Hyperhomocysteinemia-induced VCID results in visual deficits, reduced neuroinflammation and vascular alterations in the retina.

Over recent years, the retina has been increasingly investigated as a potential biomarker for dementia. A number of studies have looked at the effect of Alzheimer's disease (AD) pathology on the retina and the associations of AD with visual deficits. However, while OCT-A has been explored as a biomarker of cerebral small vessel disease (cSVD), studies identifying the specific retinal changes and mechanisms associated with cSVD are lacking.

Lewy body diseases and the gut.

Gastrointestinal (GI) involvement in Lewy body diseases (LBDs) has been observed since the initial descriptions of patients by James Parkinson. Recent experimental and human observational studies raise the possibility that pathogenic alpha-synuclein (⍺-syn) might develop in the GI tract and subsequently spread to susceptible brain regions. The cellular and mechanistic origins of ⍺-syn propagation in disease are under intense investigation.

Safety and validity of extracorporeal fenestration and in situ fenestration in patients with aortic disease involving the left subclavian artery: a prospective, single-center, randomized controlled study.

Background: Thoracic aortic pathologies involving the aortic arch are a great challenge for vascular surgeons. Maintaining the patency of supra-aortic branches while excluding the aortic lesion remains difficult. Thoracic EndoVascular Aortic Repair (TEVAR) with fenestrations provides a feasible and effective approach for this type of disease.

Graft-repositioning technique using infusion and small bubbles during Descemet's membrane endothelial keratoplasty.

Background: Descemet's membrane endothelial keratoplasty (DMEK) is a highly effective procedure for corneal endothelial dysfunction; however, once a DMEK graft is deployed, repositioning can be challenging. Therefore, this study aimed to evaluate the efficacy of a technique that utilizes infusion and small air bubbles to reposition a misaligned deployed graft.

Methods: This retrospective interventional case series enrolled patients who underwent DMEK between January 2022 and July 2023, including cases where the DMEK graft was attached and unfolded in off-center positions".

CircUCK2(2,3) promotes cancer progression and enhances synergistic cytotoxicity of lenvatinib with EGFR inhibitors via activating CNIH4-TGFα-EGFR signaling.

Background: Circular (circ)RNAs have emerged as crucial contributors to cancer progression. Nonetheless, the expression regulation, biological functions, and underlying mechanisms of circRNAs in mediating hepatocellular carcinoma (HCC) progression remain insufficiently elucidated.

Methods: We identified circUCK2(2,3) through circRNA sequencing, RT-PCR, and Sanger sequencing.

Peripheral nerve regeneration using a bioresorbable silk fibroin-based artificial nerve conduit fabricated via a novel freeze-thaw process.

While silk fibroin (SF) obtained from silkworm cocoons is expected to become a next-generation natural polymer, a fabrication method for SF-based artificial nerve conduits (SFCs) has not yet been established. Here, we report a bioresorbable SFC, fabricated using a novel freeze-thaw process, which ensures biosafety by avoiding any harmful chemical additives. The SFC demonstrated favorable biocompatibility (high hydrophilicity and porosity with a water content of > 90%), structural stability (stiffness, toughness, and elasticity), and biodegradability, making it an ideal candidate for nerve regeneration.

Toward a biological definition of neuronal and glial synucleinopathies.

Cerebral accumulation of alpha-synuclein (αSyn) aggregates is the hallmark event in a group of neurodegenerative diseases-collectively called synucleinopathies-which include Parkinson's disease, dementia with Lewy bodies and multiple system atrophy. Currently, these are diagnosed by their clinical symptoms and definitively confirmed postmortem by the presence of αSyn deposits in the brain. Here, we summarize the drawbacks of the current clinical definition of synucleinopathies and outline the rationale for moving toward an earlier, biology-anchored definition of these disorders, with or without the presence of clinical symptoms.

Concurrent inhibition of p300/CBP and FLT3 enhances cytotoxicity and overcomes resistance in acute myeloid leukemia.

FMS-like tyrosine kinase-3 (FLT3), a class 3 receptor tyrosine kinase, can be activated by mutations of internal tandem duplication (FLT3-ITD) or point mutations in the tyrosine kinase domain (FLT3-TKD), leading to constitutive activation of downstream signaling cascades, including the JAK/STAT5, PI3K/AKT/mTOR and RAS/MAPK pathways, which promote the progression of leukemic cells. Despite the initial promise of FLT3 inhibitors, the discouraging outcomes in the treatment of FLT3-ITD-positive acute myeloid leukemia (AML) promote the pursuit of more potent and enduring therapeutic approaches. The histone acetyltransferase complex comprising the E1A binding protein P300 and its paralog CREB-binding protein (p300/CBP) is a promising therapeutic target, but the development of effective p300/CBP inhibitors faces challenges due to inherent resistance and low efficacy, often exacerbated by the absence of reliable clinical biomarkers for patient stratification.

Neonatology fellow assessment and evaluation: embracing the word salad of CBME, EPAs, and milestones.

Neonatal-perinatal medicine (NPM) fellowship training aims to educate fellows and enable them to move into successful independent neonatal practice. To reach this goal, every fellow must acquire a wide range of clinical, scholarly, and professional skills that require assessment and evaluation by the fellowship program. The assessment and evaluation of fellow progression and promotion must rely on a rigorous educational framework.

Targeting ABCD1-ACOX1-MET/IGF1R axis suppresses multiple myeloma.

Multiple myeloma (MM) remains an incurable hematological malignancy that necessitates the identification of novel therapeutic strategies. Here, we report that intracellular levels of very long chain fatty acids (VLCFAs) control the cytotoxicity of MM chemotherapeutic agents. Inhibition of VLCFA biosynthesis reduced cell death in MM cells caused by the proteasome inhibitor, bortezomib.

A single-cell RNA sequencing dataset of peripheral blood cells in long COVID patients on herbal therapy.

Following the coronavirus disease 2019 (COVID-19) pandemic, the rise of long COVID, characterized by persistent respiratory and cognitive dysfunctions, has become a significant health concern. This leads to an increased role of complementary and alternative medicine in addressing this condition. However, our comprehension of the effectiveness and safety of herbal medicines for long COVID remains limited.

A study on the effect of blue light on kidney stone formation in rats via the brain-kidney axis.

Kidney stones, a common urological disease, may involve the brain-kidney axis in their formation, though the specific mechanism remains unclear. This study aimed to investigate the effects of blue light on relevant metabolic indicators and oxidative stress status in rats with kidney stones through the brain-kidney axis. A rat model of kidney stones was established by administering 1% ethylene glycol and 2% ammonium chloride.

Fish oil-loaded silver carp scale gelatin-stabilized emulsions with vitamins for the delivery of curcumin.

The encapsulation of curcumin in the emulsions has attracted much attention in functional food development. Herein, the fish oil-loaded silver carp scale gelatin-stabilized emulsions with vitamins were explored for the delivery of curcumin. The curcumin encapsulation had no obvious effect on the formation, storage stability, lipid oxidation, and in vitro droplet digestion behaviors of the emulsions.

Oligodendrocyte precursor cells facilitate neuronal lysosome release.

Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes.

Stroma-derived Dickkopf-1 contributes to the suppression of NK cell cytotoxicity in breast cancer.

Mechanisms related to tumor evasion from NK cell-mediated immune surveillance remain enigmatic. Dickkopf-1 (DKK1) is a Wnt/β-catenin inhibitor, whose levels correlate with breast cancer progression. We find DKK1 to be expressed by tumor cells and cancer-associated fibroblasts (CAFs) in patient samples and orthotopic breast tumors, and in bone.

Effects of fluconazole and amphotericin B in the control of cryptococcal pneumonia in vivo.

Cryptococcal pneumonia is a severe fungal infection of the respiratory system, predominantly caused by Cryptococcus neoformans. Its incidence is increasing, driven by evolving pathogen dynamics and heightened susceptibility among patient populations. This investigation aimed to assess the combined therapeutic efficacy of Fluconazole and Amphotericin B for cryptococcal pneumonia and to explore the roles of miR-15b and TGF-β1 in modulating treatment response.

High glucose/ChREBP-induced Hif-1α transcriptional activation in CD4 T cells reduces the risk of diabetic kidney disease by inhibiting the Th1 response.

Aims/hypothesis: Diabetic kidney disease (DKD) features intrarenal inflammation, in which T cells play a part. Hypoxia-inducible factor-1α (HIF-1α), a key transcription factor regulating cellular responses to hypoxia, is reportedly involved in the course of inflammation. The role of HIF-1α in DKD has been investigated, but the conclusions are controversial so far.

COVID-19 and influenza vaccine Hesitancy among adults hospitalized in the United States, 2019-2022.

Background: Understanding similarities and differences between hesitancy for influenza and COVID-19 vaccines could facilitate strategies to improve public receptivity toward vaccination.

Methods: We compared hesitancy for COVID-19 vaccines during the first 13 months of availability (January 2021-January 2022) with hesitancy for influenza vaccines in the 15 months prior to COVID-19 vaccine availability (October 2019-December 2020) among adults hospitalized with acute respiratory illness at 21 hospitals in the United States. We interviewed patients regarding vaccination status, willingness to be vaccinated, and perceptions of vaccine safety and efficacy.

RNA interference in protozoan parasites and its application.

RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression, via small RNA triggers derived from double-stranded RNA that can target specific genes; it is a natural process that plays a role in both the regulation of protein synthesis and in immunity. Discovery of RNAi by Fire and Mello in 1998 had a profound impact on unraveling novel aspects of eukaryotic biology. RNA interference (RNAi) has proven to be an immensely useful tool for studying gene function and validation of potential drug targets in almost all organisms.

Balloon-mounted versus self-expandable stent in failed neurothrombectomy: a post hoc analysis of the SAINT study.

Background: Previous studies have shown that when thrombectomy has failed, rescue intracranial stenting is associated with better clinical outcomes compared with failed reperfusion. However, comparative data regarding stent type are lacking.

Objective: To compare the procedural and clinical outcomes of balloon-mounted stents (BMS) with those of self-expandable stents (SES).

Comparative efficacy and safety of stent retrievers as a bailout strategy following failed contact aspiration technique in acute stroke thrombectomy.

Background: The contact aspiration (CA) technique is often used to perform endovascular thrombectomy (EVT) for acute ischemic stroke (AIS); however, rescue strategies are necessary if CA fails to achieve recanalization. This study investigates the outcomes of incorporating stent retriever (SR) thrombectomy in the rescue strategy following failed CA.

Methods: EVT patients with failed CA attempts were identified from a large multicenter registry and stratified by rescue technique: CA alone or incorporating SR in the rescue strategy.

Impact of genetic polymorphisms and drug-drug interactions mediated by carboxylesterase 1 on remimazolam deactivation.

Remimazolam (Byfavo, Acacia Pharma), a recent Food and Drug Administration-approved ester-linked benzodiazepine, offers advantages in sedation, such as rapid onset and predictable duration, making it suitable for broad anesthesia applications. Its favorable pharmacological profile is primarily attributed to rapid hydrolysis, the primary metabolism pathway for its deactivation. Thus, understanding remimazolam hydrolysis determinants is essential for optimizing its clinical use.

Effectiveness and safety of tofacitinib calcineurin inhibitor in interstitial lung disease secondary to anti-MDA5-positive dermatomyositis: a multi-centre cohort study.

Objective: To compare the effectiveness and safety of tofacitinib (TOF) calcineurin inhibitor (CNI) as initial immunosuppressive regimen for anti-melanoma differentiation-associated gene 5-positive dermatomyositis with interstitial lung disease (MDA5+DM-ILD).

Methods: Adult Chinese patients with newly-diagnosed MDA5+DM-ILD (ILD course<3 months) from five tertiary referral centres between April 2014 and January 2023 were included for this retrospective cohort study. The primary effectiveness endpoint was lung transplantation-free survival within 1 year.