Air pollution and acute kidney injury with comorbid disease: A nationwide case-crossover study in South Korea.

Emerging evidence suggests that air pollution is a significant contributor to the global burden of kidney disease. Although acute kidney injury (AKI) is a common secondary event in ill patients, evidence regarding the association between air pollution and AKI accompanied by specific comorbidities is limited. This study aimed to estimate the association between short-term exposure to air pollution (fine particulate matter ≤2.5 µm [PM2.5] and ozone [O3]) and incident AKI by comorbid diseases using the Korea National Health Information Database (NHID). Total of 160,390 incident AKI cases, defined as an emergency department (ED) visit due to AKI, were observed within the period 2015-2021 in inland South Korea. A time-stratified case-crossover design was applied for PM2.5 and O3 individually, using a conditional logistic regression model within each case and its own control (three or four days of the same day of the week in the same month) to estimate the association between short-term air pollution exposure and ED visits due to AKI. Short-term exposure to PM2.5 and O3 was associated with ED visits due to AKI with ORs of 1.008 (95% confidence interval [CI]: 0.999, 1.017) and 1.019 (95% CI: 1.005, 1.033) for an interquartile range (IQR) increase in lag 0-1 day PM2.5 and O3 respectively, although OR for PM2.5 was marginally significant. The odds of incident AKI associated with PM2.5 was evident in conjunction with ischemic heart disease, cerebrovascular disease, gastrointestinal bleeding, and pneumonia. For O3, the estimated odds was prominent for AKI with ischemic heart disease. In addition, the comorbid disease-specific odds of AKI attributed to air pollution varied by sex and age. Our findings provide epidemiological evidence of a plausible mechanism between air pollution and incident AKI and suggest the need for personalized AKI prevention strategies attributed to air pollution.

Impact of COVID-19 Infection and Its Association With Previous Vaccination in Patients With Myasthenia Gravis in Korea: A Multicenter Retrospective Study.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, patients with myasthenia gravis (MG) were more susceptible to poor outcomes owing to respiratory muscle weakness and immunotherapy. Several studies conducted in the early stages of the COVID-19 pandemic reported higher mortality in patients with MG compared to the general population. This study aimed to investigate the clinical course and prognosis of COVID-19 in patients with MG and to compare these parameters between vaccinated and unvaccinated patients in South Korea. METHODS: This multicenter, retrospective study, which was conducted at 14 tertiary hospitals in South Korea, reviewed the medical records and identified MG patients who contracted COVID-19 between February 2022 and April 2022. The demographic and clinical characteristics associated with MG and vaccination status were collected. The clinical outcomes of COVID-19 infection and MG were investigated and compared between the vaccinated and unvaccinated patients. RESULTS: Ninety-two patients with MG contracted COVID-19 during the study. Nine (9.8%) patients required hospitalization, 4 (4.3%) of whom were admitted to the intensive care unit. Seventy-five of 92 patients were vaccinated before contracting COVID-19 infection, and 17 were not. During the COVID-19 infection, 6 of 17 (35.3%) unvaccinated patients were hospitalized, whereas 3 of 75 (4.0%) vaccinated patients were hospitalized (P < 0.001). The frequencies of ICU admission and mechanical ventilation were significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.019 and P = 0.032, respectively). The rate of MG deterioration was significantly lower in the vaccinated patients than in the unvaccinated patients (P = 0.041). Logistic regression after weighting revealed that the risk of hospitalization and MG deterioration after COVID-19 infection was significantly lower in the vaccinated patients than in the unvaccinated patients. CONCLUSION: This study suggests that the clinical course and prognosis of patients with MG who contracted COVID-19 during the dominance of the omicron variant of COVID-19 may be milder than those at the early phase of the COVID-19 pandemic when vaccination was unavailable. Vaccination may reduce the morbidity of COVID-19 in patients with MG and effectively prevent MG deterioration induced by COVID-19 infection.

Association between hyperCKemia and axonal degeneration in Guillain-Barré syndrome.

BACKGROUND: Elevated serum creatine kinase (CK) levels have been reported in patients with Guillain-Barré syndrome (GBS), more frequently in patients with acute motor axonal neuropathy (AMAN) than in those with acute inflammatory demyelinating polyneuropathy (AIDP). However, some patients with AMAN show reversible conduction failure (RCF), characterized by rapid recovery without axonal degeneration. The present study tested the hypothesis that hyperCKemia is associated with axonal degeneration in GBS, regardless of the subtype. METHODS: We retrospectively enrolled 54 patients with AIDP or AMAN whose serum CK levels were measured within 4 weeks from symptom onset between January 2011 and January 2021. We divided them into hyperCKemia (serum CK ≥ 200 IU/L) and normal CK (serum CK < 200 IU/L) groups. Patients were further classified into axonal degeneration and RCF groups based on more than two nerve conduction studies. The clinical features and frequency of axonal degeneration and RCF were compared between groups. RESULTS: Clinical characteristics were similar in the hyperCKemia and normal CK groups. Compared with that in the RCF subgroup, the frequency of hyperCKemia was significantly higher in the axonal degeneration group (p = 0.007). Patients with normal serum CK levels showed better clinical prognosis, evaluated by the Hughes score at 6 months from admission (p = 0.037). CONCLUSION: HyperCKemia is associated with axonal degeneration in GBS, regardless of the electrophysiological subtype. HyperCKemia within 4 weeks from symptom onset might be a marker of axonal degeneration and poor prognosis in GBS. Serial nerve conduction studies and serum CK measurements will help clinicians understand the pathophysiology of GBS.

Clinical and molecular change induced by repeated low-dose visible light exposure in both light-skinned and dark-skinned individuals.

BACKGROUND: Visible light (VL) is known to induce pigmentation in dark-skinned individuals and immediate erythema in light-skinned individuals. However, the effects of accumulated low-dose VL exposure across skin types are not well established. METHODS: Thirty-one healthy subjects with light (Fitzpatrick skin types [FST] I-II, n = 13) and dark (FST V-VI, n = 18) skin types were enrolled. Subjects' buttocks were exposed daily to VL, wavelength 400-700 nm, with a dose of 120 J/cm2 at 50 mW/cm2 , for four consecutive days. Microarray using Affymetrix GeneChip (49,395 genes) was performed followed by qRT-PCR on skin samples. RESULTS: Repeated low-dose VL irradiation induced immediate pigment darkening and delayed tanning in dark-skinned individuals while no discernable pigmentation and erythema were observed in light-skinned individuals. Top ten upregulated genes by repeated VL exposure in microarray included melanogenic genes such as tyrosinase (TYR), tyrosinase-related protein-1 (TYRP1), dopachrome tautomerase (DCT), premelanosome protein (PMEL), melan-A (MLANA), and solute carrier family 24, member 5 (SLC24A5) and genes involved in inflammation/matrix remodeling/cell signaling including chemokine (C-C motif) ligand 18 (CCL18), BCL2-related protein A1 (BCL2A1), and cartilage oligomeric matrix protein (COMP). In qRT-PCR CCL18 was upregulated in light skin with a greater extent (mean fold change ± SD; 4.03 ± 3.28, p = .04) than in dark-skinned individuals (1.91 ± 1.32, p = .07) while TYR was not significantly upregulated in both skin types. CONCLUSION: This study highlights the genes upregulated by cumulative VL exposure involved in pigmentation, immune response, oxidation/reduction, and matrix remodeling across skin types providing relevant information on daily solar exposure.

Two Case Reports of Chronic Inflammatory Demyelinating Polyneuropathy After COVID-19 Vaccination.

The occurrence of chronic inflammatory demyelinating polyneuropathy (CIDP) related to coronavirus disease 2019 (COVID-19) has rarely been reported. We describe two patients who were diagnosed with CIDP after COVID-19 vaccination. A 72-year-old man presented with a progressive tingling sensation and weakness below both knees for two weeks. He had been vaccinated against COVID-19 (mRNA-1273 vaccine) a month before the appearance of symptoms. Demyelinating polyneuropathy was observed in the nerve conduction studies (NCS). Intravenous immunoglobulin (IVIg) was administered under the diagnosis of Guillain-Barré syndrome (GBS), and his symptoms were improved. However, his symptoms relapsed at 10 weeks from the onset. Oral prednisolone, azathioprine, and IVIg were administered as treatment. The second case was a 50-year-old man who complained of a bilateral leg tingling sensation and gait disturbance lasting four weeks. He had received the Ad26.COV2.S vaccine against COVID-19 five weeks prior. Demyelinating polyneuropathy was observed in the NCS. He was treated with oral prednisolone, azathioprine, and IVIg for CIDP because his symptoms had lasted for more than 12 weeks from the onset. A causal relationship has not been established between COVID-19 vaccination and CIDP; however, CIDP may follow COVID-19 vaccination. As CIDP treatment is different from that for GBS, clinicians should closely monitor patients diagnosed with GBS associated with COVID-19 whether they deteriorate after initial treatment.

Twenty Years of Anti-Vascular Endothelial Growth Factor Therapeutics in Neovascular Age-Related Macular Degeneration Treatment.

Neovascular age-related macular degeneration (nAMD) is the primary disastrous retinal disease that leads to blindness in the elderly population. In the early 2000s, nAMD resulted in irreversible vision loss and blindness with no available treatment options. However, there have been breakthrough advances in the drug development of anti-angiogenic biological agents over the last two decades. The primary target molecule for treating nAMD is the vascular endothelial growth factor (VEGF), and there are currently several anti-VEGF drugs such as bevacizumab, ranibizumab, and aflibercept, which have made nAMD more manageable than before, thus preventing vision loss. Nevertheless, it should be noted that these anti-VEGF drugs for nAMD treatment are not effective in more than half of the patients, and even those who initially gain visual improvements lose their vision over time, along with potential deterioration in the geography of atrophy. As a result, there have been continuous endeavors to improve anti-VEGF agents through better efficacy, fewer doses, expanded intervals, and additional targets. This review describes past and current anti-VEGF therapeutics used to treat nAMD and outlines future directions to improve the effectiveness and safety of anti-VEGF agents.

Universal healthcare coverage and health service delivery before and during the COVID-19 pandemic: A difference-in-difference study of childhood immunization coverage from 195 countries.

BACKGROUND: Several studies have indicated that universal health coverage (UHC) improves health service utilization and outcomes in countries. These studies, however, have primarily assessed UHC's peacetime impact, limiting our understanding of UHC's potential protective effects during public health crises such as the Coronavirus Disease 2019 (COVID-19) pandemic. We empirically explored whether countries' progress toward UHC is associated with differential COVID-19 impacts on childhood immunization coverage. METHODS AND FINDINGS: Using a quasi-experimental difference-in-difference (DiD) methodology, we quantified the relationship between UHC and childhood immunization coverage before and during the COVID-19 pandemic. The analysis considered 195 World Health Organization (WHO) member states and their ability to provision 12 out of 14 childhood vaccines between 2010 and 2020 as an outcome. We used the 2019 UHC Service Coverage Index (UHC SCI) to divide countries into a "high UHC index" group (UHC SCI ≥80) and the rest. All analyses included potential confounders including the calendar year, countries' income group per the World Bank classification, countries' geographical region as defined by WHO, and countries' preparedness for an epidemic/pandemic as represented by the Global Health Security Index 2019. For robustness, we replicated the analysis using a lower cutoff value of 50 for the UHC index. A total of 20,230 country-year observations were included in the study. The DiD estimators indicated that countries with a high UHC index (UHC SCI ≥80, n = 35) had a 2.70% smaller reduction in childhood immunization coverage during the pandemic year of 2020 as compared to the countries with UHC index less than 80 (DiD coefficient 2.70; 95% CI: 0.75, 4.65; p-value = 0.007). This relationship, however, became statistically nonsignificant at the lower cutoff value of UHC SCI <50 (n = 60). The study's primary limitation was scarce data availability, which restricted our ability to account for confounders and to test our hypothesis for other relevant outcomes. CONCLUSIONS: We observed that countries with greater progress toward UHC were associated with significantly smaller declines in childhood immunization coverage during the pandemic. This identified association may potentially provide support for the importance of UHC in building health system resilience. Our findings strongly suggest that policymakers should continue to advocate for achieving UHC in coming years.

Employment conditions as barriers to the adoption of COVID-19 mitigation measures: how the COVID-19 pandemic may be deepening health disparities among low-income earners and essential workers in the United States.

BACKGROUND: The COVID-19 pandemic has disproportionately impacted economically-disadvantaged populations in the United States (US). Precarious employment conditions may contribute to these disparities by impeding workers in such conditions from adopting COVID-19 mitigation measures to reduce infection risk. This study investigated the relationship between employment and economic conditions and the adoption of COVID-19 protective behaviors among US workers during the initial phase of the COVID-19 pandemic. METHODS: Employing a social media advertisement campaign, an online, self-administered survey was used to collect data from 2,845 working adults in April 2020. Hierarchical generalized linear models were performed to assess the differences in engagement with recommended protective behaviors based on employment and economic conditions, while controlling for knowledge and perceived threat of COVID-19, as would be predicted by the Health Belief Model (HBM). RESULTS: Essential workers had more precarious employment and economic conditions than non-essential workers: 67% had variable income; 30% did not have paid sick leave; 42% had lost income due to COVID-19, and 15% were food insecure. The adoption of protective behaviors was high in the sample: 77% of participants avoided leaving home, and 93% increased hand hygiene. Consistent with the HBM, COVID-19 knowledge scores and perceived threat were positively associated with engaging in all protective behaviors. However, after controlling for these, essential workers were 60% and 70% less likely than non-essential workers, who by the nature of their jobs cannot stay at home, to stay at home and increase hand hygiene, respectively. Similarly, participants who could not afford to quarantine were 50% less likely to avoid leaving home (AOR: 0.5; 95% CI: 0.4, 0.6) than those who could, whereas there were no significant differences concerning hand hygiene. CONCLUSIONS: Our findings are consistent with the accumulating evidence that the employment conditions of essential workers and other low-income earners are precarious, that they have experienced disproportionately higher rates of income loss during the initial phase of the COVID-19 pandemic and face significant barriers to adopting protective measures. Our findings underscore the importance and need of policy responses focusing on expanding social protection and benefits to prevent the further deepening of existing health disparities in the US.

What predicts people's belief in COVID-19 misinformation? A retrospective study using a nationwide online survey among adults residing in the United States.

BACKGROUND: Tackling infodemics with flooding misinformation is key to managing the COVID-19 pandemic. Yet only a few studies have attempted to understand the characteristics of the people who believe in misinformation. METHODS: Data was used from an online survey that was administered in April 2020 to 6518 English-speaking adult participants in the United States. We created binary variables to represent four misinformation categories related to COVID-19: general COVID-19-related, vaccine/anti-vaccine, COVID-19 as an act of bioterrorism, and mode of transmission. Using binary logistic regression and the LASSO regularization, we then identified the important predictors of belief in each type of misinformation. Nested vector bootstrapping approach was used to estimate the standard error of the LASSO coefficients. RESULTS: About 30% of our sample reported believing in at least one type of COVID-19-related misinformation. Belief in one type of misinformation was not strongly associated with belief in other types. We also identified 58 demographic and socioeconomic factors that predicted people's susceptibility to at least one type of COVID-19 misinformation. Different groups, characterized by distinct sets of predictors, were susceptible to different types of misinformation. There were 25 predictors for general COVID-19 misinformation, 42 for COVID-19 vaccine, 36 for COVID-19 as an act of bioterrorism, and 27 for mode of COVID-transmission. CONCLUSION: Our findings confirm the existence of groups with unique characteristics that believe in different types of COVID-19 misinformation. Findings are readily applicable by policymakers to inform careful targeting of misinformation mitigation strategies.

Frequency histograms of three high-sensitivity cardiac troponin assays in a reference population.

BACKGROUND: Cardiac troponin (cTn) values above the 99th percentile upper reference limit (URL) indicate myocardial injury. We established 99th percentile URLs for three high-sensitivity cTn (hs-cTn) assays (Beckman Coulter Access hs-cTnI, Abbott STAT hs-cTnI, and Roche Elecsys hs-cTnT) using a healthy population in Korea. METHODS: Each cTn value was measured by three assays and analyzed by dividing by gender and age. RESULTS: The frequency histograms of log-transformed cTn values for Beckman and Abbott assays exhibited a bell-shaped distribution. The 99th percentile URLs were 9.8, 17.4, and 17.3 ng/L in the total population; 10.9/9.0, 18.9/17.0, and 18.9/17.7 ng/L in the male/female population (p < 0.001 for all three assays); and 11.2/7.2, 19.9/14.5, and 22.7/9.3 ng/L in the older/younger population (p < 0.001 for all three assays) for Beckman, Abbott, and Roche assays, respectively. CONCLUSION: Among the three assays, bell-shaped distributions were observed in a frequency histogram of log-transformed cTn values for healthy population in Beckman and Abbott assays. Also, our findings show that the 99th percentile URLs for cTn levels vary not only by gender but age.

A Very Simple Suture Technique for Correction of Primary Multiple Folds in Asian Eyelids.

BACKGROUND: Upper blepharoplasty is 1 of the most popular cosmetic procedures in Asia. As people become older, they develop soft tissue atrophy and multiple folds due to a sunken upper eyelid. Furthermore, people with thin upper eyelid skin are more likely to develop multiple folds, even at a young age. The authors investigated the effectiveness of a transverse mattress suture technique to prevent recurrence during upper blepharoplasty in patients with primary multiple folds. PATIENTS/METHODS: Data on 656 patients with primary multiple folds who underwent upper blepharoplasty from March 2017 to January 2020 were retrospectively reviewed. The authors compared the operative time, patients' satisfaction, panel assessment, and complications according to whether the suture technique was used. RESULTS: Among 656 patients, 228 were lost to follow-up or had incomplete data; therefore, the files of 428 patients were analyzed. In total, 199 patients did not undergo the suture technique, whereas 229 patients did. Statistically significant differences were found between the 2 groups in patients' satisfaction, aesthetic results, and recurrence. However, between-group difference was not significant in terms of symmetry or complications such as hematoma and swelling. CONCLUSIONS: People with thin upper eyelid skin or slightly protruding eyes are more likely to develop multiple folds at a young age, even in their teens or 20s. The authors performed a skin suture during upper blepharoplasty, and then performed a transverse mattress suture on the spots where multiple folds are expected. Patients who underwent the suture technique showed better aesthetic results and a significantly lower recurrence rate.

Anti-Inflammatory Activity of Cajanin, an Isoflavonoid Derivative Isolated from Canavalia lineata Pods.

The bioactive components of Canavalia lineata (Thunb.) DC pods were investigated using bioactivity-guided isolation, and the chemical structures of flavonoids 1-3, isoflavonoid derivatives 4-11, and phenolic compounds 12 and 13 were identified by comparing NMR, MS, and CD spectral data with previously reported spectroscopic data. Compounds 1-13 were evaluated for their anti-inflammatory effects on LPS-stimulated RAW264.7 macrophages. Among these compounds, the isoflavonoid derivative cajanin (7) exhibited the most potent anti-inflammatory activity (IC50 of NO = 19.38 ± 0.05 µM; IC50 of IL-6 = 7.78 ± 0.04 µM; IC50 of TNF-α = 26.82 ± 0.11 µM), exerting its anti-inflammatory effects by suppressing the activation and nuclear translocation of the transcription factor NF-κB by phosphorylating IκB and p65. These results suggested that cajanin (7) may be a potential candidate for improving the treatment of inflammatory diseases.

Medicarpin and Homopterocarpin Isolated from Canavalia lineata as Potent and Competitive Reversible Inhibitors of Human Monoamine Oxidase-B.

Thirteen compounds were isolated from the Canavalia lineata pods and their inhibitory activities against human monoamine oxidase-A (hMAO-A) and -B (hMAO-B) were evaluated. Among them, compounds 8 (medicarpin) and 13 (homopterocarpin) showed potent inhibitory activity against hMAO-B (IC50 = 0.45 and 0.72 µM, respectively) with selectivity index (SI) values of 44.2 and 2.07, respectively. Most of the compounds weakly inhibited MAO-A, except 9 (prunetin) and 13. Compounds 8 and 13 were reversible competitive inhibitors against hMAO-B (Ki = 0.27 and 0.21 µM, respectively). Structurally, the 3-OH group at A-ring of 8 showed higher hMAO-B inhibitory activity than 3-OCH3 group at the A-ring of 13. However, the 9-OCH3 group at B-ring of 13 showed higher hMAO-B inhibitory activity than 8,9-methylenedioxygroup at the B-ring of 12 (pterocarpin). In cytotoxicity study, 8 and 13 showed non-toxicity to the normal (MDCK) and cancer (HL-60) cells and moderate toxicity to neuroblastoma (SH-SY5Y) cell. Molecular docking simulation revealed that the binding affinities of 8 and 13 for hMAO-B (-8.7 and -7.7 kcal/mol, respectively) were higher than those for hMAO-A (-3.4 and -7.1 kcal/mol, respectively). These findings suggest that compounds 8 and 13 be considered potent reversible hMAO-B inhibitors to be used for the treatment of neurological disorders.

Evolution of oxidative stress, inflammation and neovascularization in the choroid and retina in a subretinal lipid induced age-related macular degeneration model.

Oxidative stress, inflammation and neovascularization are the key pathological events that are implicated in human age-related macular degeneration (AMD). There are a limited number of animal models available for evaluating and developing new therapies. Most models represent late exudative or neovascular AMD (nAMD) but there is a relative paucity of models that mimic early events in AMD. The purpose of this study is to characterize the evolution of oxidative stress, inflammation, retinal degeneration and neovascularization in a rat model of AMD, created by subretinal injection of human lipid hydroperoxide (HpODE) that found in the sub-macular region in aged and AMD patients. Subretinal HpODE induced retinal pigment epithelium (RPE) and retinal degeneration resulting in loss of RPE cells, photoreceptors and retinal thinning. RPE degeneration and atrophy were detected by day 5, followed by neural tissue degeneration at day 12 with robust TUNEL positive cells. Western blot analysis confirmed an increase in pro-apoptotic Bak protein at day 12 in retinal tissues. Oxidative damage biomarkers (4-hydroxynonenal, malondialdehyde, 8-hydroxy-2'-deoxyguanosine, and nitrotyrosine) increased in retinal tissue from days 5-12. Müller glial activation was observed in the HpODE injected area at day 5 followed by its remodeling and migration in the outer retina by day 20. RT-qPCR analysis further indicated upregulation of pro-inflammatory genes (TNF-α, IL-1ß and IL-6) both in retinal and RPE/choroidal tissue as early as day 2 and persisted until day 12. Upregulation of oxidative stress markers such as NADPH oxidase (NOX and DOUX family) was detected early in retinal tissue by day 2 followed by its upregulation in choroidal tissue at day 5. Neovascularization was demonstrated from day 12 to day 20 post HpODE injection in choroidal tissue. The results from this study indicate that subretinal HpODE induces advanced AMD phenotypes comprising many aspects of both dry/early and late) and neovascular/late AMD as observed in humans. Within 3 weeks via oxidative damage, upregulation of reactive oxygen species and pro-inflammatory genes, pro-apoptotic Bak and pro-angiogenic VEGF upregulation occurs leading to CNV formation. This experimental model of subretinal HpODE is an appropriate model for the study of AMD and provides an important platform for translational and basic research in developing new therapies particularly for early/dry AMD where currently no viable therapies are available.

The effects of green tea on acne vulgaris: A systematic review and meta-analysis of randomized clinical trials.

Green tea extract (GTE) has been studied for the treatment of acne based on its anti-inflammatory/antioxidant properties. This systematic review and meta-analysis aimed to examine the effects of GTE on acne. Electronic databases, including PubMed, Embase, and the Cochrane Library were systematically searched up to August 2019. The effect size of acne lesion counts is presented as mean differences and 95% confidence intervals (CIs). Five randomized-controlled studies were included in the meta-analysis (N; experimental = 125, control = 122). GTE significantly reduced the number of inflammatory lesions (-9.38; 95% CI: -14.13 to -4.63). In subgroup analysis, topical GTE application significantly reduced the inflammatory lesion counts (-11.39; 95% CI: -15.91 to -6.86) whereas oral GTE intake showed minimal effect (-1.40; 95% CI: -2.50 to -0.30). Although GTE did not significantly reduce the number of non-inflammatory lesions (-21.65; 95% CI: -47.52 to 4.22), when stratified by the route of admission, non-inflammatory acne lesions were significantly reduced by topical GTE application (-32.44; 95% CI: -39.27 to -25.62) but not with oral GTE administration (0.20; 95% CI: 0.00 to 0.40). This systematic review and meta-analysis suggest that topical GTE application is beneficial for the treatment of acne without causing significant adverse events while oral GTE intake has limited effects. Further high-quality clinical trials are warranted.

The efficacy of fractional carbon dioxide laser combined with narrow-band ultraviolet B phototherapy for non-segmental vitiligo: a systematic review and meta-analysis.

Fractional carbon dioxide (CO2) laser has been used with conventional treatments for vitiligo, demonstrating more effectiveness compared with conventional treatments alone. Especially, fractional CO2 laser combined with narrow-band ultraviolet B (NB-UVB) was shown to induce more improvement compared with NB-UVB monotherapy for treating stable non-segmental vitiligo. However, the effectiveness of fractional CO2 laser plus NB-UVB for the treatment of non-segmental vitiligo remains controversial. Therefore, this study aimed to confirm the safety and efficacy of fractional CO2 laser combined with NB-UVB compared with NB-UVB monotherapy in stable non-segmental vitiligo. We searched the data from different databases, including Cochrane, Embase, and PubMed up to January 2020. Four randomized controlled trials (RCTs) for comparison between fractional CO2 laser plus NB-UVB and NB-UVB monotherapy in patients with stable non-segmental vitiligo were included. We performed meta-analyses for repigmentation improvement and patient satisfaction as well as subgroup analyses based on acral or non-acral vitiligo, according to the PRISMA guidelines. The combination treatment showed more superior results than NB-UVB monotherapy (≥ 75% repigmentation, RR 4.60, 95% CI 1.19-17.74; ≥ 50% repigmentation, RR 2.24, 95% CI 0.45-11.17; < 25% repigmentation, RR 0.81, 95% CI 0.60-1.08). Also, fractional CO2 laser plus NB-UVB significantly improved acral and non-acral vitiligo compared with NB-UVB monotherapy (standard mean difference (SMD) 1.24, 95% CI 0.66-1.82; SMD 1.14, 95% CI 0.67-1.60, respectively), while it increased markedly patient satisfaction compared with NB-UVB monotherapy (SMD 1.12, 95% CI 0.66-1.58). Collectively, this meta-analysis suggested that fractional CO2 laser combined with NB-UVB might be more effective for treating non-segmental vitiligo than NB-UVB monotherapy.

Multilaboratory Evaluation of the MALDI-TOF Mass Spectrometry System, MicroIDSys Elite, for the Identification of Medically Important Filamentous Fungi.

With the increasing number of fungal infections and immunocompromised patients, rapid and accurate fungal identification is required in clinical microbiology laboratories. We evaluated the applicability of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) system, MicroIDSys Elite (ASTA Corp., South Korea) for the identification of medically important filamentous fungi. A total of 505 strains comprising 37 genera and 90 species collected from 11 Korean hospitals were sent to the microbiology laboratory of International St. Mary's Hospital. All isolates were tested using MicroIDSys Elite, and data were analyzed using the MoldDB v.1.22 database (ASTA). Correct identification rates were compared with the multigene sequencing results. MicroIDSys Elite correctly identified 86.5% (437/505) and 88.9% (449/505) of all tested isolates at the species and genus level, respectively. About 98.2% of Aspergillus isolates were identified at the species level, including cryptic and rare species of A. calidoustus, A. tamarii, A. lentulus, A. versicolor and A. aculeatus. MicroIDSys Elite identified 75.0% of basidiomycetes, including Schizophyllum commune, and 84.3% of the dermatophytes. It also distinguished Sprothrix globosa at the species level. The mean scores of total isolates corresponding to correct species identification were significantly higher than those obtained for genus-level identification (253.5 ± 50.7 vs. 168.6 ± 30.3, P < 0.001). MicroIDSys Elite showed high accuracy for the identification of filamentous fungi, including cryptic and rare Aspergillus species. It is suitable for use in clinical laboratories as a rapid and efficient tool for clinical mold identification. Further evaluations are recommended for MicroIDSys Elite as a rapid and efficient tool for the identification of medically important filamentous fungi.

Cone-rod homeobox CRX controls presynaptic active zone formation in photoreceptors of mammalian retina.

In the mammalian retina, rod and cone photoreceptors transmit the visual information to bipolar neurons through highly specialized ribbon synapses. We have limited understanding of regulatory pathways that guide morphogenesis and organization of photoreceptor presynaptic architecture in the developing retina. While neural retina leucine zipper (NRL) transcription factor determines rod cell fate and function, cone-rod homeobox (CRX) controls the expression of both rod- and cone-specific genes and is critical for terminal differentiation of photoreceptors. A comprehensive immunohistochemical evaluation of Crx-/- (null), CrxRip/+ and CrxRip/Rip (models of dominant congenital blindness) mouse retinas revealed abnormal photoreceptor synapses, with atypical ribbon shape, number and length. Integrated analysis of retinal transcriptomes of Crx-mutants with CRX- and NRL-ChIP-Seq data identified a subset of differentially expressed CRX target genes that encode presynaptic proteins associated with the cytomatrix active zone (CAZ) and synaptic vesicles. Immunohistochemistry of Crx-mutant retina validated aberrant expression of REEP6, PSD95, MPP4, UNC119, UNC13, RGS7 and RGS11, with some reduction in Ribeye and no significant change in immunostaining of RIMS1, RIMS2, Bassoon and Pikachurin. Our studies demonstrate that CRX controls the establishment of CAZ and anchoring of ribbons, but not the formation of ribbon itself, in photoreceptor presynaptic terminals.

Systemic dendrimer-drug nanomedicines for long-term treatment of mild-moderate cerebral palsy in a rabbit model.

BACKGROUND: Neuroinflammation mediated by microglia plays a central role in the pathogenesis of perinatal/neonatal brain injury, including cerebral palsy (CP). Therapeutics mitigating neuroinflammation potentially provide an effective strategy to slow the disease progression and rescue normal brain development. Building on our prior results which showed that a generation-4 hydroxyl poly(amidoamine) (PAMAM) dendrimer could deliver drugs specifically to activated glia from systemic circulation, we evaluated the sustained efficacy of a generation-6 (G6) hydroxyl-terminated PAMAM dendrimer that showed a longer blood circulation time and increased brain accumulation. N-acetyl-L-cysteine (NAC), an antioxidant and anti-inflammatory agent that has high plasma protein binding properties and poor brain penetration, was conjugated to G6-PAMAM dendrimer-NAC (G6D-NAC). The efficacy of microglia-targeted G6D-NAC conjugate was evaluated in a clinically relevant rabbit model of CP, with a mild/moderate CP phenotype to provide a longer survival of untreated CP kits, enabling the assessment of sustained efficacy over 15 days of life. METHODS: G6D-NAC was conjugated and characterized. Cytotoxicity and anti-inflammatory assays were performed in BV-2 microglial cells. The efficacy of G6D-NAC was evaluated in a rabbit model of CP. CP kits were randomly divided into 5 groups on postnatal day 1 (PND1) and received an intravenous injection of a single dose of PBS, or G6D-NAC (2 or 5 mg/kg), or NAC (2 or 5 mg/kg). Neurobehavioral tests, microglia morphology, and neuroinflammation were evaluated at postnatal day 5 (PND5) and day 15 (PND15). RESULTS: A single dose of systemic 'long circulating' G6D-NAC showed a significant penetration across the impaired blood-brain-barrier (BBB), delivered NAC specifically to activated microglia, and significantly reduced microglia-mediated neuroinflammation in both the cortex and cerebellum white matter areas. Moreover, G6D-NAC treatment significantly improved neonatal rabbit survival rate and rescued motor function to nearly healthy control levels at least up to 15 days after birth (PND15), while CP kits treated with free NAC died before PND9. CONCLUSIONS: Targeted delivery of therapeutics to activated microglia in neonatal brain injury can ameliorate pro-inflammatory microglial responses to injury, promote survival rate, and improve neurological outcomes that can be sustained for a long period. Appropriate manipulation of activated microglia enabled by G6D-NAC can impact the injury significantly beyond inflammation.

Can Social Policies Improve Health? A Systematic Review and Meta-Analysis of 38 Randomized Trials.

Policy Points Social policies might not only improve economic well-being, but also health. Health policy experts have therefore advocated for investments in social policies both to improve population health and potentially reduce health system costs. Since the 1960s, a large number of social policies have been experimentally evaluated in the United States. Some of these experiments include health outcomes, providing a unique opportunity to inform evidence-based policymaking. Our comprehensive review and meta-analysis of these experiments find suggestive evidence of health benefits associated with investments in early life, income support, and health insurance interventions. However, most studies were underpowered to detect health outcomes. CONTEXT: Insurers and health care providers are investing heavily in nonmedical social interventions in an effort to improve health and potentially reduce health care costs. METHODS: We performed a systematic review and meta-analysis of all known randomized social experiments in the United States that included health outcomes. We reviewed 5,880 papers, reports, and data sources, ultimately including 61 publications from 38 randomized social experiments. After synthesizing the main findings narratively, we conducted risk of bias analyses, power analyses, and random-effects meta-analyses where possible. Finally, we used multivariate regressions to determine which study characteristics were associated with statistically significant improvements in health outcomes. FINDINGS: The risk of bias was low in 17 studies, moderate in 11, and high in 33. Of the 451 parameter estimates reported, 77% were underpowered to detect health outcomes. Among adequately powered parameters, 49% demonstrated a significant health improvement, 44% had no effect on health, and 7% were associated with significant worsening of health. In meta-analyses, early life and education interventions were associated with a reduction in smoking (odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.86-0.99). Income maintenance and health insurance interventions were associated with significant improvements in self-rated health (OR = 1.20, 95% CI 1.06-1.36, and OR = 1.38, 95% CI 1.10-1.73, respectively), whereas some welfare-to-work interventions had a negative impact on self-rated health (OR = 0.77, 95% CI 0.66-0.90). Housing and neighborhood trials had no effect on the outcomes included in the meta-analyses. A positive effect of the trial on its primary socioeconomic outcome was associated with higher odds of reporting health improvements. We found evidence of publication bias for studies with null findings. CONCLUSIONS: Early life, income, and health insurance interventions have the potential to improve health. However, many of the included studies were underpowered to detect health effects and were at high or moderate risk of bias. Future social policy experiments should be better designed to measure the association between interventions and health outcomes.