Methodological advances in the design of peptide-based vaccines

The tremendous advances in genomics, recombinant DNA technology, bioengineering and nanotechnology, in conjunction with the development of high-end computations, have been instrumental in the process of rational design of peptide-based vaccines. The use of peptide vaccines was limited owing to their inherent instability when systemically administered; however, advanced formulation techniques have been developed for their systemic delivery, thereby overcoming their degradation, clearance, cellular uptake and off-target effects. With the rise of sophisticated immunological predictors and experimental techniques, several methodological advances have occurred in this field. This review examines contemporary methods to identify and optimize epitopes, engineer their immunogenic properties and develop their safe and efficient delivery into the host.     

Prospective characterization of incident hepatic steatosis in pediatric and adolescent patients after total pancreatectomy with islet autotransplantation

BackgroundHepatic steatosis has been described as a common finding in adults following total pancreatectomy with islet autotransplantation (TPIAT) but it is unknown if this occurs in children and adolescents.ObjectivesTo define the frequency of post-TPIAT hepatic steatosis in a sample of children and adolescents and to identify clinical predictors of incident steatosis post-TPIAT.MethodsIn this prospective study, consecutive participants at least 1-month post-TPIAT underwent a liver MRI with proton density fat fraction (PDFF) and blood draw at our pediatric academic medical center between April 2021 and January 2022. Comparison clinical pre-TPIAT liver MRI or ultrasound and insulin use and graft function data were extracted from the medical record. T-tests were used for the comparison of means across continuous variables between participants with and without post-TPIAT steatosis.ResultsA total of 20 participants (mean: 13 ± 4 years; 12 female) were evaluated. Mean liver PDFF at research MRI was 7.4 ± 6.2% (range: 2–25%). Seven participants (35%) had categorical hepatic steatosis (PDFF>5%) post-TPIAT, five of whom had pre-TPIAT steatosis, reflecting a 13% (2/15; 95% CI: 2–40%) incidence of post-TPIAT steatosis. Participant characteristics were not significantly different between subgroups with and without post-TPIAT steatosis. Mean PDFF at research MRI was not different between graft function subgroups (7.5% optimal/good vs. 7.3% marginal/failure; p = .96).ConclusionOur study shows a moderate prevalence but low incidence of hepatic steatosis in a small sample of children and adolescents post-TPIAT. This study raises questions about a causal relationship between TPIAT and hepatic steatosis.     

Angiotensin (1−7) peptide replacement therapy with plasma transfusion in COVID-19

AimTo determine whether convalescent angiotensin (1?7) peptide replacement therapy with plasma (peptide plasma) transfusion can be beneficial in the treatment of critically ill patients with severe coronavirus 2 (SARS-CoV-2) infection.Study designCase series of 9 critically ill patients with laboratory-confirmed COVID-19 who met the following criteria: severe pneumonia with rapid progression and continuously high viral load despite antiviral treatment.Peptide plasma: Plasma with angiotensin (1?7) content 8–10 times higher than healthy plasma donors was obtained from suitable donors. Peptide plasma transfusion was applied to 9 patients whose clinical status and/or laboratory profile deteriorated and who needed intensive care for 2 days.ResultsIn our COVID-19 cases, favipiravir, low molecular weight heparin treatment, which is included in the treatment protocol of the ministry of health, was started. Nine patients with oxygen saturation of 93% and below despite nasal oxygen support, whose clinical and/or laboratory deteriorated, were identified. The youngest of the cases was 36 years old, and the oldest patient was 85 years old. 6 of the 9 cases had male gender. 3 cases had been smoking for more than 10 years. 4 cases had at least one chronic disease.In all of our cases, SARS CoV2 lung involvement was bilateral and peptide plasma therapy was administered in cases when oxygen saturation was 93% and below despite nasal oxygen support of 5 liters/minute and above, and intensive care was required. Although it was not reflected in the laboratory parameters in the early period, 8 patients whose saturations improved with treatment were discharged without the need for intensive care. However, a similar response was not obtained in one case. Oxygen requirement increased gradually and, he died in intensive care process. An increase of the platelet count was observed in all cases following the peptide plasma treatment.ConclusionIn this preliminary case series of 9 critically ill patients with COVID-19, administration of plasma containing angiotensin (1?7) was followed by improvement in their clinical status. The limited sample size and study design preclude a definitive statement about the potential effectiveness of this treatment, and these observations require evaluation in clinical trials.     

People living in disadvantaged areas faced greater challenges in staying active and using recreational facilities during the COVID-19 pandemic

This study aimed to understand the perceived effects of the COVID-19 pandemic on physical activity, recreation walking, and use of recreational facilities; and if the COVID-19 pandemic amplified disparities in physical activity, recreational walking, and use of recreational facilities related to the levels of neighborhood disadvantage. Recreational walking and the use of neighborhood streets and green spaces significantly decreased in high deprivation areas but not in low deprivation areas during the pandemic. While COVID-19 has negatively affected overall recreational activities, the inequitable impact on recreational walking and use of outdoor recreational facilities has been more evident in disadvantaged neighborhoods with greater deprivation.     

Derivation of occupational exposure limits: Differences in methods and protection levels

Frameworks for deriving occupational exposure limits (OELs) and OEL-analogue values (such as derived-no-effect levels [DNELs]) in various regulatory areas in the EU and at national level in Germany were analysed. Reasons for differences between frameworks and possible means of improving transparency and harmonisation were identified. Differences between assessment factors used for deriving exposure limits proved to be one important reason for diverging numerical values. Distributions for exposure time, interspecies and intraspecies extrapolation were combined by probabilistic methods and compared with default values of assessment factors used in the various OEL frameworks in order to investigate protection levels. In a subchronic inhalation study showing local effects in the respiratory tract, the probability that assessment factors were sufficiently high to protect 99% and 95% of the target population (workers) from adverse effects varied considerably from 9% to 71% and 17% to 87%, respectively, between the frameworks. All steps of the derivation process, including the uncertainty associated with the point of departure (POD), were further analysed with two examples of full probabilistic assessments. It is proposed that benchmark modelling should be the method of choice for deriving PODs and that all OEL frameworks should provide detailed guidance documents and clearly define their protection goals by stating the proportion of the exposed population the OEL aims to cover and the probability with which they intend to provide protection from adverse effects. Harmonisation can be achieved by agreeing on the way to perform the methodological steps for deriving OELs and on common protection goals.     

Comparison of P25 and nanobelts on Kruppel-like factor-mediated nitric oxide pathways in human umbilical vein endothelial cells

Recently, we reported that titanium dioxide (TiO₂) materials activated endothelial cells via Kruppel-like factor (KLF)-mediated nitric oxide (NO) dysfunction, but the roles of physical properties of materials are not clear. In this study, we prepared nanobelts from P25 particles and compared their adverse effects to human umbilical vein endothelial cells (HUVECs). TiO₂ nanobelts had belt-like morphology but comparable surface areas as P25 particles. When applied to HUVECs, P25 particles or nanobelts did not induce cytotoxicity, although nanobelts were much more effective to increase intracellular Ti element concentrations compared the same amounts of P25 particles. Only nanobelts significantly induced THP-1 adhesion onto HUVECs. Consistently, nanobelts were more significant to induce the expression of intracellular adhesion molecule-1 (ICAM1) and the release of soluble ICAM-1 (sICAM-1), indicating that nanobelts were more potent to induce endothelial activation in vitro. As the mechanisms for endothelial activation, both P25 and nanobelts reduced the generation of intracellular NO as well as the expression of NO regulators KLF2 and KLF4. Combined, the results from this study indicated that the different morphologies of P25 particles and nanobelts only changed their internalization into HUVECs but showed minimal impact on KLF-mediated NO signaling pathways.     

Characterizing Standardized Functional Data at Inpatient Rehabilitation Facilities

ObjectiveThe Improving Medicare Post-Acute Care Transformation Act of 2014 mandates using standardized patient functional data across post-acute settings. This study characterized similarities and differences in clinician-observed scores of self-care and transfer items for the standardized section GG functional domain and the functional independent measure (FIM) at inpatient rehabilitation facilities.DesignWe conducted secondary analyses of 2017 Uniform Data System for Medical Rehabilitation national data. Patients were assessed by clinicians on both section GG and FIM at admission and discharge. We identified 7 self-care items and 6 transfer items in section GG conceptually equivalent with FIM. Clinician-assessed scores for each pair of items were examined using score distributions, Bland-Altman plot, correlation (Pearson coefficients), and agreement (kappa and weighted kappa) analyses.Setting and ParticipantsIn all, 408,491 patients were admitted to Uniform Data System for Medical Rehabilitation-affiliated inpatient rehabilitation facilities with one of the following impairments: stroke, brain dysfunction, neurologic condition, orthopedic disorders, and debility.MeasuresSection GG and FIM.ResultsPatients were scored as more functionally independent in section GG compared with FIM, but change score distributions and score orders within impairment groups were similar. Total scores in section GG had strong positive correlations (self-care: r = 0.87 and 0.95; transfer: r = 0.82 and 0.90 at admission and discharge, respectively) with total FIM scores. Weak to moderate ranking agreements with total FIM scores were observed (self-care: kappa = 0.49 and 0.60; transfers: kappa = 0.43 and 0.52 at admission and discharge, respectively). Lower agreements were observed for less able patients at admission and for higher ability patients of their change scores.Conclusions and ImplicationsOverall, response patterns were similar in section GG and FIM across impairments. However, variations exist in score distributions and ranking agreement. Future research should examine the use of GG codes to maintain effective care, outcomes, and unbiased reimbursement across post-acute settings.     

The association between sport-related concussion and musculoskeletal injury in university rugby athletes

ObjectivesThe study aimed to analyse the association between Sports-Related Concussion (SRC) and Subsequent Musculoskeletal Injury (MSK) in United Kingdom university-aged rugby union players whilst considering the effects of sex, athlete playing position and injury location.DesignRetrospective cohort study. A period of 365 days with 0–90, 91–180 and 181–365 days sub-periods was analysed for the following variables; MSK injury incidence, occurrence, severity, injury location, playing position and sex.SettingInjury data was collected from the Sports Development Centre database at Loughborough University.ParticipantsA total of 408 injuries in 181 athletes (55 females and 126 males) were included.ResultsThe MSK injury incidence of SRC group was significantly higher than control and higher post-SRC than pre-SRC period over a 365-day period (p=0.012 and p=0.034, respectively). The odds ratios of MSK injury incidence between groups and between periods were 1.62 (95% CI, 1.10–2.25) and 1.57 (95% CI ,1.08–2.29). A SRC was not associated with a greater time loss from a subsequent MSK injury or a specific MSK injury location.ConclusionsAthletes with a second recorded injury were more likely to sustain a MSK injury if they had experienced SRC, however, there was no indication a SRC resulted in greater time loss from a MSK injury.