Enhanced biomaterials: systematic review of alternatives to supplement spine fusion including silicon nitride, bioactive glass, amino peptide bone graft, and tantalum.

OBJECTIVE: Spinal fusions are among the most common and effective spinal surgical practices; however, the current model presents some cost and safety concerns within the patient population. Therefore, enhanced biomaterials have been presented to be an innovative yet underutilized tool to supplement the success of spinal fusion surgery. Herein, the authors discuss these biomaterials, their compositions, clinical outcomes, and cost analysis through a systematic review of the literature to date. METHODS: This systematic review was conducted using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) criteria and guidelines. Article selection was performed using the PubMed electronic bibliographic databases. The search yielded 1168 articles that were assessed and filtered for relevance by the four authors. Following the screening of titles and abstracts, 62 articles were deemed significant enough for final selection. RESULTS: To date, silicon nitride, bioactive glass, amino peptide bone grafts, and tantalum are all biomaterials that could have significant roles in supporting spinal fusion. Their unique compositions allow them to be biocompatible in the spine, and their mechanisms of action stimulate osteoblast formation and support fusion success. Moreover, these biomaterials also present positive clinical and cost outcomes that support their application in spinal procedures. However, further studies with longer follow-ups are necessary to fully understand these biomaterials prior to their incorporation in mainstream spinal practice. CONCLUSIONS: The combination of their positive clinical outcomes, biocompatibility, and cost-effectiveness makes these biomaterials valuable, innovative, and effective treatment modalities that could revolutionize the current model of spinal fusion.

Both Handwashing and an Alcohol-Based Hand Sanitizer Intervention Reduce Soil and Microbial Contamination on Farmworker Hands during Harvest, but Produce Type Matters.

Hand hygiene interventions are critical for reducing farmworker hand contamination and preventing the spread of produce-associated illness. Hand hygiene effectiveness may be produce-commodity specific, which could influence implementation strategies. This study's goal was to determine if produce commodity influences the ability of handwashing with soap and water or two-step alcohol-based hand sanitizer (ABHS) interventions to reduce soil and bacteria on farmworker hands. Farmworkers (n = 326) harvested produce (cantaloupe, jalapeño, and tomato) for 30 to 90 minutes before engaging in handwashing, two-step ABHS (jalapeño and cantaloupe), or no hand hygiene. Hands were rinsed to measure amounts of soil (absorbance at 600 nm) and indicator bacteria (coliforms, Enterococcus sp., generic Escherichia coli, and Bacteroidales universal [AllBac] and human-specific [BFD] 16S rRNA gene markers). Without hand hygiene, bacterial concentrations (0.88 to 5.1 log10 CFU/hand) on hands significantly differed by the produce commodity harvested. Moderate significant correlations (ρ = -0.41 to 0.56) between soil load and bacterial concentrations were observed. There were significant produce-commodity-specific differences in the ability of handwashing and two-step ABHS interventions to reduce soil (P < 0.0001), coliforms (P = 0.002), and Enterococcus sp. (P = 0.003), but not the Bacteroidales markers AllBac (P = 0.4) or BFD (P = 0.3). Contamination on hands of farmworkers who harvested cantaloupe was more difficult to remove. Overall, we found that a two-step ABHS intervention was similar to handwashing with soap and water at reducing bacteria on farmworker hands. In summary, produce commodity type should be considered when developing hand hygiene interventions on farms.IMPORTANCE This study demonstrated that the type of produce commodity handled influences the ability of handwashing with soap and water or a two-step alcohol-based hand sanitizer (ABHS) intervention to reduce soil and bacterial hand contamination. Handwashing with soap and water, as recommended by the FDA's Produce Safety Rule, when tested in three agricultural environments, does not always reduce bacterial loads. Consistent with past results, we found that the two-step ABHS method performed similarly to handwashing with soap and water but also does not always reduce bacterial loads in these contexts. Given the ease of use of the two-step ABHS method, which may increase compliance, the two-step ABHS method should be further evaluated and possibly considered for implementation in the agricultural environment. Taken together, these results provide important information on hand hygiene effectiveness in three agricultural contexts.

Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys.

The viral reservoir represents a critical challenge for human immunodeficiency virus type 1 (HIV-1) eradication strategies. However, it remains unclear when and where the viral reservoir is seeded during acute infection and the extent to which it is susceptible to early antiretroviral therapy (ART). Here we show that the viral reservoir is seeded rapidly after mucosal simian immunodeficiency virus (SIV) infection of rhesus monkeys and before systemic viraemia. We initiated suppressive ART in groups of monkeys on days 3, 7, 10 and 14 after intrarectal SIVMAC251 infection. Treatment with ART on day 3 blocked the emergence of viral RNA and proviral DNA in peripheral blood and also substantially reduced levels of proviral DNA in lymph nodes and gastrointestinal mucosa as compared with treatment at later time points. In addition, treatment on day 3 abrogated the induction of SIV-specific humoral and cellular immune responses. Nevertheless, after discontinuation of ART following 24 weeks of fully suppressive therapy, virus rebounded in all animals, although the monkeys that were treated on day 3 exhibited a delayed viral rebound as compared with those treated on days 7, 10 and 14. The time to viral rebound correlated with total viraemia during acute infection and with proviral DNA at the time of ART discontinuation. These data demonstrate that the viral reservoir is seeded rapidly after intrarectal SIV infection of rhesus monkeys, during the 'eclipse' phase, and before detectable viraemia. This strikingly early seeding of the refractory viral reservoir raises important new challenges for HIV-1 eradication strategies.

Neutralizing Antibody Responses following Long-Term Vaccination with HIV-1 Env gp140 in Guinea Pigs.

A vaccination regimen capable of eliciting potent and broadly neutralizing antibodies (bNAbs) remains an unachieved goal of the HIV-1 vaccine field. Here, we report the immunogenicity of longitudinal prime/boost vaccination regimens with a panel of HIV-1 envelope (Env) gp140 protein immunogens over a period of 200 weeks in guinea pigs. We assessed vaccine regimens that included a monovalent clade C gp140 (C97ZA012 [C97]), a tetravalent regimen consisting of four clade C gp140s (C97ZA012, 459C, 405C, and 939C [4C]), and a tetravalent regimen consisting of clade A, B, C, and mosaic gp140s (92UG037, PVO.4, C97ZA012, and Mosaic 3.1, respectively [ABCM]). We found that the 4C and ABCM prime/boost regimens were capable of eliciting greater magnitude and breadth of binding antibody responses targeting variable loop 2 (V2) over time than the monovalent C97-only regimen. The longitudinal boosting regimen conducted over more than 2 years increased the magnitude of certain tier 1 NAb responses but did not increase the magnitude or breadth of heterologous tier 2 NAb responses. These data suggest that additional immunogen design strategies are needed to induce broad, high-titer tier 2 NAb responses.IMPORTANCE The elicitation of potent, broadly neutralizing antibodies (bNAbs) remains an elusive goal for the HIV-1 vaccine field. In this study, we explored the use of a long-term vaccination regimen with different immunogens to determine if we could elicit bNAbs in guinea pigs. We found that longitudinal boosting over more than 2 years increased tier 1 NAb responses but did not increase the magnitude and breadth of tier 2 NAb responses. These data suggest that additional immunogen designs and vaccination strategies will be necessary to induce broad tier 2 NAb responses.

A qualitative investigation of policy for youth with problematic sexual behavior.

AIMS: Community management of youth with problematic sexual behavior (PSB) is complex. Public policies and service practices have historically utilized adult-focused approaches with limited research outcomes. This descriptive case study aimed to address this gap by documenting current PSB policies and policy reforms for community-based management systems. METHOD: Semi-structured interviews with 219 professionals from eight urban and rural communities throughout the United States served as the primary data source for the study. The three-stage Framework Method was used to guide the data analysis process. RESULTS: This study covered three areas: context of policy development, attitudes, and perceptions of policy for youth with PSB, and existing policy and policy reform initiatives. CONCLUSION: Findings support benefits of collaborative multidisciplinary teams that cross agency policies and procedures on management of cases involving youth with PSB. Implications for practitioners, policymakers, and community members are discussed.

Emissions During and Real-world Frequency of Heavy-duty Diesel Particulate Filter Regeneration.

Recent tightening of particulate matter (PM) emission standards for heavy-duty engines has spurred the widespread adoption of diesel particulate filters (DPFs), which need to be regenerated periodically to remove trapped PM. The total impact of DPFs therefore depends not only on their filtering efficiency during normal operation, but also on the emissions during and the frequency of regeneration events. We performed active (parked and driving) and passive regenerations on two heavy-duty diesel vehicles (HDDVs), and report the chemical composition of emissions during these events, as well as the efficiency with which trapped PM is converted to gas-phase products. We also collected activity data from 85 HDDVs to determine how often regeneration occurs during real-world operation. PM emitted during regeneration ranged from 0.2 to 16.3 g, and the average time and distance between real-world active regenerations was 28.0 h and 599 miles. These results indicate that regeneration of real-world DPFs does not substantially offset the reduction of PM by DPFs during normal operation. The broad ranges of regeneration frequency per truck (3-100 h and 23-4078 miles) underscore the challenges in designing engines and associated aftertreatments that reduce emissions for all real-world duty cycles.

A Qualitative Evaluation of Engagement and Attrition in a Nurse Home Visiting Program: From the Participant and Provider Perspective.

Beginning parenting programs in the prenatal and early postnatal periods have a large potential for impact on later child and maternal outcomes. Home-based parenting programs, such as the Nurse Family Partnership (NFP), have been established to help address this need. Program reach and impact is dependent on successful engagement of expecting mothers with significant risks; however, NFP attrition rates remain high. The current study qualitatively examined engagement and attrition from the perspectives of NFP nurses and mothers in order to identify mechanisms that enhance service engagement. Semi-structured interviews were conducted in focus groups composed of either engaged (27 total mothers) or unengaged (15 total mothers) mothers from the NFP program. NFP nurses (25 total nurses) were recruited for individual semi-structured interviews. Results suggest that understanding engagement in the NFP program requires addressing both initial and sustained engagement. Themes associated with enhanced initial engagement include nurse characteristics (e.g., flexible, supportive, caring) and establishment of a solid nurse-family relationship founded on these characteristics. Factors impacting sustained engagement include nurse characteristics, provision of educational materials on child development, individualized services for families, and available family support. Identified barriers to completing services include competing demands and lack of support. Findings of this study have direct relevance for workforce planning, including hiring and training through integrating results regarding effective nurse characteristics. Additional program supports to enhance parent engagement may be implemented across home-based parenting programs in light of the current study's findings.

A multivalent clade C HIV-1 Env trimer cocktail elicits a higher magnitude of neutralizing antibodies than any individual component.

UNLABELLED: The sequence diversity of human immunodeficiency virus type 1 (HIV-1) presents a formidable challenge to the generation of an HIV-1 vaccine. One strategy to address such sequence diversity and to improve the magnitude of neutralizing antibodies (NAbs) is to utilize multivalent mixtures of HIV-1 envelope (Env) immunogens. Here we report the generation and characterization of three novel, acute clade C HIV-1 Env gp140 trimers (459C, 405C, and 939C), each with unique antigenic properties. Among the single trimers tested, 459C elicited the most potent NAb responses in vaccinated guinea pigs. We evaluated the immunogenicity of various mixtures of clade C Env trimers and found that a quadrivalent cocktail of clade C trimers elicited a greater magnitude of NAbs against a panel of tier 1A and 1B viruses than any single clade C trimer alone, demonstrating that the mixture had an advantage over all individual components of the cocktail. These data suggest that vaccination with a mixture of clade C Env trimers represents a promising strategy to augment vaccine-elicited NAb responses. IMPORTANCE: It is currently not known how to generate potent NAbs to the diverse circulating HIV-1 Envs by vaccination. One strategy to address this diversity is to utilize mixtures of different soluble HIV-1 envelope proteins. In this study, we generated and characterized three distinct, novel, acute clade C soluble trimers. We vaccinated guinea pigs with single trimers as well as mixtures of trimers, and we found that a mixture of four trimers elicited a greater magnitude of NAbs than any single trimer within the mixture. The results of this study suggest that further development of Env trimer cocktails is warranted.

Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer.

UNLABELLED: The extraordinary diversity of the human immunodeficiency virus type 1 (HIV-1) envelope (Env) glycoprotein poses a major challenge for the development of an HIV-1 vaccine. One strategy to circumvent this problem utilizes bioinformatically optimized mosaic antigens. However, mosaic Env proteins expressed as trimers have not been previously evaluated for their stability, antigenicity, and immunogenicity. Here, we report the production and characterization of a stable HIV-1 mosaic M gp140 Env trimer. The mosaic M trimer bound CD4 as well as multiple broadly neutralizing monoclonal antibodies, and biophysical characterization suggested substantial stability. The mosaic M trimer elicited higher neutralizing antibody (nAb) titers against clade B viruses than a previously described clade C (C97ZA.012) gp140 trimer in guinea pigs, whereas the clade C trimer elicited higher nAb titers than the mosaic M trimer against clade A and C viruses. A mixture of the clade C and mosaic M trimers elicited nAb responses that were comparable to the better component of the mixture for each virus tested. These data suggest that combinations of relatively small numbers of immunologically complementary Env trimers may improve nAb responses. IMPORTANCE: The development of an HIV-1 vaccine remains a formidable challenge due to multiple circulating strains of HIV-1 worldwide. This study describes a candidate HIV-1 Env protein vaccine whose sequence has been designed by computational methods to address HIV-1 diversity. The characteristics and immunogenicity of this Env protein, both alone and mixed together with a clade C Env protein vaccine, are described.

Use of Bacteroidales microbial source tracking to monitor fecal contamination in fresh produce production.

In recent decades, fresh and minimally processed produce items have been associated with an increasing proportion of food-borne illnesses. Most pathogens associated with fresh produce are enteric (fecal) in origin, and contamination can occur anywhere along the farm-to-fork chain. Microbial source tracking (MST) is a tool developed in the environmental microbiology field to identify and quantify the dominant source(s) of fecal contamination. This study investigated the utility of an MST method based on Bacteroidales 16S rRNA gene sequences as a means of identifying potential fecal contamination, and its source, in the fresh produce production environment. The method was applied to rinses of fresh produce, source and irrigation waters, and harvester hand rinses collected over the course of 1 year from nine farms (growing tomatoes, jalapeño peppers, and cantaloupe) in Northern Mexico. Of 174 samples, 39% were positive for a universal Bacteroidales marker (AllBac), including 66% of samples from cantaloupe farms (3.6 log10 genome equivalence copies [GEC]/100 ml), 31% of samples from tomato farms (1.7 log10 GEC/100 ml), and 18% of samples from jalapeño farms (1.5 log10 GEC/100 ml). Of 68 AllBac-positive samples, 46% were positive for one of three human-specific markers, and none were positive for a bovine-specific marker. There was no statistically significant correlation between Bacteroidales and generic Escherichia coli across all samples. This study provides evidence that Bacteroidales markers may serve as alternative indicators for fecal contamination in fresh produce production, allowing for determination of both general contamination and that derived from the human host.

A Comprehensive Overview of Pediatric Neoplasms at the Craniocervical Junction: Meningiomas, Schwannomas, and Chordomas.

Tumors of the craniocervical junction (CCJ) are complicated pathologies with high patient mortality or low quality of life. In the pediatric population, these tumors are less prevalent, with various symptomatic presentations that include motor and neurological manifestations. Three of the most common neoplasms at the CCJ in children are meningiomas, schwannomas, and chordomas. In this review, we will characterize the tissue biomarkers, clinical presentation, treatment methods, and surgical outcomes for these pediatric tumors at the CCJ. A comprehensive literature review was used using the PubMed Database. Keywords used were "craniocervical junction", "pediatric", "meningiomas", schwannomas", and "meningiomas". Articles that were not related to the CCJ, included only adult cases, and non-English studies were filtered. Our search yielded a total of 11 studies, with a total of 239 pediatric patients with tumors at the CCJ. These studies were broken down as five for meningiomas, one for schwannomas, and eight for chordomas. In conclusion, resection of pediatric neoplasms at the CCJ is challenging due to anatomical limitations and the size of the patient. Within the CCJ, chordomas were the most prevalent tumor type, with schwannomas being the least prevalent. Literature findings indicate that genetic mutations of the NF2 gene associated with neurofibromatosis type II, as well as incomplete tumor resection, are predictors of poor outcomes. Further developments of monoclonal antibody chemotherapy and endoscopic approaches could expand treatment options for aggressive pediatric neoplasms at the skull base.

How does COVID-19 impact intrafamilial child sexual abuse? Comparison analysis of reports by practitioners in Israel and the US.

BACKGROUND: There is consensus in child sexual abuse (CSA) literature that intrafamilial child sexual abuse (IFCSA) has a tremendous impact on children and families while simultaneously creating challenges for practitioners. COVID-19 impacted countries worldwide and generated a global crisis resulting in impacts on daily life, however, it's effect on IFCSA is unknown. OBJECTIVE: This study aimed to compare professional perspectives and experiences working with IFCSA with respect to the context of the COVID-19 pandemic within the United States and Israel. PARTICIPANTS AND SETTING: Participants were therapeutic, child welfare and legal professionals, who provided services to children involved in IFCSA. METHODS: This qualitative cross-cultural comparative study analyzes professional experiences of IFCSA during COVID-19 based on an open-ended questionnaire answered online, with 37 responses from the US and 23 responses from Israel. RESULTS: Findings reveal mostly negative changes in the dynamics of IFCSA families during COVID-19, including financial, environmental, and emotional hardships, as well as some positive changes in the relationships among family members. In terms of professional interventions, concerns were raised that COVID-19 has been detrimental to the disclosure of IFCSA, with plummeting child abuse reports. Further, risk and benefits of transferring to internet based or telephonic therapeutic interventions were shared. CONCLUSIONS: Governmental and community efforts are needed to develop a safety net of protective factors to reduce IFCSA risks and increase resiliency during the COVID-19 pandemic and future global crises. Moreover, enhanced strategies to accessing and supporting families remotely such as using technology could improve identification and response to IFCSA.

Determination and optimization of ideal patient candidacy for anterior odontoid screw fixation.

BACKGROUND: Odontoid process fractures are one of the most common spine fractures, especially in patients over age 70. There is still much controversy over the ideal candidate for anterior odontoid screw fixation (AOSF), with outcomes affected by characteristics such as fracture morphology, nonideal body habitus, and osteoporosis. Therefore, this systematic review seeks to discuss the optimal criteria, indications, and adverse postoperative considerations when deciding to pursue AOSF. METHODS: This investigation was conducted from experiential recall and article selection performed using the PubMed electronic bibliographic databases. The search yielded 124 articles that were assessed and filtered for relevance. Following the screening of titles and abstracts, 48 articles were deemed significant for final selection. RESULTS: AOSF is often utilized to treat Type IIB odontoid fractures, which has been shown to preserve atlantoaxial motion, limit soft-tissue injuries/blood loss/vertebral artery injury/reduce operative time, provide adequate osteosynthesis, incur immediate spinal stabilization, and allow motion preservation of C1 and C2. However, this technique is limited by patient characteristics such as fracture morphology, transverse ligament rupture, remote injuries, short neck or inability to extend neck, barrel chested, and severe spinal kyphosis, in addition to adverse postoperative outcomes such as dysphagia and vocal cord paralysis. CONCLUSION: Due to the fact that odontoid fractures have a significant morbidity in elderly population, treatment with AOSF is generally recommended for this population with higher risk for nonoperative fusion. Considerations should be made to achieve fracture stability and fusion, while lowering the risk for operative and postoperative complications.

Stereoelectroencephalography versus Subdural Electrode Implantation to Determine Whether Patients with Drug-resistant Epilepsy Are Candidates for Epilepsy Surgery.

Epilepsy is a chronic condition that affects about 50 million individuals worldwide. While its challenges are profound, there are increasing instances where antiepileptic drugs (AEDs) fail to provide relief to epileptic manifestations. For these pharmacoresistant cases, epilepsy surgery often is an effective route for treatment. However, the complexity and challenges associated with presurgical evaluations have prevented more widespread utilization of epilepsy surgery in pharmacoresistant cases. While preliminary work-ups and non-invasive diagnostic imaging have allowed for limited identification of the epileptogenic zone (EZ), there is yet to be an established pre-determined algorithm for surgical evaluation of patients with epilepsy. However, two modalities are currently being used for localization of the EZ and in determining candidates for surgery: stereoelectroencephalography (SEEG) and subdural electrodes (SDEs). SDE has been used in the United States for decades; however, SEEG now provides a less invasive option for mapping brain regions. We seek to address which intracranial monitoring technique is superior. Through a review of the outcomes of various clinical studies, SEEG was found to have greater safety and efficiency benefits than SDE, such as lower morbidity rates, lower prevalence of neurological deficits, and shorter recovery times. Moreover, SEEG was also found to have further functional benefits by allowing for deeper targeting of cerebral tissue along with bilateral hemispheric monitoring. This has led to increased rates of seizure freedom and control among SEEG patients. Nevertheless, further studies on the limitations and advancements of SEEG and SDE are still required to provide a more comprehensive understanding regarding their application.

Fetal alcohol spectrum disorders: an overview of current evidence and activities in the UK.

Estimates for the UK suggest that alcohol consumption during pregnancy and prevalence of fetal alcohol spectrum disorder (FASD)-the most common neurodevelopmental condition-are high. Considering the significant health and social impacts of FASD, there is a public health imperative to prioritise prevention, interventions and support. In this article, we outline the current state of play regarding FASD knowledge and research in the UK, which is characterised by a lack of evidence, a lack of dedicated funding and services, and consequently little policy formulation and strategic direction. We highlight progress made to date, as well as current knowledge and service gaps to propose a way forward for UK research.

Phosphopantetheinylation and specificity of acyl carrier proteins in the mupirocin biosynthetic cluster.

Acyl carrier proteins are vital for the biosynthesis of fatty acids and polyketides. The mupirocin biosynthetic cluster of Pseudomonas fluorescens encodes eleven type I ACPs embedded in its multifunctional polyketide synthase (PKS) proteins plus five predicted type II ACPs (mAcpA-E) that are known to be essential for mupirocin biosynthesis by deletion and complementation analysis. MupN is a putative Sfp-type phosphopantetheinyl transferase. Overexpression of three type I and three type II mupirocin ACPs in Escherichia coli, with or without mupN, followed by mass spectroscopy revealed that MupN can modify both mupirocin type I and type II ACPs to their holo-form. The endogenous phosphopantetheinyl transferase of E. coli modified mAcpA but not mAcpC or D. Overexpression of the type II ACPs in macp deletion mutants of the mupirocin producer P. fluorescens 10586 showed that they cannot substitute for each other while hybrids between mAcpA and mAcpB indicated that, at least for mAcpB, the C-terminal domain determines functional specificity. Amino acid alignments identified mACPs A and D as having C-terminal extensions. Mutation of these regions generated defective ACPs, the activity of which could be restored by overexpression of the macp genes on separate plasmids.

Early identification of youth with problematic sexual behavior: A qualitative study.

BACKGROUND: Early intervention efforts designed for youth with problematic sexual behavior (PSB) have strong promise. Prompt identification of youth with PSB is critical to ensuring early intervention and effective response. OBJECTIVE: The current study explored the complexities of how PSB of youth is identified in the community. SETTING: A qualitative semi-structured interview approach was utilized to explore the perceptions and experiences of community members involved in cases of youth with PSB. PARTICIPANTS: Participants included 100 community members from eight geographically diverse locations in the United States. METHOD: Themes involving identification of PSB were classified by qualitative analyses, beginning with thematic analysis followed by focused coding. RESULTS: Results indicated multiple pathways for the identification of youth with PSB involving a variety of professionals and agencies. Victim disclosure and witnessing the PSB were the most common identification pathways, with caregivers and school personnel the most common initial identifiers. Once identified, cases were reported to child welfare, law enforcement, and/or behavioral health agencies. Complications due to unclear response pathways and fears held by caregivers were notable. CONCLUSIONS: Developmentally appropriate, evidence-informed policies and procedures for the identification of and response to PSB in youth within and across professions would facilitate a public health response to for prevention and early responses to PSB of youth.

HIV-1 Neutralizing Antibody Signatures and Application to Epitope-Targeted Vaccine Design.

Eliciting HIV-1-specific broadly neutralizing antibodies (bNAbs) remains a challenge for vaccine development, and the potential of passively delivered bNAbs for prophylaxis and therapeutics is being explored. We used neutralization data from four large virus panels to comprehensively map viral signatures associated with bNAb sensitivity, including amino acids, hypervariable region characteristics, and clade effects across four different classes of bNAbs. The bNAb signatures defined for the variable loop 2 (V2) epitope region of HIV-1 Env were then employed to inform immunogen design in a proof-of-concept exploration of signature-based epitope targeted (SET) vaccines. V2 bNAb signature-guided mutations were introduced into Env 459C to create a trivalent vaccine, and immunization of guinea pigs with V2-SET vaccines resulted in increased breadth of NAb responses compared with Env 459C alone. These data demonstrate that bNAb signatures can be utilized to engineer HIV-1 Env vaccine immunogens capable of eliciting antibody responses with greater neutralization breadth.

In vivo mutational analysis of the mupirocin gene cluster reveals labile points in the biosynthetic pathway: the "leaky hosepipe" mechanism.

A common feature of the mupirocin and other gene clusters of the AT-less polyketide synthase (PKS) family of metabolites is the introduction of carbon branches by a gene cassette that contains a beta-hydroxy-beta-methylglutaryl CoA synthase (HMC) homologue and acyl carrier protein (ACP), ketosynthase (KS) and two crotonase superfamily homologues. In vivo studies of Pseudomonas fluorescens strains in which any of these components have been mutated reveal a common phenotype in which the two major isolable metabolites are the truncated hexaketide mupirocin H and the tetraketide mupiric acid. The structure of the latter has been confirmed by stereoselective synthesis. Mupiric acid is also the major metabolite arising from inactivation of the ketoreductase (KR) domain of module 4 of the modular PKS. A number of other mutations in the tailoring region of the mupirocin gene cluster also result in production of both mupirocin H and mupiric acid. To explain this common phenotype we propose a mechanistic rationale in which both mupirocin H and mupiric acid represent the products of selective and spontaneous release from labile points in the pathway that occur at significant levels when mutations block the pathway either close to or distant from the labile points.

Immunizing Children: A Qualitative Analysis of Future Parental Decision Making.

Vaccinations are considered one of public health's greatest accomplishments. Despite evidence for vaccine effectiveness, uptake levels are still well below the Centers for Disease Control and Prevention's guidelines. The immunization decision-making process for parents is complex and depends on factors associated with knowledge and experiences. This qualitative study sought to expand on a previous decision-making model for immunizations by examining how individuals receive vaccination information, determining the role of experience in influencing decisions, and understanding how young adults might locate vaccination information in the future. Three focus groups were conducted with 29 undergraduate students without children. Results suggest that young adults exhibit an awareness of information regarding vaccine use and effectiveness, value doctor opinions and recommendations, and desire more robust research on vaccinations. Implications of these results include the importance of (1) disseminating vaccination education to young adults, (2) enhancing consistency/trust between medical professionals and youth, and (3) expanding public policy to increase vaccine uptake.