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Background: Total hip arthroplasty (THA) allows for the replacement of impaired parts of the hip joint with artificial ones. This study aimed to compare the differences in preoperative patient profiles, postoperative complications, and clinical outcomes of two patient groups: those who underwent THA for fractures and those who underwent THA electively for diseases such as osteoarthritis (OA) and avascular necrosis (AVN). Methods: We retrospectively analyzed the data of patients who underwent THA between March 2012 and December 2021. Of 232 patients, 173 patients who met the exclusion and inclusion criteria were included. Patients were divided into two groups (Group 1: 113 patients diagnosed with OA or AVN; Group 2: 60 patients diagnosed with hip fracture). Pre- and postoperative Visual Analogue Scale (VAS), Koval scores, and postoperative modified Harris Hip Score (mHHS) were used to assess clinical outcomes. Demographic data and postoperative complications of the two groups were compared. After surgery, a rehabilitation protocol was initiated. Results: Patients in Group 2 (fracture) had more preoperative comorbidities than those in Group 1 (elective). Follow-up months are 26.22 ± 19.78 (Group 1), and 27.42 ± 17.02 (Group 2) respectively (P > 0.05). There were no statistical differences in the prevalence of postoperative complications between two groups (P > 0.05). Compared with Group 1(elective), Group 2(fracture) showed lower VAS (P < 0.01) at last follow-up, and no difference in Koval score (P = 0.77) and mHHS (P = 0.96) at last follow-up. Conclusion: Considering the characteristics of the two groups and their perioperative multidisciplinary care, THA for hip fractures can provide good clinical results compared to those with elective THA.
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Porcine delta-coronavirus (PDCoV) spillovers were recently detected in febrile children, underscoring the recurrent zoonoses of divergent CoVs. To date, no vaccines or specific therapeutics are approved for use in humans against PDCoV. To prepare for possible future PDCoV epidemics, we isolated PDCoV spike (S)-directed monoclonal antibodies (mAbs) from humanized mice and found that two, designated PD33 and PD41, broadly neutralized a panel of PDCoV variants. Cryoelectron microscopy (cryo-EM) structures of PD33 and PD41 in complex with the S receptor-binding domain (RBD) and ectodomain trimer revealed the epitopes recognized by these mAbs, rationalizing their broad inhibitory activity. We show that both mAbs competitively interfere with host aminopeptidase N binding to neutralize PDCoV and used deep-mutational scanning epitope mapping to associate RBD antigenic sites with mAb-mediated neutralization potency. Our results indicate a PD33-PD41 mAb cocktail may heighten the barrier to escape. PD33 and PD41 are candidates for clinical advancement against future PDCoV outbreaks.
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Background: Medullary thyroid carcinoma (MTC) has a poorer prognosis than differentiated thyroid cancers; however, comprehensive data on the long-term outcomes of MTC remain scarce. This study investigated the extended clinical outcomes of MTC and aimed to identify prognostic factors. Methods: Patients diagnosed with MTC between 1980 and 2020 were retrospectively reviewed. Their clinical characteristics, longterm clinical outcomes, and prognostic factors for recurrence and mortality were analyzed. Results: The study included 226 patients (144 women, 82 men). The disease-specific survival (DSS) rates for all MTC patients at 5-, 10-, 20-, and 30-year intervals were 92.7%, 89.4%, 74.3%, and 68.1%, respectively. The recurrence-free survival (RFS) rates were 71.1%, 56.1%, 40.2%, and 32.1% at these intervals. DSS was comparable between the groups from 1980-2009 and 2010-2020 (P=0.995); however, the 1980-2009 group had significantly lower RFS rates (P=0.031). The 2010-2020 group exhibited greater extents of surgical and lymph node dissection (P=0.003) and smaller tumors (P=0.003). Multivariate analysis identified extrathyroidal extension as the strongest prognostic factor for both RFS and DSS. Age >55 years and tumor size of ≥2 cm were also significant prognostic factors for DSS, while hereditary disease and lymph node metastasis were significant for RFS. Survival analysis after propensity-score matching of rearranged during transfection (RET)-negative and non-screened RET-positive groups showed comparable DSS but longer RFS in the RET-negative group. Conclusion: Extrathyroidal extension was identified as the strongest prognostic factor for RFS and DSS. Older age and larger tumor size were associated with decreased DSS, while RET mutation and lymph node metastasis significantly impacted RFS.
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BACKGROUND: The tall cell variant of papillary thyroid cancer generally has a worse prognosis compared with the classical variant. Thyroid GuidePx is a genomic classifier capable of classifying papillary thyroid cancer into 3 molecular subtypes using fine-needle aspirate. Type 1 and 2 have low recurrence rates, particularly in early tumors (1-4 cm and N0). Type 3 is characterized by aggressive biology and high recurrence rates regardless of size and lymph node status. The study examines the interaction of tall cell variant histology with Thyroid GuidePx risk stratification. METHODS: Gene expression data from 736 patients (The Cancer Genome Atlas, Canada, and South Korea), were submitted to the Thyroid GuidePx classifier. Results across the 3 molecular subtypes were further dichotomized into "early" papillary thyroid cancer (tumor size 1-4 cm and N0) (n = 369; 51%) or "advanced" papillary thyroid cancer (n = 359; 49%). Structural recurrence was the primary outcome measure in our analysis. Transcriptomic and genomic analysis was conducted to explore what biological differences could account for clinical differences between tall cell variant and non- tall cell variants. RESULTS: Thyroid GuidePx identified 369 early papillary thyroid cancers: 129 (35%) type 1, 168 (45.5%) type 2, and 72 (19.5%) type 3. The recurrence rates for early type 1, type 2, and type 3 papillary thyroid cancers were 3.9%, 1.9%, and 19.4%, respectively. There were no type 1 tall cell variants. In type 2 papillary thyroid cancers, the incidence of tall cell variant was greater in advanced than early papillary thyroid cancers (10.2% vs 4.2%, P = .04). Notably, none of the 7 early type 2 tall cell variants recurred. In type 3 papillary thyroid cancers, the prevalence of tall cell variants was similar in early and advanced tumors (10% vs 9%, NS). When compared with non-tall cell variants, early type 3 tall cell variants trended toward greater recurrence (28.6% vs 18.5%, not significant) whereas advanced type 3 tall cell variants had a significantly greater recurrence rate (50% vs 28.6%, P = .01). Biologically, type 3 tall cell variants had had a pronounced enrichment in cell proliferation, epithelial-mesenchymal transition, invasion, and inflammation. CONCLUSION: Thyroid GuidePx reliably identifies a low-risk subgroup (early type 1 and early type 2 papillary thyroid cancers) for which conservative procedures would be appropriate. Tall cell variants in this subgroup are uncommon (1.2%), and none of the tall cell variants in this subgroup recurred. Type 3 papillary thyroid cancers have greater recurrence rates in both early and advanced papillary thyroid cancers. Tall cell variant appears to further increase recurrence in this subgroup.
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This study investigates the relationship between institutional investors and the inventory performance of companies engaged in mergers and acquisitions (M&As). Specifically, we examine the role of institutional ownership in the selection of target firms and their post-M&A performance. Additionally, we analyze how the effects of institutional investors vary based on their investment horizons and strategies. Our regression analysis reveals that acquiring firms with a large proportion of short-term institutional investors are more inclined to target firms with low inventory levels. This tendency stems from the preference of short-term institutional investors for better current operational performance, which drives decision-makers to merge with leaner firms. In contrast, acquiring firms with long-term institutional investors are more focused on performance improvement, even if the target firms have large inventories at the time of the M&A.
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Transcriptional enhanced associate domain (TEAD) transcription factors undergo auto-palmitoylation, which is critical to mediate their function and maintain stability. Targeting the palmitate binding pocket of TEAD holds considerable promise for drug discovery, and it can be characterised into three components: a conserved cysteine, a hydrophobic main pocket, and a hydrophilic side pocket. Endogenous palmitate and several known TEAD inhibitors interact with the cysteine and hydrophobic residues in the deep hydrophobic pocket. We anticipate that precise targeting of the polar side pocket could facilitate the discovery of inhibitors with enhanced potencies and properties. Herein, we selected niflumic acid as the core scaffold suitable for targeting the three characteristic components of TEAD palmitate pocket. Reversible and irreversible compounds with substituents capable of directing each part of the palmitate pocket were designed. The newly synthesised compounds inhibited the palmitoylation and transcriptional activity of TEAD and elicited growth-inhibitory effects against several carcinomas, including mesothelioma.
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Antineoplásicos , Proliferación Celular , Relación Dosis-Respuesta a Droga , Diseño de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Ácido Niflúmico , Factores de Transcripción , Humanos , Relación Estructura-Actividad , Estructura Molecular , Proliferación Celular/efectos de los fármacos , Ácido Niflúmico/farmacología , Ácido Niflúmico/química , Ácido Niflúmico/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/metabolismo , Factores de Transcripción de Dominio TEA , Proteínas de Unión al ADN/antagonistas & inhibidores , Proteínas de Unión al ADN/metabolismo , Proteínas de Unión al ADN/química , Línea Celular TumoralRESUMEN
Background: Renal function deterioration during systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is a long-term concern in treatment planning. Although hypertension (HTN) and diabetes mellitus (DM) are the most common factors that affect chronic kidney disease (CKD) development and progression, their impact on renal function during targeted therapy is unclear. This study investigated whether DM and HTN were associated with a decline in renal function during first-line targeted therapy for mRCC. Methods: This retrospective multicenter study analyzed patients receiving first-line targeted therapy for mRCC. They were classified as follows: group 1: HTN-, DM-; group 2: HTN+, DM-; group 3: HTN-, DM+; and group 4: HTN+, DM+. Changes in renal function and factors affecting progression to stage 4 CKD after targeted therapy were analyzed. Results: Among the 424 enrolled patients, 303 (71.5%) and 121 (28.5%) were treated with sunitinib and pazopanib, respectively [median duration: 10.3 months, interquartile range (IQR), 3.1-37.0 months]. Although all groups showed a decreased mean estimated glomerular filtration rate (eGFR) after treatment (P<0.001 for group 1, group 2, and group 4, P=0.02 for group 3, respectively), there were no significant differences in changes in eGFR (∆eGFR) between groups (P=0.10). However, actual renal function change calculated using percent ∆eGFR (%∆eGFR) showed differences between groups (P=0.02); the %∆eGFR of group 4 was significantly lower compared with group 1 (P=0.008). The mean progression time to stage 4 CKD in group 4 (38.6 months) was significantly shorter compared to the other groups (P<0.001). Multivariate analysis identified increased age (P=0.008), increased number of metastatic sites (P=0.047), and DM and HTN coexistence (P<0.001) as predictors of progression to stage 4 CKD. Conclusions: Patients with DM and HTN experienced further decline in renal function and had a higher risk of progression to stage 4 CKD after targeted therapy compared to patients without these risk factors. Recognition and proactive management of DM and HTN are necessary to facilitate the proper administration of life-prolonging oncological treatments.
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BACKGROUND & AIMS: Hyperglycemia is associated with an increased risk of gallbladder cancer (GBC), potentially by inhibiting gallbladder motility and inducing prolonged cholestasis. Although intermediate hyperglycemia (or prediabetes) is highly reversible, evidence is lacking about whether prediabetes persistence or remission is associated with an altered GBC risk. METHODS: This nationwide cohort study included 6058,662 adults without diabetes or cancer who underwent national health examinations twice in 2-year intervals between 2009 (S1) and 2011 (S2) and were followed-up until 2018. Prediabetes was defined as a fasting plasma glucose level of 100-125 mg/dL. We categorized changes in prediabetes status into: stable normoglycemia, new-onset prediabetes, prediabetes remission, and persistent prediabetes groups. GBC risk was estimated using Cox proportional hazards models, after adjusting for potential confounders. RESULTS: During 38.6 million person-years (median 6.4 years) of follow-up, 1349 new GBC cases were identified. Among 1409,474 individuals with prediabetes at S1, 768,515 achieved prediabetes remission at S2, outnumbering the 640,959 individuals with persistent prediabetes. GBC incidence probability was consistently higher among individuals with persistent prediabetes than in individuals with stable normoglycemia or prediabetes remission (all log-rank P < 0.01). Compared with stable normoglycemia, persistent prediabetes was associated with increased GBC risk (adjusted hazard ratio [aHR], 95 % CI: 1.21, 1.04 to 1.41). The aHRs of GBC were 1.14 (95 % CI, 0.99 to 1.33) and 1.03 (95 % CI, 0.88 to 1.21) for new-onset prediabetes and prediabetes remission, respectively. CONCLUSIONS: Individuals with persistent prediabetes had a significantly increased risk of GBC, whereas those with prediabetes remission had no increased risk. Achieving prediabetes remission has a significant potential to reduce the risk of GBC.
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Purpose: Bariatric surgery is the gold standard for the treatment of morbid obesity, but postoperative pain impedes recovery. Currently available pain-recovery treatments have patient safety concerns. This led to a noninferiority study of Welpass (Genewel Co., Ltd.) vs. On-Q PainBuster (B. Braun), each used alongside a traditional method of continuous local anesthetic administration, in patients undergoing bariatric surgery. Methods: In this single-center prospective randomized clinical trial, patients were assigned in a 1:1 ratio to the treatment group (Welpass) and the control group (On-Q PainBuster), with ketorolac administered as needed after surgery according to the protocol. To assess efficacy, the total amount of ketorolac used up to 72 hours postoperatively was measured. Additionally, ketorolac usage and numerical rating scales (NRS) were recorded at 6, 24, 48, and 72 hours after operation. Results: The total amounts of ketorolac used in the 72 hours postoperatively were 188.0 ± 84.6 mg in the treatment group and 198.7 ± 50.0 mg in the control group. The efficacy of the treatment group was noninferior to that of the control group, since the lower limit (-29.9 mg) of the confidence interval for the difference with the control group was greater than the prespecified noninferiority margin (-35.0 mg). Furthermore, when the NRS was evaluated after bariatric surgery, there was no significant difference in scores between the 2 groups at each time point (P > 0.05). Conclusion: We found no difference in effect on pain between the 2 groups, supporting the use of Welpass in clinical practice for pain management in patients undergoing bariatric surgery.
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Microorganisms can be engineered to sustainably produce a variety of products including fuels, pharmaceuticals, materials, and food. However, highly engineered strains often result in low production yield, due to undesired effects such as metabolic burden and the toxicity of intermediates. Drawing inspiration from natural ecosystems, the construction of a synthetic community with division of labor can offer advantages for bioproduction. This approach involves dividing specific tasks among community members, thereby enhancing the functionality of each member. In this study, we identify six pairs out of fifteen composed of six auxotrophs of Yarrowia lipolytica that spontaneously form robust syntrophic and synergistic communities. We characterize the stability and growth dynamics of these communities. Furthermore, we validate the existence of syntrophic interactions between two yeast species, Y. lipolytica and Saccharomyces cerevisiae, and find a strain combination, Δtrp2 and Δtrp4, forming a stable syntrophic community between two species. Subsequently, we introduce a 3-hydroxypropionic acid (3-HP) biosynthesis pathway into the syntrophic community by dividing the pathway among different strains. Our results demonstrate improved production of 3-HP in both intra- and interspecies communities compared to monocultures. Our results show the stable formation of synthetic syntrophic communities, and their potential in improving bioproduction processes.
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Ingeniería Metabólica , Saccharomyces cerevisiae , Yarrowia , Yarrowia/metabolismo , Yarrowia/genética , Yarrowia/crecimiento & desarrollo , Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/genética , Ingeniería Metabólica/métodos , Ácido Láctico/metabolismo , Ácido Láctico/biosíntesis , Interacciones Microbianas , Biología Sintética/métodosRESUMEN
PURPOSE: Hemophilia A is a genetic disorder characterized by a lack of factor VIII (FVIII). Emicizumab, a recombinant humanized bispecific monoclonal antibody, mimics the function of FVIII. In this article, we present data on an initial real-world evaluation of emicizumab use in Korean children with severe hemophilia A without inhibitors. METHODS: This study was conducted from June 2020 to March 2024 at 4 centers in Korea. The participants were pediatric patients with severe hemophilia A without inhibitors who had received emicizumab treatment for over 6 months. The mean and median annualized bleeding rates (ABRs) and mean and median annual joint bleeding rates (AJBRs) were compared. RESULTS: Each of the 21 patients in the study received an emicizumab loading regimen of 3 mg/kg weekly for 4 weeks, followed by a modified maintenance regimen of which 2 patients (9.5%) received a 1.5 mg/kg weekly dose, 3 patients (14.3%) received a 6 mg/kg dose every 4 weeks, and the remaining 16 patients (76.2%) received a 3 mg/kg dose every 2 weeks. Before emicizumab prophylaxis initiation, the mean and median ABRs for all patients were 7.04 (SD ± 5.83) and 6.52 (range 0-21.74), respectively. After receiving emicizumab treatment, the mean and mediam ABRs decreased to 0.41 and zero, respectively. Additionally, 85.7% of the patients achieved no bleeding events within 6 months of starting the treatment. CONCLUSION: These first real-world data in Korea indicate that emicizumab is effective and safe for pediatric patients with severe hemophilia A without inhibitors.
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Breast cancer remains a significant health concern, with triple-negative breast cancer (TNBC) being an aggressive subtype with poor prognosis. Epithelial-mesenchymal transition (EMT) is important in early-stage tumor to invasive malignancy progression. Snail, a central EMT component, is tightly regulated and may be subjected to proteasomal degradation. We report a novel proteasomal independent pathway involving chaperone-mediated autophagy (CMA) in Snail degradation, mediated via its cytosolic interaction with HSC70 and lysosomal targeting, which prevented its accumulation in luminal-type breast cancer cells. Conversely, Snail predominantly localized to the nucleus, thus evading CMA-mediated degradation in TNBC cells. Starvation-induced CMA activation downregulated Snail in TNBC cells by promoting cytoplasmic translocation. Evasion of CMA-mediated Snail degradation induced EMT, and enhanced metastatic potential of luminal-type breast cancer cells. Our findings elucidate a previously unrecognized role of CMA in Snail regulation, highlight its significance in breast cancer, and provide a potential therapeutic target for clinical interventions.
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Autofagia Mediada por Chaperones , Transición Epitelial-Mesenquimal , Lisosomas , Estabilidad Proteica , Factores de Transcripción de la Familia Snail , Animales , Femenino , Humanos , Ratones , Autofagia , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Línea Celular Tumoral , Proteínas del Choque Térmico HSC70/metabolismo , Lisosomas/metabolismo , Metástasis de la Neoplasia , Proteolisis , Factores de Transcripción de la Familia Snail/metabolismo , Neoplasias de la Mama Triple Negativas/metabolismo , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evolution has resulted in viral escape from clinically authorized monoclonal antibodies (mAbs), creating a need for mAbs that are resilient to epitope diversification. Broadly neutralizing coronavirus mAbs that are sufficiently potent for clinical development and retain activity despite viral evolution remain elusive. We identified a human mAb, designated VIR-7229, which targets the viral receptor-binding motif (RBM) with unprecedented cross-reactivity to all sarbecovirus clades, including non-ACE2-utilizing bat sarbecoviruses, while potently neutralizing SARS-CoV-2 variants since 2019, including the recent EG.5, BA.2.86, and JN.1. VIR-7229 tolerates extraordinary epitope variability, partly attributed to its high binding affinity, receptor molecular mimicry, and interactions with RBM backbone atoms. Consequently, VIR-7229 features a high barrier for selection of escape mutants, which are rare and associated with reduced viral fitness, underscoring its potential to be resilient to future viral evolution. VIR-7229 is a strong candidate to become a next-generation medicine.
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This corrects the article on p. 327 in vol. 24, PMID: 38960891.
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Introduction: Both regimens of TAS-102 (trifluridine/tipiracil) with and without bevacizumab are considered standard options for salvage treatment in patients with refractory metastatic colorectal cancer. Materials and methods: This analysis included patients with metastatic colorectal cancer who received either TAS-102 plus bevacizumab or TAS-102 alone between July 2022 and November 2023 at Samsung Medical Center. We evaluated the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and safety profile of both regimens. Results: In total, 139 patients were included in this analysis. Median age was 60.8 years, and median number of previous lines of therapy was four (range: 2.45-6.55). More than half of the subjects (56.8%) had RAS mutations and 92.9% received previous anti-VEGF therapy. 83 (59.7%) patients received the combination of TAS-102 and bevacizumab and 56 (40.3%) received TAS-102 alone. The number of patients with prior regorafenib treatment was 14 in the TAS-102 with bevacizumab group and 5 in the TAS-102 alone group. The disease control rate was 51.8% in the combination group and 32.1% in the TAS-102 alone group. The median PFS was 3.3 months (95% CI, 2.7-6.6) in the combination group and 2.5 months (95% CI, 2.0-3.8) in the TAS-102 alone group (HR, 0.56; 95% CI, 0.38-0.82; p=0.003). The median OS in these two groups was 10.8 months (95% CI, 8.4-NA) and 6.0 months (95% CI, 4.8-9.8), respectively (HR, 0.62; 95% CI, 0.40-0.97, p=0.033). In the exploratory analysis of TAS-102 + Bev group, patients with the KRAS G12 mutation had inferior OS compared to those without the mutation (HR, 2.01, 95% CI, 1.04-3.90, p=0.035). Commonly observed adverse events were hematologic-related, including neutropenia, anemia, and thrombocytopenia, as well as nausea. While any grade neutropenia was observed at similar frequencies in the two groups (57.8% and 57.1%), grade 3 or higher neutropenia was more frequent in the combination group than the TAS-102 alone group (31.3% vs. 17.9%). Among patients who received subsequent anticancer therapy after treatment failure, 74.1% received regorafenib. Conclusions: The combination of TAS-102 and bevacizumab resulted in a better survival outcome than TAS-102 monotherapy, consistent with previous studies. This analysis supports the use of the combination of TAS-102 and bevacizumab as the best therapeutic option for patients with refractory metastatic colorectal cancer in clinical practice.
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Marine debris, particularly microplastics, is an important environmental problem for Indonesia, impacting vast coastline and diverse marine ecosystems. However, little is known about the microplastics flux to the seafloor in the Indonesian Seas. This study employs HYCOM data and Lagrangian particle tracking model to analyze the distribution of microplastics flux to the seafloor from 68 rivers in Indonesia. Microplastics accumulation can be found in coastal waters near major islands, typically within 50-100 km of the coast. Accumulation regions within the Fisheries Management Area (FMA) in Indonesia are mostly located in Karimata Strait, Java Sea and South Java. This study highlights the importance of understanding sinking particles behavior for effective waste management strategies, as well as for mitigating environmental impacts in Indonesian waters.
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To identify genetic influences on subfoveal choroidal thickness of older adults using a genome-wide association study (GWAS). We recruited 300 participants from the population-based Korean Longitudinal Study on Health and Aging (KLoSHA) and Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD) cohort studies and 500 participants from the Bundang age-related macular degeneration (AMD) cohort study dataset. We conducted a GWAS on older adult populations in the KLoSHA and KLOSCAD cohorts. Single nucleotide polymorphisms (SNPs) associated with choroidal thickness were identified with P values < 1.0 × 10-4 in both the right and left eyes, followed by validation using the Bundang AMD cohort dataset. This association was further confirmed by a functional in vitro study using human umbilical vein endothelial cells (HUVECs). The ages of the cohort participants in the discovery and validation datasets were 73.5 ± 3.3 and 71.3 ± 7.9 years, respectively. In the discovery dataset, three SNPs (rs1916762, rs7587019, and rs13320098) were significantly associated with choroidal thickness in both eyes. This association was confirmed for rs1916762 (genotypes GG, GA, and AA) and rs7587019 (genotypes GG, GA, and AA), but not for rs13320098. The mean choroidal thickness decreased by 56.7 µm (AA, 73.8%) and 31.1 µm (GA, 85.6%) compared with that of the GG genotype of rs1916762, and by 55.4 µm (AA, 74.2%) and 28.2 µm (GA, 86.7%) compared with that of the GG genotype of rs7587019. The SNPs rs1916762 and rs7587019 were located close to the FAM124B gene near its cis-regulatory region. Moreover, FAM124B was highly expressed in vascular endothelial cells. In vitro HUVEC experiments showed that the inhibition of FAM124B was associated with decreased vascular endothelial proliferation, suggesting a potential mechanism of choroidal thinning. FAM124B was identified as a susceptibility gene affecting subfoveal choroidal thickness in older adults. This gene may be involved in mechanisms underlying retinal diseases associated with altered choroidal thickness, such as age-related macular degeneration.
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Coroides , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Humanos , Coroides/patología , Anciano , Masculino , Femenino , Estudios Longitudinales , Anciano de 80 o más Años , Degeneración Macular/genética , Degeneración Macular/patología , Células Endoteliales de la Vena Umbilical Humana , Estudios de Cohortes , Predisposición Genética a la Enfermedad , GenotipoRESUMEN
INTRODUCTION: Cardiovascular autonomic neuropathy (CAN) is a chronic complication of diabetes. As obesity is a major risk factor for CAN, we hypothesized that metabolic bariatric surgery (MBS) could improve CAN indices in Korean patients with obesity. MATERIALS AND METHODS: Patients who underwent bariatric surgery between February 2020 and June 2022 were prospectively recruited. CAN was conducted once before surgery and again after surgery, using the Ewing method and heart rate variability (HRV) analysis (standard deviation of the NN interval [SDNN], root mean square of successive RR interval difference [RMSSD], and spectral analysis). RESULTS: A total of 47 patients were included. The mean age was 39.8 ± 8.7 years, 15 (31.9%) were male, and 26 (55.3%) had diabetes. Resting HR before surgery was 81.0 ± 12.3 bpm, which decreased significantly to 68.0 ± 9.3 bpm after surgery (P < 0.001). Changes in HR and BP according to the Valsalva maneuver, postural changes, and handgrip were not significantly different before and after surgery. However, SDNN significantly increased from 25.2 [15.1, 33.5] to 38.0 [25.4, 45.0] ms (P < 0.001), and RMSSD also significantly increased from 17.0 [9.2, 31.8] to 28.2 [15.3, 45.6] ms (P = 0.001). Both low-frequency power (LF) and high-frequency power (HF) increased significantly, and the LF/HF ratio significantly decreased from 2.1 ± 1.6 to 1.3 ± 1.3 (P = 0.010). Loss of weight, fat mass, and lean body mass were independently associated with improving the HRV variables. CONCLUSIONS: MBS improved HRV variables, and these changes were mainly associated with postoperative weight loss.