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1.
Resuscitation ; 194: 110044, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37952574

ABSTRACT

BACKGROUND: Law enforcement (LE) professionals are often dispatched to out-of-hospital cardiac arrests (OHCA) to provide early cardiopulmonary resuscitation (CPR) and automated external defibrillator (AED) application with mixed evidence of a survival benefit. Our objective was to comprehensively evaluate LE care in OHCA. METHODS: This is a secondary analysis of adults with non-traumatic OHCA not witnessed by EMS and without bystander AED use from 2018-2021. Our primary outcome was survival with Cerebral Perfusion Category score ≤ 2 (functional survival). Our exposures included: LE On-scene Only (without providing care); LE CPR Only (without applying an AED); LE Ideal Care (ensuring CPR and AED application). Our control group had no LE arrival before EMS. We performed multivariable logistic regression analyses adjusting for confounders and stratified our analyses by patients with and without bystander CPR. RESULTS: There were 2569 adult, non-traumatic OHCAs from 2018-2021 meeting inclusion criteria. There were no differences in the odds of functional survival for LE On-scene Only (adjusted odds ratio [95% CI]: 1.28 [0.47-3.45]), LE CPR Only (1.26 [0.80-1.99]), or LE Ideal Care (1.36 [0.79-2.33]). In patients without bystander CPR, LE Ideal Care had significantly higher odds of functional survival (2.01 [1.06-3.81]) compared to no LE on-scene, with no significant associations for LE On-scene Only or LE CPR Only. There were no significant differences by LE care in patients already receiving bystander CPR. CONCLUSIONS: LE arrival before EMS and ensuring both CPR and AED application is associated with significantly improved functional survival in OHCA patients not already receiving bystander CPR.


Subject(s)
Cardiopulmonary Resuscitation , Emergency Medical Services , Out-of-Hospital Cardiac Arrest , Adult , Humans , Out-of-Hospital Cardiac Arrest/therapy , Law Enforcement , Defibrillators
2.
Transl Anim Sci ; 7(1): txac166, 2023 Jan.
Article in English | MEDLINE | ID: mdl-36816826

ABSTRACT

The U.S. pork production system is sensitive to supply chain disruptions, including those that can create challenges of feed delivery and feed management during the event of a foreign animal disease outbreak. Therefore, the objective was to evaluate feeding strategies during a prolonged feed availability shortage in group-housed finishing pigs and assess the impacts on pig performance. A total of 1,407 mixed-sex pigs (92 ± 11 kg BW) were randomly allocated to one of five treatments across 60 pens (N = 12 pens per treatment, 22 pigs per pen) and were blocked by initial body weight (BW) within the replicate, over a 21-d test period. Treatments were fed for 14 d (P1), and thereafter all pens returned to ad libitum access to a standard commercial diet for 7 d (P2). Treatments included: 1) Pens fed ad libitum (CON); 2) Pens fed at 1.45X ME maintenance requirement daily of CON diet (1.45X); 3) Pens fed 2X ME maintenance requirement daily of CON diet (2X); 4) Tightened feeders to the lowest setting, fed ad libitum of CON diet (CF); and 5) whole corn kernels, fed ad libitum (WC). P1 and P2 BW and feed disappearance were recorded to calculate ADG, ADFI, and G:F. Data were analyzed with pen as the experimental unit and least-squares means values reported by treatment. Compared to CON, pens fed 1.45X, 2X, CF, and WC treatments had significantly reduced P1 ADG (1.09 vs. 0.02, 0.34, 0.72, 0.41 kg/d, respectively), ADFI (3.21 vs. 1.42, 1.90, 2.49, 2.40 kg/d, respectively) and G:F (P < 0.05). During P2, ADG and G:F were increased (P < 0.05) compared to CON across all treatments. However, ADFI increased only in the 2X, CF, and WC diet from the CON (P < 0.05). Overall (days 0 to 21), all strategies attenuated BW, ADG, and ADFI (P < 0.01) compared to CON. However, G:F was only reduced (P < 0.01) in 1.45X and WC, but not 2X and CF (P > 0.05) compared to CON. In conclusion, all strategies explored could extend feed budgets. Even though these strategies were successful, increased BW variability was reported with more restrictive strategies. Further, adverse pig behaviors and welfare implications needs to be considered in adopting any restrictive feeding strategy.

3.
Health Mark Q ; 40(3): 309-325, 2023.
Article in English | MEDLINE | ID: mdl-35762706

ABSTRACT

PURPOSE: This paper addresses what variables predict and mediate relationships involving accessing telemedicine in the form of online birth control websites that are often advertised online on social media. BASIC PROCEDURES: This is a survey study of N = 252 under 60 women (Mage = 24.71); multiple linear regression and mediation analyses were done to examine the influence of IBM variables on behavioral intentions. MAIN FINDINGS: Women who currently use contraceptives report comfort and likelihood to use telemedicine services if they have positive attitudes about telemedicine and DTC advertising. Comfort with using an online contraceptive prescription service mediated the relationship between contraceptive use and likelihood to use telemedical services and between positive telemedicine attitudes and likelihood. PRINCIPAL CONCLUSIONS: Women who are positive about telemedicine and DTC ads are comfortable using these resources, and comfort is a salient mediator. Comfort and its antecedents are important predictors and facilitators of telemedicine intentions and behaviors. Using telemedicine can improve the patient experience by offering alternatives to face-to-face visits (i.e., removing barriers to provider-to-patient communication).

5.
J Palliat Med ; 25(8): 1236-1242, 2022 08.
Article in English | MEDLINE | ID: mdl-35285675

ABSTRACT

Background: Communication challenges in the neonatal intensive care unit include fragmented communication, challenges managing expectations amidst uncertainty, and navigating complex medical information. Social workers are well suited to mitigate these challenges. Objective: In this study, we aimed to characterize the extent and nature of social worker participation in family conferences for critically ill infants. Design: We used a longitudinal observational mixed-methods design, enrolling infants with a neurological condition, their parent(s), and their clinicians. All audio-recorded conferences were transcribed and de-identified. Emergent themes and subthemes were identified using conventional content analysis. Results: We enrolled 40 infants and 61 parents. Sixty-eight conferences were held and audio recorded for 24 infants. Social workers were present for 51 of these conferences (n = 51/68, 75%) across 18 cases (n = 18/24, 75%). We identified four themes, conceptualized as distinct roles played by social workers in family conferences: (1) Translator: social workers served as a communicative bridge between parents and the medical team; (2) Coordinator: social workers simplified logistics and connected parents to community resources, including home health agencies and financial assistance; (3) Expectation manager: social workers provided anticipatory guidance and helped parents conceptualize the remainder of the hospital stay, discharge, and life at home; and (4) Advocate: social workers validated parental values and concerns and provided immediate emotional support. Conclusions: Social workers participated in three-quarters of family conferences for critically ill infants. When they participated, they facilitated communication, coordinated care, managed expectations, and advocated for families. These findings underscore the important, varied, and concurrent roles social workers play in the care of critically ill infants. Future communication and family support interventions should leverage these distinct roles.


Subject(s)
Critical Illness , Social Workers , Communication , Family/psychology , Humans , Infant , Infant, Newborn , Intensive Care Units, Neonatal , Parents/psychology , Professional-Family Relations
6.
Dev Neurorehabil ; 25(7): 501-504, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35289718

ABSTRACT

The aim of this study was to examine the relationship between perceived fatigue and perceptions of walking abilities and difficulty in people with cerebral palsy (CP). Twenty individuals with CP (range 10-21y; mean age 14.8y) who usually walk in the community were recruited. Community mobility was assessed using the Functional Mobility Scale. Participants were asked about their walking ability and frequency, perceived effort during walking (using the Children's Effort Rating Table), and perceived fatigue (using the Fatigue Impact and Severity Self-Assessment). Community mobility, frequency, and perceived effort during walking were significantly related to fatigue. No relationship was found between time spent walking (maximum walking time) and fatigue. Here we demonstrate that perceived fatigue is related to walking in people with CP.


Subject(s)
Cerebral Palsy , Adolescent , Child , Fatigue , Humans , Walking
7.
Cureus ; 13(11): e19240, 2021 Nov.
Article in English | MEDLINE | ID: mdl-34877217

ABSTRACT

BACKGROUND: Myocarditis is being increasingly reported as a potential complication of both Pfizer-BioNTech and Moderna vaccines for COVID-19. One thousand five hundred and twenty-two cases were reported as of September 02, 2021, as per CDC's (Centers for Disease Control) vaccine adverse event reporting system. Most of the published data is available in the form of case reports and series. There is a need to compile the demographic data, clinical features, and outcomes in these patients.  Methods: A systematic search was conducted in PubMed, Embase, Web of science, and google scholar for published literature between January 01, 2020, and July 17, 2021. Individual data of 69 patients were pooled from 25 qualifying case reports and case series. RESULTS: The median age of onset was 21 years. 92.7% of the patients were male. 76.8% of patients received the Pfizer-BioNTech vaccine, and 23.2% received the Moderna vaccine. 88.5% developed symptoms after the second dose. Patients were admitted to the hospital a median of three days post-vaccination. All the patients had chest pain and elevated troponin. The myocarditis was confirmed on cardiac MRI in 87% of the patients. Most of the patients had late gadolinium enhancement on MRI. The median length of stay was four days. All the reported patients recovered and were discharged. CONCLUSION: Post-mRNA vaccination myocarditis is seen predominantly in young males within a few days after their second dose of vaccination. The pathophysiology of myocarditis is not well known. The prognosis is good as all the reported patients recovered. The presence of late gadolinium enhancement on cardiac MRI indicated myocardial necrosis/fibrosis and further studies are needed to establish the long-term prognosis of the condition.

8.
AIDS ; 35(11): 1785-1793, 2021 09 01.
Article in English | MEDLINE | ID: mdl-34033588

ABSTRACT

OBJECTIVE: Peripheral neuropathies (PNPs) in HIV-infected patients are highly debilitating because of neuropathic pain and physical disabilities. We defined prevalence and associated predictive variables for PNP subtypes in a cohort of persons living with HIV. DESIGN: Adult persons living with HIV in clinical care were recruited to a longitudinal study examining neurological complications. METHODS: Each patient was assessed for symptoms and signs of PNP with demographic, laboratory, and clinical variables. Univariate, multiple logistic regression and machine learning analyses were performed by comparing patients with and without PNP. RESULTS: Three patient groups were identified: PNP (n = 111) that included HIV-associated distal sensory polyneuropathy (n = 90) or mononeuropathy (n = 21), and non-neuropathy (n = 408). Univariate analyses showed multiple variables differed significantly between the non-neuropathy and PNP groups including age, estimated HIV type 1 (HIV-1) duration, education, employment, neuropathic pain, peak viral load, polypharmacy, diabetes, cardiovascular disorders, AIDS, and prior neurotoxic nucleoside antiretroviral drug exposure. Classification algorithms distinguished those with PNP, all with area under the receiver operating characteristic curve values of more than 0.80. Random forest models showed greater accuracy and area under the receiver operating characteristic curve values compared with the multiple logistic regression analysis. Relative importance plots showed that the foremost predictive variables of PNP were HIV-1 duration, peak plasma viral load, age, and low CD4+ T-cell levels. CONCLUSION: PNP in HIV-1 infection remains common affecting 21.4% of patients in care. Machine-learning models uncovered variables related to PNP that were undetected by conventional analyses, emphasizing the importance of statistical algorithmic approaches to understanding complex neurological syndromes.


Subject(s)
HIV Infections , Peripheral Nervous System Diseases , HIV Infections/complications , HIV Infections/drug therapy , Humans , Longitudinal Studies , Machine Learning , Peripheral Nervous System Diseases/epidemiology , Viral Load
9.
J Neurovirol ; 26(5): 743-753, 2020 10.
Article in English | MEDLINE | ID: mdl-32720232

ABSTRACT

Despite the availability of modern antiretroviral therapy (ART), neurocognitive impairment persists among some persons with HIV (PWH). We investigated the role of exposure to four major classes of ARTs in neurocognitive impairment in PWH. A single-site cohort of 343 PWH was recruited. Lifetime ART medication history was obtained from medical health records. We evaluated the role of ART exposure as a predictor of neurocognitive impairment using univariate analyses and machine learning, while accounting for potential effects of demographic, clinical, and comorbidity-related risk factors. Out of a total of 26 tested variables, two random forest analyses identified the most important characteristics of a neurocognitively impaired group (N = 59): Compared with a neurocognitively high-performing group (N = 132; F1-score = 0.79), we uncovered 13 important risk factors; compared with an intermediate-performing group (N = 152; F1-score = 0.75), 16 risk factors emerged. Longer lifetime ART exposure, especially to integrase inhibitors, was one of the most important predictors of neurocognitive impairment in both analyses (rank 2 of 13 and rank 4 of 16, respectively), superseding effects of age (rank 11/13, rank 15/16) and HIV duration (rank 13/13, rank 16/16). Concerning specific integrase inhibitors, the impaired group had significantly longer dolutegravir exposure (p = 0.011) compared with the high-performing group (p = 0.012; trend compared with the intermediate group p = 0.063). A longer duration to integrase inhibitor intake was negatively related to cognition in this cohort. Our findings suggest that possible cognitive complications of long-term exposure to integrase inhibitors, in particular dolutegravir, should be closely monitored in PWH.


Subject(s)
Anti-HIV Agents/toxicity , Central Nervous System/drug effects , Cognitive Dysfunction/chemically induced , HIV Infections/drug therapy , HIV Protease Inhibitors/toxicity , Heterocyclic Compounds, 3-Ring/toxicity , Oxazines/toxicity , Piperazines/toxicity , Pyridones/toxicity , Reverse Transcriptase Inhibitors/toxicity , Adult , Antiretroviral Therapy, Highly Active/methods , Central Nervous System/pathology , Central Nervous System/virology , Cognitive Dysfunction/pathology , Cognitive Dysfunction/prevention & control , Cognitive Dysfunction/virology , Cohort Studies , Depression/physiopathology , Female , HIV Infections/pathology , HIV Infections/virology , Humans , Machine Learning , Male , Mental Disorders/physiopathology , Middle Aged , Neuropsychological Tests , Risk Factors , Suicidal Ideation
10.
J Anim Sci ; 98(5)2020 May 01.
Article in English | MEDLINE | ID: mdl-32219327

ABSTRACT

Rendered products from the meat industry can provide economical quality sources of proteins to the animal and feed industry. Similar to lipids, rendered proteins are susceptible to oxidation, yet the stability of these proteins is unclear. In addition, interest in understanding how oxidative stress can impact efficiency in production animals is increasing. Recent studies show that consumption of oxidized lipids can lead to a change in the oxidative status of the animal as well as decreases in production efficiency. To date, little is known about how consumption of oxidized proteins impacts oxidative status and growth performance. The objectives of this study were to determine if feeding diets high in oxidized protein to growing pigs would: 1) impact growth performance and 2) induce oxidative stress. Thirty pigs (42 d old; initial body weight [BW] 12.49 ± 1.45 kg) were randomly assigned to one of three dietary treatments with increasing levels of oxidized protein. Spray-dried bovine plasma was used as the protein source and was either unheated upon arrival, heated at 45 °C for 4 d, or heated at 100 °C for 3 d. Diets were fed for 19 d and growth performance was measured. Blood plasma (days 0 and 18), jejunum, colon, and liver tissues (day 19) were collected to analyze for markers of oxidative stress (e.g., protein oxidation, lipid oxidation, DNA damage, and glutathione peroxidase activity). Average daily gain (ADG;P < 0.01) and average daily feed intake (ADFI;P < 0.01) had a positive linear relationship to increased protein oxidation, but there was no effect on gain to feed ratio. Furthermore, protein (P = 0.03) and fat (P < 0.01) digestibility were reduced with increased protein oxidation in the diet. Crypt depth showed a positive linear relationship with dietary protein oxidation levels (P = 0.02). A trend was observed in liver samples where pigs fed the plasma heated to 45 °C had increased lipid oxidation compared with pigs fed the plasma either unheated or heated to 100 °C (P = 0.09). DNA damage in the jejunum tended to have a linear relationship with the dietary protein oxidation level (P = 0.07). Even though results suggest dietary oxidized protein did not induce oxidative stress during short-term feeding, differences in performance, gut morphology, and digestibility are likely a result of reduced protein availability.


Subject(s)
Dietary Proteins/analysis , Oxidative Stress/drug effects , Swine/physiology , Animal Feed/analysis , Animals , Cattle , Diet/veterinary , Digestion , Female , Gastrointestinal Tract/physiology , Hot Temperature , Lipid Metabolism , Liver/physiology , Oxidation-Reduction , Random Allocation , Swine/growth & development
12.
Epilepsy Behav ; 94: 301-306, 2019 05.
Article in English | MEDLINE | ID: mdl-30975571

ABSTRACT

Depression and worse quality of life (QOL) are significantly associated with epilepsy. However, limited descriptive data on depression and quality of life among African Americans with epilepsy are available. This study sought to describe the prevalence of depression among African Americans with epilepsy participating in self-management studies and to examine the relationship between depression and QOL. Using data from the Managing Epilepsy Well (MEW) research network, a subgroup of African Americans with epilepsy were selected for the analytic sample. Descriptive statistics indicated the prevalence of depression (Patient Health Questionnaire-9 [PHQ-9]) and reports of epilepsy-specific QOL (Quality of Life in Epilepsy-10 [QOLIE-10]) in the sample. Multiple linear regression examined the relationship between depression and QOL while controlling for sociodemographic characteristics and seizure frequency. The prevalence of depression (PHQ-9 ≥; 10) was 47.7%. Quality of life was the only variable significantly associated with depressive symptoms in multivariable analyses, suggesting that depressive symptoms have a stronger relationship with QOL than seizure frequency. With the high levels of depression and the significant relationship with QOL, regular screening of depression is needed among African Americans with epilepsy. Self-management programs that improve mood may also play an important role in improving the lives of African Americans with epilepsy.


Subject(s)
Black or African American/ethnology , Databases, Factual , Depression/ethnology , Depressive Disorder/ethnology , Epilepsy/ethnology , Quality of Life , Adult , Comorbidity , Female , Humans , Male , Middle Aged , Self-Management
13.
Nutr Clin Pract ; 33(4): 454-466, 2018 Aug.
Article in English | MEDLINE | ID: mdl-29926935

ABSTRACT

Short bowel syndrome (SBS) occurs in patients who have had extensive resection. The primary physiologic consequence is malabsorption, resulting in fluid and electrolyte abnormalities and malnutrition. Nutrient digestion, absorption, and assimilation may also be diminished by disturbances in the production of bile acids and digestive enzymes. Small bowel dilation, dysmotility, loss of ileocecal valve, and anatomical changes combined with acid suppression and antimotility drugs increase the risk of small intestinal bacterial overgrowth, further contributing to malabsorption. Metabolic changes that occur in SBS due to loss of colonic regulation of gastric and small bowel function can also lead to depletion of calcium, magnesium, and vitamin D, resulting in demineralization of bone and the eventual development of bone disease. Persistent inflammation, steroid use, parenteral nutrition, chronic metabolic acidosis, and renal insufficiency may exacerbate the problem and contribute to the development of osteoporosis. Multiple factors increase the risk of nephrolithiasis in SBS. In the setting of fat malabsorption, increased free fatty acids are available to bind to calcium, resulting in an increased concentration of unbound oxalate, which is readily absorbed across the colonic mucosa where it travels to the kidney. In addition, there is an increase in colonic permeability to oxalate stemming from the effects of unabsorbed bile salts. The risk of nephrolithiasis is compounded by volume depletion, metabolic acidosis, and hypomagnesemia, resulting in a decrease in renal perfusion, urine output, pH, and citrate excretion. This review examines the causes and treatments of small intestinal bacterial overgrowth, bone demineralization, and nephrolithiasis in SBS.


Subject(s)
Bacteria/growth & development , Bone and Bones/metabolism , Calcium/metabolism , Intestine, Small , Kidney Calculi/etiology , Short Bowel Syndrome/complications , Bone Density , Colon/metabolism , Humans , Intestinal Mucosa/metabolism , Intestinal Mucosa/microbiology , Intestine, Small/metabolism , Intestine, Small/microbiology , Kidney/metabolism , Kidney/pathology , Kidney Calculi/metabolism , Osteoporosis/etiology , Oxalates/metabolism
14.
Infect Drug Resist ; 11: 417-425, 2018.
Article in English | MEDLINE | ID: mdl-29588605

ABSTRACT

BACKGROUND: The prescription of topical antibiotics for the prevention of infections in uncomplicated wounds is common. However, the efficacy is not well reported. Therefore, the objective of the study was to conduct a systematic review and meta-analysis of the available evidence on prevention of uncomplicated wound infections by prophylactic topical antibiotics. MATERIALS AND METHODS: The search included Pubmed, Google Scholar, SCOPUS, Embase, Cochrane, ClinicalTrials.gov, International Clinical Trials Registry Platform, National Technical Information Service, and the National Guidelines Clearinghouse. RESULTS: We identified eight randomized controlled trials and four quasi-randomized trials that met the criteria for the systematic review. Of these trials, 11 studies were pooled for meta-analysis to compare the effects of topical antibiotics versus placebo and 4 studies were pooled for comparison of effects of topical antibiotics versus topical antiseptics on uncomplicated wounds. Fewer wound infections occurred in the topical antibiotic arms compared to placebo (pooled risk ratio: 0.57 [95% CI: 0.37 to 0.86]; p=0.01 and pooled risk difference: -3.1% [95% CI: -5.8% to -0.34%]; p=0.03). Compared to antiseptics, topical antibiotics demonstrated statistically significant relative risk reduction (pooled risk ratio: 0.56 [95% CI: 0.23 to 0.91]; p=0.02), while there was no significant absolute risk reduction (pooled risk difference: -3.7% [95% CI: -7.9% to +0.6%]; p=0.09). CONCLUSION: Topical antibiotics are effective in reducing wound infections after surgical procedures, but the absolute benefit is small. Given the global emergence of antimicrobial resistance, judicious use of antibiotics is encouraged and use of antiseptics should be considered as a reasonable alternative to topical antibiotics.

15.
Med Ref Serv Q ; 36(4): 334-347, 2017.
Article in English | MEDLINE | ID: mdl-29043943

ABSTRACT

In 2013, the librarians at a small academic health sciences library reevaluated their mission, vision, and strategic plan to expand their roles. The school was transitioning to a new pedagogical culture and a new building designed to emphasize interprofessional education and active learning methodologies. Subsequent efforts to implement the new strategic plan resulted in the librarians joining curriculum committees and other institutional initiatives, such as an Active Learning Task Force, and participating in faculty development workshops. This participation has increased visibility and led to new roles and opportunities for librarians.


Subject(s)
Academic Medical Centers/organization & administration , Librarians , Libraries, Medical/organization & administration , Professional Role , Humans , Problem-Based Learning , United States
16.
Mol Hum Reprod ; 22(12): 842-851, 2016 12.
Article in English | MEDLINE | ID: mdl-27698028

ABSTRACT

STUDY QUESTION: Can host fertility be rescued by grafting of a fragment of a healthy ovary soon after chemotherapy? SUMMARY ANSWER: We found that grafting a green fluorescent protein (GFP)-positive fragment from a healthy isogenic ovary to the left ovary of a chemo-treated host rescued function and fertility of the grafted host ovary, and resulted in the production of host-derived offspring as late as the sixth litter after chemotherapy (CTx) treatment, whereas none of the ungrafted controls produced a second litter. WHAT IS KNOWN ALREADY: In women and girls undergoing chemotherapy, infertility and premature ovarian failure are frequent outcomes. There are accumulating reports of improved endocrine function after autotransplantation of an ovarian fragment, raising the possibility that the transplant is beneficial to the endogenous ovary. STUDY DESIGN, SIZE, DURATION: We first established a CTx treatment regimen that resulted in the permanent loss of fertility in 100% of female mice of the FVB inbred strain. We grafted an isogenic ovary fragment from a healthy female homozygous for a GFP transgene to the left ovary of 100 CTx-treated hosts, and compared fertility to 39 ungrafted controls in 6 months of continuous matings, using GFP to distinguish offspring derived from the graft, and those derived from the host. PARTICIPANTS/MATERIALS, SETTING, METHODS: Immunofluoresece and western blot analysis of 39 treated ovaries during and 15 days after CTx treatment revealed elevated apoptosis, rapid loss of granulosa cells and an increased recruitment of growing follicles. Using immunofluorescence and confocal imaging, we tracked the outcome of the grafted tissue over 4 months and its effect on the adjacent and contralateral ovary of the host. MAIN RESULTS AND THE ROLE OF CHANCE: Fifty-three percent of grafted females produced a second litter whereas none of the ungrafted females produced a second litter. The likelihood that this could occur by chance is very low (P < 0.0001). LIMITATIONS, REASONS FOR CAUTION: These results are shown only in mice, and whether or how they might apply to chemotherapy patients subjected to different CTx regimens is not yet clear. WIDER IMPLICATIONS OF THE FINDINGS: Our experiments prove that rescue of a chemo-treated ovary is possible, and establish a system to investigate the mechanism of rescue and to identify the factors responsible with the long-term goal of developing therapies for preservation of ovarian endocrine function and fertility in women undergoing chemotherapy. LARGE SCALE DATA: No large datasets were produced. STUDY FUNDING/COMPETING INTERESTS: Duke University Medical Center Chancellor's Discovery Grant to BC; ESJ was supported by an NRSA 5F31CA165545; SK was supported by NIH RO1 GM08033; RWT was supported by the Duke University School of Medicine Ovarian Cancer Research Fellowship; XBM was supported by CONICYT. The authors have no conflicts of interest to declare.


Subject(s)
Ovary/transplantation , Animals , Apoptosis/drug effects , Blotting, Western , Busulfan/adverse effects , Cyclophosphamide/adverse effects , Female , Fertility Preservation/methods , Granulosa Cells/drug effects , Green Fluorescent Proteins , Humans , Immunohistochemistry , Male , Mice , Oocytes/drug effects , Ovary/drug effects , Ovary/physiology , Ovary/surgery , Primary Ovarian Insufficiency/surgery
17.
ISRN Obes ; 2014: 638936, 2014.
Article in English | MEDLINE | ID: mdl-24701367

ABSTRACT

Objective. The correlation between obesity and deficient wound healing has long been established. This review examines the current literature on the mechanisms involved in obesity-related perioperative morbidity. Methods. A literature search was performed using Medline, PubMed, Cochrane Library, and Internet searches. Keywords used include obesity, wound healing, adipose healing, and bariatric and surgical complications. Results. Substantial evidence exists demonstrating that obesity is associated with a number of postoperative complications. Specifically in relation to wound healing, explanations include inherent anatomic features of adipose tissue, vascular insufficiencies, cellular and composition modifications, oxidative stress, alterations in immune mediators, and nutritional deficiencies. Most recently, advances made in the field of gene array have allowed researchers to determine a few plausible alterations and deficiencies in obese individuals that contribute to their increased risk of morbidity and mortality, especially wound complications. Conclusion. While the literature discusses how obesity may negatively affect health on various of medical fronts, there is yet to be a comprehensive study detailing all the mechanisms involved in obesity-related morbidities in their entirety. Improved knowledge and understanding of obesity-induced physiological, cellular, molecular, and chemical changes will facilitate better assessments of surgical risks and outcomes and create efficient treatment protocols for improved patient care of the obese patient population.

18.
MLO Med Lab Obs ; 45(1): 7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-24133870
19.
J Biol Chem ; 288(20): 14463-14475, 2013 May 17.
Article in English | MEDLINE | ID: mdl-23553630

ABSTRACT

The accumulation of long-chain fatty acids (LCFAs) in non-adipose tissues results in lipid-induced cytotoxicity (or lipoapoptosis). Lipoapoptosis has been proposed to play an important role in the pathogenesis of several metabolic diseases, including non-alcoholic fatty liver disease, diabetes mellitus, and cardiovascular disease. In this report, we demonstrate a novel role for caspase-2 as an initiator of lipoapoptosis. Using a metabolomics approach, we discovered that the activation of caspase-2, the initiator of apoptosis in Xenopus egg extracts, is associated with an accumulation of LCFA metabolites. Metabolic treatments that blocked the buildup of LCFAs potently inhibited caspase-2 activation, whereas adding back an LCFA in this scenario restored caspase activation. Extending these findings to mammalian cells, we show that caspase-2 was engaged and activated in response to treatment with the saturated LCFA palmitate. Down-regulation of caspase-2 significantly impaired cell death induced by saturated LCFAs, suggesting that caspase-2 plays a pivotal role in lipid-induced cytotoxicity. Together, these findings reveal a previously unknown role for caspase-2 as an initiator caspase in lipoapoptosis and suggest that caspase-2 may be an attractive therapeutic target for inhibiting pathological lipid-induced apoptosis.


Subject(s)
Apoptosis , Caspase 2/metabolism , Fatty Acids/metabolism , Gene Expression Regulation, Enzymologic , Metabolomics/methods , Aminooxyacetic Acid/metabolism , Animals , Carnitine/analogs & derivatives , Carnitine/metabolism , Cell Death , Chromatography, Gel , Enzyme Activation , HEK293 Cells , Hepatocytes/cytology , Humans , Palmitates/metabolism , RNA, Small Interfering/metabolism , Xenopus laevis/metabolism
20.
Curr Opin Cell Biol ; 24(6): 876-80, 2012 Dec.
Article in English | MEDLINE | ID: mdl-23103123

ABSTRACT

The complex signaling pathways that control cellular fate can be intimately influenced by metabolic status. Although the ability of nutrients to influence intracellular decisions has been appreciated for some time, the complex signaling mechanisms linking metabolic inputs to cell proliferation and death are not fully understood. An emerging theme in the literature is that intracellular metabolite levels can directly influence cell fate decisions through modulation of nutrient-derived protein modifications. It appears that varying the level of intracellular metabolites can alter the abundance of post-translational modifications, both by altering the availability of donor substrates and changing the activity of the nutrient-sensitive enzymes regulating these reactions. We focus here on protein acetylation, a modification that can modulate both cell proliferation and cell death in response to changes in extracellular nutrient supply.


Subject(s)
Acetylation , Cells/cytology , Cells/metabolism , Protein Processing, Post-Translational , Acetyltransferases/metabolism , Animals , Cell Death , Cell Proliferation , Cell Survival , Humans , Signal Transduction
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