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1.
PLoS One ; 18(8): e0288984, 2023.
Article in English | MEDLINE | ID: mdl-37531381

ABSTRACT

BACKGROUND: The COVID-19 pandemic (March 2020-May 2023) had a profound effect around the world with vulnerable people being particularly affected, including worsening existing health inequalities. This article explores the impact of the pandemic on health services for First Nations people living with HIV (FN-PWLE) in Manitoba, Canada. This study investigated perceptions of both health care providers and FN-PWLE through qualitative interviews occurring between July 2020 and February 2022 to understand their experience and identify lessons learned that could be translated into health system changes. METHODS: Using a qualitative, participatory-action, intentional decolonizing approach for this study we included an Indigenous knowledge keeper and Indigenous research associates with lived experience as part of the study team. A total of twenty-five [25] in-depth semi-structured interviews were conducted with eleven healthcare providers (HCPs) and fourteen First Nation people with lived HIV experience (FN-PWLE). In total, 18/25 or 72% of the study participants self-identified as First Nation people. RESULTS: The COVID-19 pandemic negatively impacted health services access for FN-PWLE, a) disrupted relationships between FN-PWLE and healthcare providers, b) disrupted access to testing, in-person appointments, and medications, and c) intersectional stigma was compounded. Though, the COVID-19 pandemic also led to positive effects, including the creation of innovative solutions for the health system overall. CONCLUSIONS: The COVID-19 pandemic exaggerated pre-existing barriers and facilitators for Manitoba FN-PWLE accessing and using the healthcare system. COVID-19 impacted health system facilitators such as relationships and supports, particularly for First Nation people who are structurally disadvantaged and needing more wrap-around care to address social determinants of health. Innovations during times of crisis, included novel ways to improve access to care and medications, illustrated how the health system can quickly provide solutions to long-standing barriers, especially for geographical barriers. Lessons learned from the COVID-19 pandemic should be considered for improvements to the health system's HIV cascade of care for FN-PWLE and other health system improvements for First Nations people with other chronic diseases and conditions. Finally, this study illustrates the value of qualitative and First Nation decolonizing research methods. Further studies are needed, working together with First Nations organizations and communities, to apply these recommendations and innovations to change health care and people's lives.


Subject(s)
COVID-19 , HIV Infections , Humans , Manitoba/epidemiology , Pandemics , COVID-19/epidemiology , Canada , Indigenous Peoples , HIV Infections/epidemiology , HIV Infections/therapy
2.
Antimicrob Agents Chemother ; 67(7): e0046223, 2023 07 18.
Article in English | MEDLINE | ID: mdl-37310224

ABSTRACT

HIV-1 integrase-LEDGF allosteric inhibitors (INLAIs) share the binding site on the viral protein with the host factor LEDGF/p75. These small molecules act as molecular glues promoting hyper-multimerization of HIV-1 IN protein to severely perturb maturation of viral particles. Herein, we describe a new series of INLAIs based on a benzene scaffold that display antiviral activity in the single digit nanomolar range. Akin to other compounds of this class, the INLAIs predominantly inhibit the late stages of HIV-1 replication. A series of high-resolution crystal structures revealed how these small molecules engage the catalytic core and the C-terminal domains of HIV-1 IN. No antagonism was observed between our lead INLAI compound BDM-2 and a panel of 16 clinical antiretrovirals. Moreover, we show that compounds retained high antiviral activity against HIV-1 variants resistant to IN strand transfer inhibitors and other classes of antiretroviral drugs. The virologic profile of BDM-2 and the recently completed single ascending dose phase I trial (ClinicalTrials.gov identifier: NCT03634085) warrant further clinical investigation for use in combination with other antiretroviral drugs. Moreover, our results suggest routes for further improvement of this emerging drug class.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , HIV Integrase , Humans , Virus Replication , HIV Integrase Inhibitors/pharmacology , HIV Integrase Inhibitors/therapeutic use , Antiviral Agents/pharmacology , HIV Integrase/metabolism , HIV Infections/drug therapy , Allosteric Regulation
3.
mBio ; 14(1): e0356022, 2023 02 28.
Article in English | MEDLINE | ID: mdl-36744954

ABSTRACT

Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are an emerging class of small molecules that disrupt viral maturation by inducing the aberrant multimerization of IN. Here, we present cocrystal structures of HIV-1 IN with two potent ALLINIs, namely, BI-D and the drug candidate Pirmitegravir. The structures reveal atomistic details of the ALLINI-induced interface between the HIV-1 IN catalytic core and carboxyl-terminal domains (CCD and CTD). Projecting from their principal binding pocket on the IN CCD dimer, the compounds act as molecular glue by engaging a triad of invariant HIV-1 IN CTD residues, namely, Tyr226, Trp235, and Lys266, to nucleate the CTD-CCD interaction. The drug-induced interface involves the CTD SH3-like fold and extends to the beginning of the IN carboxyl-terminal tail region. We show that mutations of HIV-1 IN CTD residues that participate in the interface with the CCD greatly reduce the IN-aggregation properties of Pirmitegravir. Our results explain the mechanism of the ALLINI-induced condensation of HIV-1 IN and provide a reliable template for the rational development of this series of antiretrovirals through the optimization of their key contacts with the viral target. IMPORTANCE Despite the remarkable success of combination antiretroviral therapy, HIV-1 remains among the major causes of human suffering and loss of life in poor and developing nations. To prevail in this drawn-out battle with the pandemic, it is essential to continue developing advanced antiviral agents to fight drug resistant HIV-1 variants. Allosteric integrase inhibitors (ALLINIs) are an emerging class of HIV-1 antagonists that are orthogonal to the current antiretroviral drugs. These small molecules act as highly specific molecular glue, which triggers the aggregation of HIV-1 integrase. In this work, we present high-resolution crystal structures that reveal the crucial interactions made by two potent ALLINIs, namely, BI-D and Pirmitegravir, with HIV-1 integrase. Our results explain the mechanism of drug action and will inform the development of this promising class of small molecules for future use in antiretroviral regimens.


Subject(s)
HIV Infections , HIV Integrase Inhibitors , Humans , Allosteric Regulation , HIV Integrase Inhibitors/pharmacology , Antiviral Agents/therapeutic use , HIV Infections/drug therapy
4.
Am Surg ; 88(10): 2451-2455, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35549566

ABSTRACT

INTRODUCTION: Trauma patients who develop indications for therapeutic anticoagulation (TAC) present a challenge due to concern for bleeding. Transfusion requirement has been described as a common complication of TAC after trauma but its clinical relevance is unclear. OBJECTIVE: Determine risk factors for and clinical outcomes associated with transfusion requirement on TAC after trauma. METHODS: All trauma patients admitted to an academic urban level I trauma center from January 2010 to August 2020 who received TAC were included in this retrospective cohort study. Data included injury characteristics; TAC indication and timing; transfusions; and interventions. Patients who required transfusion after TAC were compared to those who did not. RESULTS: Eighty-two patients were included. The most common reasons for TAC were deep vein thrombosis (67.1%) and pulmonary embolism (31.7%). Two (2.4%) patients developed gastrointestinal bleeding. One (1.2%) underwent endoscopic intervention. Two patients (4.9%) had intracranial hemorrhage progression. Blood transfusion after TAC initiation was required in 43.9% of patients. Patients who were transfused started TAC more quickly after traumatic injury (5.5 vs 10.0 days, P = .03), had fewer hospital-free days (54 vs 64 days, P < .01), ICU-free days (8.5 vs 16.5 days, P = .01), and higher mortality (13.9% vs 2.1%, P = .04). CONCLUSION: Transfusions are common after starting TAC in trauma patients. Requiring transfusion after starting TAC was associated with shorter time from injury to starting TAC, higher mortality, and fewer ICU and hospital-free days.


Subject(s)
Blood Transfusion , Trauma Centers , Anticoagulants/therapeutic use , Hemorrhage/etiology , Hemorrhage/therapy , Humans , Retrospective Studies
5.
J Alzheimers Dis ; 87(3): 1367-1378, 2022.
Article in English | MEDLINE | ID: mdl-35431246

ABSTRACT

BACKGROUND: Aging dogs may suffer from canine cognitive dysfunction syndrome (CCDS), a condition in which cognitive decline is associated with amyloid pathology and cortical atrophy. Presumptive diagnosis is made through physical examination, exclusion of systemic/metabolic conditions, and completion of screening questionnaires by owners. OBJECTIVE: This study aimed to determine whether cognitive function could be quantified in aging pet dogs, and to correlate cognitive testing with validated questionnaires and plasma neurofilament light chain (pNfL) concentration. METHODS: Thirty-nine dogs from fifteen breeds were recruited (9.3 to 15.3 years). Owners completed the Canine Dementia Scale (CADES) and Canine Cognitive Dysfunction Rating scale (CCDR). Executive control and social cues were tested, and pNfL was measured with single molecule array assay. Comparisons were made between cognitive testing scores, CADES, CCDR scores, and pNfL. RESULTS: CADES scoring classified five dogs as severe CCDS, six as moderate, ten as mild, and eighteen as normal. CCDR identified seven dogs at risk of CCDS and thirty-two as normal. Cognitive testing was possible in the majority of dogs, although severely affected dogs were unable to learn tasks. CADES score correlated with sustained attention duration (r = -0.47, p = 0.002), inhibitory control (r = -0.51, p = 0.002), detour (r = -0.43, p = 0.001), and pNfL (r = 0.41, p = 0.025). Concentration of pNfL correlated with inhibitory control (r = -0.7, p≤0.001). The CCDR scale correlated with performance on inhibitory control (r = -0.46, p = 0.005). CONCLUSION: Our findings suggest that a multi-dimensional approach using a combination of questionnaires, specific cognitive tests, and pNfL concentration can be used to quantify cognitive decline in aging pet dogs.


Subject(s)
Cognitive Dysfunction , Aging , Animals , Biomarkers , Cognitive Dysfunction/diagnostic imaging , Dogs , Humans , Neuropsychological Tests , Surveys and Questionnaires
6.
Engineering (Beijing) ; 17: 75-81, 2022 Oct.
Article in English | MEDLINE | ID: mdl-38149108

ABSTRACT

Subwavelength manipulation of light waves with high precision can enable new and exciting applications in spectroscopy, sensing, and medical imaging. For these applications, miniaturized spectrometers are desirable to enable the on-chip analysis of spectral information. In particular, for imaging-based spectroscopic sensing mechanisms, the key challenge is to determine the spatial-shift information accurately (i.e., the spatial displacement introduced by wavelength shift or biological or chemical surface binding), which is similar to the challenge presented by super-resolution imaging. Here, we report a unique "rainbow" trapping metasurface for on-chip spectrometers and sensors. Combined with super-resolution image processing, the low-setting 4× optical microscope system resolves a displacement of the resonant position within 35 nm on the plasmonic rainbow trapping metasurface with a tiny area as small as 0.002 mm2. This unique feature of the spatial manipulation of efficiently coupled rainbow plasmonic resonances reveals a new platform for miniaturized on-chip spectroscopic analysis with a spectral resolution of 0.032 nm in wavelength shift. Using this low-setting 4× microscope imaging system, we demonstrate a biosensing resolution of 1.92 × 109 exosomes per milliliter for A549-derived exosomes and distinguish between patient samples and healthy controls using exosomal epidermal growth factor receptor (EGFR) expression values, thereby demonstrating a new on-chip sensing system for personalized accurate bio/chemical sensing applications.

7.
Int J Circumpolar Health ; 79(1): 1717278, 2020 12.
Article in English | MEDLINE | ID: mdl-31964318

ABSTRACT

The Truth and Reconciliation Commission of Canada determined that the Dene people, among other Indigenous groups, experienced cultural genocide through policies that separated them from their lands and resources, and from their families, languages, cultures, and by forcibly sending children to Indian Residential Schools. The resultant social inequity is manifested in conditions of social injustice including inadequate housing. The Dene healthy housing research was a continuing partnership between the two Dene First Nation communities, the university and a provincial First Nation non-government organisation. This project engaged the creative energies of university students and Dene senior-high students to create and articulate Dene healthy housing so that concepts/plans/designs are ready for future funding interventions. We co-developed methods and networks to reframe housing as a social determinant of health and an important factor in social justice. This project reflects the fundamental requirement for a respectful understanding of Dene perspectives on housing and health and the need for Dene control over their built environment.


Subject(s)
Capacity Building/organization & administration , Health Equity/organization & administration , Health Promotion/methods , Health Services, Indigenous/organization & administration , Indians, North American/statistics & numerical data , Canada , Humans , Minority Groups/statistics & numerical data , Vulnerable Populations
8.
Int J Circumpolar Health ; 78(1): 1588092, 2019 12.
Article in English | MEDLINE | ID: mdl-30935345

ABSTRACT

BACKGROUND: Among Indigenous people in Canada the incidence of HIV is 3.5 times higher than other ethnicities. In Manitoba First Nations, Metis and Inuit people are disproportionately represented (40%) among people who are new to HIV care. Northlands Denesuline First Nation (NDFN) identified the need to revisit their level of knowledge and preparedness for responding to the increasing rates of HIV. NDFN piloted a community readiness assessment (CRA) tool to assess its appropriateness for use in northern Manitoba. METHODS: A First Nation and non-First Nation research team trained to administer the CRA tool at NDFN in Manitoba. Five informants were interviewed using the CRA tool and the responses were scored, analysed and reviewed at community workshops and with stakeholders to develop a 1-year action plan. RESULTS: CRA training was best conducted in the community. Using the readiness score of 2.4 along with feedback from two workshops, community members, the research team and stakeholders, we identified priorities for adult education and youth involvement in programmes and planning. CONCLUSIONS: In response to the increasing incidence of HIV, a northern First Nation community successfully modified and implemented a CRA tool to develop an action plan for culturally appropriate interventions and programmes.


Subject(s)
Community Participation/methods , HIV Infections/ethnology , HIV Infections/prevention & control , Health Services, Indigenous/organization & administration , Inuit , Acquired Immunodeficiency Syndrome/prevention & control , Acquired Immunodeficiency Syndrome/therapy , Arctic Regions , Canada , HIV Infections/therapy , Health Knowledge, Attitudes, Practice , Humans , Leadership , Pilot Projects
9.
Surg Infect (Larchmt) ; 20(5): 351-358, 2019 Jul.
Article in English | MEDLINE | ID: mdl-30900946

ABSTRACT

Background: The United States is currently experiencing a heroin epidemic. Recent reports have demonstrated a three-fold increase in heroin use among Americans since 2007 with a shift in demographics to more women and white Americans. Furthermore, there has been a correlation between the recent opioid epidemic and an increase in heroin abuse. Much has been written about epidemiology and prevention of heroin abuse, but little has been dedicated to the surgical implications, complications, and resource utilization. Discussion: This article focuses on the surgical problems encountered from heroin abuse and how to manage them in a constant effort to improve morbidity and mortality for these heroin abusers.


Subject(s)
Epidemics , Heroin/administration & dosage , Narcotics/administration & dosage , Skin Diseases, Bacterial/epidemiology , Soft Tissue Infections/epidemiology , Substance Abuse, Intravenous/complications , Substance Abuse, Intravenous/epidemiology , Humans , Skin Diseases, Bacterial/surgery , Soft Tissue Infections/surgery , United States/epidemiology
10.
Adv Sci (Weinh) ; 5(8): 1800222, 2018 Aug.
Article in English | MEDLINE | ID: mdl-30128237

ABSTRACT

100% efficiency is the ultimate goal for all energy harvesting and conversion applications. However, no energy conversion process is reported to reach this ideal limit before. Here, an example with near perfect energy conversion efficiency in the process of solar vapor generation below room temperature is reported. Remarkably, when the operational temperature of the system is below that of the surroundings (i.e., under low density solar illumination), the total vapor generation rate is higher than the upper limit that can be produced by the input solar energy because of extra energy taken from the warmer environment. Experimental results are provided to validate this intriguing strategy under 1 sun illumination. The best measured rate is ≈2.20 kg m-2 h-1 under 1 sun illumination, well beyond its corresponding upper limit of 1.68 kg m-2 h-1 and is even faster than the one reported by other systems under 2 sun illumination.

11.
Int J Breast Cancer ; 2017: 4259704, 2017.
Article in English | MEDLINE | ID: mdl-28487775

ABSTRACT

Objectives. The objectives of this study were to identify the randomised controlled trials in breast cancer occurring in low and middle income countries (LMICs) generally and within Sub-Saharan Africa specifically, to describe the current status and identify opportunities for further research in these areas. Materials and Methods. Data for this study were obtained from ClinicalTrials.gov. The search term "Breast Cancer Research" was used, and relevant information extracted and analysed. Results. 2414 trials were identified, of which 1099 were eligible for inclusion. 69 of these trials occurred in LMICs. Of the 52 LMICs globally, 30% were participating in breast cancer research. Of the 17 LMICs in Africa, 77% are situated in Sub-Saharan Africa; 23% were participating in breast cancer research, which accounted for 9% of total Sub-Saharan African studies. Conclusion. This study provides current evidence for the need for breast cancer research in LMICs globally and within Sub-Saharan Africa. Within LMIC regions where research is active, the type and numbers of studies are unevenly distributed. High quality research within such areas should be encouraged as the results may have both local and global applications, particularly in the provision of affordable health care.

12.
Burns ; 43(3): e38-e42, 2017 May.
Article in English | MEDLINE | ID: mdl-28277273

ABSTRACT

The use of electronic cigarettes has become increasingly popular with claims suggesting healthier alternatives to tobacco cigarettes. However, research regarding the safety of such devices has been limited to an analysis of the inhaled vapor and the short and long-term effects on the body. A lesser recognized risk of electronic cigarette use is that of lithium-ion battery failure causing ignition, leading to severe thermal injury. Such incidents have been reported in the media but with inconsistencies from a lack of focus on the injuries sustained and a cause of ignition. The cases presented here are among the first recognized thermal injuries sustained from electronic cigarette lithium-ion battery failure, the potential rationale for these failures, and a need for increased awareness of the safety hazards of these devices.


Subject(s)
Burns/etiology , Electric Power Supplies/adverse effects , Electronic Nicotine Delivery Systems/adverse effects , Leg Injuries/etiology , Adult , Bandages , Burns/therapy , Debridement , Humans , Leg Injuries/therapy , Male , Middle Aged , Skin Transplantation , Thigh , Wound Infection/therapy , Young Adult
13.
PeerJ ; 4: e2352, 2016.
Article in English | MEDLINE | ID: mdl-27635325

ABSTRACT

Zebrafish (Danio rerio) have emerged as a popular model for studying the pharmacology and behavior of anxiety. While there have been numerous studies documenting the anxiolytic and anxiogenic effects of common drugs in zebrafish, many do not report or test for behavioral differences between the sexes. Previous studies have indicated that males and females differ in their baseline level of anxiety. In this study, we test for a sex interaction with fluoxetine and nicotine. We exposed fish to system water (control), 10 mg/L fluoxetine, or 1 mg/L nicotine for three minutes prior to being subjected to four minutes in an open-field drop test. Video recordings were tracked using ProAnalyst. Fish from both drug treatments reduced swimming speed, increased vertical position, and increased use of the top half of the open field when compared with the control, though fluoxetine had a larger effect on depth related behaviors while nicotine mostly affected swimming speed. A significant sex effect was observed where females swam at a slower and more constant speed than males, however neither drug produced a sex-dependent response.

14.
Acta Biomater ; 44: 65-72, 2016 10 15.
Article in English | MEDLINE | ID: mdl-27554017

ABSTRACT

UNLABELLED: Trabecular bone is an intricate 3D network of struts and plates. Although the structure-function relations in trabecular bone have been studied since the time of Julius Wolff, controversy still exists regarding the architectural parameters responsible for its stability and resilience. We present a parameter that measures the angle between two connected trabeculae - the Inter-Trabecular Angle (ITA). We studied the ITA values derived from µCT scans of different regions of the proximal femora of 5 individuals of different age and sex. We show that the ITA angle distribution of nodes with 3 connecting trabeculae has a mean close to 120°, nodes with 4 connecting trabeculae has a mean close to 109° and nodes of higher connectivity have mean ITA values around 100°. This tendency to spread the ITAs around geometrically symmetrical motifs is highly conserved. The implication is that the ITAs are optimized such that the smallest amount of material spans the maximal 3D volume, and possibly by so doing trabecular bone might be better adapted to multidirectional loading. We also draw a parallel between trabecular bone and tensegrity structures - where lightweight, resilient and stable tetrahedron-based shapes contribute to strain redistribution amongst all the elements and to collective impact dampening. STATEMENT OF SIGNIFICANCE: The Inter-Trabecular Angle (ITA) is a new topological parameter of trabecular bone. The ITA characterizes the way trabeculae connect with each other at nodes, regardless of their thickness and shape. The mean ITA value of nodes with 3 trabeculae is close to 120°, of nodes with 4 trabeculae is just below 109°, and the mean ITA of nodes with 5 and more trabeculae is around 100°. Thus the connections of trabeculae trend towards adopting symmetrical shapes. This implies that trabeculae can maximally span 3D space using the minimal amount of material. We draw a parallel between this motif and the concept of tensegrity - an engineering premise to which many living creatures conform at multiple levels of organization.


Subject(s)
Cancellous Bone/anatomy & histology , Cancellous Bone/physiology , Femur/anatomy & histology , Femur/physiology , Aged , Algorithms , Biomechanical Phenomena , Female , Femur Neck/anatomy & histology , Humans , Male , Middle Aged , Young Adult
15.
Am Surg ; 81(10): 983-7, 2015 Oct.
Article in English | MEDLINE | ID: mdl-26463294

ABSTRACT

Pancreaticoduodenectomy (PD) has historically required perioperative blood transfusion in 40 to 60 per cent of cases. Growing data suggest that transfusions may be deleterious in the surgical patient. We recently initiated a minimal transfusion approach to PD consisting of limited postoperative blood draws, early iron supplementation, changes in surgical technique, and elimination of hemoglobin transfusion triggers. Predictors of perioperative transfusion were analyzed in 130 consecutive patients undergoing PD by a single surgeon between 2008 and 2013, divided into two eras with 65 patients each. Patients in each era were similar with respect to age, comorbidities, American Society of Anesthesiologists class, body mass index, and diagnosis. The transfusion rate for the entire group was 22 per cent. Nonsignificant predictors of perioperative transfusion include American Society of Anesthesiologists class ≥3 (P = 0.41), vascular resections (P = 0.56), body mass index ≥30 (P = 0.72), and intraoperative blood loss (P = 0.89). Significant predictors of transfusion include PD performed in Era 1 as well as preoperative hemoglobin levels <10 g/dL. In Era 1, 38 per cent of patients required transfusion compared with 6 per cent in Era 2 (P < 0.01). Shorter length of stay and a trend toward decreased pancreatic fistulae were seen in Era 2. Transfusions can be almost completely eliminated in PD and this may contribute to improved outcomes.


Subject(s)
Blood Loss, Surgical/prevention & control , Blood Transfusion/statistics & numerical data , Pancreaticoduodenectomy/methods , Preoperative Care/methods , Aged , Blood Loss, Surgical/mortality , California/epidemiology , Female , Follow-Up Studies , Hospital Mortality/trends , Humans , Male , Retrospective Studies , Survival Rate/trends , Time Factors , Treatment Outcome
16.
Int J Circumpolar Health ; 74: 28952, 2015.
Article in English | MEDLINE | ID: mdl-26294193

ABSTRACT

BACKGROUND: Canadian First Nation populations have experienced endemic and epidemic tuberculosis (TB) for decades. Vitamin D-mediated induction of the host defence peptide LL-37 is known to enhance control of pathogens such as Mycobacterium tuberculosis. OBJECTIVE: Evaluate associations between serum levels of 25-hydroxy vitamin D (25(OH)D) and LL-37, in adult Dene First Nation participants (N = 34) and assess correlations with single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP). DESIGN: Venous blood was collected from all participants at baseline (winter and summer) and in conjunction with taking vitamin D supplements (1,000 IU/day) (winter and summer). Samples were analysed using ELISA for concentrations of vitamin D and LL-37, and SNPs in the VDR and VDBP regions were genotyped. RESULTS: Circulating levels of 25(OH)D were not altered by vitamin D supplementation, but LL-37 levels were significantly decreased. VDBP and VDR SNPs did not correlate with serum concentrations of 25(OH)D, but LL-37 levels significantly decreased in individuals with VDBP D432E T/G and T/T, and with VDR SNP Bsm1 T/T genotypes. CONCLUSIONS: Our findings suggest that vitamin D supplementation may not be beneficial as an intervention to boost innate immune resistance to M. tuberculosis in the Dene population.


Subject(s)
Antimicrobial Cationic Peptides/genetics , Endemic Diseases , Receptors, Calcitriol/genetics , Tuberculosis/epidemiology , Vitamin D-Binding Protein/genetics , Vitamin D/analogs & derivatives , Adult , Canada/epidemiology , Cohort Studies , Female , Genetic Markers , Humans , Incidence , Male , Middle Aged , Polymorphism, Single Nucleotide , Population Groups , Prospective Studies , Risk Assessment , Tuberculosis/blood , Tuberculosis/drug therapy , Tuberculosis/genetics , Vitamin D/administration & dosage , Vitamin D/blood , Cathelicidins
17.
J Trauma Acute Care Surg ; 75(4): 682-6, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24064883

ABSTRACT

BACKGROUND: Gender may influence outcomes following traumatic brain injury (TBI) although the mechanism is unknown. Animal TBI studies suggest that gender differences in endogenous hormone production may be the source. Limited retrospective clinical studies on gender present varied conclusions. Pediatric patients represent a unique population as pubescent children experience up-regulation of endogenous hormones that varies dramatically by gender. Younger children do not have these hormonal differences. The aim of this study was to compare pubescent and prepubescent females with males after isolated TBI to identify independent predictors of mortality. METHODS: We performed a retrospective review of the National Trauma Data Bank Research Data Sets from 2007 and 2008 looking at all blunt trauma patients 18 years or younger who required hospital admission after isolated, moderate-to-severe TBI, defined as head Abbreviated Injury Scale (AIS) score 3 or greater. We excluded all individuals with AIS score of 3 or greater for any other region to limit the confounding effect of comorbidities. Based on the median age of menarche, we defined two age groups as follows: prepubescent (0-12 years) and pubescent (>12 years). Analysis was performed to compare trauma profiles and outcomes between groups. Our primary outcome measure was in-hospital mortality. RESULTS: A total of 20,280 patients met inclusion criteria; 10,135 were prepubescent, and 10,145 were pubescent. Overall mortality was 6.9%, and lower mortality was noted among prepubescent patients compared with pubescent (5.2% vs. 8.6%, p < 0.0001). Although female gender did not predict reduced mortality in the prepubescent cohort (adjusted odds ratio, 1.05; 95% confidence interval, 0.85-1.30; p = 0.63), female gender was associated with reduced mortality in the pubescent (adjusted odds ratio, 0.78; 95% confidence interval, 0.65-0.93; p = 0.007). CONCLUSION: In contrast to prepubescent female gender, pubescent female gender predicts reduced mortality following isolated, moderate-to-severe TBI. Endogenous hormonal differences may be a contributing factor and require further investigation. LEVEL OF EVIDENCE: Prognostic study, level III.


Subject(s)
Brain Injuries/mortality , Abbreviated Injury Scale , Adolescent , Age Factors , Child , Child, Preschool , Databases, Factual , Female , Glasgow Coma Scale , Hospital Mortality , Humans , Infant , Infant, Newborn , Injury Severity Score , Male , Retrospective Studies , Sex Factors , United States/epidemiology
18.
Article in English | MEDLINE | ID: mdl-23984265

ABSTRACT

BACKGROUND: Increased awareness of the wide spectrum of activity of vitamin D has focused interest on its role in the health of Canada's Aboriginal peoples, who bear a high burden of both infectious and chronic disease. Cutaneous vitamin D synthesis is limited at northern latitudes, and the transition from nutrient-dense traditional to nutrient-poor market foods has left many Canadian Aboriginal populations food insecure and nutritionally vulnerable. OBJECTIVE: The study was undertaken to determine the level of dietary vitamin D in a northern Canadian Aboriginal (Dené) community and to determine the primary food sources of vitamin D. DESIGN: Cross-sectional study. METHODS: Dietary vitamin D intakes of 46 adult Dené men and women were assessed using a food frequency questionnaire and compared across age, gender, season and body mass index. The adequacy of dietary vitamin D intake was assessed using the 2007 Adequate Intake (AI) and the 2011 Recommended Dietary Allowance (RDA) values for Dietary Reference Intake (DRI). RESULTS: Mean daily vitamin D intake was 271.4 IU in winter and 298.3 IU in summer. Forty percent and 47.8% of participants met the vitamin D 1997 AI values in winter and summer, respectively; this dropped to 11.1 and 13.0% in winter and summer using 2011 RDA values. Supplements, milk, and local fish were positively associated with adequate vitamin D intake. Milk and local fish were the major dietary sources of vitamin D. CONCLUSIONS: Dietary intake of vitamin D in the study population was low. Only 2 food sources, fluid milk and fish, provided the majority of dietary vitamin D. Addressing low vitamin D intake in this population requires action aimed at food insecurity present in northern Aboriginal populations.


Subject(s)
Diet/statistics & numerical data , Indians, North American/statistics & numerical data , Vitamin D/administration & dosage , Adult , Aged , Aged, 80 and over , Canada/epidemiology , Diet Surveys , Female , Humans , Male , Middle Aged , Seasons , Surveys and Questionnaires , Young Adult
20.
J Surg Res ; 184(1): 501-6, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23731689

ABSTRACT

INTRODUCTION: High-dose vancomycin is increasingly prescribed for critically ill trauma patients at risk for methicillin-resistant Staphylococcus aureus pneumonia. Although trauma patients have multiple known risk factors for acute kidney injury (AKI), a link between vancomycin and AKI or mortality has not been established. We hypothesize that high vancomycin trough concentration (VT) after trauma is associated with AKI and increased mortality. METHODS: This was a retrospective analysis from a single institution Level I trauma center. Data were reviewed for all adult trauma patients who were admitted between 2006 and 2010. Patients were included if they received intravenous vancomycin, had serum creatinine levels before and after vancomycin administration, and had at least one recorded VT. Patients were stratified by VT into four groups: VT1 = 0-10 mg/L, VT2 = 10.1-15 mg/L, VT3 = 15.1-20 mg/L, VT4 >20 mg/L. Multivariable logistic regression was performed to determine the association between VT, AKI, and mortality. RESULTS: Of the 6781 trauma patients reviewed, 263 (3.9%) fit inclusion criteria. Ninety-seven (36.9%) patients developed AKI and 25 (9.5%) died. AKI and mortality increased progressively with VT. Ninety-one patients (34.6%) had troughs >20 mg/L and VT4 was independently associated with AKI (AOR 4.7, P < 0.01) and mortality (AOR 4.8, P = 0.05). CONCLUSION: AKI is common in trauma patients who receive intravenous vancomycin. A supratherapeutic trough level of >20 mg/L is an independent predictor of AKI and mortality in trauma patients.


Subject(s)
Acute Kidney Injury/mortality , Methicillin-Resistant Staphylococcus aureus/drug effects , Pneumonia, Bacterial/drug therapy , Staphylococcal Infections/drug therapy , Vancomycin/administration & dosage , Wounds and Injuries/mortality , Acute Kidney Injury/chemically induced , Adult , Aged , Anti-Bacterial Agents/administration & dosage , Dose-Response Relationship, Drug , Female , Hospital Mortality , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , Pneumonia, Bacterial/mortality , Predictive Value of Tests , Retrospective Studies , Risk Factors , Staphylococcal Infections/mortality , Trauma Centers/statistics & numerical data , Vancomycin/adverse effects
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