The forecasted prevalence of comorbidities and multimorbidity in people with HIV in the United States through the year 2030: A modeling study.

BACKGROUND: Estimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030. METHODS AND FINDINGS: Using the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts. CONCLUSIONS: The PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

Repeated-dose toxicity and toxicokinetic study of isobutylparaben in rats subcutaneously treated for 13 weeks.

Parabens have historically served as antimicrobial preservatives in a range of consumables such as food, beverages, medications, and personal care products due to their broad-spectrum antibacterial and antifungal properties. Traditionally, these compounds were believed to exhibit low toxicity, causing minimal irritation, and possessing limited sensitization potential. However, recent evidence suggests that parabens might function as endocrine-disrupting chemicals (EDCs). Consequently, extensive research is underway to elucidate potential human health implications arising from exposure to these substances. Among these parabens, particular concerns have been raised regarding the potential adverse effects of iso-butylparaben (IBP). Studies have specifically highlighted its potential for inducing hormonal disruption, significant ocular damage, and allergic skin reactions. This study aimed to evaluate the prolonged systemic toxicity, semen quality, and estrus cycle in relation to endocrine disruption endpoints, alongside assessing the toxicokinetic behavior of IBP in Sprague-Dawley rats following a 13-week repeated subcutaneous administration. The rats were administered either the vehicle (4% Tween 80) or IBP at dosage levels of 2, 10, and 50 mg/kg/day for 13 weeks. Blood collection for toxicokinetic study was conducted on three specified days: day 1 (1st), day 30 (2nd), and day 91 (3rd). Systemic toxicity assessment and potential endocrine effects were based on various parameters including mortality rates, clinical signs, body weights, food and water consumption, ophthalmological findings, urinalysis, hematological and clinical biochemistry tests, organ weights, necropsy and histopathological findings, estrus cycle regularity, semen quality, and toxicokinetic behavior. The findings revealed that IBP induced local irritation at the injection site in males at doses ≥ 10 mg/kg/day and in females at 50 mg/kg/day; however, systemic toxicity was not observed. Consequently, the no-observed-adverse-effect level (NOAEL) for IBP was determined to be 50 mg/kg/day in rats of both sexes, indicating no impact on the endocrine system. The toxicokinetics of IBP exhibited dose-dependent systemic exposure, reaching a maximum dose of 50 mg/kg/day, and repeated administration over 13 weeks showed no signs of accumulation.

Mass spectrometry (MS)-based metabolomics of plasma and urine in dry eye disease (DED)-induced rat model.

Dry eye disease (DED) is an ophthalmic disease associated with poor quality and quantity of tears, and the number of patients is steadily increasing. The aim of this study was to determine plasma and urine metabolites obtained from DED scopolamine animal model where dry eye conditions (DRY) are induced. It was also of interest to examine whether DED (scopolamine) rat model was exacerbated by treatment with benzalkonium chloride (BAC). Subsequently, plasma and urine metabolites were analyzed using liquid chromatography (LC) and gas chromatography (GC)-mass spectrometry (MS), respectively. Data demonstrated that DED indicators such as tear volume, tear breakup time (TBUT), and corneal damage in the DED groups (DRY and BAC group) differed from those of control (CON). Similar results were noted in inflammatory factors such as interleukin (IL-1ß), IL-6, and tumor necrosis factor (TNF)-α. In the partial least squares-discriminant analysis (PLS-DA) score plots, the three groups were distinctly separated from each other. In addition, the related metabolites were also associated with these distinct separations as evidenced by 9 and 14 in plasma and urine, respectively. Almost all of the selected metabolites were decreased in the DRY group compared to CON, and the BAC group was lower than the DRY. In plasma and urine, lysophosphatidylcholine/lysophosphatidylethanolamine, organic acids, amino acids, and sugars varied between three groups, and these metabolites were related to inflammation and oxidative stress. Data suggest that treatment with scopolamine with/without BAC-induced DED and affected the level of systemic metabolites involved in inflammation and oxidative stress.

Severe mpox requiring colostomy in a patient with advanced HIV disease: A case report and literature review.

This severe monkeypox case described a 23-year-old male with advanced HIV-1 disease presenting perirectal abscess, extensive anal ulcerative lesions requiring colostomy, and tecovirimat resistance. Radiologically non-liquefied perirectal abscess presented diagnostic challenges highlighting the complexity of aggressive monkeypox manifestations in immunocompromised individuals.

A Motivational Technology Perspective on the Use of Smart Wrist-Worn Wearables for Postpartum Exercise and Weight Management.

Exercise and weight management is crucial in preventing postpartum depression and long-term obesity that carries the risk of chronic illness among postpartum women. Although communication devices, such as a smart wrist-worn wearable (SWW), can help users be more physically active, the extent to which postpartum women might benefit from this technology is unknown. We examined how SWWs promoted exercise and helped postpartum women return to pre-pregnancy weight. We tested a model based on the premise that a motivational device that prompts users to engage with it can establish healthy daily routines. An online survey of 309 postpartum women who were living in the United States and were current users of SWWs revealed that the device encouraged them to spend time completing workout goals. Technological affordances (i.e. customization, navigability, and interactivity) and subsequent user engagement with the device positively predicted total workout hours among postpartum women. We present practical implications for postpartum care programs and smart wearable developers.

Understanding the Dynamics of Online Social Support Among Postpartum Mothers in Online Communities.

INTRODUCTION: Despite previous attempts to identify types of social support among postpartum mothers, researchers have overlooked how and why postpartum mothers seek and offer social support as well as the dynamics of participation in online communities. OBJECTIVE AND METHODS: The objective of the current study was to explore possible answers through grounded theory approach of interviews with 24 mothers who have experienced postpartum depression and psychological distress. RESULTS: The primary motivation to join the community was a desire for connectedness and reassurance. Initially engaged to seek information, users began to share not only informational and tangible support, but also emotional and esteem support as they gained comfort with their membership in these groups. CONCLUSION: Findings suggest that affirming normalcy while coping with postpartum distress is an integral part of the social support shared among postpartum mothers. Moreover, the findings indicated that to maximize the sustainability as well as the effectiveness of online communities for postpartum mothers, motivating silent users to participate and reciprocate is crucial.

What is already known Many postpartum mothers have joined online communities to exchange information and social support with fellow moms in the group. Previous studies have found various motivations for postpartum moms joining online communities and what types of social support they share. However, what motivates postpartum mothers to get involved, stay in or leave online communities based on level of satisfaction with those communities remains unclear.What this study can add to the literature Two major motivations among postpartum mothers to join online social support groups were a need to communicate to end their sense of isolation and a desire to gather information from experienced people. After gaining a sense of group reliability, they began posting to seek and provide support. Through experiencing and observing the exchange of support within the community, postpartum mothers felt more attached to the group. They also developed the need to reciprocate support through empathy based on their development of in-group identity. In addition, the motivation to reciprocate stemmed from enhanced confidence in their own knowledge of postpartum symptoms.

A Simple Laser-Induced Breakdown Spectroscopy Method for Quantification and Classification of Edible Sea Salts Assisted by Surface-Hydrophilicity-Enhanced Silicon Wafer Substrates.

Salt, one of the most commonly consumed food additives worldwide, is produced in many countries. The chemical composition of edible salts is essential information for quality assessment and origin distinction. In this work, a simple laser-induced breakdown spectroscopy instrument was assembled with a diode-pumped solid-state laser and a miniature spectrometer. Its performances in analyzing Mg and Ca in six popular edible sea salts consumed in South Korea and classification of the products were investigated. Each salt was dissolved in water and a tiny amount of the solution was dropped and dried on the hydrophilicity-enhanced silicon wafer substrate, providing homogeneous distribution of salt crystals. Strong Mg II and Ca II emissions were chosen for both quantification and classification. Calibration curves could be constructed with limits-of-detection of 87 mg/kg for Mg and 45 mg/kg for Ca. Also, the Mg II and Ca II emission peak intensities were used in a k-nearest neighbors model providing 98.6% classification accuracy. In both quantification and classification, intensity normalization using a Na I emission line as a reference signal was effective. A concept of interclass distance was introduced, and the increase in the classification accuracy due to the intensity normalization was rationalized based on it. Our methodology will be useful for analyzing major mineral nutrients in various food materials in liquid phase or soluble in water, including salts.

Combination of LIBS-based elemental analysis and near-infrared molecular fingerprinting of bile juice to enhance identification of gallbladder cancer.

Laser-induced breakdown spectroscopy (LIBS) and near-infrared (NIR) spectroscopy, enabling the measurement of raw bile directly without sample pretreatment, were cooperatively combined to enhance the discrimination of gallbladder cancer (GBC) from other diseases of gallstone and gallbladder (GB) polyp. Since elemental contents and metabolite compositions of bile vary according to the pathological conditions of pancreaticobiliary patients, the use of complementary information could be synergetic to improve disease identification accuracy. The ratios of Mg and Na peak areas (AMg/ANa) and Na and K peak areas (ANa/AK) in the LIBS spectra of GBC samples were different from those of the remaining samples. Also, the intensity ratios of main NIR peaks differed in GBC. Nonetheless, the use of only element peak area ratio or NIR peak intensity ratio was not sufficient to clearly discriminate GBC. On the other hand, when the ANa/AK values and second NIR principal component scores were combined, the discrimination of GBC from normal/gallstone/GB polyp was substantially enhanced owing to incorporation of both complementary GBC-discriminant spectroscopic signatures.

Metabolomics profiling of valproic acid-induced symptoms resembling autism spectrum disorders using 1H NMR spectral analysis in rat model.

Prenatal exposure to valproic acid (VPA) has been implicated in the manifestation of autism spectrum disorder (ASD)-like behavioral and functional changes both in human and rodents including mice and rats. The objective of this study was to determine metabolomics profiling and biomarkers related to VPA-induced symptoms resembling ASD using proton nuclear magnetic resonance (1H-NMR) spectral data. VPA was administered to pregnant rats at gestation day 12.5 and effects measured subsequently in male 4-week-old offspring pups. The sociability of VPA-treated animals was significantly diminished and exhibited ASD-like behavior as evidenced by reduction of social adaptation disorder and lack of social interactions. To find biomarkers related to ASD, the following were collected prefrontal brain cortices, urine bladder and blood samples directly from heart puncture. In all samples, principal component analysis (PCA) and partial least-squares discriminant analysis (PLS-DA) displayed significant clustering pattern differences between control and treated groups. Valine, taurine, myo-inositol, 3-hydroxybutyrate and 1,3-dihydroxyacetone were significantly decreased in brain cortices in treated rats. Serum metabolites of glucose, creatine phosphate, lactate, glutamine and threonine were significantly increased in VPA-administered animals. Urinary metabolites of pimelate, 3-hydroxyisovalerate and valerate were significantly reduced in VPA-treated rat, whereas galactose and galactonate levels were elevated. Various metabolites were associated with mitochondrial dysfunction metabolism and central nervous system disorders. Data demonstrated that VPA-induced alterations in endogenous metabolites of serum, urine, and brain cortex which might prove useful as biomarkers for symptoms resembling ASD as a model of this disorder.

Nursing home staff's perceptions of barriers and needs in implementing person-centred care for people living with dementia: A qualitative study.

AIMS AND OBJECTIVES: This study explored nursing home staff's barriers and needs in implementing person-centred care for people with dementia. BACKGROUND: Person-centred care is an imperative international policy and the best-practice standard for dementia care. However, a gap exists between policy and practice. Moreover, there is a lack of qualitative studies that explored nursing home staff's barriers and needs in implementing person-centred care for people living with dementia. DESIGN: A qualitative descriptive approach was adopted. METHODS: Using convenience sampling method, a total of 24 staff members (nurses, nurse's aides, or care workers) were recruited from six nursing homes in Korea. Two in-depth, face-to-face, one-to-one interviews were conducted with all participants (a total of 48 interviews). A semi-structured interview guide was used and field notes were written after each interview. Data were collected until data saturation was reached. Qualitative content analysis was used. This study followed the COREQ guidelines. RESULTS: Four themes emerged from data analysis: insufficient resources, lack of education, negative mindset and poor relationships. This study showed that nursing home staff experienced many barriers and unmet needs in implementing person-centred care for people with dementia. CONCLUSION: The findings indicated that nursing home staff faced many barriers and needs in implementing person-centred care for people with dementia. Nursing home staff need more legitimate, financial, educational and emotional support. RELEVANCE TO CLINICAL PRACTICE: The study indicates more national and organisational support are needed for nursing home staff to successfully implement person-centred care for people living with dementia. Nursing home leaders need to recognise the importance of their role in overcoming the barriers and provide effective support for staff in implementing person-centred dementia care.

Identification and Characterization of PSEUDO-RESPONSE REGULATOR (PRR) 1a and 1b Genes by CRISPR/Cas9-Targeted Mutagenesis in Chinese Cabbage (Brassica rapa L.).

The CRISPR/Cas9 site-directed gene-editing system offers great advantages for identifying gene function and crop improvement. The circadian clock measures and conveys day length information to control rhythmic hypocotyl growth in photoperiodic conditions, to achieve optimal fitness, but operates through largely unknown mechanisms. Here, we generated core circadian clock evening components, Brassica rapa PSEUDO-RESPONSE REGULATOR (BrPRR) 1a, 1b, and 1ab (both 1a and 1b double knockout) mutants, using CRISPR/Cas9 genome editing in Chinese cabbage, where 9-16 genetic edited lines of each mutant were obtained. The targeted deep sequencing showed that each mutant had 2-4 different mutation types at the target sites in the BrPRR1a and BrPRR1b genes. To identify the functions of BrPRR1a and 1b genes, hypocotyl length, and mRNA and protein levels of core circadian clock morning components, BrCCA1 (CIRCADIAN CLOCK-ASSOCIATED 1) and BrLHY (LATE ELONGATED HYPOCOTYL) a and b were examined under light/dark cycles and continuous light conditions. The BrPRR1a and 1ab double mutants showed longer hypocotyls, lower core circadian clock morning component mRNA and protein levels, and a shorter circadian rhythm than wildtype (WT). On the other hand, the BrPRR1b mutant was not significantly different from WT. These results suggested that two paralogous genes may not be associated with the same regulatory function in Chinese cabbage. Taken together, our results demonstrated that CRISPR/Cas9 is an efficient tool for achieving targeted genome modifications and elucidating the biological functions of circadian clock genes in B. rapa, for both breeding and improvement.

Is it reciprocating or self-serving?: Understanding coping strategies for postpartum depression in an online community for Korean mothers.

The proliferation of online health communities creates opportunities to exchange social support. Given the growing need to investigate the extent to which social support helps mothers with postpartum depression (PPD) and psychological distress, we conducted a content analysis of 3,073 posts from a PPD-related message board in a prominent online community for Korean mothers. We found that community members tended to provide rather than seek support, indicating potential reciprocity in the community. We also found that emotion-focused coping strategies were much more prevalent than problem-focused coping strategies. Thus, the message board had an ambiguous identity, potentially undermining its actual purpose.

Metabolomics approach to biomarkers of dry eye disease using 1H-NMR in rats.

Dry eye disease (DED) is a chronic and progressive lesion on the ocular surface and induces symptoms, such as burning sensation, itchy eyes, heavy eyes, tired eyes, dry feeling, facial flushing, and blurred vision. The present study was performed to develop DED biomarkers using metabolomics in a rat model. DED was induced by injecting scopolamine and exposing rats to a dry condition. Scopolamine (12 mg/kg/day for 7 days) was subcutaneously injected to male Sprague-Dawley rats. The rats were placed in dry condition with air-flow and dehumidifier. Tear volume and tear breakup time (TBUT) were measured, and eyes were examined through fluorescein staining to assess DED. Mucosal damage and immune reactions were also determined. Plasma and urinary endogenous metabolites were determined using 1H-NMR analysis. Compared with control tear and TBUT levels were significantly decreased in the DED group whereas corneal damage was significantly increased. The levels of interleukins (IL-6) and IL-1ß significantly elevated in the cornea and lacrimal glands in the DED group. TNF-α was numerically increased but not significantly different between groups. Pattern recognition using principal component analysis (PCA) and orthogonal projections to latent structure-discriminant analysis (OPLS-DA) of the NMR spectra in global profiling revealed different clusters between DED and control groups. Target profiling demonstrated that PCA and OPLS-DA score plots were separated between DED and controls in plasma and urine. Subsequently, 9 plasma metabolites were selected to examine different clustering between groups, and 26 urinary metabolites were also selected. Plasma metabolites showed a non-significant rising tendency in the DED group. Urinary phenylalanine, phenylacetate, pantothenate, glycine, succinate, methanol, valine, propylene glycol, histidine, threonine, lactate, and acetate were significantly different between control and DED rats. These results may contribute to understanding the metabolic regulation that is involved in DED and might be useful for potential biomarkers related to DED in rats.

Racial/Ethnic Disparities in Patient-Provider Communication and the Role of E-Health Use.

Although the health care industry has strived to address racial/ethnic disparities in health communication, several gaps remain. Previous findings suggest that communication technology might help narrow the gaps; however, they do not provide a comprehensive picture of how or why. To answer these questions, we examined the potential role of communication technology in mitigating the racial/ethnic disparities in patient-provider communication. Data analysis of the 2018 Health Information National Trends Survey (N= 3,504) revealed that the levels of perceived quality of communication with health care providers were lower among Asians and Hispanics than non-Hispanic Whites while no difference emerged between Blacks and non-Hispanic Whites. Although the adoption of communication technology was relatively high across minority groups, its use appeared to play different roles in different racial/ethnic populations. The Internet and patient portals showed no particular associations with patient-provider communication except for Black Internet users, who reported poorer experiences with patient-provider communication than non-users. Among Asians and Hispanics, social media and mobile communication appeared to play different roles in impacting communication experiences with health care providers. The findings suggest that communication technologies need to be strategically utilized and tailored to better meet the communication needs of racial/ethnic minorities.

Cycling kinematics in healthy adults for musculoskeletal rehabilitation guidance.

BACKGROUND: Stationary cycling is commonly used for postoperative rehabilitation of physical disabilities; however, few studies have focused on the three-dimensional (3D) kinematics of rehabilitation. This study aimed to elucidate the three-dimensional lower limb kinematics of people with healthy musculoskeletal function and the effect of sex and age on kinematics using a controlled bicycle configuration. METHODS: Thirty-one healthy adults participated in the study. The position of the stationary cycle was standardized using the LeMond method by setting the saddle height to 85.5% of the participant's inseam. The participants maintained a pedaling rate of 10-12 km/h, and the average value of three successive cycles of the right leg was used for analysis. The pelvis, hip, knee, and ankle joint motions during cycling were evaluated in the sagittal, coronal, and transverse planes. Kinematic data were normalized to 0-100% of the cycling cycle. The Kolmogorov-Smirnov test, Mann-Whitney U test, Kruskal-Wallis test, and k-fold cross-validation were used to analyze the data. RESULTS: In the sagittal plane, the cycling ranges of motion (ROMs) were 1.6° (pelvis), 43.9° (hip), 75.2° (knee), and 26.9° (ankle). The coronal plane movement was observed in all joints, and the specific ROMs were 6.6° (knee) and 5.8° (ankle). There was significant internal and external rotation of the hip (ROM: 11.6°), knee (ROM: 6.6°), and ankle (ROM: 10.3°) during cycling. There was no difference in kinematic data of the pelvis, hip, knee, and ankle between the sexes (p = 0.12 to 0.95) and between different age groups (p = 0.11 to 0.96) in all anatomical planes. CONCLUSIONS: The kinematic results support the view that cycling is highly beneficial for comprehensive musculoskeletal rehabilitation. These results might help clinicians set a target of recovery ROM based on healthy and non-elite individuals and issue suitable guidelines to patients.

Systematic review of longitudinal studies on chemotherapy-associated subjective cognitive impairment in cancer patients.

OBJECTIVES: This systematic review of longitudinal studies, assessing subjective cognitive impairment (SCI) reported by adult cancer patients, aimed to summarize evidence on the impact of chemotherapy on SCI, identify moderators of SCI, and evaluate methodological issues. METHODS: Data accrued from Pubmed, EMBASE, CINAHL, PsychInfo, and the Cochrane library. Inclusion criteria were original studies, an exclusively adult sample, valid and reliable subjective cognitive measures, and at least one baseline data point prior to and another after the initiation of chemotherapy. Data were collected on the sample composition, data-collection time points, outcome measures, statistical analysis, and major findings (ie, longitudinal changes in prevalence, severity, and associated factors). RESULTS: Forty articles published between 2004 and 2019 were retained: 21 examined chemotherapy-treated patients only, and 19 employed control groups. Findings were mixed, with slightly more studies supporting the impact of chemotherapy on SCI. SCI tended to be more prevalent and severe after initiating chemotherapy, compared with patients' own baseline and controls not treated with chemotherapy. Impact appeared to be acute and more likely limited to subsamples. Most studies examining non-breast-cancer samples reported the lack or limited impact of chemotherapy on SCI. The most consistent moderators were depression and fatigue. Methodological issues regarding sampling design, measurement, and statistical analysis were discussed. CONCLUSION: More rigorously designed longitudinal studies would clarify direct and indirect effects of chemotherapy on SCI.

Comparison of Amyloid in Cerebrospinal Fluid, Brain Imaging, and Autopsy in a Case of Progressive Supranuclear Palsy.

Cerebrospinal fluid (CSF) amyloid-beta 1-42 (Aß1-42) and amyloid positron emission tomography (PET) are the 2 main Alzheimer disease amyloid biomarkers that have been validated in neuropathologically confirmed Alzheimer disease cases. Although many studies have shown concordance of amyloid positivity or negativity between CSF Aß1-42 and amyloid PET, several studies also reported discrepancies between these 2 Aß biomarkers. We conducted a comparison of CSF Aß1-42 level, amyloid PET, and autopsy findings in a case with progressive supranuclear palsy in which biomarker acquisition and postmortem pathologic examination were conducted almost at the same time. Our case with antemortem CSF Aß1-42 (+)/amyloid PET (-) who was pathologically confirmed with Aß pathology in the cerebral cortex may indicate CSF Aß1-42 is more sensitive for assessing in vivo Aß than amyloid PET.

Integration of transcriptomics, proteomics and metabolomics identifies biomarkers for pulmonary injury by polyhexamethylene guanidine phosphate (PHMG-p), a humidifier disinfectant, in rats.

Polyhexamethylene guanidine phosphate (PHMG-p) was used as a humidifier disinfectant in Korea. PHMG induced severe pulmonary fibrosis in Koreans. The objective of this study was to elucidate mechanism of pulmonary toxicity caused by PHMG-p in rats using multi-omics analysis. Wistar rats were intratracheally instilled with PHMG-p by single (1.5 mg/kg) administration or 4-week (0.1 mg/kg, 2 times/week) repeated administration. Histopathologic examination was performed with hematoxylin and eosin staining. Alveolar macrophage aggregation and granulomatous inflammation were observed in rats treated with single dose of PHMG-p. Pulmonary fibrosis, chronic inflammation, bronchiol-alveolar fibrosis, and metaplasia of squamous cell were observed in repeated dose group. Next generation sequencing (NGS) was performed for transcriptome profiling after mRNA isolation from bronchiol-alveoli. Bronchiol-alveoli proteomic profiling was performed using an Orbitrap Q-exactive mass spectrometer. Serum and urinary metabolites were determined using 1H-NMR. Among 418 differentially expressed genes (DEGs) and 67 differentially expressed proteins (DEPs), changes of 16 mRNA levels were significantly correlated with changes of their protein levels in both single and repeated dose groups. Remarkable biological processes represented by both DEGs and DEPs were defense response, inflammatory response, response to stress, and immune response. Arginase 1 (Arg1) and lipocalin 2 (Lcn2) were identified to be major regulators for PHMG-p-induced pulmonary toxicity based on merged analysis using DEGs and DEPs. In metabolomics study, 52 metabolites (VIP > 0.5) were determined in serum and urine of single and repeated-dose groups. Glutamate and choline were selected as major metabolites. They were found to be major factors affecting inflammatory response in association with DEGs and DEPs. Arg1 and Lcn2 were suggested to be major gene and protein related to pulmonary damage by PHMG-p while serum or urinary glutamate and choline were endogenous metabolites related to pulmonary damage by PHMG-p.

Effects of anti-wrinkle and skin-whitening fermented black ginseng on human subjects and underlying mechanism of action.

The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks FBG cream significantly reduced appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.

Effects of anti-wrinkle and skin-whitening fermented black ginseng on human subjects and underlying mechanism of action.

The aim of this study was to determine the effects of anti-wrinkle and skin-whitening of fermented black ginseng (FBG) in human subjects and to examine underlying biochemical mechanisms of action. A clinical study was performed to evaluate efficacy and safety using a 1% FBG cream formulation. Twenty-three subjects were recruited and instructed to apply control or FBG creams each on half of their face twice daily for 8 weeks. After 8 weeks, FBG cream significantly reduced the appearance of eye wrinkles compared to prior to exposure and control cream. Skin color was significantly brightened using FBG cream in comparison with a control cream. To determine the mechanism of actions involved in anti-wrinkle and skin-whitening effects various concentrations of FBG were applied to human fibroblast CCD-986sk and mouse melanoma B16F1 cells. Collagen synthesis in CCD-986sk cells was improved significantly at 1, 3, 10, or 30 µg/ml of FBG. At 30 µg/ml, FBG significantly inhibited (73%) collagenase, and matrix metalloproteinase-1 (MMP-1) compared to control. Tyrosinase activity and DOPA (3,4-dihydroxy-L-phenylalanine) oxidation were significantly decreased at all tested concentrations. Melanin production in B16F1 cells was concentration-dependently reduced from 15% to 60% by all concentrations of FBG. These results suggested that a 1% FBG cream exerted anti-wrinkle and skin-whitening effects.