Explainable multimodal prediction of treatment-resistance in patients with depression leveraging brain morphometry and natural language processing.

Although 20 % of patients with depression receiving treatment do not achieve remission, predicting treatment-resistant depression (TRD) remains challenging. In this study, we aimed to develop an explainable multimodal prediction model for TRD using structured electronic medical record data, brain morphometry, and natural language processing. In total, 247 patients with a new depressive episode were included. TRD-predictive models were developed based on the combination of following parameters: selected tabular dataset features, independent components-map weightings from brain T1-weighted magnetic resonance imaging (MRI), and topic probabilities from clinical notes. All models applied the extreme gradient boosting (XGBoost) algorithm via five-fold cross-validation. The model using all data sources showed the highest area under the receiver operating characteristic of 0.794, followed by models that used combined brain MRI and structured data, brain MRI and clinical notes, clinical notes and structured data, brain MRI only, structured data only, and clinical notes only (0.770, 0.762, 0.728, 0.703, 0.684, and 0.569, respectively). Classifications of TRD were driven by several predictors, such as previous exposure to antidepressants and antihypertensive medications, sensorimotor network, default mode network, and somatic symptoms. Our findings suggest that a combination of clinical data with neuroimaging and natural language processing variables improves the prediction of TRD.

Diagnostic uplift through the implementation of short tandem repeat analysis using exome sequencing.

To date, approximately 50 short tandem repeat (STR) disorders have been identified; yet, clinical laboratories rarely conduct STR analysis on exomes. To assess its diagnostic value, we analyzed STRs in 6099 exomes from 2510 families with mostly suspected neurogenetic disorders. We employed ExpansionHunter and REViewer to detect pathogenic repeat expansions, confirming them using orthogonal methods. Genotype-phenotype correlations led to the diagnosis of thirteen individuals in seven previously undiagnosed families, identifying three autosomal dominant disorders: dentatorubral-pallidoluysian atrophy (n = 3), spinocerebellar ataxia type 7 (n = 2), and myotonic dystrophy type 1 (n = 2), resulting in a diagnostic gain of 0.28% (7/2510). Additionally, we found expanded ATXN1 alleles (≥39 repeats) with varying patterns of CAT interruptions in twelve individuals, accounting for approximately 0.19% in the Korean population. Our study underscores the importance of integrating STR analysis into exome sequencing pipeline, broadening the application of exome sequencing for STR assessments.

Double-chambered left ventricle with a thrombus in an asymptomatic patient: A case report.

BACKGROUND: Double-chambered left ventricle (DCLV) is an extremely rare congenital disease in which the left ventricle (LV) is divided by abnormal muscle tissue. Due to its rarity, there is a lack of data on the disease, including its diagnosis, treatment, and prognosis. Accordingly, we report a case in which DCLV was diagnosed and followed up. CASE SUMMARY: A 45-year-old man presented to our hospital due to abnormal findings on an electrocardiogram recorded during a health check. He had no specific cardiac symptoms, comorbidities or relevant past medical history. Echocardiography revealed that the LV was divided into two by muscle fibers. There were no findings of ischemia on coronary angiography and coronary computed tomography angiography performed to exclude differential diagnoses. After comprehensive analysis of the images, DCLV was diagnosed. As it seemed to be asymptomatic DCLV, we decided the patient was to be observed without administering any medication. However, follow-up echocardiography revealed a thrombus in the accessory chamber (AC). Anticoagulant medication was initiated, the thrombus resolved, and the patient is currently undergoing follow-up without any specific symptoms. CONCLUSION: Asymptomatic, uncomplicated DCLV was diagnosed through multimodal imaging; however, a thrombus in the AC occurred during the follow-up. The findings highlight that multimodal imaging is essential in diagnosing DCLV, and that anticoagulation is important in its management.

Higher HbA1c Is Associated With Greater 2-Year Progression of White Matter Hyperintensities.

White matter hyperintensity (WMH) lesions on brain MRI images are surrogate markers of cerebral small vessel disease. Longitudinal studies examining the association between diabetes and WMH progression have yielded mixed results. Thus, in this study, we investigated the association between HbA1c, a biomarker for the presence and severity of hyperglycemia, and longitudinal WMH change after adjusting for known risk factors for WMH progression. We recruited 64 participants from South Korean memory clinics to undergo brain MRI at the baseline and a 2-year follow-up. We found the following. First, higher HbA1c was associated with greater global WMH volume (WMHV) changes after adjusting for known risk factors (ß = 7.7 × 10-4; P = 0.025). Second, the association between baseline WMHV and WMHV progression was only significant at diabetic levels of HbA1c (P < 0.05, when HbA1c >6.51%), and non-apolipoprotein E (APOE) ε4 carriers had a stronger association between HbA1c and WMHV progression (ß = -2.59 × 10-3; P = 0.004). Third, associations of WMHV progression with HbA1c were particularly apparent for deep WMHV change (ß = 7.17 × 10-4; P < 0.01) compared with periventricular WMHV change and, for frontal (ß = 5.00 × 10-4; P < 0.001) and parietal (ß = 1.53 × 10-4; P < 0.05) lobes, WMHV change compared with occipital and temporal WMHV change. In conclusion, higher HbA1c levels were associated with greater 2-year WMHV progression, especially in non-APOE ε4 participants or those with diabetic levels of HbA1c. These findings demonstrate that diabetes may potentially exacerbate cerebrovascular and white matter disease.

Post-Hair Transplantation Complication: Kinky or Severely Curly Hair.

OBJECTIVE: To investigate the etiology and preventive measures of posttransplant kinky or curly hair growth after female hairline correction surgery. BACKGROUND: Hair transplant surgery can be accompanied by various adverse effects, one of which is severely kinky or curly hair after surgery. Posttransplant kinky or curly hair is not well-understood for its cause or prevention. METHODS: The study was targeted at a total of 980 patients who were confirmed whether they developed kinky or curly hair after female hairline correction surgery. Incidence, surgical method, degree of curliness, predisposed location, characteristics, hair caliber (thin, medium, and thick), and left-right differences were examined. RESULTS: Among the total 980 patients, posttransplant curly hair (PTCH) was manifested in 38(3.9%) patients. None of the patients who underwent surgery at the present clinic developed posttransplant kinky hair; all 38 patients showed PTCH growth. In 36 cases, transplanted hair started to grow in curly patterns around 4 months after surgery. However, the remaining 2 cases showed no curly growth pattern when the transplanted hair was short at postoperative 4 months, but started to grow curly starting at 6 to 8 months after surgery as the hair growth direction was obstructed or compressed by the existing hair. CONCLUSION: Familiarity with the cause, prevention, and management of posttransplant kinky hair and PTCH will be of great help to hair surgeons.

Precise base editing without unintended indels in human cells and mouse primary myoblasts.

Base editors are powerful tools for making precise single-nucleotide changes in the genome. However, they can lead to unintended insertions and deletions at the target sites, which is a significant limitation for clinical applications. In this study, we aimed to eliminate unwanted indels at the target sites caused by various evolved base editors. Accordingly, we applied dead Cas9 instead of nickase Cas9 in the base editors to induce accurate substitutions without indels. Additionally, we tested the use of chromatin-modulating peptides in the base editors to improve nucleotide conversion efficiency. We found that using both dead Cas9 and chromatin-modulating peptides in base editing improved the nucleotide substitution efficiency without unintended indel mutations at the desired target sites in human cell lines and mouse primary myoblasts. Furthermore, the proposed scheme had fewer off-target effects than conventional base editors at the DNA level. These results indicate that the suggested approach is promising for the development of more accurate and safer base editing techniques for use in clinical applications.

Identification of bacterial pathogens in brain abscesses by metagenomic approach using nanopore 16S amplicon sequencing.

Brain abscess is medically challenging. In this study, we applied nanopore sequencing for 16S rRNA analysis and investigated its efficacy and diagnostic value for patients with brain abscesses. Genomic DNA was extracted from the pus samples (n = 27) of brain abscess, and 16S rRNA genes were amplified by PCR. Sequencing libraries were generated using a rapid barcoding kit, and the generated reads were analyzed using the EPI2ME16S workflow. A conventional culture study was performed. More sensitive identification of pathogens was made by 16S sequencing, faster than the culture study. The proportion of anaerobic bacteria identified by 16S sequencing was higher (75%) than that obtained by culturing (32%). Polymicrobial infections were identified in 10 cases (40%) by 16S sequencing, while the culture study identified multiple bacteria in only 2 cases (8%). 16S sequencing was useful for identifying the composition of polymicrobial infections, including rare pathogens, and for the initial diagnosis of space-occupying lesions.

Determining efficacy of dynamic multimedia bowel preparation instructions versus standard instructions on adenoma detection and patient reported measures (DIGICLEAN trial): a study protocol for a multicentre, colonoscopist-blinded, randomised controlled trial.

INTRODUCTION: Colonoscopy plays important roles in bowel cancer screening and treatment. Poor bowel preparation occurs in 20-25% of colonoscopies. This negatively impacts adenoma and sessile serrated lesion detection rates, procedural time, requirement for repeat colonoscopies, healthcare costs and likelihood of patient withdrawal from screening programmes. It is unclear whether a combination of multimedia modalities can improve bowel preparation quality, adenoma detection rates and patient-reported measures in those undergoing colonoscopy assessment. METHODS: The DIGICLEAN trial is a prospective, parallel, multicentre, colonoscopist-blinded, randomised controlled trial. The trial will enrol 1294 participants aged 45 years and older who are indicated for a colonoscopy as an outpatient with a positive faecal occult blood test, iron deficiency anaemia or rectal bleeding. Participants will be randomised into the interventional arm, where bowel preparation instructions are delivered via a web-based application which uses scheduled short messaging service, regular patient survey assessment, email and videos; or the control arm, where routine standard written, verbal or emailed instructions are administered. The web-based application will assess patient-reported bloating, constipation and dietary adherence leading up to the colonoscopy. Depending on patient responses, additional aperients may be encouraged digitally in the interventional arm with same instructions made available in written format for the control arm. Patient-reported measures will be collected in both arms the day after the procedure using the validated Newcastle ENDOPREM questionnaire. In some sites, participants will undergo digital pre-anaesthetic screening as well. The co-primary endpoints are the adenoma detection rates and patient-reported measures taken after the colonoscopy. ETHICS AND DISSEMINATION: Ethics approval for this study was obtained from the Western Sydney Local Health District Human Research Ethics Committee (2022/ETH00059). Findings will be reported at national and international gastroenterology meetings and published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: ACTRN12622000747729.

Talaromyces rugulosus ventriculitis diagnosed by nanopore amplicon sequencing, 2022.

Ventriculitis has serious complications and a high mortality rate, so it is important to early identification of the pathogen for appropriate treatment. We report case of ventriculitis caused by Talaromyces rugulosus, a rare pathogen, in South Korea. Affected patient was immunocompromised. Repeated cerebrospinal fluid culture tests were negative, but the pathogen was identified by fungal internal transcribed spacer amplicon nanopore sequencing. The pathogen was detected outside the endemic area of talaromycosis.

Cholesterol sulfate inhibits osteoclast differentiation and survival by regulating the AMPK-Sirt1-NF-κB pathway.

Cholesterol sulfate (CS) is an activator of retinoic acid-related orphan receptor α (RORα). CS treatment or RORα overexpression attenuates osteoclastogenesis in a collagen-induced arthritis mouse model. However, the mechanism by which CS and RORα regulate osteoclast differentiation remains largely unknown. Thus, we aimed to investigate the role of CS and RORα in osteoclastogenesis and their underlying mechanism. CS inhibited osteoclast differentiation, but RORα deficiency did not affect osteoclast differentiation and CS-mediated inhibition of osteoclastogenesis. CS enhanced adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and sirtuin1 (Sirt1) activity, leading to nuclear factor-κB (NF-κB) inhibition by decreasing acetylation at Lys310 of p65. The NF-κB inhibition was restored by AMPK inhibitor, but the effects of CS on AMPK and NF-κB were not altered by RORα deficiency. CS also induced osteoclast apoptosis, which may be due to sustained AMPK activation and consequent NF-κB inhibition, and the effects of CS were significantly reversed by interleukin-1ß treatment. Collectively, these results indicate that CS inhibits osteoclast differentiation and survival by suppressing NF-κB via the AMPK-Sirt1 axis in a RORα-independent manner. Furthermore, CS protects against bone destruction in lipopolysaccharide- and ovariectomy-mediated bone loss mouse models, suggesting that CS is a useful therapeutic candidate for treating inflammation-induced bone diseases and postmenopausal osteoporosis.

Do age-based discontinuation recommendations influence cervical cancer screening rates? Evidence from the United States' Behavioral Risk Factor Surveillance System, 2016 and 2018.

The United States Preventive Services Task Force (USPSTF) recommends that women with adequate prior screening and average cervical cancer risk discontinue routine cervical cancer screening after age 65. This study's objective was to estimate how the USPSTF recommendation affects Papanicolaou (Pap) test rates among women at age 66 in the United States. We used nationally representative 2016 and 2018 Behavioral Risk Factor Surveillance System data for women ages 56-76 (n = 226,031) and a regression discontinuity design to estimate changes in annual Pap test rates at age 66. Among women age 66-76, 22.5% reported receiving a Pap test within the past one year. At age 66, annual Pap rates declined by 5.9 percentage points (p.p.) (95% Confidence Interval [CI]: -7.7, -4.1) off a pre-66 rate of 39%. The change varied by race/ethnicity, education, and marital status. Pap rates did not change discretely for non-Hispanic Black women (0.8 p.p.; 95% CI: -5.4, 7.1) but did for women from other racial/ethnic groups. The decline was larger for women who graduated college (-9.0 p.p.; 95% CI: -12.0, -5.9) than for women without a college degree and for women who were never married (-9.4 p.p., 95% CI: -17.3, -1.5) than for women who were married/partnered or divorced/separated. The USPSTF recommendation to discontinue cervical cancer screening after age 65 leads to a sharp decline in Pap test rates at age 66 but disparately affects women based on race, education and marital status. Further study is needed to assess the consequences of these changes.

Gastric mucosal swab as an alternative to biopsy for Helicobacter pylori detection.

BACKGROUND AND AIMS: Gastric mucosal swab may be a more sensitive sampling method than a biopsy since Helicobacter pylori (H. pylori) resides within the mucus layer. We compared the diagnostic performance of the rapid urease test (RUT) and bacterial load of H. pylori between swabs and tissue biopsy. METHODS: Overall, 276 RUTs (138 swab-RUTs (S-RUT) and 138 tissue-RUTs (T-RUT)) were performed. To diagnose H. pylori infection, RUT, H. pylori PCR, and 16S ribosomal RNA gene sequencing of tissue and swab were used, and its infection was defined as at least two positives of the six test results. The diagnostic performances of RUTs and the H. pylori bacterial load using qPCR were compared between swab and biopsy. RESULTS: The positivity rates of S-RUT and T-RUT were 35.5% (49/138) and 25.4% (35/138), respectively. The sensitivity, specificity, and accuracy of S-RUT were 98.0%, 100.0%, and 99.2%, while those of T-RUT were 70.0%, 100%, and 89.1%, respectively. The sensitivity and accuracy were significantly higher for S-RUT than for T-RUT (p < 0.05). In the patients with atrophic gastritis and intestinal metaplasia, S-RUT showed significantly higher sensitivity than T-RUT. qPCR showed that the swab contained a significantly higher H. pylori bacterial load than tissue biopsy (22.92-fold and 31.61-fold in the antrum and body (p < 0.05), respectively). CONCLUSIONS: Gastric mucosal swabs showed higher RUT accuracy and H. pylori bacterial load than a tissue biopsy. This may be an alternative to a biopsy when diagnosing H. pylori infection during endoscopy is necessary. (ClinicalTrials.gov, NCT05349578).

Effectiveness and cost-effectiveness of palliative care in natural experiments: a systematic review.

CONTEXT: Investigators in palliative care rely heavily on routinely collected data, which carry risk of unobserved confounding and selection bias. 'Natural experiments' offer opportunities to generate credible causal treatment effect estimates from observational data. OBJECTIVES: We aimed first to review studies that employed 'natural experiments' to evaluate palliative care, and second to consider implications for expanding use of these methods. METHODS: We searched systematically seven databases to identify studies using 'natural experiments' to evaluate palliative care's effect on outcomes and costs. We searched three grey literature repositories, and hand-searched journals and prior systematic reviews. We assessed reporting using the Strengthening the Reporting of Observational Studies in Epidemiology checklist and a bespoke methodological quality tool, using two reviewers at each stage. We combined results in a narrative synthesis. RESULTS: We included 17 studies, which evaluated a wide range of interventions and populations. Seven studies employed a difference-in-differences design; five each used instrumental variables and interrupted time series analysis. Outcomes of interest related mostly to healthcare use. Reporting quality was variable. Most studies reported lower costs and improved outcomes associated with palliative care, but a third of utilisation and place of death evaluations found no effect. CONCLUSION: Among the large number of observational studies in palliative care, a small minority have employed causal mechanisms. High-volume routine data collection, the expansion of palliative care services worldwide and recent methodological advances offer potential for increased use of 'natural experiments'. Such studies would improve the quality of the evidence base.

An Oscillatory Path to Vaccination: The Roles of Normative and Epistemic Factors in Explaining Vaccination Hesitancy in COVID-19.

This study examined the roles of normative and epistemic factors in influencing individuals' reluctance to be vaccinated during the COVID-19 pandemic. Individuals' ethical orientations (IEO; teleology vs. deontology) were introduced as normative characteristics, while COVID-19 vaccine conspiracy beliefs and vaccine knowledge were addressed as issue-specific epistemic factors. We conducted two online surveys to investigate each of these three factors' influences on the level of Americans' reluctance to receive COVID-19 vaccines. Combinations of these factors that predict COVID-19 vaccination hesitancy levels were also explored to provide integrated perspectives in the specific vaccination context. Our findings demonstrated the positive association between IEO and reluctance to receive COVID-19 vaccines. Significant interactions between 1) COVID-19 vaccine conspiracy beliefs and IEO and 2) conspiracy beliefs and vaccine knowledge were also identified. Implications, limitations, and suggestions for future study were addressed.

Intranasal Immunization With Nanoparticles Containing an Orientia tsutsugamushi Protein Vaccine Candidate and a Polysorbitol Transporter Adjuvant Enhances Both Humoral and Cellular Immune Responses.

Scrub typhus, a mite-borne infectious disease, is caused by Orientia tsutsugamushi. Despite many attempts to develop a protective strategy, an effective preventive vaccine has not been developed. The identification of appropriate Ags that cover diverse antigenic strains and provide long-lasting immunity is a fundamental challenge in the development of a scrub typhus vaccine. We investigated whether this limitation could be overcome by harnessing the nanoparticle-forming polysorbitol transporter (PST) for an O. tsutsugamushi vaccine strategy. Two target proteins, 56-kDa type-specific Ag (TSA56) and surface cell Ag A (ScaA) were used as vaccine candidates. PST formed stable nano-size complexes with TSA56 (TSA56-PST) and ScaA (ScaA-PST); neither exhibited cytotoxicity. The formation of Ag-specific IgG2a, IgG2b, and IgA in mice was enhanced by intranasal vaccination with TSA56-PST or ScaA-PST. The vaccines containing PST induced Ag-specific proliferation of CD8+ and CD4+ T cells. Furthermore, the vaccines containing PST improved the mouse survival against O. tsutsugamushi infection. Collectively, the present study indicated that PST could enhance both Ag-specific humoral immunity and T cell response, which are essential to effectively confer protective immunity against O. tsutsugamushi infection. These findings suggest that PST has potential for use in an intranasal vaccination strategy.

Native Americans' Responses to Obesity Attributions and Message Sources in an Obesity Prevention Campaign.

This study investigated the effectiveness of Native American (NA) targeted obesity prevention messages. The researchers manipulated obesity attributions (internal vs. external) and message sources (NAs vs. non-NAs) in a 2 × 2 mixed experimental design to examine the way these message attributes influence NAs' emotional, attitudinal, cognitive, and behavioral responses. One-hundred and eighteen Cheyenne and Arapaho (C&A) tribal citizens read two paper-based obesity prevention PSAs and then answered questions that assessed their message responses. The key findings demonstrated that the match between participants' ethnicity and the message source's ethnicity had a significant effect, as it reduced anger and promoted positive message attitudes and favorable source evaluations. Implications, limitations, and suggestions for future research and NA targeted health campaigns are discussed.

Nanopore 16S amplicon sequencing enables rapid detection of pathogen in knee periprosthetic joint infection.

OBJECTIVES: We investigated whether nanopore 16S amplicon sequencing is capable of bacterial identification in patients with knee prosthetic joint infection (PJI), and we compared its efficacy with conventional culture studies. METHODS: In total, 36 patients who had clinical manifestation suspected of PJI were enrolled in this study. To begin, synovial fluids were aspirated from the affected knee using aseptic technique and tissues specimens were obtained during the surgery. Next, DNA was extracted from the synovial fluid or tissues, and 16S rDNA PCR was performed. In PCR positive cases, nanopore amplicon sequencing was then performed for up to 3 h. The results of amplicon sequencing were compared to those of conventional culture studies. RESULTS: Of the 36 patients enrolled, 22 were classified as true infections according to the MSIS criteria whereas 14 were considered uninfected. Among the 22 PJI cases, 19 cases were culture positive (CP-PJI) while three cases were culture negative (CN-PJI). In 14 of 19 (73.7 %) CP- PJI cases, 16S sequencing identified concordant bacteria with conventional culture studies with a significantly shorter turnaround time. In some cases, nanopore 16S sequencing was superior to culture studies in the species-level identification of pathogen and detection of polymicrobial infections. Altogether, in the majority of PJI candidate patients (32 of 36, 88.9 %), 16S sequencing achieved identical results to cultures studies with a significantly reduced turnaround time (100.9 ± 32.5 h vs. 10.8 ± 7.7 h, p < 0.001). CONCLUSIONS: Nanopore 16S sequencing was found to be particularly useful for pathogen identification in knee PJI. Although the sensitivity was not superior to culture studies, the nanopore 16S sequencing was much faster, and species-level identification and detection of polymicrobial infections were superior to culture studies.

Comparison of catastrophic out-of-pocket medical expenditure among older adults in the United States and South Korea: what affects the apparent difference?

BACKGROUND: Medical spending rises sharply with age. Even with universal health insurance, older adults may be at risk of catastrophic out-of-pocket medical spending. We aimed to compare catastrophic out-of-pocket medical spending among adults ages 65 and older in the United States, where seniors have near-universal coverage through Medicare, versus South Korea, where all residents have national health insurance. METHODS: We used the 2016 Health and Retirement Study and the Korean Longitudinal Study of Aging. The study population were adults ages 65 and over in the US (n = 9,909) and South Korea (n = 4,450; N = 14,359). The primary outcome of interest was older adults' exposure to catastrophic out-of-pocket medical expenditure, defined as out-of-pocket medical spending over the past two years that exceeded 50% of annual household income. To examine the factors affecting catastrophic out-of-pocket medical spending of older adults in both countries, we performed logistic regression analyses. To compare the contribution of demographic factors versus health system-level factors to catastrophic out-of-pocket medical spending, we performed a Blinder-Oaxaca decomposition. RESULTS: The proportion of respondents with catastrophic out-of-pocket medical expenditure was 5.8% and 3.0% in the US and South Korea, respectively. A Blinder-Oaxaca decomposition showed that the difference in the rate of catastrophic out-of-pocket medical expenditure spending between the two countries was attributable largely to unobservable system-level factors, rather than observed differences in the sociodemographic characteristics. CONCLUSIONS: Exposure to catastrophic out-of-pocket medical spending is considerably higher in the US than South Korea. Most of the difference can be attributed to unobserved health system-level factors.

Bifidobacterium longum and Galactooligosaccharide Improve Skin Barrier Dysfunction and Atopic Dermatitis-like Skin.

PURPOSE: The beneficial effects of a combination therapy using Bifidobacterium longum and galactooligosaccharide (GOS) for the treatment of atopic dermatitis (AD) have not been elucidated. METHODS: Gene expressions of interleukin (IL)-4 and IL-13 from peripheral blood mononuclear cells and fecal abundance of B. longum from 12-month-old infants were evaluated. Human primary epidermal keratinocytes (HEKs) and hairless mice were treated with B. longum, GOS, B. longum-derived extracellular vesicles (BLEVs), dinitrochlorobenzene (DNCB), or a synbiotic mixture of B. longum and GOS. Expression of epidermal barrier proteins and cytokines as well as serum immunoglobulin E (IgE) levels were analyzed in HEKs and mice. Dermatitis scores, transepidermal water loss (TEWL), epidermal thickness, and fecal B. longum abundance were evaluated in mice. RESULTS: Fecal abundance of B. longum was negatively correlated with blood IL-13 expression in infants. B. longum or BLEVs increased expression of filaggrin (FLG) and loricrin (LOR) in HEKs. B. longum increased the efficacy of GOS to upregulate FLG and LOR expressions in HEKs. Oral administration of GOS increased fecal abundance of B. longum in mice. Oral administration of B. longum attenuated DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, and deficiency of epidermal barrier proteins. Moreover, the combination of B. longum and GOS showed greater effects to improve DNCB-induced skin inflammation, abnormal TEWL, AD-like skin, serum IgE levels, IL-4 over-expression, and the deficiency of epidermal barrier proteins than the administration of B. longum alone. CONCLUSIONS: B. longum and GOS improve DNCB-induced skin barrier dysfunction and AD-like skin.