Invasive Group A Streptococcal Infection in Older Adults in Long-term Care Facilities and the Community, United States, 1998–20031

Invasive infection develops almost 6 times as frequently in the elderly in long-term care facilities

Outcome of ATP-based tumor chemosensitivity assay directed chemotherapy in heavily pre-treated recurrent ovarian carcinoma

BACKGROUND: We wished to evaluate the clinical response following ATP-Tumor Chemosensitivity Assay (ATP-TCA) directed salvage chemotherapy in a series of UK patients with advanced ovarian cancer. The results are compared with that of a similar assay used in a different country in terms of evaluability and clinical endpoints. METHODS: From November 1998 to November 2001, 46 patients with pre-treated, advanced ovarian cancer were given a total of 56 courses of chemotherapy based on in-vitro ATP-TCA responses obtained from fresh tumor samples or ascites. Forty-four patients were evaluable for results. Of these, 18 patients had clinically platinum resistant disease (relapse < 6 months after first course of chemotherapy). There was evidence of cisplatin resistance in 31 patients from their first ATP-TCA. Response to treatment was assessed by radiology, clinical assessment and tumor marker level (CA 125). RESULTS: The overall response rate was 59% (33/56) per course of chemotherapy, including 12 complete responses, 21 partial responses, 6 with stable disease, and 15 with progressive disease. Two patients were not evaluable for response having received just one cycle of chemotherapy: if these were excluded the response rate is 61%. Fifteen patients are still alive. Median progression free survival (PFS) was 6.6 months per course of chemotherapy; median overall survival (OAS) for each patient following the start of TCA-directed therapy was 10.4 months (95% confidence interval 7.9-12.8 months). CONCLUSION: The results show similar response rates to previous studies using ATP-TCA directed therapy in recurrent ovarian cancer. The assay shows high evaluability and this study adds weight to the reproducibility of results from different centre

Rectal Transmission of Transmitted/Founder HIV-1 Is Efficiently Prevented by Topical 1% Tenofovir in BLT Humanized Mice

Rectal microbicides are being developed to prevent new HIV infections in both men and women. We focused our in vivo preclinical efficacy study on rectally-applied tenofovir. BLT humanized mice (n = 43) were rectally inoculated with either the primary isolate HIV-1(JRCSF) or the MSM-derived transmitted/founder (T/F) virus HIV-1(THRO) within 30 minutes following treatment with topical 1% tenofovir or vehicle. Under our experimental conditions, in the absence of drug treatment we observed 50% and 60% rectal transmission by HIV-1(JRCSF) and HIV-1(THRO), respectively. Topical tenofovir reduced rectal transmission to 8% (1/12; log rank p = 0.03) for HIV-1(JRCSF) and 0% (0/6; log rank p = 0.02) for HIV-1(THRO). This is the first demonstration that any human T/F HIV-1 rectally infects humanized mice and that transmission of the T/F virus can be efficiently blocked by rectally applied 1% tenofovir. These results obtained in BLT mice, along with recent ex vivo, Phase 1 trial and non-human primate reports, provide a critically important step forward in the development of tenofovir-based rectal microbicides

Pooled Individual Data Analysis of 5 Randomized Trials of Infant Nevirapine Prophylaxis to Prevent Breast-Milk HIV-1 Transmission

Background. In resource-limited settings, mothers infected with human immunodeficiency virus type 1 (HIV-1) face a difficult choice: breastfeed their infants but risk transmitting HIV-1 or not breastfeed their infants and risk the infants dying of other infectious diseases or malnutrition. Recent results from observational studies and randomized clinical trials indicate daily administration of nevirapine to the infant can prevent breast-milk HIV-1 transmission

HIV-1 Drug Resistance Emergence among Breastfeeding Infants Born to HIV-Infected Mothers during a Single-Arm Trial of Triple-Antiretroviral Prophylaxis for Prevention of Mother-To-Child Transmission: A Secondary Analysis

Analysis of a substudy of the Kisumu breastfeeding trial by Clement Zeh and colleagues reveals the emergence of HIV drug resistance in HIV-positive infants born to HIV-infected mothers treated with antiretroviral drugs

Triple-Antiretroviral Prophylaxis to Prevent Mother-To-Child HIV Transmission through Breastfeeding—The Kisumu Breastfeeding Study, Kenya: A Clinical Trial

Timothy Thomas and colleagues report the results of the Kisumu breastfeeding study (Kenya), a single-arm trial that assessed the feasibility and safety of a triple-antiretroviral regimen to suppress maternal HIV load in late pregnancy

Group B <em>Streptococcus </em>engages an inhibitory siglec through sialic acid mimicry to blunt innate immune and inflammatory responses <em>in vivo</em>

Group B Streptococcus (GBS) is a common agent of bacterial sepsis and meningitis in newborns. The GBS surface capsule contains sialic acids (Sia) that engage Sia-binding immunoglobulin-like lectins (Siglecs) on leukocytes. Here we use mice lacking Siglec-E, an inhibitory Siglec of myelomonocytic cells, to study the significance of GBS Siglec engagement during in vivo infection. We found GBS bound to Siglec-E in a Sia-specific fashion to blunt NF-κB and MAPK activation. As a consequence, Siglec-E-deficient macrophages had enhanced pro-inflammatory cytokine secretion, phagocytosis and bactericidal activity against the pathogen. Following pulmonary or low-dose intravenous GBS challenge, Siglec-E KO mice produced more pro-inflammatory cytokines and exhibited reduced GBS invasion of the central nervous system. In contrast, upon high dose lethal challenges, cytokine storm in Siglec-E KO mice was associated with accelerated mortality. We conclude that GBS Sia mimicry influences host innate immune and inflammatory responses in vivo through engagement of an inhibitory Siglec, with the ultimate outcome of the host response varying depending upon the site, stage and magnitude of infection

Effect of Dam Emplacement and Water Level Changes on Sublacustrine Geomorphology and Recent Sedimentation in Jackson Lake, Grand Teton National Park (Wyoming, United States)

Dam installation on a deep hydrologically open lake provides the experimental framework necessary to study the influence of outlet engineering and changing base levels on limnogeological processes. Here, high-resolution seismic reflection profiles, sediment cores, and historical water level elevation datasets were employed to assess the recent depositional history of Jackson Lake, a dammed glacial lake located adjacent to the Teton fault in western Wyoming (USA). Prograding clinoforms imaged in the shallow stratigraphy indicate a recent lake-wide episode of delta abandonment. Submerged ∼11–12 m below the lake surface, these Gilbert-type paleo-deltas represent extensive submerged coarse-grained deposits along the axial and lateral margins of Jackson Lake that resulted from shoreline transgression following dam construction in the early 20th century. Other paleo-lake margin environments, including delta plain, shoreline, and glacial (drumlins, moraines) landforms were likewise inundated following dam installation, and now form prominent features on the lake floor. In deepwater, a detailed chronology was established using 137Cs, 210Pb, and reservoir-corrected 14C for a sediment core that spans ∼1654–2019 Common Era (CE). Dam emplacement (1908–1916 CE) correlates with a nearly five-fold acceleration in accumulation rates and a depositional shift towards carbonaceous sediments. Interbedded organic-rich black diatomaceous oozes and tan silts track changes in reservoir water level elevation, which oscillated in response to regional climate and downstream water needs between 1908 and 2019 CE. Chemostratigraphic patterns of carbon, phosphorus, and sulfur are consistent with a change in nutrient status and productivity, controlled initially by transgression-driven flooding of supralittoral soils and vegetation, and subsequently with water level changes. A thin gravity flow deposit punctuates the deepwater strata and provides a benchmark for turbidite characterization driven by hydroclimate change. Because the Teton fault is a major seismic hazard, end-member characterization of turbidites is a critical first step for accurate discrimination of mass transport deposits controlled by earthquakes in more ancient Jackson Lake strata. Results from this study illustrate the influence of dam installation on sublacustrine geomorphology and sedimentation, which has implications for lake management and ecosystem services. Further, this study demonstrates that Jackson Lake contains an expanded, untapped sedimentary archive recording environmental changes in the American West