Publications by authors named "D Scott Schmid"

678 Publications

TV viewing during childhood and adult type 2 diabetes mellitus.

Sci Rep 2021 Mar 4;11(1):5157. Epub 2021 Mar 4.

Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Elsässerstr. 2, 79110, Freiburg, Germany.

We examined whether regular television (TV) viewing at ages 3-5 and 5-10 years is related to the incidence of type 2 diabetes mellitus (T2D) in adult women. We used data from 34,512 mother-nurse daughter dyads in the Nurses' Health Study (NHS) II and the Nurses' Mothers' Cohort Study. Mothers of NHS II participants completed a questionnaire on their pregnancy with the nurse and her early life experience. During 391,442 person-years of follow-up from 2001 to 2013, 1515 nurses developed T2D. Increasing levels of TV viewing at 3-5 years of age retrospectively reported by the mothers were related to a greater risk of T2D in adulthood: multivariable-adjusted hazard ratios (HRs) for ≤ 1, 2, and ≥ 3 h/day vs. no TV viewing were 1.11 [95% confidence interval (CI) 0.96-1.28], 1.20 (95% CI 1.02-1.41), and 1.35 (95% CI 1.11-1.65), p trend = 0.002, respectively, after adjustment for early life variables, including childhood physical activity and adiposity. Retrospectively reported TV viewing for ≥ 3 h/day at 5-10 years of age was associated with a 34% greater risk of adult T2D (HR 1.34, 95% CI 1.05-1.70, p trend < 0.001). Additional adjustments for adult variables, including adult TV viewing and current BMI attenuated the effect estimates (≥ 3 h/day TV viewing at 3-5 years: HR 1.22, 95% CI 0.99-1.49, p trend = 0.07; TV viewing at 5-10 years: 1.16, 95% CI 0.91-1.49, p trend = 0.09). The present study suggests that TV viewing during early childhood increases risk of T2D in adult women; adult BMI explains part of this association. Further research is required to confirm this observation and understand the mediating pathways.
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http://dx.doi.org/10.1038/s41598-021-83746-4DOI Listing
March 2021

Performance of four IgM antibody assays in the diagnosis of Measles virus primary infection and cases with a serological profile indicating reinfection.

J Clin Microbiol 2021 Feb 24. Epub 2021 Feb 24.

Center for Virology, Medical University of Vienna, Vienna, Austria

To determine the diagnostic performance of four commercially available IgM tests in the diagnosis of measles virus (MeV) primary infection and cases with a serological profile indicating reinfection. Sera from 187 patients with MeV primary infection, 30 patients with suspected reinfection (after vaccine failure) and 153 patients with rash-like symptoms after exclusion of MeV infection were retested with four IgM tests. MeV infection was verified by RT-PCR, primary and suspected reinfections were differentiated by IgG avidity and neutralization assays. All IgM assays displayed significant agreement (Cohen's κ≥0.604, all p<0.001) and a higher diagnostic accuracy in primary infection than in suspected reinfection (indicated by high IgG avidity and significantly higher Anti-MeV-IgG and neutralizing titers). In the overall cohort, the area under the curves (AUC) were comparable among all tests, ranging from 0.875 to 0.931, with ranges increasing to 0.911-0.930 in the primary infection and decreasing to 0.765-0.940 in the setting of high Anti-MeV-IgG avidity, and all tests displayed high specificity (81.1-92.2%). Of note, IgM tests with the highest diagnostic accuracy had discriminatory abilities not significantly different than PCR from serum. Although reinfections pose a challenge for IgM testing, IgM assays remain a cornerstone in the diagnosis of MeV infections. Especially in samples with a serological profile indicating reinfections, IgM tests displayed an equal or even superior diagnostic ability as compared to PCR from serum.
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http://dx.doi.org/10.1128/JCM.02047-20DOI Listing
February 2021

Isolate-Based Surveillance of Bordetella pertussis, Austria, 2018-2020.

Emerg Infect Dis 2021 Mar;27(3):862-871

Pertussis is a vaccine-preventable disease, and its recent resurgence might be attributable to the emergence of strains that differ genetically from the vaccine strain. We describe a novel pertussis isolate-based surveillance system and a core genome multilocus sequence typing scheme to assess Bordetella pertussis genetic variability and investigate the increased incidence of pertussis in Austria. During 2018-2020, we obtained 123 B. pertussis isolates and typed them with the new scheme (2,983 targets and preliminary cluster threshold of <6 alleles). B. pertussis isolates in Austria differed genetically from the vaccine strain, both in their core genomes and in their vaccine antigen genes; 31.7% of the isolates were pertactin-deficient. We detected 8 clusters, 1 of them with pertactin-deficient isolates and possibly part of a local outbreak. National expansion of the isolate-based surveillance system is needed to implement pertussis-control strategies.
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http://dx.doi.org/10.3201/eid2703.202314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920692PMC
March 2021

Noise pollution on coral reefs? - A yet underestimated threat to coral reef communities.

Mar Pollut Bull 2021 Feb 12;165:112129. Epub 2021 Feb 12.

Centre Scientifique de Monaco, Coral Ecophysiology Team, 8 Quai Antoine 1er, MC-98000, Monaco.

Noise pollution is an anthropogenic stressor that is increasingly recognized for its negative impact on the physiology, behavior and fitness of marine organisms. Driven by the recent expansion of maritime shipping, artisanal fishing and tourism (e.g., motorboats used for recreational purpose), underwater noise increased greatly on coral reefs. In this review, we first provide an overview on how reef organisms sense and use sound. Thereafter we review the current knowledge on how underwater noise affects different reef organisms. Although the majority of available examples are limited to few fish species, we emphasize how the impact of noise differs based on an organisms' acoustic sensitivity, mobility and developmental stage, as well as between noise type, source and duration. Finally, we highlight measures available to governments, the shipping industry and individual users and provide directions for polices and research aimed to manage this global issue of noise emission on coral reefs.
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http://dx.doi.org/10.1016/j.marpolbul.2021.112129DOI Listing
February 2021

Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients.

Am J Transplant 2021 Feb 10. Epub 2021 Feb 10.

Transplant Infectious Diseases and Ajmera Transplant Centre, University Health Network, Toronto, ON, Canada.

Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17-2.89) after the first (median OD 3.41, IQR 2.54-3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39-3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 10 CD4+ T cells; IQR: 46-180) to the first (median 128 per 10 CD4+ T cells; IQR: 82-353; p = .023) and after the second dose (median 361 per 10 CD4+ T cells; IQR: 146-848; p < .0001). Tenderness (83.0%; 95%CI: 69.2-92.4%) and redness (31.9%; 95%CI: 19.1-47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.
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http://dx.doi.org/10.1111/ajt.16534DOI Listing
February 2021

Limited Utility of Reverse Algorithm Syphilis Testing in HIV Clinic among Men who have Sex with Men.

Sex Transm Dis 2021 Feb 1. Epub 2021 Feb 1.

Division of Infectious Diseases, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama School of Public Health, University of Alabama at Birmingham, Birmingham, Alabama.

Background: The reverse algorithm for syphilis diagnosis consists of a treponemal antibody screening immunoassay followed by confirmatory non-treponemal antibody testing. It is increasingly used in the US despite studies suggesting limited cost-effectiveness in high-prevalence groups.

Methods: In this retrospective cross-sectional study, we included men who have sex with men (MSM) tested with the reverse algorithm in an Alabama HIV clinic between March 2015 and February 2017. Trepsure enzyme immunoassay (EIA) was used for the initial screen, followed by reflex non-treponemal reactive plasma reagin (RPR) testing of specimens with positive results. Sociodemographic and clinical data were extracted from the electronic medical record and stratified according to EIA screen positivity. Quantitative EIA antibody index values were collected to assess test performance at various thresholds.

Results: Among 1693 men tested for syphilis with the reverse algorithm in HIV clinic, 808 (48%) had a positive initial EIA screen. A majority (53%) of men with subsequent RPR testing had a non-reactive RPR (EIA+/RPR-) and 19% (19/98) of these EIA+/RPR- samples tested had negative confirmatory TPPA testing. Analysis of quantitative EIA index values using a receiver operating characteristics curve suggested that a threshold >8 (rather the current threshold of antibody index 1.2) improved the performance of the test.

Conclusions: Among MSM tested in HIV clinic, the syphilis reverse algorithm was inefficient due to high rates of prior syphilis and false positive EIA screening. Frequent syphilis screening in high prevalence populations is an important part of the US epidemic response and the traditional algorithm is preferred.
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http://dx.doi.org/10.1097/OLQ.0000000000001386DOI Listing
February 2021

Evaluation of Recombinant Herpes Zoster Vaccine for Primary Immunization of Varicella-seronegative Transplant Recipients.

Transplantation 2021 Jan 19. Epub 2021 Jan 19.

1 Pediatric Infectious Diseases Unit, Geneva University Hospitals and Faculty of Medicine, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 4, Switzerland 2 Division of Infectious Diseases, Inselspital, Freiburgstrasse 18, 3010 Bern, Switzerland 3 Ajmera Transplant Centre, University Health Network, 585 University Avenue, Toronto, Ontario M5G 2N2, Canada 4 Centers for Disease Control and Prevention, Division of Viral Diseases, 1600 Clifton Road, Atlanta, GA 30333, USA.

Background: Immunization of VZV-seronegative solid organ transplant (SOT) patients using the live-attenuated varicella vaccine is generally contraindicated, leaving no widely applicable immunization option. The recombinant subunit herpes zoster vaccine (RZV) is indicated for VZV seropositive persons to prevent shingles but could potentially also protect VZV-seronegative persons against varicella. We performed a safety and immunogenicity evaluation of RZV in VZV-seronegative SOT recipients as an option for protection.

Methods: VZV-seronegative adult SOT patients with no history of varicella/shingles vaccine or disease were given 2 doses of RZV vaccine 2-6 months apart. Blood was drawn prevaccination (V1), prior to the second dose (V2) and 4 weeks after second dose (V3). Humoral (anti-gE) and cell-mediated immunity was evaluated, with polyfunctional cells defined as cells producing ≥2 cytokines.

Results: Among 31 eligible VZV-seronegative SOT patients screened, 23 were enrolled. Median age was 38 years and median time since transplant procedure was 38 years. The most frequent transplant types were liver (35%) and lung (30%). Median anti-gE levels significantly increased from V1 to V3 (p=0001) and V2 to V3 (p<0001), even though only 55% had a positive seroresponse. Median polyfunctional CD4 T-cells counts increased from V1 to V2 (54/10 vs 104/10 cells; p=0041), and from V2 to V3 (380/10; p=0002). Most adverse events were mild with no rejection episodes.

Conclusion: RZV was safe and elicited significant humoral and cellular responses in VZV-seronegative SOT patients, and has the potential to be considered as a preventive strategy against primary varicella.
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http://dx.doi.org/10.1097/TP.0000000000003621DOI Listing
January 2021

Real-time monitoring shows substantial excess all-cause mortality during second wave of COVID-19 in Europe, October to December 2020.

Euro Surveill 2021 01;26(2)

Department of Veterinary and Animal Science, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

The European monitoring of excess mortality for public health action (EuroMOMO) network monitors weekly excess all-cause mortality in 27 European countries or subnational areas. During the first wave of the coronavirus disease (COVID-19) pandemic in Europe in spring 2020, several countries experienced extraordinarily high levels of excess mortality. Europe is currently seeing another upsurge in COVID-19 cases, and EuroMOMO is again witnessing a substantial excess all-cause mortality attributable to COVID-19.
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http://dx.doi.org/10.2807/1560-7917.ES.2021.26.1.2002023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7809719PMC
January 2021

Vaccination Status and Attitude among Measles Cluster Cases in Austria, 2019.

Int J Environ Res Public Health 2020 12 15;17(24). Epub 2020 Dec 15.

Austrian Agency for Health and Food Safety (AGES), 1090 Vienna, Austria.

On 21 January 2019, public health authorities of two neighboring Austrian provinces reported an increase in measles cases. We investigated this occurrence to identify clusters of epidemiologically linked cases and the associated vaccination status in order to generate hypotheses on those factors explaining the size of the measles clusters. Probable cases were residents of the provinces of Styria or Salzburg with clinical presentation of measles after 1 January 2019 who were linked to a confirmed case using RNA virus detection. We collected data on age, rash onset, certificate-based vaccination status and reasons for being unvaccinated. Contact history was used to identify chains of transmission. By 11 March, we identified 47 cases, with 40 (85.1%) in unvaccinated patients. A cluster of 35 cases with a median age of seven years (IQR: 1-11) occurred between 9 January and 20 February in the province of Styria due to one transmission chain with four case generations. Of 31 vaccine-eligible cases, 25 (80.6%) were unvaccinated, of which 13 refused vaccination. Between 10 January and 1 March, we identified 12 cases as part of five unlinked clusters in the province of Salzburg. Each of these five clusters consisted of two generations: the primary case and the successive cases (median age: 22 years, IQR: 11-35). Eleven of 12 cases occurred in unvaccinated patients, with none of the 11 having a vaccination-refusing attitude. An extended measles cluster in a vaccination-refusing community, compared to five short-lived clusters concurrently occurring in the neighboring province, illustrates how vaccine refusal may hamper control of transmission.
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http://dx.doi.org/10.3390/ijerph17249377DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7765158PMC
December 2020

A Tale of Two Viruses: Coinfections of Monkeypox and Varicella Zoster Virus in the Democratic Republic of Congo.

Am J Trop Med Hyg 2020 Dec 7. Epub 2020 Dec 7.

Poxvirus and Rabies Branch, Division of High-Consequence Pathogens and Pathology, National Center for Emerging and Zoonotic Infectious Diseases, U.S. Centers for Disease Control and Prevention, Atlanta, Georgia.

Recent enhanced monkeypox (MPX) surveillance in the Democratic Republic of Congo, where MPX is endemic, has uncovered multiple cases of MPX and varicella zoster virus (VZV) coinfections. The purpose of this study was to verify if coinfections occur and to characterize the clinical nature of these cases. Clinical, epidemiological, and laboratory results were used to investigate MPX/VZV coinfections. A coinfection was defined as a patient with at least one /MPX-positive sample and at least one VZV-positive sample within the same disease event. Between September 2009 and April 2014, 134 of the 1,107 (12.1%) suspected MPX cases were confirmed as MPX/VZV coinfections. Coinfections were more likely to report symptoms than VZV-alone cases and less likely than MPX-alone cases. Significantly higher lesion counts were observed for coinfection cases than for VZV-alone but less than MPX-alone cases. Discernible differences in symptom and rash severity were detected for coinfection cases compared with those with MPX or VZV alone. Findings indicate infection with both MPX and VZV could modulate infection severity. Collection of multiple lesion samples allows for the opportunity to detect coinfections. As this program continues, it will be important to continue these procedures to assess variations in the proportion of coinfected cases over time.
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http://dx.doi.org/10.4269/ajtmh.20-0589DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7866336PMC
December 2020

Type-Independent Characterization of Spacelike Separated Resources.

Phys Rev Lett 2020 Nov;125(21):210402

Graduate School of Informatics, Nagoya University, Chikusa-ku, Nagoya 464-8601, Japan.

Quantum theory describes multipartite objects of various types: quantum states, nonlocal boxes, steering assemblages, teleportages, distributed measurements, channels, and so on. Such objects describe, for example, the resources shared in quantum networks. Not all such objects are useful, however. In the context of spacelike separated parties, devices which can be simulated using local operations and shared randomness are useless, and it is of paramount importance to be able to practically distinguish useful from useless quantum resources. Accordingly, a body of literature has arisen to provide tools for witnessing and quantifying the nonclassicality of objects of each specific type. In the present Letter, we provide a framework which subsumes and generalizes all of these resources, as well as the tools for witnessing and quantifying their nonclassicality.
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http://dx.doi.org/10.1103/PhysRevLett.125.210402DOI Listing
November 2020

Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2.

Sci Transl Med 2020 12 23;12(573). Epub 2020 Nov 23.

CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, Austria.

Superspreading events shaped the coronavirus disease 2019 (COVID-19) pandemic, and their rapid identification and containment are essential for disease control. Here, we provide a national-scale analysis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) superspreading during the first wave of infections in Austria, a country that played a major role in initial virus transmissions in Europe. Capitalizing on Austria's well-developed epidemiological surveillance system, we identified major SARS-CoV-2 clusters during the first wave of infections and performed deep whole-genome sequencing of more than 500 virus samples. Phylogenetic-epidemiological analysis enabled the reconstruction of superspreading events and charts a map of tourism-related viral spread originating from Austria in spring 2020. Moreover, we exploited epidemiologically well-defined clusters to quantify SARS-CoV-2 mutational dynamics, including the observation of low-frequency mutations that progressed to fixation within the infection chain. Time-resolved virus sequencing unveiled viral mutation dynamics within individuals with COVID-19, and epidemiologically validated infector-infectee pairs enabled us to determine an average transmission bottleneck size of 10 SARS-CoV-2 particles. In conclusion, this study illustrates the power of combining epidemiological analysis with deep viral genome sequencing to unravel the spread of SARS-CoV-2 and to gain fundamental insights into mutational dynamics and transmission properties.
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http://dx.doi.org/10.1126/scitranslmed.abe2555DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7857414PMC
December 2020

Human Immunodeficiency Virus Continuum of Care in 11 European Union Countries at the End of 2016 Overall and by Key Population: Have We Made Progress?

Clin Infect Dis 2020 Dec;71(11):2905-2916

Medical School, National and Kapodistrian University of Athens, Athens, Greece.

Background: High uptake of antiretroviral treatment (ART) is essential to reduce human immunodeficiency virus (HIV) transmission and related mortality; however, gaps in care exist. We aimed to construct the continuum of HIV care (CoC) in 2016 in 11 European Union (EU) countries, overall and by key population and sex. To estimate progress toward the Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 target, we compared 2016 to 2013 estimates for the same countries, representing 73% of the population in the region.

Methods: A CoC with the following 4 stages was constructed: number of people living with HIV (PLHIV); proportion of PLHIV diagnosed; proportion of those diagnosed who ever initiated ART; and proportion of those ever treated who achieved viral suppression at their last visit.

Results: We estimated that 87% of PLHIV were diagnosed; 92% of those diagnosed had ever initiated ART; and 91% of those ever on ART, or 73% of all PLHIV, were virally suppressed. Corresponding figures for men having sex with men were: 86%, 93%, 93%, 74%; for people who inject drugs: 94%, 88%, 85%, 70%; and for heterosexuals: 86%, 92%, 91%, 72%. The proportion suppressed of all PLHIV ranged from 59% to 86% across countries.

Conclusions: The EU is close to the 90-90-90 target and achieved the UNAIDS target of 73% of all PLHIV virally suppressed, significant progress since 2013 when 60% of all PLHIV were virally suppressed. Strengthening of testing programs and treatment support, along with prevention interventions, are needed to achieve HIV epidemic control.
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http://dx.doi.org/10.1093/cid/ciaa696DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7778352PMC
December 2020

Interleukin-2 signals converge in a lymphoid-dendritic cell pathway that promotes anticancer immunity.

Sci Transl Med 2020 09;12(561)

Department of Immunology, University Hospital Zurich, CH-8091 Zurich, Switzerland.

Tumor-infiltrating dendritic cells (DCs) correlate with effective anticancer immunity and improved responsiveness to anti-PD-1 checkpoint immunotherapy. However, the drivers of DC expansion and intratumoral accumulation are ill-defined. We found that interleukin-2 (IL-2) stimulated DC formation through innate and adaptive lymphoid cells in mice and humans, and this increase in DCs improved anticancer immunity. Administration of IL-2 to humans within a clinical trial and of IL-2 receptor (IL-2R)-biased IL-2 to mice resulted in pronounced expansion of type 1 DCs, including migratory and cross-presenting subsets, and type 2 DCs, although neither DC precursors nor mature DCs had functional IL-2Rs. In mechanistic studies, IL-2 signals stimulated innate lymphoid cells, natural killer cells, and T cells to synthesize the cytokines FLT3L, CSF-2, and TNF. These cytokines redundantly caused DC expansion and activation, which resulted in improved antigen processing and correlated with favorable anticancer responses in mice and patients. Thus, IL-2 immunotherapy-mediated stimulation of DCs contributes to anticancer immunity by rendering tumors more immunogenic.
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http://dx.doi.org/10.1126/scitranslmed.aba5464DOI Listing
September 2020

Emergence of coronavirus disease 2019 (COVID-19) in Austria.

Wien Klin Wochenschr 2020 Nov 20;132(21-22):645-652. Epub 2020 Aug 20.

Österreichische Agentur für Gesundheit und Ernährungssicherheit (AGES), Spargelfeldstr. 191, 1220, Vienna, Austria.

This is a report on the first identified cases of coronavirus disease 2019 (COVID-19) in Austria. The first documented case was a person who stayed in Kühtai, Tyrol, from 24 to 26 January 2020, and had been infected by a Chinese instructor in Starnberg (Germany) between 20 and 22 January. This counts as a German case since her diagnosis was eventually made in Munich (Germany) on 28 January. On 25 February, two cases imported from Italy were diagnosed in Innsbruck but again no secondary cases were identified in Austria. The first three infections of Austrian inhabitants were detected on 27 February in Vienna. The two resulting clusters finally included 6 (source of initial infection unknown) and 61 cases. Most likely, Italy was the source of the latter cluster. On 12 March the first fatal case of COVID-19 in Austria was reported, a 69-year-old Viennese who died in a Vienna hospital after returning from a cruise ship tour in Italy. On 6 March three autochthonously acquired cases were reported in the Tyrol, all related to the ski resort Ischgl. Of the first 14 Islandic COVID-19 cases infected in Ischgl, 11 had already returned to Iceland on 29 February. We consider that the incriminated barkeeper, who tested PCR positive on 7 March, was neither the primary case nor a superspreader. In our opinion, undetected transmission of SARS-CoV‑2 had been ongoing in Ischgl prior to the first laboratory confirmed cases. Our data also underline that the introduction of SARS-CoV‑2 into Austria was not one single event.
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http://dx.doi.org/10.1007/s00508-020-01723-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439636PMC
November 2020

Amylin, Aβ42, and Amyloid in VZV Vasculopathy Cerebrospinal Fluid and Infected Vascular Cells.

J Infect Dis 2020 Aug 18. Epub 2020 Aug 18.

Department of Neurology, University of Colorado School of Medicine, Aurora, Colorado, USA.

Background: VZV vasculopathy is characterized by persistent arterial inflammation leading to stroke. Studies show that VZV induces amyloid formation that may aggravate vasculitis. Thus, we determined if VZV central nervous system (CNS) infection produces amyloid.

Methods: Aβ peptides, amylin, and amyloid were measured in CSF from 16 VZV vasculopathy subjects and 36 stroke controls. To determine if infection induced amyloid deposition, mock- and VZV-infected quiescent primary human perineurial cells (qHPNCs), present in vasculature, were analyzed for intracellular amyloidogenic transcripts/proteins and amyloid. Supernatants were assayed for amyloidogenic peptides and ability to induce amyloid formation. To determine amylin's function during infection, amylin was knocked down with siRNA and viral cDNA quantitated.

Results: Compared to controls, VZV vasculopathy CSF had increased amyloid that positively correlated with amylin and anti-VZV antibody levels; Aβ40 was reduced and Aβ42 unchanged. Intracellular amylin, Aβ42, and amyloid were seen only in VZV-infected qHPNCs. VZV-infected supernatant formed amyloid fibrils following addition of amyloidogenic peptides. Amylin knockdown decreased viral cDNA.

Conclusions: VZV infection increased levels of amyloidogenic peptides and amyloid in CSF and qHPNCs, indicating that VZV-induced amyloid deposition may contribute to persistent arterial inflammation in VZV vasculopathy. In addition, we identified a novel proviral function of amylin.
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http://dx.doi.org/10.1093/infdis/jiaa513DOI Listing
August 2020

Sleep-dependent motor memory consolidation in healthy adults: A meta-analysis.

Neurosci Biobehav Rev 2020 11 27;118:270-281. Epub 2020 Jul 27.

Institute of Sport Science, University of Bern, Bern, Switzerland.

It is widely accepted that sleep better facilitates the consolidation of motor memories than does a corresponding wake interval (King et al., 2017). However, no in-depth analysis of the various motor tasks and their relative sleep gain has been conducted so far. Therefore, the present meta-analysis considered 48 studies with a total of 53 sleep (n = 829) and 53 wake (n = 825) groups. An overall comparison between all sleep and wake groups resulted in a small effect for the relative sleep gain in motor memory consolidation (g = 0.43). While no subgroup differences were identified for differing designs, a small effect for the finger tapping task (g = 0.47) and a medium effect for the mirror tracing task (g = 0.62) were found. In summary, the meta-analysis substantiates that sleep generally benefits the consolidation of motor memories. However, to further our understanding of the mechanisms underlying this effect, examining certain task dimensions and their relative sleep gain would be a promising direction for future research.
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http://dx.doi.org/10.1016/j.neubiorev.2020.07.028DOI Listing
November 2020

Excess all-cause mortality during the COVID-19 pandemic in Europe - preliminary pooled estimates from the EuroMOMO network, March to April 2020.

Euro Surveill 2020 07;25(26)

Department of Veterinary and Animal Science, Faculty of Health and Medical Science, University of Copenhagen, Copenhagen, Denmark.

A remarkable excess mortality has coincided with the COVID-19 pandemic in Europe. We present preliminary pooled estimates of all-cause mortality for 24 European countries/federal states participating in the European monitoring of excess mortality for public health action (EuroMOMO) network, for the period March-April 2020. Excess mortality particularly affected  ≥ 65 year olds (91% of all excess deaths), but also 45-64 (8%) and 15-44 year olds (1%). No excess mortality was observed in 0-14 year olds.
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http://dx.doi.org/10.2807/1560-7917.ES.2020.25.26.2001214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7346364PMC
July 2020

Dexpanthenol in Wound Healing after Medical and Cosmetic Interventions (Postprocedure Wound Healing).

Pharmaceuticals (Basel) 2020 Jun 29;13(7). Epub 2020 Jun 29.

Bayer Consumer Care AG, Peter Merian-Strasse 84, CH-4002 Basel, Switzerland.

With the availability of new technologies, the number of subjects undergoing medical and cosmetic interventions is increasing. Many procedures (e.g., ablative fractional laser treatment) resulting in superficial/minor wounds require appropriate aftercare to prevent complications in wound healing and poor cosmetic outcome. We review the published evidence of the usefulness of topical dexpanthenol in postprocedure wound healing and the associated mechanisms of action at the molecular level. A search in the PubMed and Embase databases was performed to query the terms dexpanthenol, panthenol, superficial wound, minor wound, wound healing, skin repair, and postprocedure. Search results were categorized as clinical trials and in vitro studies. In vitro and clinical studies provided evidence that topically applied dexpanthenol promotes superficial and postprocedure wound healing. Latest findings confirmed that dexpanthenol upregulates genes that are critical for the healing process. The gene expression data are of clinical relevance as evidenced by prospective clinical studies indicating that topical dexpanthenol accelerates wound healing with rapid re-epithelialization and restoration of skin barrier function following skin injury. It can therefore be inferred that topical dexpanthenol represents an appropriate and state-of-the-art treatment option for superficial postprocedure wounds, especially when applied early after the superficial skin damage.
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http://dx.doi.org/10.3390/ph13070138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7407203PMC
June 2020

Relation of anxiety and other psychometric measures, balance deficits, impaired quality of life, and perceived state of health to dizziness handicap inventory scores for patients with dizziness.

Health Qual Life Outcomes 2020 Jun 26;18(1):204. Epub 2020 Jun 26.

Department of Psychosomatic Medicine, Faculty of Medicine, University of Basel and University Hospital Basel, Hebelstr 2, CH-4031, Basel, Switzerland.

Background: An important question influencing therapy for dizziness is whether the strengths of the relationships of emotional and functional aspects of dizziness to 1) anxiety and other mental states, 2) perceived state of health (SoH) and quality of life (QoL) are different in patients with and without normal balance control. We attempted to answer this question by examining these dimensions' regression strengths with Dizziness Handicap Inventory (DHI) scores.

Methods: We divided 40 patients receiving group cognitive behavioural therapy (CBT) and vestibular rehabilitation for dizziness, into 2 groups: dizziness only (DO) and normal balance control; dizziness and a quantified balance deficit (QBD). Group-wise, we first performed stepwise multivariate regression analysis relating total DHI scores with Brief Symptom Inventory (BSI) sub-scores obtained pre- and post-therapy. Then, regression analysis was expanded to include SoH, QoL, and balance scores. Finally, we performed regressions with DHI sub-scores.

Results: In both groups, the BSI phobic anxiety state score was selected first in the multivariate regression analysis. In the DO group, obsessiveness/compulsiveness was also selected. The correlation coefficient, R, was 0.74 and 0.55 for the DO and QBD groups, respectively. When QoL and SoH scores were included, R values increased to 0.86 and 0.74, explaining in total 74, and 55% of the DHI variance for DO and QBD groups, respectively. Correlations with balance scores were not significant (R ≤ 0.21). The psychometric scores selected showed the strongest correlations with emotional DHI sub-scores, and perceived QoL and SoH scores with functional DHI sub-scores.

Conclusions: Our findings suggest that reducing phobic anxiety and obsessiveness/compulsiveness during CBT may improve emotional aspects of dizziness and targeting perceived SoH and QoL may improve functional aspects of dizziness for those with and without normal balance control.
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http://dx.doi.org/10.1186/s12955-020-01445-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7320574PMC
June 2020

Inducing lucid dreams by olfactory-cued reactivation of reality testing during early-morning sleep: A proof of concept.

Conscious Cogn 2020 08 20;83:102975. Epub 2020 Jun 20.

Department of Psychology, University of Fribourg, Switzerland.

The reliable induction of lucid dreams is a challenge in lucid dream research. In a previous study by our research group we were able to induce in about 50% of the participants a lucid dream in a single sleep laboratory night by combining a wake-up-back-to-bed sleep protocol and a mnemonic technique. In the present study, we extended our previous procedure by additional presentation of an odor during sleep to reactivate memory traces about reality testing. In total 16 male participants spent a single night in the sleep lab whereas the procedure induced in two participants a lucid dream (12.5%). The induction rate stays below the success rate of our previous study and therefore odor-cueing seems not a promising technique for inducing lucid dreams. Beside the odor presentation, several other methodological changes have been made, which will be discussed and hopefully help further dream engineering to improve induction techniques.
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http://dx.doi.org/10.1016/j.concog.2020.102975DOI Listing
August 2020

From Near-Optimal Bayesian Integration to Neuromorphic Hardware: A Neural Network Model of Multisensory Integration.

Front Neurorobot 2020 15;14:29. Epub 2020 May 15.

Vision and Perception Science Lab, Institute of Neural Information Processing, Ulm University, Ulm, Germany.

While interacting with the world our senses and nervous system are constantly challenged to identify the origin and coherence of sensory input signals of various intensities. This problem becomes apparent when stimuli from different modalities need to be combined, e.g., to find out whether an auditory stimulus and a visual stimulus belong to the same object. To cope with this problem, humans and most other animal species are equipped with complex neural circuits to enable fast and reliable combination of signals from various sensory organs. This multisensory integration starts in the brain stem to facilitate unconscious reflexes and continues on ascending pathways to cortical areas for further processing. To investigate the underlying mechanisms in detail, we developed a canonical neural network model for multisensory integration that resembles neurophysiological findings. For example, the model comprises multisensory integration neurons that receive excitatory and inhibitory inputs from unimodal auditory and visual neurons, respectively, as well as feedback from cortex. Such feedback projections facilitate multisensory response enhancement and lead to the commonly observed inverse effectiveness of neural activity in multisensory neurons. Two versions of the model are implemented, a rate-based neural network model for qualitative analysis and a variant that employs spiking neurons for deployment on a neuromorphic processing. This dual approach allows to create an evaluation environment with the ability to test model performances with real world inputs. As a platform for deployment we chose IBM's neurosynaptic chip TrueNorth. Behavioral studies in humans indicate that temporal and spatial offsets as well as reliability of stimuli are critical parameters for integrating signals from different modalities. The model reproduces such behavior in experiments with different sets of stimuli. In particular, model performance for stimuli with varying spatial offset is tested. In addition, we demonstrate that due to the emergent properties of network dynamics model performance is close to optimal Bayesian inference for integration of multimodal sensory signals. Furthermore, the implementation of the model on a neuromorphic processing chip enables a complete neuromorphic processing cascade from sensory perception to multisensory integration and the evaluation of model performance for real world inputs.
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http://dx.doi.org/10.3389/fnbot.2020.00029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7243343PMC
May 2020

Analysis of the reiteration regions (R1 to R5) of varicella-zoster virus.

Virology 2020 07 4;546:38-50. Epub 2020 Apr 4.

Division of Viral Diseases, National Center for Immunizations and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA, USA. Electronic address:

The varicella-zoster virus (VZV) genome, comprises both unique and repeated regions. The genome also includes reiteration regions, designated R1 to R5, which are tandemly repeating sequences termed elements. These regions represent an understudied feature of the VZV genome. The R4 region is duplicated, with one copy in the internal repeat short (IRs) which we designated R4A and a second copy in the terminal repeat short (TRs) termed R4B. We developed primers to amplify and Sanger sequence these regions, including independent amplification of both R4 regions. Reiteration regions from >80 cases of PCR-confirmed shingles were sequenced and analyzed. Complete genome sequences for the remaining portions of these viruses were determined using Illumina MiSeq. We identified 28 elements not previously reported, including at least one element for each R region. Length heterogeneity was substantial in R3, R4A and R4B. Length heterogeneity between the two copies of R4 was common.
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http://dx.doi.org/10.1016/j.virol.2020.03.008DOI Listing
July 2020

Persistence of Varicella-Zoster Virus-Specific Plasma Cells in Adult Human Bone Marrow following Childhood Vaccination.

J Virol 2020 06 16;94(13). Epub 2020 Jun 16.

Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia, USA

Childhood immunization with the live-attenuated varicella-zoster virus (VZV) vaccine induces protective immune responses. Routine VZV vaccination started only 2 decades ago, and thus, there are few studies examining the longevity of vaccine-induced immunity. Here, we analyzed the quantity of VZV-specific plasma cells (PCs) and CD4 T cells in the bone marrow (BM) of healthy young adults ( = 15) following childhood VZV immunization. Long-lived BM resident plasma cells constitutively secrete antibodies, and we detected VZV-specific PCs in the BM of all subjects. Anti-VZV plasma antibody titers correlated positively with the number of VZV-specific BM PCs. Furthermore, we quantified the number of interferon gamma (IFN-γ)-producing CD4 T cells specific for VZV glycoprotein E and all other structural and nonstructural VZV proteins in both BM and blood (peripheral blood mononuclear cells [PBMCs]). The frequency of VZV-specific IFN-γ-producing CD4 T cells was significantly higher in PBMCs than BM. Our study shows that VZV-specific PCs and VZV-specific CD4 memory T cells persist up to 20 years after vaccination. These findings indicate that childhood VZV vaccination can elicit long-lived immune memory responses in the bone marrow. Childhood varicella-zoster virus (VZV) immunization induces immune memory responses that protect against primary VZV infection, chicken pox. In the United States, routine childhood VZV vaccination was introduced only 2 decades ago. Hence, there is limited information on the longevity of B and CD4 T cell memory, which are both important for protection. Here, we showed in 15 healthy young adults that VZV-specific B and CD4 T cell responses are detectable in bone marrow (BM) and blood up to 20 years after vaccination. Specifically, we measured antibody-secreting plasma cells in the BM and VZV-specific CD4 T cells in BM and blood. These findings suggest that childhood VZV vaccination induces long-lived immunity.
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http://dx.doi.org/10.1128/JVI.02127-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307153PMC
June 2020

Active transport of rhodamine 123 by the human multidrug transporter P-glycoprotein involves two independent outer gates.

Pharmacol Res Perspect 2020 04;8(2):e00572

Institute of Pharmacology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.

Human P-glycoprotein (P-gp) is a multispecific drug-efflux transporter, which plays an important role in drug resistance and drug disposition. Recent cryo-electron microscopy structures confirmed its rotationally symmetric architecture, which allows dual interaction with ATP and substrates. We here report the existence of two distinct, symmetry-related outer gates. Experiments were aided by availability of the X-ray structure of a homodimeric eukaryotic homolog of P-gp from red alga (CmABCB1), which defined the role of an apical tyrosine residue (Y358) in outer gate formation. We mutated analogous tyrosine residues in each half of the human full-length transporter (Y310, Y953) to alanine. These mutants were introduced in engineered transporters which bind rhodamine 123 in one of two symmetry-related binding modes only. Outer gate dysfunction was detected by a loss of active transport characteristics, while these mutants retained the ability for outward downhill transport. Our data demonstrate that symmetric tyrosine residues Y310 and Y953 are involved in formation of two distinct symmetry-related outer gates, which operate contingent on the rhodamine 123 binding mode. Hence, the rotationally symmetric architecture of P-gp, which determines duality in ATP binding and rhodamine 123 interaction, also forms the basis for the existence of two independently operating outer gates.
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http://dx.doi.org/10.1002/prp2.572DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7105846PMC
April 2020

Four-Step Access to the Sesquiterpene Natural Product Presilphiperfolan-1β-ol and Unnatural Derivatives via Supramolecular Catalysis.

J Am Chem Soc 2020 03 16;142(12):5894-5900. Epub 2020 Mar 16.

Department of Chemistry, University of Basel, Mattenstrasse 24a, 4058 Basel, Switzerland.

Terpenes constitute one of the most structurally varied classes of natural products. A wide range of these structures are produced in nature by type I terpene cyclase enzymes from one single substrate. However, such reactivity has proven difficult to reproduce in solution with man-made systems. Herein we report the shortest synthesis of the tricyclic sesquiterpene presilphiperfolan-1β-ol to date, utilizing the supramolecular resorcinarene capsule as catalyst for the key step. This synthetic approach also allows access to unnatural derivatives of the natural product, which would not be accessible through the biosynthetic machinery. Additionally, this study provides useful insight into the biosynthesis of the presilphiperfolanol natural products, including the first experimental evidence consistent with the proposed biosynthetic connection between caryophyllene and the presilphiperfolanols.
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http://dx.doi.org/10.1021/jacs.0c01464DOI Listing
March 2020

Clinical Diagnostic Testing for Human Cytomegalovirus Infections.

J Infect Dis 2020 03;221(Suppl 1):S74-S85

Viral Vaccine Preventable Diseases Branch, Division of Viral Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Human cytomegalovirus (HCMV) infections are among the most common complications arising in transplant patients, elevating the risk of various complications including loss of graft and death. HCMV infections are also responsible for more congenital infections worldwide than any other agent. Congenital HCMV (cCMV) infections are the leading nongenetic cause of sensorineural hearing loss and a source of significant neurological disabilities in children. While there is overlap in the clinical and laboratory approaches to diagnosis of HCMV infections in these settings, the management, follow-up, treatment, and diagnostic strategies differ considerably. As yet, no country has implemented a universal screening program for cCMV. Here, we summarize the issues, limitations, and application of diagnostic strategies for transplant recipients and congenital infection, including examples of screening programs for congenital HCMV that have been implemented at several centers in Japan, Italy, and the United States.
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http://dx.doi.org/10.1093/infdis/jiz601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7057790PMC
March 2020

Maternal and Infant Anthropometric Characteristics and Breast Cancer Incidence in the Daughter.

Sci Rep 2020 02 13;10(1):2550. Epub 2020 Feb 13.

Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.

The intrauterine and early life environments have been linked to the etiology of breast cancer in prior studies. We prospectively examined whether maternal and newborn anthropometric factors as reported by the mother are related to an increased incidence of adult breast cancer in the daughter. We used data from 35,133 mother-daughter dyads of the Nurses' Health Study (NHS) II and the Nurses' Mothers' Cohort Study. In 2001, living mothers of NHS II participants who were free of cancer completed a questionnaire on their pregnancy with the nurse and their nurse daughter's early life experience. During 403,786 years of follow-up, 865 daughters developed incident cases of invasive breast cancer. Nurses with a birthweight of ≥4000 g had a 32% greater risk for breast cancer (multivariable-adjusted hazard ratio (HR) = 1.32, 95% confidence interval (CI) = 1.02-1.71, p-trend = 0.09) compared with those with birthweights of 3000-3499 g. Higher birth length tended to increase risk of premenopausal breast cancer (p for trend = 0.05). We further noted a modest U-shaped relation between maternal weight gain during pregnancy and premenopausal breast cancer incidence in the daughter. Fetal growth may contribute to shaping later life risk for breast cancer, especially prior to menopause.
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http://dx.doi.org/10.1038/s41598-020-59527-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018761PMC
February 2020

Yogurt consumption in relation to mortality from cardiovascular disease, cancer, and all causes: a prospective investigation in 2 cohorts of US women and men.

Am J Clin Nutr 2020 03;111(3):689-697

Institute for Prevention and Cancer Epidemiology, Faculty of Medicine and Medical Center, University of Freiburg, Freiburg, Germany.

Background: Although a link between regular yogurt consumption and mortality appears plausible, data are sparse and have yielded inconsistent results.

Objectives: We examined the association between regular yogurt consumption and risk of all-cause and cause-specific mortality among US women and men.

Methods: A total of 82,348 women in the Nurses' Health Study and 40,278 men in the Health Professionals Follow-Up Study without a history of cardiovascular disease (CVD) and cancer in 1980 (women) or 1986 (men) were followed up until 2012. Yogurt consumption was assessed by updated validated FFQs.

Results: During 3,354,957 person-years of follow-up, 20,831 women and 12,397 men died. Compared with no yogurt consumption, the multivariable-adjusted HRs (95% CIs) of mortality were 0.89 (0.86, 0.93), 0.85 (0.81, 0.89), 0.88 (0.84, 0.91), and 0.91 (0.85, 0.98) for ≤1-3 servings/mo, 1 serving/wk, 2-4 servings/wk, and >4 servings/wk in women (P-trend = 0.34), respectively. For men, the corresponding HRs (95% CIs) were 0.99 (0.94, 1.03), 0.98 (0.91, 1.05), 1.04 (0.98, 1.10), and 1.05 (0.95, 1.16), respectively. We further noted inverse associations for cancer mortality (multivariable-adjusted HR comparing extreme categories: 0.87; 95% CI: 0.78, 0.98; P-trend = 0.04) and CVD mortality (HR: 0.92; 95% CI: 0.79, 1.08; P-trend = 0.41) in women, although the latter was attenuated in the multivariable-adjusted model. Replacement of 1 serving/d of yogurt with 1 serving/d of nuts (women and men) or whole grains (women) was associated with a lower risk of all-cause mortality, whereas replacement of yogurt with red meat, processed meat (women and men), and milk or other dairy foods (women) was associated with a greater mortality.

Conclusions: In our study, regular yogurt consumption was related to lower mortality risk among women. Given that no clear dose-response relation was apparent, this result must be interpreted with caution.
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http://dx.doi.org/10.1093/ajcn/nqz345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7049530PMC
March 2020