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Selection for feed efficiency, the ratio of output (e.g., milk yield) to feed intake, has traditionally been limited on commercial dairy farms by the necessity for detailed individual animal intake and performance data within large animal populations. The objective of the experiment was to evaluate the effects of individual animal characteristics (animal breed, genetic potential, milk production, body weight (BW), daily total dry matter intake (TDMI), and energy balance) on a cost-effective production efficiency parameter calculated as the annual fat and protein (milk solids) production per unit of mid-lactation BW (MSperBW lact ). A total of 1,788 individual animal intake records measured at various stages of lactation (early, mid, and late lactation) from 207 Holstein-Friesian and 200 Jersey × Holstein-Friesian cows were used. The derived efficiency traits included daily kilograms of milk solids produced per 100 kg of BW (dMSperBW int ) and daily kilograms of milk solids produced per kilogram of TDMI (dMSperTDMI). The TDMI per 100 kg of BW was also calculated (TDMI/BW int ) at each stage of lactation. Animals were subsequently either ranked as the top 25% (Heff) or bottom 25% (Leff) based on their lactation production efficiency (MSperBW lact ). Dairy cow breed significantly affected animal characteristics over the entire lactation and during specific periods of intake measurements. Jersey crossbred animals produced more milk, based on a lower TDMI, and achieved an increased intake per kilogram of BW. Similarly, Heff produced more milk over longer lactations, weighed less, were older, and achieved a higher TDMI compared with the Leff animals. Both Jersey × Holstein-Friesian and Heff cows achieved superior production efficiency due to lower maintenance energy requirements, and consequentially increased milk solids production per kilogram of BW and per kilogram of TDMI at all stages of lactation. Indeed, within breed, Heff animals weighed 20 kg less and produced 15% more milk solids over the total lactation than Leff. In addition, Heff achieved increased daily milk solids yield (+0.16 kg) and milk solids yield per kilogram of TDMI (+ 0.23 kg/kg DM) during intake measurement periods. Moreover, the strong and consistently positive correlations between MSperBW lact and detailed production efficiency traits (dMSperBW int , dMSperTDMI) reported here demonstrate that MSperBW lact is a robust measure that can be applied within commercial grazing dairy systems to increase the selection intensity for highly efficient animals., (The Authors. Published by Elsevier Inc. and Fass Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

BackgroundThe PCR quantification cycle (C q ) is a proxy measure of the viral load of a SARS-CoV-2-infected individual.AimTo investigate if C q values vary according to different population characteristics, in particular demographic ones, and within the COVID-19 pandemic context, notably the SARS-CoV-2 type/variant individuals get infected with.MethodsWe considered all positive PCR results from Cheshire and Merseyside, England, between 6 November 2020 and 8 September 2021. C q distributions were inspected with Kernel density estimates. Multivariable quantile regression models assessed associations between people's features and C q .ResultsWe report C q values for 188,821 SARS-CoV-2 positive individuals. Median C q s increased with decreasing age for suspected wild-type virus and Alpha variant infections, but less so, if not, for Delta. For example, compared to 30-39-year-olds (median age group), 5-11-year-olds exhibited 1.8 (95% CI: 1.5 to 2.1), 2.2 (95% CI: 1.8 to 2.6) and 0.8 (95% CI: 0.6 to 0.9) higher median C q s for suspected wild-type, Alpha and Delta positives, respectively, in multivariable analysis. 12-18-year-olds also had higher C q s for wild-type and Alpha positives, however, not for Delta. Overall, in univariable analysis, suspected Delta positives reported 2.8 lower median C q s than wild-type positives (95% CI: 2.7 to 2.8; p < 0.001). Suspected Alpha positives had 1.5 (95% CI: 1.4 to 1.5; p < 0.001) lower median C q s than wild type.ConclusionsWild-type- or Alpha-infected school-aged children (5-11-year-olds) might transmit less than adults (> 18 years old), but have greater mixing exposures. Smaller differences in viral loads with age occurred in suspected Delta infections. Suspected-Alpha- or Delta-infections involved higher viral loads than wild type, suggesting increased transmission risk. COVID-19 control strategies should consider age and dominant variant.

Microgravity-induced bone loss is a major concern for space travelers. Ground-based microgravity simulators are crucial to study the effect of microgravity exposure on biological systems and to address the limitations posed by restricted access to real space. In this work, for the first time, we adopt a multidisciplinary approach to characterize the morphological, biochemical, and molecular changes underlying the response of human bone marrow stromal cells to long-term simulated microgravity exposure during osteogenic differentiation. Our results show that osteogenic differentiation is reduced while energy metabolism is promoted. We found novel proteins were dysregulated under simulated microgravity, including CSC1-like protein, involved in the mechanotransduction of pressure signals, and PTPN11, SLC44A1 and MME which are involved in osteoblast differentiation pathways and which may become the focus of future translational projects. The investigation of cell proteome highlighted how simulated microgravity affects a relatively low number of proteins compared to time and/or osteogenic factors and has allowed us to reconstruct a hypothetical pipeline for cell response to simulated microgravity. Further investigation focused on the application of nanomaterials may help to increase understanding of how to treat or minimize the effects of microgravity., (© 2022. The Author(s).)

Background: Covid-19 test-to-release from quarantine policies affect many lives. The SMART Release pilot was the foundation of these policies and an element of the world's largest population cohort study of community-wide, SARS-CoV-2 rapid antigen testing. The objective of the study was to evaluate daily lateral flow testing (LFT) as an alternative to 10-14 days quarantine for key worker contacts of known Covid-19 (or SARS-CoV-2 infection) cases., Methods: Prospective cohort study incorporating quantitative and qualitative research methods to consider how serial LFT compares with PCR testing to detect SARS-CoV-2 infections and to understand experiences/compliance with testing and the viability of this quarantine harm-reduction strategy. Participants were residents of the Liverpool area who were key workers at participating fire, police, NHS and local government organisations in Liverpool, and who were identified as close contacts of cases between December 2020 and August 2021. Thematic qualitative analysis was used to evaluate stakeholder meetings., Findings: Compliance with the daily testing regime was good across the three main organisations in this study with 96·9%, 93·7% and 92·8% compliance for Merseyside Police, Merseyside Fire & Rescue Service and Alder Hey Children's Hospital respectively. Out of 1657 participants, 34 positive Covid-19 cases were identified and 3 undetected by the daily LFT regime. A total of 8291 workdays would have been lost to self-isolation but were prevented due to negative daily tests. Organisations reported that daily contact testing proved useful, flexible and well-tolerated initiative to sustain key worker services., Interpretation: Compliance with daily testing among key workers was high, helping sustain service continuity during periods of very high risk of staffing shortage. Services reported that the pilot was a "lifeline" and its successful delivery in Liverpool has been replicated elsewhere., Funding: This report is independent research commissioned by DHSC and part funded by DHSC and NIHR. Further funding was received from Liverpool City Council, the EPSRC and MRC., Competing Interests: IB reports consultancy fees from Astra Zeneca for work not related to this manuscript, and is a member of the UK Testing Initiatives Evaluation Board. IB received grants from the Department of Health and Social Care and from the National Institute for Health Research. DMH reports a small grant from the Psoriasis and Psoriatic Arthritis Alliance for work unrelated to this manuscript. DMH received grants from the Department for Health and Social Care, MRC and Halton Borough Council. MGF reports participation on advisory boards for UK DPFS, UK NC3Rs, and HRCI-HRC-JFS-2022 - Review Panel. This was unrelated to this work. MGF received grants from the Department for Health and Social Care and Halton Borough Council. All the other authors report no conflicts., (© 2022 The Authors.)

Targeted memory reactivation (TMR) during post-learning sleep is known to enhance motor memory consolidation but the underlying neurophysiological processes remain unclear. Here, we confirm the beneficial effect of auditory TMR on motor performance. At the neural level, TMR enhanced slow wave (SW) characteristics. Additionally, greater TMR-related phase-amplitude coupling between slow (0.5-2 Hz) and sigma (12-16 Hz) oscillations after the SW peak was related to higher TMR effect on performance. Importantly, sounds that were not associated to learning strengthened SW-sigma coupling at the SW trough. Moreover, the increase in sigma power nested in the trough of the potential evoked by the unassociated sounds was related to the TMR benefit. Altogether, our data suggest that, depending on their precise temporal coordination during post learning sleep, slow and sigma oscillations play a crucial role in either memory reinstatement or protection against irrelevant information; two processes that critically contribute to motor memory consolidation., Competing Interests: JN, BK, DL, LL, EC, SS, JD, JC, GA No competing interests declared, (© 2022, Nicolas et al.)

Large-scale phosphoproteome profiling using mass spectrometry (MS) provides functional insight that is crucial for disease biology and drug discovery. However, extracting biological understanding from these data is an arduous task requiring multiple analysis platforms that are not adapted for automated high-dimensional data analysis. Here, we introduce an integrated pipeline that combines several R packages to extract high-level biological understanding from large-scale phosphoproteomic data by seamless integration with existing databases and knowledge resources. In a single run, PhosPiR provides data clean-up, fast data overview, multiple statistical testing, differential expression analysis, phosphosite annotation and translation across species, multilevel enrichment analyses, proteome-wide kinase activity and substrate mapping and network hub analysis. Data output includes graphical formats such as heatmap, box-, volcano- and circos-plots. This resource is designed to assist proteome-wide data mining of pathophysiological mechanism without a need for programming knowledge., (© The Author(s) 2021. Published by Oxford University Press.)

Background: Cervical cancer is a leading cause of cancer deaths among women of reproductive age in Peru. Screening and early identification of pre-cancerous lesions are a cornerstone of the cervical cancer prevention strategy. Yet, there is limited literature on barriers to screening among Peruvian women. In this cross-sectional study, we aimed to examine Peruvian women's knowledge, attitudes, and practices regarding cervical cancer screening and identify possible reasons for the gap between knowledge and screening., Methods: The study was conducted in metropolitan Lima from June-August 2019. We purposefully recruited 12 women who had previously been screened, and 12 who had never been screened for cervical cancer. The women completed a 40-question knowledge and attitude survey and an in-depth interview about barriers to screening. Descriptive analysis was used to calculate a knowledge and attitude score and qualitative analysis was guided by the Health Belief Model constructs., Results: Previously screened participants had greater knowledge of cervical cancer symptoms, risk factors, and prevention (mean score = 28.08, S.D. = 4.18) compared to participants who had never been screened (mean score = 21.25, S.D. = 6.35). Both groups described lack of priority and embarrassment as barriers to cervical cancer screening. For participants who had never been screened before, major barriers included the fear of a cancer diagnosis and lack of information about screening services. Pregnancy, unusual gynecological symptoms and encouragement from friends and family were cues to action for participants seeking screening. Most participants in both groups recognized the benefits of getting screened for cervical cancer. Being previously screened increased participants' self-efficacy for engaging in screening behaviors again. Misconceptions regarding screening procedures and cervical cancer were also noted as barriers for participants accessing screening services., Conclusions: Improving knowledge and awareness about cervical cancer and screening programs may improve screening behaviors among women. Targeting women who have never been screened before and addressing their fears and concerns around embarrassment may be other areas for intervention. Misconceptions that deter women from screening services are an important issue that should be addressed in order to increase the number of women who get timely screenings., (© 2021. The Author(s).)

An approximately 1-year-old male intact Shih Tzu dog was referred to a tertiary facility with a history of progressive tachypnea, increased respiratory effort, and weight loss over a 3-month period that failed to improve with empirical antimicrobial treatment. Upon completion of a comprehensive respiratory evaluation, the dog was diagnosed with severe Pneumocystis pneumonia and secondary pulmonary hypertension. Clinical signs resolved and disease resolution was confirmed after completion of an 8-week course of trimethoprim-sulfonamide, 4-week tapering dose of prednisone to decrease an inflammatory response secondary to acute die-off of organisms, a 2-week course of clopidogrel to prevent clot formation, and a 2-week course of a phosphodiesterase-5 inhibitor to treat pulmonary hypertension. Immunodiagnostic testing and genetic sequencing were performed to evaluate for potential immunodeficiency as an underlying cause for the development Pneumocystis pneumonia, and identified an X-linked CD40 ligand deficiency., (© 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC. on behalf of the American College of Veterinary Internal Medicine.)

Quadriceps tendon is a promising alternative graft option for anterior cruciate ligament (ACL) reconstruction, which can be harvested with or without a bone block as well as a full or partial thickness graft. Therefore, quadriceps tendon graft could be used in primary and revision ACL reconstruction based on the requirements (tunnel size, tunnel position, etc.). The all soft tissue, partial thickness quadriceps tendon graft in detail and pitfalls of the harvest are described in the present review. After quadriceps tendon harvest, especially in soccer players, who need a strong quadriceps to strike a ball with power, the postoperative rehabilitation may need to be adapted. LEVEL OF EVIDENCE: V.

Astrocyte dysfunction is implicated in clinical depression. There is a paucity of animal models to assess the role of astrocytes in depression pathogenesis. Refinement of an existing model is described here. Administration of the astrocytic toxin L-alpha aminoadipic acid (L-AAA) to the pre-limbic cortex (PLC) was assessed in rats and mice in tests of anxiety and depression related behaviours. Delivery of L-AAA to the PLC of Wistar rats produced an increase in immobility in the forced swimming test (FST) and reduced exploration in the open field. Delivery to the CA3 subfield of the hippocampus produced a deficit in the novel object relocation task. Delivery of single or two successive doses of L-AAA to the PLC of C57Bl6/J mice was sufficient to induce an increase in immobility in the mouse tail suspension (TST) and FST independently of administration of anaesthetic agent or the surgical procedure. In both mice and rats, L-AAA produced a reduction in immunoreactivity of the astrocytic marker glial fibrillary acidic protein (GFAP) for up to 72 h. L-AAA provoked an increase in the density of apical and basal dendritic spines in mice exposed to the FST when compared to non-FST controls. In summary, L-AAA provokes a region-dependent change in behaviour, a reduction in GFAP immunoreactivity and FST-provoked increased in dendritic spine density in the PLC. This model may be further employed to assess the impact of astroglial integrity on the structural plasticity of neurons and the effect of antidepressant agents on L-AAA-related changes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Special staining and grading of canine liver cytology samples aids in detection of increased copper content. The prevalence of copper in routine diagnostic liver cytology samples, clinical findings associated with high cytologic copper (cCu) grade, and the correlation between cCu grade and histologic findings, including histologic copper (hCu) grade, are unknown. This data may be helpful in ascertaining when to determine a cCu grade and when interpreting cCu grade. Clinical data and available archived hepatic histologic and cytologic samples from 198 dogs were collected, evaluated, rhodanine stained, and graded for copper. Prevalence of increased cCu >5 in a randomly collected group of 163 individuals, and the correlation between cCu and clinical data (n = 198), hCu grade (n = 37), or findings on hematoxylin and eosin-stained hepatic sections (n = 32) were evaluated. The observed prevalence was 1.23%. Dogs with elevated alanine transaminase >180 IU/L or aspartate transaminase >90 IU/L and patients who subsequently had hepatic copper quantification were statistically more likely to have pathologic levels of copper detected by cytology. There was significant and modest correlation between cCu and hCu, interface hepatitis, portal inflammation, and fibrosis. Evidence of hepatocellular leakage may be indications for determination of cCu.

Like many other countries, Ghana relies on biomass (mainly wood and charcoal) for most of its cooking needs. A national action plan aims to expand liquefied petroleum gas (LPG) access to 50% of the country's population by 2020. While the country's southern urban areas have made progress toward this goal, LPG use for cooking remains low in the north. The aim of this cross-sectional study was to characterize the current state of the LPG market in this area and examine opportunities and barriers to scale up LPG adoption. We interviewed 16 LPG suppliers (stove, cylinder, and fuel vendors) as well as 592 households in the Kassena-Nankana Districts (KND) of Ghana. We find large rural-urban differences in LPG uptake: less than 10% of rural households own LPG stoves compared with over half of urban households. Awareness of LPG is high across the region, but accessibility of fuel supply is highly limited, with just one refilling station located in the KND. Affordability is perceived as the main barrier to LPG adoption, and acceptability is also limited by widespread concerns about the safety of cooking with LPG. Transitioning to a cylinder recirculation model, and providing more targeted subsidies and credit options, should be explored to expand access to cleaner cooking in this region.

A large fraction of the global population relies on the inefficient combustion of solid fuels for cooking and home heating, resulting in household exposure to combustion byproducts. In the southwestern United States, unhealthy air quality has been observed in some homes that use solid fuels as a primary source of heat on the Navajo Nation. In order to better understand how home heating fuel choice can influence indoor air quality in this region, we used recently developed low-cost electrochemical sensors to measure carbon monoxide (CO) air mole fractions continuously inside and outside 41 homes in two communities on the Navajo Nation. Using low-cost sensors in this study, which don't require extensive training to operate, enabled collaboration with local Diné College students and faculty in the planning and implementation of home deployments. Households used natural gas, propane, pellets, wood, and/or coal for heating. We developed quantification methods that included uncertainty estimation for Alphasense CO-B4 sensors, for measurements both inside and outside homes. CO concentrations elevated above background were observed in homes in each heating fuel group, but the highest hourly concentrations were observed in wood and coal burning homes, some of which exceeded World Health Organization Guidelines on both an hourly and eight-hourly basis. In order to probe the many factors that can influence indoor pollutant concentrations, we developed and implemented methods that employ CO emission and decay time periods observed in homes during everyday activities to estimate air exchange rates as well as CO emission rates on the basis of a given well-mixed volume of air. The air quality measurement tools and methods demonstrated in this study can be readily extended to indoor air quality studies in other communities around the world to inform how home heating and cooking practices are influencing indoor air quality during normal daily activities., (Copyright © 2018 Elsevier B.V. All rights reserved.)

The increased use of low-cost air quality sensor systems, particularly by communities, calls for the further development of best-practices to ensure these systems collect usable data. One area identified as requiring more attention is that of deployment logistics, that is, how to select deployment sites and how to strategically place sensors at these sites. Given that sensors are often placed at homes and businesses, ideal placement is not always possible. Considerations such as convenience, access, aesthetics, and safety are also important. To explore this issue, we placed multiple sensor systems at an existing field site allowing us to examine both neighborhood-level and building-level variability during a concurrent period for CO₂ (a primary pollutant) and O₃ (a secondary pollutant). In line with previous studies, we found that local and transported emissions as well as thermal differences in sensor systems drive variability, particularly for high-time resolution data. While this level of variability is unlikely to affect data on larger averaging scales, this variability could impact analysis if the user is interested in high-time resolution or examining local sources. However, with thoughtful placement and thorough documentation, high-time resolution data at the neighborhood level has the potential to provide us with entirely new information on local air quality trends and emissions.

The objective of this experiment was to evaluate the effect of stocking rate (SR) and animal genotype (BR) on milk production, body weight (BW), and body condition score (BCS) within intensive pasture-based systems. A total of 533 lactation records, from 246 elite genetic merit dairy cows were available for analysis; 68 Holstein-Friesian (HF) and 71 Jersey × Holstein-Friesian (JxHF) crossbred cows in each of 4 consecutive years (2013-2016, inclusive). Cows from each BR were randomly allocated to 1 of 3 whole-farm comparative SR treatments, low (LSR; 1,200 kg of BW/ha), medium (MSR; 1,400 kg of BW/ha), and high (HSR; 1,600 kg of BW/ha), and remained in the same SR treatments for the duration of the experiment. The effects of SR, BR, and their interaction on milk production/cow and per hectare, BW, BCS, and grazing characteristics were analyzed. Total pasture utilization per hectare consumed in the form of grazed pasture increased linearly as SR increased: least in LSR (10,237 kg of dry matter/ha), intermediate in MSR (11,016 kg of dry matter/ha), and greatest in HSR (11,809 kg of dry matter/ha). Milk and milk solids (MS) yield per hectare was greatest for HSR (15,942 and 1,354 kg, respectively), intermediate for MSR (14,191 and 1,220 kg, respectively), and least for LSR (13,186 and 1,139 kg, respectively) with similar trends evident for fat, protein, and lactose yield/ha. At higher SR (MSR and HSR), MS yield per kg of BW per ha was reduced (0.85 and 0.82 kg of MS/kg of BW, respectively) compared with LSR (0.93 kg of MS/kg of BW/ha). Holstein-Friesian cows achieved fewer grazing days per hectare (-37 d), and produced more milk (+561 kg/ha) but less fat plus protein (-57 kg/ha) compared with JxHF cows; the JxHF cows were lighter. At similar BW per hectare, JxHF cows produced more fat plus protein/ha during the grazing season at low (1,164 vs. 1,113 kg), medium (1,254 vs. 1,185 kg), and high (1,327 vs. 1,380 kg) SR. In addition, JxHF cows produced more fat plus protein per kg of BW/ha (0.90 kg) compared with HF cows (0.84 kg). The results highlight the superior productive efficiency of high genetic potential crossbred dairy cows within intensive pasture-based production systems., (Copyright © 2018 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.)

REACCTING (Research on Emissions Air Quality, Climate, and Cooking Technologies in Northern Ghana) was a 200-home cookstove intervention study from 2013 to 2015. Study households were divided into four groups: a control group, a group given two locally made rocket stoves, a group given two Philips forced draft stoves, and a group given a locally made rocket stove and a Philips stove. In a subset of study households, 48-hour PM 2.5 exposure samples were collected for adults and children, as well as in the primary cooking area. Further, weekly ambient background PM 2.5 samples were collected for the first nine months of the study. All PM 2.5 samples were analyzed for elemental and organic carbon (EC/OC), and a subset was also analyzed for organics. Mixed effects modeling was applied to quantify differences in PM exposures between the groups and to assess relationships between exposures and cooking area measurements. Results showed that personal OC exposure for the intervention groups was 56.6% lower than the control group (p≤0.01). Both intervention groups given Philips stoves had significantly lower EC exposure than the control group (60.6% reduction, p≤0.02). Only weak relationships were found between personal and cooking area EC or OC. Source apportionment modeling was performed on both the personal/microenvironment and the ambient organics PM 2.5 data sets to assess the sources of the observed PM. We identified six PM sources. The identified source factors were similar among the data sets, as well as with previous work in Navrongo. Two sources, one characterized by the presence of methoxyphenols, and one by the presence of polyaromatic hydrocarbons and EC, were associated with biomass burning, and accounted for a median of 9.2% of OC and 15.3% of EC personal exposure. Here, we demonstrate the utility of using the cooking-related source apportionment factors within a mixed effects model for more precise estimation of exposures due to cooking, rather than other combustion sources unrelated to the intervention., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Background: Canine hepatic copper content has been increasing. Recognition of canine copper-associated hepatopathies is becoming more common., Objectives: The purpose of the study was to assess the diagnostic performance of Wright-Giemsa (WG) and rhodanine staining for detection of increased canine hepatic copper following a proposed cytologic protocol for semi-quantitative evaluation of liver aspirates and the effect of previous WG staining., Methods: Retrospectively, 40 canine hepatic WG-stained cytology cases were rhodanine stained. Diagnostic performance of WG staining for increased hepatic copper was evaluated. A rhodanine-stained cytologic copper grading system was developed. Prospectively, 67 canine liver samples with quantitative copper measurement, a WG-then rhodanine-stained slide, and a non-WG rhodanine-stained slide were used to assess the performance of the grading system and the effect of previous WG staining., Results: Copper was not described in 40 retrospective cases on initial cytologic evaluation; 8/40 cases had increased copper content after rhodanine staining or quantitative copper assessment. Prior WG staining and destaining significantly affected the cytologic copper grade but not the diagnostic performance as measured by receiver-operating characteristic curve analysis. Quantitative copper concentration and previously WG-stained copper grade were moderately correlated (n = 67, ρ = .79 [.68-.87]). For detection of ≥ 600 ppm, dry weight (dw) copper, sensitivity was .75 and specificity was .97. For detection of ≥ 1500 ppm, dw copper, sensitivity was 1.0 and specificity was .97., Conclusions: Wright-Giemsa staining alone does not reliably detect hepatic copper. Grading of rhodanine-stained canine hepatic cytologic samples demonstrates acceptable diagnostic performance for detection of copper content., (© 2016 American Society for Veterinary Clinical Pathology.)

A 6-year-old, male castrated, mixed-breed dog was referred to the James L. Voss Veterinary Teaching Hospital at Colorado State University for bicavitary effusion. On examination, the dog was tachycardic and tachypneic with bilaterally decreased lung sounds. Thoracic and abdominal ultrasonic examination revealed pleural and peritoneal effusions, which were aspirated and submitted for fluid analysis and cytology. Both cavity fluids were classified as exudates with a large population of vacuolated mononuclear cells. Multiplex immunocytochemistry (ICC) for cytokeratin and vimentin demonstrated exclusively cytokeratin expression, indicating these cells were of epithelial origin. A full diagnostic evaluation was performed, including CBC, clinical chemistry, a pet-side test for heartworm disease, ehrlichiosis, Lyme disease, and anaplasmosis, imaging modalities of thorax, abdomen, and heart, urinalysis, and fine-needle aspirations of spleen, liver, and popliteal lymph nodes. The dog was diagnosed with pleural and peritoneal carcinoma with presumed carcinomatosis. A single dose of intracavitary carboplatin was administered before discharge, and over a period of 2 weeks, 5 thoracocenteses were performed. A subcutaneous mass was noted at a thoracocentesis site one week after initial presentation. Cytology of the mass was consistent with carcinoma, and neoplastic seeding of the tumor cells from the thoracocentesis was suspected. The dog was euthanized 15 days after the first visit, and a necropsy was performed. Findings were consistent with carcinomatosis secondary to anaplastic pulmonary carcinoma with transient subcutaneous seeding of neoplastic cells during routine thoracocentesis. This case demonstrates the utility of multiplex ICC in the clinical setting., (© 2016 American Society for Veterinary Clinical Pathology.)

We describe multidrug-resistant (MDR) Salmonella Heidelberg infections associated with mechanically separated chicken (MSC) served at a county correctional facility. Twenty-three inmates met the case definition. All reported diarrhea, 19 (83%) reported fever, 16 (70%) reported vomiting, 4 (17%) had fever ≥103°F, and 3 (13%) were hospitalized. A case-control study found no single food item significantly associated with illness. Salmonella Heidelberg with an indistinguishable pulsed-field gel electrophoresis pattern was isolated from nine stool specimens; two isolates displayed resistance to a total of five drug classes, including the third-generation cephalosporin, ceftriaxone. MDR Salmonella Heidelberg might have contributed to the severity of illness. Salmonella Heidelberg indistinguishable from the outbreak subtype was isolated from unopened MSC. The environmental health assessment identified cross-contamination through poor food-handling practices as a possible contributing factor. Proper hand-washing techniques and safe food-handling practices were reviewed with the kitchen supervisor.

Background: Cooking over open fires using solid fuels is both common practice throughout much of the world and widely recognized to contribute to human health, environmental, and social problems. The public health burden of household air pollution includes an estimated four million premature deaths each year. To be effective and generate useful insight into potential solutions, cookstove intervention studies must select cooking technologies that are appropriate for local socioeconomic conditions and cooking culture, and include interdisciplinary measurement strategies along a continuum of outcomes., Methods/design: REACCTING (Research on Emissions, Air quality, Climate, and Cooking Technologies in Northern Ghana) is an ongoing interdisciplinary randomized cookstove intervention study in the Kassena-Nankana District of Northern Ghana. The study tests two types of biomass burning stoves that have the potential to meet local cooking needs and represent different "rungs" in the cookstove technology ladder: a locally-made low-tech rocket stove and the imported, highly efficient Philips gasifier stove. Intervention households were randomized into four different groups, three of which received different combinations of two improved stoves, while the fourth group serves as a control for the duration of the study. Diverse measurements assess different points along the causal chain linking the intervention to final outcomes of interest. We assess stove use and cooking behavior, cooking emissions, household air pollution and personal exposure, health burden, and local to regional air quality. Integrated analysis and modeling will tackle a range of interdisciplinary science questions, including examining ambient exposures among the regional population, assessing how those exposures might change with different technologies and behaviors, and estimating the comparative impact of local behavior and technological changes versus regional climate variability and change on local air quality and health outcomes., Discussion: REACCTING is well-poised to generate useful data on the impact of a cookstove intervention on a wide range of outcomes. By comparing different technologies side by side and employing an interdisciplinary approach to study this issue from multiple perspectives, this study may help to inform future efforts to improve health and quality of life for populations currently relying on open fires for their cooking needs.

Mutation in presenilin 1 (PS1) is one of the leading causes of familial Alzheimer's disease (fAD). PS1 mutation exacerbates the autophagic and lysosomal pathology in AD patients, leading to accumulation of partially degraded material in bloated lysosomes and autophagosomes - a pathology that bears some resemblance to other diseases characterized by elevated lysosomal pH, like age-related macular degeneration. In this study, we examined the effect of the PS1-fAD mutation A246E on lysosomal pH and lysosomal function, and asked whether restoration of lysosomal pH could reverse some of these changes. Lysosomal pH was elevated by 0.2-0.3 pH units in human fibroblasts with the PS1-fAD mutation. The lysosomal alkalization in PS1-fAD fibroblasts was supported by a reduction in the pH-dependent cleavage of cathepsin D and by a reduction in binding of boron-dipyrromethene (BODIPY) FL-pepstatin A to the cathepsin D active site. PS1-fAD cells had increased LC3B-II/-I ratios and p62 levels, consistent with impaired lysosomal degradation and analogous to changes induced by lysosomal alkalinization with chloroquine. PS1-fAD fibroblasts had increased expression of ATP6V1B2, ATG5, BECN1 TFEB mRNA, and of ATP6V1B2, ATG5 and beclin at the protein level, consistent with chronic impairment of autophagic and lysosomal functions in the mutant cells. Critically, cyclic adenosine monophosphate (cAMP) treatment reacidified lysosomal pH in mutant PS1-fAD; cAMP also increased the availability of active cathepsin D and lowered the LC3B-II/-I ratio. These results confirm a small elevation in the lysosomal pH of human PS1-fAD fibroblasts, demonstrate that this lysosomal alkalization is associated with chronic changes in autophagy and degradation, and suggest that treatment to reacidify the lysosomes with cAMP can reverse these changes., (Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.)

The fibroblast growth factor (FGF) family of signaling ligands contributes significantly to lung development and maintenance in the adult. FGF9 is involved in control of epithelial branching and mesenchymal proliferation and expansion in developing lungs. However, its activity and expression in the normal adult lung and by epithelial and interstitial cells in fibroproliferative diseases like idiopathic pulmonary fibrosis (IPF) are unknown. Tissue samples from normal organ donor human lungs and those of a cohort of patients with mild to severe IPF were sectioned and stained for the immunolocalization of FGF9. In normal lungs, FGF9 was confined to smooth muscle surrounding airways, alveolar ducts and sacs, and blood vessels. In addition to these same sites, lungs of IPF patients expressed FGF9 in a population of myofibroblasts within fibroblastic foci, hypertrophic and hyperplastic epithelium of airways and alveoli, and smooth muscle cells surrounding vessels embedded in thickened interstitium. The results demonstrate that FGF9 protein increased in regions of active cellular hyperplasia, metaplasia, and fibrotic expansion of IPF lungs, and in isolated human lung fibroblasts treated with TGF-β1 and/or overexpressing Wnt7B. The cellular distribution and established biologic activity of FGF9 make it a potentially strong candidate for contributing to the progression of IPF.

Objective: Because patients with mental illness can die prematurely, we sought to determine if undetected cardiovascular disease might be present in a psychiatric day treatment population., Method: We studied 96 patients in a day treatment program seen between February 2011 and August 2012. Data were obtained through an electronic medical record database. Electrocardiographic diagnoses were assigned by 1 investigator (M.L.). Medications were categorized into classes, and problem lists revealed comorbid diagnoses. Fisher exact test (2-tailed) and analysis of variance were used to compare findings between patient groups. Electrocardiogram (ECG) findings were the primary outcome measure., Results: Ninety-two ECGs were performed in 37 patients. Of these 37 patients, 70% were women, 65% were 50 years of age or younger, and 54% were people of color. ECGs were performed mainly for chest pain/dyspnea (46%) and overdose/altered mental status (27%). Of these 37 patients, 20 (54%) had abnormal ECGs, 7 (19%) had borderline findings, and 10 (27%) had normal studies. When compared with the larger group of 59 patients without ECG testing, those with abnormal ECGs were more likely to be older (mean age = 47 vs 37 years, P < .001) and have more comorbid conditions (mean no. = 10.0 vs 3.8, P < .0001). The most common abnormalities were conduction disorders (prolonged QRS ≥ 105 ms, or prolonged QTc ≥ 450 ms in men or ≥ 460 ms in women), coronary artery disease, and arrhythmias., Conclusions: In psychiatric outpatients who underwent ECG testing, mainly for chest pain or altered mental status, over 50% had concerning findings. Older patients with multiple comorbidities were at higher risk of having abnormal ECGs. Generalizability of these findings depends on validation in larger samples in multiple settings.

Background: In Liverpool, injecting drug users (IDUs), men-who-have-sex-with-men (MSM) and UK Africans experience a disproportionate burden of HIV, yet services do not reach out to these groups and late presentations continue. We set out to: increase testing uptake in targeted marginalized groups through a community and genitourinary medicine (GUM)-based point of care testing (POCT) programme; and conduct a process evaluation to examine service provider inputs and document service user perceptions of the programme., Methods: Mixed quantitative, qualitative and process evaluation methods were used. Service providers were trained to use fourth generation rapid antibody/antigen HIV tests. Existing outreach services incorporated POCT into routine practice. Clients completed a semi-structured questionnaire and focus group discussions (FGDs) were held with service providers., Results: Between September 2009 and June 2010, 953 individuals underwent POCT (GUM: 556 [59%]; community-based sites: 397 [42%]). Participants in the community were more likely to be male (p = 0.028), older (p < 0.001), of UK African origin (p < 0.001) and IDUs (p < 0.001) than participants from the GUM clinic. Seventeen new HIV diagnoses were confirmed (prevalence = 1.8%), 16 of whom were in risk exposure categories (prevalence: 16/517, 3.1%). Questionnaires and FGDs showed that clients and service providers were supportive of POCT, highlighting benefits of reaching out to marginalised communities and incorporating HIV prevention messages., Conclusions: Community and GUM clinic-based POCT for HIV was feasible and acceptable to clients and service providers in a low prevalence setting. It successfully reached target groups, many of whom would not have otherwise tested. We recommend POCT be considered among strategies to increase the uptake of HIV testing among groups who are currently underserved.

Activation-induced cytidine deaminase (AID) is required for somatic hypermutation and immunoglobulin class switching in activated B cells. Because AID has no known target-site specificity, there have been efforts to identify non-immunoglobulin AID targets. We show here that AID acts promiscuously, generating widespread DNA double-strand breaks (DSBs), genomic instability and cytotoxicity in B cells with less homologous recombination ability. We demonstrate that the homologous-recombination factor XRCC2 suppressed AID-induced off-target DSBs, promoting B cell survival. Finally, we suggest that aberrations that affect human chromosome 7q36, including XRCC2, correlate with genomic instability in B cell cancers. Our findings demonstrate that AID has promiscuous genomic DSB-inducing activity, identify homologous recombination as a safeguard against off-target AID action, and have implications for genomic instability in B cell cancers.

IL-12 and IL-18 are essential for Th1 differentiation, whereas the role of IFN-alpha in Th1 development is less understood. In this microarray-based study, we searched for genes that are regulated by IFN-alpha, IL-12, or the combination of IL-12 plus IL-18 during the early differentiation of human umbilical cord blood CD4(+) Th cells. Twenty-six genes were similarly regulated in response to treatment with IL-12, IFN-alpha, or the combination of IL-12 plus IL-18. These genes could therefore play a role in Th1 lineage decision. Transcription factor activating transcription factor (ATF) 3 was upregulated by these cytokines and selected for further study. Ectopic expression of ATF3 in CD4(+) T cells enhanced the production of IFN-gamma, the hallmark cytokine of Th1 cells, whereas small interfering RNA knockdown of ATF3 reduced IFN-gamma production. Furthermore, ATF3 formed an endogenous complex with JUN in CD4(+) T cells induced to Th1. Chromatin immunoprecipitation and luciferase reporter assays showed that both ATF3 and JUN are recruited to and transactivate the IFNG promoter during early Th1 differentiation. Collectively, these data indicate that ATF3 promotes human Th1 differentiation.

This study describes the effects of a psychoeducational multiple-family group program for families of people with severe mental illness in post-war Kosovo that was developed by a Kosovar-American professional collaborative. The subjects were 30 families of people with severe mental illnesses living in two cities in Kosovo. All subjects participated in multiple-family groups and received family home visits. The program documented medication compliance, number of psychiatric hospitalizations, family mental health services use, and several other characteristics, for the year prior to the groups and the first year of the groups. The families attended an average of 5.5 (out of 7) groups, and 93% of these families attended four or more meetings. The uncontrolled pre- to post-intervention comparison demonstrated decreases in medication non-compliance and hospitalizations, and increases in family mental health service use. The program provided training for mental health professionals, led to policy change in the Ministry of Health, and resulted in dissemination to other community mental health centers. This study provides preliminary evidence that a collaboratively designed and implemented psychoeducational, multiple-family program is a feasible and beneficial intervention for families of people with severe mental illness in impoverished post-war settings.

Family processes of communication, mutual support, and sustenance of cultural values can play vital roles in recovery from psychological and material damage in societies afflicted by terror. This is particularly the case when a campaign of terror has specifically targeted family life and its traditions, when the culture is one whose identity has been centered in its families, and when public mental health resources have been scarce. At the end of the 1999 war in Kosova, the Kosovar Family Professional Educational Collaborative (KFPEC) was initiated to counter mental health sequelae of war in Kosova. This initiative focused upon the recovery and strengthening of Kosovar families, rather than the psychiatric treatment of individuals for post-traumatic symptoms. Findings and outcomes from this project may usefully inform the design of other international public mental health initiatives.

Previously, it was shown that the recruitment of RET into lipid rafts by glial cell line-derived neurotrophic factor (GDNF)/GFRalpha1 is crucial for efficient signal transduction. Here, we show that the mouse GFRalpha4 is a functional, N-glycosylated, glycosylphosphatidylinositol (GPI)-anchored protein, which mediates persephin (PSPN)-induced phosphorylation of RET, but has an almost undetectable capacity to recruit RET into the 0.1% Triton X-100 insoluble membrane fraction. In spite of this, PSPN/mGFRalpha4 promotes neurite outgrowth in PC6-3 cells and survival of cerebellar granule neurons. As we show that also human PSPN/GFRalpha4 is unable to recruit RET into lipid rafts, we propose that the mammalian GFRalpha4 in this respect differs from GFRalpha1.

This study examined the different facets of emotional intelligence, alexithymia, and mood awareness. Undergraduate students (N = 129) completed the Trait Meta-Mood Scale (TMMS), the Toronto Alexithymia Scale (TAS-20), and the Mood Awareness Scale (MAS). A factor analysis revealed two dimensions, attention to and clarity of emotions, that cut across all three instruments. These two dimensions were differentially associated with personality, as measured by the neuroticism, extraversion, and openness to experience portions of the NEO-FFI, and with performance on an emotional Stroop task. We discuss the implications for the conceptualisation of broad constructs such as emotional intelligence and alexithymia, as well as the potential utility of more narrowly defined individual differences.

This essay is based on a pilot study that examined the effects of managed care on the treatment of children and families, with special attention to community mental health. We embarked on the pilot study to test the accuracy and generalizability of our impression that family therapy and other systemic practices have been marginalized in ordinary clinics and agencies, and to understand the reasons why. We interviewed managed care providers, researchers, family therapy trainers, and clinicians in the Northeast. Our findings led to seven themes that support our impression that, even though there is a consensus about the need for coordinated family-based services, there is a disconnection between state policies, contractual requirements and what is actually occurring at the implementation level. This study suggests that our knowledge of human systems may be in danger of being disqualified and lost, with damaging consequences for the care of children. Yet, as systemic thinkers and practitioners, it is our belief that ethical and effective treatment need not be at odds with care that is cost-efficient. The direction of our future research will be to study whether the involvement of all stakeholders at all levels of planning and training leads to systemic family-based practices that consistently save costs and provide high-quality care.

In this study we report the activation of c-Jun N-terminal kinase (JNK) in human K562 erythroleukemia cells undergoing hemin-mediated erythroid differentiation, which occurs concomitantly with activation of heat shock factor 2 (HSF2) and leads to a simultaneous in vivo phosphorylation of c-Jun. The activation of JNK occurs through activation of mitogen-activated protein kinase kinase (MKK) 4 and not by activation of MKK7 or inhibition of JNK-directed phosphatases. We have previously shown that overexpression of the HSF2-beta isoform inhibits the activation of HSF2 upon hemin-induced erythroid differentiation. Here we demonstrate that HSF2-beta overexpression blocks the hemin-induced activation of the MKK4-JNK pathway, suggesting an erythroid lineage-specific JNK activation likely to be regulated by HSF2.

We describe a flexible system for gene expression profiling using arrays of tens of thousands of oligonucleotides synthesized in situ by an ink-jet printing method employing standard phosphoramidite chemistry. We have characterized the dependence of hybridization specificity and sensitivity on parameters including oligonucleotide length, hybridization stringency, sequence identity, sample abundance, and sample preparation method. We find that 60-mer oligonucleotides reliably detect transcript ratios at one copy per cell in complex biological samples, and that ink-jet arrays are compatible with several different sample amplification and labeling techniques. Furthermore, results using only a single carefully selected oligonucleotide per gene correlate closely with those obtained using complementary DNA (cDNA) arrays. Most of the genes for which measurements differ are members of gene families that can only be distinguished by oligonucleotides. Because different oligonucleotide sequences can be specified for each array, we anticipate that ink-jet oligonucleotide array technology will be useful in a wide variety of DNA microarray applications.

Because of the significance of the Boston Naming Test (BNT) in the differential diagnosis of the dementias, especially Alzheimer's disease, adequate norms from community-dwelling elderly individuals are essential. The present study describes the development of two new empirically derived equivalent short forms (30 items each) of the test. Normative data for the total BNT and the two equivalent 30-item halves based on item difficulty are presented using the performance of 314 community-dwelling individuals aged 65 and over. Age and education norms are presented using an overlapping midpoint interval strategy.

c-Jun N-terminal kinases (JNKs) typically respond strongly to stress, are implicated in brain development, and are believed to mediate neuronal apoptosis. Surprisingly, however, JNK does not respond characteristically to stress in cultured cerebellar granule (CBG) neurons, a widely exploited CNS model for studies of death and development, despite the regulation of its substrate c-Jun. To understand this anomaly, we characterized JNK regulation in CBG neurons. We find that the specific activity of CBG JNK is elevated considerably above that from neuron-like cell lines (SH-SY5Y, PC12); however, similar elevated activities are found in brain extracts. This activity does not result from cellular stress because the stress-activated protein kinase p38 is not activated. We identify a minor stress-sensitive pool of JNK that translocates with mitogen-activated protein kinase kinase-4 (MKK4) into the nucleus. However, the major pool of total activity is cytoplasmic, residing largely in the neurites, suggesting a non-nuclear role for JNK in neurons. A third JNK pool is colocalized with MKK7 in the nucleus, and specific activities of both increase during neuritogenesis, nuclear JNK activity increasing 10-fold, whereas c-Jun expression and activity decrease. A role for JNK during differentiation is supported by modulation of neuritic architecture after expression of dominant inhibitory regulators of the JNK pathway. Channeling of JNK signaling away from c-Jun during differentiation is consistent with the presence in the nucleus of the JNK/MKK7 scaffold protein JNK-interacting protein, which inhibits JNK-c-Jun interaction. We propose a model in which distinct pools of JNK serve different functions, providing a basis for understanding multifunctional JNK signaling in differentiating neurons.

A burn injury may occur as an unexpected consequence of medical treatment. We examined the burn prevention implications of injuries received in a medical treatment facility or as a direct result of medical care. The records of 4510 consecutive admissions to 1 burn center between January 1978 and July 1997 were retrospectively reviewed. A cohort of 54 patients burned as a result of medical therapy was identified and stratified by location (home vs medical facility) and by mechanism of injury. Twenty-two patients were burned in a medical treatment facility, including 12 patients who were burned as a result of careless or unsupervised use of tobacco products. Thirty-two patients were burned as a result of home medical therapy, including 9 patients who had scald injuries from vaporizers, 8 patients who were burned by simultaneous use of cigarettes and home nasal oxygen therapy, and 11 patients who were burned by therapeutic application of heat. In contrast to previous studies, no patient was burned by the use of medical laser devices. To further decrease burn risk from medical therapy we advocate the prohibition of cigarette smoking in any medical facility. Continued tobacco use may represent a contraindication to home oxygen therapy. Given the lack of proof of efficacy combined with the potential for burn injury, the use of vaporizers to treat upper respiratory symptoms should be discouraged. Patients with diminished sensation or altered mental status are at increased risk of burn injury from bathing or topical heat application and merit closer monitoring during these activities.

Neurotoxicity is one of the side-effects of the therapeutically useful antitumour agent, Ara-C (or 1-beta-d-arabinofuranosyl-cytosine, cytarabine). This agent is also reported to induce cell death of cultured neurons. In this study, we show that Ara-C-induced death of differentiating rat cerebellar granule neurons is prevented by cycloheximide at concentrations corresponding to its action in preventing protein synthesis. The death is accompanied by cleavage of the caspase substrate poly ADP ribose polymerase (PARP) and c-Abl-dependent activation of the stress-activated protein kinases c-Jun N-terminal kinase and p38. However, c-Jun levels do not rise and the activation of the stress-activated protein kinases is not required for this form of neuronal death. Cyclin-dependent kinase (cdk) activity and inappropriate cell-cycle re-entry have been implicated in some forms of death in differentiated neurons. Here we show that Ara-C-induced death of cerebellar granule neurons is prevented by an inhibitor of cdk4, whereas inhibition of cdk1, -2 and -5 mimics the death, and non-cdk4/6 cdks are inhibited by Ara-C treatment. Cdk1 and -2 are dramatically down-regulated during neuronal differentiation, and neither Ara-C nor inhibition of these cdks induces death in mature neurons. This mechanism could also play a significant role in the neurotoxicity associated with the therapeutic use of Ara-C, as cdk levels can be upregulated in stressed neurons of adult brain. We propose that the balance between cdk4/6 and cdk1/2/5 activity may determine the survival of early differentiating neurons, and that DNA-damaging agents may induce neuronal death by inhibiting cdk1/2/5 under conditions which require these activities for survival.

Jurkat T cells undergo rapid apoptosis upon stimulation of the Fas/APO-1 (CD95) receptor. We examined the role of the mitogen-activated protein kinase (MAPK) cascade as a negative regulator of Fas-mediated apoptosis. To this end, we used both physiologic and artificial activators of MAPK, all of which activate MAPK by distinct routes. MAPK activity could be efficiently elevated by two T cell mitogens, the lectin PHA and an agonistic Ab to the T cell receptor complex as well as by the type 1 and 2A phosphatase inhibitor, calyculin A, and the protein kinase C-activating phorbol ester, tetradecanoyl phorbol acetate. All these treatments were effective in preventing the characteristic early and late features of Fas-mediated apoptosis, including activation of caspases. Our results indicate that the elevated MAPK activities intervene upstream of caspase activation. The degree of MAPK activation by the different stimuli used in our study corresponds well to their potency to inhibit apoptosis, indicating that MAPK activation serves as an efficient modulator of Fas-mediated apoptosis. The role of MAPK in modulation of Fas-mediated apoptosis was further corroborated by transient transfection with constitutively active MAPK kinase, resulting in complete inhibition of the Fas response, whereas transfection with a dominant negative form of MAPK kinase had no effect. Furthermore, the apoptosis inhibitory effect of the MAPK activators could be abolished by the specific MAPK kinase inhibitor PD 098059. Modulation of Fas responses by MAPK signaling may determine the persistence of an immune response and may explain the insensitivity of recently activated T cells to Fas receptor stimulation.

An effective technique was developed, which allowed rapid isolation of highly pure myelin basic protein (MBP) including its distinct isoforms. The procedure employs homogenization of central nervous system (CNS) tissue in chloroform, which specifically extracts MBP. Subsequently, methanol was used to convert the protein susceptible to quantitative transfer into the acidic aqueous phase. MBP was purified from bovine, chicken, fish, human, guinea-pig, mouse, rabbit, rat, and swine brains. Analysis on SDS-PAGE and immunoblotting using polyclonal MBP-specific serum recognized proteins corresponding to the sizes of previously identified MBP isoforms of 21.5, 18.5, 17.2, and 14.2 kDa and three predicted isoforms of 20.2, 16.0, and 13 kDa. The MBP obtained was readily soluble in water and possessed the capacity to induce experimental autoimmune encephalomyelitis in susceptible mice. The protein was also suitable for use as a substrate for protein kinases., (Copyright 1997 Academic Press.)

Cerebellar granule neurons cultured with serum develop a mature neuronal phenotype, including stimulus-coupled release of glutamate, and depend on elevated potassium for survival. We find that cells cultured with serum undergo two phases of cell death. By 6 d in vitro, 30-50% of the cells present are dead; after this time the remaining cells die. Elevated potassium prevents only this later phase of death, whereas neurotrophins protect these cells against the early phase of death. Factors that bind p75(NTR) or TNF-R, members of the same receptor family, exhibit voltage-sensitive calcium channel-dependent protection, whereas ligands of expressed Trk receptors show additional calcium channel-independent protection. The cells express TrkB protein and show elevated c-Fos and c-Jun levels in response to BDNF. No TrkA is detected, although p75(NTR) protein is expressed and NGF induces depolarization-dependent elevation of c-Jun levels. In the presence of the protein kinase C inhibitor bisindolylmaleimide, BDNF-induced survival promotion is reduced partially, whereas NGF-induced death is unmasked. Basal survival mechanisms are insensitive to inhibition of PK-C or PI-3 kinase. We conclude that BDNF promotes survival in part via its TrkB receptor, whereas there is an additional pathway promoting survival and elevating c-Jun evoked by both NGF and BDNF via a non-Trk receptor.

Objective: To assess the impact of pharmacist-operated refill clinics on practitioner (physician/physician assistant) time. Secondary objectives included assessment of disease state control, drug acquisition costs, and human resource allocation., Design: The study ran from October 1, 1993 through January 31, 1994. At one clinic the pharmacist performed chart review only and did not see the patient. At the second site the pharmacist also interviewed the patient. The pharmacist used no treatment algorithms. Practitioner and pharmacist time before and after implementation of the refill clinics was measured on 3 consecutive days of normal clinic operation., Setting: Two state correctional facilities., Patients: The study population consisted of patients receiving chronic care who were observed during regular clinic hours., Main Outcome Measures: We evaluated pharmacist and practitioner time before and after pharmacist involvement. Hypertension was the only disease state yielding sufficient numbers for statistical analysis. We used a two-tailed paired t-test with the priori level set at 0.05. We also evaluated the number of patients with disease state control before and after clinic implementation, drug acquisition costs, and human resource allocation., Results: The refill clinic pharmacist reduced practitioner time commitment in both clinics. The greatest impact on practitioner time was found in the interview clinic. Quality of care was maintained equally between the two clinics, with a positive impact on human resource allocation., Conclusions: In the managed care environment, pharmacist-run refill clinics can decrease practitioner time commitment allowing reallocation of human resources while maintaining current quality of care.