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Pathogens of the enterovirus genus, including poliovirus and coxsackieviruses, typically circulate in the summer months suggesting a possible positive association between warmer weather and transmission. Here we evaluate the environmental and demographic drivers of enterovirus transmission, as well as the implications of climate change for future enterovirus circulation. We leverage pre-vaccination era data on polio in the US as well as data on two enterovirus A serotypes in China and Japan that are known to cause hand, foot, and mouth disease. Using mechanistic modeling and statistical approaches, we find that enterovirus transmission appears positively correlated with temperature although demographic factors, particularly the timing of school semesters, remain important. We use temperature projections from Coupled Model Intercomparison Project Phase 6 (CMIP6) to simulate future outbreaks under late 21st-century climate change for Chinese provinces. We find that outbreak size increases with climate change on average, though results differ across climate models depending on the degree of wintertime warming. In the worst-case scenario, we project peak outbreaks in some locations could increase by up to 40%. Climate change is likely to impact the circulation of many infectious diseases. Here, the authors characterize the impact of climatic and demographic factors on enterovirus disease transmission and project how changes in climate may impact future transmission. [ABSTRACT FROM AUTHOR]

Purpose: We examined the association of activities of daily living (ADL) and cognitive function with the upper extremity muscle thickness and upper extremity range of motion (ROM) and spasticity in children and adults with cerebral palsy (CP). Methods: The subjects were 20 children and adults with CP. The ADL performed using the upper extremities and cognitive function were assessed using the self-care domain of the Pediatric Evaluation of Disability Inventory (PEDI) and the full-scale intelligence quotient (FSIQ) of the Wechsler Intelligence Scale for Children, fourth edition (WISC-IV), respectively. The WISC-IV was assessed in only seven of 20 subjects able to undergo evaluation. The thickness of the upper extremity muscles was measured using an ultrasound imaging device. Moreover, ROM and spasticity of the upper extremities were assessed using the Modified Ashworth Scale (MAS). Manual manipulation ability was also assessed using the Manual Ability Classification System (MACS). Results: Stepwise regression analysis revealed that the extensor digitorum muscle thickness and MACS level were significant and independent factors of self-care in the PEDI. Partial correlation analysis with MACS level and age as control variables showed that the FSIQ of the WISC-IV was significantly associated with the thickness of the anterior fibers of the deltoid and flexor digitorum superficialis muscles. Conclusion: Reduced ADL performed using the upper extremities is associated with decreased extensor digitorum muscle thickness rather than ROM and spasticity of the upper extremities in children and adults with CP. [ABSTRACT FROM AUTHOR]

Background and Objective: Unbound daptomycin concentrations are responsible for pharmacologically beneficial and adverse effects, although most previous reports have been limited to the use of total concentrations. We developed a population pharmacokinetic model to predict both total and unbound daptomycin concentrations. Methods: Clinical data were collected from 58 patients with methicillin-resistant Staphylococcus aureus including patients undergoing hemodialysis. A total of 339 serum total and 329 unbound daptomycin concentrations were used for model construction. Results: Total and unbound daptomycin concentration was explained by a model that assumed first-order distribution with two compartments, and first-order elimination. Normal fat body mass was identified as covariates. Renal function was incorporated as a linear function of renal clearance and independent non-renal clearance. The unbound fraction was estimated to be 0.066 with a standard albumin of 45 g/L and standard creatinine clearance of 100 mL/min. Simulated unbound daptomycin concentration was compared with minimum inhibitory concentration as a measure of clinical effectiveness and exposure-level-related induction of creatine phosphokinase elevation. The recommended doses were 4 mg/kg for patients with severe renal function [creatinine clearance (CLcr) ≤ 30 mL/min] and 6 mg/kg for patients with mild to moderate renal function (CLcr > 30 and ≤ 60 mL/min). A simulation indicated that dose adjusted by body weight and renal function improved target attainment. Conclusions: This population pharmacokinetics model for unbound daptomycin could help clinicians to select the appropriate dose regimen for patients undergoing daptomycin treatment and reduce associated adverse effects. [ABSTRACT FROM AUTHOR]

As SARS-CoV-2 continues to spread and vaccines are rolled-out, the "double burden" of disparities in exposure and vaccination intersect to determine patterns of infection, immunity, and mortality. Serology provides a unique opportunity to measure prior infection and vaccination simultaneously. Leveraging algorithmically-selected residual sera from two hospital networks in the city of San Francisco, cross-sectional samples from 1,014 individuals from February 4–17, 2021 were each tested on two assays (Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 and Roche Elecsys Anti-SARS-CoV-2), capturing the first year of the epidemic and early roll-out of vaccination. We estimated, using Bayesian estimation of infection and vaccination, that infection risk of Hispanic/Latinx residents was five times greater than of White residents aged 18–64 (95% Credible Interval (CrI): 3.2–10.3), and that White residents over 65 were twice as likely to be vaccinated as Black/African American residents (95% CrI: 1.1–4.6). We found that socioeconomically-deprived zipcodes had higher infection probabilities and lower vaccination coverage than wealthier zipcodes. While vaccination has created a 'light at the end of the tunnel' for this pandemic, ongoing challenges in achieving and maintaining equity must also be considered. Continued monitoring of SARS-CoV-2 at the population level is important for identifying at-risk groups. Here the authors analyse data from a serological surveillance platform in San Francisco and find considerable variation in infection and vaccination history by race/ethnicity and socioeconomic status. [ABSTRACT FROM AUTHOR]

Serosurveillance provides a unique opportunity to quantify the proportion of the population that has been exposed to pathogens. Here, we developed and piloted Serosurveillance for Continuous, ActionabLe Epidemiologic Intelligence of Transmission (SCALE-IT), a platform through which we systematically tested remnant samples from routine blood draws in two major hospital networks in San Francisco for SARS-CoV-2 antibodies during the early months of the pandemic. Importantly, SCALE-IT allows for algorithmic sample selection and rich data on covariates by leveraging electronic health record data. We estimated overall seroprevalence at 4.2%, corresponding to a case ascertainment rate of only 4.9%, and identified important heterogeneities by neighborhood, homelessness status, and race/ethnicity. Neighborhood seroprevalence estimates from SCALE-IT were comparable to local community-based surveys, while providing results encompassing the entire city that have been previously unavailable. Leveraging this hybrid serosurveillance approach has strong potential for application beyond this local context and for diseases other than SARS-CoV-2. Population-based surveys are the gold standard for estimating seroprevalence but are expensive and often only capture a small geographic area or window of time. This study describes a new platform, SCALE-IT, for serosurveillance based on algorithmic sampling of electronic health records, and uses it to estimate the seroprevalence of SARS-CoV-2 in San Francisco. [ABSTRACT FROM AUTHOR]

Numerous studies of native proteins have been reported on protein folding in this half century. Recently, post-translationally modified proteins are also focused on protein folding. However, it is still difficult to prepare such types of proteins because it requires not only the chemical but also the recombinant techniques. Native chemical ligation (NCL) is a powerful technique for producing target proteins when combined with recombinant techniques, such as expressed protein ligation (EPL). NCL basically requires an N-terminal peptide with a thioester and a C-terminal peptide which should possess a Cys residue at the N-terminus. Numerous efforts have been made to prepare N-terminal peptides carrying a thioester or a derivative thereof. However, a method for preparing C-terminal Cys-peptides with post-translational modifications has not been well developed, making it difficult to prepare such C-terminal Cys-peptides, except for chemical syntheses or enzymatic digestion. We report here on the development of a convenient technique that involves acid hydrolysis at the -Asp-Cys- sequence, to effectively obtain a C-terminal peptide fragment that can be used for any protein synthesis when combined with EPL, even under denatured conditions. Thus, this chemical digestion strategy permits the NCL strategy to be dramatically accelerated for protein syntheses in which post-translational modifications, such as glycosylation, phosphorylation, etc. are involved. In addition, this method should be useful to prepare the post-translationally modified proteins for protein folding. [ABSTRACT FROM AUTHOR]

The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. National immunization programs offer childhood vaccines through fixed and outreach services within the health system and often, additional supplementary immunization activities (SIAs) are undertaken to fill gaps and boost coverage. Here, we map predicted coverage at 1 × 1 km spatial resolution in five low- and middle-income countries to identify areas that are under-vaccinated via each delivery method using Demographic and Health Surveys data. We compare estimates of the coverage of the third dose of diphtheria-tetanus-pertussis-containing vaccine (DTP3), which is typically delivered through routine immunization (RI), with those of measles-containing vaccine (MCV) for which SIAs are also undertaken. We find that SIAs have boosted MCV coverage in some places, but not in others, particularly where RI had been deficient, as depicted by DTP coverage. The modelling approaches outlined here can help to guide geographical prioritization and strategy design. The success of vaccination programs depends largely on the mechanisms used in vaccine delivery. Here, the authors evaluate the relative effectiveness of two major vaccine delivery strategies, namely routine immunization and supplementary immunization activities in five study countries. [ABSTRACT FROM AUTHOR]

Expanded access to measles vaccination was among the most successful public health interventions of recent decades. All WHO regions currently target measles elimination by 2020, yet continued measles circulation makes that goal seem elusive. Using Demographic and Health Surveys with generalized additive models, we quantify spatial patterns of measles vaccination in ten contiguous countries in the African Great Lakes region between 2009-2014. Seven countries have 'coldspots' where vaccine coverage is below the WHO target of 80%. Over 14 million children under 5 years of age live in coldspots across the region, and a total of 8-12 million children are unvaccinated. Spatial patterns of vaccination do not map directly onto sub-national administrative units and transnational coldspots exist. Clustering of low vaccination areas may allow for pockets of susceptibility that sustain circulation despite high overall coverage. Targeting at-risk areas and transnational coordination are likely required to eliminate measles in the region. [ABSTRACT FROM AUTHOR]