Perceptions and Knowledge About the MenB Vaccine Among Parents of High School Students.

Serogroup B meningococcal disease (MenB) causes almost 60% of meningitis cases among adolescents and young adults. Yet, MenB vaccine coverage among adolescents remains below 10%. Since parents are the primary medical decision makers for adolescents, we examined MenB vaccination rates and parent attitudes about meningitis and the MenB vaccine. In 2018, in conjunction with a county-wide, school-based immunization campaign, we conducted a mixed methods study among parents of 16- to 17-year-olds. We facilitated focus groups asking parents about their knowledge of meningitis and reactions to educational materials and sent behavioral surveys based on Health Belief Model constructs to parents through the county high school system. Parents in three focus groups (n = 8; participation rate = 13%) expressed confusion about their child's need to receive the MenB vaccine in addition to the meningococcal conjugate vaccine (MenACWY), but conveyed strong trust in their physicians' recommendation. Among survey participants (n = 170), 70 (41%) had heard of the MenB vaccine. Among those 70 parents, the most common barriers to vaccination were concerns about side effects (55%) and uncertainty of susceptibility due to receipt of the MenACWY vaccine (30%). The percentage of teens that received at least one dose of the MenB vaccine was 50% (n = 35) by parent report and 23% (n = 16) by state vaccination records. Parents demonstrated uncertainty and confusion about the MenB vaccine particularly due to the existence of another meningitis vaccine and limited health care provider recommendations. Confirmatory studies of parent confusion about the MenB vaccine are needed to develop interventions.

Safety of a 2-Day Antibiotic Regimen After Delayed Chest Closure Post Pediatric Cardiac Surgery.

BACKGROUND: There is no consensus for the length of prophylactic antibiotics after delayed chest closure (DCC) postcardiac surgery in pediatrics. In September 2014, our institution's pediatric cardiac intensive care unit changed the policy on length of prophylactic antibiotics after DCC from 5 days (control) to 2 days (study group). The objective of the study was to determine whether a 2-day course of antibiotics is as effective as a 5-day course in preventing blood stream and sternal wound infections in pediatric DCC. METHODS: Retrospective and prospective study. Primary end points included incidence of sternal wound infections and positive sternal imaging for infection. Surrogate markers of infection were collected at 4 time points. RESULTS: During the study period, 139 patients had DCC postcardiac surgery of which 110 patients were included for analysis, 54 patients in the control and 56 in the study group. There was no difference in total number of positive wound cultures/chest computed tomography (CT) findings (4/54 [7.5%] control vs 5/56 [8.9%] study group, P = .3), positive blood cultures (P = .586), median postsurgical length of stay (P = .4), or readmissions within 30 days postsurgery (P = .6). All secondary end points were similar in both groups except peak heart rate between weeks 2 and 4 (P = .041). CONCLUSION: Two days of prophylactic antibiotics is not inferior to 5 days of prophylactic antibiotics after DCC following pediatric cardiac surgery.

Biographical films as a person-centered approach to reduce neuropsychiatric symptoms of dementia in residential care: A feasibility study.

OBJECTIVE: Neuropsychiatric symptoms are a major component of dementia irrespective of severity or subtype. We aimed to determine the feasibility of biographical films to reduce neuropsychiatric symptoms in people with moderate to severe dementia over a 32-week period. METHOD: A total of 11 people with dementia situated in a residential care home took part in this mixed-method feasibility study. Carers reported neuropsychiatric symptoms of residents at three time-points, and their experience of the study was obtained at a feedback session. RESULTS: There was a significant reduction in neuropsychiatric symptoms in residents with neuropsychiatric impairment from baseline to the end of study (p = .042; d = .98). Thematic analysis identified three major themes: Triggered memories, knowledge gained to support care, and perceived changes in the resident. CONCLUSION: The findings suggest that it is feasible to use biographical films long-term to reduce neuropsychiatric symptoms of dementia, alongside routine care.

Concentration of Sindbis virus with optimized gradient insulator-based dielectrophoresis.

Biotechnology, separation science, and clinical research are impacted by microfluidic devices. Separation and manipulation of bioparticles such as DNA, protein and viruses are performed on these platforms. Microfluidic systems provide many attractive features, including small sample size, rapid detection, high sensitivity and short processing time. Dielectrophoresis (DEP) and electrophoresis are especially well suited to microscale bioparticle control and have been demonstrated in many formats. In this work, an optimized gradient insulator-based DEP device was utilized for concentration of Sindbis virus, an animal virus with a diameter of 68 nm. Within only a few seconds, the concentration of Sindbis virus can be increased by two to six times in the channel under easily accessible voltages as low as about 70 V. Compared with traditional diagnostic methods used in virology, DEP-based microfluidics can enable faster isolation, detection and concentration of viruses in a single step within a short time.

B-Cell depletion and immunomodulation before initiation of enzyme replacement therapy blocks the immune response to acid alpha-glucosidase in infantile-onset Pompe disease.

OBJECTIVE: To evaluate whether B-cell depletion before enzyme replacement therapy (ERT) initiation can block acid alpha-glucosidase (GAA) antibody responses and improve clinical outcomes. STUDY DESIGN: Six subjects with Pompe disease (including 4 cross-reacting immunologic material-negative infants) aged 2-8 months received rituximab and sirolimus or mycophenolate before ERT. Four subjects continued to receive sirolimus, rituximab every 12 weeks, and intravenous immunoglobulin monthly for the duration of ERT. Sirolimus trough levels, IgG, CD3, CD4, CD8, CD19, CD20, N-terminal pro-brain natriuretic peptide, creatine kinase, creatine kinase-MB, C-reactive protein, platelets, alkaline phosphatase, gamma-glutamyl transferase, aspartate aminotransferase, and alanine aminotransferase were measured regularly. RESULTS: Immunomodulation achieved B-cell depletion without adverse effects. After 17-36 months of rituximab, sirolimus and ERT, all subjects lacked antibodies against GAA, 4 continued to gain motor milestones, yet 2 progressed to require invasive ventilation. The absence of infusion-associated reactions allowed the use of accelerated infusion rates. CONCLUSION: B-cell depletion and T-cell immunomodulation in infants naïve to ERT was accomplished safely and eliminated immune responses against GAA, thereby optimizing clinical outcome; however, this approach did not necessarily influence sustained independent ventilation. Importantly, study outcomes support the initiation of immunomodulation before starting ERT, because the study regimen allowed for prompt initiation of treatment.

Recombinant production and purification of the subunit c of chloroplast ATP synthase.

In chloroplasts, the multimeric ATP synthase produces the adenosine triphosphate (ATP) that is required for photosynthetic metabolism. The synthesis of ATP is mechanically coupled to the rotation of a ring of c-subunits, which is imbedded in the thylakoid membrane. The rotation of this c-subunit ring is driven by the translocation of protons across this membrane, along an electrochemical gradient. The ratio of protons translocated to ATP synthesized varies according to the number of c-subunits (n) per oligomeric ring (c(n)) in the enzyme, which is organism dependent. Although this ratio is inherently related to the metabolism of the organism, the exact cause of the c(n) variability is not well understood. In order to investigate the factors that may contribute to this stoichiometric variation, we have developed a recombinant bacterial expression and column purification system for the c1 monomeric subunit. Using a plasmid with a codon optimized gene insert, the hydrophobic c1 subunit is first expressed as a soluble MBP-c1 fusion protein, then cleaved from the maltose binding protein (MBP) and purified on a reversed phase column. This novel approach enables the soluble expression of an eukaryotic membrane protein in BL21 derivative Escherichia coli cells. We have obtained significant quantities of highly purified c1 subunit using these methods, and we have confirmed that the purified c1 has the correct alpha-helical secondary structure. This work will enable further investigation into the undefined factors that affect the c-ring stoichiometry and structure. The c-subunit chosen for this work is that of spinach (Spinacia oleracea) chloroplast ATP synthase.

ABM Clinical Protocol #35: Supporting Breastfeeding During Maternal or Child Hospitalization.

A central goal of the Academy of Breastfeeding Medicine is the development of clinical protocols for managing common medical problems that may impact breastfeeding success. These protocols serve only as guidelines for the care of breastfeeding mothers and infants and do not delineate an exclusive course of treatment or serve as standards of medical care. Variations in treatment may be appropriate according to the needs of an individual patient. The Academy of Breastfeeding Medicine recognizes that not all lactating individuals identify as female. Using gender-inclusive language, however, is not possible in all languages and all countries and for all readers. The position of the Academy of Breastfeeding Medicine (https://doi.org/10.1089/bfm.2021.29188.abm) is to interpret clinical protocols within the framework of inclusivity of all breastfeeding, chestfeeding, and human milk-feeding individuals.

Increasing awareness and uptake of the MenB vaccine on a large university campus.

Objective: At a large public university, we aimed to evaluate an intervention designed to increase serogroup B meningococcal (MenB) vaccine uptake and awareness.Methods: Using a pretest-posttest design with a double posttest, we evaluated an intervention conducted by a local foundation and the Florida Department of Health that distributed MenB vaccine on campus and conducted an educational campaign. Prior to intervention activities, we recruited students to complete a survey about their MenB knowledge and attitudes. For survey participants who provided contact information, we sent two follow-up surveys and assessed MenB vaccine records. We used chi-square tests, adjusted for nonindependence, to compare preintervention to postintervention (three-month and one-year) vaccination and attitudes.Results: Among the 686 students with accessible vaccine records, MenB vaccine initiation increased 9% (from 24% to 33%) and completion increased 8% (from 13% to 21%) from before the intervention to one year after the intervention. When restricting to students who completed the relevant follow-up surveys, the percentage of students who heard of the MenB vaccine increased by 15% (p > .001) from before the intervention to three months after (n = 188 students) and maintained a 10% increase (p > .001) one year after the intervention (n = 261 students). Among students that heard of the MenB vaccine, the percentage of students who thought they needed the MenB vaccine even though they received the MenACWY increased 14% (p = .03) by the three-month postintervention survey and up to 18% by the one-year follow-up (p = .002).Conclusions: A university-wide, on-campus vaccination and educational campaign increased college students' MenB vaccine initiation, completion, and knowledge.Clinicaltrials.gov ID: NCT02975596.

Does insulin resistance influence neurodegeneration in non-diabetic Alzheimer's subjects?

BACKGROUND: Type 2 diabetes is a risk factor for Alzheimer's disease (AD), and AD brain shows impaired insulin signalling. The role of peripheral insulin resistance on AD aetiopathogenesis in non-diabetic patients is still debated. Here we evaluated the influence of insulin resistance on brain glucose metabolism, grey matter volume and white matter lesions (WMLs) in non-diabetic AD subjects. METHODS: In total, 130 non-diabetic AD subjects underwent MRI and [18F]FDG PET scans with arterial cannula insertion for radioactivity measurement. T1 Volumetric and FLAIR sequences were acquired on a 3-T MRI scanner. These subjects also had measurement of glucose and insulin levels after a 4-h fast on the same day of the scan. Insulin resistance was calculated by the updated homeostatic model assessment (HOMA2). For [18F]FDG analysis, cerebral glucose metabolic rate (rCMRGlc) parametric images were generated using spectral analysis with arterial plasma input function. RESULTS: In this non-diabetic AD population, HOMA2 was negatively associated with hippocampal rCMRGlc, along with total grey matter volumes. No significant correlation was observed between HOMA2, hippocampal volume and WMLs. CONCLUSIONS: In non-diabetic AD, peripheral insulin resistance is independently associated with reduced hippocampal glucose metabolism and with lower grey matter volume, suggesting that peripheral insulin resistance might influence AD pathology by its action on cerebral glucose metabolism and on neurodegeneration.

Intravenous Immunoglobulin as a Therapeutic Option for Mycoplasma pneumoniae Encephalitis.

OBJECTIVE: To analyze the outcomes of a cohort of children diagnosed with Mycoplasma pneumoniae encephalitis whose treatment regimens included intravenous immunoglobulin (IVIG). METHODS: A retrospective study was performed at a single center between 2011 and 2016 of children diagnosed with Mycoplasma pneumoniae encephalitis whose acute treatment regimen included IVIG. Details of therapeutic interventions and the clinical course were retrieved from medical records via an institutionally approved protocol. The modified Rankin score was used to quantify outcomes. RESULTS: Four children met inclusion criteria, 3 of whom had prodromal symptoms of infection lasting 5 to 7 days before onset of their neurologic symptoms. One patient presented with neurologic symptoms with no clinical prodrome. The initial treatment regimen included systemic corticosteroids, antibiotics, or both. IVIG was administered for a total dose of 2 g/kg divided over 2 to 4 days to all 4 children. All children showed clinical improvement after IVIG. The 3 children with prodromal symptoms showed immediate and dramatic clinical improvement after IVIG therapy. DISCUSSION: The immediate response to immunomodulatory therapy in the patients with prodrome suggests that the neurologic syndrome may be caused at least in part by an autoimmune process. The child who did not respond to IVIG had no prodrome, and also had normal electroencephalographic (EEG) and brain magnetic resonance imaging (MRI) findings. These cases suggest that early administration of IVIG should be considered in patients suspected of having Mycoplasma encephalitis, particularly in those who have had prodromal symptoms.

Effects of sepsis on neonatal thrombopoiesis.

We serially evaluated the effects of sepsis and/or necrotizing enterocolitis (NEC) on neonatal thrombopoiesis, using a panel of tests that included platelet counts, thrombopoietin concentrations (Tpo), circulating megakaryocyte progenitor concentrations (CMPs), and reticulated platelets (RPs). Variables analyzed included sepsis type, time after onset of sepsis, platelet counts, and gestational (GA) and postconceptional ages (PCA). Twenty neonates were enrolled. Ten had Gram-negative, six had Gram-positive, and four had presumed sepsis. Four neonates had NEC stage II or higher, and six developed thrombocytopenia. Overall, septic neonates had significantly elevated Tpo concentrations and circulating megakaryocyte progenitors. The highest Tpo levels were associated with Gram-negative or presumed sepsis. RP percentages were increased only in neonates with low platelet counts, while RP counts (RP% x platelet count) were elevated in neonates with high platelet counts. Our findings suggest that septic neonates up-regulate Tpo production, leading to increased megakaryocytopoiesis and platelet release, although the degree of upregulation is moderate. The changes in RP% and RP count most likely reflect increased thrombopoiesis with variable degrees of platelet consumption. In addition, our findings suggest that different factors, likely including level of illness and/or specific platelet or bacterial products, can down-regulate the magnitude of the thrombopoietic response.

Innate Immunity and Breast Milk.

Human milk is a dynamic source of nutrients and bioactive factors; unique in providing for the human infant's optimal growth and development. The growing infant's immune system has a number of developmental immune deficiencies placing the infant at increased risk of infection. This review focuses on how human milk directly contributes to the infant's innate immunity. Remarkable new findings clarify the multifunctional nature of human milk bioactive components. New research techniques have expanded our understanding of the potential for human milk's effect on the infant that will never be possible with milk formulas. Human milk microbiome directly shapes the infant's intestinal microbiome, while the human milk oligosaccharides drive the growth of these microbes within the gut. New techniques such as genomics, metabolomics, proteomics, and glycomics are being used to describe this symbiotic relationship. An expanded role for antimicrobial proteins/peptides within human milk in innate immune protection is described. The unique milieu of enhanced immune protection with diminished inflammation results from a complex interaction of anti-inflammatory and antioxidative factors provided by human milk to the intestine. New data support the concept of mucosal-associated lymphoid tissue and its contribution to the cellular content of human milk. Human milk stem cells (hMSCs) have recently been discovered. Their direct role in the infant for repair and regeneration is being investigated. The existence of these hMSCs could prove to be an easily harvested source of multilineage stem cells for the study of cancer and tissue regeneration. As the infant's gastrointestinal tract and immune system develop, there is a comparable transition in human milk over time to provide fewer immune factors and more calories and nutrients for growth. Each of these new findings opens the door to future studies of human milk and its effect on the innate immune system and the developing infant.

Corrigendum: Diffraction data of core-shell nanoparticles from an X-ray free electron laser.

This corrects the article DOI: 10.1038/sdata.2017.48.

Diffraction data of core-shell nanoparticles from an X-ray free electron laser.

X-ray free-electron lasers provide novel opportunities to conduct single particle analysis on nanoscale particles. Coherent diffractive imaging experiments were performed at the Linac Coherent Light Source (LCLS), SLAC National Laboratory, exposing single inorganic core-shell nanoparticles to femtosecond hard-X-ray pulses. Each facetted nanoparticle consisted of a crystalline gold core and a differently shaped palladium shell. Scattered intensities were observed up to about 7 nm resolution. Analysis of the scattering patterns revealed the size distribution of the samples, which is consistent with that obtained from direct real-space imaging by electron microscopy. Scattering patterns resulting from single particles were selected and compiled into a dataset which can be valuable for algorithm developments in single particle scattering research.

Full inactivation of alphaviruses in single particle and crystallized forms.

Inherent in the study of viruses is the risk of pathogenic exposure, which necessitates appropriate levels of biosafety containment. Unfortunately, this also limits the availability of useful research instruments that are located at facilities not equipped to handle infectious pathogens. Abrogation of viral infectivity can be accomplished without severely disrupting the physical structure of the virus particle. Virus samples that are verifiably intact but not infectious may be enabled for study at research facilities where they would otherwise not be allowed. Inactivated viruses are also used in the development of vaccines, where immunogenicity is sought in the absence of active infection. We demonstrate the inactivation of Sindbis alphavirus particles in solution, as well as in crystallized form. Inactivation was accomplished by two different approaches: crosslinking of proteins by glutaraldehyde treatment, and crosslinking of nucleic acids by UV irradiation. Biophysical characterization methods, including dynamic light scattering and transmission electron microscopy, were used to demonstrate that the glutaraldehyde and UV inactivated Sindbis virus particles remain intact structurally. SDS-PAGE was also used to show evidence of the protein crosslinking that was expected with glutaraldehyde treatment, but also observed with UV irradiation.

Review article: BK virus in systemic lupus erythematosus.

BK virus (BKV) is a human polyomavirus with a seroprevalence of 60-80 % in the general population. In renal transplant patients, it is known to cause renal failure, ureteric stenosis and hemorrhagic cystitis. In bone marrow transplant patients, it is evident that BKV can also cause hemorrhagic cystitis along with BK virus nephropathy (BKVN) in the native kidneys, with subsequent renal failure. However, little is known about BVKN in non-transplanted immune-compromised patients, such as systemic lupus erythematosus (SLE) who may have underlying nephritis and have a compromised immune system due to therapy and/or systemic illness. Thus, this article will focus on the clinical aspects of BKV and its association in patients with SLE.

Serial femtosecond X-ray diffraction of enveloped virus microcrystals.

Serial femtosecond crystallography (SFX) using X-ray free-electron lasers has produced high-resolution, room temperature, time-resolved protein structures. We report preliminary SFX of Sindbis virus, an enveloped icosahedral RNA virus with ∼700 Šdiameter. Microcrystals delivered in viscous agarose medium diffracted to ∼40 Šresolution. Small-angle diffuse X-ray scattering overlaid Bragg peaks and analysis suggests this results from molecular transforms of individual particles. Viral proteins undergo structural changes during entry and infection, which could, in principle, be studied with SFX. This is an important step toward determining room temperature structures from virus microcrystals that may enable time-resolved studies of enveloped viruses.

Breast milk and infection.

Three viruses (CMV, HIV, and HTLV-I) frequently cause infection or disease as a result of breast-milk transmission. Reasonable guidelines have been pro-posed for when and how to avoid breast milk in the case of maternal infection. For other viruses, prophylactic immune therapy to protect the infant against all modes of transmission are indicated (VZV, varicella-zoster immunoglobulin, HAV and immunoglobulin, HBV, and HBIg + HBV vaccine). In most maternal viral infections, breast milk is not an important mode of transmission, and continuation of breastfeeding is in the best interest of the infant and mother (see Tables 2 and 3). Maternal bacterial infections rarely are complicated by transmission of infection to their infants through breast milk. In a few situations, temporary cessation of breastfeeding or the avoidance of breast milk is appropriate for a limited time (24 hours for N gonorrheae, H infiuenzae, Group B streptococci, and staphylococci and longer for others including B burgdorferi, T pallidum, and M tuberculosis). In certain situations, prophylactic or empiric therapy may be advised for the infant (eg, T pallidum, M tuberculosis, H influenzae) (see Table 1). Antimicrobial use by the mother should not be a reason not to breastfeed. Alternative regimens that are compatible with breastfeeding can be chosen to treat the mother effectively. In most cases of suspected infection in the breastfeeding mother, the delay in seeking medical care and making the diagnosis means the infant has been ex-posed already. Stopping breastfeeding at this time only deprives the infant of the nutritional and potential immunologic benefits. Breastfeeding or the use of expressed breast milk, even if temporarily suspended, should be encouraged and supported. Decisions about breast milk and infection should balance the potential risk compared with the innumerable benefits of breast milk.