Extended megadroughts in the southwestern United States during Pleistocene interglacials.

The potential for increased drought frequency and severity linked to anthropogenic climate change in the semi-arid regions of the southwestern United States (US) is a serious concern. Multi-year droughts during the instrumental period and decadal-length droughts of the past two millennia were shorter and climatically different from the future permanent, 'dust-bowl-like' megadrought conditions, lasting decades to a century, that are predicted as a consequence of warming. So far, it has been unclear whether or not such megadroughts occurred in the southwestern US, and, if so, with what regularity and intensity. Here we show that periods of aridity lasting centuries to millennia occurred in the southwestern US during mid-Pleistocene interglacials. Using molecular palaeotemperature proxies to reconstruct the mean annual temperature (MAT) in mid-Pleistocene lacustrine sediment from the Valles Caldera, New Mexico, we found that the driest conditions occurred during the warmest phases of interglacials, when the MAT was comparable to or higher than the modern MAT. A collapse of drought-tolerant C(4) plant communities during these warm, dry intervals indicates a significant reduction in summer precipitation, possibly in response to a poleward migration of the subtropical dry zone. Three MAT cycles ∼2 °C in amplitude occurred within Marine Isotope Stage (MIS) 11 and seem to correspond to the muted precessional cycles within this interglacial. In comparison with MIS 11, MIS 13 experienced higher precessional-cycle amplitudes, larger variations in MAT (4-6 °C) and a longer period of extended warmth, suggesting that local insolation variations were important to interglacial climatic variability in the southwestern US. Comparison of the early MIS 11 climate record with the Holocene record shows many similarities and implies that, in the absence of anthropogenic forcing, the region should be entering a cooler and wetter phase.

Residential mobility and mental health.

We examine the extent to which residential relocation within and between tenure types is associated with changes in mental health. We focus on four types of housing transition - rent-to-own, own-to-rent, own-to-own, and rent-to-rent - using Australian and UK panel data sets from 2001 to 2017. In both countries, transitions into homeownership and moves away from the mortgaged edges toward the unburdened mainstream of outright ownership are positively associated with mental health. On the other hand, shifts by mortgagors towards more precarious positions on the edges of ownership precipitate dips in mental health when there is exposure to high levels of payment and investment risks. Clearly, residential moves can both alleviate and introduce different kinds of risks that affect affordability. Moreover, tenure transitions have impacts on mental health beyond the impacts of payment and investment risks. However, we observe some cross-national differences in findings. In Australia, loss of homeownership has a negative impact on mental health that outweighs the mental health impacts of attaining ownership. In the UK, these findings are reversed. Acute housing affordability problems following moves in Australia, but not in the UK, are a significant driver of mental health outcomes. These differences have institutional explanations.

Arabidopsis root K+-efflux conductance activated by hydroxyl radicals: single-channel properties, genetic basis and involvement in stress-induced cell death.

Reactive oxygen species (ROS) are central to plant stress response, signalling, development and a multitude of other processes. In this study, the plasma-membrane hydroxyl radical (HR)-activated K(+) channel responsible for K(+) efflux from root cells during stress accompanied by ROS generation is characterised. The channel showed 16-pS unitary conductance and was sensitive to Ca(2+), tetraethylammonium, Ba(2+), Cs(+) and free-radical scavengers. The channel was not found in the gork1-1 mutant, which lacks a major plasma-membrane outwardly rectifying K(+) channel. In intact Arabidopsis roots, both HRs and stress induced a dramatic K(+) efflux that was much smaller in gork1-1 plants. Tests with electron paramagnetic resonance spectroscopy showed that NaCl can stimulate HR generation in roots and this might lead to K(+)-channel activation. In animals, activation of K(+)-efflux channels by HRs can trigger programmed cell death (PCD). PCD symptoms in Arabidopsis roots developed much more slowly in gork1-1 and wild-type plants treated with K(+)-channel blockers or HR scavengers. Therefore, similar to animal counterparts, plant HR-activated K(+) channels are also involved in PCD. Overall, this study provides new insight into the regulation of plant cation transport by ROS and demonstrates possible physiological properties of plant HR-activated K(+) channels.

A randomized placebo-controlled study of noninvasive cortical electrostimulation in the treatment of fibromyalgia patients.

OBJECTIVE: The aim of this multicenter study was to evaluate the efficacy, safety, and tolerability of noninvasive cortical electrostimulation in the management of fibromyalgia (FM). DESIGN: A prospective, randomized, double-blind, placebo-controlled design was used. Setting. Subjects received therapy at two different outpatient clinical locations. PATIENTS: There were 77 subjects meeting the American College of Rheumatology 1990 classification criteria for FM. Intervention. Thirty-nine (39) active treatment (AT) FM patients and 38 placebo controls received 22 applications of either noninvasive cortical electrostimulation or a sham therapy over an 11-week period. OUTCOME MEASURES: The primary outcome measures were the number of tender points (TePs) and pressure pain threshold (PPT). Secondary outcome measures were responses to the Fibromyalgia Impact Questionnaire (FIQ), Symptom Checklist-90 (SCL-90), Beck Depression Inventory-II, and a novel sleep questionnaire, all evaluated at baseline and at the end of treatment. RESULTS: Intervention provided significant improvements in TeP measures: compared with placebo, the AT patients improved in the number of positive TePs (-7.4 vs -0.2, P<0.001) and the PPT (19.6 vs -3.2, P<0.001). Most secondary outcomes also improved more in the AT group: total FIQ score (-15.5 vs -5.6, P=0.03), FIQ pain (-2.0 vs -0.6, P=0.03), FIQ fatigue (-2.0 vs -0.4, P=0.02), and FIQ refreshing sleep (-2.1 vs -0.7, P=0.02); and while FIQ function improved (-1.0 vs -0.2), the between-group change had a 14% likelihood of occurring due to chance (P=0.14). There were no significant side effects observed. CONCLUSIONS: Noninvasive cortical electrostimulation in FM patients provided modest improvements in pain, TeP measures, fatigue, and sleep; and the treatment was well tolerated. This form of therapy could potentially provide worthwhile adjunctive symptom relief for FM patients.

NEMO oligomerization and its ubiquitin-binding properties.

The IKK [IkappaB (inhibitory kappaB) kinase] complex is a key regulatory component of NF-kappaB (nuclear factor kappaB) activation and is responsible for mediating the degradation of IkappaB, thereby allowing nuclear translocation of NF-kappaB and transcription of target genes. NEMO (NF-kappaB essential modulator), the regulatory subunit of the IKK complex, plays a pivotal role in this process by integrating upstream signals, in particular the recognition of polyubiquitin chains, and relaying these to the activation of IKKalpha and IKKbeta, the catalytic subunits of the IKK complex. The oligomeric state of NEMO is controversial and the mechanism by which it regulates activation of the IKK complex is poorly understood. Using a combination of hydrodynamic techniques we now show that apo-NEMO is a highly elongated, dimeric protein that is in weak equilibrium with a tetrameric assembly. Interaction with peptides derived from IKKbeta disrupts formation of the tetrameric NEMO complex, indicating that interaction with IKKalpha and IKKbeta and tetramerization are mutually exclusive. Furthermore, we show that NEMO binds to linear di-ubiquitin with a stoichiometry of one molecule of di-ubiquitin per NEMO dimer. This stoichiometry is preserved in a construct comprising the second coiled-coil region and the leucine zipper and in one that essentially spans the full-length protein. However, our data show that at high di-ubiquitin concentrations a second weaker binding site becomes apparent, implying that two different NEMO-di-ubiquitin complexes are formed during the IKK activation process. We propose that the role of these two complexes is to provide a threshold for activation, thereby ensuring sufficient specificity during NF-kappaB signalling.

Linking rhizoplane pH and bacterial density at the microhabitat scale.

Ion-selective microelectrodes and a novel micro-sampling technique were used to investigate the relationship in field soil between Brassica napus rhizoplane pH and bacterial density at a spatial scale approximating a microhabitat. Bacterial densities were observed to increase with decreasing pH, rhizoplane pH measurements varied by up to 1 pH unit over a distance of 1 mm and the mean pH of the rhizoplane at the root base varied by more than 1 pH unit between plants. These findings highlight the appropriateness of investigating the interactions between bacterial communities and their environment at the micro-spatial scale and the utility of the micro-sampling method.

From housing wealth to well-being?

The positive health effects of owner-occupation, compared to renting, are well documented. But home ownership is itself heterogeneous, as is the health profile of its incumbents, and this is less well recognised. Drawing from a mixed-methods study, which includes 150 qualitative interviews with a cross-section of UK mortgage holders, this paper examines the health implications of a definitive feature of owned housing: its role as a financial tool. In particular, we ask whether there is anything about the process of accumulating wealth into housing or spending from this resource, that enhances well-being (or that adds to psycho-social stress). This question is timely, coming at the end of a long-wave of house-price appreciation, in a setting where it is easy to borrow from housing wealth, under a policy regime that looks increasingly to owned homes as an asset base for welfare. The answer casts light on whether, in what circumstances, to what extent, and by what mechanism, home ownership - the dominant housing tenure of the English-speaking world - might enhance the well-being of individuals, communities and societies.

Amino acids and nitrate as signals for the regulation of nitrogen acquisition.

The uptake of nitrogen (N) by roots is known to change with supply in a manner that suggests that the N status of plants is somehow sensed and can feedback to regulate this process. The most abundant source of N in soils for crops is nitrate. Uptake systems for nitrate, ammonium, and amino acids are present in the roots of most plants including crops. As nitrate is assimilated via conversion to nitrite, then ammonium into amino acids, it has been suggested that the internal pools of amino acids within plants may indicate nitrogen status by providing a signal that can regulate nitrate uptake by the plant. In support of this idea, both nitrate and ammonium influx and transporter transcript were shown to decrease in root tissue treated with exogenously applied amino acids. Several different amino acids have been tested for their effects on influx and transcription and glutamine was most effective. The feedback regulation occurs by changing the expression of transporters, but may also involve the post-translational modification of proteins. For example, some of the cytoplasmic enzymes responsible for nitrate assimilation are regulated by phosphorylation and binding of a 14-3-3 protein. The effects of treating plants with glutamine have been examined, first to identify the uptake of the amino acid and then to measure tissue nitrate reductase activity and cellular pools of nitrate. These results are reviewed in terms of feedback regulation and the putative cell sensing systems for N status including a possible specific role for cytosolic nitrate.

Cytosolic nitrate ion homeostasis: could it have a role in sensing nitrogen status?

BACKGROUND AND AIMS: question of whether homeostasis occurs for some nutrients and, if so, what are the consequences for how plants sense their nutrient status. Particularly for nitrate, this controversy has focused on the methods used and the cellular pools which they measure. Cytoplasm and cytosol have been distinguished and it has been suggested that two ranges of nitrate values can be separated depending on whether the method separates the pools found in organelles. SCOPE: The present study defines homeostasis of nutrient ions and discusses how whole organ averaging techniques can hide important cellular differences that can help to explain some of the discrepancies between results reported by various methods. These results are considered in relation to a possible role in signalling nutrient status, and have relevance to other averaging techniques such as the use of 'omics' technologies.

Primary care after psychiatric crisis: a qualitative analysis.

PURPOSE: Patients with serious psychiatric problems experience difficulty accessing primary care. The goals of this study were to assess whether care managers improved access and to understand patients' experiences with health care after a psychiatric crisis. METHODS: A total of 175 consecutive patients seeking care in a psychiatric emergency department were randomly assigned to an intervention group with care managers or a control group. Brief, semistructured interviews about health care encounters were conducted at baseline and 1 year later. Five raters, using the content-driven, immersion-crystallization approach, analyzed 112 baseline and year-end interviews from 28 participants in each group. The main outcomes were patients' responses about their care experiences, connections with primary care, and integration of medical and mental health care. Scores for physical function and mental function were compared by analysis of variance (ANOVA). RESULTS: At baseline, most participants described negative experiences in receiving care and emphasized the importance of listening, sensitivity, and respect. Fully 71% of patients in the intervention group said that having a care manager to assist them with primary care connections was beneficial. Patients in the intervention group had significantly better physical and mental function than their counterparts in the control group at 6 months (P = .03 for each) but not at 12 months. There was also a trend toward functional improvement over the course of the study in the intervention group. CONCLUSIONS: This analysis suggests that care management is effective in helping patients access primary care after a psychiatric crisis. It provides evidence on and insight into how care may be delivered more effectively for this population. Future work should assess the sustainability of care connections and longer-term patient health outcomes.

How patients view primary care: differences by minority status after psychiatric emergency.

BACKGROUND: Patients' race or ethnic background may affect their ability to access health care due to their socioeconomic status, hereditary predispositions to illnesses, or discrimination either perceived or actual by those providing health care. For patients with mental health disorders, additional barriers are created due to poor experiences with the health care system. METHODS: This was a mixed methods randomized control study examining the effectiveness of care managers linking patients to primary care after psychiatric crisis. The aim reported in this paper was to analyze differences by minority status in patients' quantitative and qualitative responses before and after facilitation to primary care (N=85). Patients responded to a "patient enablement" and primary care index assessing their feelings of empowerment after a primary care visit; and to qualitative questions about their experiences and perceptions of care. FINDINGS: Following a primary care visit, responses by minority and non-minority individuals did not differ significantly on either the patient enablement or primary care index score. On qualitative inquiry, both non-minorities and minorities reported positive and negative views of their health, with corresponding positive and negative health experiences. DISCUSSION: In sum, there were no differences in patient enablement between the minority and non-minority subgroups over the course of the study, nor were there any changes in patient's perception of their relationship with healthcare providers. However, this cohort found primary care services less satisfactory than a general population without mental illness. Patients with psychiatric disorders experience stigmatization in their attempts to access health care. This stigma may have a greater impact than race and ethnicity, thereby leading to a similarity in perception of health care between minorities and non-minorities with mental illness.

How patients view primary care: differences by minority status after psychiatric emergency.

BACKGROUND: Patients' race or ethnic background may affect their ability to access health care due to their socioeconomic status, hereditary predispositions to illnesses, or discrimination either perceived or actual by those providing health care. For patients with mental health disorders, additional barriers are created due to poor experiences with the health care system. METHODS: This was a mixed methods randomized control study examining the effectiveness of care managers linking patients to primary care after psychiatric crisis. The aim reported in this paper was to analyze differences by minority status in patients' quantitative and qualitative responses before and after facilitation to primary care (N=85). Patients responded to a "patient enablement" and primary care index assessing their feelings of empowerment after a primary care visit; and to qualitative questions about their experiences and perceptions of care. FINDINGS: Following a primary care visit, responses by minority and non-minority individuals did not differ significantly on either the patient enablement or primary care index score. On qualitative inquiry, both non-minorities and minorities reported positive and negative views of their health, with corresponding positive and negative health experiences. DISCUSSION: In sum, there were no differences in patient enablement between the minority and non-minority subgroups over the course of the study, nor were there any changes in patient's perception of their relationship with healthcare providers. However, this cohort found primary care services less satisfactory than a general population without mental illness. Patients with psychiatric disorders experience stigmatization in their attempts to access health care. This stigma may have a greater impact than race and ethnicity, thereby leading to a similarity in perception of health care between minorities and non-minorities with mental illness.

When Coaching Meets Mentoring: Impact of Incorporating Coaching into an Existing Mentoring Program at a Community Hospital.

Introduction One in two physicians experiences professional burnout. Resident coaching is a novel method to provide emotional support and professional development to residents. The feasibility of implementing coaching at a community hospital has not been reported. This curricular innovation examined the feasibility and impact of integrating positive psychology coaching at a community hospital. Methods The Massachusetts General Hospital (MGH) Professional Development Coaching Program (PDCP) curriculum was used to train faculty coaches and for the informal pre-coaching session refreshers. Participants were paired and expected to participate in four 1:1 coaching sessions. The impact of the PDCP was assessed through pre- and post-PDCP online surveys. Results Twelve interns and nine faculty coaches were included in the program and surveyed. Survey completion was 10/12 (83%) and 6/9 (67%) at baseline and 9/12 (75%) and 7/9 (78%) at end of year (EOY) for interns and coaches, respectively. For interns, Emotional Exhaustion (EE) using the Maslach Burnout Inventory (MBI) was high or medium for 60% of respondents at baseline, and 56% at EOY. Fifty percent of coaches scored medium on EE at baseline, compared to only 14.3% at EOY. Seventy-five percent of respondents rated their PDCP experience as excellent or good. Nearly all interns rated the quality of communication with their coaches highly on a five-point Likert Scale. Conclusions Implementation of a coaching program in a community hospital residency program is feasible. Burnout using the MBI was stable from beginning to EOY for interns, but improved for coaches. Interns and coaches rated their professional development coaching program experience highly, and would recommend it to others.

A QI initiative for bridging the health literacy gap by Educating internal medicine residents at a community hospital.

Introduction: Only 12% of Americans have proficient health literacy (HL). Patients hide this fact from others including physicians. This quality improvement (QI) project was developed to compare internal medicine (IM) resident physicians' (RPs) ability to accurately predict patients with low HL and to improve IM-RPs' understanding of low HL and its impact on patients. Aim statement: Over six-months, our aim was to increase the IM residents' HL-knowledge by 30% as measured by an HL-Knowledge-Based-Survey. Methods: After IRB exemption, patients visiting the residency-clinic within a two-week period were screened for low HL with the REALM-R, a validated tool. Post-visit, IM-RPs were asked to predict their patients' HL. A comparison of predicted-HL and measured-HL was made. IM-RPs were emailed an HL-Knowledge-Based-Survey (pre-education and post-education) to measure their background knowledge of HL. Education included HL-workshop, pre-clinic conference and lectures. Pre-education and post-education scores were compared. Results: HL-RPs' prediction and patients' REALM-R results were completed by 108 RP-patient pairs. IM-RPs correctly identified 5 of 40 patients who were at risk for low HL (sensitivity = 12.5%). They correctly identified 97.1% of 68 who were not at risk (specificity = 97.1%). Our residents' knowledge pre-education and post-education did not improve - 58% (n = 18) vs 62% (n = 10). Conclusion: Our QI result verified that IM-RPs overestimate patients' HL and do not understand the magnitude or consequences of low HL nor techniques to improve such patients' understanding. This suggests an area for residency curricular development in order to improve patients' ability to navigate the healthcare system successfully.

Genetics, insurance and participation: how a Citizens' Jury reached its verdict.

Access to life insurance is subject to health discrimination. Whether this discrimination should take into account the results of predictive genetic tests is a topic of public debate. This paper draws from the deliberations of the Edinburgh (Scotland) Citizens' Jury on Genetic Test Results and Life Insurance to evaluate the capacity of one participatory research method to inform debates on genetics and insurance. We show that through a process of knowledge-building, cross-examination and deliberation, 'lay' jurors are able to assimilate complex information, engage in subtle argument and arrive at well-reasoned, clearly warranted conclusions. The Citizens' Jury approach has a further key advantage: it embraces the formation and articulation of normative ideas. It brings public understandings of how things ought to be into an arena dominated by 'expert' opinion. These normative indicators, which in this case relate to fairness and trust, are often overlooked by policy makers. However, they are key to democratic decision-taking and relevant for health promotion.

Buprenorphine and methadone: a comparison of patient completion rates during inpatient detoxification.

Buprenorphine and methadone are both effective for the control of the acute signs and symptoms of opiate withdrawal, but it is not known if there are differences between these two medications for other important clinical outcomes. This observational, non-randomized study evaluated completion rates of patients over a 13-month period when buprenorphine replaced methadone as the medication used for short-term inpatient opiate detoxification. Of the 644 patients in the study, the 303 treated with buprenorphine were more likely to complete detoxification than the 341 treated with methadone (89% vs. 78%; P < .001). Improvement in completion rates coincided with the introduction of buprenorphine. We conclude that as compared to methadone, buprenorphine is associated with greater rates of completion of inpatient detoxification.

A method for measuring intracellular free magnesium concentration in platelets using flow cytometry.

Magnesium is the fourth most abundant cation in the body and is involved in over 302 enzymatic reactions. Basic science research has implicated magnesium deficiency as a cause of insulin resistance which is related to hypertension, diabetes, hyperlipidemia and increased cardiovascular risk. Research in magnesium deficiency states has been hindered because magnesium is an intracellular ion and difficult to measure. Our goal was to develop a reproducible assay to measure intracellular magnesium in platelets. Healthy volunteers agreed to have blood drawn for magnesium measurement. Platelet rich plasma was harvested from a venipuncture specimen and run through the flow cytometer. A standard titer curve using known increasing concentrations of magnesium chloride was created for each specimen, and then with the other half the specimen was run to measure the true intracellular free magnesium concentration. 15 adults agreed to volunteer for this experiment. All standard titer curves for all specimens had a correlation of > 0.99. The mean concentration of intracellular free magnesium was 450.05 microM with a range of 203.68 microM to 673.50 microM. Intracellular free magnesium can reliably and reproducibly be measured in platelets using Mag Green fluorescent dye and flow cytometry. This should advance our ability to study magnesium deficient states.

Differences among those who complete and fail to complete inpatient detoxification.

Some individuals hospitalized for alcohol or drug detoxification leave against medical advice (AMA). We hypothesized that certain characteristics would be associated with AMA discharges. A case-control study of 1,426 hospital admissions for detoxification (representing 1,080 individuals) was conducted to compare patients leaving the hospital AMA (n=231) with a random sample of those completing detoxification (n=286). Latino ethnicity, detoxification from drugs, Friday or Saturday discharge, Medicaid or no health insurance, and not being treated by one specific attending physician were characteristics associated with an AMA discharge in a backward logistic regression model. Although 85% of the patients with all these characteristics left AMA, only one patient, without any of these five characteristics, did so. We conclude that clinicians can use certain clinical features to predict AMA discharge. Additional research could evaluate if treatment strategies that consider these ethnic and socioeconomic disparities may reduce rates of AMA discharge.

Specific CXC but not CC chemokines cause elevated monocyte migration in COPD: a role for CXCR2.

Leukocyte migration is critical to maintaining host defense, but uncontrolled cellular infiltration into tissues can lead to chronic inflammation. In the lung, such diseases include chronic obstructive pulmonary disease (COPD), a debilitating, respiratory condition characterized by progressive and largely irreversible airflow limitation for which cigarette smoking is the major risk factor. COPD is associated with an increased inflammatory cell influx including increased macrophage numbers in the airways and tissue. Alveolar macrophages develop from immigrating blood monocytes and have the capacity to cause the pathological changes associated with COPD. This study addressed the hypothesis that increased macrophage numbers in COPD are a result of increased recruitment of monocytes from the circulation. Chemotaxis assays of peripheral blood mononuclear cells (PBMC)/monocytes from nonsmokers, smokers, and COPD patients demonstrated increased chemotactic responses for cells from COPD patients when compared with controls toward growth-related oncogene (GRO)alpha and neutrophil-activating peptide (NAP)-2 but not toward monocyte chemoattractant protein, interleukin-8, or epithelial-derived NAP(ENA)-78. The enhanced chemotactic response toward GROalpha and NAP-2 was not mediated by differences in expression of their cellular receptors, CXCR1 or CXCR2. Receptor expression studies using flow cytometry indicated that in COPD, monocyte expression of CXCR2 is regulated differently from nonsmokers and smokers, which may account for the enhanced migration toward GROalpha and NAP-2. The results highlight the potential of CXCR2 antagonists as therapy for COPD and demonstrate that an enhanced PBMC/monocyte response to specific CXC chemokines in these patients may contribute to increased recruitment and activation of macrophages in the lungs.

Effects of dexamethasone on TNF-alpha-induced release of cytokines from purified human blood eosinophils.

BACKGROUND: TNF-alpha is an important mediator in allergy also for its effects on eosinophils. METHODS: The effect of dexamethasone on TNF-alpha induced eosinophils survival, degranulation (ECP), cytokines release (IL-8, GM-CSF) and adhesion to VCAM-1, ICAM-1 and IgG coated wells (EPO release) were evaluated. RESULTS: The drug inhibited IL-8 and GM-CSF production, but not viability, degranulation or adhesion in human peripheral blood eosinophils. CONCLUSION: These results indicate that part of the activity of glucocorticosteroids on eosinophils may be mediated by their ability to inhibit cytokine secretion that in turn is important for the perpetuation of the allergic inflammation.