Search

Mitochondrial proteins are organized in an unexpectedly large number of protein complexes, supercomplexes, and dynamic protein networks. Protein networks have been observed for different categories of mitochondrial function, such as preprotein transport, energetics, membrane organization, and quality control. The mitochondrial import network (MitimNet) forms an overarching cross-cutting network that couples mitochondrial protein translocases to machineries of energy conversion, metabolite transport, cellular proteostasis, and membrane contact sites. MitimNet is highly dynamic to ensure the plasticity of mitochondrial biogenesis, function, and quality control in response to cellular and mitochondrial demands. Mitochondria perform crucial functions in cellular metabolism, protein and lipid biogenesis, quality control, and signaling. The systematic analysis of protein complexes and interaction networks provided exciting insights into the structural and functional organization of mitochondria. Most mitochondrial proteins do not act as independent units, but are interconnected by stable or dynamic protein–protein interactions. Protein translocases are responsible for importing precursor proteins into mitochondria and form central elements of several protein interaction networks. These networks include molecular chaperones and quality control factors, metabolite channels and respiratory chain complexes, and membrane and organellar contact sites. Protein translocases link the distinct networks into an overarching network, the mitochondrial import network (MitimNet), to coordinate biogenesis, membrane organization and function of mitochondria. [ABSTRACT FROM AUTHOR]

Mogk and den Brave discuss exciting results from a comprehensive screen of heat shock response components in yeast, published in this issue by Pincus and colleagues (https://doi.org/10.1083/jcb.202401082). Their work reveals modulatory regulatory loops that fine-tune the timing of the shutdown of this highly conserved pathway. [ABSTRACT FROM AUTHOR]

Introduction: Root canal debridement, irrigation and a microorganism-free environment are key factors in the success of root canal treatment. Intracanal medicaments are used to enhance root canal disinfection. Simvastatin is derived from lovastatin and is a semisynthetic medication. This study compares and evaluates the effect of simvastatin and double antibiotic paste (DAP) as an intracanal medicament in single-rooted teeth with apical periodontitis using colony-forming units (CFUs)/ml. Materials and Methods: Twenty-eight patients with single-rooted teeth diagnosed with apical periodontitis were selected. Under aseptic conditions, patency was gained, sterile saline solution was deposited in the canal and the first sample (S1) was collected. Cleaning and shaping were then carried out following an appropriate technique depending on the configuration of the canal. After irrigation and biomechanical preparation, teeth were randomly assigned to two different groups, and the test intracanal medicament was applied to the root canals. Coronal openings were sealed with temporary restorative cement. The second sample (S2) was collected after 7 days. The samples obtained were checked for a reduction in the bacterial load. They were incubated aerobically for 48 h, and the CFUs were calculated. The Mann–Whitney U and Wilcoxon's signed-rank tests were used to analyse the results statistically. Results: A significant reduction in bacterial count was present after administration of the intracanal medicament. On intergroup comparison, there was no statistically significant difference in bacterial decrease between the two groups. Comparatively, the mean reduction in the bacterial count was higher in the DAP group. Conclusion: It can be concluded that DAP and simvastatin were effective in the reduction of the bacterial count in single-rooted teeth diagnosed with apical periodontitis. However, DAP demonstrated a better performance in the reduction of bacterial counts. [ABSTRACT FROM AUTHOR]

Objective: Robot-assisted gait training (RAGT) is often used as a rehabilitation tool for neurological impairments. The purpose of this study is to investigate the effects of rehabilitation with robotic devices on quality of life and depression. Data sources: Two electronic databases (MEDLINE and Scopus) were searched for studies from inception up to December 2022. Review methods: Randomized controlled trials (RCTs) and non-RCTs were pooled separately for analyses, studying each one's mental and physical health and depression. Random effect meta-analyses were run using standardized mean difference and 95% confidence interval (CI). Results: A total of 853 studies were identified from the literature search. 31 studies (17 RCTs and 14 non-RCTs) including 1151 subjects met the inclusion criteria. 31 studies were selected for the systematic review and 27 studies for the meta-analysis. The outcome measure of mental health significantly improved in favor of the RAGT group in RCTs and non-RCTs (adjusted Hedges'g 0.72, 95% CI: 0.34–1.10, adjusted Hedges g = 0.80, 95% CI 0.21-1.39, respectively). We observed a significant effect of RAGT on physical health in RCTs and non-RCTs (adjusted Hedges'g 0.58, 95% CI 0.28, 0.88, adjusted Hedges g = 0.73, 95% CI 0.12, 1.33). After realizing a sensitivity analysis in RCTs, a positive impact on depression is observed (Hedges' g of −0.66, 95% CI −1.08 to −0.24). Conclusion: This study suggests that RAGT could improve the quality of life of patients with neurological impairments. A positive impact on depression is also observed in the short term. Further studies are needed to differentiate grounded and overgrounded exoskeletons as well as RCT comparing overground exoskeletons with a control group. [ABSTRACT FROM AUTHOR]

Background: Literature shows that newly qualified nurse-midwives face challenges integrating into the workforce during their transition period from education to practice. However, little is known about the needs and challenges of Malawian nurse-midwives during their transition from education to practice. The aim of the study was to explore the transition experiences of newly qualified nurse-midwives working in selected midwifery units in Northern Malawi. Methodology: A qualitative descriptive approach was used. Data were collected through in-depth interviews using semi-structured interview guides from a purposive sample of 19 participants (13 newly qualified nurse-midwives and 6 key informants). The researchers developed two interview guides; one for the newly qualified nurse-midwives and another one for the key informants. The interview guides had questions related to newly qualified nurse-midwives experiences of transitioning to practice and the support they received. Participants were from three selected hospitals in the Northern part of Malawi that have maternity units. Data were analysed manually using thematic analysis. Findings: Five themes related to challenges faced by newly qualified nurse-midwives during their transition to practice in midwifery units emerged from the thematic analysis of the data. These included (1) Theory—practice gap, (2) Lack of confidence and skills, (3) Inadequate resources, (4) Transition support system, and (5) Workplace conflict. Conclusion: Newly qualified nurse-midwives in Malawi encounter many challenges while transitioning from education to practice. The study findings underscore the need to develop a national framework support system that could not only help newly qualified midwives adjust positively to their new role but also create more opportunities for learning and developing and strengthening a collaborative partnership between colleges and hospitals. [ABSTRACT FROM AUTHOR]

Objective: Academic physical therapy has no universal metrics by which educational programs can measure outcomes, limiting their ability to benchmark to their own historical performance, to peer institutions, or to other health care professions. The PT-Graduation Questionnaire (GQ) survey, adapted from the Association of American Medical Colleges' GQ, addresses this gap by offering both inter-professional insight and fine-scale assessment of physical therapist education. This study reports the first wave of findings from an ongoing multi-site trial of the PT-GQ among diverse academic physical therapy programs, including (1) benchmarks for academic physical therapy, and (2) a comparison of the physical therapist student experience to medical education benchmarks. Methods: Thirty-four doctor of physical therapy (DPT) programs (13.2% nationwide sample) administered the online survey to DPT graduates during the 2019 to 2020 academic year. PT-GQ and Association of American Medical Colleges data were contrasted via Welch's unequal-variance t test and Hedges g (effect size). Results: A total of 1025 respondents participated in the study (response rate: 63.9%). The average survey duration was 31.8 minutes. Overall educational satisfaction was comparable with medicine, and respondents identified areas of curricular strength (eg, anatomy) and weakness (eg, pharmacology). DPT respondents provided higher ratings of faculty professionalism than medicine, lower rates of student mistreatment, and a lesser impact of within-program diversity on their training. One-third of respondents were less than "satisfied" with student mental health services. DPT respondents reported significantly higher exhaustion but lower disengagement than medical students, along with lower tolerance for ambiguity. Of DPT respondents who reported educational debt, one-third reported debt exceeding $150,000, the threshold above which the DPT degree loses economic power. Conclusions: These academic benchmarks, using the PT-GQ, provided insight into physical therapist education and identified differences between physical therapist and medical student perceptions. Impact: This ongoing trial will establish a comprehensive set of benchmarks to better understand academic physical therapy outcomes. [ABSTRACT FROM AUTHOR]

Mitochondria import about 1000 proteins that are produced as precursors on cytosolic ribosomes. Defects in mitochondrial protein import result in the accumulation of nonimported precursor proteins and proteotoxic stress. The cell is equipped with different quality control mechanisms to monitor protein transport into mitochondria. First, molecular chaperones guide unfolded proteins to mitochondria and deliver non-imported proteins to proteasomal degradation. Second, quality control factors remove translocation stalled precursor proteins from protein translocases. Third, protein translocases monitor protein sorting to mitochondrial subcompartments. Fourth, AAA proteases of the mitochondrial subcompartments remove mislocalized or unassembled proteins. Finally, impaired efficiency of protein transport is an important sensor for mitochondrial dysfunction and causes the induction of cellular stress responses, which could eventually result in the removal of the defective mitochondria by mitophagy. In this review, we summarize our current understanding of quality control mechanisms that govern mitochondrial protein transport. [ABSTRACT FROM AUTHOR]

Manipulative-based instructional sequences have proven to be successful with students with disabilities. However, instruction must not only support the acquisition of conceptual and procedural knowledge but also build on students’ strengths. This article describes how teachers can use manipulative-based instructional sequences to support the fractional understanding of students who are diagnosed with mathematical learning disabilities. We begin by describing common misconceptions that may affect students’ abilities to reason with and calculate fractions. We then explain how teachers can use a concrete-semi-concrete representational-abstract (CRA) model to plan and implement lessons that maximize learning and minimize frustration. Readers are also provided with detailed descriptions of how teachers can assess fraction knowledge, reinforce conceptual understanding, and promote procedural fluency. [ABSTRACT FROM AUTHOR]

Economic development strategies centered on the presence of industry clusters have become quite popular with local policy makers. With this in mind, we test whether or not the degree of cluster complementarity in a given urban area does in fact lead to it having a persistent economic advantage over its peers. Using a spatial factor model built on growth accounting principles, we show that this is indeed the case by identifying key agglomeration factors influencing urban growth. However, our results suggest substantial heterogeneity exists in the types of policies that are likely to best support local economies based on their cluster complementarity. [ABSTRACT FROM AUTHOR]

Mitochondria import 1000–1300 different precursor proteins from the cytosol. The main mitochondrial entry gate is formed by the translocase of the outer membrane (TOM complex). Molecular coupling and modification of TOM subunits control and modulate protein import in response to cellular signaling. The TOM complex functions as regulatory hub to integrate mitochondrial protein biogenesis and quality control into the cellular proteostasis network. • Multifunctional properties of translocase of outer mitochondrial membrane (TOM) • TOM complex interacts with preproteins, cytosolic chaperones and translocases. • TOM participates in quality control pathways and stress response reactions. • TOM as regulatory hub in protein biogenesis, cellular proteostasis and signaling [ABSTRACT FROM AUTHOR]

Corridors are intended to increase species survival by abating landscape fragmentation resulting from the conversion of natural habitats into human‐dominated matrices. Conservation scientists often rely on 1 type of corridor model, typically the least‐cost model or current‐flow model, to construct a linkage design, and their choice is not usually based on theory or empirical evidence. We developed a method to empirically confirm whether corridors produced by these 2 models are used by target species under current landscape conditions. We applied this method in the Gamba landscape between 2 national parks in southwestern Gabon. We collected signs of presence of African forest elephant (Loxodonta cyclotis), forest buffalo (Syncerus caffer nanus), and 2 apes, western lowland gorilla (Gorilla gorilla gorilla) and central chimpanzee (Pan troglodytes troglodytes), on transects. We used patch‐occupancy models to identify least‐cost and current‐flow corridors for these 4 species. On average, 28.7% of current‐flow corridors overlapped with least‐cost corridors, confirming that the choice of corridor model can affect the location of the resulting linkage design. We validated these corridors by monitoring signs and examining camera detections on new transects within and outside modeled corridors. Current‐flow corridors performed better than least‐cost corridors for elephants, whereas the opposite was found for buffalo and apes. Locations of the highest priority corridors for the 3 taxa did not overlap, and only 18.3% of their combined surface was common among 2 species. We used centrality metrics to calculate the average contribution of corridor pixels to landscape connectivity and derived an index that can be used to prioritize corridors. As a result, we recommend protecting at least 17.4% of the land surface area around Gamba town to preserve the preferred travel routes of the target species. Article impact statement: Choice of corridor model affects corridor locations and needs empirical validation before linkage design is approved. [ABSTRACT FROM AUTHOR]

Purpose: To examine the prevalence of common psychiatric disorders and associated treatment-seeking, stratified by gender, among American Indians/Alaska Natives and non-Hispanic whites in the United States. Lifetime and 12-month rates are estimated, both unadjusted and adjusted for sociodemographic correlates.Method: Analyses were conducted with the American Indians/Alaska Native (n = 701) and Non-Hispanic white (n = 24,507) samples in the 2001-2002 National Epidemiologic Survey on Alcohol and Related Conditions [(NESARC) n = 43,093].Results: Overall, 70 % of the American Indian/Alaska Native men and 63 % of the women met criteria for at least one Diagnostic and Statistical Manual-IV lifetime disorder, compared to 62 and 53 % of Non-Hispanic white men and women, respectively. Adjusting for sociodemographic correlates attenuated the differences found. Nearly half of American Indians/Alaska Natives had a psychiatric disorder in the previous year; again, sociodemographic adjustments explained some of the differences found. Overall, the comparisons to non-Hispanic whites showed differences were more common among American Indian/Alaska Native women than men. Among those with a disorder, American Indian/Alaska Native women had greater odds of treatment-seeking for 12-month anxiety disorders.Conclusion: As the first study to provide national estimates, by gender, of the prevalence and treatment of a broad range of psychiatric disorders among American Indians/Alaska Natives, a pattern of higher prevalence of psychiatric disorder was found relative to Non-Hispanic whites. Such differences were more common among women than men. Prevalence may be overestimated due to cultural limitations in measurement. Unmeasured risk factors, some specific to American Indians/Alaska Natives, may also partially explain these results. [ABSTRACT FROM AUTHOR]

Modification by the ubiquitin-like protein SUMO affects hundreds of cellular substrate proteins and regulates a wide variety of physiological processes. While the SUMO system appears to predominantly target nuclear proteins and, to a lesser extent, cytosolic proteins, hardly anything is known about the SUMOylation of proteins targeted to membrane-enclosed organelles. Here, we identify a large set of structurally and functionally unrelated mitochondrial proteins as substrates of the SUMO pathway in yeast. We show that SUMO modification of mitochondrial proteins does not rely on mitochondrial targeting and, in fact, is strongly enhanced upon import failure, consistent with the modification occurring in the cytosol. Moreover, SUMOylated forms of mitochondrial proteins particularly accumulate in HSP70- and proteasome-deficient cells, suggesting that SUMOylation participates in cellular protein quality control. Wetherefore propose thatSUMOserves as a mark for nonfunctional mitochondrial proteins, which only sporadically arise in unstressed cells but strongly accumulate upon defective mitochondrial import and impaired proteostasis. Overall, our findings provide support for a role of SUMO in the cytosolic response to aberrant proteins. [ABSTRACT FROM AUTHOR]

Twenty six samples of Permian high latitude sedimentary rocks from the southern Sydney Basin were analysed using organic geochemical methods for their thermal maturity, organic matter inputs, and depositional environment. Fourteen samples are from the Elecom Clyde River (ECR) DDH01 borehole (inland; Southern Highlands), and 12 are from the ECR-DDH07 borehole (coastal; near Nowra). The analysed formations are the Berry Siltstone, the Nowra Sandstone, the Wandrawandian Siltstone, the Snapper Point Formation and the Pebbley Beach Formation. This study is the first organic geochemical study of samples from the Berry Siltstone and Nowra Sandstone. The formations mostly have total organic carbon varying from 1 to 2 wt%, but the Snapper Point Formation is leaner in TOC (0.2–0.7 wt%). The samples vary from low to very high thermal maturity. The samples from the ECR-DDH01 borehole are in the early to middle of the oil window (vitrinite reflectance equivalent = 0.60–0.80%), based on hopane, sterane, alkylnaphthalene, alkylphenanthrene, alkylbiphenyl, and alkyldibenzothiophene thermal maturity parameters. The samples from the ECR-DDH07 borehole are much more thermally mature, in the late part of the oil window to the early gas window (vitrinite reflectance equivalent = 1.2–1.7%). This high thermal maturity has led to the loss of nearly all polycyclic biomarkers, and the thermal rearrangement of many groups of compounds, including monomethylalkanes. The ECR-DDH01 borehole location and time-equivalent outcrop samples south-west of Ulladulla have similar thermal maturities and are close to the margins of the Sydney Basin, and it is estimated to have previously been covered by about 3 km of overburden. In contrast, the samples in the ECR-DDH07 borehole were buried much deeper, with about 4–5 km of overburden, which means that only limited information about their source inputs and depositional environment could be recovered. Aliphatic biomarker, n -alkane and aromatic data are consistent with an overall strong terrigenous organic matter input for the samples from the ECR-DDH01 borehole. Sterane/hopane ratios are mostly low, but only a few compounds diagnostic of specific source inputs were identified. There is a microbially-dominated sample near the base of the Snapper Point Formation (high C 29 αβ hopane/C 30 αβ hopane ratio and 2α-methylhopanes), and high amounts of parent polycyclic aromatic hydrocarbons in some samples from the Berry Siltstone, likely reflecting an occasional pyrogenic signature from palaeo-forest fires. Several parameters, including sterane carbon number distributions, terpane ratios and the relative abundance of dibenzofuran compared to phenanthrene show that the samples from the ECR-DDH01 borehole have a more strongly terrigenous signal than the previously analysed outcrop samples. This is inferred to be because the ECR-DDH01 location was closer to the palaeo-shoreline than the likely more distal outcrop samples. Based on the pristane/phytane ratio and hopane distributions, deposition of the sediments was under varying oxicity conditions, from highly oxic to suboxic. The inferred environments are marine shale/lacustrine and fluvial/deltaic, so the organic geochemical data agrees with the Permian depositional history of the southmost part of the Sydney Basin previously inferred from sedimentological and palaeogeographic studies. • Biomarker and HC distributions reported for Permian high latitude sedimentary rocks in southern Sydney Basin, Australia. • Geochemical data consistent with a strong terrigenous organic matter input for the samples from the inland borehole. • High amounts of parent PAH in the inland borehole likely reflects a spasmodic pyrogenic signature from palaeo-forest fires. • Based on Pr/Ph and hopane distributions, deposition was under varying oxicity conditions, from highly oxic to suboxic. • Thermal maturity greater in the coastal borehole (1.2–1.7% VRE) than inland (0.60–0.80% VRE), due to greater burial. [ABSTRACT FROM AUTHOR]

In this text we are reporting back on the practice-based research project Precarity Pilot. The starting point for this research is the fact that in today's Europe, design graduates are entering into a landscape of precarious work. This research-in-progress thus enquires into how formal and informal design education can be a space where to empower young designers to transformatively engage with the precarious work politics of their profession. As a mid-way result, here we present a series of didactic proposals and strategic questions for how issues of socio-economic precariousness can be transformatively addressed. This result is based on a series of half-day workshops we have been running between 2014 and 2016 with design students, recent graduates and design educators in the United Kingdom, Germany, Poland and Italy. We address these proposals to educators, managers and students alike as we are convinced that everyone involved in education has agency over how the learning process unfolds. [ABSTRACT FROM AUTHOR]

Objective: Rare co-existance of disease or pathology Background: Mucinous ovarian adenocarcinoma is one of the less common epithelial cancers of the ovaries, and typically does not occur in younger women. Nearly all mucinous ovarian adenocarcinomas present with early-stage disease without significant sequelae of cancer, such as clotting. Anchoring bias is a common problem in medicine that has been shown to significantly affect physician decision-making. Case Report: We present the case of a 24-year-old healthy female Chinese immigrant with no significant past medical history, who presented with a subacute history of nonproductive cough and shortness of breath with exertion. Initial workup was directed towards diagnosis of tuberculosis and other infectious etiologies due to anchoring to patient's nationality and her positive family history for tuberculosis. She was eventually diagnosed with extensive bilateral pulmonary emboli and bilateral deep vein thromboses as well as a right ventricular thrombus. This extensive clot burden helped lead to the diagnosis of mucinous ovarian adenocarcinoma. Conclusions: This case is significant not only because the diagnosis of mucinous ovarian adenocarcinoma is uncommon in healthy young females under the age of 25, but, more importantly, because such extensive pulmonary emboli and deep vein thromboses in a young female with local/early-stage ovarian cancer is very rare. This case is also significant because it serves as an important reminder of the risks of anchoring bias in skewing perceptions and delaying the correct diagnosis by physicians. [ABSTRACT FROM AUTHOR]

The article discusses effective applications for hyperbaric oxygen (HBO2) therapy including its contraindications, nursing considerations and safety issues. Topics include the reference to the one hundred percent oxygen-pressurized hyperbaric chambers, greater than atmospheric conditions relative to body's ambient pressure as well as Henry's Law on gas behaviors as with carbon dioxide (CO2). Also mentioned are oxygen dissolution in blood plasma, oxygen therapeutic levels and hemoglobin.

Although there is literature concentrating on cross-cultural approaches to academic and community partnerships with Native communities, few address the process and experiences of American Indian women leading federally funded and culturally grounded behavioral health intervention research in Native communities. This paper summarizes relevant literature on community-engaged research with Native communities, examines traditional roles and modern challenges for American Indian women, describes the culturally grounded collaborative process for the authors' behavioral health intervention development with Native communities, and considers emergent themes from our own research experiences navigating competing demands from mainstream and Native communities. It concludes with recommendations for supporting and enhancing resilience. [ABSTRACT FROM AUTHOR]

We describe the new command margte, which computes marginal and average treatment effects for a model with a binary treatment and a continuous outcome given selection on unobservables and returns. Marginal treatment effects differ from average treatment effects in instances where the impact of treatment varies within a population in correlation with unobserved characteristics. Both parametric and semiparametric estimation methods can be used with margte, and we provide evidence from a Monte Carlo simulation for when each is preferable. [ABSTRACT FROM AUTHOR]

We examined health disparities among American Indian men and boys within the framework of historical trauma, which incorporates the historical context of collective massive group trauma across generations. We reviewed the impact of collective traumatic experiences among Lakota men, who have faced cross--generational challenges to enacting traditional tribal roles. We describe historical trauma-informed interventions used with two tribal groups: Lakota men and Southwestern American Indian boys. These two interventions represent novel approaches to addressing historical trauma and the health disparities that American Indians face. We offer public health implications and recommendations for strategies to use in the planning and implementation of policy, research, and program development with American Indian boys and men. [ABSTRACT FROM AUTHOR]

Indigenous Peoples of the Americas have experienced devastating collective, intergenerational massive group trauma and compounding discrimination, racism, and oppression. There is increasing evidence of emotional responses to collective trauma and losses among Indigenous Peoples, which may help to inform ways of alleviating psychological suffering and unresolved grief. Tribal cultural and regional differences exist which may impact how the wounding across generations and within an individual's lifespan are experienced and addressed. This article will review the conceptual framework of historical trauma, current efforts to measure the impact of historical trauma upon emotional distress, and research as well as clinical innovations aimed at addressing historical trauma among American Indians/Alaska Natives and other Indigenous Peoples of the Americas. We will discuss assessment of historical trauma and implications for research and clinical as well as community interventions, and conclude with recommendations. [ABSTRACT FROM AUTHOR]

Purpose: On December 15, 2008, the US Food and Drug Administration approved plerixafor (Mozobil®; Genzyme Corp.), a new small-molecule inhibitor of the CXCR4 chemokine receptor, for use in combination with granulocyte colony-stimulating factor (G-CSF) to mobilize hematopoietic stem cells (HSC) to the peripheral blood for collection and subsequent autologous transplantation in patients with non-Hodgkin’s lymphoma (NHL) and multiple myeloma (MM). This summary reviews the database supporting this approval. Experimental Design: The safety and efficacy of plerixafor were demonstrated by 2 multicenter, randomized, placebo-controlled studies in patients with NHL and MM who were eligible for autologous HSC transplantation. The primary efficacy end points were the collection of ≥5 × 106 CD34+ cells/kg from the peripheral blood in 4 or fewer apheresis sessions in patients with NHL or ≥6 × 106 CD34+ cells/kg from the peripheral blood in 2 or fewer apheresis sessions in patients with MM. Results: The 2 randomized studies combined enrolled 600 patients (298 with NHL and 302 with MM). Fifty-nine percent of patients with NHL who were mobilized with G-CSF and plerixafor had peripheral blood HSC collections of ≥5 × 106 CD34+ cells/kg in 4 or fewer apheresis sessions, compared with 20% of patients with NHL who were mobilized with G-CSF and placebo (p < 0.001). Seventy-two percent of patients with MM who were mobilized with Mozobil and G-CSF had peripheral blood HSC collections of ≥6 × 106 CD34+ cells/kg in 2 or fewer apheresis sessions, compared with 34% of patients with MM who were mobilized with placebo and G-CSF (p < 0.001). Common adverse reactions included diarrhea, nausea, vomiting, flatulence, injection site reactions, fatigue, arthralgia, headache, dizziness, and insomnia. Conclusions: This report describes the Food and Drug Administration review supporting the approval of plerixafor. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Delivery of DNA encoding foreign antigens into mammalian cells can induce adaptive immune responses. There are currently many DNA-based vaccines in clinical trials against infectious diseases and cancer but there is a lack of adjuvants for improvement of responses to DNA-based vaccines. Here, we show augmented systemic and mucosa-associated B cell responses after immunization with a cocktail of seven different plasmids (3 env, 2 gag, 1 rev, 1 RT) combined with mitogen activated apoptotic syngeneic lymphocytes in mice. In addition we show that apoptotic cells can function as adjuvant for induction of cellular immune responses in a magnitude comparable to the cytokine adjuvant GM-CSF in mice. These data suggest that activated apoptotic lymphocytes can act independent as adjuvants to improve antigen-specific DNA vaccines. [Copyright &y& Elsevier]

Human Plants, Human Harvest: The Hidden History of California Eugenics is the first-ever exhibition on the history of eugenics in California. The disappearance of this history for half a century, and the consequent absence of a "collective memory," were the primary factors determining the exhibit's structure and content. Responses to the exhibit confirmed that most visitors "never knew" about this history. The exhibit is described in some detail, with selected imagery from the exhibit reproduced. After the initial exhibition, responses of other museums and foundation officials revealed a continuing resistance to this history being publicly displayed, though the sources of resistance varied. [ABSTRACT FROM AUTHOR]

Abstract: Embodied computer agents are becoming an increasingly popular human–computer interaction technique. Often, these agents are programmed with the capacity for emotional expression. This paper investigates the psychological effects of emotion in agents upon users. In particular, two types of emotion were evaluated: self-oriented emotion and other-oriented, empathic emotion. In a 2 (self-oriented emotion: absent vs. present) by 2 (empathic emotion: absent vs. present) by 2 (gender dyad: male vs. female) between-subjects experiment , empathic emotion was found to lead to more positive ratings of the agent by users, including greater likeability and trustworthiness, as well as greater perceived caring and felt support. No such effect was found for the presence of self-oriented emotion. Implications for the design of embodied computer agents are discussed and directions for future research suggested. [Copyright &y& Elsevier]

Discusses the relationship of historical trauma (HT) response with substance abuse among Lakota Indians. Ways to incorporate HT theory in treatment, research and evaluation; Description of massive cumulative trauma across generations; Limitation in the diagnosis of posttraumatic stress disorder.

The historical trauma response is a constellation of characteristics associated with massive cumulative group trauma across generations, similar to those found among Jewish Holocaust survivors and descendants. Trauma response features include elevated mortality rates and health problems emanating from heart disease, hypertension, alcohol abuse, and suicidal behavior. This article explores gender differences in the historical trauma response among the Lakota (Teton Sioux) and the correlation with health and mental health statistics. The theory of a Lakota historical trauma response is first explained. Traditional gender roles are described in combination with modifications engendered by traumatic Lakota history. Then, data from a study on Lakota historical trauma are presented, including gender differences in response to an experimental intervention aimed at facilitating a trauma resolution process. The data revealed significant gender differences. The sample of women presented initially with a greater degree of conscious affective experience of historical trauma. In contrast, the men reported more lifespan trauma associated with boarding school attendance and appeared to be at an earlier stage of grief. However, at the end of the intervention, women's experience of survivor guilt--a significant trauma response feature--decreased while men's consciousness of historical trauma and unresolved grief increased. Degree of traditional presentation-of-self, including phenotype, appeared to interact with gender to place male participants at greater risk for being traumatized over the lifespan and perhaps subsequently utilizing more rigid defenses against the conscious experience of the trauma with the exception of survivor guilt. The article concludes with a discussion of health and mental health implications for prevention and treatment of the trauma response which could positively impact the health status of the Lakota. Recommendations for future research are suggested. [ABSTRACT FROM AUTHOR]

This article, based on research conducted with Lakota human service providers, concludes that the Lakota (Teton Sioux) suffer from impaired grief of an enduring and pervasive quality. Impaired grief results from massive cumulative trauma associated with such cataclvsnuic events as the assassination of Sitting Built , the Wounded Knee Massacre, and the forced removal of Lakota children to boarding schools. The research studied a culturally syntonic four-day psycho educational intervention designed to initiate a grief resolution process for a group of 45 Lakota human service providers. The methodology included assessment at three intervals: (a) a pre- and post-test, utilizing a Lakota Grief Experience Questionnaire and the semantic differential, (b) a self-report evaluation instrument at the end of the intervention, and (c) a six-week-follow-up questionnaire. The results confirmed the hypotheses that: (a) education about historical trauma would lead to increased awareness of the impact and associated grief-related affects of the traumatic Lakota history, (b) sharing these affects with other Lakota in a traditional context would provide cathartic relief, and (c) grief resolution would be initiated, including a reduction in grief affects, more positive identity, and a commitment to individual and community healing. [ABSTRACT FROM AUTHOR]

Respiratory and pulmonary diseases are among the leading causes of death globally. Despite tremendous advancements, there are no effective pharmacological therapies capable of curing diseases such as COPD (chronic obstructive pulmonary disease), ARDS (acute respiratory distress syndrome), and COVID-19. Novel and innovative therapies such as advanced therapy medicinal products (ATMPs) are still in early development. However, they have exhibited significant potential preclinically and clinically. There are several longitudinal studies published, primarily focusing on the use of cell therapies for respiratory diseases due to their anti-inflammatory and reparative properties, thereby hinting that they have the capability of reducing mortality and improving the quality of life for patients. The primary objective of this paper is to set out a state of the art review on the use of aerosolized MSCs and their potential to treat these incurable diseases. This review will examine selected respiratory and pulmonary diseases, present an overview of the therapeutic potential of cell therapy and finally provide insight into potential routes of administration, with a focus on aerosol-mediated ATMP delivery. [ABSTRACT FROM AUTHOR]

The Journal of Architectural Education features an interview with Brett Story, Emily Kassie, and Julian Brave NoiseCat, discussing their documentary filmmaking practices within the context of worlding. They explore colonial and capitalist violence through projects like Sugarcane and The Prison in Twelve Landscapes, delving into the politics and radical imaginaries these films evoke. The conversation touches on the importance of storytelling, the impact of residential schools and the prison-industrial complex on communities, and the need for truth-telling and reconciliation. The filmmakers highlight the significance of stewardship, self-determination, and the generational divide in addressing systemic issues and envisioning new worlds. [Extracted from the article]

Purpose: Risks of handheld electrical weapons include head impact trauma associated with uncontrolled falls, ocular probe penetration injuries, thermal injuries from the ignition of volatile fumes, and weapon confusion police-involved shooting. There is also an uncommon but critical risk of a shooting after a subject gained control of an officer's electrical weapons. Methods: The authors searched for police shooting incidents involving loss of control of TASER® weapons via open-source media reports, crowd-sourced internet sites, litigation filings, and a survey of Axon law-enforcement master instructors. Results: The authors report 131 incidents of subjects attempting to or gaining control of an officer's electrical weapon from 2004 to 2020, 53 of which resulting in a shooting. These incidents demonstrated a risk of 11.8 shootings per million electrical weapon discharges (95% confidence limits of 9.0 to 15.1 per million by Wilson score interval). Conclusions: The use of electrical weapons presents a rare but real risk of injury and death from a shooting following a subject's attempts to gain control of the weapon. [ABSTRACT FROM AUTHOR]

Background: Acquired thrombophilia is a potential sequela of malignancy, chronic inflammation, and conditions characterized by severe protein deficiency (for example, nephrotic syndrome, protein-losing enteropathy). As such, venous thrombosis is often a feature, and occasionally a presenting sign, of systemic disease. Ménétrier's disease is a rare hyperplastic gastropathy that may lead to gastrointestinal protein loss and hypoalbuminemia. To date, reports of venous thrombosis associated with Ménétrier's disease are exceedingly scarce.Case Presentation: We report the case of a 40-year-old white man who presented with unprovoked deep venous thrombosis, pulmonary embolism, and renal vein thrombosis. Upon receiving therapeutic anticoagulation, he developed severe gastrointestinal bleeding, and endoscopic evaluation led to a diagnosis of Ménétrier's disease. A laboratory workup revealed deficiency of protein C, protein S, and antithrombin III, as well as markedly elevated levels of factor VIII. He was determined to have an acquired thrombophilia as a direct result of Ménétrier's disease.Conclusions: This case describes an acquired thrombophilic state in a patient with Ménétrier's disease and profound hypoalbuminemia. Although this association is rarely described, we discuss the probable mechanisms leading to our patient's thrombosis. Specifically, we posit that his gastrointestinal protein loss led to a deficiency of several anticoagulant proteins and a compensatory elevation in factor VIII, as occurs in nephrotic syndrome and inflammatory bowel disease. Of note, this patient's recurrent venous thrombosis was the initial clinical sign of his gastrointestinal pathology. [ABSTRACT FROM AUTHOR]