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Life-threatening thrombotic events and neurological symptoms are prevalent in COVID-19 and are persistent in patients with long COVID experiencing post-acute sequelae of SARS-CoV-2 infection1-4. Despite the clinical evidence1,5-7, the underlying mechanisms of coagulopathy in COVID-19 and its consequences in inflammation and neuropathology remain poorly understood and treatment options are insufficient. Fibrinogen, the central structural component of blood clots, is abundantly deposited in the lungs and brains of patients with COVID-19, correlates with disease severity and is a predictive biomarker for post-COVID-19 cognitive deficits1,5,8-10. Here we show that fibrin binds to the SARS-CoV-2 spike protein, forming proinflammatory blood clots that drive systemic thromboinflammation and neuropathology in COVID-19. Fibrin, acting through its inflammatory domain, is required for oxidative stress and macrophage activation in the lungs, whereas it suppresses natural killer cells, after SARS-CoV-2 infection. Fibrin promotes neuroinflammation and neuronal loss after infection, as well as innate immune activation in the brain and lungs independently of active infection. A monoclonal antibody targeting the inflammatory fibrin domain provides protection from microglial activation and neuronal injury, as well as from thromboinflammation in the lung after infection. Thus, fibrin drives inflammation and neuropathology in SARS-CoV-2 infection, and fibrin-targeting immunotherapy may represent a therapeutic intervention for patients with acute COVID-19 and long COVID.

Abstract Background To prospectively evaluate binocular visual outcomes after implantation of trifocal intraocular lenses (IOLs) with high-water-content hydrophobic acrylic material in Japanese patients. Methods In 59 patients (mean age 65.1 ± 7.9 years), Clareon PanOptix (CNWTT0: Alcon) with a high-water-content hydrophobic acrylic material was implanted bilaterally. Three months postoperatively, binocular uncorrected visual acuity (BUCVA) and distance-corrected visual acuity (BDCVA) at distances of 5 m, 80, 60, and 40 cm, binocular defocus curves, and binocular photopic contrast sensitivity were examined. Subjective symptoms (night vision disturbance, glare, halos, haze, or blurry vision) were also assessed. Results The mean postoperative BUCVA/BDCVA at 5 m, 80 cm, 60 cm, and 40 cm were − 0.115/-0.163, -0.052/-0.047, -0.054/-0.075, and − 0.043/-0.067 logMAR, respectively. A smooth defocus curve, contrast sensitivity within the normal range, and acceptable subjective symptom rates were obtained. Conclusions The trifocal IOL, composed of a high-water-content hydrophobic acrylic material, provides good continuous binocular vision from distance to near. Trial registration This investigator-initiated study was registered in the Japan Registry for Clinical Trials (identifier: jRCTs032220042) on April 26, 2022.

Introdução: A contaminação bacteriana dos concentrados de Plaquetas (CPs) é um problema que afeta os bancos de sangue no mundo inteiro, sendo seu controle obrigatório em diversos países e um desafio relacionado à segurança transfusional. Considerando que existe elevada taxa de morbi-mortalidade associada a contaminação de concentrados plaquetários, torna-se necessário o desenvolvimento de protocolos de triagem pré-transfusional que sejam rápidos e aplicáveis a rotina dos hemocentros, de forma a aumentar a biossegurança das transfusões sanguíneas realizadas pelo SUS. O emprego de protocolos moleculares baseados em PCR de tempo real consiste em uma estratégia promissora que pode ser aplicada diretamente na triagem de hemocomponentes que serão transfundidos. Objetivos: Geral: Desenvolver e validar um teste molecular para a qualificação segura e estendida de concentrados de plaquetas. Específicos: Validar a detecção de bactérias em concentrados de plaquetas por método molecular; Elaborar esboço de protocolo de atenção diagnóstica. Material e métodos: Tipo de estudo: Estudo experimental, prospectivo, baseado em coleta de dados primários. Local e período: HEMOCE, de março de 2023 a dezembro de 2024. Fases do estudo: O estudo é estruturado em três fases distintas, com atividades em comum: i): coleta de bolsas de CP descartadas por validade no 5º dia às 23:59 h; ii): semeio e cultivo das culturas de bactérias e o preparo de diluições seriadas; iii): extração de DNA e testes de PCR; e iv): testes realizados no dia seguinte ao descarte por validade e 24 e 48 h depois. Fase I: Testes piloto; Fase II: Validação do ensaio; Fase III: Ensaio completo de avaliação de contaminação bacteriana. Definição e seleção das bactérias: Levantamento bibliográfico na literatura científica identificando as bactérias mais prevalentes na contaminação de CPs e cepas ATCC de conveniência. Obtenção das amostras biológicas: Bolsas CP descartadas por validade. Avaliação da contaminação microbiológica dos CPs - Método Microbiológico: Hemocultura. Método molecular - Extração de DNA: extração dos ácidos nucleicos realizada por meio de três métodos distintos: a) de forma manual; b) automatizado; e c) semiautomatizado e três protocolos distintos. PCR em tempo real: Reação em Cadeia da Polimerase (PCR) utilizando quatro ensaios distintos e controles: a) controle negativo; b) controle positivo; c) controle interno; e d) referência passiva. Resultados: Os resultados preliminares apontam para a eficiência dos testes de PCR como recurso complementar para detecção de contaminação microbiológica de CPs. Após 384 reações de PCR realizadas, três dos quatro ensaios testados se mostram promissores. Mesmo em concentrações mais altas o tempo para alcance dos resultados do teste molecular foi mais eficiente quando comparado aos testes de cultura. Discussão: Os resultados alcançados até o momento indicam números semelhantes aos encontrados na literatura, reagentes para a contaminação bacteriana. Valores de Ct (threshold cycle) entre 20 e 30 indicam potencial de eficiência dos ensaios testados, necessitando a validação para valores mais baixos de concentrações, 1-101UFC/mL, corroborando ou refutando resultados de outras pesquisas semelhantes. Conclusão: Apesar dos resultados promissores, testes adicionais estão sendo realizado para possibilitar maior força de evidência aos achados e permitir atestar a potencial utilização como teste secundário de detecção rápida de contaminação microbiológica em CPs.

Dynapenia and multimorbidity are common health problems affecting older adults. However, few studies have systematically reviewed the association between dynapenia and multimorbidity. Therefore, this systematic review aimed to provide a comprehensive overview of studies on the association between these conditions. We searched four electronic databases for relevant articles published in July 2023. The main inclusion criteria were the following: a description of dynapenia, which indicates loss of muscle strength, and a description of multimorbidity with two or more chronic diseases. Five studies met these inclusion criteria. In all five of these studies, the participants were community-dwelling older adults. All the studies showed an association between dynapenia and multimorbidity. The prevalence of dynapenia and multimorbidity ranged from 16% to 25.9%. The results of our systematic review demonstrated that dynapenia in older adults increases the risk of multimorbidity. We propose that interventions and reversible changes in dynapenia can prevent multimorbidity. (PROSPERO Registration No. CRD42023443282)

Abstract Introduction The aim of this prospective and comparative study was to investigate the association of perimetry parameters on visual acuity and contrast sensitivity in primary open-angle glaucoma (POAG) eyes with diffractive extended depth-of-focus (EDoF) and monofocal intraocular lenses (IOLs). Methods In cataract eyes with medicinally controlled POAG with no defects in the central visual field and mean deviation (MD) values of − 10 dB or better, EDoF and monofocal IOLs with the same platform except for echelette optics for EDoF were implanted in 22 and 24 eyes, respectively. Corrected distance visual acuity (CDVA), contrast sensitivity at 3 to 18 cycles per degree (cpd), and automated perimetry using 30-2 and 10-2 Swedish Interactive Threshold Algorithm programs were examined 3 months postoperatively. The influences of perimetry parameters including MD, foveal sensitivity (FS), and the means of the central four points (central MD and central FS) on CDVA and contrast sensitivity were evaluated using linear and multiple regression analyses. Results In POAG eyes with EDoF IOLs, contrast sensitivities at 12 and 18 cpd were associated with 30-2 and 10-2 perimetry parameters. In POAG eyes with monofocal IOLs, associations of 30-2 parameters were found in CDVA and 3-cpd contrast sensitivity. Conclusions The visual function of POAG eyes with EDoF IOLs was associated with perimetry parameters in high spatial frequency contrast sensitivity, which was different from that of POAG eyes with monofocal IOL. Trial Registration Japan Registry for Clinical Research: jRCTs032200218.

A Dauphiné twin (DT) in a deformed quartz was visualized for the first time by using orientation-optimized electron channelling contrast imaging (ooECCI) under Bragg conditions of the rhombohedral planes. The visualization in backscattered electron (BSE) imaging with a scanning electron microscope (SEM) is possible due to the electron excitations of positive and negative rhombohedral planes from respective twin domains. Those diffraction planes have different structure factors and scattering amplitudes in electron diffraction and are exchanged in a pair of DT domains. The large-angle convergent beam diffraction (LACBED) patterns on the <011‾0> zone axis were displayed with the absence of two-fold symmetry axis along the [0001] direction in an individual twin domain but with a 180° rotation relation along the c direction between a pair of the twin domains. Related to the DT law, the LACBED pattern across a DT boundary showed the higher six-fold rotation symmetry, which is the same as that of the high-temperature β quartz. The off-axis LACBED patterns displaying Bragg lines demonstrated no angular misfit over the twin boundary. This non-orientation misfit on the twin domains allows us to confirm the visualization mechanism of DT in ECCI. The different contrast of a pair of DT domains in the BSE images originates not from a misorientation between the two domains but from different diffraction intensities between positive and negative rhombohedral planes in quartz. The observation procedure from ECCI with SEM to LACBED with TEM (transmission electron microscope) imaging presented here is indispensable for a deep understanding of the role of twinning, ranging spatially from the micrometre scale for a SEM of the bulk specimen to the nanometre scale for a TEM of the interaction with crystal defects in deformation because of their optical invisibility in a conventional petrological microscopy. Following this procedure, dislocations on a rhombohedral plane were characterized in the vicinity of DTs in naturally deformed quartz. This result implies that non-basal slips, e.g. a rhombohedral slip system, i.e. 1/3<1‾1‾20>{101‾1} ({r}) and 1/3<11‾20>{101‾2} ({π}), were activated in the vicinity of DTs. The activity of dislocations on a non-basal plane resulted from the interaction between DTs and dislocations during plastic deformation.

Introduction Transplant renal vein thrombosis is a serious post‐transplant complication. We report a case in which a thrombus was found in the transplant renal vein and rescued the transplanted kidney utilizing interventional radiology. Case presentation A 56‐year‐old woman underwent ABO‐compatible living donor renal transplantation due to impaired renal function caused by IgA nephropathy. On postoperative Day 13, there was a finding on transplant renal echocardiography that appeared to be an interruption of peripheral renal blood flow in diastole. Contrast‐enhanced computed tomography revealed that the vein was occluded due to the hematoma, and thrombosis was observed within, and distal contrast showed regurgitation into the collateral vessels. The stenosis was breached and balloon dilation restored progressive blood flow through interventional radiology. Conclusion Although open surgical thrombectomy is mainly considered for treatment for transplant renal vein thrombosis, interventional radiology might be the alternative treatment option.

ABSTRACT DNA detection by agarose gel electrophoresis (AGE) is commonly used in molecular biology. AGE is a separation method that provides opportunities for students to learn about the topology and size of DNA molecules. Recently, several fluorescent dyes have been used for DNA staining owing to their convenience, safety, reduced toxicity, and high sensitivity. A blue light-emitting diode (LED) transilluminator is required to detect DNA using fluorescent dyes; however, the associated high cost may limit its availability in classrooms or small laboratories. Therefore, we have designed a simple, low-cost blue LED illuminator to enable easy assembly for instructors and students. We evaluated the performance of the proposed illuminator by observing fluorescent dye-stained DNA markers using AGE, revealing clear DNA marker bands. Despite its limited functionality, the ease of construction and affordability of the proposed illuminator make it sufficient for hands-on molecular biology training in classrooms, thereby enhancing the learning environment and educational efficiency.

ABSTRACT A 34-year-old man developed severe envenomation after being bitten by a Crotalus durissus (rattlesnake), which was treated with anticrotalic serum. Three weeks later, the patient reported paresthesia and neuropathic pain in the left hand, which had progressed to all four limbs. Electroneuromyography revealed asymmetric axonal sensorimotor multiple mononeuropathy. The patient was treated with prednisone, and six months later there was significant improvement in sensorimotor conduction. This is the first reported case of multiple mononeuropathy associated with C. durissus envenomation. Post-snake envenomation peripheral neuropathy is a rare complication requiring prompt recognition and treatment to optimize nerve function and enhance patient outcomes.

Helicobacter species are classified into enterohepatic and gastric species. Human infections with enterohepatic species have been reported mainly as bloodstream infections caused by H. cinaedi and H. fennelliae in the [...]

Abstract Background The Mt FUJI study was a multicenter, prospective, randomized, single‐blind, controlled trial comparing delivery catheter‐based and stylet‐based right ventricular (RV) lead placement at the RV septum. This study extended the follow‐up duration to 1 year after implantation. Methods Seventy patients with pacemaker indications for atrioventricular block were randomly assigned to the delivery catheter and stylet groups. We compared the mid‐term efficacy and safety between the two groups at 1 year after implantation. The primary outcome was the change in the left ventricular ejection fraction (LVEF), and the secondary outcomes were changes in brain natriuretic peptide (BNP) levels, lead parameters, paced QRS duration, and the incidence of adverse events. Results At the 1‐year follow‐up, no significant differences were observed in the changes in the LVEF (+1.0% ± 8.6% vs. +3.1% ± 8.1%, p = .332), BNP levels (+8.0 [−11.1, 26.5] pg/mL vs. −8.7 [−15.3, 13.2] pg/mL, p = .193), or lead performance between the delivery catheter and stylet groups. The QRS duration was significantly shorter in the delivery catheter group than in the stylet group (128 ± 23 ms vs. 146 ± 17 ms, p

Summary: Background and aims: Muscle mass is an important component of nutritional status. At intensive care unit (ICU) admission, ultrasound is an important tool to assess the muscle mass, but there are currently no established cut-off values. Therefore, we retrospectively analyzed cut-off values for an ultrasound-based muscle mass assessment at ICU admission. Methods: We retrospectively analyzed data collected in an observational study. These data included a muscle mass assessment of lower limb thickness and cross-sectional area (CSA), upper limb thickness and CSA, and diaphragm thickness at ICU admission. Skeletal muscle mass was calculated from computed tomography (CT) imaging of the third lumbar vertebra for comparison. Cut-off values were estimated from the relationship between the ultrasound-based muscle mass assessment and CT-derived skeletal muscle index at 7.0 kg/m2 in males and 5.4 kg/m2 in females. Results: Lower limb, upper limb, and diaphragm assessments included 89, 52, and 79 patients, respectively. The age was 70 ± 13 years and body mass index was 22.2 ± 4.4 kg/m2. Cut-off values were 22.5 mm (male) and 19.0 mm (female) for femoral thickness and 5.0 cm2 (male) and 4.5 cm2 (female) for rectus femoris CSA. Cut-off values were 26.9mm (male) and 20.6 mm (female) for upper limb thickness and 6.5 cm2 (male) and 4.0 cm2 (female) for biceps brachii CSA. Cut-off values were 1.8 mm (male) and 1.5 mm (female) for diaphragm. Conclusion: We proposed cut-off values for ultrasound-based muscle mass assessment at ICU admission. Further studies are needed to validate these cut-off values.

Abstract It is known that maternal immunoglobulins (Igs) are transferred to the offspring across the placenta. However, receiving maternal Igs, especially before the blood–brain barrier (BBB) is formed in the offspring’s brain, carries the risk of transferring some brain-reactive Igs. It is thus hypothesized that there may be some unknown benefit to the offspring’s brain that overweighs this risk. In this study, we show that the Ig detected in the embryonic/perinatal mouse brain is IgG not produced by the pups themselves, but is basically transferred from the mother across the placenta using the neonatal Fc receptor (FcRn) during embryonic stages. The amount of IgG in the brain gradually decreases after birth, and almost disappears within 3 weeks postnatally. IgG is detected on axon bundles, microglia, and some meningeal cells, including border-associated macrophages (BAMs), endothelial cells, and fibroblasts. Using Fcer1g knock-out (KO) mice, we show that BAMs and microglia receive maternal IgG in an Fc receptor γ chain (FcRγ)-dependent manner, but IgG on other meningeal cells and axon bundles is received independently of the FcRγ. These results suggest that maternal IgG may be used in multiple ways by different mechanisms. In maternal IgG-deficient mice, the number of interneurons in the cerebral cortex is not altered around birth but is reduced postnatally, suggesting that receipt of maternal IgG is necessary for the maintenance of cortical interneurons in the postnatal period. These data suggest that maternal IgG has an important function in the developing brain, where neither obvious inflammation nor infection is observed.

Abstract Lipid-mediated inflammation is involved in the development and malignancy of cancer. We previously demonstrated the existence of a novel oncogenic mechanism utilizing membrane lipids of extracellular vesicles in Epstein–Barr virus (EBV)-positive lymphomas and found that the lipid composition of lymphoma cells is skewed toward ω-3 fatty acids, which are anti-inflammatory lipids, suggesting an alteration in systemic lipid composition. The results showed that arachidonic acid (AA), an inflammatory lipid, was significantly reduced in the infected cells but detected at high levels in the sera of EBV-positive patients lead to the finding of the blockade of extracellular AA influx by downregulating FATP2, a long-chain fatty acid transporter that mainly transports AA in EBV-infected lymphoma cells. Low AA levels in tumor cells induced by downregulation of FATP2 expression confer resistance to ferroptosis and support tumor growth. TCGA data analysis and xenograft models have demonstrated that the axis plays a critical role in several types of cancers, especially poor prognostic cancers, such as glioblastoma and melanoma. Overall, our in vitro, in vivo, in silico, and clinical data suggest that several cancers exert oncogenic activity by maintaining their special lipid composition via extracellular blockade.