24 months without treatment intensification. The dominant association with earlier attainment of uMRD was concurrent rituximab (P = .012). Complex karyotype was associated with inferior uMRD attainment after 12 months of therapy (P = .015), and patients attaining uMRD whose disease harbored TP53 abnormalities demonstrated a trend toward earlier recrudescence (P = .089). Of patients who received venetoclax dose escalations, 4 (27%) of 15 achieved improvements in response. For patients with R/R CLL receiving venetoclax, PB uMRD commonly correlates with BM uMRD and is associated with a comparable longer-term prognosis. Concurrent rituximab augments uMRD attainment, but dose escalation and further treatment beyond 24 months infrequently deepen responses.

Introduction: True non-traumatic radial artery aneurysms (RAAs) are extremely rare, and few cases have been described. The majority of RAAs are post-traumatic or iatrogenic pseudo-aneurysms following arterial cannulation. However, RAAs due to other causes have also been described. Here a rare case of true idiopathic distal RAA, which was managed by surgical resection and repair with interposition vein graft, is described. Report: A 62 year old female with a known medical history of hypertension and hyperlipidaemia presented with left wrist swelling of one year duration, associated with a pulsatile lump that was increasing in size. Duplex ultrasound and computed tomography angiography revealed a distal RAA. She underwent open surgical resection and repair with interposition vein graft using the distal left cephalic vein. Histopathology of the specimen revealed an aneurysm with atherosclerosis. She recovered well post-operatively with no complications. Discussion: True idiopathic RAAs are rare. Surgical treatment is almost always recommended in view of the risk of complications. A case of true idiopathic distal RAA is presented here, which was managed successfully by surgical resection and repair with interposition vein graft.

Background: Originally designed for computerized image analysis, ThinPrep is underutilized in that role outside gynecological cytology. It can be used to address the inter/intra-observer variability in the evaluation of thyroid fine needle aspiration (TFNA) biopsy and help pathologists to gain additional insight into thyroid cytomorphology. Methods: We designed and validated a feature engineering and supervised machine learning-based digital image analysis method using ImageJ and Python scikit-learn. The method was trained and validated from 400 low power (100x) and 400 high power (400x) images generated from 40 TFNA cases. Result: The area under the curve (AUC) for receiver operating characteristics (ROC) is 0.75 (0.74–0.82) for model based from low-power images and 0.74 (0.69–0.79) for the model based from high-power images. Cytomorphologic features were synthesized using feature engineering and when performed in isolation, they achieved AUC of 0.71 (0.64–0.77) for chromatin, 0.70 (0.64–0.73) for cellularity, 0.65 (0.60–0.69) for cytoarchitecture, 0.57 (0.51–0.61) for nuclear size, and 0.63 (0.57–0.68) for nuclear shape. Conclusion: Our study proves that ThinPrep is an excellent preparation method for digital image analysis of thyroid cytomorphology. It can be used to quantitatively harvest morphologic information for diagnostic purpose.

We discuss a shift in the treatment paradigm for OFF episode management in patients with Parkinson’s disease, based on clinical experience in the United States (US). Three “on-demand” treatments are currently available in the US as follows: subcutaneous apomorphine, levodopa inhalation powder, and sublingual apomorphine. We empirically propose that “on-demand” treatments can be utilized as a complementary treatment when OFF episodes emerge and can be utilized when needed rather than reserving these treatments only until other treatment approaches (adjustment of baseline treatment and/or addition of adjunctive treatment with “ON-extenders”) have failed. Current treatment approaches combine “ON-extenders” with increasing levodopa dosing and/or frequency to treat OFF episodes. Yet, OFF episodes often persist, with a substantial amount of daily OFF time. OFF episode treatment is hindered by variable gastrointestinal (GI) absorption of oral levodopa, reflecting GI dysmotility and protein competition. Novel “on-demand” treatments bypass the gut and can improve OFF symptoms more rapidly and reliably than oral levodopa. With the emergence of novel “on-demand” treatments, we conclude that a shift in treatment paradigm to the earlier, complementary use of these medications be considered.

Background: While numerous studies have examined the developmental trajectory of task-based neural oscillations during childhood and adolescence, far less is known about the evolution of spontaneous cortical activity during this time period. Likewise, many studies have shown robust sex differences in task-based oscillations during this developmental period, but whether such sex differences extend to spontaneous activity is not understood. Methods: Herein, we examined spontaneous cortical activity in 111 typically-developing youth (ages 9–15 years; 55 male). Participants completed a resting state magnetoencephalographic (MEG) recording and a structural MRI. MEG data were source imaged and the power within five canonical frequency bands (delta, theta, alpha, beta, gamma) was computed. The resulting power spectral density maps were analyzed via vertex-wise ANCOVAs to identify spatially-specific effects of age, sex, and their interaction. Results: We found robust increases in power with age in all frequencies except delta, which decreased over time, with findings largely confined to frontal cortices. Sex effects were distributed across frontal and temporal regions; females tended to have greater delta and beta power, whereas males had greater alpha. Importantly, there was a significant age-by-sex interaction in theta power, such that males exhibited decreasing power with age while females showed increasing power with age in the bilateral superior temporal cortices. Discussion: These data suggest that the strength of spontaneous activity undergoes robust change during the transition from childhood to adolescence (i.e., puberty onset), with intriguing sex differences in some cortical areas. Future developmental studies should probe task-related oscillations and spontaneous activity in parallel.