Modeling Respiratory Syncytial Virus Adult Vaccination in the United States With a Dynamic Transmission Model.

BACKGROUND: Respiratory syncytial virus (RSV) is shown to cause substantial morbidity, hospitalization, and mortality in infants and older adults. Population-level modeling of RSV allows to estimate the full burden of disease and the potential epidemiological impact of novel prophylactics. METHODS: We modeled the RSV epidemiology in the United States across all ages using a deterministic compartmental transmission model. Population-level symptomatic RSV acute respiratory tract infection (ARI) cases were projected across different natural history scenarios with and without vaccination of adults aged ≥60 years. The impact of vaccine efficacy against ARIs, infectiousness and vaccine coverage on ARI incidence were assessed. The impact on medical attendance, hospitalization, complications, death, and other outcomes was also derived. RESULTS: Without a vaccine, we project 17.5-22.6 million symptomatic RSV ARI cases annually in adults aged ≥18 years in the US, with 3.6-4.8 million/year occurring in adults aged ≥60 years. Modeling indicates that up to 2.0 million symptomatic RSV-ARI cases could be prevented annually in ≥60-year-olds with a hypothetical vaccine (70% vaccine efficacy against symptomatic ARI and 60% vaccine coverage) and that up to 0.69 million/year could be prevented in the nonvaccinated population, assuming 50% vaccine impact on infectiousness. CONCLUSIONS: The model provides estimated burden of RSV in the US across all age groups, with substantial burden projected specifically in older adults. Vaccination of adults aged ≥60 years could significantly reduce the burden of disease in this population, with additional indirect effect in adults aged <60 years due to reduced transmissibility.

The risk of anti-osteoporotic agent-induced severe cutaneous adverse drug reactions and their association with HLA.

BACKGROUND: There is increasing use of anti-osteoporotic agents (AOA) worldwide for prevention or management of patients with osteoporosis. However, there have been reports of severe cutaneous adverse reactions (SCAR) induced by AOA. A recent study showed weak association between HLA and strontium ranelate (SR)-SCAR. OBJECTIVE: To characterize patients with AOA-SCAR and investigate the HLA association and utility of in vitro diagnostic methods. METHODS: We enrolled 16 cases with AOA-cutaneous adverse drug reactions (cADR), including SCAR (n = 10: 8 with Stevens-Johnson syndrome [SJS] and 2 with drug rash with eosinophilia and systemic symptoms [DRESS]) and maculopapular exanthema (MPE) (n = 6) from Taiwan and Hong Kong. We analysed the clinical characteristics, outcomes, HLA alleles and in vitro testing of AOA-SCAR, and tolerability to alternative drugs. We further performed literature review and meta-analysis on the HLA association of AOA-SCAR. RESULTS: Our data showed strontium ranelate is the most common causality of AOA-SCAR in Asian populations. There was no cross-hypersensitivity of SR-SCAR with other AOA. HLA genotyping showed that SR-SJS was most significantly associated with HLA-A*33:03 (Pc = 5.17 × 10-3 , OR: 25.97, 95% CI: 3.08-219.33). Meta-analysis showed that HLA-A*33:03 was associated with SR-SJS (P = 5.01 × 10-5 ; sensitivity: 85.7%) in Asians. The sensitivity of lymphocyte activation test (LAT) for identifying the culprit drug of SR-SJS was 83.3%. CONCLUSIONS: Strontium ranelate is identified as the most notorious AOA associated with SCAR. The HLA-A*33:03 genetic allele and LAT testing may add benefits to the diagnosis of SR-SCAR in patients whose reaction developed while taking multiple drugs.

Epidemiological characteristics and associated factors of acute hepatitis A outbreak among HIV-coinfected men who have sex with men in Taiwan, June 2015-December 2016.

In Taiwan, an outbreak of acute hepatitis A (AHA) infection has been identified since June 2015. Approximately half of the cases occurred in HIV-infected men who have sex with men (MSM). We used the Taiwan Centers for Disease Control (TCDC)-operated National Disease Surveillance Systems (NDSS) to identify the incidence of AHA during 2011-2016. Between June 2015 and December 2016, a total of 1268 AHA cases were documented, and 601 cases (47.4%) were co-infected with HIV; the majority of whom were MSM (98.4%). Each AHA case was matched to two HIV-infected controls without AHA reported in the NDSS on age (± 5 years), risk factor of HIV infection, HIV diagnosis date (± 30 days) and county/city of residence at HIV diagnosis. Three hundred forty-three HIV/AHA cases were matched to 686 controls. In multivariable conditional logistic regression analysis, a previous gonorrhoea (adjusted OR=1.77, 95% CI 1.16-2.70) and recent (aOR=6.77, 95% CI 4.34-10.55) or remote syphilis report (aOR=3.56, 95% CI 2.48-5.13) were independently associated with AHA. The epidemic persisted till December 2016, and the cases with a new diagnosis of HIV infection after AHA (28/301, 9.3%) increased after July 2016 (P = .001). HIV/AHA cases were centralized in northern and central metropolitan areas and HIV-infected MSM with a recent history of sexually transmitted diseases in Taiwan. We recommend surveillance of associated behavioural and virologic characteristics and HAV counselling and testing for HIV-infected men.

Delayed-type hypersensitivity reactions induced by proton pump inhibitors: A clinical and in vitro T-cell reactivity study.

BACKGROUND: Proton pump inhibitors (PPIs) have been known to induce type I hypersensitivity reactions. However, severe delayed-type hypersensitivity reactions (DHR) induced by PPI, such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), or drug rash with eosinophilia and systemic symptoms (DRESS), are rarely reported. We conducted a study of a large series of PPI-related DHR, followed up their tolerability to alternative anti-ulcer agents, and investigated the T-cell reactivity to PPI in PPI-related DHR patients. METHODS: We retrospectively analyzed patients with PPI-related DHR from multiple medical centers in Taiwan during the study period January 2003 to April 2016. We analyzed the causative PPI, clinical manifestations, organ involvement, treatment, and complications. We also followed up the potential risk of cross-hypersensitivity or tolerability to other PPI after their hypersensitivity episodes. Drug lymphocyte activation test (LAT) was conducted by measuring granulysin and interferon-γ to confirm the causalities. RESULTS: There were 69 cases of PPI-related DHR, including SJS/TEN (n=27) and DRESS (n=10). The LAT by measuring granulysin showed a sensitivity of 59.3% and specificity of 96.4%. Esomeprazole was the most commonly involved in PPI-related DHR (51%). Thirteen patients allergic to one kind of PPI could tolerate other structurally different PPI without cross-hypersensitivity reactions, whereas three patients developed cross-hypersensitivity reactions to alternative structurally similar PPI. The cross-reactivity to structurally similar PPI was also observed in LAT assay. CONCLUSIONS: PPIs have the potential to induce life-threatening DHR. In patients when PPI is necessary for treatment, switching to structurally different alternatives should be considered.

Autophagy inhibition increased the anti-tumor effect of cisplatin on drug-resistant esophageal cancer cells.

The sensitivity of tumor cells to treatment can be affected by autophagy. The drug resistance of esophageal cancer cells against cisplatin occurs during the long period of chemotherapy drug treatment. This study was designed to observe the effect autophagy has on the occurrence of esophageal cancer cell drug resistance against cisplatin and investigate its molecular mechanism in order to provide new details and strategies for the clinical treatment of esophageal cancer, especially cisplatin treatment. The detection methods used in this study were 3-(4,5-dimethylthiazd-2-yl)-2,5-dipheny-ltetrazolium bromide (MTT) colorimetric assay, clone survival technique, small interfering RNA (siRNA) transfection, and Western blot. Autophagy is a protection mechanism of drug-resistant cells processed by cisplatin, and maintains the cell clone survival ability. Autophagy activation requires the involvement of Atg5 and Atg7.

Vitamin D insufficiency and cognitive impairment in Asians: a multi-ethnic population-based study and meta-analysis.

BACKGROUND: The relationship between vitamin D insufficiency and cognitive impairment remains equivocal in Asians. We examined the association between circulating 25-hydroxyvitamin D (25OHD) concentration and cognitive performance in a large multi-ethnic Singaporean population-based study. We also conducted a meta-analysis of 25OHD concentrations amongst cognitively impaired older adults in Asia. METHODS: Our population-based cross-sectional study included 2273 persons ≥60 years of age from the Singapore Epidemiology of Eye Diseases (SEED) study (mean ± SD age 70.4 ± 6.2 years; 44.7% female), who were categorized according to 25OHD concentration (i.e. ≤10, 10.1-20 and >20 ng mL(-1) ). The 25OHD concentration was measured and adjusted to reflect a deseasonalized value. Cognition was assessed using the total and domain scores of the Abbreviated Mental Test (AMT). Global cognitive impairment was defined as AMT score of ≤6 if 0-6 years of education and AMT score of ≤8 if >7 years of education. Fully adjusted multivariate models were used. We included seven studies in a meta-analysis of 25OHD and cognition in Asia (6068 participants; 1179 cognitively impaired cases). RESULTS: Participants with 25OHD levels >20 ng mL(-1) (n = 1302) had higher AMT total scores (mean ± SD 8.5 ± 1.9) and were less likely to have cognitive impairment (14.1%) than participants with lower 25OHD levels (overall P < 0.001, P-trend < 0.001). Deseasonalized 25OHD concentration was associated with AMT score (ß = 0.10 per 10 ng mL(-1) , P = 0.035). Vitamin D insufficiency (25OHD ≤20 ng mL(-1) ) was associated with global cognitive impairment (OR 1.56, P = 0.028). Specifically, 25OHD concentration correlated with semantic memory (r = 0.08, P = 0.009) and orientation in time (r = 0.09, P = 0.003). In the meta-analysis, the pooled mean 25OHD difference was -6.83 ng mL(-1) (95% confidence interval -11.36; -2.30), indicating lower 25OHD concentrations amongst cognitively impaired compared to cognitively healthy participants in Asia. CONCLUSION: Vitamin D insufficiency is associated with a greater likelihood of and more severe cognitive impairment in Asian populations.

Febuxostat-associated drug reaction with eosinophilia and systemic symptoms (DRESS).

WHAT IS KNOWN AND OBJECTIVE: Febuxostat is recommended as an alternative drug for gouty patients with a history of allopurinol hypersensitivity or carrying the HLA-B*5801 allele. CASE SUMMARY: An 81-year-old man with the medical history of gout presented to our clinic with generalized rashes for 2 days. After taking febuxostat for 2 days, he developed generalized skin rash with high fever. Laboratory tests showed elevated liver enzymes and acute kidney injury. WHAT IS KNOWN AND OBJECTIVE: This is the first identified case of febuxostat-associated DRESS. Febuxostat should be withdrawn immediately when DRESS is observed to avoid further serious complications.

Inhibition of melanogenesis by ß-caryophyllene from lime mint essential oil in mouse B16 melanoma cells.

OBJECTIVE: Volatile essential oils of mint species are used for cosmetics and in skin care products. In this study, we evaluated the main chemical components of the lime mint and the anti-melanogenic properties of its main components. METHODS: The essential oil was analysed by gas chromatography-mass spectrometry (GC/MS). The anti-melanogenic effects of mint essential oil and ß-caryophyllene were investigated in B16F10 murine melanoma cells. RESULTS: The main components of lime mint essential oil were found to be D-limonene (41.10%), D-carvone (8.58%), δ-selinene (6.73%) and ß-caryophyllene (6.24%). The lime mint essential oil reduced melanin production in a dose-dependent manner in murine B16F10 cells. ß-Caryophyllene, one of the main compounds in lime mint essential oil, could reduce melanogenesis by down-regulating the expression of MITF, TRP-1, TRP-2 and tyrosinase, resulting in a decrease in melanin content decrease. CONCLUSION: These results reveal that lime mint essential oil and ß-caryophyllene are considered to be valuable as potential skin-whitening agents.

Effects of supplemental nanoparticle trivalent chromium on the nutrient utilization, growth performance and serum traits of broilers.

The aim of this study was to investigate the effect of dietary supplementation of nanoparticle trivalent chromium on nutrient utilization, growth performance and serum traits of broilers. This study included two trials. In trial 1, 32 three-week-old broilers were divided into four groups: the control, chromium chloride (CrCl3), chromium picolinate (CrPic) and nanoparticle chromium picolinate (NanoCrPic). Chromium was added at a 1200 µg/kg level to evaluate the nutrient and chromium utilization. In trial 2, 160 one-day-old broilers were randomly divided into four groups as in trial 1, with four replicates. The results of trial 1 indicated that the chromium utilization is as follows: NanoCrPic > CrPic > CrCl3 and control groups, with significant differences between groups (p < 0.05). Crude fat utilization in CrCl3 group was lower than in that the control group (p < 0.05). The results of trial 2 indicated that feed intake of 4-5 weeks showed better result in the CrCl3 group than that in the CrPic group (p < 0.05). The results of serum traits indicated that the LDL-cholesterol in the NanoCrPic groups was lower than that in the CrPic group (p < 0.05). The NanoCrpic and CrPic groups showed significantly increased serum chromium concentration when compared with the control and CrCl3 groups; the triglyceride level in the CrCl3 group was lower than that in the CrPic group (p < 0.05). This study concluded that compared with CrPic, NanoCrpic supplementation could increase chromium utilization and lower the serum LDL-cholesterol of broilers.

Perinatal stress, fatigue, depressive symptoms, and immune modulation in late pregnancy and one month postpartum.

Stress and fatigue are common complaints of pregnant and postpartum women as is depression. These symptoms may be related to immunomodulation. However, few studies have examined these relationships. The aim of this study was to examine the relationships among stress, fatigue, depression, and cytokines as markers of immune modulation in prenatal and postpartum women. Women completed questionnaires and gave blood samples during late pregnancy and again at 4-6 weeks postpartum. Blood was analyzed for cytokines as measures of immune modulation. Stress, fatigue, and depression were experienced at moderately high levels, with higher levels of fatigue and depression in the postpartum but higher stress in the prenatal period. Levels of several cytokines were increased in the postpartum over the prenatal period. Stress and depression were related in the prenatal period and stress, depression, and fatigue were related in the postpartum. While various cytokines were related to each other in both periods, only stress was related to MIP-1ß, a cytokine that may be important for childbirth processes. More studies, especially longitudinal and interventional studies, are needed to increase our knowledge about etiology, patterns, symptoms, factors, and management of maternal distress. The search for reliable biomarkers for at-risk mothers remains a priority.

Effects of maltitol and xylitol chewing-gums on parameters involved in dental caries development.

AIM: The effects on plaque parameters of sugar free chewing-gums (CG) sweetened with either maltitol or xylitol were assessed to better understand the role polyols can play in dental caries prevention. MATERIALS AND METHODS: A double-blind, parallel, randomised, controlled study was conducted in China. Subjects (N = 258, age = 13 to 15 years-old) were divided into 4 groups: 2 receiving polyols CG, containing respectively maltitol or xylitol, a group receiving gum base (placebo) and a negative control group not receiving any gum. CG were chewed for 30 days. This corresponds to a 10 g consumption of polyol per day. Plaque parameters (growth, pH, bacteria and insoluble glucans) were evaluated throughout the experimental period. RESULTS: All parameters studied were significantly modified with gum base compared to no-gum: plaque pH increased; plaque growth, bacteria (S. mutans, S. sobrinus, A. viscosus and Lactobacillus) and insoluble glucans decreased. Maltitol and xylitol CG led similarly to a higher plaque pH (AUC, p⋜0.05) on short (at baseline after the first CG consumption) and long term (after 4 weeks of daily CG consumption), with or without saliva stimulation compared to both control and placebo groups. They led to a decrease in plaque growth (p=0.02) over the experimental period compared to controls. Moreover, they significantly reduced the concentration of 4 cariogenic bacteria species (p⋜0.05) in dental plaque compared to gum base. CONCLUSION: Sugar free CG sweetened with either maltitol or xylitol can similarly reduce plaque acidogenicity compared to gum base through a decrease in oral bacteria presence. The use of a gum base placebo allowed to isolate effects on parameters involved in dental caries development specific to maltitol and xylitol, and to show these effects were similar.

Spermatogonial stem cells alone are not sufficient to re-initiate spermatogenesis in the rat testis following adjudin-induced infertility.

The blood-testis barrier (BTB) is a unique ultrastructure in the testis, which creates a specialized microenvironment in the seminiferous epithelium known as the apical (or adluminal) compartment for post-meiotic germ-cell development and for maintenance of an immunological barrier. In this study, we have demonstrated unequivocally that a functional and intact BTB is crucial for the initiation of spermatogenesis, in particular, the differentiation of spermatogonial stem cells (SSCs). It was shown that adult rats (∼300 g body weight, b.w.) treated with adjudin at 50 (low-dose) or 250 (high-dose) mg/kg b.w. by gavage led to germ-cell depletion from the seminiferous tubules and that >98% of the tubules were devoid of germ cells by ∼2 week and rats became infertile in both groups after the sperm reserve in the epididymis was exhausted. While the population of SSC/spermatogonia in the seminiferous tubules from both groups was similar to that of normal rats, only rats from the low-dose group were capable of re-initiating spermatogenesis; and by 20 weeks, greater than 75% of the tubules displayed normal spermatogenesis and the fertility of these rats rebounded. Detailed analysis by dual-labelled immunofluorescence analysis and a functional BTB integrity assay revealed that in both treatment groups, the BTB was disrupted from week 6 to week 12. However, the disrupted BTB 'resealed' in the low-dose group, but not in the high-dose group. Our findings illustrate that SSC/spermatogonia failed to differentiate into spermatocytes beyond A(aligned) spermatogonia in the high-dose group with a disrupted BTB. In short, these findings illustrate the critical significance of the BTB for re-initiation of spermatogenesis besides SSC and spermatogonia.

Increased Incident Alzheimer's Disease among Individuals with Varicose Veins: A Population-Based Cohort Study.

BACKGROUND: Varicose vein may be related to increased risk of comorbidities and decreased cognitive function in the elderly, but little is known about the association between varicose vein and Alzheimer's disease. OBJECTIVES: To evaluate whether there is an association between varicose veins and Alzheimer's disease. DESIGN: The study subjects of this cohort study were selected based on Chang Gung Research Database from January 1, 2003, to December 31, 2012. Follow-up ended December 31, 2017. SETTING: A population-based study Participants: Patients aged 45 years and older with varicose veins were enrolled, and the participants of control group were selected by matching with gender, age, and index date at a 4:1 ratio. MEASUREMENTS: The hazard ratios associated with varicose veins were estimated using Cox regression analysis with competitive risk model. Incidence rates of Alzheimer's disease, was assessed in people with and without varicose veins. RESULTS: A total of 9,601 patients with varicose veins and 38,404 matched controls were enrolled in the study. The varicose veins group had higher incidence rates than the control group for Alzheimer's disease (12.60 vs 6.24 per 10,000 person-years; Hazard ratio, 1.647 [95% confidence interval, 1.326- 2.045, p<0.001]). Patients with complicated varicose veins had increased incidence of Alzheimer's disease than uncomplicated cases (adjusted HR, 1.474; 95% CI, 1.034-2.101, P=0.032). CONCLUSION: The present study demonstrated a positive association between the varicose veins and Alzheimer's disease. Physicians should be alerted to cognitive function in patients with varicose veins, especially those with presence of inflammation and ulcerations.

Seroprevalence of Toxocara canis infection among children in Swaziland, southern Africa.

As there appeared to be no data available on Toxocara canis infection in the children of Swaziland, a serological survey of T. canis infection was recently conducted among 92 children aged 3-12 years from rural slums in the low- and middle-veld. A child was considered seropositive if, in western blots based on the excretory-secretory antigens of larval T. canis, his or her serum gave a positive result when diluted 1 : 64. Forty-one (44.6%) of the children were found seropositive. There were no statistically significant differences in seroprevalence between the 49 boys and 43 girls investigated (46.9% v. 41.8%) or between the eight subjects aged 12 years and the 47 aged < or = 5 years (62.5% v. 38.3%); the corresponding odds ratios were 0.81 (95% confidence interval=0.36-1.86; P=0.62) and 2.69 (95% confidence interval=0.57-12.62; P=0.20), respectively. The 66 subjects from the middleveld were, however, significantly more likely to be seropositive than the 26 subjects from the lowveld (54.5% v. 19.2%; odds ratio=5.04, with a 95% confidence interval of 1.70-14.98; P<0.01). It seems likely that T. canis infection is common among the children who live in slums in Swaziland, particularly in the country's middleveld, probably as the result of poor hygiene and poor sanitation.

Prostacyclin protects renal tubular cells from gentamicin-induced apoptosis via a PPARalpha-dependent pathway.

To study the protective effect of prostacyclin (PGI2) we increased PGI2 production by infected NRK-52E cells with an adenovirus carrying cyclooxygenase-1 and prostacyclin synthase. PGI2 overexpression protected these cells from gentamicin-induced apoptosis by reducing cleaved caspase-3 and caspase-9, cytochrome c, and decreasing generation of reactive oxygen species. Expression of the nuclear receptor of PGI2, peroxisome proliferator-activated receptor-alpha (PPARalpha), was reduced during gentamicin treatment of the cells, while its overexpression significantly inhibited gentamicin-induced apoptosis and the amount of cleaved caspase-3. Transformation with PPARalpha short interfering RNA abolished the protective effect of PGI2 overproduction in gentamicin-treated cells. The PPARalpha activator docosahexaenoic acid given to gentamicin-treated mice significantly reduced the number of apoptotic cells in renal cortex, but this protective effect was not seen in PPARalpha knockout mice. Our study suggests that increased endogenous PGI2 production protects renal tubular cells from gentamicin-induced apoptosis through a PPARalpha-signaling pathway.

The antimicrobial activity of heyneanol A extracted from the root of Taiwanese wild grape.

AIMS: To search for antimicrobial compounds against pathogenic bacteria from grape vines (Vitis spp.). To investigate the antimicrobial efficacy of active compounds towards methicillin-resistant Staphylococcus aureus (MRSA). METHODS AND RESULTS: The root extracts of taiwanese wild grape (Vitis thunbergii var. taiwaniana) showed marked activities against Gram-positive bacteria using the disc diffusion method. After purification, the active compound 1 was confirmed as heyneanol A by mass spectroscopy and nuclear magnetic resonance. Heyneanol A showed an minimum inhibitory concentration (MIC) value of 2 microg ml(-1) towards MRSA and a value of 2 to 4 microg ml(-1) for Enterococcus faecium, S. aureus, Streptococcus agalactiae and Streptococcus pyogenes. In addition, the contents of heyneanol A were determined as 36 mg g(-1) in roots of taiwanese wild grape. CONCLUSIONS: The root extracts of grapevines have good antimicrobial activities towards some strains of Gram-positive pathogens. Heyneanol A, the major antimicrobial compound, is especially active towards MRSA. In addition, the abundances of heyneanol A and other stilbenes in the roots of grapevines make it possible to produce natural antimicrobial compounds from this plant species. SIGNIFICANCE AND IMPACT OF THE STUDY: This study reports for the first time the antimicrobial compounds in the root extracts of grapevines. The results will have clinical significance owing to their activities against MRSA.

The effect of rigid versus flexible spinal orthosis on the gait pattern of patients with adolescent idiopathic scoliosis.

The conventional rigid spinal orthosis and the flexible spinal orthosis, SpineCor, have different treatment principles in the management of adolescent idiopathic scoliosis (AIS). These may influence the patients' gait pattern and clinical outcome. In this study, gait analysis on patients with AIS undergoing these two orthotic interventions were conducted. The patients' lower limb kinematic and kinetic data during level walking were collected using a motion analysis system and two force platforms in four test conditions: pre-intervention, having used the orthosis for 1 month and 1 year (in and out of the orthosis). Twenty-one subjects were randomly assigned to the rigid spinal orthosis group (10 subjects) and the SpineCor group (11 subjects). Neither group showed gait asymmetry when comparing the convex and concave sides in the four test conditions. However, significant reduction in the range of motion of the pelvis and hip joints in the coronal plane were found. Although patients with AIS undergoing these two orthotic interventions showed significant changes in walking pattern within the study period, their long-term effect on gait and function requires further investigation through long-term prospective studies.