Menopausal stages and overactive bladder symptoms in middle-aged women: A cross-sectional study.

OBJECTIVE: To examine the prevalence of overactive bladder (OAB) according to menopausal stages in middle-aged women. DESIGN: Cross-sectional study. SETTING: Total Healthcare Center in South Korea. POPULATION: Middle-aged Korean women (n=3469, mean age, 49.5 ± 2.9 years). METHODS: Menopausal stages were defined according to the Stages of Reproductive Aging Workshop +10 criteria, and menopausal symptoms were assessed using the Korean version of Menopause-Specific Quality of Life (MENQOL). Logistic regression models were used to estimate prevalence ratios with 95% confidence intervals for OAB according to menopausal stage and to assess the associations with menopausal symptoms. MAIN OUTCOME MEASURES: OAB symptoms were evaluated using the Overactive Bladder Symptom Score (OABSS). RESULTS: The prevalence of OAB increased with menopausal stage; however, the multivariable-adjusted prevalence ratios for women in menopausal transition and postmenopausal stage were insignificant (ptrend = 0.160) compared to those for premenopausal women. Among individual OAB symptoms, the multivariable-adjusted prevalence ratios for nocturia increased with menopausal stage in a dose-response manner (ptrend = 0.005 for 1 time/day; ptrend < 0.001 for ≥2 times/day). The association between menopausal stages and nocturia occurring ≥2 times/day was evident in women without OAB and with relatively high MENQOL scores, vasomotor symptoms and difficulty sleeping. CONCLUSIONS: The prevalence of OAB, particularly nocturia, increased with menopausal stage, and the association was obvious in women with other menopausal symptoms. This finding underscores the importance of addressing nocturia as a potential menopausal symptom in middle-aged women. Further studies are required to understand the mechanisms linking OAB with menopausal symptoms in middle-aged women.

Overactive bladder and cognitive impairment in middle-aged women: A cross-sectional study.

BACKGROUND: Overactive bladder (OAB) is a common condition in middle-aged and older women. It has been reported to be potentially linked to cognitive decline, particularly in older adults. This study investigated the association between OAB symptoms and cognitive impairment in middle-aged women. MATERIALS AND METHODS: This cross-sectional study had a sample of 1652 women (mean age 49.3 ± 2.8 years) who were not taking medication for either urinary tract infection or OAB. OAB symptoms and cognitive function were evaluated by self-administered questionnaires: the Overactive Bladder Symptom Score and the Alzheimer's disease 8. Logistic regression models estimated prevalence ratios (PRs) with 95 % confidence intervals (CI) for cognitive impairment according to the presence/absence of OAB. Mediation analyses assessed the impact of poor sleep quality on this association. RESULTS: Cognitive impairment was more prevalent in women with OAB than in those without OAB (multivariable-adjusted PR: 1.88 [95 % CI: 1.52-2.24]). Women experiencing nocturia (≥twice a night), urinary urgency at least once a week, and urgency urinary incontinence at least once a week had multivariable-adjusted PRs (95 % CI) for cognitive impairment of 2.08 (1.50-2.65), 2.12 (1.66-2.58), and 1.75 (1.17-2.34), respectively. Poor sleep quality mediated 10.81 % [95 % CI: 4.55-19.44 %] of the relationship between OAB and cognitive impairment. CONCLUSIONS: Among middle-aged women not taking OAB medications, OAB symptoms were associated with cognitive impairment, partly because of poor sleep quality. Further research is needed to determine whether early screening of patients with OAB can help identify those susceptible to cognitive impairment associated with OAB medication and if preventive measures should be targeted at this group.

Probiotic LB101 alleviates dry eye in mice by suppressing matrix metalloproteinase-9 expression through the regulation of gut microbiota-involved NF-κB signaling.

Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1ß, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1ß expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1ß, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1ß expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1ß, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1ß expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1ß with the regulation of gut microbiota-involved NF-κB signaling.

A novel method of evaluating the non-invasive tear film break-up time and progression of corneal opacification in dogs using imaging video.

This study aimed to determine the correlation of the parameters that indicate the status of the ocular surface with the prognosis of corneal opacification. Fifty dogs (96 eyes) were examined using a grid-line illuminator (non-invasive tear film break-up time (NIBUT)). Thirty dogs (54 eyes) were included in the final analysis based on the criteria. The NIBUT and tear film break-up time (TFBUT) results of the eyes included in the study were divided into three groups: Group 1 (< 5 s), Group 2 (5 to <10 s), and Group 3 (≥ 10 s). The Schirmer's tear Test 1 (STT-1) results of the included patients were also divided into three groups: Group 1 (< 5 mm/min), Group 2 (5 to <10 mm/min), and Group 3 (≥ 10 mm/min). The corneal opacity grades are divided into four scores, ranging from 0 to 3. The corneal opacity grade score (COS) of 0 indicates a completely clear cornea or only a trace of opacity. COS of 1, 2, 3 indicate the presence of a prominent corneal opacity that does not interfere with the visualization of the fine iris details, the opacity obscures the visibility of the iris and lens details and severe obstruction of the intraocular structure visibility, respectively. The mean difference in COS during the follow-ups for each group of NIBUT were 0.61 ± 0.92 (n = 28), 0.10 ± 0.32 (n = 10), 0.19 ± 0.40 (n = 16). The NIBUT groups were significantly correlated with COS (p-value = 0.073) at a 10% level of significance. Post-hoc test at a 10% level of significance revealed significant correlations between Groups 1 and 2 (p-value = 0.041) and between Groups 1 and 3 (p-value 0.104). Although the TFBUT and STT-1 groups did not show any significant correlation with COS. Eyes with NIBUT of <5 s were found to have a significantly higher chance of increased COS compared with eyes with NIBUT of >5 s in the grid-line illumination plate NIBUT test. Among NIBUT, STT-1, and TFBUT, NIBUT was the only test that showed significant associations with the changes in COS.

Loranthus tanakae Franch. and Sav. Attenuates Respiratory Inflammation Caused by Asian Sand Dust.

Asian sand dust (ASD), generally produced in East Asia, including China, Japan, and Korea, directly leads to the development of pulmonary disease and exacerbates underlying pulmonary diseases. Loranthus tanakae Franch. and Sav. is a traditional herbal medicine applied to improve various inflammatory conditions. Here, we evaluated the curative properties of L. tanakae ethanol extract (LTE) against pulmonary inflammation caused by ASD. Additionally, to investigate the mechanism of action of LTE, we performed network pharmacological analysis. ASD was administrated on day 1, 3, and 5 by intranasal instillation, and LTE was orally administered for 6 days. Administration of LTE significantly decreased inflammatory cytokines and the number of inflammatory cells in bronchoalveolar lavage fluid, which was accompanied by a decrease in inflammatory cell accumulation in pulmonary tissue. Administration of LTE decreased the expression of cyclooxygenase2 and matrix metalloproteinase-9 in mice exposed to ASD with the decline in p65 phosphorylation. Additionally, administration of LTE significantly elevated hemeoxygenase (HO)-1 expression in the pulmonary tissue of mice exposed to ASD. These results were consistent with the data of network pharmacological analysis. This experiment showed that LTE attenuated pulmonary inflammation caused by ASD via inhibition of NF-κB and elevation of HO-1. Therefore, LTE may have potential as a therapeutic agent to treat pulmonary inflammation caused by ASD.

An Integrative Study of Scrophularia takesimensis Nakai in an Ovalbumin-Induced Murine Model of Asthma: The Effect on T Helper 2 Cell Activation.

Scrophularia have traditionally been used as herbal medicines to treat neuritis, sore throats, and laryngitis. In particular, S. takesimensis, a Korean endemic species with restricted distribution on Ulleung Island, holds significant resource and genetic value. However, its pharmacological properties have not been thoroughly evaluated. Thus, we provide detailed morphological characteristics and genomic information for S. takesimensis in this study. Moreover, its pharmacological activity was evaluated in an ovalbumin-induced asthma rat model, using extracts of S. takesimensis roots (100 or 200 mg/kg). The distinguishing features of S. takesimensis from related species include the presence or absence of stem wings, leaf shape, and habitat. The chloroplast (cp) genome of this species is 152,420 bp long and exhibits a conserved quadripartite structure. A total of 114 genes were identified, which included 80 protein-coding genes, 30 transfer RNA (tRNA) genes, and 4 ribosomal RNA (rRNA) genes. The gene order, content, and orientation of the S. takesimensis cp genome was highly conserved and consistent with the general structure observed in S. buergeriana and S. ningpoensis cp genomes. Confirming the anti-inflammatory effects of S. takesimensis extract (STE) using an established mouse model of ovalbumin-induced asthma, we observed reduced asthmatic phenotypes, including inflammatory cell infiltration, mucus production, and suppression of T helper 2 (Th2) cell. Furthermore, STE treatment reduced Th2 cell activation and differentiation. This study underscores the medicinal value of S. takesimensis. The importance of preserving S. takesimensis was revealed and crucial insights were provided for further research on its utilization as a medicinal resource.

Design of a Self-Measuring Device Based on Bioelectrical Impedance Analysis for Regular Monitoring of Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic disease, in which permanent joint deformation is largely preventable with the timely introduction of appropriate treatment strategies. However, there is no consensus for patients with RA to monitor their progress and communicate it to the rheumatologist till the condition progresses to remission. In response to this unmet need, we proposed the design of a self-measuring device based on bioelectrical impedance analysis (BIA) for regular monitoring of inflammation levels. Twenty joints of both hands were measured to monitor trends in inflammation levels. Three electrodes were used to measure two joints of each finger. A central electrode was used for two consecutive measurements. A suitable form factor for the device was proposed for the vertical placement of the hand. To ensure the stability of measurements, an air cushion was incorporated into the back of the hand, hand containers were designed on both sides, and a mobile application was designed. We conducted a convergence-assessment experiment with five air pressures to validate the consistency and convergence of bioimpedance measurements. A heuristic evaluation of the usability around the product and mobile application was conducted in parallel by six subject matter experts and validated the design. This study underscores the significance of considering patients' disease activity during intervals between hospital visits and introduces a novel approach to self-RA care.

Human epidermal growth factor receptor-2 expression and subsequent dynamic changes in patients with ovarian cancer.

Human epidermal growth factor receptor-2 (HER2)-targeting drugs are increasingly being incorporated into therapeutic paradigms for non-breast cancers, yet studies on HER2 expression in ovarian cancer (OC) are inadequate. Here, we studied the HER2 status and dynamic changes in OC by reviewing the records of patients who underwent HER2 testing at a single institution. Clinical parameters, including histology, BRCA status, and immunohistochemistry (IHC), were evaluated alongside HER2 expression, timing, and anatomical location. Among 200 patients, 28% and 6% exhibited expression scores of 2+ and 3+, respectively. HER2 3+ scores were observed in 23%, 11%, 9%, and 5% of mucinous, endometrioid, clear cell, and high-grade serous tumors, respectively, and were exclusively identified in BRCA-wildtype, mismatch repair-proficient, or PD-L1-low-expressing tumors. The TP53 mutation rate was low, whereas ARID1A, KRAS, and PIK3CA mutations were relatively more prevalent with HER2 scores of 2+ or 3+ than with 0 or 1+. Four of the five tumors with an HER2 3+ score exhibited ERBB2 amplification. Among 19 patients who underwent multiple time-lagged biopsies, 11 showed increased HER2 expression in subsequent biopsies. Patients with HER2-overexpressing OC exhibited distinct histological, IHC, and genomic profiles. HER2-targeting agents are potential options for BRCA-wildtype patients, particularly as later lines of treatment.

Longitudinal change in mitochondrial heteroplasmy exhibits positive selection for deleterious variants.

A common feature of human aging is the acquisition of somatic mutations, and mitochondria are particularly prone to mutation due to their inefficient DNA repair and close proximity to reactive oxygen species, leading to a state of mitochondrial DNA heteroplasmy1,2. Cross-sectional studies have demonstrated that detection of heteroplasmy increases with participant age3, a phenomenon that has been attributed to genetic drift4-7. In this first large-scale longitudinal study, we measured heteroplasmy in two prospective cohorts (combined n=1405) at two timepoints (mean time between visits, 8.6 years), demonstrating that deleterious heteroplasmies were more likely to increase in variant allele fraction (VAF). We further demonstrated that increase in VAF was associated with increased risk of overall mortality. These results challenge the claim that somatic mtDNA mutations arise mainly due to genetic drift, instead demonstrating positive selection for predicted deleterious mutations at the cellular level, despite an negative impact on overall mortality.

The association of blood eosinophil counts and FEV1 decline: a cohort study.

BACKGROUND: Accelerated lung function decline is characteristic of COPD. However, the association between blood eosinophil counts and lung function decline, accounting for current smoking status, in young individuals without prevalent lung disease is not fully understood. METHODS: This is a cohort study of 629 784 Korean adults without COPD or a history of asthma at baseline who participated in health screening examinations including spirometry and differential white blood cell counts. We used a linear mixed-effects model to estimate the annual change in forced expiratory volume in 1 s (FEV1) (mL) by baseline blood eosinophil count, adjusting for covariates including smoking status. In addition, we performed a stratified analysis by baseline and time-varying smoking status. RESULTS: During a mean follow-up of 6.5 years (maximum 17.8 years), the annual change in FEV1 (95% CI) in participants with eosinophil counts <100, 100-199, 200-299, 300-499 and ≥500 cells·µL-1 in the fully adjusted model were -23.3 (-23.9--22.7) mL, -24.3 (-24.9--23.7) mL, -24.8 (-25.5--24.2) mL, -25.5 (-26.2--24.8) mL and -26.8 (-27.7--25.9) mL, respectively. When stratified by smoking status, participants with higher eosinophil count had a faster decline in FEV1 than those with lower eosinophil count in both never- and ever-smokers, which persisted when time-varying smoking status was used. CONCLUSIONS: Higher blood eosinophil counts were associated with a faster lung function decline among healthy individuals without lung disease, independent of smoking status. The findings suggest that higher blood eosinophil counts contribute to the risk of faster lung function decline, particularly among younger adults without a history of lung disease.

Early-onset vasomotor symptoms and development of depressive symptoms among premenopausal women.

BACKGROUND: We investigated the association between vasomotor symptoms (VMSs) and the onset of depressive symptoms among premenopausal women. METHODS: This cross-sectional study included 4376 premenopausal women aged 42-52 years, and the cohort study included 2832 women without clinically relevant depressive symptoms at baseline. VMSs included the symptoms of hot flashes and night sweats. Depressive symptoms were evaluated using the Center for Epidemiological Studies Depression Scale; a score of ≥16 was considered to define clinically relevant depressive symptoms. RESULTS: Premenopausal Women with VMSs at baseline exhibited a higher prevalence of depressive symptoms compared with women without VMSs at baseline (multivariable-adjusted prevalence ratio 1.76, 95 % confidence interval [CI] 1.47-2.11). Among the 2832 women followed up (median, 6.1 years), 406 developed clinically relevant depressive symptoms. Women with versus without VMSs had a significantly higher risk of developing clinically relevant depressive symptoms (multivariable-adjusted hazard ratio, 1.72; 95 % CI 1.39-2.14). VMS severity exhibited a dose-response relationship with depressive symptoms (P for trend <0.05). LIMITATIONS: Self-reported questionnaires were only used to obtain VMSs and depressive symptoms, which could have led to misclassification. We also could not directly measure sex hormone levels. CONCLUSIONS: Even in the premenopausal stage, women who experience hot flashes or night sweats have an increased risk of present and developed clinically relevant depressive symptoms. It is important to conduct mental health screenings and provide appropriate support to middle-aged women who experience early-onset VMSs.

Anti-Atopic Effect of Scutellaria baicalensis and Raphanus sativus on Atopic Dermatitis-like Lesions in Mice by Experimental Verification and Compound-Target Prediction.

Scutellaria baicalensis Georgi and Raphanus Sativus Linne herbal mixture (SRE) is a Chinese herbal medicine. In this study, we aimed to evaluate the therapeutic efficacy of SRE as an active ingredient for 2,4-dinitrochlorobenzene (DNCB)-induced atopic dermatitis (AD) and to predict the underlying therapeutic mechanisms and involved pathways using network pharmacological analysis. Treatment with SRE accelerated the development of AD-like lesions, improving thickness and edema of the epidermis. Moreover, administering the SRE to AD-like mice suppressed immunoglobulin E and interleukin-4 cytokine and reduced T lymphocyte differentiation. In silico, network analysis was used to predict the exact genes, proteins, and pathways responsible for the therapeutic effect of the SRE against DNCB-induced AD. These results indicated that the SRE exerted protective effects on the DNCB-induced AD-like model by attenuating histopathological changes and suppressing the levels of inflammatory mediators. Therefore, the SRE can potentially be a new remedy for improving AD and other inflammatory diseases and predicting the intracellular signaling pathways and target genes involved. This therapeutic effect of the SRE on AD can be used to treat DNCB-induced AD and its associated symptoms.

Preoperative DLco and FEV1 are correlated with postoperative pulmonary complications in patients after esophagectomy.

Limited information is available regarding the association between preoperative lung function and postoperative pulmonary complications (PPCs) in patients with esophageal cancer who undergo esophagectomy. This is a retrospective cohort study. Patients were classified into low and high lung function groups by the cutoff of the lowest fifth quintile of forced expiratory volume in 1 s (FEV1) %predicted (%pred) and diffusing capacity of the carbon monoxide (DLco) %pred. The PPCs compromised of atelectasis requiring bronchoscopic intervention, pneumonia, and acute lung injury/acute respiratory distress syndrome. Modified multivariable-adjusted Poisson regression model using robust error variances and inverse probability treatment weighting (IPTW) were used to assess the relative risk (RR) for the PPCs. A joint effect model considered FEV1%pred and DLco %pred together for the estimation of RR for the PPCs. Of 810 patients with esophageal cancer who underwent esophagectomy, 159 (19.6%) developed PPCs. The adjusted RR for PPCs in the low FEV1 group relative to high FEV1 group was 1.48 (95% confidence interval [CI] = 1.09-2.00) and 1.98 (95% CI = 1.46-2.68) in the low DLco group relative to the high DLco group. A joint effect model showed adjusted RR of PPCs was highest in patients with low DLco and low FEV1 followed by low DLco and high FEV1, high DLco and low FEV1, and high DLco and high FEV1 (Reference). Results were consistent with the IPTW. Reduced preoperative lung function (FEV1 and DLco) is associated with post-esophagectomy PPCs. The risk was further strengthened when both values decreased together.

Nox4-SH3YL1 complex is involved in diabetic nephropathy.

Nox4-derived H2O2 generation plays an important role in the pathogenesis of chronic kidney diseases (CKDs) such as diabetic nephropathy (DN). Here, we showed that SH3 domain-containing Ysc84-like 1 (SH3YL1), a Nox4 cytosolic activator, regulated DN. Streptozotocin (STZ)-induced type Ⅰ diabetic models in SH3YL1 whole-body knockout (KO) mice and podocyte-specific SH3YL1 conditional KO (Nphs2-Cre/SH3YL1fl/fl) mice were established to investigate the function of SH3YL1 in DN. The expression of fibrosis markers and inflammatory cytokines, the generation of oxidative stress, and the loss of podocytes were suppressed in diabetic SH3YL1 KO and Nphs2-Cre/SH3YL1fl/fl mice, compared to diabetic control mice. To extrapolate the observations derived from diabetic mice to clinical implication, we measured the protein level of SH3YL1 in patients DN. In fact, the SH3YL1 level was increased in patients DN. Overall, the SH3YL1-Nox4 complex was identified to play an important role in renal inflammation and fibrosis, resulting in the development of DN.

Maternal histone methyltransferases antagonistically regulate monoallelic expression in C. elegans.

Undefined epigenetic programs act to probabilistically silence individual autosomal alleles, generating unique individuals, even from genetic clones. This sort of random monoallelic expression can explain variation in traits and diseases that differences in genes and environments cannot. Here, we developed the nematode Caenorhabditis elegans to study monoallelic expression in whole tissues, and defined a developmental genetic regulation pathway. We found maternal H3K9 histone methyltransferase (HMT) SET-25/SUV39/G9a works with HPL-2/HP1 and LIN-61/L3MBTL2 to randomly silence alleles in the intestinal progenitor E-cell of 8-cell embryos to cause monoallelic expression. SET-25 was antagonized by another maternal H3K9 HMT, MET-2/SETDB1, which works with LIN-65/ATF7ZIP and ARLE-14/ARL14EP to prevent monoallelic expression. The HMT-catalytic SET domains of both MET-2 and SET-25 were required for regulating monoallelic expression. Our data support a model wherein SET-25 and MET-2 regulate histones during development to generate patterns of somatic monoallelic expression that are persistent but not heritable.

Effect of Hyperprolactinemia on Bone Metabolism: Focusing on Osteopenia/Osteoporosis.

Prolactin is a hormone secreted from lactotroph cells in the anterior pituitary gland to induce lactation after birth. Hyperprolactinemia unrelated to lactation is a common cause of amenorrhea in women of a childbearing age, and a consequent decrease in the gonadotropin-releasing hormone (GnRH) by a high prolactin level can result in decreased bone mineral density. Osteoporosis is a common skeletal disorder characterized by decreased bone mineral density (BMD) and quality, which results in decreased bone strength. In patients with hyperprolactinemia, changes in BMD can be induced indirectly by the inhibition of the GnRH-gonadal axis due to increased prolactin levels or by the direct action of prolactin on osteoblasts and, possibly, osteoclast cells. This review highlights the recent work on bone remodeling and discusses our knowledge of how prolactin modulates these interactions, with a brief literature review on the relationship between prolactin and bone metabolism and suggestions for new possibilities.

Comparative Morphology of Island and Inland Agastache rugosa and Their Gastroprotective Effects in EtOH/HCl-Induced Gastric Mucosal Gastritis.

Agastache rugosa Kuntze (Lamiaceae; Labiatae), a medicinal and functional herb used to treat gastrointestinal diseases, grows well both on islands and inland areas in South Korea. Thus, we aimed to reveal the morphological and micromorphological differences between A. rugosa grown on island and inland areas and their pharmacological effects on gastritis in an animal model by combining morphological and mass spectrophotometric analyses. Morphological analysis showed that island A. rugosa had slightly smaller plants and leaves than inland plants; however, the density of all types of trichomes on the leaves, petioles, and stems of island A. rugosa was significantly higher than that of inland plants. The essential oil component analysis revealed that pulegone levels were substantially higher in island A. rugosa than in inland A. rugosa. Despite the differences between island and inland A. rugosa, treatment with both island and inland A. rugosa reduced gastric damages by more than 40% compared to the gastritis induction group. In addition, expression of inflammatory protein was reduced by about 30% by treatment of island and inland A. rugosa. The present study demonstrates quantitative differences in morphology and volatile components between island and inland plants; significant differences were not observed between the gastritis-inhibitory effects of island and inland A. rugosa, and the efficacy of island A. rugosa was found to be similar to that of A. rugosa grown in inland areas.

Correction: Lactobacillus plantarum and Bifidobacterium bifidum alleviate dry eye in mice with exorbital lacrimal gland excision by modulating gut inflammation and microbiota.

Correction for 'Lactobacillus plantarum and Bifidobacterium bifidum alleviate dry eye in mice with exorbital lacrimal gland excision by modulating gut inflammation and microbiota' by Soo-won Yun et al., Food Funct., 2021, 12, 2489-2497, https://doi.org/10.1039/d0fo02984j.

Mitochondrial DNA Copy Number Variation in Asthma Risk, Severity, and Exacerbations.

Rationale: Although airway oxidative stress and inflammation are central to asthma pathogenesis, there is limited knowledge of the relationship of asthma risk, severity, or exacerbations to mitochondrial dysfunction, which is pivotal to oxidant generation and inflammation. Objectives: We investigated whether mitochondrial DNA copy number (mtDNA-CN) as a measure of mitochondrial function is associated with asthma diagnosis, severity, oxidative stress, and exacerbations. Methods: We measured mtDNA-CN in blood in two cohorts. In the UK Biobank (UKB), we compared mtDNA-CN in mild and moderate-severe asthmatics to non-asthmatics. In the Severe Asthma Research Program (SARP), we evaluated mtDNA-CN in relation to asthma severity, biomarkers of oxidative stress and inflammation, and exacerbations. Measures and Main Results: In UK Biobank, asthmatics (n = 29,768) have lower mtDNA-CN compared to non-asthmatics (n = 239,158) (beta, -0.026 [95% CI, -0.038 to -0.014], P = 2.46×10-5). While lower mtDNA-CN is associated with asthma, mtDNA-CN did not differ by asthma severity in either UKB or SARP. Biomarkers of inflammation show that asthmatics have higher white blood cells (WBC), neutrophils, eosinophils, fraction exhaled nitric oxide (FENO), and lower superoxide dismutase (SOD) than non-asthmatics, confirming greater oxidative stress in asthma. In one year follow-up in SARP, higher mtDNA-CN is associated with reduced risk of three or more exacerbations in the subsequent year (OR 0.352 [95% CI, 0.164 to 0.753], P = 0.007). Conclusions: Asthma is characterized by mitochondrial dysfunction. Higher mtDNA-CN identifies an exacerbation-resistant asthma phenotype, suggesting mitochondrial function is important in exacerbation risk.