Helicobacter pylori Treatment and Gastric Cancer Risk After Endoscopic Resection of Dysplasia: A Nationwide Cohort Study.

BACKGROUND & AIMS: The study investigated the association between Helicobacter pylori treatment and the risk of gastric cancer after endoscopic resection of gastric dysplasia. METHODS: Patients who received endoscopic resection for gastric dysplasia between 2010 and 2020 from Korean nationwide insurance data were included. We verified the occurrence of new-onset gastric cancer and metachronous gastric neoplasm, which encompasses both cancer and dysplasia, >1 year after the index endoscopic resection. Newly diagnosed gastric cancer ≥3 years and ≥5 years was regarded as late-onset gastric cancer. A multivariable Cox regression model with H pylori treatment status as a time-dependent covariate was used to determine the risk of gastric cancer and metachronous gastric neoplasms. RESULTS: Gastric dysplasia in 69,722 patients was treated with endoscopy, and 49.5% were administered H pylori therapy. During the median 5.6 years of follow-up, gastric cancer developed in 2406 patients and metachronous gastric neoplasms developed in 3342 patients. Receiving H pylori therapy was closely related to lower gastric cancer risk (adjusted hazard ratio [aHR], 0.88; 95% confidence interval [CI], 0.80-0.96). H pylori treatment also significantly decreased metachronous gastric neoplasm development (aHR, 0.76; 95% CI, 0.70-0.82). Furthermore, H pylori therapy showed a prominent protective effect for late-onset gastric cancer development at ≥3 years (aHR, 0.84; 95% CI, 0.75-0.94) and ≥5 years (aHR, 0.80; 95% CI, 0.68-0.95). CONCLUSIONS: In this nationwide cohort, H pylori therapy after endoscopic resection of gastric dysplasia was associated with a reduced risk of gastric cancer and metachronous gastric neoplasm occurrence.

Meningeal lymphatic vessels at the skull base drain cerebrospinal fluid.

Recent work has shown that meningeal lymphatic vessels (mLVs), mainly in the dorsal part of the skull, are involved in the clearance of cerebrospinal fluid (CSF), but the precise route of CSF drainage is still unknown. Here we reveal the importance of mLVs in the basal part of the skull for this process by visualizing their distinct anatomical location and characterizing their specialized morphological features, which facilitate the uptake and drainage of CSF. Unlike dorsal mLVs, basal mLVs have lymphatic valves and capillaries located adjacent to the subarachnoid space in mice. We also show that basal mLVs are hotspots for the clearance of CSF macromolecules and that both mLV integrity and CSF drainage are impaired with ageing. Our findings should increase the understanding of how mLVs contribute to the neuropathophysiological processes that are associated with ageing.

Production of Recombinant Single-Chain Eel Luteinizing Hormone and Follicle-Stimulating Hormone Analogs in Chinese Hamster Ovary Suspension Cell Culture.

We produced rec-single chain eel luteinizing (rec-eel LH) and follicle-stimulating (rec- eel FSH) hormones displaying high biological activity in Chinese hamster ovary suspension (CHO-S) cells. We constructed several mutants, in which a linker, including an O-linked glycosylated carboxyl-terminal peptide (CTP) of an equine chorionic gonadotropin (eCG) ß-subunit, was attached between the ß- and α-subunit (LH-M and FSH-M) or in the N-terminal (C-LH and C-FSH) or C-terminal (LH-C and FSH-C) regions. The plasmids were transfected into CHO-S cells, and culture supernatants were collected. The secretion of mutants from the CHO-S cells was faster than that of eel LHß/α-wt and FSHß/α-wt proteins. The molecular weight of eel LHß/α-wt and eel FSHß/α-wt was 32-34 and 34-36 kDa, respectively, and that of LH-M and FSH-M was 40-43 and 42-45 kDa, respectively. Peptide-N-glycanase F-treatment markedly decreased the molecular weight by approximately 8-10 kDa. The EC50 value and the maximal responsiveness of the eel LH-M and eel FSH-M increased compared with the wild-type proteins. These results show that the CTP region plays a pivotal role in early secretion and signal transduction. We suggest that novel rec-eel LH and FSH proteins, exhibiting potent activity, could be produced in large quantities using a stable CHO cell system.

Stable Production of a Tethered Recombinant Eel Luteinizing Hormone Analog with High Potency in CHO DG44 Cells.

We produced a recombinant eel luteinizing hormone (rec-eel LH) analog with high potency in Chinese hamster ovary DG44 (CHO DG44) cells. The tethered eel LH mutant (LH-M), which had a linker comprising the equine chorionic gonadotropin (eLH/CG) ß-subunit carboxyl-terminal peptide (CTP) region (amino acids 115 to 149), was inserted between the ß-subunit and α-subunit of wild-type tethered eel LH (LH-wt). Monoclonal cells transfected with the tethered eel LH-wt and eel LH-M plasmids were isolated from five to nine clones of CHO DG44 cells, respectively. The secreted quantities abruptly increased on day 3, with peak levels of 5000-7500 ng/mL on day 9. The molecular weight of tethered rec-eel LH-wt was 32-36 kDa, while that of tethered rec-eel LH-M increased to approximately 38-44 kDa, indicating the detection of two bands. Treatment with the peptide N-glycanase F decreased the molecular weight by approximately 8 kDa. The oligosaccharides at the eCG ß-subunit O-linked glycosylation sites were appropriately modified post-translation. The EC50 value and maximal responsiveness of eel LH-M increased by approximately 2.90- and 1.29-fold, respectively, indicating that the mutant exhibited more potent biological activity than eel LH-wt. Phosphorylated extracellular regulated kinase (pERK1/2) activation resulted in a sharp peak 5 min after agonist treatment, with a rapid decrease thereafter. These results indicate that the new tethered rec-eel LH analog had more potent activity in cAMP response than the tethered eel LH-wt in vitro. Taken together, this new eel LH analog can be produced in large quantities using a stable CHO DG44 cell system.

Preliminary Findings of mRNA Covid-19 Vaccine Safety in Pregnant Persons.

BACKGROUND: Many pregnant persons in the United States are receiving messenger RNA (mRNA) coronavirus disease 2019 (Covid-19) vaccines, but data are limited on their safety in pregnancy. METHODS: From December 14, 2020, to February 28, 2021, we used data from the "v-safe after vaccination health checker" surveillance system, the v-safe pregnancy registry, and the Vaccine Adverse Event Reporting System (VAERS) to characterize the initial safety of mRNA Covid-19 vaccines in pregnant persons. RESULTS: A total of 35,691 v-safe participants 16 to 54 years of age identified as pregnant. Injection-site pain was reported more frequently among pregnant persons than among nonpregnant women, whereas headache, myalgia, chills, and fever were reported less frequently. Among 3958 participants enrolled in the v-safe pregnancy registry, 827 had a completed pregnancy, of which 115 (13.9%) resulted in a pregnancy loss and 712 (86.1%) resulted in a live birth (mostly among participants with vaccination in the third trimester). Adverse neonatal outcomes included preterm birth (in 9.4%) and small size for gestational age (in 3.2%); no neonatal deaths were reported. Although not directly comparable, calculated proportions of adverse pregnancy and neonatal outcomes in persons vaccinated against Covid-19 who had a completed pregnancy were similar to incidences reported in studies involving pregnant women that were conducted before the Covid-19 pandemic. Among 221 pregnancy-related adverse events reported to the VAERS, the most frequently reported event was spontaneous abortion (46 cases). CONCLUSIONS: Preliminary findings did not show obvious safety signals among pregnant persons who received mRNA Covid-19 vaccines. However, more longitudinal follow-up, including follow-up of large numbers of women vaccinated earlier in pregnancy, is necessary to inform maternal, pregnancy, and infant outcomes.

Deterministic Formation and Growth of Dendritic Crystals of Attractive Colloids.

Dendrites are ubiquitous crystals produced in supersaturated solutions and supercooled melts, but considerably less is known about their formation and growth kinetics. Here, the key factors are explored that dictate dendrite formation and growth, utilizing experimental colloidal models in which the particles act as molecules with Mie potential. Depletion attraction is employed to colloids and manipulate their strength to control supersaturation. Dendrites are predominantly produced under conditions of low supersaturation, where the separation between crystals is large due to slow nucleation. The dendrites do not emerge directly from nuclei. Instead, isotropic grains, initially produced from nuclei, morph into polygons. Arms then sprout from the vertices of these polygons, eventually giving rise to dendrites. Triggering this polygon-to-dendrite transformation requires a high diffusional flux. This necessitates a prolonged diffusion time to maintain a steep concentration gradient in the surrounding environment even after the transformation from circular grains to polygons.

Designing Tough Hydrogel Shells for Glucose Sensing.

Conventional hydrogel microcapsules often suffer from inadequate mechanical stability, hindering their use. Here, water-cored double-network (DN) hydrogel shells are designed, formed by polyacrylamide and calcium alginate networks using triple-emulsion templates. These DN hydrogel shells offer robust mechanical stability, optical transparency, and a precisely-defined cut-off threshold. The feasibility of this platform is demonstrated through the development of a fluorometric glucose sensor. Glucose oxidase is enclosed within the water core, while a pH-responsive fluorescent dye is incorporated into the DN shells. Glucose diffuses into the core through the DN shells, where the glucose oxidase converts glucose into gluconic acid, leading to pH reduction and a subsequent decrease in fluorescence intensity of DN shells. Additionally, the pH-sensitive colorant dissolved in the medium enables visual pH assessment. Thus, glucose levels can be determined using both fluorometric and colorimetric methods. Notably, the DN shells exhibit exceptional stability, enduring intense mechanical stress and cycles of drying and rehydration without leakage. Moreover, the DN shells act as effective barriers, safeguarding glucose oxidase against proteolysis by large disruptive proteins, like pancreatin. This versatile DN shell platform extends beyond glucose oxidase encapsulation, serving as a foundation for various capsule sensors utilizing enzymes and heterogeneous catalysts.

Centrifugation-Mediated Crystal Growth of Attractive Colloids for Band Edge Lasing.

Attractive depletion interactions are utilized to organize colloidal particles into crystalline arrays with high crystallinity through spontaneous phase separation. However, uncontrolled nucleation frequently leads to the formation of crystalline grains with varied crystal orientations, which hampers the optical performance of photonic crystals. Here, colloidal crystals have been engineered with uniform orientation and high surface coverage by applying centrifugal force during the depletion-induced assembly of polystyrene particles. The centrifugal force encourages the particles to move toward the bottom surface, which fosters heterogeneous nucleation and supports rapid crystal growth, yielding densely-packed and uniformly-arranged crystal grains with high reflectivity. This study has observed that the nucleation and crystal growth behavior is significantly influenced by the salt concentration. Based on the pair potentials, the transition boundary has been quantitatively analyzed between fluid and crystal phases and identified the threshold for homogeneous nucleation. Utilizing the high-reflectivity colloidal crystals, band-edge lasing is achieved by dissolving the water-soluble dye into the aqueous suspensions. Upon optical excitation, a lasing emission characterized is observed by a narrow spectral width at the short-wavelength band edge. Notably, the laser wavelength can be adjusted by altering the salt concentration or particle diameter, offering a versatile approach to tuning the optical properties.

Reconsidering neurogenetic indication in the human brain: Broad expression of doublecortin transcript in the hippocampal and cortical cell populations.

INTRODUCTION: Neurogenesis in the adult brain may play an important role in memory and cognition; however, knowledge of neurogenic markers in the human brain remains limited. We compared the single-nucleus transcriptome of the hippocampus with that of other cortical regions to identify hippocampus-specific neurogenic markers. METHODS: We analyzed 26,189 nuclei from four human brains collected within 16 hours of death. Clustering and annotation were performed to examine differential expression, gene ontology, and intercellular communication. DCX expression was validated by droplet ddPCR. RESULTS: Immature markers such as DCX, CALB2, NES, SOX2, PAX6, DPYSL3 and TUBB3 were expressed in both hippocampus and prefrontal cortex, with higher levels in the prefrontal cortex. ddPCR confirmed higher expression of DCX in the prefrontal cortex. DCX was involved in both neurogenesis and neuroprotection pathways. CONCLUSION: Neurogenic markers are not definitive indicators of adult neurogenesis, as their roles are more complex than previously understood.

Concentric Capillary Microfluidic Devices Designed for Robust Production of Multiple-Emulsion Droplets.

Multiple emulsions are used as templates for producing functional microcapsules due to their unique core-shell geometry. Employing glass capillary devices with coaxial channels has proven effective in creating uniform multiple-emulsion droplets. However, the use of partially miscible fluids, crucial for microcapsule production, often results in clogging and disrupts the stability of these devices. Here, we introduce innovative capillary microfluidic devices with concentric capillary channels, specifically designed to optimize the production of multiple-emulsion droplets while mitigating issues of precipitation and clogging. The key aspect of these devices is their configuration of two or three concentrically aligned capillaries, which form separate, coaxial microchannels for fluid injection. This unique alignment, achieved through rotational adjustments that leverage the natural off-center positioning of tapered capillaries, facilitates the simultaneous coaxial injection of various fluids into a droplet-forming junction, significantly reducing fluid contact before emulsification. The devices, featuring double and triple concentric capillary channels, consistently produce highly uniform double-, triple-, and quadruple-emulsion droplets with precisely controlled diameters and layer thicknesses. The minimal contact between fluids prior to emulsification in these devices broadens the usable range of fluid combinations, heralding new possibilities in microcapsule development for pharmaceutical and cosmetic applications.

Association of Depression With the Progression of Multimorbidity in Older Adults: A Population-Based Cohort Study.

BACKGROUND: The relationship between depression and the risk of multimorbidity progression has rarely been studied in older adults. This study was aimed to determine whether depression is associated with progression in the severity and complexity of multimorbidity, considering the influence of depression's severity and subtype. METHODS: As a part of the Korean Longitudinal Study on Cognitive Aging and Dementia, this population-based cohort study followed a random sample of community-dwelling Koreans aged 60 and older for 8 years at 2-year intervals starting in 2010. Participants included those who completed mood and multimorbidity assessments and did not exhibit complex multimorbidity at the study's outset. Depression was assessed using the Geriatric Depression Scale, while multimorbidity was evaluated using the Cumulative Illness Rating Scale. The study quantified multimorbidity complexity by counting affected body systems and measured multimorbidity severity by averaging scores across 14 body systems. FINDINGS: The 2,486 participants (age = 69.1 ± 6.5 years, 57.6% women) were followed for 5.9 ± 2.4 years. Linear mixed models revealed that participants with depression had a faster increase in multimorbidity complexity score (ß = .065, SE = 0.019, p = 0.001) than those without depression, but a comparable increase in multimorbidity severity score (ß = .001, SE = .009, p = 0.870) to those without depression. Cox proportional hazard models revealed that depression was associated with the risk of developing highly complex multimorbidity affecting five or more body systems, particularly in severe or anhedonic depression. INTERPRETATION: Depression was associated with the worsening of multimorbidity in Korean older adults, particularly when severe or anhedonic. Early screening and management of depression may help to reduce the burden of multimorbidity in older adults.

The role of Pim-1 kinases in inflammatory signaling pathways.

OBJECTIVE AND DESIGN: This observational study investigated the regulatory mechanism of Pim-1 in inflammatory signaling pathways. MATERIALS: THP-1, RAW 264.7, BV2, and Jurkat human T cell lines were used. TREATMENT: None. METHODS: Lipopolysaccharide (LPS) was used to induce inflammation, followed by PIM1 knockdown. Western blot, immunoprecipitation, immunofluorescence, and RT-PCR assays were used to assess the effect of PIM1 knockdown on LPS-induced inflammation. RESULTS: PIM1 knockdown in macrophage-like THP-1 cells suppressed LPS-induced upregulation of pro-inflammatory cytokines, inducible nitric oxide synthase, cyclooxygenase-2, phosphorylated Janus kinase, signal transducer and activator of transcription 3, extracellular signal-regulated kinase, c-Jun N-terminal kinase, p38, and nuclear factor kappa B p65 (NF-κB p65). It also suppressed upregulation of inhibitor of NF-κB kinase α/ß and enhanced the nuclear translocation of NF-κB p65. Moreover, it inhibited the upregulation of Nod-like receptor family pyrin domain-containing 3 (NLRP3) and cleavage of caspase-1 induced by co-treatment of LPS with adenosine triphosphate. Additionally, p-transforming growth factor-ß-activated kinase 1 (TAK1) interacted with Pim-1. All three members of Pim kinases (Pim-1, Pim-2, and Pim-3) were required for LPS-mediated inflammation in macrophages; however, unlike Pim-1 and Pim-3, Pim-2 functioned as a negative regulator of T cell activity. CONCLUSIONS: Pim-1 interacts with TAK1 in LPS-induced inflammatory responses and is involved in MAPK/NF-κB/NLRP3 signaling pathways. Additionally, considering the negative regulatory role of Pim-2 in T cells, further in-depth studies on their respective functions are needed.

Anti-rheumatic property and physiological safety of KMU-11342 in in vitro and in vivo models.

Rheumatoid arthritis (RA) is a chronic, systemic inflammatory disorder characterized by joint destruction due to synovial hypertrophy and the infiltration of inflammatory cells. Despite substantial progress in RA treatment, challenges persist, including suboptimal treatment responses and adverse effects associated with current therapies. This study investigates the anti-rheumatic capabilities of the newly identified multi-protein kinase inhibitor, KMU-11342, aiming to develop innovative agents targeting RA. In this study, we synthesized the novel multi-protein kinase inhibitor KMU-11342, based on indolin-2-one. We assessed its cardiac electrophysiological safety using the Langendorff system in rat hearts and evaluated its toxicity in zebrafish in vivo. Additionally, we examined the anti-rheumatic effects of KMU-11342 on human rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS), THP-1 cells, and osteoclastogenesis in RAW264.7 cells. KMU-11342 demonstrated the ability to inhibit LPS-induced chemokine inhibition and the upregulation of pro-inflammatory cytokines, cyclooxygenase-2, inducible nitric oxide synthase, p-IKKα/ß, p-NF-κB p65, and the nuclear translocation of NF-κB p65 in RA-FLS. It effectively suppressed the upregulation of NLR family pyrin domain containing 3 (NLRP3) and caspase-1 cleavage. Furthermore, KMU-11342 hindered the activation of osteoclast differentiation factors such as RANKL-induced TRAP, cathepsin K, NFATc-1, and c-Fos in RAW264.7 cells. KMU-11342 mitigates LPS-mediated inflammatory responses in THP-1 cells by inhibiting the activation of NLRP3 inflammasome. Notably, KMU-11342 exhibited minimal cytotoxicity in vivo and electrophysiological cardiotoxicity ex vivo. Consequently, KMU-11342 holds promise for development as a therapeutic agent in RA treatment.

Toxicity of Aged Paint Particles to Soil Ecosystems: Insights from Caenorhabditis elegans.

Despite the extensive global consumption of architectural paint, the toxicological effects of aged exterior paint particles on terrestrial biota remain largely uncharacterized. Herein, we assessed the toxic effect of aged paint particles on soil environments using the nematode Caenorhabditis elegans (C. elegans) as a test organism. Various types of paint particles were generated by fragmentation and sequential sieving (500-1000, 250-500, 100-250, 50-100, 20-50 µm) of paint coatings collected from two old residential areas. The paint particles exerted different levels of toxicity, as indicated by a reduction in the number of C. elegans offspring, depending on their size, color, and layer structure. These physical characteristics were found to be closely associated with the chemical heterogeneity of additives present in the paint particles. Since the paint particle sizes were larger than what C. elegans typically consume, we attributed the toxicity to leachable additives present in the paint particles. To assess the toxicity of these leachable additives, we performed sequential washings of the paint particles with distilled water and ethanol. Ethanol washing of the paint particles significantly reduced the soil toxicity of the hydrophobic additives, indicating their potential environmental risk. Liquid chromatography-mass spectrometry analysis of the ethanol leachate revealed the presence of alkyl amines, which exhibited a high correlation with the toxicity of the paint particles. Further toxicity testing using an alkyl amine standard demonstrated that a paint particle concentration of 1.2% in soil could significantly reduce the number of C. elegans offspring. Our findings provide insights into the potential hazards posed by aged paint particles and their leachable additives in the terrestrial environment.

Management of Immunosuppressive Therapy in Kidney Transplant Recipients with Sepsis: A Multicenter Retrospective Study.

BACKGROUND: Up to 6% of kidney transplant recipients (KTRs) experience life-threatening complications requiring intensive care unit (ICU) admission, and one of the most common medical complications requiring ICU admission is infection. This study aimed to evaluate the effect of immunosuppressive therapy (IST) modification on prognosis of KTRs with sepsis. METHODS: We conducted a multicenter retrospective study in 4 university-affiliated hospitals to evaluate the effect of adjusting the IST in KTRs with sepsis. Only patients who either maintained IST after ICU admission or those who underwent immediate (within 24 h of ICU admission) reduction or withdrawal of IST following ICU admission were included in this study. "Any reduction" was defined as a dosage reduction of any IST or discontinuation of at least 1 IST. "Complete withdrawal of IST" was defined as concomitant discontinuation of all ISTs, except steroids. RESULTS: During the study period, 1596 of the KTRs were admitted to the ICU, and 112 episodes of sepsis or septic shock were identified. The overall in-hospital mortality rate was 35.7%. In-hospital mortality was associated with higher sequential organ failure assessment score, simplified acute physiology score 3, non-identical human leukocyte antigen relation, presence of septic shock, and complete withdrawal of IST. After adjusting for potential confounding factors, complete withdrawal of IST remained significantly associated with in-hospital mortality (adjusted coefficient, 1.029; 95% confidence interval, 0.024-2.035) and graft failure (adjusted coefficient, 2.001; 95% confidence interval, 0.961-3.058). CONCLUSIONS: Complete IST withdrawal was common and associated with worse outcomes in critically ill KTRs with sepsis.

Influence of frailty status on the health-related quality of life in older patients with chronic low back pain: a retrospective observational study.

PURPOSE: Understanding the influence of frailty on health-related quality of life (HRQoL) in older individuals experiencing chronic low back pain can provide valuable insights into the impact of frailty. Therefore, the aim of our study is to assess how different frailty statuses among older outpatients with chronic low back pain affect their HRQoL. METHODS: Patients aged 60 and above with chronic low back pain were recruited from March 2022 to February 2023. Frailty was assessed via the frailty phenotype questionnaire, and HRQoL was evaluated using the EQ-5D-5L. Multiple regression models were used to explore the influence of frailty status on the EQ-5D-5L index and EQ-VAS. Logistic regression was used to determine odds ratios for the impact of frailty status on belonging to the lowest EQ-5D-5L index quartile. RESULTS: A total of 1,054 participants were classified into robust (29.8%), pre-frail (47.7%), and frail (22.5%) groups. Frailty was significantly associated with declining HRQoL. Pre-frail and frail statuses were inversely linked to the EQ-5D-5L index, with significantly higher odds of scoring in the lowest quartile compared to robust individuals. Stratification analysis identified sex as an effect modifier, emphasizing a more substantial association between frailty and the lowest EQ-5D-5L index quartile in female patients. CONCLUSIONS: A significant association exists between frailty and reduced HRQoL in patients with chronic low back pain. This association was predominant in female patients. Furthermore, considering the dynamic nature of frailty, early detection and effective interventions targeting pre-frailty are essential to delaying the transition to full frailty and improving HRQoL.

Genome editing in the mouse brain with minimally immunogenic Cas9 RNPs.

Transient delivery of CRISPR-Cas9 ribonucleoproteins (RNPs) into the central nervous system (CNS) for therapeutic genome editing could avoid limitations of viral vector-based delivery including cargo capacity, immunogenicity, and cost. Here, we tested the ability of cell-penetrant Cas9 RNPs to edit the mouse striatum when introduced using a convection-enhanced delivery system. These transient Cas9 RNPs showed comparable editing of neurons and reduced adaptive immune responses relative to one formulation of Cas9 delivered using AAV serotype 9. The production of ultra-low endotoxin Cas9 protein manufactured at scale further improved innate immunity. We conclude that injection-based delivery of minimally immunogenic CRISPR genome editing RNPs into the CNS provides a valuable alternative to virus-mediated genome editing.

Overcoming the age-dependent SARS-CoV-2 vaccine response through hybrid immunity: analysis of humoral and cellular immunity with mass cytometry profiling.

BACKGROUND: Age-dependent immune responses to coronavirus disease 2019 (COVID-19) vaccinations and breakthrough infections (BIs) in young and middle-aged individuals are unclear. METHODS: This nationwide multicenter prospective cohort study analyzed immune responses in participants of the ChAdOx1 (ChAd)-ChAd-mRNA vaccine group using cytometry by time-of-flight, anti-spike protein antibody (Sab) and anti-nucleocapsid antibody (Nab) titers, plaque reduction neutralization tests (PRNTs), and interferon-gamma (IFN-γ) release assays at various time points. RESULTS: We evaluated 347 participants with an average age of 38.9 ± 9.4 years (range: 21-63). There was a significant inverse correlation between age and Sab levels after the second dose (slope - 14.96, P = 0.032), and this was more pronounced after the third dose (slope - 208.9, P < 0.001). After BIs, older participants showed significantly higher Sab titers (slope 398.8, P = 0.001), reversing the age-related decline observed post-vaccination. This reversal was also observed in PRNTs against wild-type SARS-CoV-2 and the BA.1 and BA.5 variants. IFN-γ responses increased markedly after the third dose and Bis, but showed a weak positive correlation with age, without statistical significance. Immune cell profiling revealed an age-dependent decrease in the proportions of B-cell lineage cells. The proportions of naive CD4+ and CD8+ T cells were inversely correlated with age, whereas the proportions of mature T cell subsets with memory function, including memory CD4+ T, CD8+ TEM, CD8+ TEMRA, and TFH cells, increased with age. CONCLUSIONS: Age-dependent waning of the serologic response to COVID-19 vaccines occurred even in middle-aged individuals, but was reversed after BIs. IFN-γ responses were preserved, compensating for the decrease in naive T cell populations, with an increase in memory T cell populations.

Performance of calf circumference in identifying sarcopenia in older patients with chronic low back pain: a retrospective cross-sectional study.

BACKGROUND: Calf circumference is currently recommended as a case-finding marker for sarcopenia, but its usefulness has not been determined in chronic pain conditions. Therefore, the present study aimed to evaluate the predictive performance of calf circumference in diagnosing sarcopenia in older patients with chronic low back pain. METHODS: Ambulatory adult patients aged ≥ 65 years with chronic low back pain were enrolled. A diagnosis of sarcopenia was established based on the criteria outlined by the Asian Working Group for Sarcopenia in 2019. Patient demographics, pain-related factors, clinical factors, and sarcopenia-related measurements were compared between non-sarcopenic and sarcopenic patients. Linear regression analysis was used to evaluate the correlation of calf circumference with muscle mass, strength, and physical performance. Also, a receiver operating characteristic curve analysis for calf circumference in predicting sarcopenia was conducted; and area under the curve (AUC) values, along with their corresponding 95% confidence intervals (CI), were calculated. RESULTS: Data from 592 patients were included in the analysis. Eighty-five patients were diagnosed with sarcopenia (14.3%), 71 of whom had severe sarcopenia (11.9%). A higher prevalence of sarcopenia was observed in female patients (9.0% vs. 16.7%, p = 0.016). After adjusting for age, BMI, and comorbidities, calf circumference correlated positively with muscle mass but not with muscle strength and physical performance. The AUC values for sarcopenia were 0.754 (95% CI = 0.636-0.871, p = 0.001) in males and 0.721 (95% CI = 0.657-0.786, p < 0.001) in females. The cut-offs for calf circumference in predicting sarcopenia were 34 cm (sensitivity 67.1%, specificity 70.6%) in males, and 31 cm (sensitivity 82.5%, specificity 51.5%) in females. CONCLUSIONS: Even though sex differences in its predictive value for sarcopenia should be considered, our findings suggest that calf circumference can be used as an indicator for predicting muscle mass and may serve as a potential marker for identifying sarcopenia in older patients with chronic low back pain.

Birth Outcomes Among People with Hepatitis C in Pregnancy - Three U.S. States, 2018-2021.

INTRODUCTION: There are limited and conflicting data regarding the impact of hepatitis C in pregnancy on adverse birth outcomes. METHODS: Using the Surveillance for Emerging Threats to Pregnant People and Infants Network (SET-NET), a large surveillance cohort, we describe birth outcomes among a cohort of people with HCV in pregnancy in total and by reported substance use. RESULTS: Among 1418 infants, 89% were born to people with reported substance use during pregnancy. The proportion born preterm was 20%, 13% were small-for-gestational age and 34% of term infants required intensive care. CONCLUSIONS: Assessments of recent changes to recommendations for HCV screening in pregnancy should evaluate the impact on maternal access to care for both HCV treatment as well as comorbidities such as substance use disorder which may contribute to adverse birth outcomes.