Genome-wide CNV analysis revealed variants associated with growth traits in African indigenous goats.

Using the CaprineSNP50 data generated by the AGIN consortium, we detected common CNVs in 126 samples from four African indigenous goat breeds. A total of 30 CNVs ranging from 30,237 bp to 4,910,757 bp were identified. These CNVs were then associated with six growth traits by a linear regression analysis. Three significant associations were identified between two CNVs and two body traits after false discovery rate (FDR) correction (P < .05). One of them (CNV27) was significantly associated with both chest width and width of pin bones. It overlaps the SNX29 gene, the Gene Ontology (GO) annotations of which indicate CNV27 could be a potential functional candidate for meat production, health and reproduction traits. To our knowledge, this study is the first CNV-based association test of growth traits using SNP chip data in African meat goats.

Immediate Interventions for Presyncope of Vasovagal or Orthostatic Origin: A Systematic Review.

Background: Syncope is a common condition that may be prevented. There are non-pharmacological interventions that may be of benefit during the acute episode preceding syncope (presyncope), including physical counter-pressure maneuvers (PCM) or change of body position. We performed a systematic review of interventions that may be applied during presyncope as an immediate, first aid tactic. Methods: We searched Medline, Embase, and CINAHL and used the Grading of Recommendations Assessment, Development and Evaluation methods, and risk of bias assessments to determine the certainty of the evidence. We included randomized controlled trials (RCTs), non-randomized studies, and case series investigating adults and children with signs and symptoms of presyncope of suspected vasovagal or orthostatic origin who applied any intervention that could be used as an immediate, first aid intervention. We examined the following outcomes: prevention of syncope, adverse events, symptom improvement, and vital signs. We conducted a sub-group analysis based on the etiology of vasovagal or orthostatic presyncope. Results: We screened 5,160 titles and abstracts followed by 81 full text articles. We identified 8 studies meeting inclusion criteria, including 2 RCTs and 6 observational studies. All studies used PCM in adults and all were judged to be of low and very low certainty of evidence. For prevention of syncope, one RCT demonstrated benefit with the use of PCM (RR = 1.80 [1.26-1.89]), while observational studies failed to show benefit (RR = 1.31 [0.98 - 1.75]). Two RCTs showed benefit in symptom improvement (RR = 6.00 [2.21 - 8.61] and (RR = 1.57 [1.06 - 1.93]). Blood pressure (BP) improved with the use of PCM: systolic BP mean difference (MD) 21 mmHg higher (95% CI: 18.25 to 23.41 BPM) and diastolic BP MD 11 mmHg higher (95% CI: 9.39 to 13.10 mmHg higher). No adverse events were reported. Conclusion: While there is a minimal amount of evidence available and the findings were mixed, PCM may provide benefit for prevention of syncope during acute episodes of presyncope and may be tried in the first aid setting. No evidence was found for other non-pharmacologic interventions or for the use of PCM in children.

Incidence of mortality due to rebound toxicity after 'treat and release' practices in prehospital opioid overdose care: a systematic review.

INTRODUCTION: Death due to opioid overdose was declared a public health crisis in Canada in 2015. Traditionally, patients who have overdosed on opioids that are managed by emergency medical services (EMS) are treated with the opioid antagonist naloxone, provided ventilatory support and subsequently transported to hospital. However, certain EMS agencies have permitted patients who have been reversed from opioid overdose to refuse transport, if the patient exhibits capacity to do so. Evidence on the safety of this practice is limited. Therefore, our intent was to examine the available literature to determine mortality and serious adverse events within 48 hours of EMS treat and release due to suspected rebound opioid toxicity after naloxone administration. METHODS: A systematic search was performed on 11 May 2017 in PubMed, Cochrane Central, Embase and CINHAL. Studies that reported on the outcome of patients treated with prehospital naloxone and released at the scene were included. Analyses for incidence of mortality and adverse events at the scene were conducted. Risk of bias and assessment of publication bias was also done. RESULTS: 1401 records were screened after duplicate removal. Eighteen full-text studies were reviewed with seven selected for inclusion. None were found to be high risk of bias. In most studies, heroin was the source of the overdose. Mortality within 48 hours was infrequent with only four deaths among 4912 patients ï´¾0.081%ï´¿ in the seven studies. Only one study reported on adverse events and found no incidence of adverse events from their sample of 71 released patients. CONCLUSION: Mortality or serious adverse events due to suspected rebound toxicity in patients released on scene post-EMS treatment with naloxone were rare. However, studies involving longer-acting opioids were rare and no study involved fentanyl.

Acceleration Strategies to Enhance Metabolic Ensemble Modeling Performance.

Developing reliable, predictive kinetic models of metabolism is a difficult, yet necessary, priority toward understanding and deliberately altering cellular behavior. Constraint-based modeling has enabled the fields of metabolic engineering and systems biology to make great strides in interrogating cellular metabolism but does not provide sufficient insight into regulation or kinetic limitations of metabolic pathways. Moreover, the growth-optimized assumptions that constraint-based models often rely on do not hold when studying stationary or persistor cell populations. However, developing kinetic models provides many unique challenges, as many of the kinetic parameters and rate laws governing individual enzymes are unknown. Ensemble modeling (EM) was developed to circumnavigate this challenge and effectively sample the large kinetic parameter solution space using consistent experimental datasets. Unfortunately, EM, in its base form, requires long solve times to complete and often leads to unstable kinetic model predictions. Furthermore, these limitations scale prohibitively with increasing model size. As larger metabolic models are developed with increasing genetic information and experimental validation, the demand to incorporate kinetic information increases. Therefore, in this work, we have begun to tackle the challenges of EM by introducing additional steps to the existing method framework specifically through reducing computation time and optimizing parameter sampling. We first reduce the structural complexity of the network by removing dependent species, and second, we sample locally stable parameter sets to reflect realistic biological states of cells. Lastly, we presort the screening data to eliminate the most incorrect predictions in the earliest screening stages, saving further calculations in later stages. Our complementary improvements to this EM framework are easily incorporated into concurrent EM efforts and broaden the application opportunities and accessibility of kinetic modeling across the field.

Evaluating enzymatic synthesis of small molecule drugs.

There have been many achievements in applying biochemical synthetic routes to the synthesis of commodity chemicals. However, most of these endeavors have focused on optimizing and increasing the yields of naturally existing pathways. We sought to evaluate the potential for biosynthesis beyond the limits of known biochemistry towards the production of small molecule drugs that do not exist in nature. Because of the potential for improved yields compared to total synthesis, and therefore lower manufacturing costs, we focused on drugs for diseases endemic to many resource poor regions, like tuberculosis and HIV. Using generalized biochemical reaction rules, we were able to design biochemical pathways for the production of eight small molecule drugs or drug precursors and identify potential enzyme-substrate pairs for nearly every predicted reaction. All pathways begin from native metabolites, abrogating the need for specialized precursors. The simulated pathways showed several trends with the sequential ordering of reactions as well as the types of chemistries used. For some compounds, the main obstacles to finding feasible biochemical pathways were the lack of appropriate, natural starting compounds and a low diversity of biochemical coupling reactions necessary to synthesize molecules with larger molecular size.

Blockade of CD40-TRAF2,3 or CD40-TRAF6 is sufficient to inhibit pro-inflammatory responses in non-haematopoietic cells.

Inhibition of the CD40-CD154 pathway controls inflammatory disorders. Unfortunately, administration of anti-CD154 monoclonal antibodies causes thromboembolism. Blockade of signalling downstream of CD40 may represent an approach to treat CD40-driven inflammatory disorders. Blocking tumour necrosis factor receptor-associated factor 6 (TRAF6) signalling downstream of CD40 in MHC II(+) cells diminishes inflammation. However, CD40-TRAF6 blockade may cause immunosuppression. We examined the role of CD40-TRAF2,3 and CD40-TRAF6 signalling in the development of pro-inflammatory responses in human non-haematopoietic and monocytic cells. Human aortic endothelial cells, aortic smooth muscle cells, renal proximal tubule epithelial cells, renal mesangial cells and monocytic cells were transduced with retroviral vectors that encode wild-type CD40, CD40 with a mutation that prevents TRAF2,3 recruitment (ΔT2,3), TRAF6 recruitment (ΔT6) or both TRAF2,3 plus TRAF6 recruitment (ΔT2,3,6). Non-haematopoietic cells that expressed CD40 ΔT2,3 exhibited marked inhibition in CD154-induced up-regulation of vascular cell adhesion molecule 1, intercellular adhesion molecule 1 (ICAM-1), monocyte chemotactic protein 1 (MCP-1), tissue factor and matrix metalloproteinase 9. Similar results were obtained with cells that expressed CD40 ΔT6. Although both mutations impaired ICAM-1 up-regulation in monocytic cells, only expression of CD40 ΔT6 reduced MCP-1 and tissue factor up-regulation in these cells. Treatment of endothelial and smooth muscle cells with cell-permeable peptides that block CD40-TRAF2,3 or CD40-TRAF6 signalling impaired pro-inflammatory responses. In contrast, while the CD40-TRAF2,3 blocking peptide did not reduce CD154-induced dendritic cell maturation, the CD40-TRAF6 blocking peptide impaired this response. Hence, preventing CD40-TRAF2,3 or CD40-TRAF6 interaction inhibits pro-inflammatory responses in human non-haematopoietic cells. In contrast to inhibition of CD40-TRAF6 signalling, inhibition of CD40-TRAF2,3 signalling did not impair dendritic cell maturation. Blocking CD40-TRAF2,3 signalling may control CD40-CD154-dependent inflammatory disorders.

Improving home-based providers' communication to primary care providers to enhance care coordination.

OBJECTIVES: Health care system fragmentation is a pervasive problem. Research has not delineated concrete behavioral strategies to guide providers to communicate with personnel in other organizations to coordinate care. We addressed this gap within a particular context: home-based providers delivering depression care management (DCM) to older adults requiring coordination with primary care personnel. Our objective was to pilot test a communication protocol ('BRIDGE - BRinging Inter-Disciplinary Guidelines to Elders') in conjunction with DCM. METHOD: In an open pilot trial (N = 7), home-based providers delivered DCM to participants. Following the BRIDGE protocol, home-based providers made scripted telephone calls and sent structured progress reports to personnel in participants' primary care practices with concise information and requests for assistance. Home-based providers documented visits with participants, contacts to and responses from primary care personnel. A research interviewer assessed participant outcomes [Symptom Checklist-20 (depressive symptoms), World Health Organization Disability Assessment Schedule-12, satisfaction] at baseline, three months, and six months. RESULTS: Over 12 months, home-based providers made 2.4 telephone calls and sent 6.3 faxes to other personnel, on average per participant. Primary care personnel responded to 18 of 22 requests (81.8%; 2 requests dropped, 2 ongoing), with at least one response per participant. Participants' depressive symptoms and disability improved significantly at both post-tests with large effect sizes (d ranged 0.73-2.3). Participants were satisfied. CONCLUSION: Using BRIDGE, home-based providers expended a small amount of effort to communicate with primary care personnel, who responded to almost all requests. Larger scale research is needed to confirm findings and potentially extend BRIDGE to other client problems, professions, and service sectors.

The emergence of mixing methods in the field of evaluation.

When and how did the contemporary practice of mixing methods in social inquiry get started? What events transpired to catalyze the explosive conceptual development and practical adoption of mixed methods social inquiry over recent decades? How has this development progressed? What "next steps" would be most constructive? These questions are engaged in this personally narrative account of the beginnings of the contemporary mixed methods phenomenon in the field of evaluation from the perspective of a methodologist who was there.

CD40 promotes the development of early diabetic retinopathy in mice.

AIMS/HYPOTHESIS: Microangiopathy is a leading complication of diabetes that commonly affects the retina. Degenerate capillaries are a central feature of diabetic retinopathy. An inflammatory process has been linked to the development of diabetic retinopathy but its regulation is incompletely understood. Cluster of differentiation (CD) 40 is a member of the TNF receptor superfamily that promotes the development of certain inflammatory disorders. The role of CD40 in diabetic microangiopathy is unknown. METHODS: B6 and Cd40−/− mice were administered streptozotocin to induce diabetes. Leucostasis was assessed using fluorescein isothiocyanate-conjugated concanavalin A. Retinal Icam1 and Cd40 mRNA levels were examined using real-time PCR. Protein nitration was assessed by immunohistochemistry. Histopathology was examined in the retinal vasculature. CD40 expression was assessed by flow cytometry and immunohistochemistry. Intercellular adhesion molecule 1 (ICAM-1) and nitric oxide synthase 2 (NOS2) were examined by immunoblot and/or flow cytometry. Nitric oxide production was examined by immunoblot and Griess reaction. RESULTS: In mouse models of diabetes, Cd40−/− mice exhibited reduced retinal leucostasis and did not develop capillary degeneration in comparison with B6 mice. Diabetic Cd40−/− mice had diminished ICAM-1 upregulation and decreased protein nitration. Cd40 mRNA levels were increased in the retinas of diabetic B6 mice compared with non-diabetic controls. CD40 expression increased in retinal Müller cells, endothelial cells and microglia of diabetic animals. CD40 stimulation upregulated ICAM-1 in retinal endothelial cells and Müller cells. CD40 ligation upregulated NOS2 and nitric oxide production by Müller cells. CONCLUSIONS/INTERPRETATION: CD40-deficient mice were protected fromthe development of diabetic retinopathy. These mice exhibited diminished inflammatory responses linked to diabetic retinopathy. CD40 stimulation of retinal cells triggered these pro-inflammatory responses.

Mass spectrometry-based identification of S-nitrosocysteine in vivo using organic mercury assisted enrichment.

Protein S-nitrosylation is considered as one of the molecular mechanisms by which nitric oxide regulates signaling events and protein function. The present review presents an updated method which allows for the site-specific detection of S-nitrosylated proteins in vivo. The method is based on enrichment of S-nitrosylated proteins or peptides using organomercury compounds followed by LC-MS/MS detection. Technical aspects for determining the reaction and binding efficiency of the mercury resin that assists enrichment of S-nitrosylated proteins are presented and discussed. In addition, emphasis is given to the specificity of the method by providing technical details for the generation of four chemically distinct negative controls. Finally it is provided an overview of the key steps for generation and evaluation of mass spectrometry derived data.

Strategies and tools to explore protein S-nitrosylation.

BACKGROUND: A biochemical pathway by which nitric oxide accomplishes functional diversity is the specific modification of protein cysteine residues to form S-nitrosocysteine. This post-translational modification, S-nitrosylation, impacts protein function, interactions and location. However, comprehensive studies exploring protein signaling pathways or interrelated protein clusters that are regulated by S-nitrosylation have not been performed on a global scale. SCOPE OF REVIEW: To provide insights to these important biological questions, sensitive, validated and quantitative proteomic approaches are required. This review summarizes current approaches for the global identification of S-nitrosylated proteins. MAJOR CONCLUSIONS: The application of novel methods for identifying S-nitrosylated proteins, especially when combined with mass-spectrometry based proteomics to provide site-specific identification of the modified cysteine residues, promises to deliver critical clues for the regulatory role of this dynamic posttranslational modification in cellular processes. GENERAL SIGNIFICANCE: Though several studies have established S-nitrosylation as a regulator of protein function in individual proteins, the biological chemistry and the structural elements that govern the specificity of this modification in vivo are vastly unknown. Additionally, a gap in knowledge exists concerning the potential global regulatory role(s) this modification may play in cellular physiology. By further studying S-nitrosylation at a global scale, a greater appreciation of nitric oxide and protein S-nitrosylation in cellular function can be achieved. This article is part of a Special Issue entitled Regulation of Cellular Processes by S-nitrosylation.

The role of adipose tissue-associated macrophages and T lymphocytes in the pathogenesis of inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are chronic inflammatory disorders of the gastrointestinal tract that affect more than 3 million people worldwide, but the pathological etiology is still unknown. The overall purpose of our investigations was to elucidate the possibility of pathological causes of IBD, and therefore, we determined the difference of inflammatory cytokine profiles in adipose tissue macrophages (ATMs) and T lymphocytes (ATTs) obtained near active lesions of IBD; investigated whether the alteration in ATM activation induces genes involved in collagen formation; and evaluated the effects of fatty acid oxidation inhibitors on factors involved in inflammation and collagen production by ATMs in IBD. Adipose tissues (ATs) were collected near active lesions and also at the margin of resected segments of the bowel from IBD patients with ulcerative colitis (UC) and CD (n=14/group). Normal appearing ATs from control subjects (n=14) who had colon resection for adenocarcinoma were collected as far away from the cancer lesion as possible to rule out possible changes. Compared with inactive disease lesions, ATMs and ATTs from active lesions released more IL-6, IL-4 and IL-13. Treatments of cytokine IL-4 and/or IL-13 to ATMs reduced iNOS expression but increased Arg-I expression which were exacerbated when treated with T cell- and adipocyte-conditioned medium. However, fatty acid oxidation inhibitors prevented the effects of cytokines IL-4 and/or IL-13 on iNOS and Arg-I expressions. This study was the first to show the effect of IL-4 and IL-13 on collagen formation, through iNOS and Arg-I expressions, that was exacerbated in a condition that mimics in vivo condition of active lesions. Moreover, our study was the first to provide potential benefits of fatty acid oxidation inhibitors to ATMs on preventing collagen formation; thus, providing therapeutic implications for individuals with intestinal fibrosis and stricture lesions, although future study should be guaranteed to elucidate the underlying mechanisms.

Mucus and adiponectin deficiency: role in chronic inflammation-induced colon cancer.

PURPOSE: This study aims to define the role of adiponectin (APN) in preventing goblet cell apoptosis and in differentiation of epithelial cells to goblet cell lineage resulting in greater mucus production and hence greater protection from chronic inflammation-induced colon cancer (CICC). METHODS: Six- to eight-week-old male APNKO and C57BL/6 (WT) mice were randomly distributed to three treatment groups: DSS, DMH, DSS + DMH and control. Chronic inflammation was induced in DSS and DSS + DMH group by administrating 2 % DSS in drinking water for 5 days followed by 5 days of normal drinking water and this constitutes one DSS cycle. Three cycles of DSS were administered to induce chronic inflammation. Cancer was induced in both APNKO and WT mice in DMH and DSS + DMH groups by intraperitoneal injections of DMH (20 mg/kg body weight) once for DSS + DMH group and once per week for 12 weeks for DMH group. On day 129, the colon tissue was dissected for mucus thickness measurements and for genomic studies. HT29-C1.16E and Ls174T cells were used for several genomic and siRNA studies. RESULTS: APNKO mice have more tumors and tumor area in DSS + DMH group than WT mice. APN deficiency downregulated goblet to epithelial cell ratio and enhanced the colonic mucosal erosion with reduced mucus thickness. APN increases Muc2 production with no affect on Muc1 production. APN abated goblet cell apoptosis, while APN deficiency reduced epithelial to goblet cell differentiation. CONCLUSION: APN may be involved in reducing the severity of CICC by preventing goblet cell apoptosis and increasing epithelial to goblet cell differentiation.

Structural profiling of endogenous S-nitrosocysteine residues reveals unique features that accommodate diverse mechanisms for protein S-nitrosylation.

S-nitrosylation, the selective posttranslational modification of protein cysteine residues to form S-nitrosocysteine, is one of the molecular mechanisms by which nitric oxide influences diverse biological functions. In this study, unique MS-based proteomic approaches precisely pinpointed the site of S-nitrosylation in 328 peptides in 192 proteins endogenously modified in WT mouse liver. Structural analyses revealed that S-nitrosylated cysteine residues were equally distributed in hydrophobic and hydrophilic areas of proteins with an average predicted pK(a) of 10.01 ± 2.1. S-nitrosylation sites were over-represented in α-helices and under-represented in coils as compared with unmodified cysteine residues in the same proteins (χ(2) test, P < 0.02). A quantile-quantile probability plot indicated that the distribution of S-nitrosocysteine residues was skewed toward larger surface accessible areas compared with the unmodified cysteine residues in the same proteins. Seventy percent of the S-nitrosylated cysteine residues were surrounded by negatively or positively charged amino acids within a 6-Å distance. The location of cysteine residues in α-helices and coils in highly accessible surfaces bordered by charged amino acids implies site directed S-nitrosylation mediated by protein-protein or small molecule interactions. Moreover, 13 modified cysteine residues were coordinated with metals and 15 metalloproteins were endogenously modified supporting metal-catalyzed S-nitrosylation mechanisms. Collectively, the endogenous S-nitrosoproteome in the liver has structural features that accommodate multiple mechanisms for selective site-directed S-nitrosylation.

Clinical Roles in the Medical Communications Centre: A Rapid Scoping Review.

In recent years, 911 call volumes have increased, and emergency medical services (EMS) are routinely stretched beyond capacity. To better match resources with patient needs, some EMS systems have integrated clinician roles into the emergency medical communications centre (MCC). Our objective was to explore the nature and scope of clinical roles in emergency MCCs. Using a rapid scoping review methodology, we searched PubMed for studies related to any clinical role employed within an emergency MCC. We accepted reviews, experimental and observational designs, as well as expert opinions. Studies reporting on dispatcher recognition and pre-arrival instructions were excluded. Title and abstract screening were conducted by a single reviewer, included studies were verified by two reviewers, and data extraction was completed in duplicate, all using Covidence review software. The level of evidence was assessed using the prehospital evidence-based practice (PEP) scale. The protocol was registered in Open Science Framework (10.17605/OSF.IO/NX4T8).  Our search yielded 1071 titles, and four were added from other sources; 44 studies were reviewed at the full-text stage and 31 were included. The included studies were published from 2002 to 2022 and represent 17 countries. Studies meeting inclusion criteria consisted of level I (n=4, 11%), II (n=13, 37%), and III (N=6, 17%) methodologies, as well as 12 other studies (34%) with qualitative or other designs. Most of the included studies reported systems that employ nurses in the MCC (n=29, 83%). Twelve (34%) studies reported on the inclusion of paramedics in the MCC, and five (14%) reported physician involvement. The roles of these clinicians chiefly consisted of triage (n=25, 71%), advice (n=20, 57%), referral to non-emergency care (n=14, 40%), and peer-to-peer consulting (n=2, 4%). Alternative dispositions (as opposed to emergency ambulance transport) for low acuity callers included self-care, as well as referral to a general practitioner, pharmacist, or other outreach programs. There is a wide range of literature reporting on clinical roles integrated within MCCs. Our findings revealed that MCC nurses, physicians, and paramedics assist substantively with triage, advice, and referrals to better match resources to patient needs, with or without the requirement for ambulance dispatch.

Paramedic supportive discharge programmes to improve health system efficiency and patient outcomes: a scoping review protocol.

INTRODUCTION: Discharging older adults with frailty home from the emergency department (ED) poses unique challenges due to multiple interacting physical and social problems. Paramedic supportive discharge services help overcome these challenges by adding in-home assessment and/or interventions. Our objective is to describe existing paramedic programmes designed to support discharge from the ED or hospital to avoid unnecessary hospital admissions. A comprehensive description of paramedic supportive discharge services will be conducted by mapping the literature to describe: (1) why such programmes are needed; (2) who is being targeted, making referrals and delivering the services and (3) what assessments and interventions are offered. METHODS AND ANALYSIS: We will include studies that focus on expanded paramedic roles (community paramedicine) and extended scope postdischarge from the ED or hospital. All study designs will be included with no limit by language. We will include peer-reviewed articles and preprints and a targeted search of grey literature from January 2000 to June 2022. The proposed scoping review will be conducted in accordance with the Joanna Briggs Institute methodology. We will use a search strategy designed by a health science librarian to search MEDLINE All (Ovid), CINAHL Full Text (EBSCO), Embase (Elsevier) and Scopus (Elsevier) for eligible studies from 2000 to present. Two independent reviewers will conduct screening and full-text review. Data extraction will be conducted by one reviewer and verified by another. We will report our findings descriptively by charting trends in the research. ETHICS AND DISSEMINATION: Research ethics review is not required as this is a scoping review comprised published studies. The results of this research will be published in a manuscript and presented at national and international geriatric and emergency medicine conferences. This research will inform future implementation studies on community paramedic supportive discharge services. REGISTRATION: This scoping review protocol was registered in Open Science Framework and can be found here: https://doi.org/10.17605/OSF.IO/X52P7.

Univariate and Multivariate Base Rates of Score Elevations, Reliable Change, and Inter-Rater Discrepancies in the BRIEF-A Standardization Samples.

The Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A) is a standardized rating scale of subjective executive functioning. We provide univariate and multivariate base rates (BRs) for scale/index scores in the clinical range (T scores ≥65), reliable change, and inter-rater information not included in the Professional Manual. Participants were adults (ages = 18-90 years) from the BRIEF-A self-report (N = 1,050) and informant report (N = 1,200) standardization samples, as well as test-retest (n = 50 for self, n = 44 for informant) and inter-rater (n = 180) samples. Univariate BRs of elevated T scores were low (self-report = 3.3%-15.4%, informant report = 4.5%-16.3%). Multivariate BRs revealed the common occurrence of obtaining at least one elevated T-score across scales (self-report = 26.5%-37.3%, informant report = 22.7%-30.3%), whereas virtually none had elevated scores on all scales. Test-retest scores were highly correlated (self = .82-.94; informant = .91-.96). Inter-rater correlations ranged from .44 to .68. Significant (p < .05) test-retest T-score differences ranged from 7 to 12 for self-report, from 6 to 8 for informant report, and from 16 to 21 points for inter-rater T-score differences. Applications of these findings are discussed.

Toll-like receptor polymorphisms and cerebral malaria: TLR2 Δ22 polymorphism is associated with protection from cerebral malaria in a case control study.

BACKGROUND: In malaria endemic areas, host genetics influence whether a Plasmodium falciparum-infected child develops uncomplicated or severe malaria. TLR2 has been identified as a receptor for P. falciparum-derived glycosylphosphatidylinositol (GPI), and polymorphisms within the TLR2 gene may affect disease pathogenesis. There are two common polymorphisms in the 5' un-translated region (UTR) of TLR2, a 22 base pair deletion in the first unstranslated exon (Δ22), and a GT dinucleotide repeat in the second intron (GTn). METHODS: These polymorphisms were examined in a Ugandan case control study on children with either cerebral malaria or uncomplicated malaria. Serum cytokine levels were analysed by ELISA, according to genotype and disease status. In vitro TLR2 expression was measured according to genotype. RESULTS: Both Δ22 and GTn polymorphisms were highly frequent, but only Δ22 heterozygosity was associated with protection from cerebral malaria (OR 0.34, 95% confidence intervals 0.16, 0.73). In vitro, heterozygosity for Δ22 was associated with reduced pam3cys inducible TLR2 expression in human monocyte derived macrophages. In uncomplicated malaria patients, Δ22 homozygosity was associated with elevated serum IL-6 (p = 0.04), and long GT repeat alleles were associated with elevated TNF (p = 0.007). CONCLUSION: Reduced inducible TLR2 expression may lead to attenuated pro-inflammatory responses, a potential mechanism of protection from cerebral malaria present in individuals heterozygous for the TLR2 Δ22 polymorphism.

Counseling psychology trainees' perceptions of training and commitments to social justice.

This mixed methods study examined social justice commitments of counseling psychology graduate trainees. In the quantitative portion of the study, a national sample of trainees (n = 260) completed a web-based survey assessing their commitments to social justice and related personal and training variables. Results suggested that students desired greater social justice training than what they experienced in their programs. In the qualitative portion, we used a phenomenological approach to expand and elaborate upon quantitative results. A subsample (n = 7) of trainees who identified as strong social justice activists were interviewed regarding their personal, professional, and training experiences. Eleven themes related to participants' meanings of and experiences with social justice emerged within 4 broad categories: nature of social justice, motivation for activism, role of training, and personal and professional integration. Thematic findings as well as descriptive statistics informed the selection and ordering of variables in a hierarchical regression analysis that examined predictors of social justice commitment. Results indicated that trainees' perceptions of training environment significantly predicted their social justice commitment over and above their general activist orientation and spirituality. Findings are discussed collectively, and implications for training and future research are provided.

Adverse Health Effects Related to Shift Work Patterns and Work Schedule Tolerance in Emergency Medical Services Personnel: A Scoping Review.

Paramedicine as a profession is continually evolving in clinical practice, responsibilities, and workload. Changes over time in both population demographics and distribution have altered the demand for, and availability of, prehospital emergency medical services (EMS). These factors may also affect scheduling policies in many EMS organizations. However, there is little evidence that suggests optimal shift scheduling patterns to reduce adverse health events such as increased stress or fatigue in prehospital emergency health care providers. Our objective was to describe associations between variations in shift scheduling patterns and EMS provider health outcomes, such as fatigue, stress, sleep quality, and general mental and physiological health. We also sought to identify knowledge gaps. We performed searches of PubMed, CINAHL, Embase, and Cochrane databases for primary studies, systematic reviews, and meta-analyses published between January 2000 and December 2020. Studies reporting measurable health care outcomes in prehospital personnel with defined shift schedule patterns in land-based ambulance systems were included. Our search strategy yielded 188 studies, of which 11 met eligibility criteria (eight cross-sectional surveys, one single case report, one retrospective cohort study, one prospective cohort study, and one systematic review), with one additional study found through reference list screening, leaving 12 studies for review. All publications contained a description of shift schedule characteristics and shared similar outcomes of interest, although there was variation in comparators and assessment of outcomes. Most studies showed high rates of fatigue, stress, mental health concerns, and negative general health outcomes in paramedic shift worker populations. The case study reported improved fatigue, alertness, and sleep quality levels following a switch from a 24-hour shift pattern to an eight-hour shift. We did not complete an in-depth risk of bias assessment for any of the studies. Melnyk evidence ratings varied from IV to VI, indicating a low quality of evidence evaluating the impacts of shift schedule patterns in paramedics, with the retrospective cohort study design, ranked as IV, systematic review as a V, and prospective cohort study, case report and surveys ranked as VI. The low quality and quantity of evidence indicate the need for further research to definitively assess relationships between specific schedule patterns and health outcomes.