Nontargeted biomonitoring of halogenated organic compounds in two ecotypes of bottlenose dolphins (Tursiops truncatus) from the Southern California Bight.

Targeted environmental monitoring reveals contamination by known chemicals, but may exclude potentially pervasive but unknown compounds. Marine mammals are sentinels of persistent and bioaccumulative contaminants due to their longevity and high trophic position. Using nontargeted analysis, we constructed a mass spectral library of 327 persistent and bioaccumulative compounds identified in blubber from two ecotypes of common bottlenose dolphins (Tursiops truncatus) sampled in the Southern California Bight. This library of halogenated organic compounds (HOCs) consisted of 180 anthropogenic contaminants, 41 natural products, 4 with mixed sources, 8 with unknown sources, and 94 with partial structural characterization and unknown sources. The abundance of compounds whose structures could not be fully elucidated highlights the prevalence of undiscovered HOCs accumulating in marine food webs. Eighty-six percent of the identified compounds are not currently monitored, including 133 known anthropogenic chemicals. Compounds related to dichlorodiphenyltrichloroethane (DDT) were the most abundant. Natural products were, in some cases, detected at abundances similar to anthropogenic compounds. The profile of naturally occurring HOCs differed between ecotypes, suggesting more abundant offshore sources of these compounds. This nontargeted analytical framework provided a comprehensive list of HOCs that may be characteristic of the region, and its application within monitoring surveys may suggest new chemicals for evaluation

Individual nutrition therapy and exercise regime: A controlled trial of injured, vulnerable elderly (INTERACTIVE trial)

© 2008 Thomas et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background Proximal femoral fractures are amongst the most devastating consequences of osteoporosis and injurious accidental falls with 25–35% of patients dying in the first year post-fracture. Effective rehabilitation strategies are evolving however, despite established associations between nutrition, mobility, strength and strength-related functional outcomes; there has been only one small study with older adults immediately following fragility fracture where a combination of both exercise and nutrition have been provided. The aim of the INTERACTIVE trial is to establish whether a six month, individualised exercise and nutrition program commencing within fourteen days of surgery for proximal femur fracture, results in clinically and statistically significant improvements in physical function, body composition and quality of life at an acceptable level of cost and resource use and without increasing the burden of caregivers. Methods and Design This randomised controlled trial will be performed across two sites, a 500 bed acute hospital in Adelaide, South Australia and a 250 bed acute hospital in Sydney, New South Wales. Four hundred and sixty community-dwelling older adults aged > 70 will be recruited after suffering a proximal femoral fracture and followed into the community over a 12-month period. Participants allocated to the intervention group will receive a six month individualised care plan combining resistance training and nutrition therapy commencing within 14 days post-surgery. Outcomes will be assessed by an individual masked to treatment allocation at six and 12 months. To determine differences between the groups at the primary end-point (six months), ANCOVA or logistic regression will be used with models adjusted according to potential confounders. Discussion The INTERACTIVE trial is among the first to combine nutrition and exercise therapy as an early intervention to address the serious consequence of rapid deconditioning and weight loss and subsequent ability to regain pre-morbid function in older patients post proximal femoral fracture. The results of this trial will guide the development of more effective rehabilitation programs, which may ultimately lead to reduced health care costs, and improvements in mobility, independence and quality of life for proximal femoral fracture sufferers. Trial registration Australian Clinical Trials Registry: ACTRN12607000017426

Testing in Mice the Hypothesis That Melanin Is Protective in Malaria Infections

Malaria has had the largest impact of any infectious disease on shaping the human genome, exerting enormous selective pressure on genes that improve survival in severe malaria infections. Modern humans originated in Africa and lost skin melanization as they migrated to temperate regions of the globe. Although it is well documented that loss of melanization improved cutaneous Vitamin D synthesis, melanin plays an evolutionary ancient role in insect immunity to malaria and in some instances melanin has been implicated to play an immunoregulatory role in vertebrates. Thus, we tested the hypothesis that melanization may be protective in malaria infections using mouse models. Congenic C57BL/6 mice that differed only in the gene encoding tyrosinase, a key enzyme in the synthesis of melanin, showed no difference in the clinical course of infection by Plasmodium yoelii 17XL, that causes severe anemia, Plasmodium berghei ANKA, that causes severe cerebral malaria or Plasmodium chabaudi AS that causes uncomplicated chronic disease. Moreover, neither genetic deficiencies in vitamin D synthesis nor vitamin D supplementation had an effect on survival in cerebral malaria. Taken together, these results indicate that neither melanin nor vitamin D production improve survival in severe malaria

Compassion: a scoping review of the healthcare literature

BACKGROUND: Recent concerns about suboptimal patient care and a lack of compassion have prompted policymakers to question the preparedness of clinicians for the challenging environment in which they practice. Compassionate care is expected by patients and is a professional obligation of clinicians; however, little is known about the state of research on clinical compassion. The purpose of this scoping review was to map the literature on compassion in clinical healthcare. METHODS: Searches of eight electronic databases and the grey literature were conducted to identify empirical studies published over the last 25 years. Eligible studies explored perceptions or interventions of compassionate care in clinical populations, healthcare professionals, and healthcare students. Following the title and abstract review, two reviewers independently screened full-texts articles, and extracted study data. A narrative approach to synthesizing and mapping the literature was used. RESULTS AND DISCUSSION: Of 36,637 records, 648 studies were retrieved and 44 studies were included in the review. Less than one third of studies included patients. Six themes emerged from studies that explored perceptions of compassionate care: nature of compassion, development of compassion, interpersonal factors related to compassion, action and practical compassion, barriers and enablers of compassion, and outcomes of compassion. Intervention studies included two compassionate care trials with patients and eight educational programs that aimed to improve compassionate care in clinicians and students. CONCLUSIONS: This review identifies the limited empirical understanding of compassion in healthcare, highlighting the lack of patient and family voices in compassion research. A deeper understanding of the key behaviors and attitudes that lead to improved patient-reported outcomes through compassionate care is necessary

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Nontargeted biomonitoring of halogenated organic compounds in two ecotypes of bottlenose dolphins (Tursiops truncatus) from the Southern California Bight.

Targeted environmental monitoring reveals contamination by known chemicals, but may exclude potentially pervasive but unknown compounds. Marine mammals are sentinels of persistent and bioaccumulative contaminants due to their longevity and high trophic position. Using nontargeted analysis, we constructed a mass spectral library of 327 persistent and bioaccumulative compounds identified in blubber from two ecotypes of common bottlenose dolphins (Tursiops truncatus) sampled in the Southern California Bight. This library of halogenated organic compounds (HOCs) consisted of 180 anthropogenic contaminants, 41 natural products, 4 with mixed sources, 8 with unknown sources, and 94 with partial structural characterization and unknown sources. The abundance of compounds whose structures could not be fully elucidated highlights the prevalence of undiscovered HOCs accumulating in marine food webs. Eighty-six percent of the identified compounds are not currently monitored, including 133 known anthropogenic chemicals. Compounds related to dichlorodiphenyltrichloroethane (DDT) were the most abundant. Natural products were, in some cases, detected at abundances similar to anthropogenic compounds. The profile of naturally occurring HOCs differed between ecotypes, suggesting more abundant offshore sources of these compounds. This nontargeted analytical framework provided a comprehensive list of HOCs that may be characteristic of the region, and its application within monitoring surveys may suggest new chemicals for evaluation

A single amino acid is critical for the expression of B-cell epitopes on the helicase domain of the pestivirus NS3 protein

Truncated NS3 proteins, expressed by recombinant baculoviruses, were used to investigate the location of conserved B-cell epitopes on this non-structural bovine viral diarrhoea virus (BVDV) protein. A goat anti-pestivirus antiserum, and a panel of anti-NS3 monoclonal antibodies, including the BVDV-1 specific antibody P1D8, were used to verify the presence or absence of the epitopes. Interestingly, the monoclonal antibodies reacted only with the truncated protein encompassing the helicase domain of NS3. Expression of the B-cell epitopes was dependent on, but not within, a 57 amino acid sequence at the carboxy-terminal end of this protein, supporting observations that these conserved epitopes are conformational in nature. A comparison of deduced amino acid sequences of the helicase domain from BVDV-1, BVDV-2, BDV and CSFV isolates highlighted a single amino acid that appeared to be unique to P1D8-reactive BVDV-1 isolates. Site-directed mutagenesis studies confirmed that this amino acid is critical for the expression of the BVDV-1 specific NS3 epitope recognised by the P1D8 monoclonal antibody. Surprisingly, the amino acid was also important for an epitope recognised by two group-specific monoclonal antibodies, P1H11 and P4A11. Protein modelling studies, based on the structure of the hepatitis C NS3 helicase domain, indicated that this amino acid occupies a prominent position on the surface of the protein

Identifying Bioaccumulative Halogenated Organic Compounds Using a Nontargeted Analytical Approach: Seabirds as Sentinels

<div><p>Persistent organic pollutants (POPs) are typically monitored via targeted mass spectrometry, which potentially identifies only a fraction of the contaminants actually present in environmental samples. With new anthropogenic compounds continuously introduced to the environment, novel and proactive approaches that provide a comprehensive alternative to targeted methods are needed in order to more completely characterize the diversity of known and unknown compounds likely to cause adverse effects. Nontargeted mass spectrometry attempts to extensively screen for compounds, providing a feasible approach for identifying contaminants that warrant future monitoring. We employed a nontargeted analytical method using comprehensive two-dimensional gas chromatography coupled to time-of-flight mass spectrometry (GC×GC/TOF-MS) to characterize halogenated organic compounds (HOCs) in California Black skimmer (<i>Rynchops niger</i>) eggs. Our study identified 111 HOCs; 84 of these compounds were regularly detected via targeted approaches, while 27 were classified as typically unmonitored or unknown. Typically unmonitored compounds of note in bird eggs included tris(4-chlorophenyl)methane (TCPM), tris(4-chlorophenyl)methanol (TCPMOH), triclosan, permethrin, heptachloro-1'-methyl-1,2'-bipyrrole (MBP), as well as four halogenated unknown compounds that could not be identified through database searching or the literature. The presence of these compounds in Black skimmer eggs suggests they are persistent, bioaccumulative, potentially biomagnifying, and maternally transferring. Our results highlight the utility and importance of employing nontargeted analytical tools to assess true contaminant burdens in organisms, as well as to demonstrate the value in using environmental sentinels to proactively identify novel contaminants.</p></div

Relative Abundance of Individual Compounds, excluding PCBs.

<p>Each point represents one egg sample (n = 4), including non-detects. Non-detects are shown with a value of zero (multiple non-detects overlap). PCBs are included in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0127205#pone.0127205.s003" target="_blank">S1 Fig</a>.</p

Relative Abundance of Compound Classes.

<p>Each point represents detection in a single egg sample (n = 4). The abundance is the sum total of the normalized peak areas for all compounds in the class, in each sample. The line is the median abundance for the compound class. The source of each compound class is indicated in the legend. Non-detects are shown with a value of zero (multiple non-detects overlap).</p