New Detection Systems of Bacteria Using Highly Selective Media Designed by SMART: Selective Medium-Design Algorithm Restricted by Two Constraints

Culturing is an indispensable technique in microbiological research, and culturing with selective media has played a crucial role in the detection of pathogenic microorganisms and the isolation of commercially useful microorganisms from environmental samples. Although numerous selective media have been developed in empirical studies, unintended microorganisms often grow on such media probably due to the enormous numbers of microorganisms in the environment. Here, we present a novel strategy for designing highly selective media based on two selective agents, a carbon source and antimicrobials. We named our strategy SMART for highly Selective Medium-design Algorithm Restricted by Two constraints. To test whether the SMART method is applicable to a wide range of microorganisms, we developed selective media for Burkholderia glumae, Acidovorax avenae, Pectobacterium carotovorum, Ralstonia solanacearum, and Xanthomonas campestris. The series of media developed by SMART specifically allowed growth of the targeted bacteria. Because these selective media exhibited high specificity for growth of the target bacteria compared to established selective media, we applied three notable detection technologies: paper-based, flow cytometry-based, and color change-based detection systems for target bacteria species. SMART facilitates not only the development of novel techniques for detecting specific bacteria, but also our understanding of the ecology and epidemiology of the targeted bacteria

Opposing Role of NMDA Receptor GluN2B and GluN2D in Somatosensory Development and Maturation

Development of correct topographical connections between peripheral receptors and central somatosensory stations requires activity-dependent synapse refinement, in which the NMDA type of glutamate receptors plays a key role. Here we compared functional roles of GluN2B (GluR epsilon 2 or NR2B) and GluN2D (GluR epsilon 4 or NR2D), two major regulatory subunits of neonatal NMDA receptors, in development of whisker-related patterning at trigeminal relay stations. Compared with control littermates, both the appearance of whisker-related patterning and the termination of the critical period, as assessed by unilateral infraorbital nerve transection, were delayed by nearly a day in the somatosensory cortex of GluN2B(+/-) mice but advanced by nearly a day in GluN2D(-/-) mice. Similar temporal shifts were found at subcortical relay stations in the thalamus and brainstem of GluN2B(+/-) and GluN2D(-/-) mice. In comparison, the magnitude of lesion-induced critical period plasticity in the somatosensory cortex, as assessed following row-C whisker removal, was normal in both mutants. Thus, GluN2B and GluN2D play counteractive roles in temporal development and maturation of somatosensory maps without affecting the magnitude of critical period plasticity. To understand the opposing action, we then examined neuronal and synaptic expressions of the two subunits along the trigeminal pathway. At each trigeminal station, GluN2B was predominant at asymmetrical synapses of non-GABAergic neurons, whereas GluN2D was selective to asymmetrical synapses of GABAergic neurons. Together, our findings suggest that GluN2B expressed at glutamatergic synapses on glutamatergic projection neurons facilitates refinement of ascending pathway synapses directly, whereas GluN2D expressed at glutamatergic synapses on GABAergic interneurons delays it indirectly

Safety and immunogenicity of a 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A Phase I study (V114-028)

This Phase I study evaluated the safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine (PCV), via subcutaneous (SC) or intramuscular (IM) administration, in healthy Japanese infants 3 months of age. A total of 133 participants were randomized to receive four doses (3 + 1 regimen) of V114-SC (n = 44), V114-IM (n = 45), or 13-valent PCV (PCV13)-SC (n = 44) at 3, 4, 5, and 12–15 months of age. Diphtheria, tetanus, and pertussis–inactivated poliovirus (DTaP–IPV) vaccine was administered concomitantly at all vaccination visits. The primary objective was to assess the safety and tolerability of V114-SC and V114-IM. Secondary objectives were to assess the immunogenicity of PCV and DTaP–IPV at 1-month post-dose 3 (PD3). On days 1–14 following each vaccination, the proportions of participants with systemic adverse events (AEs) were comparable across interventions, whereas injection-site AEs were higher with V114-SC (100.0%) and PCV13-SC (100.0%) than with V114-IM (88.9%). Most AEs were mild or moderate in severity and no vaccine-related serious AEs or deaths were reported. Serotype-specific immunoglobulin G (IgG) response rates at 1-month PD3 were comparable across groups for most shared serotypes between V114 and PCV13. For additional V114 serotypes 22F and 33F, IgG response rates were higher with V114-SC and V114-IM than with PCV13-SC. DTaP–IPV antibody response rates at 1-month PD3 for V114-SC and V114-IM were comparable with PCV13-SC. Findings suggest that vaccination with V114-SC or V114-IM in healthy Japanese infants is generally well tolerated and immunogenic

Preemptive anti-cytomegalovirus therapy in high-risk (donor-positive, recipient-negative cytomegalovirus serostatus) kidney transplant recipients

Objectives: Universal prophylaxis and preemptive therapy are used to prevent cytomegalovirus (CMV) disease post-transplantation. Data regarding which strategy is superior are sparse, especially in high-risk recipients (donor CMV seropositive (D+) and recipient CMV seronegative (Râ)). Methods: This retrospective, single-center cohort study included recipients who underwent kidney transplantation between 2009 and 2015. The incidence of CMV infection/disease and patient and graft outcomes were analyzed and compared between high-risk recipients (D+/Râ) and intermediate-risk recipients (D+/R+ or Dâ/R+), all managed with preemptive therapy. Results: Of 118 kidney transplant recipients, 21 were high-risk and 97 were intermediate-risk. Over a median follow-up period of 3 years, asymptomatic CMV infection developed significantly more frequently in high-risk patients than in intermediate-risk patients (38.1% vs. 16.5%, p = 0.04), and CMV disease developed in a similar manner (28.6% vs. 3.1%, p < 0.01). Among high-risk patients, CMV infection developed within the first 3 months post-transplantation and CMV disease within the first 9 months post-transplantation. KaplanâMeier analysis showed no difference in the probability of mortality (log-rank p = 0.63) or graft loss (log-rank p = 0.50) between the patient groups. Graft rejection occurred more frequently in high-risk than in intermediate-risk patients, but the difference was not significant (log-rank p = 0.24). Conclusions: These results suggest that further studies on universal prophylaxis in high-risk patients are needed to elucidate whether preventing CMV infection/disease during the early post-transplant period leads to better outcomes, especially in terms of reducing graft rejection. Keywords: Cytomegalovirus, Prophylaxis, Preemptive therapy, Kidney transplantation, Acute rejectio