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An abstract of the article "Role of Intestinal Microbiota in Shaping the B Cell Repertoire in HIV Infection and Env Vaccination" by Nathan Vandergrift, G. D. Tomaras, D. J. Marshall, and colleagues is presented.

The potential performance of a hypothetical colloidal-activated carbon (CAC) in situ remedy for perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS) in groundwater in coastal zones was evaluated using estimated hydrogeologic and geochemical parameters for a coastal site in the United States. With these parameters, a reactive transport model (ISR-MT3DMS) was used to assess the effects of tidal fluctuations and near-shore geochemistry on CAC performance. The average near-shore ionic strength of 84 mM at the site was conservatively estimated to result in an increase in the adsorption of PFOA to CAC by about 50% relative to non-coastal sites with ionic strength <10 mM. The modeling also confirmed the hypothesis that tidally induced groundwater flow reversals near the shore would result in the accumulation of PFOA at the downgradient edge of the CAC zone. Slow desorption of PFOA from this downgradient CAC boundary may sustain downgradient plume concentrations above a strict cleanup criterion (e.g., USEPA MCL of 0.004 μg/L), for decades; however, there was still a large PFOA mass flux reduction (>99.9%) achieved after several decades at the shore. CAC longevity was substantially greater for PFOS with a similar source concentration; however, the higher PFOS distribution coefficient (K d ) in soil downgradient from the CAC zone resulted in substantially longer flushing times. It is recommended that short-term remedial action objectives for CAC remedies at coastal sites be based on mass flux reduction targets over a period of several decades, given the demonstrated challenges in trying to achieve very low cleanup criteria downgradient of a CAC zone in the short term., (© 2024 The Author(s). Groundwater published by Wiley Periodicals LLC on behalf of National Ground Water Association.)

Background: Minnesota enacted legislation in 2007 that requires all health care providers in the state to implement an interoperable electronic health record (EHR) system by 2015. 100% of hospitals and 98% of clinics had adopted EHR systems by end of 2015. Minnesota's 2008 health reform included a health care home (HCH) program, Minnesota's patient centered medical home. By end of 2014, 43% of HCH eligible clinics were certified with 335 certified HCHs and 430 eligible but not certified clinics., Objectives: To study the association between adoption and use of EHRs in primary care clinics and HCH certification, including use of clinical decision support tools, patient registries, electronic exchange of patient information, and availability of patient portals., Methods: Study utilized data from the 2015 Minnesota Health Information Technology Clinic Survey conducted annually by the Minnesota Department of Health. The response rate was 80% with 1,181 of 1,473 Minnesota clinics, including 662 HCH eligible primary care clinics. The comparative analysis focused on certified HCHs (311) and eligible but not certified clinics (351)., Results: HCH clinics utilized the various tools of EHR technology at a higher rate than non-HCH clinics. This greater utilization was noted across a range of functionalities: clinical decision support, patient disease registries, EHR to support quality improvement, electronic exchange of summary care records and availability of patient portals. HCH certification was significant for clinical decision support tools, registries and quality improvement., Conclusions: HCH requirements of care management, care coordination and quality improvement can be better supported with EHR technology, which underscores the higher rate of utilization of EHR tools by HCH clinics. Optimizing electronic exchange of health information remains a challenge for all clinics, including HCH certified clinics. This research presents the synergy between complementary initiatives supporting EHR adoption and HCH certification. Ultimately, improvement in health outcomes depends on effective intersection of people, processes and technology.

Enhancement of HIV-specific immunity is likely required to eliminate latent HIV infection. Here, we have developed an immunotherapeutic modality aimed to improve T cell-mediated clearance of HIV-1-infected cells. Specifically, we employed Dual-Affinity Re-Targeting (DART) proteins, which are bispecific, antibody-based molecules that can bind 2 distinct cell-surface molecules simultaneously. We designed DARTs with a monovalent HIV-1 envelope-binding (Env-binding) arm that was derived from broadly binding, antibody-dependent cellular cytotoxicity-mediating antibodies known to bind to HIV-infected target cells coupled to a monovalent CD3 binding arm designed to engage cytolytic effector T cells (referred to as HIVxCD3 DARTs). Thus, these DARTs redirected polyclonal T cells to specifically engage with and kill Env-expressing cells, including CD4+ T cells infected with different HIV-1 subtypes, thereby obviating the requirement for HIV-specific immunity. Using lymphocytes from patients on suppressive antiretroviral therapy (ART), we demonstrated that DARTs mediate CD8+ T cell clearance of CD4+ T cells that are superinfected with the HIV-1 strain JR-CSF or infected with autologous reservoir viruses isolated from HIV-infected-patient resting CD4+ T cells. Moreover, DARTs mediated CD8+ T cell clearance of HIV from resting CD4+ T cell cultures following induction of latent virus expression. Combined with HIV latency reversing agents, HIVxCD3 DARTs have the potential to be effective immunotherapeutic agents to clear latent HIV-1 reservoirs in HIV-infected individuals.

Background: Immunization information systems (IIS) operate in an evolving health care landscape with technology changes driven by initiatives such as the Centers for Medicare and Medicaid Services EHR incentive program, promoting adoption and use of electronic health record (EHR) systems, including standards-based public health reporting. There is flux in organizational affiliations to support models such as accountable care organizations (ACO). These impact institutional structure of how reporting of immunizations occurs and the methods adopted., Objectives: To evaluate the technical and organizational characteristics of healthcare provider reporting of immunizations to public health in Minnesota and to assess the adoption of standardized codes, formats and transport., Methods: Data on organizations and reporting status was obtained from Minnesota IIS (Minnesota Immunization Information Connection: MIIC) by collating information from existing lists, specialized queries and review of annual reports. EHR adoption data of clinics was obtained in collaboration with informatics office supporting the Minnesota e-Health Initiative. These data from various sources were merged, checked for quality to create a current state assessment of immunization reporting and results validated with subject matter experts., Results: Standards-based reporting of immunizations to MIIC increased to 708 sites over the last 3 years. A growth in automated real-time reporting occurred in 2013 with 143 new sites adopting the method. Though the uptake of message standards (HL7) has increased, the adoption of current version of HL7 and web services transport remains low. The EHR landscape is dominated by a single vendor (used by 40% of clinics) in the state. There is trend towards centralized reporting of immunizations with an organizational unit reporting for many sites ranging from 4 to 140 sites., Conclusion: High EHR adoption in Minnesota, predominance of a vendor in the market, and centralized reporting models present opportunities for better interoperability and also adaptation of strategies to fit this landscape. It is essential for IIS managers to have a good understanding of their constituent landscape for technical assistance and program planning purposes.

Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In 2007, Minnesota passed a law requiring all health care providers in the state to implement an interoperable electronic health record (EHR) system by January 1, 2015. Since then, the Minnesota Department of Health has been monitoring progress each year by surveying hospitals, clinics and other health and health care facilities about their EHR use. This article summarizes findings from the 2013 survey of ambulatory clinics. Those results show Minnesota clinics are well on the way to achieving the state's goals for using EHRs to exchange information: 87% of clinics have adopted EHRs, 80% routinely use medication guides and alerts, and 36% exchange health information with unaffiliated settings.

Background: HIV-1-infected individuals with higher viral set points progress to AIDS more rapidly than those with lower set points. Predicting viral set point early following infection can contribute to our understanding of early control of HIV-1 replication, to predicting long-term clinical outcomes, and to the choice of optimal therapeutic regimens., Methods: In a longitudinal study of 10 untreated HIV-1-infected patients, we used gene expression profiling of peripheral blood mononuclear cells to identify transcriptional networks for viral set point prediction. At each sampling time, a statistical analysis inferred the optimal transcriptional network that best predicted viral set point. We then assessed the accuracy of this transcriptional model by predicting viral set point in an independent cohort of 10 untreated HIV-1-infected patients from Malawi., Results: The gene network inferred at time of enrollment predicted viral set point 24 weeks later in the independent Malawian cohort with an accuracy of 87.5%. As expected, the predictive accuracy of the networks inferred at later time points was even greater, exceeding 90% after week 4. The composition of the inferred networks was largely conserved between time points. The 12 genes comprising this dynamic signature of viral set point implicated the involvement of two major canonical pathways: interferon signaling (p<0.0003) and membrane fraction (p<0.02). A silico knockout study showed that HLA-DRB1 and C4BPA may contribute to restricting HIV-1 replication., Conclusions: Longitudinal gene expression profiling of peripheral blood mononuclear cells from patients with acute HIV-1 infection can be used to create transcriptional network models to early predict viral set point with a high degree of accuracy.

Broadly neutralizing antibodies to the CD4 binding site (CD4bs) of gp120 are generated by some HIV-1-infected individuals, but little is known about the prevalence and evolution of this antibody response during the course of HIV-1 infection. We analyzed the sera of 113 HIV-1 seroconverters from three cohorts for binding to a panel of gp120 core proteins and their corresponding CD4bs knockout mutants. Among sera collected between 99 and 258 weeks post-HIV-1 infection, 88% contained antibodies to the CD4bs and 47% contained antibodies to resurfaced stabilized core (RSC) probes that react preferentially with broadly neutralizing CD4bs antibodies (BNCD4), such as monoclonal antibodies (MAbs) VRC01 and VRC-CH31. Analysis of longitudinal serum samples from a subset of 18 subjects revealed that CD4bs antibodies to gp120 arose within the first 4 to 16 weeks of infection, while the development of RSC-reactive antibodies was more varied, occurring between 10 and 152 weeks post-HIV-1 infection. Despite the presence of these antibodies, serum neutralization mediated by RSC-reactive antibodies was detected in sera from only a few donors infected for more than 3 years. Thus, CD4bs antibodies that bind a VRC01-like epitope are often induced during HIV-1 infection, but the level and potency required to mediate serum neutralization may take years to develop. An improved understanding of the immunological factors associated with the development and maturation of neutralizing CD4bs antibodies during HIV-1 infection may provide insights into the requirements for eliciting this response by vaccination.

Objectives: This report presents state-level estimates of the percentage of adults and children living in households that did not have a landline telephone but did have at least one wireless telephone. National estimates for the 12-month time period from July 2009 through June 2010 indicate that 23.9% of adults and 27.5% of children were living in these wireless-only households. Estimates are also presented for selected U.S. counties and groups of counties, for other household telephone service use categories (e.g., those that had only landlines and those that had landlines yet received all or almost all calls on wireless telephones), and for 12-month time periods since January-December 2007., Methods: Small-area statistical modeling techniques were used to estimate the prevalence of adults and children living in households with various household telephone service types for 93 disjoint geographic areas that make up the entire United States. This modeling was based on January 2007-June 2010 data from the National Health Interview Survey, 2006-2009 data from the American Community Survey, and auxiliary information on the number of listed telephone lines per capita in 2007-2010., Results: The prevalence of wireless-only adults and children varied substantially across states. State-level estimates for July 2009-June 2010 ranged from 12.8% (Rhode Island and New Jersey) to 35.2% (Arkansas) of adults and from 12.6% (Connecticut and New Jersey) to 46.2% (Arkansas) of children. For adults, the magnitude of the increase from 2007 to 2010 was lowest in New Jersey (7.2 percentage points) and highest in Arkansas (14.5 percentage points).

Objectives: This report presents state-level estimates of the percentage of households that do not have a landline telephone, but do have at least one wireless telephone. These wireless-only households made up 14.7% of U.S. households in 2007. The report also presents state-level estimates of the percentage of adults living in wireless-only households. These wireless-only adults made up 13.6% of U.S. adults in 2007., Methods: A two-sample modeling strategy was used to estimate the prevalence of wireless-only households and adults by state. This modeling was based on data from the 2007 National Health Interview Survey and the 2008 Current Population Survey's Annual and Social Economic Supplement., Results: The results show that the prevalence of wireless-only households and adults in 2007 varied substantially across states. State-level estimates ranged from 5.1% (Vermont) to 26.2% (Oklahoma) of households and from 4.0% (Delaware) to 25.1% (Oklahoma) of adults. In addition, approximately one out of four adults (25.4%) living in the District of Columbia were wireless-only.

Accidental hydrofluoric acid (HF) splashes often occur in industrial settings. HF easily penetrates into tissues by initial acid action allowing fluoride ions to penetrate deeply, chelating calcium and magnesium. Resultant hypocalcemia and hypomagnesemia can be fatal. This report describes the utilization of Hexafluorine--a hypertonic, amphoteric, chelating decontamination solution--in workplaces where water decontamination followed by calcium gluconate inunction failed to prevent HF burns and systemic toxicity. Between 1998 and 1999, 16 cases of ocular and dermal HF splashes with either 70% HF or 6% HF/15% nitric acid (HNO3) were decontaminated with Hexafluorine at the worksite. HF burns did not develop and medical treatment other than initial decontamination was not reQuired in 12/16 (75%). In 7/16 (44%) cases, lost work time corresponded to duration of hospital observation (mean < 1 d).

Herpes simplex virus (HSV) type 2 infection occurs primarily at the genital mucosal surfaces and is a leading cause of ulcerative lesions. Despite the availability of animal models for HSV-2 infection, little is known regarding the mechanism of immune induction within the vaginal mucosa. Here, we examined the cell types responsible for the initiation of protective Th1 immunity to HSV-2. Intravaginal inoculation of HSV-2 led to a rapid recruitment of submucosal dendritic cells (DCs) to the infected epithelium. Subsequently, CD11c(+) DCs harboring viral peptides in the context of MHC class II molecules emerged in the draining lymph nodes and were found to be responsible for the stimulation of IFNgamma secretion from HSV-specific CD4(+) T cells. Other antigen-presenting cells including B cells and macrophages did not present viral peptides to T cells in the draining lymph nodes. Next, we assessed the relative contribution to immune generation by the Langerhans cells in the vaginal epithelium, the submucosal CD11b(+) DCs, and the CD8alpha(+) lymph node DCs. Analysis of these DC populations from the draining lymph nodes revealed that only the CD11b(+) submucosal DCs, but not Langerhans cell-derived or CD8alpha(+) DCs, presented viral antigens to CD4(+) T cells and induced IFNgamma secretion. These results demonstrate a previously unanticipated role for submucosal DCs in the generation of protective Th1 immune responses to HSV-2 in the vaginal mucosa, and suggest their importance in immunity to other sexually transmitted diseases.

A recombinant simian immunodeficiency virus (SIV) derived from strain 239 (SIVmac239) with reverse transcriptase (RT) sequences from human immunodeficiency virus type 1 (HIV-1) strain HXB2 was severely impaired for replication. Detectable p27(Gag) levels were not observed until day 65 and peak p27(Gag) levels were not reached until day 75 after transfection of CEMx174 cells with the recombinant DNA. Sequences from the latter time point did not contain amino acid substitutions in HIV-1 RT; however, a single nucleotide substitution (thymine to cytosine) was found at position eight of the SIV primer binding site. We engineered an RT/SHIV genome with the thymine-to-cytosine substitution, called RT/SHIV/TC, and observed dramatically faster replication kinetics than were observed with the parental RT/SHIV from which this variant was derived. RT/SHIV/TC provides an improved system for study of the impact of drug resistance mutations in HIV-1 RT in a relevant animal model.

Background: Based on the current understanding that venous thrombosis starts perioperatively, administration of just-in-time low-molecular-weight heparin immediately before or in close proximity after hip arthroplasty may be more effective than usual clinical practice., Methods: We performed a randomized, double-blind trial comparing subcutaneous dalteparin sodium given once daily immediately before or early after surgery with the use of postoperative warfarin sodium in 1472 patients undergoing elective hip arthroplasties. The primary end point was deep vein thrombosis detected using contrast venography performed after surgery (mean, 5. 7 days) in each group., Results: The frequencies of deep vein thrombosis for patients with interpretable venograms receiving preoperative and postoperative dalteparin for all deep vein thrombosis were 36 (10.7%) of 337 (P<.001) and 44 (13.1%) of 336 (P<.001), respectively, vs 81 (24.0%) of 338 for warfarin; for proximal deep vein thrombosis, 3 (0.8%) of 354 (P =.04) and 3 (0.8%) of 358 (P =.03), respectively, vs 11 (3.0%) of 363. Relative risk reductions for the dalteparin groups ranged from 45% to 72%. Symptomatic thrombi were less frequent in the preoperative dalteparin group (5/337 patients [1.5%]) vs the warfarin group (15/338 patients [4.4%]) (P =.02). Serious bleeding was similar among groups. Increased major bleeding at the surgical site was observed for patients receiving preoperative dalteparin vs warfarin (P =.01)., Conclusions: A modified dalteparin regimen in close proximity to surgery resulted in substantive risk reductions for all and proximal deep vein thrombosis, compared with warfarin therapy. Such findings have not been observed with low-molecular-weight heparin therapy commenced 12 hours preoperatively or 12 to 24 hours postoperatively vs oral anticoagulants. Increased major but not serious bleeding occurred in patients receiving preoperative dalteparin. Dalteparin therapy initiated postoperatively provided superior efficacy vs warfarin without significantly increased overt bleeding.

Background: No randomized trials have directly evaluated the need for extended out-of-hospital thromboprophylaxis for patients who have hip arthroplasty in the United States or Canada. The uncertainty as to the need for extended prophylaxis in North American patients is complicated by early hospital discharge, resulting in a short thromboprophylaxis interval., Methods: To resolve this uncertainty, we performed a randomized double-blind trial in 569 patients who underwent hip arthroplasty comparing the use of dalteparin sodium started immediately before surgery or early after surgery and extended out-of-hospital to an overall interval of 35 days with the use of warfarin sodium in-hospital and placebo out-of-hospital., Results: For patients with interpretable venograms in the preoperative, postoperative, and combined dalteparin groups, new proximal vein thrombosis out-of-hospital was observed in 1.3%, 0. 7% (P =.04), and 1.0% (P =.02) of patients, respectively, compared with 4.8% in the in-hospital warfarin/out-of-hospital placebo group. The respective overall cumulative frequencies of all deep vein thrombosis were 30 (17.2%) of 174 patients (P<.001), 38 (22.2%) of 171 (P =.003), and 68 (19.7%) of 345 (P<.001) in the dalteparin groups compared with 69 (36.7%) of 188 for the in-hospital warfarin/out-of-hospital placebo group. For proximal deep vein thrombosis, the respective frequencies were 5 (3.1%) of 162 (P =.02), 3 (2.0%) of 151 (P =.007), and 8 (2.6%) of 313 (P =.002) compared with 14 (9.2%) of 153. No major bleeding occurred during the extended prophylaxis interval., Conclusions: Extended dalteparin prophylaxis resulted in significantly lower frequencies of deep vein thrombosis compared with in-hospital warfarin therapy. Despite in-hospital thromboprophylaxis, patients having hip arthroplasty in the United States and Canada remain at moderate risk out-of-hospital. The number needed to treat provides a public health focus; only 24 to 28 patients require extended prophylaxis to prevent 1 new out-of-hospital proximal vein thrombosis. Recent studies demonstrate that asymptomatic deep vein thrombi cause the postphlebitic syndrome; thus, extended out-of-hospital prophylaxis will lessen the burden to both the patient and society.

Objective: This study aimed to investigate the occurrence of an "open" form of congenital cholesteatoma to facilitate better understanding of the different histopathologic forms and their differing clinical presentations., Study Design: Retrospective case review., Setting: Tertiary referral center., Patients: Ten patients diagnosed with congenital cholesteatoma, that is, a white "pearl" behind an intact tympanic membrane with no history of trauma, ear surgery, perforation, or otorrhea., Main Outcome Measures: Audiometry, high-resolution computed tomography scan of the temporal bones and intraoperative findings., Results: Two of 10 patients had lesions located in the anterosuperior quadrant of the mesotympanum. Four patients had lesions involving the entire middle ear cleft. Four patients had lesions in the posterosuperior quadrant. Seven of the patients were found to have a typical "closed" cyst, whereas the remaining three patients showed an open cholesteatoma matrix., Conclusions: Apparently, there are two types of congenital middle ear cholesteatoma: a closed keratotic cyst and an open matrix. Patients with open cholesteatomas may have a clinical presentation that is uniquely different from the classical description of congenital cholesteatoma.

The relationships among 93 strains of Pseudomonas fluorescens were investigated by (1) a numerical taxonomic analysis on the results of 150 phenotypic tests, (2) DNA hybridization studies using 16 reference strains, (3) quantitative microcomplement fixation studies using six reference strains with antibodies directed against the protein azurin. In general, the strains fell into distinct clusters. Assignment to these clusters on the basis of azurin immunological similarity showed 98% agreement with assignment based on DNA homology, suggesting that many genes will follow the same pattern. Of the strains that clustered on the basis of genotype (DNA, azurin) 88% also clustered on the basis of phenotype. The occasional noncongruency observed between the genotypic and phenotypic data may be due to the variable rates of phenotypic evolution. These results provide a perspective on the roles of horizontal and vertical transfer of genes in the evolution of this bacterial group.