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1.
Clin Neurophysiol ; 164: 168-179, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38901112

ABSTRACT

OBJECTIVE: This study investigated the efficacy of combining at-home anodal transcranial direct current stimulation (tDCS) of the left primary motor cortex (M1) with mindfulness meditation (MM) in fibromyalgia patients trained in mindfulness. METHODS: Thirty-seven patients were allocated to receive ten daily sessions of MM paired with either anodal or sham tDCS over the primary motor cortex. Primary outcomes were pain intensity and quality of life. Secondary outcomes were psychological impairment, sleep quality, mood, affective pain, mindfulness level, and transcranial magnetic stimulation (TMS) measures of cortical excitability. Outcomes were analyzed pre- and post-treatment, with a one-month follow-up. RESULTS: We found post-tDCS improvement in all clinical outcomes, including mindfulness level, except for positive affect and stress, in both groups without significant difference between active and sham conditions. No significant group*time interaction was found for all clinical and TMS outcomes. CONCLUSIONS: Our findings demonstrate no synergistic or add-on efffect of anodal tDCS of the left M1 compared to the proper effect of MM in patients with fibromyalgia. SIGNIFICANCE: Our findings challenge the potential of combining anodal tDCS of the left M1 and MM in fibromyalgia.


Subject(s)
Fibromyalgia , Meditation , Mindfulness , Motor Cortex , Transcranial Direct Current Stimulation , Adult , Female , Humans , Male , Middle Aged , Fibromyalgia/therapy , Fibromyalgia/psychology , Fibromyalgia/physiopathology , Meditation/methods , Mindfulness/methods , Motor Cortex/physiopathology , Motor Cortex/physiology , Transcranial Direct Current Stimulation/methods , Treatment Outcome
2.
J Eur Acad Dermatol Venereol ; 37(2): 402-410, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36196047

ABSTRACT

BACKGROUND: Epidermolysis bullosa (EB) is a rare genetic disorder manifesting with skin and mucosal membrane blistering in different degrees of severity. OBJECTIVE: Epidemiological data from different countries have been published, but none are available from Germany. METHODS: In this population-based cross-sectional study, people living with EB in Germany were identified using the following sources: academic hospitals, diagnostic laboratories and patient organization. RESULTS: Our study indicates an overall EB incidence of 45 per million live births in Germany. With 14.23 per million live births for junctional EB, the incidence is higher than in other countries, possibly reflecting the availability of early molecular genetic diagnostics in severely affected neonates. Dystrophic EB was assessed at 15.58 cases per million live births. The relatively low incidence found for EB simplex, 14.93 per million live births, could be explained by late or missed diagnosis, but also by 33% of cases remaining not otherwise specified. Using log-linear models, we estimated a prevalence of 54 per million for all EB types, 2.44 for junctional EB, 12.16 for dystrophic EB and 28.44 per million for EB simplex. These figures are comparable to previously reported data from other countries. CONCLUSIONS: Altogether, there are at least 2000 patients with EB in the German population. These results should support national policies and pharmaceutical companies in decision-making, allow more precise planning of drug development and clinical trials, and aid patient advocacy groups in their effort to improve quality of life of people with this orphan disease.


Subject(s)
Epidermolysis Bullosa Dystrophica , Epidermolysis Bullosa Simplex , Epidermolysis Bullosa, Junctional , Epidermolysis Bullosa , Infant, Newborn , Humans , Cross-Sectional Studies , Quality of Life , Epidermolysis Bullosa/epidemiology , Skin , Epidermolysis Bullosa Dystrophica/genetics , Epidermolysis Bullosa Simplex/genetics
3.
Int J Public Health ; 66: 634904, 2021.
Article in English | MEDLINE | ID: mdl-34335139

ABSTRACT

Objectives: We explored the association of underlying health conditions (UHC) with depression and anxiety, and examined the modification effects of suspected COVID-19 symptoms (S-COVID-19-S), health-related behaviors (HB), and preventive behaviors (PB). Methods: A cross-sectional study was conducted on 8,291 outpatients aged 18-85 years, in 18 hospitals and health centers across Vietnam from 14th February to May 31, 2020. We collected the data regarding participant's characteristics, UHC, HB, PB, depression, and anxiety. Results: People with UHC had higher odds of depression (OR = 2.11; p < 0.001) and anxiety (OR = 2.86; p < 0.001) than those without UHC. The odds of depression and anxiety were significantly higher for those with UHC and S-COVID-19-S (p < 0.001); and were significantly lower for those had UHC and interacted with "unchanged/more" physical activity (p < 0.001), or "unchanged/more" drinking (p < 0.001 for only anxiety), or "unchanged/healthier" eating (p < 0.001), and high PB score (p < 0.001), as compared to those without UHC and without S-COVID-19-S, "never/stopped/less" physical activity, drinking, "less healthy" eating, and low PB score, respectively. Conclusion: S-COVID-19-S worsen psychological health in patients with UHC. Physical activity, drinking, healthier eating, and high PB score were protective factors.


Subject(s)
Anxiety , COVID-19 , Comorbidity , Depression , Outpatients , Adolescent , Adult , Aged , Aged, 80 and over , Anxiety/epidemiology , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19/psychology , Cross-Sectional Studies , Depression/epidemiology , Female , Humans , Male , Middle Aged , Outpatients/psychology , Outpatients/statistics & numerical data , Vietnam/epidemiology , Young Adult
4.
Article in English | MEDLINE | ID: mdl-34066312

ABSTRACT

BACKGROUND: The COVID-19 pandemic has been disseminating fear in the community, which has affected people's quality of life, especially those with health problems. Health literacy (HL), eHealth literacy (eHEAL), and digital healthy diet literacy (DDL) may have potential impacts on containing the pandemic and its consequences. This study aimed to examine the association between the fear of COVID-19 scale (FCoV-19S) and the health-related quality of life (HRQoL), and to examine the effect modification by HL, eHEAL, and DDL on this association. METHODS: A cross-sectional study was conducted in 11 hospitals across Vietnam from 7 April to 31 May 2020. Data were collected on 4348 outpatients, including demographic characteristics, HL, eHEAL, DDL, FCoV-19S, and HRQoL. Multiple linear regression and interaction models were used to explore associations. RESULTS: Patients with higher FCoV-19S scores had lower HRQoL scores (unstandardized coefficient, B = -0.78, p < 0.001). HL (B = 0.20, p < 0.001), eHEAL (B = 0.24, p < 0.001), and DDL (B = 0.20, p < 0.001) were positively associated with higher HRQoL scores. The negative impact of FCoV-19S on HRQoL was significantly attenuated by higher eHEAL score groups (from one standard deviation (SD) below the mean, B = -0.93, p < 0.001; to the mean, B = -0.85, p < 0.001; and one SD above the mean, B = -0.77, p < 0.001); and by higher DDL score groups (from one SD below the mean, B = -0.92, p < 0.001; to the mean, B = -0.82, p < 0.001; and one SD above the mean, B = -0.72, p < 0.001). CONCLUSIONS: eHealth literacy and digital healthy diet literacy could help to protect patients' health-related quality of life from the negative impact of the fear of COVID-19 during the pandemic.


Subject(s)
COVID-19 , Health Literacy , Telemedicine , Cross-Sectional Studies , Diet, Healthy , Fear , Hospitals , Humans , Pandemics , Quality of Life , SARS-CoV-2 , Surveys and Questionnaires , Vietnam
5.
Int J Infect Dis ; 105: 277-285, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33596479

ABSTRACT

OBJECTIVES: Rotavirus (RV) genotypes vary geographically, and this can affect vaccine effectiveness (VE). This study investigated the genotype distribution of RV and explored VE before introducing the RV vaccine to the national immunization programme in Vietnam. METHODS: This hospital-based surveillance study was conducted at Children's Hospital 1, Ho Chi Minh City in 2013-2018. Stool samples and relevant data, including vaccination history, were collected from children aged <5 years who were hospitalized with gastroenteritis. RV was detected using enzyme immunoassays and then genotyped. Children aged ≥6 months were included in the VE analysis. RESULTS: Overall, 5176 children were included in this study. RV was detected in 2421 children (46.8%). RV positivity decreased over the study period and was associated with age, seasonality, location and previous vaccination. Among 1105 RV-positive samples, G3P[8] was the most prevalent genotype (43.1%), followed by G8P[8] (19.7%), G1P[8] (12.9%) and G2P[4] (12.9%). Overall VE was 69.7% [95% confidence interval (CI) 53.3-80.6%] in fully vaccinated children and 58.6% (95% CI 44.1-69.4%) in children who had received at least one dose of RV vaccine. VE was highest for G3P[8] (95% CI 75.1-84.5%) and lowest for G2P[4] (95% CI 32.4-57.2%). CONCLUSIONS: RV remains a major cause of acute gastroenteritis requiring hospitalization in southern Vietnam. The RV vaccine is effective, but its effectiveness varies with RV genotype.


Subject(s)
Genotype , Rotavirus Vaccines/immunology , Rotavirus/genetics , Rotavirus/immunology , Vaccination/statistics & numerical data , Child , Child, Preschool , Feces/virology , Female , Gastroenteritis/epidemiology , Gastroenteritis/prevention & control , Hospitalization , Humans , Infant , Male , Outcome Assessment, Health Care , Rotavirus/physiology , Vietnam/epidemiology
6.
Eur J Heart Fail ; 23(5): 743-750, 2021 05.
Article in English | MEDLINE | ID: mdl-32946151

ABSTRACT

AIMS: Arginine vasopressin (AVP) mediates deleterious effects via vascular V1a and renal V2 receptors in heart failure (HF). Despite positive short-term decongestive effects in phase II HF studies, selective V2 receptor antagonism has shown no long-term mortality benefit, potentially related to unopposed V1a receptor activation. We compared the novel dual V1a/V2 receptor antagonist pecavaptan with the selective V2 receptor antagonist tolvaptan in pre-clinical HF models. METHODS AND RESULTS: In vitro IC50 determination in recombinant cell lines revealed similar receptor selectivity profiles (V2:V1a) of tolvaptan and pecavaptan for human and dog AVP receptors, respectively. Two canine models were used to compare haemodynamic and aquaretic effects: (i) anaesthetised dogs with tachypacing-induced HF, and (ii) conscious telemetric dogs with a non-invasive cardiac output (CO) monitor. Tolvaptan and pecavaptan exhibited no differences in urinary output. In HF dogs, pecavaptan counteracted the AVP-induced increase in afterload and decrease in CO (pecavaptan: 1.83 ± 0.31 L/min; vs. tolvaptan: 1.46 ± 0.07 L/min, P < 0.05). In conscious telemetric animals, pecavaptan led to a significant increase in CO (+0.26 ± 0.17 L/min, P = 0.0086 vs. placebo), in cardiac index (+0.58 ± 0.39 L/min/m2 , P = 0.009 vs. placebo) and a significant decrease in total peripheral resistance (-5348.6 ± 3601.3 dyn × s/cm5 , P < 0.0001 vs. placebo), whereas tolvaptan was without any significant effect. CONCLUSIONS: Simultaneous blockade of vascular V1a and renal V2 receptors efficiently induces aquaresis and counteracts AVP-mediated haemodynamic aggravation in HF models. Dual V1a/V2 antagonism may lead to improved outcomes in HF.


Subject(s)
Heart Failure , Receptors, Vasopressin , Animals , Antidiuretic Hormone Receptor Antagonists , Cardiac Output , Dogs , Vasopressins
7.
Front Nutr ; 7: 581043, 2020.
Article in English | MEDLINE | ID: mdl-33304917

ABSTRACT

Background: The COVID-19 pandemic causes a huge burden for affected countries. Several public health interventions were applied to contain the infection. However, the pandemic itself and the lockdown measure negatively influence people's lifestyles and psychological health. Purpose: To explore determinants of healthy dietary intake and depression, and examine the interaction between healthy dietary intake and COVID-19 lockdown on depression. Methods: A cross-sectional study was conducted at 18 hospitals and health centers from February 14 to May 31, 2020. Data of 8,291 outpatients were collected including patients' characteristics, clinical parameters, health literacy, healthy dietary intake (using the healthy eating score, HES), other health-related behaviors, and depression (using the patient health questionnaire, PHQ). Depression was defined as PHQ score ≥ 10. Results: Protective factors of healthy dietary intake and depression were higher education, better medication payment ability, higher social status, more physical activity, and higher health literacy, whereas older age, ever married, own business or other types of occupation, lockdown, suspected COVID-19 symptoms, and comorbidity were associated with lower HES scores and a higher depression likelihood. Besides, overweight/obesity and alcohol drinking were associated with lower HES scores. As compared with patients not under lockdown and with lowest HES score, those who were under lockdown and with lowest HES score had 10.6 times higher depression likelihood (odds ratio, OR, 10.60; 95% CI 6.88, 16.32; p < 0.001), whereas people with higher HES score had 15% lower depression likelihood (OR 0.85; 95% CI 0.82, 0.89; p < 0.001). Conclusions: Healthy dietary intake and depression were determined by several sociodemographic, clinical, and behavioral factors. Lockdown measure affects people's dietary intake behavior and depression. Importantly, healthy dietary intake potentially modifies the negative effect of lockdown on depression.

8.
Trop Med Infect Dis ; 5(4)2020 Nov 30.
Article in English | MEDLINE | ID: mdl-33265972

ABSTRACT

To accelerate the reduction in tuberculosis (TB) incidence, it is necessary to optimize the use of innovative tools and approaches available within a local context. This study evaluated the use of an existing network of community health workers (CHW) for active case finding, in combination with mobile chest X-ray (CXR) screening events and the expansion of Xpert MTB/RIF testing eligibility, in order to reach people with TB who had been missed by the current system. A controlled intervention study was conducted from January 2018 to March 2019 in five intervention and four control districts of two low to medium TB burden cities in Viet Nam. CHWs screened and referred eligible persons for CXR to TB care facilities or mobile screening events in the community. The initial diagnostic test was Xpert MTB/RIF for persons with parenchymal abnormalities suggestive of TB on CXR or otherwise on smear microscopy. We analyzed the TB care cascade by calculating the yield and number needed to screen (NNS), estimated the impact on TB notifications and conducted a pre-/postintervention comparison of TB notification rates using controlled, interrupted time series (ITS) analyses. We screened 30,336 individuals in both cities to detect and treat 243 individuals with TB, 88.9% of whom completed treatment successfully. All forms of TB notifications rose by +18.3% (95% CI: +15.8%, +20.8%). The ITS detected a significant postintervention step-increase in the intervention area for all-form TB notification rates (IRR(ß6) = 1.221 (95% CI: 1.011, 1.475); p = 0.038). The combined use of CHWs for active case findings and mobile CXR screening expanded the access to and uptake of Xpert MTB/RIF testing and resulted in a significant increase in TB notifications. This model could serve as a blueprint for expansion throughout Vietnam. Moreover, the results demonstrate the need to optimize the use of the best available tools and approaches in order to end TB.

9.
Trop Med Infect Dis ; 5(3)2020 Sep 14.
Article in English | MEDLINE | ID: mdl-32937757

ABSTRACT

Under-detection and -reporting in the private sector constitute a major barrier in Viet Nam's fight to end tuberculosis (TB). Effective private-sector engagement requires innovative approaches. We established an intermediary agency that incentivized private providers in two districts of Ho Chi Minh City to refer persons with presumptive TB and share data of unreported TB treatment from July 2017 to March 2019. We subsidized chest x-ray screening and Xpert MTB/RIF testing, and supported test logistics, recording, and reporting. Among 393 participating private providers, 32.1% (126/393) referred at least one symptomatic person, and 3.6% (14/393) reported TB patients treated in their practice. In total, the study identified 1203 people with TB through private provider engagement. Of these, 7.6% (91/1203) were referred for treatment in government facilities. The referrals led to a post-intervention increase of +8.5% in All Forms TB notifications in the intervention districts. The remaining 92.4% (1112/1203) of identified people with TB elected private-sector treatment and were not notified to the NTP. Had this private TB treatment been included in official notifications, the increase in All Forms TB notifications would have been +68.3%. Our evaluation showed that an intermediary agency model can potentially engage private providers in Viet Nam to notify many people with TB who are not being captured by the current system. This could have a substantial impact on transparency into disease burden and contribute significantly to the progress towards ending TB.

10.
Plants (Basel) ; 9(6)2020 Jun 03.
Article in English | MEDLINE | ID: mdl-32503327

ABSTRACT

Macadamia is an Australian native rainforest tree that has been domesticated and traded internationally for its premium nuts. Common cultivars rely upon a limited gene pool that has exploited only two of the four species. Introducing a more diverse germplasm will broaden the genetic base for future crop improvement and better adaptation for changing environments. This study investigated the genetic structure of 302 accessions of wild germplasm using 2872 SNP and 8415 silicoDArT markers. Structure analysis and principal coordinate analysis (PCoA) assigned the 302 accessions into four distinct groups: (i) Macadamia integrifolia, (ii) M. tetraphylla, and (iii) M. jansenii and M. ternifolia, and (iv) admixtures or hybrids. Assignment of the four species matched well with previous characterisations, except for one M. integrifolia and four M. tetraphylla accessions. Using SNP markers, 94 previously unidentified accessions were assigned into the four distinct groups. Finally, 287 accessions were identified as pure examples of one of the four species and 15 as hybrids of M. integrifolia and M. tetraphylla. The admixed accessions showed the highest genetic diversity followed by M. integrifolia, while M. ternifolia and M. jansenii accessions were the least diverse. Mantel test analysis showed a significant correlation between genetic and geographic distance for M. integrifolia (r = 0.51, p = 0.05) and a positive but not significant correlation for M. tetraphylla (r = 0.45, p = 0.06). This study provides a population genetics overview of macadamia germplasm as a background for a conservation strategy and provides directions for future macadamia breeding.

11.
J Infect Dis ; 216(11): 1371-1379, 2017 12 12.
Article in English | MEDLINE | ID: mdl-29029128

ABSTRACT

Background: Enterovirus A71 (EV-A71) is the major cause of severe hand, foot, and mouth disease and viral encephalitis in children across the Asia-Pacific region, including in Vietnam, which has experienced a high burden of disease in recent years. Multiple subgenogroups (C1, C4, C5, and B5) concurrently circulate in the region with a large variation in epidemic severity. The relative differences in their evolution and epidemiology were examined within Vietnam and globally. Methods: A total of 752 VP1 gene sequences were analyzed (413 generated in this study combined with 339 obtained from GenBank), collected from patients in 36 provinces in Vietnam during 2003-2013, along with epidemiological metadata. Globally representative VP1 gene datasets of subgenogroups were used to coestimate time-resolved phylogenies and relative genetic diversity to infer virus origins and regional transmission network. Results: Despite frequent virus migration between countries, the highest genetic diversity of individual subgenogroups was maintained independently for several years in specific Asian countries representing genogroup-specific sources of EV-A71 diversity. Conclusion: This study highlights a persistent transmission network of EV-A71, with specific Asian countries seeding other countries in the region and beyond, emphasizing the need for improved EV-A71 surveillance and detailed genetic and antigenic characterization.


Subject(s)
Enterovirus A, Human/classification , Enterovirus A, Human/genetics , Enterovirus Infections/epidemiology , Enterovirus Infections/virology , Genotype , Spatio-Temporal Analysis , Antigens, Viral , Asia/epidemiology , Child , Child, Preschool , Disease Outbreaks , Enterovirus A, Human/isolation & purification , Enterovirus A, Human/pathogenicity , Enterovirus Infections/transmission , Genetic Variation , Humans , Infant , Infant, Newborn , Phylogeny , Sequence Analysis , Vietnam/epidemiology
12.
J Infect Dis ; 216(suppl_4): S529-S538, 2017 09 15.
Article in English | MEDLINE | ID: mdl-28934457

ABSTRACT

Mutation and reassortment of highly pathogenic avian influenza A(H5N1) viruses at the animal-human interface remain a major concern for emergence of viruses with pandemic potential. To understand the relationship of H5N1 viruses circulating in poultry and those isolated from humans, comprehensive phylogenetic and molecular analyses of viruses collected from both hosts in Vietnam between 2003 and 2010 were performed. We examined the temporal and spatial distribution of human cases relative to H5N1 poultry outbreaks and characterized the genetic lineages and amino acid substitutions in each gene segment identified in humans relative to closely related viruses from avian hosts. Six hemagglutinin clades and 8 genotypes were identified in humans, all of which were initially identified in poultry. Several amino acid mutations throughout the genomes of viruses isolated from humans were identified, indicating the potential for poultry viruses infecting humans to rapidly acquire molecular markers associated with mammalian adaptation and antiviral resistance.


Subject(s)
Influenza A Virus, H5N1 Subtype/isolation & purification , Influenza in Birds/epidemiology , Influenza, Human/epidemiology , Amino Acid Sequence , Animals , Drug Resistance, Multiple, Viral , Genotype , Genotyping Techniques , Humans , Influenza A Virus, H5N1 Subtype/genetics , Influenza in Birds/drug therapy , Influenza in Birds/transmission , Influenza, Human/drug therapy , Pandemics , Phylogeny , Poultry/virology , RNA, Viral/genetics , Sequence Analysis, RNA , Spatio-Temporal Analysis , Vietnam/epidemiology , Viral Proteins/genetics
13.
J Gen Virol ; 98(8): 2011-2016, 2017 Aug.
Article in English | MEDLINE | ID: mdl-28771136

ABSTRACT

Rural farming communities in northern Vietnam do not routinely practice vaccination for influenza A viruses (IAV) for either humans or poultry, which enables us to study transmission intensity via seroepidemiology. Using samples from a longitudinal cohort of farming households, we determined the number of symptomatic and asymptomatic human infections for seasonal IAV and avian A/H9 over 2 years. As expected, we detected virologically confirmed acute cases of seasonal IAV in humans, as well as large numbers of subclinical seroconversions to A/H1pdm [55/265 (21 %)], A/H3 [95/265 (36 %)] and A/H9 [24/265 (9 %)]. Five of the A/H9 human seroconverters likely represented true infections rather than heterosubtypic immunity, because the individuals seroconverted solely to A/H9. Among co-located poultry, we found significantly higher seroprevalance for A/H5 compared to A/H9 in both chickens and ducks [for northern study sites overall, 337/1105 (30.5 %) seropositive for A/H5 and 123/1105 (11.1 %) seropositive for A/H9].


Subject(s)
Influenza A Virus, H9N2 Subtype/isolation & purification , Influenza in Birds/virology , Influenza, Human/virology , Poultry Diseases/virology , Adolescent , Adult , Aged , Agriculture , Animals , Antibodies, Viral/blood , Chickens , Child , Child, Preschool , Ducks , Female , Humans , Infant , Influenza A Virus, H9N2 Subtype/classification , Influenza A Virus, H9N2 Subtype/genetics , Influenza A Virus, H9N2 Subtype/immunology , Influenza in Birds/blood , Influenza in Birds/epidemiology , Influenza in Birds/transmission , Influenza, Human/blood , Influenza, Human/epidemiology , Influenza, Human/transmission , Male , Middle Aged , Poultry Diseases/blood , Poultry Diseases/epidemiology , Poultry Diseases/transmission , Rural Population/statistics & numerical data , Seroepidemiologic Studies , Vietnam , Young Adult
14.
Sci Transl Med ; 8(357): 357ra124, 2016 09 21.
Article in English | MEDLINE | ID: mdl-27655850

ABSTRACT

New therapeutic approaches are urgently needed to improve survival outcomes for patients with necrotizing pneumonia caused by Staphylococcus aureus One such approach is adjunctive treatment with intravenous immunoglobulin (IVIG), but clinical practice guidelines offer conflicting recommendations. In a preclinical rabbit model, prophylaxis with IVIG conferred protection against necrotizing pneumonia caused by five different epidemic strains of community-associated methicillin-resistant S. aureus (MRSA) as well as a widespread strain of hospital-associated MRSA. Treatment with IVIG, either alone or in combination with vancomycin or linezolid, improved survival outcomes in this rabbit model. Two specific IVIG antibodies that neutralized the toxic effects of α-hemolysin (Hla) and Panton-Valentine leukocidin (PVL) conferred protection against necrotizing pneumonia in the rabbit model. This mechanism of action of IVIG was uncovered by analyzing loss-of-function mutant bacterial strains containing deletions in 17 genes encoding staphylococcal exotoxins, which revealed only Hla and PVL as having an impact on necrotizing pneumonia. These results demonstrate the potential clinical utility of IVIG in the treatment of severe pneumonia induced by S. aureus.


Subject(s)
Immunoglobulins, Intravenous/therapeutic use , Methicillin-Resistant Staphylococcus aureus/physiology , Pneumonia, Necrotizing/drug therapy , Pneumonia, Necrotizing/microbiology , Acute Lung Injury/drug therapy , Acute Lung Injury/microbiology , Acute Lung Injury/pathology , Animals , Antibiotic Prophylaxis , Antibodies, Neutralizing/immunology , Bacterial Toxins/immunology , Disease Models, Animal , Exotoxins/immunology , Hemolysin Proteins/immunology , Humans , Leukocidins/immunology , Linezolid/pharmacology , Linezolid/therapeutic use , Methicillin-Resistant Staphylococcus aureus/immunology , Rabbits , Vancomycin/pharmacology , Vancomycin/therapeutic use
15.
ACS Appl Mater Interfaces ; 8(37): 24870-9, 2016 Sep 21.
Article in English | MEDLINE | ID: mdl-27560306

ABSTRACT

A new strategy for the fabrication of micropatterns of surface-attached hydrogels with well-controlled chemistry is reported. The "grafting onto" approach is preferred to the "grafting from" approach. It consists of cross-linking and grafting preformed and functionalized polymer chains through thiol-ene click chemistry. The advantage is a very good control without adding initiators. A powerful consequence of thiol-ene click reaction by UV irradiation is the facile fabrication of micropatterned hydrogel thin films by photolithography. It is achieved either with photomasks using common UV lamp or without photomasks by direct drawing due to laser technology. Our versatile approach allows the fabrication of various chemical polymer networks on various solid substrates. It is demonstrated here with silicon wafers, glass and gold surfaces as substrates, and two responsive hydrogels, poly(N-isopropylacrylamide) for its responsiveness to temperature and poly(acrylic acid) for its pH-sensitivity. We also demonstrate the fabrication of stable hydrogel multilayers (or stacked layers) in which each elementary layer height can widely range from a few nanometers to several micrometers, providing an additional degree of freedom to the internal architecture of hydrogel patterns. This facile route for the synthesis of micrometer-resolute hydrogel patterns with tailored architecture and multiresponsive properties should have a strong impact.

16.
mBio ; 6(1): e02272-14, 2015 Feb 17.
Article in English | MEDLINE | ID: mdl-25691592

ABSTRACT

UNLABELLED: Staphylococcus aureus is a Gram-positive, commensal bacterium known to asymptomatically colonize the human skin, nares, and gastrointestinal tract. Colonized individuals are at increased risk for developing S. aureus infections, which range from mild skin and soft tissue infections to more severe diseases, such as endocarditis, bacteremia, sepsis, and osteomyelitis. Different virulence factors are required for S. aureus to infect different body sites. In this study, virulence gene expression was analyzed in two S. aureus isolates during nasal colonization, bacteremia and in the heart during sepsis. These models were chosen to represent the stepwise progression of S. aureus from an asymptomatic colonizer to an invasive pathogen. Expression of 23 putative S. aureus virulence determinants, representing protein and carbohydrate adhesins, secreted toxins, and proteins involved in metal cation acquisition and immune evasion were analyzed. Consistent upregulation of sdrC, fnbA, fhuD, sstD, and hla was observed in the shift between colonization and invasive pathogen, suggesting a prominent role for these genes in staphylococcal pathogenesis. Finally, gene expression data were correlated to the roles of the genes in pathogenesis by using knockout mutants in the animal models. These results provide insights into how S. aureus modifies virulence gene expression between commensal and invasive pathogens. IMPORTANCE: Many bacteria, such as Staphylococcus aureus, asymptomatically colonize human skin and nasal passages but can also cause invasive diseases, such as bacteremia, pneumonia, sepsis, and osteomyelitis. The goal of this study was to analyze differences in the expression of selected S. aureus genes during a commensal lifestyle and as an invasive pathogen to gain insight into the commensal-to-pathogen transition and how a bacterial pathogen adapts to different environments within a host (e.g., from nasal colonization to invasive pathogen). The gene expression data were also used to select genes for which to construct knockout mutants to assess the role of several proteins in nasal colonization and lethal bacteremia. These results not only provide insight into the factors involved in S. aureus disease pathogenesis but also provide potential therapeutic targets.


Subject(s)
Carrier State/microbiology , Gene Expression Regulation, Bacterial , Osteomyelitis/microbiology , Sepsis/microbiology , Staphylococcal Infections/microbiology , Staphylococcus aureus/physiology , Virulence Factors/biosynthesis , Animals , Disease Models, Animal , Gene Expression Profiling , Gene Knockout Techniques , Mice, Inbred BALB C , Sigmodontinae , Staphylococcus aureus/genetics , Staphylococcus aureus/isolation & purification , Staphylococcus aureus/pathogenicity , Virulence , Virulence Factors/genetics
17.
J Infect Dis ; 209(10): 1533-41, 2014 May 15.
Article in English | MEDLINE | ID: mdl-24280367

ABSTRACT

BACKGROUND: Detailed knowledge on protein repertoire of a pathogen during host infection is needed for both developing a better understanding of the pathogenesis and defining potential therapeutic targets. Such data, however, have been missing for Staphylococcus aureus, a major human pathogen. METHODS: We determined the surface proteome of methicillin-resistant S. aureus (MRSA) clone usa300 derived directly from murine systemic infectiON. RESULTS: The majority of the in vivo-expressed surface-associated proteins were lipoproteins involved in nutrient acquisition, especially uptake of metal ions. Enzyme-linked immunosorbent assay (ELISA) of convalescent human serum samples revealed that proteins that were highly produced during murine experimental infection were also produced during natural human infection. We found that among the 7 highly abundant lipoproteins only MntC, which is the manganese-binding protein of the MntABC system, was essential for MRSA virulence during murine systemic infection. Moreover, we show that MntA and MntB are equally important for MRSA virulence. CONCLUSIONS: Besides providing experimental evidence that MntABC might be a potential therapeutic target for the development of antibiotics, our in vivo proteomics data will serve as a valuable basis for defining potential antigen combinations for multicomponent vaccines.


Subject(s)
Anti-Bacterial Agents/pharmacology , Bacterial Proteins/metabolism , Gene Expression Regulation, Bacterial/physiology , Methicillin-Resistant Staphylococcus aureus/drug effects , Methicillin-Resistant Staphylococcus aureus/metabolism , Proteomics , Animals , Bacterial Proteins/genetics , Enzyme-Linked Immunosorbent Assay/methods , Humans , Kidney/microbiology , Lipoproteins/genetics , Lipoproteins/metabolism , Membrane Proteins/genetics , Membrane Proteins/metabolism , Methicillin-Resistant Staphylococcus aureus/pathogenicity , Mice , Serum/immunology , Staphylococcal Infections/immunology , Staphylococcal Infections/microbiology , Staphylococcal Infections/prevention & control , Staphylococcal Vaccines/immunology , Virulence
18.
J Pediatr Urol ; 9(4): 424-6, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23103130

ABSTRACT

This is the first report of a single trocar nephrectomy for poorly functioning dysplastic kidney and ectopic ureter, performed in 5 patients from 2010 to 2011. The mean operative time was 63 min and mean postoperative hospital stay was 31 h. There were no perioperative complications. The single trocar nephrectomy is a feasible and safe procedure for patients with dysplastic kidney and ectopic ureter.


Subject(s)
Choristoma/surgery , Kidney Diseases/surgery , Kidney/abnormalities , Nephrectomy/methods , Retroperitoneal Space/surgery , Ureter/surgery , Child, Preschool , Female , Humans , Kidney/surgery , Kidney Diseases/pathology , Male , Nephrectomy/instrumentation , Surgical Instruments , Treatment Outcome
19.
Clin Infect Dis ; 55(6): 781-8, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22670044

ABSTRACT

BACKGROUND: Since its emergence in 2000, epidemic spread of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 has led to a high burden of skin and soft tissue infections (SSTIs) in the United States, yet its impact on MRSA bloodstream infections (BSIs) is poorly characterized. METHODS: To assess clonality of the MRSA isolates causing SSTI and BSI during the epidemic period, a stratified, random sample of 1350 unique infection isolates (from a total of 7252) recovered at the Community Health Network of San Francisco from 2000 to 2008 were selected for genotyping. Risk factors and outcomes for 549 BSI cases caused by the USA300 epidemic clone and non-USA300 MRSA clones were assessed by retrospective review of patient medical records. RESULTS: From 2000 to 2008, secular trends of USA300 SSTI and USA300 BSI were strongly correlated (Pearson r = 0.953). USA300 accounted for 55% (304/549) of BSIs as it was the predominant MRSA clone that caused community-associated (115/160), healthcare-associated community-onset (125/207), and hospital-onset (64/182) BSIs. Length of hospitalization after BSI diagnosis and mortality rates for USA300 and non-USA300 were similar. Two independent risk factors for USA300 BSI were identified: concurrent SSTI (adjusted relative risk, 1.4 [95% confidence interval {CI}, 1.2-1.6]) and anti-MRSA antimicrobial use in the preceding 30 days (0.7 [95% CI, .6-.8]). Isolates from concurrent SSTI were indistinguishable genotypically from the USA300 isolates that caused BSI. CONCLUSIONS: USA300 SSTIs serve as a source for BSI. Strategies to control the USA300 SSTI epidemic may lessen the severity of the concurrent USA300 BSI epidemic.


Subject(s)
Bacteremia/epidemiology , Community-Acquired Infections/epidemiology , Epidemics , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Soft Tissue Infections/epidemiology , Staphylococcal Skin Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Bacteremia/microbiology , Child, Preschool , Community-Acquired Infections/microbiology , Female , Humans , Male , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/genetics , Middle Aged , Molecular Typing , Retrospective Studies , San Francisco/epidemiology , Soft Tissue Infections/microbiology , Staphylococcal Skin Infections/microbiology , Young Adult
20.
Vet Microbiol ; 145(3-4): 220-9, 2010 Oct 26.
Article in English | MEDLINE | ID: mdl-20478669

ABSTRACT

Six field foot-and-mouth disease viruses (FMDVs), including four serotype O and two serotype Asia 1 strains, were collected from endemic outbreaks in 2005, 2006, and 2007 from four different provinces in Vietnam. The viruses were isolated and genetically characterized for their complete genomic sequences. The genetic analysis based on the complete genomic coding sequences revealed that the four serotype O FMDVs were related to each other, sharing 95.2% nucleotide (nt) identity and 97.5-97.6% amino acid (aa) identity. Genetic analysis and a phylogenetic tree, based on the VP1 gene of FMDV, showed that the four present Vietnamese serotype O strains have a high level of identity with other serotype O representatives of the Mya-98 lineage of the Southeast Asian (SEA) topotype. The four viruses were all clustered into the Mya-98 lineage of the SEA topotype, sharing 92.3-95.6% nt and 93.4-96.7% aa identity. This finding of the Mya-98 lineage was different from previous reports that the Vietnamese serotype O strains belonged to the Cam-94 lineage of the SEA topotype and two other topotypes, Middle East-South Asia (ME-SA) and Cathay. For the two serotype Asia 1 FMDVs, the genetic analysis based on the complete genomic coding sequences as well as on the VP1 gene revealed that they belonged to two genogroups, IV and V. Of note, the As1/VN/QT03/2007 strain of genogroup V, isolated in 2007, was very closely related to the pandemic Asia 1 strain which caused FMD outbreaks in China (Asia1/WHN/CHA/06, FJ906802) and Mongolia (Asia1/MOG/05, EF614458) in 2005, sharing 99.0-99.3% nt and 99.5-100% aa identity. In contrast, the second strain As1/VN/LC04/2005 of genogroup IV, isolated in 2005, was closely related to all referenced Vietnamese serotype Asia 1 strains found in the GenBank databases, sharing 86.4-100% nt and 90.9-100% aa identity with each. This study is the first description of the full-length genomic sequence of Vietnamese FMDV serotypes O and Asia 1 and may provide the evidence of the concurrent circulation of different serotypes and subtypes of FMDV in recent years in Vietnam.


Subject(s)
Disease Outbreaks/veterinary , Foot-and-Mouth Disease Virus/genetics , Foot-and-Mouth Disease/virology , Amino Acid Sequence , Animals , Base Sequence , Capsid Proteins/chemistry , Capsid Proteins/genetics , Cluster Analysis , Foot-and-Mouth Disease/epidemiology , Molecular Sequence Data , RNA, Viral/chemistry , RNA, Viral/genetics , Reverse Transcriptase Polymerase Chain Reaction , Sequence Alignment , Sequence Analysis, DNA , Vietnam/epidemiology
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