Introduction: Given the characteristics of meningococcal carriage and transmission and the sudden, often severe onset and long-term consequences of disease, vaccination can most effectively provide ...large-scale control of invasive disease. Six serogroups (A, B, C, W, X, and Y) cause nearly all meningococcal disease globally. Capsular polysaccharide conjugate vaccines can prevent serogroups A, C, W, and Y disease. More recently, recombinant protein vaccines for preventing serogroup B meningococcal (MenB) disease have become available, with a major target of vaccine-induced immune response for both vaccines being bacterial factor H binding protein (FHbp). Importantly, FHbp segregates into only two distinct subfamilies (A also classified as variants 2 and 3 and B variant 1). This review summarizes the complete clinical development program supporting licensure of MenB-FHbp (Trumenba®, Bivalent rLP2086), the only MenB vaccine containing antigens from both FHbp subfamilies.
Areas covered: Eleven published clinical studies assessing MenB-FHbp efficacy and safety among 20,803 adolescents and adults are examined. Particular focus is on the methodology of immunogenicity assessments used as a surrogate for clinical efficacy.
Expert commentary: Clinical studies in adolescents and adults consistently demonstrated MenB-FHbp safety and induction of immunologic responses against antigenically and epidemiologically diverse MenB isolates, supporting licensure and immunization recommendations.
Sinking organic particles transfer ∼10 gigatonnes of carbon into the deep ocean each year, keeping the atmospheric CO₂ concentration significantly lower than would otherwise be the case. The exact ...size of this effect is strongly influenced by biological activity in the ocean's twilight zone (∼50–1,000 m beneath the surface). Recent work suggests that the resident zooplankton fragment, rather than ingest, the majority of encountered organic particles, thereby stimulating bacterial proliferation and the deep‐ocean microbial food web. Here we speculate that this apparently counterintuitive behaviour is an example of ‘microbial gardening’, a strategy that exploits the enzymatic and biosynthetic capabilities of microorganisms to facilitate the ‘gardener's’ access to a suite of otherwise unavailable compounds that are essential for metazoan life. We demonstrate the potential gains that zooplankton stand to make from microbial gardening using a simple steady state model, and we suggest avenues for future research.
•The supra-patellar approach for tibial intra-medullary nailing achieves improved insertion accuracy in the coronal plane.•The supra-patellar technique reduces the variability in nail insertion entry ...point in both sagittal and coronal planes.•Accurate nail insertion reduces the risk of damage to intra-articular structures and aids fracture reduction.
The anatomical safe zone for intra-medullary nail insertion through the tibial plateau is small, insertion outside of this area risks damage to intra-articular structures and poor fracture reduction. The purpose of this retrospective study was to determine if the new supra-patella (SP) approach confers improved nail insertion accuracy, when compared with the standard infra-patella (IP) technique.
Two hundred cases were included in the study (SP 95, IP 105). Insertion accuracy was assessed on AP and lateral radiographic imaging, and measured as the distances between the central axis of the proximal nail and the ideal entry point.
The median distance from the ideal entry point was 4.4 mm (SP) and 5.1 mm (IP) (p = 0.046) in the coronal plane, and 4.0 mm (SP) and 3.7 mm (IP) (p = 0.527) in the sagittal plane. A narrower range in measurements was observed in the SP technique in both sagittal and coronal planes, 17.8 mm vs 28.6 mm, and 19.7 mm vs 30.3 mm respectively.
We found that the SP technique achieved significantly improved nail insertion accuracy in the coronal plane. Insertion accuracy was equivocal between the two techniques in the sagittal plane. A narrower range in entry points was observed in the SP cohort in both planes suggesting improved control in nail insertion using this technique.
Long and complicated grief is a relevant factor contributing to the deterioration of the older adults’ later life quality. In China, the unintentional consequence of the one-child policy has emerged. ...There, the group of older adults who lost their only child is called shiduers. The current study compared 42 older adults who lost their only child to 33 older adults who have a child, in term of their physical and mental health, and social support. The results confirmed the general deteriorating trend in those aspects of the bereaved Chinese parents’ life after their only child’s death. The results also revealed the impairments on the shiduers’ physical, mental, and social aspects were significant, compared to the clinical diagnosis cutoff points used in Western countries. Unique policy and cultural characteristics are the main factors contributing to the severe impairment of shiduers. Results have implications for policy advocacy and practice intervention in specific cultural environments.
Developing strategies to regulate the immune response poses significant challenges with respect to the clinical translation of tissue-engineered scaffolds. Prominent advancements have been made ...relating to macrophage-based therapies and biomaterials. Macrophages exhibit the potential to influence healing trajectory, and predominance of particular subtypes during early onset of healing influences repair outcomes. This study evaluated short- and long-term healing response and postoperative mechanical properties of genipin-cross-linked, electrochemically aligned collagen biotextiles with comparative administration of M0, M1, and M2 subtypes. Irrespective of macrophage subtype seeded, all the groups demonstrated existence of M2 macrophages at both time points as typified by arginase and Ym-1 expressions, and distinct absence of M1 macrophages, as indicated by lack of inducible nitric oxide synthase (iNOS) and interleukin-1β expression in all the groups for both time points. M2 macrophage-seeded collagen biotextiles revealed promising host tissue responses, such as reduced fibrous capsule thickness and minimal granulation tissue formation. Furthermore, the M2-seeded group displayed more abundant interstitial collagen deposition following degradation of the collagen threads. M2 macrophage supplementation improved structural and mechanical properties at the tissue and cellular level as indicated by increased modulus and stiffness. This study demonstrates improved biomechanical and histological outcomes following incorporation of M2 macrophages into genipin-cross-linked collagen biotextiles for tissue repair and offers future strategies focused on connective tissue regeneration. Impact statement Macrophages exhibit significant plasticity with complex phenotypes ranging from proinflammatory (M1) to proregenerative (M2). They release cytokines and chemokines governing immunological stability, inflammation resolution, and tissue healing and regeneration. However, utilization of macrophages as therapeutic tools for tissue engineering remains limited. In this study, genipin-cross-linked collagen biotextiles were employed to deliver M0, M1, and M2 macrophages and evaluate tissue responses and postsurgical mechanical properties
. M2-seeded collagen biotextiles showed reduced fibrous capsule and favorable healing response. These outcomes shed new light on designing tissue-engineered constructs that offer a novel cell-based therapeutic approach for applications requiring structural augmentation.
With an unplanned pregnancy rate of 50% or more in many countries, there is an urgent need for contraceptives that are more accessible and acceptable. To meet the growing demand for new ...contraceptives, ZabBio developed ZB-06, a vaginal film containing HC4-N, a human contraceptive antibody that inactivates sperm.
This study aimed to assess the potential contraceptive activity of the ZB-06 film using a surrogate assessment for contraceptive efficacy, the postcoital test. We also assessed clinical safety of film use among healthy heterosexual couples. Serum, cervical mucus, and vaginal fluid HC4-N antibody concentrations and sperm agglutination potency were determined after single film use. Changes in the concentration of soluble proinflammatory cytokines and vaginal Nugent score after film use were measured as subclinical safety endpoints.
This was a phase 1, first-in-woman, open-label, proof-of-concept, postcoital test and safety study.
A total of 20 healthy women were enrolled in the study, and 8 heterosexual couples completed all study visits. The product was safe for both female participants and their male sexual partners. The postcoital test performed on ovulatory cervical mucus at baseline (no product use) revealed a mean of 25.9 (±30.6) progressively motile sperm per high-power field. After use of a single ZB-06 film before intercourse, this number dropped to 0.04 (±0.06) progressively motile sperm per high-power field (P<.0001). At the follow-up postcoital test visit approximately 1 month later (no product use), a mean of 47.4 (±37.4) progressively motile sperm per high-power field was observed, indicating contraceptive reversibility.
A single dose of the ZB-06 film applied before intercourse was safe and met efficacy surrogate benchmarks of excluding progressively motile sperm from ovulatory cervical mucus. These data indicate that ZB-06 is a viable contraceptive candidate warranting further development and testing.
Elevated temperature causes metabolism and respiration to increase in poikilothermic organisms. We hypothesized that invertebrate consumers will therefore require increasingly carbon-rich diets in a ...warming environment because the increased energetic demands are primarily met using compounds rich in carbon, that is, carbohydrates and lipids. Here, we test this hypothesis using a new stoichiometric model that has carbon (C) and nitrogen (N) as currencies. Model predictions did not support the hypothesis, indicating instead that the nutritional requirements of invertebrates, at least in terms of food quality expressed as C:N ratio, may change little, if at all, at elevated temperature. Two factors contribute to this conclusion. First, invertebrates facing limitation by nutrient elements such as N have, by default, excess C in their food that can be used to meet the increased demand for energy in a warming environment, without recourse to extra dietary C. Second, increased feeding at elevated temperature compensates for the extra demands of metabolism to the extent that, when metabolism and intake scale equally with temperature (have the same Q
10), the relative requirement for dietary C and N remains unaltered. Our analysis demonstrates that future climate-driven increases in the C:N ratios of autotroph biomass will likely exacerbate the stoichiometric mismatch between nutrient-limited invertebrate grazers and their food, with important consequences for C sequestration and nutrient cycling in ecosystems.
•5-Fu significantly compromised the dendritic architecture.•5-Fu decreased spine density and modulated spine morphology throughout Hippocampus.•5-Fu upregulated pro-inflammatory and anti-inflammatory ...cytokines.
5-Fluorouracil (5-Fu) is commonly used chemotherapy drug, but it can lead to the impairment of cognitive function. The pathogenesis of this injury is unknown but may involve modifications to dendritic structure and/or alterations in dendritic spine density and morphology. Dendritic spines are sites of excitatory synaptic transmission and changes in spine structure and dendrite morphology are thought to represent a morphological correlate of altered brain functions associated with hippocampal dependent learning and memory. A total of 28 one-year-old C57BL6/J male mice were used in this study; 14 mice received 5-Fu treatment and 14 were given saline injections. One month post treatment, 14 cytokines were measured at the same time Golgi samples were taken. 8 analytes were significantly elevated in mice treated with 5-Fu. 5-Fu significantly compromised the dendritic architecture and reduced spine density throughout the hippocampal tri-synaptic network. The present data provide the evidence that 5-Fu has deleterious effects on mature neurons associated with hippocampal learning and memory.
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