Development of a Multiplex Real-Time PCR Assay for Predicting Macrolide and Tetracycline Resistance Associated with Bacterial Pathogens of Bovine Respiratory Disease

Antimicrobial resistance (AMR) in bovine respiratory disease (BRD) is an emerging concern that may threaten both animal and public health. Rapid and accurate detection of AMR is essential for prudent drug therapy selection during BRD outbreaks. This study aimed to develop a multiplex quantitative real-time polymerase chain reaction assay (qPCR) to provide culture-independent information regarding the phenotypic AMR status of BRD cases and an alternative to the gold-standard, culture-dependent test. Bovine clinical samples (297 lung and 111 nasal) collected in Nebraska were subjected to qPCR quantification of macrolide (MAC) and tetracycline (TET) resistance genes and gold-standard determinations of AMR of BRD pathogens. Receiver operating characteristic curve analysis was used to classify AMR based on the qPCR results. For lung tissues, the qPCR method showed good agreement with the gold-standard test for both MACs and TETs, with a sensitivity of 67–81% and a specificity higher than 80%. For nasal swabs, qPCR results passed validation criteria only for TET resistance detection, with a sensitivity of 88%, a specificity of 80% and moderate agreement. The culture-independent assay developed here provides the potential for more rapid AMR characterization of BRD cases directly from clinical samples at equivalent accuracy and higher time efficiency compared with the gold-standard, culture-based test

Association of Central Arterial Stiffness and Pressure Pulsatility with Mild Cognitive Impairment and Dementia: The Atherosclerosis Risk in Communities Study-Neurocognitive Study (ARIC-NCS)

The association of central arterial stiffness and pressure pulsatility with mild cognitive impairment and dementia is not well characterized in the population-based setting

What is the Impact of Regional Training Centers on Practice Location and Specialty Choice of Medical Students?

In comparison to Indianapolis students, those who train at regional campuses are more likely to go into Primary Care and Family Medicine, in particular. Regional campus students are more likely to return to the region to practice medicine after completing training.AAMC Central Group on Education Affairs (CGEA) Spring Meetin

Natural and Induced Environment around the International Space Station (ISS) as Observed during On-Orbit Operations of the Robotic External Leak Locator (RELL)

Final Document is attached. The Robotic External Leak Locator (RELL) was deployed to the International Space Station (ISS) with the goal of detecting and locating on-orbit leaks around the ISS. Three activities to investigate and corroborate the background natural and induced environment of ISS were performed with RELL as part of the on-orbit validation and demonstration conducted in November December 2016. The first demonstration activity pointed RELL directly in the ram and wake directions for one orbit each. The ram facing measurements showed high partial pressure for mass-to-charge ratio 16, corresponding to atomic oxygen (AO), as well as the presence of mass-to-charge ratio 17. RELLs view in the wake-facing direction included more ISS structure and several Environmental Control and Life Support System (ECLSS) on-orbit vents were detected, including the Carbon Dioxide Removal Assembly (CDRA), Russian segment ECLSS, and Sabatier vents. The second demonstration activity pointed RELL at three faces of the P1 Truss segment. Effluents from ECLSS and European Space Agency (ESA) Columbus module on-orbit vents were detected by RELL. The partial pressures of mass-to-charge ratios 17 and 18 remained consistent with the first on-orbit activity of characterizing the natural environment. The third demonstration activity involved RELL scanning an Active Thermal Control System (ATCS) radiator. Three locations along the radiator were scanned and the angular position of RELL with respect to the radiator was varied. Mass-to-charge ratios 16 and 17 both had upward shifts in partial pressure when pointing toward the Radiator Beam Valve Modules (RBVMs), likely corresponding to a known, small ammonia leak

International Space Station (ISS) Environmental Control and Life Support System (ECLSS) Vent Flow Reflection and Detection by Robotic External Leak Locator (RELL)

On-orbit Robotic External Leak Locator (RELL) (i.e., mass spectrometer and ion gauge) measurements on the International Space Station (ISS) are presented to show the detection of recurring Environmental Control and Life Support System (ECLSS) vents at multiple ISS locations and RELL pointing directions. The path of ECLSS effluents to the RELL detectors is not entirely obvious at some locations, but the data indicates that diffuse gas-surface reflection or scattering resulting from plume interaction with vehicle surfaces is responsible. RELL was also able to confirm the ISS ECLSS constituents and distinguish them from the ammonia leak based on the ion mass spectra and known venting times during its operation to locate a leak in the ISS port-side External Active Thermal Control System (EATCS) coolant loop

Symptom Monitoring With Patient-Reported Outcomes During Routine Cancer Treatment: A Randomized Controlled Trial

There is growing interest to enhance symptom monitoring during routine cancer care using patient-reported outcomes, but evidence of impact on clinical outcomes is limited

Young Women with Locally Advanced Breast Cancer Who Achieve Breast Conservation after Neoadjuvant Chemotherapy Have a Low Local Recurrence Rate

Women with locally advanced breast cancer (LABC) who are breast conservation (BCT) candidates after neoadjuvant chemotherapy have the best long-term outcome and low local–regional recurrence (LRR) rates. However, young women are thought to have a higher risk of LRR based on historical data. This study sought to evaluate LRR rates in young women who undergo BCT after neoadjuvant chemotherapy. We identified 122 women aged 45 years or younger with American Joint Committee on Cancer (AJCC) Stage II to III breast cancer, excluding T4d, treated with neoadjuvant chemotherapy from 1991 to 2007 from a prospective, Institutional Review Board-approved, single-institution database. Data were analyzed using Fisher eExact test, Wilcoxon tests, and the Kaplan-Meier method. Median follow-up was 6.4 years. Fifty-four (44%) patients had BCT and 68 (56%) mastectomy. Forty-six per cent were estrogen receptor-positivity and 28 per cent overexpressed Her2. Mean pretreatment T size was 5.6 cm in the BCT group and 6.7 cm in the mastectomy group (P = 0.04). LRR rates were no different after BCT compared with mastectomy (13 vs 18%, P = 0.6). Higher posttreatment N stage (P <0.001) and AJCC stage (P = 0.008) were associated with LRR but not pretreatment staging. Disease-free survival was better for patients achieving BCT, with 5-year disease-free survival rates of 82 per cent (95% CI, 69 to 90%) compared with 58 per cent (95% CI, 45 to 69%) for mastectomy (P = 0.03). Young women with LABC who undergo BCT after neoadjuvant chemotherapy appear to have similar LRR rates compared with those with mastectomy. This suggests that neoadjuvant chemotherapy may identify young women for whom BCT may have an acceptable risk of LRR

Complex -Glycans Influence the Spatial Arrangement of Voltage Gated Potassium Channels in Membranes of Neuronal-Derived Cells

The intrinsic electrical properties of a neuron depend on expression of voltage gated potassium (Kv) channel isoforms, as well as their distribution and density in the plasma membrane. Recently, we showed that N-glycosylation site occupancy of Kv3.1b modulated its placement in the cell body and neurites of a neuronal-derived cell line, B35 neuroblastoma cells. To extrapolate this mechanism to other N-glycosylated Kv channels, we evaluated the impact of N-glycosylation occupancy of Kv3.1a and Kv1.1 channels. Western blots revealed that wild type Kv3.1a and Kv1.1 α-subunits had complex and oligomannose N-glycans, respectively, and that abolishment of the N-glycosylation site(s) generated Kv proteins without N-glycans. Total internal reflection fluorescence microscopy images revealed that N-glycans of Kv3.1a contributed to its placement in the cell membrane while N-glycans had no effect on the distribution of Kv1.1. Based on particle analysis of EGFP-Kv proteins in the adhered membrane, glycosylated forms of Kv3.1a, Kv1.1, and Kv3.1b had differences in the number, size or density of Kv protein clusters in the cell membrane of neurites and cell body of B35 cells. Differences were also observed between the unglycosylated forms of the Kv proteins. Cell dissociation assays revealed that cell-cell adhesion was increased by the presence of complex N-glycans of Kv3.1a, like Kv3.1b, whereas cell adhesion was similar in the oligomannose and unglycosylated Kv1.1 subunit containing B35 cells. Our findings provide direct evidence that N-glycans of Kv3.1 splice variants contribute to the placement of these glycoproteins in the plasma membrane of neuronal-derived cells while those of Kv1.1 were absent. Further when the cell membrane distribution of the Kv channel was modified by N-glycans then the cell-cell adhesion properties were altered. Our study demonstrates that N-glycosylation of Kv3.1a, like Kv3.1b, provides a mechanism for the distribution of these proteins to the cell body and outgrowths and thereby can generate different voltage-dependent conductances in these membranes

Prevalence of Concurrent Functional Vision and Hearing Impairment and Association With Dementia in Community-Dwelling Medicare Beneficiaries.

IMPORTANCE: Impairments in vision or hearing are common and have been independently linked to higher risk of dementia in older adults. There is a limited understanding of the prevalence of concurrent functional vision and hearing impairment (dual sensory impairment) and its contribution to dementia risk. OBJECTIVE: To examine the age-specific prevalence of functional dual sensory impairment among older adults, and to investigate the cross-sectional and 7-year longitudinal associations between functional dual sensory impairment and dementia. DESIGN, SETTING, AND PARTICIPANTS: This cohort study of 7562 older adults used data from the US National Health and Aging Trends Study (NHATS), a nationally representative cohort study of community-dwelling, Medicare beneficiaries aged 65 years and older in the US. Participants in the study with complete data on hearing, vision, and dementia were included in analysis. Data were collected between 2011 and 2018, and between March 2018 and May 2020. EXPOSURES: Self-reported functional sensory impairments (ie, no sensory impairment, functional vision impairment only, functional hearing impairment only, and functional dual sensory impairment). MAIN OUTCOMES AND MEASURES: Age-specific prevalence of functional sensory impairments was calculated. Generalized linear regression with a complementary log-log link and a discrete time proportional hazards model with a complementary log-log link were used to assess the cross-sectional and 7-year longitudinal hazard of dementia. RESULTS: Of 7562 participants, 3073 (40.7%) were ages 80 years or older and 4411 (58.3%) were women. Overall, 5.4% (95% CI, 4.7%-6.1%) of participants reported functional vision impairment only, 18.9% (95% CI, 18.9%-17.8%) reported functional hearing impairment only, and 3.1% (95% CI, 2.7%-3.5%) reported functional dual sensory impairment (prevalence estimates are weighted). Participants reporting sensory impairments were older (no impairment: age ≥90 years, 2.12% [95% CI, 1.79%-2.46%] vs functional dual sensory impairment: age ≥90 years, 20.06% [95% CI, 16.02%-24.10%]), had lower education (no impairment: <high school, 19.05% [95% CI, 17.27%-20.83%] vs functional dual sensory impairment: <high school, 46.15% [95% CI, 38.38%-53.92%]), and greater disease burden (eg, heart disease: no impairment, 15.30% [95% CI, 14.04%-16.55%] vs functional dual sensory impairment, 25.49% [95% CI, 19.96%-31.02%]). Compared with no impairment, functional vision impairment (adjusted hazard ratio [aHR], 1.89; 95% CI, 1.57-2.28), functional hearing impairment (aHR, 1.14; 95% CI, 1.00-1.31), and functional dual sensory impairment (aHR, 2.00; 95% CI, 1.57-2.53) were associated with a higher cross-sectional hazard of dementia. Over 7 years, functional vision impairment (aHR, 1.40; 95% CI, 1.12-1.74), functional hearing impairment (aHR, 1.09; 95% CI, 0.95-1.24), and functional dual sensory impairment (aHR, 1.50; 95% CI, 1.12-2.02) were associated with a higher hazard of incident dementia compared with no impairment. CONCLUSIONS AND RELEVANCE: In this cohort study of US Medicare beneficiaries, dual sensory impairment was prevalent in older adults and associated with increased risk of dementia. These findings suggest that sensory rehabilitative interventions for multiple impairments may be an additional resource in efforts to reduce dementia risk

No barrier to emergence of bathyal king crabs on the Antarctic shelf

Cold-water conditions have excluded durophagous (skeleton-breaking) predators from the Antarctic seafloor for millions of years. Rapidly warming seas off the western Antarctic Peninsula could now facilitate their return to the continental shelf, with profound consequences for the endemic fauna. Among the likely first arrivals are king crabs (Lithodidae), which were discovered recently on the adjacent continental slope. During the austral summer of 2010‒2011, we used underwater imagery to survey a slope-dwelling population of the lithodid Paralomis birsteini off Marguerite Bay, western Antarctic Peninsula for environmental or trophic impediments to shoreward expansion. The population density averaged ∼4.5 individuals × 1,000 m(−2) within a depth range of 1,100‒1,500 m (overall observed depth range 841–2,266 m). Images of juveniles, discarded molts, and precopulatory behavior, as well as gravid females in a trapping study, suggested a reproductively viable population on the slope. At the time of the survey, there was no thermal barrier to prevent the lithodids from expanding upward and emerging on the outer shelf (400- to 550-m depth); however, near-surface temperatures remained too cold for them to survive in inner-shelf and coastal environments (<200 m). Ambient salinity, composition of the substrate, and the depth distribution of potential predators likewise indicated no barriers to expansion of lithodids onto the outer shelf. Primary food resources for lithodids—echinoderms and mollusks—were abundant on the upper slope (550–800 m) and outer shelf. As sea temperatures continue to rise, lithodids will likely play an increasingly important role in the trophic structure of subtidal communities closer to shore