Marine protected areas, marine heatwaves, and the resilience of nearshore fish communities.

Anthropogenic stressors from climate change can affect individual species, community structure, and ecosystem function. Marine heatwaves (MHWs) are intense thermal anomalies where water temperature is significantly elevated for five or more days. Climate projections suggest an increase in the frequency and severity of MHWs in the coming decades. While there is evidence that marine protected areas (MPAs) may be able to buffer individual species from climate impacts, there is not sufficient evidence to support the idea that MPAs can mitigate large-scale changes in marine communities in response to MHWs. California experienced an intense MHW and subsequent El Niño Southern Oscillation event from 2014 to 2016. We sought to examine changes in rocky reef fish communities at four MPAs and associated reference sites in relation to the MHW. We observed a decline in taxonomic diversity and a profound shift in trophic diversity inside and outside MPAs following the MHW. However, MPAs seemed to dampen the loss of trophic diversity and in the four years following the MHW, taxonomic diversity recovered 75% faster in the MPAs compared to reference sites. Our results suggest that MPAs may contribute to long-term resilience of nearshore fish communities through both resistance to change and recovery from warming events.

Effectiveness of self-financing patient-led support groups in the management of hypertension and diabetes in low- and middle-income countries: Systematic review.

OBJECTIVE: There is insufficient evidence on the role of self-financing patient support groups in the control of blood pressure (BP) and/or diabetes in low- and middle-income countries (LMICs). We conducted a systematic review to investigate the effectiveness of these groups in BP and glycaemic control. METHODS: We searched PubMed, Embase, SCOPUS, Web of Science, Global Health, African Journals Online, CINAHL and African Index Medicus for published peer-reviewed articles from inception up to November 2021. Grey literature was obtained from OpenGrey. Studies on patient support groups for hypertension and/or diabetes with a component of pooling financial resources, conducted in LMICs, were included. Narrative reviews, commentaries, editorials and articles published in languages other than English and French were excluded. Study quality and risk of bias were assessed using the National Institutes of Health Quality assessment tool and the revised Cochrane risk-of-bias tool. Results are reported according to PRISMA guidelines. RESULTS: Of 724 records screened, three studies met the criteria: two trials conducted in Kenya and a retrospective cohort study conducted in Cambodia. All studies reported improvement in BP control after 12 months follow-up with reductions in systolic BP of 23, 14.8, and 16.9 mmHg, respectively. Two studies reported diabetes parameters. The first reported improvement in HbA1c (reduction from baseline 10.8%, to 10.6% at 6 months) and random blood sugar (baseline 8.9 mmol/L, to 8.5 mmol/L at 6 months) but these changes did not achieve statistical significance. The second reported a reduction in fasting blood glucose (baseline-216 mg/dl, 12 months-159 mg/dl) in diabetic patients on medication. CONCLUSION: Self-financing patient support groups for diabetes and hypertension are potentially effective in the control of BP and diabetes in LMICs. More studies are needed to add to the scarce evidence base on the role of self-financing patient support groups.

Cooperative amyloid fibre binding and disassembly by the Hsp70 disaggregase.

Although amyloid fibres are highly stable protein aggregates, a specific combination of human Hsp70 system chaperones can disassemble them, including fibres formed of α-synuclein, huntingtin, or Tau. Disaggregation requires the ATPase activity of the constitutively expressed Hsp70 family member, Hsc70, together with the J domain protein DNAJB1 and the nucleotide exchange factor Apg2. Clustering of Hsc70 on the fibrils appears to be necessary for disassembly. Here we use atomic force microscopy to show that segments of in vitro assembled α-synuclein fibrils are first coated with chaperones and then undergo bursts of rapid, unidirectional disassembly. Cryo-electron tomography and total internal reflection fluorescence microscopy reveal fibrils with regions of densely bound chaperones, preferentially at one end of the fibre. Sub-stoichiometric amounts of Apg2 relative to Hsc70 dramatically increase recruitment of Hsc70 to the fibres, creating localised active zones that then undergo rapid disassembly at a rate of ~ 4 subunits per second. The observed unidirectional bursts of Hsc70 loading and unravelling may be explained by differences between the two ends of the polar fibre structure.

Seminary Students and Physical Health: Beliefs, Behaviors, and Barriers.

As an occupational group, clergy exhibit numerous physical health problems. Given the physical health problems faced by clergy, understanding where physical health falls within the priorities of seminary students, the ways students conceptualize physical health, and how seminary students do or do not attend to their physical health in the years immediately prior to becoming clergy, can inform intervention development for both seminary students and clergy. Moreover, understanding and shaping the health practices of aspiring clergy may be particularly impactful, with cascading effects, as clergy serve as important role models for their congregants. Drawing on 36 in-depth, qualitative interviews with first-year seminary students, this study examines the complex dynamics between religious frameworks related to physical health, explicit intentions to maintain healthy practices, and reported physical health behaviors. Our findings suggest that even students who deploy religious frameworks in relation to their physical health-and who, as a result, possess positive intentions to implement and maintain healthy behaviors-often report being unable to live up to their aspirations, especially in the face of barriers to health practices posed by the seminary program itself. After reviewing these findings, we offer suggestions for physical health focused interventions, including action and coping planning, which could be implemented at seminaries to reduce the intention-behavior gap and improve clergy health.

The Financial Impacts of COVID-19 on United Methodist Churches in North Carolina: a Qualitative Study of Pastors' Perspectives and Strategies.

Background: In the wake of the COVID-19 pandemic, churches in the United States were forced to stop meeting in person and move to remote forms of worship and congregational life. This shift likely impacted congregational finances, which are primarily driven by individual donations. Initial research has suggested that there is a great deal of heterogeneity in the financial impact on congregations, but there has been scant research examining how pastors and congregations are managing finances during this period. Purpose: This research examines the impact of COVID-19 and its associated restrictions on congregational finances and the strategies pastors used to adapt their church's finances to the health restrictions. Methods: We conducted in-depth, qualitative interviews with 50 pastors in the North Carolina and Western North Carolina Conferences of the United Methodist Church appointed to 70 congregations. Using applied thematic analysis, we analyzed transcripts at both the pastor and congregation-level to identify similarities and differences in financial impact, financial strategies, and pastor experiences during the pandemic. Results: Most congregations reported small decreases in giving that were offset by federal Paycheck Protection Program (PPP) loans and other grants from the denomination. Some congregations, mostly urban and fairly large, reported significant increases in giving, while several other, predominantly small congregations, reported their church's finances had been negatively impacted by the pandemic. Even in cases where the net impact of the pandemic was small or non-existent, pastors were forced to adopt a host of new strategies to manage finances. In general, small and large congregations experienced and responded to the financial impact of the pandemic very differently.and Implications. Conclusions: This research suggests that the pandemic's impact on congregational finances were more than just on the bottom line. And while most churches weathered the economic challenges without severe impacts, questions remain as to the long-term impact of the pandemic on church finances. Supplementary Information: The online version contains supplementary material available at 10.1007/s13644-021-00474-x.

Pastoral Ministry in Unsettled Times: A Qualitative Study of the Experiences of Clergy During the COVID-19 Pandemic.

Background: COVID-19 and its associated restrictions around in-person gatherings have created unprecedented challenges for religious congregations and those who lead them. While several surveys have attempted to describe how pastors and congregations responded to COVID-19, these provide a relatively thin picture of how COVID-19 is impacting religious life. There is scant qualitative data describing the lived reality of religious leaders and communities during the pandemic. Purpose and methods: This paper provides a more detailed look at how pastors and congregations experienced and responded to COVID-19 and its associated restrictions in the early period of the pandemic. To do so, we draw from 26 in-depth interviews with church-appointed United Methodist pastors conducted between June and August 2020. Pastors were asked to describe how their ministry changed as a result of COVID-19 and interviews were analyzed using applied thematic analysis approaches to identify the most common emergent themes. Results: Pastors reported that COVID-19 fundamentally unsettled routine ways of doing ministry. This disruption generated both challenges and opportunities for clergy and their congregations. In the findings, we describe how clergy responded in key areas of ministry-worship and pastoral care-and analyze how the pandemic is (re)shaping the way that clergy understood their role as pastors and envisioned the future of the Church. We argue for the value of examining the pandemic as an "unsettled" cultural period (Swidler 1986) in which religious leaders found creative ways to (re)do ministry in the context of social distancing. Rather than starting from scratch, we found that pastors drew from and modified existing symbolic and practical tools to fit pandemic-related constraints on religious life. Notably, however, we found that "redoing" ministry was easier and more effective in some areas (worship) than others (pastoral care). Conclusions and Implications: The impact of COVID-19 on pastors and congregations is complex and not fully captured by survey research. This study provides a baseline for investigating similarities and differences in the responses of pastors within and across denominations and traditions. It also provides a baseline for assessing whether changes in ministry implemented during the early stages of the pandemic remain in place in the post-COVID world.

Frontal Brain Activity and Subjective Arousal During Emotional Picture Viewing in Nightmare Sufferers.

Nightmares are intensely negative dreams that awaken the dreamer. Frequent nightmares are thought to reflect an executive deficit in regulating arousal. Within a diathesis-stress framework, this arousal is specific to negative contexts, though a differential susceptibility framework predicts elevated arousal in response to both negative and positive contexts. The current study tested these predictions by assessing subjective arousal and changes in frontal oxyhemoglobin (oxyHB) concentrations during negative and positive picture-viewing in nightmare sufferers (NM) and control subjects (CTL). 27 NM and 27 CTL subjects aged 18-35 rated subjective arousal on a 1-9 scale following sequences of negative, neutral and positive images; changes in oxyHB were measured by Near-Infrared Spectroscopy (NIRS) using a 2 × 4 template on the frontal pole. Participants also completed the Highly Sensitive Person Scale, a trait marker for differential susceptibility; and completed a dream diary reporting negative and positive dream emotionality. The NM group had higher trait sensitivity, yet higher ratings of negative but not positive emotion in diary dreams. NM compared to CTL subjects reported higher subjective arousal in response to picture-viewing regardless of valence. Dysphoric dream distress, measured prospectively, was negatively associated with frontal activation when viewing negative pictures. Results suggest NM sufferers are highly sensitive to images regardless of valence according to subjective measures, and that there is a neural basis to level of trait and prospective nightmare distress. Future longitudinal or intervention studies should further explore positive emotion sensitivity and imagery in NM sufferers.

The effects of hibernation and forced disuse (neurectomy) on bone properties in arctic ground squirrels.

Bone loss is a well-known medical consequence of disuse such as in long-term space flight. Immobilization in many animals mimics the effects of space flight on bone mineral density. Decreases in metabolism are also thought to contribute to a loss of skeletal mass. Hibernating mammals provide a natural model of disuse and metabolic suppression. Hibernating ground squirrels have been shown to maintain bone strength despite long periods of disuse and decreased metabolism during torpor. This study examined if the lack of bone loss during torpor was a result of the decrease in metabolic rate during torpor or an evolutionary change in these animals affording protection against disuse. We delineated changes in bone density during natural disuse (torpor) and forced disuse (sciatic neurectomy) in the hind limbs of the arctic ground squirrel (AGS) over an entire year. We hypothesized that the animals would be resistant to bone loss due to immobilization and disuse during the winter hibernation season when metabolism is depressed but not the summer active season. This hypothesis was not supported. The animals maintained bone density (dual-energy X-ray absorptiometry) and most bone structural and mechanical properties in both seasons. This was observed in both natural and forced disuse, regardless of the known metabolic rate increase during the summer. However, trabecular bone volume fraction (microcomputed tomography) in the distal femur was lower in neurectomized AGS at the study endpoint. These results demonstrate a need to better understand the relationship between skeletal load (use) and bone density that may lead to therapeutics or strategies to maintain bone density in disuse conditions.

Recombinant pigment epithelium-derived factor PEDF binds vascular endothelial growth factor receptors 1 and 2.

Angiogenesis, or the formation of new blood vessels, is stimulated by angiogenic factors such as vascular endothelial growth factor (VEGF). Pigment epithelium-derived factor (PEDF) is a potent inhibitor of angiogenesis. To explore the mechanism by which PEDF acts, recombinant PEDF was expressed with a 6x-His tag (for purification) and a green fluorescent protein (GFP) tag. The PEDF fusion protein was confirmed to be active in inhibition of endothelial cell proliferation and migration. Direct binding of PEDF to both vascular endothelial growth factor receptor-1 (VEGFR-1) and VEGFR-2 was demonstrated in an in vitro assay similar to an enzyme-linked immunosorbent assay (ELISA). PEDF was shown by immune-confocal microscopy to be localized within treated endothelial cells. When VEGF-stimulated endothelial cells were incubated with PEDF the VEGF receptors showed intracellular localization. These data suggest that the interaction between PEDF and VEGFR-1 or VEGFR-2 may be a possible mechanism for inhibiting angiogenesis. PEDF may be binding to the VEGF receptors to promote their internalization and/or degradation to limit VEGF responses in treated cells.

1H-NMR metabolomic biomarkers of poor outcome after hemorrhagic shock are absent in hibernators.

BACKGROUND: Hemorrhagic shock (HS) following trauma is a leading cause of death among persons under the age of 40. During HS the body undergoes systemic warm ischemia followed by reperfusion during medical intervention. Ischemia/reperfusion (I/R) results in a disruption of cellular metabolic processes that ultimately lead to tissue and organ dysfunction or failure. Resistance to I/R injury is a characteristic of hibernating mammals. The present study sought to identify circulating metabolites in the rat as biomarkers for metabolic alterations associated with poor outcome after HS. Arctic ground squirrels (AGS), a hibernating species that resists I/R injury independent of decreased body temperature (warm I/R), was used as a negative control. METHODOLOGY/PRINCIPAL FINDINGS: Male Sprague-Dawley rats and AGS were subject to HS by withdrawing blood to a mean arterial pressure (MAP) of 35 mmHg and maintaining the low MAP for 20 min before reperfusing with Ringers. The animals' temperature was maintained at 37 ± 0.5 °C for the duration of the experiment. Plasma samples were taken immediately before hemorrhage and three hours after reperfusion. Hydrophilic and lipid metabolites from plasma were then analyzed via 1H-NMR from unprocessed plasma and lipid extracts, respectively. Rats, susceptible to I/R injury, had a qualitative shift in their hydrophilic metabolic fingerprint including differential activation of glucose and anaerobic metabolism and had alterations in several metabolites during I/R indicative of metabolic adjustments and organ damage. In contrast, I/R injury resistant AGS, regardless of season or body temperature, maintained a stable metabolic homeostasis revealed by a qualitative 1H-NMR metabolic profile with few changes in quantified metabolites during HS-induced global I/R. CONCLUSIONS/SIGNIFICANCE: An increase in circulating metabolites indicative of anaerobic metabolism and activation of glycolytic pathways is associated with poor prognosis after HS in rats. These same biomarkers are absent in AGS after HS with warm I/R.

Pre-hospital ambulance notification and initiation of treatment of ST elevation myocardial infarction is associated with significant reduction in door-to-balloon time for primary PCI.

BACKGROUND: Mortality in ST elevation myocardial infarction (STEMI) is strongly predicted by the time from first medical contact to reperfusion. The aim of this study was to examine the impact of pre-hospital diagnosis by paramedics in the field on the door-to-balloon (DTB) times of patients with ST elevation myocardial infarction undergoing primary percutaneous intervention. METHODS: Paramedics in the field identified patients with ST elevation myocardial infarction on a 12-lead electrocardiograph, activated the cardiac catheter laboratory team from the field and initiated therapy with anticoagulants and antiplatelet agents in the pre-hospital setting. This cohort of patients was compared to a similar group of patients without pre-hospital diagnosis and notification. The primary outcome measure was DTB times. A secondary end point was mortality at 30 days and mortality at six months. RESULTS: A total of 281 patients, mean age of 61.1±12.9 years underwent primary percutaneous intervention with pre-hospital notification occurring in 63 cases. DTB times were lower in those with pre notification than in those without pre-hospital notification (40.4 vs. 75.6 minutes, p<0.001). This represented a 47.6% shorter DTB time. A non-statistically significant mortality reduction at one month and six months was observed in the pre-hospital notification group (1.6 versus 4.3%, p= 0.307 and 1.6 versus 6.4%, p= 0.203, respectively). CONCLUSION: Pre-hospital intervention at our centre had a powerful effect in reducing the time to reperfusion in patients with STEMI undergoing primary percutaneous intervention.

Generation and characterization of rat anti-mouse ST2L monoclonal antibodies.

ST2L is a transmembrane receptor that belongs to the IL-1 receptor family. The receptor is expressed on various cell types including Th2 cells, mast cells, basophils, growth-activated fibroblasts, and vascular endothelial cells. ST2L activation by its ligand IL-33 has been implicated in Th2-mediated immunity, inflammation, and allergic responses in vivo. Inhibition of ST2L activity can attenuate Th2-dominated immune responses such as lung eosinophilia, airway hyper-responsiveness, and arthritis in animal models. Here we report the generation and in vitro characterization of a panel of rat anti-mouse ST2L monoclonal antibodies. We demonstrate that the antibodies specifically bind to recombinant receptor protein and that a subset of the binders inhibits mouse ST2L activity in multiple in vitro assays. Four of the identified anti-mouse ST2L antibodies were shown to prevent IL-33 from binding to ST2L, down-regulate IL-33-induced NF-κB signaling, and neutralize the ability of IL-33 to stimulate mouse Th2 cell proliferation. The characterized monoclonal antibodies are important tools that will be used to study mouse ST2L receptor functionality in vivo.

Binding kinetics, uptake and intracellular accumulation of F105, an anti-gp120 human IgG1kappa monoclonal antibody, in HIV-1 infected cells.

The use of targeting moieties is a new and exciting field of scientific research for facilitating the specific delivery of therapeutic agents in HIV-infected patients. The interaction of a potential targeting moiety with its ligand is a crucial factor in the evaluation of a targeted approach for chemotherapeutic intervention. Therefore, we have further characterized the interaction between a potential targeting agent, the monoclonal human antibody F105, and its ligand gp120, a glycoprotein expressed on the surface of HIV-1 infected cells. We demonstrate the specificity of binding and entry of F105 to infected cells. F105 was rapidly taken up into the cell and accumulated in the Golgi apparatus. Kinetic analysis of the F105-gp120 interaction revealed an equilibrium dissociation constant (K(D)) of 0.62 nM, compared with the gp120-CD4 interaction where the K(D) was determined at 35 nM. Consequently, F105 displayed a higher gp120 affinity. This was due to a slower dissociation as compared with the natural ligand. These data further underline the potential of monoclonal antibodies as targeting agents, and offer new insights into the possibility of F105 as a targeting moiety for the delivery of antiretroviral drugs to HIV-1 infected cells.

Enhancing the quality of supportive supervisory behavior in long-term care facilities.

The practices of managers and registered nurses (RNs) in long-term care facilities are frequently ineffective in assisting the licensed practical nurses (LPNs) and healthcare aides (HCAs) whom they supervise. Little research exists that examines the area of supportive relationships between nursing staff and supervisors in these settings. The purpose of this study was to gather data that could improve management practices in long-term care residential facilities and enhance the quality of the supervisory relationships between supervisors (nurse managers and RNs) and care providers (HCAs and LPNs) in these settings. The study also identified factors that influence the supervisors' ability to establish supportive relationships with care providers. The challenges and barriers to nurse managers and leaders related to enacting supportive behaviors are discussed as well as their implications for long-term care settings.