Conectar
by Longgang Zhao, Yuan Wang, Eric Mishio Bawa, Zichun Meng, Jingkai Wei, Sarah Newman-Norlund, Tushar Trivedi, Hatice Hasturk, Roger D. Newman-Norlund, Julius Fridriksson, Anwar T. Merchant
BackgroundCognitive impairment has multiple risk factors spanning several domains, but few studies have evaluated risk factor clusters. We aimed to identify naturally occurring clusters of risk factors of poor cognition among middle-aged and older adults and evaluate associations between measures of cognition and these risk factor clusters.
MethodsWe used data from the National Health and Nutrition Examination Survey (NHANES) III (training dataset, n = 4074) and the NHANES 2011–2014 (validation dataset, n = 2510). Risk factors were selected based on the literature. We used both traditional logistic models and support vector machine methods to construct a composite score of risk factor clusters. We evaluated associations between the risk score and cognitive performance using the logistic model by estimating odds ratios (OR) and 95% confidence intervals (CI).
ResultsUsing the training dataset, we developed a composite risk score that predicted undiagnosed cognitive decline based on ten selected predictive risk factors including age, waist circumference, healthy eating index, race, education, income, physical activity, diabetes, hypercholesterolemia, and annual visit to dentist. The risk score was significantly associated with poor cognitive performance both in the training dataset (OR Tertile 3 verse tertile 1 = 8.15, 95% CI: 5.36–12.4) and validation dataset (OR Tertile 3 verse tertile 1 = 4.31, 95% CI: 2.62–7.08). The area under the receiver operating characteristics curve for the predictive model was 0.74 and 0.77 for crude model and model adjusted for age, sex, and race.
ConclusionThe model based on selected risk factors may be used to identify high risk individuals with cognitive impairment.
by Levi Matthies, Hendrik Amir-Kabirian, Medhanie T. Gebrekidan, Andreas S. Braeuer, Ulrike S. Speth, Ralf Smeets, Christian Hagel, Martin Gosau, Christian Knipfer, Reinhard E. Friedrich
In Neurofibromatosis type 1 (NF1), peripheral nerve sheaths tumors are common, with cutaneous neurofibromas resulting in significant aesthetic, painful and functional problems requiring surgical removal. To date, determination of adequate surgical resection margins–complete tumor removal while attempting to preserve viable tissue–remains largely subjective. Thus, residual tumor extension beyond surgical margins or recurrence of the disease may frequently be observed. Here, we introduce Shifted-Excitation Raman Spectroscopy in combination with deep neural networks for the future perspective of objective, real-time diagnosis, and guided surgical ablation. The obtained results are validated through established histological methods. In this study, we evaluated the discrimination between cutaneous neurofibroma (n = 9) and adjacent physiological tissues (n = 25) in 34 surgical pathological specimens ex vivo at a total of 82 distinct measurement loci. Based on a convolutional neural network (U-Net), the mean raw Raman spectra (n = 8,200) were processed and refined, and afterwards the spectral peaks were assigned to their respective molecular origin. Principal component and linear discriminant analysis was used to discriminate cutaneous neurofibromas from physiological tissues with a sensitivity of 100%, specificity of 97.3%, and overall classification accuracy of 97.6%. The results enable the presented optical, non-invasive technique in combination with artificial intelligence as a promising candidate to ameliorate both, diagnosis and treatment of patients affected by cutaneous neurofibroma and NF1.by Sonal Singh, Noelle M. Cocoros, Xiaojuan Li, Kathleen M. Mazor, Mary T. Antonelli, Lauren Parlett, Mark Paullin, Thomas P. Harkins, Yunping Zhou, Paula A. Rochon, Richard Platt, Inna Dashevsky, Carly Massino, Cassandra Saphirak, Sybil L. Crawford, Jerry H. Gurwitz
ContextPotentially inappropriate prescribing of medications in older adults, particular those with dementia, can lead to adverse drug events including falls and fractures, worsening cognitive impairment, emergency department visits, and hospitalizations. Educational mailings from health plans to patients and their providers to encourage deprescribing conversations may represent an effective, low-cost, “light touch”, approach to reducing the burden of potentially inappropriate prescription use in older adults with dementia.
ObjectivesThe objective of the Developing a PRogram to Educate and Sensitize Caregivers to Reduce the Inappropriate Prescription Burden in Elderly with Alzheimer’s Disease (D-PRESCRIBE-AD) trial is to evaluate the effect of a health plan based multi-faceted educational outreach intervention to community dwelling patients with dementia who are currently prescribed sedative/hypnotics, antipsychotics, or strong anticholinergics.
MethodsThe D-PRESCRIBE-AD is an open-label pragmatic, prospective randomized controlled trial (RCT) comparing three arms: 1) educational mailing to both the health plan patient and their prescribing physician (patient plus physician arm, n = 4814); 2) educational mailing to prescribing physician only (physician only arm, n = 4814); and 3) usual care (n = 4814) among patients with dementia enrolled in two large United States based health plans. The primary outcome is the absence of any dispensing of the targeted potentially inappropriate prescription during the 6-month study observation period after a 3-month black out period following the mailing. Secondary outcomes include dose-reduction, polypharmacy, healthcare utilization, mortality and therapeutic switching within targeted drug classes.
ConclusionThis large pragmatic RCT will contribute to the evidence base on promoting deprescribing of potentially inappropriate medications among older adults with dementia. If successful, such light touch, inexpensive and highly scalable interventions have the potential to reduce the burden of potentially inappropriate prescribing for patients with dementia.ClinicalTrials.gov Identifier: NCT05147428.
by Emelda E. Chukwu, Dennis Abuh, Ifeoma E. Idigbe, Kazeem A. Osuolale, Vivian Chuka-Ebene, Oluwatoyin Awoderu, Rosemary A. Audu, Folasade T. Ogunsola
BackgroundDespite promising signs of the benefits associated with Antimicrobial Stewardship Programs (ASPs), there remains limited knowledge on how to implement ASPs in peculiar settings for a more elaborate impact. This study explored prescriber experiences and perceptions of the usefulness, and feasibility of strategies employed for the implementation of antimicrobial stewardship (AMS) interventions as well as challenges encountered.
MethodsThis is a cross-sectional mixed-method survey of prescribers’ perspective of the facilitators and barriers of implementing ASP. The quantitative approach comprised of a semi-structured questionnaire and data collected were analyzed using SPSS version 26 while the qualitative approach used focus group discussions followed by content analysis.
ResultsOut of the thirty people that participated in the workshop, twenty-five completed the questionnaires which were analyzed. The respondents included 15 (60.0%) medical doctors and 10 (40.0%) pharmacists. The mean age of the respondents was 36.39±7.23 years with mean year of practice of 9.48±6.01 years. Majority of them (84.0%) were in a position to provide input on the implementation of AMS in their facilities, although their managements had the final decision. The pharmacists (100%) were more likely to agree that antibiotic resistance was a problem for their practice than the medical doctors (78.6%) while equal number (80.0%) of respondents (pharmacists and medical doctors) believed that inappropriate prescribing was a problem. Having a specialized and dedicated team with effective monitoring was recognized as crucial for effective ASP while inadequate personnel was identified as a major barrier. We identified stakeholder’s engagement, policies and regulation, as well as education as themes for improving AMS in the country.
ConclusionThe results gave insight into the prescribers’ perspective on the facilitators and barriers to antimicrobial stewardship; challenges and possible solutions to implementing ASPs in health facilities in Lagos State. We further identified pertinent contextual factors that need to be addressed when developing ASPs in healthcare facilities in a resource-poor setting.
by Daniel W. Flowers, Brian T. Swanson, Stephen M. Shaffer, Derek J. Clewley, Sean P. Riley
The primary objective of this review was to create a ‘trustworthy,’ living systematic review and meta-analysis for the application of manual therapy interventions in treating patients with shoulder dysfunction. Included studies were English-language randomized controlled trials published between 1/1/2010 and 8/3/2023, with searches performed in: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), CINHAL, ProQuest Nursing & Allied Health, EBSCO Medline, and PEDro. The population of focus included adults 18 years and older with musculoskeletal impairments related to shoulder dysfunction. Our primary outcomes included pain and region-specific outcome measures. We excluded trials, including participants having shoulder dysfunction resulting from surgery, radicular pain, instability/dislocation, fracture, lymphedema, and radiation. Our screening methodology was based upon a previously published ‘trustworthy’ systematic review protocol. This included the application of our PICOTS criteria in addition to screening for prospective clinical trial registration and following of prospective intent, as well as assessment of PEDro scores, risk-of-bias ratings, GRADE scoring, and examination of confidence in estimated effects. Twenty-six randomized controlled trials met our PICOTS criteria; however, only 15 of these were registered. Only three were registered prospectively. Two of these did not have discussions and conclusions that aligned with their primary outcome. The remaining single study was found to have a high risk-of-bias, meaning the remainder of the protocol could not be employed and that no randomized controlled trials could undergo further assessment or meta-analysis. The results of this systematic review indicate there are no ‘trustworthy’ randomized controlled trials examining the effectiveness of manual therapy interventions for the treatment of patients with shoulder dysfunction, as defined by the prospectively established methodology. Therefore, these findings signal that creating a ‘trustworthy,’ living systematic review on this clinically relevant topic is not yet possible due to a lack of ‘trustworthy’ randomized controlled trials.by Ashley M. Brooks, Andrea Vornoli, Ramesh C. Kovi, Thai Vu T. Ton, Miaofei Xu, Ahmed Mashal, Eva Tibaldi, Federica Gnudi, Jian-Liang Li, Robert C. Sills, John R. Bucher, Daniele Mandrioli, Fiorella Belpoggi, Arun R. Pandiri
The cancer hazard associated with lifetime exposure to radiofrequency radiation (RFR) was examined in Sprague Dawley (SD) rats at the Ramazzini Institute (RI), Italy. There were increased incidences of gliomas and cardiac schwannomas. The translational relevance of these rare rat tumors for human disease is poorly understood. We examined the genetic alterations in RFR-derived rat tumors through molecular characterization of important cancer genes relevant for human gliomagenesis. A targeted next-generation sequencing (NGS) panel was designed for rats based on the top 23 orthologous human glioma-related genes. Single-nucleotide variants (SNVs) and small insertion and deletions (indels) were characterized in the rat gliomas and cardiac schwannomas. Translational relevance of these genetic alterations in rat tumors to human disease was determined through comparison with the Catalogue of Somatic Mutations in Cancer (COSMIC) database. These data suggest that rat gliomas resulting from life-time exposure to RFR histologically resemble low grade human gliomas but surprisingly no mutations were detected in rat gliomas that had homology to the human IDH1 p.R132 or IDH2 p.R172 suggesting that rat gliomas are primarily wild-type for IDH hotspot mutations implicated in human gliomas. The rat gliomas appear to share some genetic alterations with IDH1 wildtype human gliomas and rat cardiac schwannomas also harbor mutations in some of the queried cancer genes. These data demonstrate that targeted NGS panels based on tumor specific orthologous human cancer driver genes are an important tool to examine the translational relevance of rodent tumors resulting from chronic/life-time rodent bioassays.by Laith A. I. K. Al-Kaif, Hussain Al-Ameri, Wael Rasheed Obaead Alfatlawi, Ammar Eesa Mahdi, Younis A. K. Al-Khafaji, Mohammad Abd-Kadhum Al-Saadi, Alaa H. Al-Charrakh, Raheem T. Al-Mammori, Mohammed Ahmed Akkaif
BackgroundEvaluating immune responses following COVID-19 vaccination is paramount to understanding vaccine effectiveness and optimizing public health interventions. This study seeks to elucidate individuals’ immune status after administering a second dose of diverse COVID-19 vaccines. By analyzing immune responses through serological markers, we aim to contribute valuable insights into the uniformity of vaccine performance.
MethodsA total of 80 participants were enrolled in this study, with demographic and COVID-19 infection-related data collected for categorization. Serum samples were acquired within a specified timeframe, and SARS-CoV-2 IgM/IgG rapid tests were conducted. Moreover, CTLA-4 levels were measured through ELISA assays, allowing us to assess the immune responses comprehensively. The participants were divided into eight groups based on various factors, facilitating a multifaceted analysis.
ResultsThe outcomes of our investigation demonstrated consistent immune responses across the diverse types of COVID-19 vaccines administered in Iraq. Statistical analysis revealed no significant distinctions among the vaccine categories. In contrast, significant differences were observed in CTLA-4 among the control group (non-infected/non-vaccinated, infected/non-vaccinated) and infected/Pfizer, non-infected/Pfizer, and infected/Sinopharm, non-infected/sinopharm (P = 0.001, Conclusions
In conclusion, our study’s results underscore the lack of discriminatory variations between different COVID-19 vaccine types utilized in Iraq. The uniform immune responses observed signify the equitable efficacy and performance of these vaccines. Despite minor quantitative discrepancies, these variations do not hold statistical significance, reaffirming the notion that the various vaccines serve a similar purpose in conferring protection against COVID-19.
by Alex Buga, David G. Harper, Teryn N. Sapper, Parker N. Hyde, Brandon Fell, Ryan Dickerson, Justen T. Stoner, Madison L. Kackley, Christopher D. Crabtree, Drew D. Decker, Bradley T. Robinson, Gerald Krystal, Katherine Binzel, Maryam B. Lustberg, Jeff S. Volek
PurposeKetogenic diets may positively influence cancer through pleiotropic mechanisms, but only a few small and short-term studies have addressed feasibility and efficacy in cancer patients. The primary goals of this study were to evaluate the feasibility and the sustained metabolic effects of a personalized well-formulated ketogenic diet (WFKD) designed to achieve consistent blood beta-hydroxybutyrate (βHB) >0.5 mM in women diagnosed with stage IV metastatic breast cancer (MBC) undergoing chemotherapy.
MethodsWomen (n = 20) were enrolled in a six month, two-phase, single-arm WFKD intervention (NCT03535701). Phase I was a highly-supervised, ad libitum, personalized WFKD, where women were provided with ketogenic-appropriate food daily for three months. Phase II transitioned women to a self-administered WFKD with ongoing coaching for an additional three months. Fasting capillary βHB and glucose were collected daily; weight, body composition, plasma insulin, and insulin resistance were collected at baseline, three and six months.
ResultsCapillary βHB indicated women achieved nutritional ketosis (Phase I mean: 0.8 mM (n = 15); Phase II mean: 0.7 mM (n = 9)). Body weight decreased 10% after three months, primarily from body fat. Fasting plasma glucose, plasma insulin, and insulin resistance also decreased significantly after three months (p Conclusions
Women diagnosed with MBC undergoing chemotherapy can safely achieve and maintain nutritional ketosis, while improving body composition and insulin resistance, out to six months.
by Jason M. Blaylock, Evan C. Ewers, Elizabeth J. Bianchi, David B. King, Rosemary O. Casimier, Hector Erazo, Stephen Grieco, Jenny Lay, Sheila A. Peel, Kayvon Modjarrad, Charmagne G. Beckett, Jason F. Okulicz, Paul T. Scott, Shilpa Hakre
BackgroundThe evidence for an increased incidence of sexually transmitted infections (STIs) among patients utilizing HIV pre-exposure prophylaxis (PrEP) has been inconsistent. We assessed the risk of incident STI while on PrEP compared to periods off PrEP among military service members starting PrEP.
MethodsIncidence rates of chlamydia, gonorrhea, syphilis, hepatitis C virus, and HIV were determined among military service members without HIV prescribed daily oral tenofovir disoproxil fumarate and emtricitabine for HIV PrEP from February 1, 2014 through June 10, 2016. Hazard ratios for incident STIs were calculated using an Anderson-Gill recurrent event proportional hazard regression model.
ResultsAmong 755 male service members, 477 (63%) were diagnosed with incident STIs (overall incidence 21.4 per 100 person-years). Male service members had a significantly lower risk of any STIs (adjusted hazard ratio (aHR) 0.21, 95% CI 0.11–0.40) while using PrEP compared to periods off PrEP after adjustment for socio-demographic characteristics, reasons for initiating PrEP, surveillance period prior to PrEP initiation, and the effect of PrEP on site and type of infection in multivariate analysis. However, when stratifying for anatomical site and type of infection, the risk of extragenital gonorrhea infection (pharyngeal NG: aHR 1.84, 95% CI 0.82–4.13, p = 0.30; rectal NG: aHR 1.23, 95% CI 0.60–2.51, p = 1.00) and extragenital CT infection (pharyngeal CT: aHR 2.30, 95% CI 0.46–11.46, p = 0.81; rectal CT: aHR 1.36, 95% CI 0.81–2.31, p = 0.66) was greater on PrEP compared to off PrEP although these values did not reach statistical significance.
ConclusionsThe data suggest entry into PrEP care reduced the overall risk of STIs following adjustment for anatomical site of STI and treatment. Service members engaged in PrEP services also receive more STI prevention counseling, which might contribute to decreases in STI risk while on PrEP.
by Jane Jere, Allison Ruark, Julie T. Bidwell, Rita M. Butterfield, Torsten B. Neilands, Sheri D. Weiser, Nancy Mulauzi, James Mkandawire, Amy A. Conroy
Cardiometabolic disorders (CMD) such as hypertension and diabetes are increasingly prevalent in sub-Saharan Africa, placing people living with HIV at risk for cardiovascular disease and threatening the success of HIV care. Spouses are often the primary caregivers for people living with CMD, and understanding patients’ and partners’ conceptions of CMD could inform care. We conducted semi-structured interviews with 25 couples having a partner living with HIV and either hypertension or diabetes. Couples were recruited from HIV clinics in Malawi and were interviewed on beliefs around symptoms, causation, prevention, and treatment for CMD. Data were analyzed at the individual and dyadic levels using framework analysis and Kleinman’s theory of explanatory models as a lens. On average, participants were 51 years old and married for 21 years. Approximately 57%, 14%, and 80% had hypertension, diabetes, and HIV. Couples endorsed a combination of biomedical explanatory models (beliefs around physical and mental health) and traditional explanatory models (beliefs around religion and natural remedies), although tended to emphasize the biomedical model. Half of couples believed stress was the main cause of hypertension. For diabetes, diet was believed to be a common cause. In terms of prevention, dietary changes and physical activity were most frequently mentioned. For disease management, medication adherence and diet modifications were emphasized, with some couples also supporting herbal remedies, stress reduction, and faith in God as strategies. Participants were generally more concerned about CMD than HIV due to poor access to CMD medications and beliefs that CMD could lead to sudden death. Within couples, partners often held many of the same beliefs but diverged around which etiological or preventive factors were most important (e.g., stress versus diet) and the best diet for CMD. Health education programs should involve primary partners to build knowledge of CMD and address overlap with HIV, and reinforce accurate information on lifestyle factors for the prevention and treatment of CMD.by Patricia Escobedo, Daniel Garcia, Liam Cascelli, Gabriela Chavira, Gilberto E. Flores, Jodi L. Constantine Brown, David Boyns, Andrew T. Ainsworth
In March 2020, the COVID-19 pandemic forced many in person undergraduate research experiences (UREs) to pivot to remote online training. To investigate how the COVID-19 quarantine disrupted student URE outcomes over time, the current study examines Building Infrastructure Leading to Diversity (BUILD) Promoting Opportunities for Diversity in Education and Research (PODER) URE outcomes across different platforms (in-person, remote, and hybrid models) by comparing student survey data from 2019 to 2021. Participants consisted of three cohorts: 2019 (n = 26 students), 2020 (n = 33), 2021 (n = 34). The BUILD PODER Summer JumpStart program (SJS), which aims to increase diversity in Science, Technology, Engineering, and Mathematics (STEM) by recruiting mostly underrepresented students, was conducted in person in 2019, remotely in 2020 and using a hybrid model in 2021. All students completed an online survey on the first and last day of the four-week SJS program. We used one-way and mixed ANOVA models to analyze Cohort, Time (pre-test vs. post-test scores), and interaction of Cohort and Time for Research Self-Efficacy, Sense of Belonging, Mentor Relationship, Mentee Knowledge, Health, Stress, and Student Program Satisfaction measures. Despite the platform changes, student scores increased significantly over time for all measures. There was a significant main effect of Time for Research Self-Efficacy, Sense of Belonging, Mentor Relationship, Mentee Knowledge, Health Assessment, and Stress Management. Findings indicate that URE programs that are implemented remotely and using a hybrid format can provide students with experiences similar to in-person URE programs. In addition, remote UREs may provide added benefits compared to in-person programs. For instance, remote UREs could engage more historically minoritized students, who may experience barriers to access, such as work/family commitments, financial constraints, and geographic limitations.by Cole Etherington, Amelia Palumbo, Kelly Holloway, Samantha Meyer, Maximillian Labrecque, Kyle Rubini, Risa Shorr, Vivian Welch, Emily Gibson, Terrie Foster, Jennie Haw, Elisabeth Vesnaver, Manavi T. Maharshi, Sheila F. O’Brien, Paul MacPherson, Joyce Dogba, Tony Steed, Mindy Goldman, Justin Presseau
IntroductionThe growing demand for plasma protein products has caused concern in many countries who largely rely on importing plasma products produced from plasma collected in the United States and Europe. Optimizing recruitment and retention of a diversity of plasma donors is therefore important for supporting national donation systems that can reliably meet the most critical needs of health services. This series of three systematic reviews aims to synthesize the known barriers and enablers to source plasma donation from the qualitative and survey-based literature and identify which strategies that have shown to be effective in promoting increased intention to, and actual donation of, source plasma.
Methods and analysisPrimary studies involving source or convalescent plasma donation via plasmapheresis will be included. The search strategy will capture all potentially relevant studies to each of the three reviews, creating a database of plasma donation literature. Study designs will be subsequently identified in the screening process to facilitate analysis according to the unique inclusion criteria of each review (i.e., qualitative, survey, and experimental designs). The search will be conducted in the electronic databases SCOPUS, MEDLINE, EMBASE, PsycINFO, and CINAHL without date or language restrictions. Studies will be screened, and data will be extracted, in duplicate by two independent reviewers with disagreements resolved through consensus. Reviews 1 and 2 will draw on the Theoretical Domains Framework and Intersectionality, while Review 3 will be informed by Behaviour Change Intervention Ontologies. Directed content analysis and framework analysis (Review 1), and descriptive and inferential syntheses (Reviews 2 and 3), will be used, including meta-analyses if appropriate.
DiscussionThis series of related reviews will serve to provide a foundation of what is known from the published literature about barriers and enablers to, and strategies for promoting, plasma donation worldwide.
by M. E. Coleman, T. P. Oscar, T. L. Negley, M. M. Stephenson
Conflicting claims exist regarding pathogen growth in raw milk. A small pilot study was designed to provide definitive data on trends for pathogen growth and decline in raw bovine milk hygienically produced for direct human consumption. An independent laboratory conducted the study, monitoring growth and decline of pathogens inoculated into raw milk. Raw milk samples were inoculated with foodborne pathogens (Campylobacter, E. coli O157:H7, Listeria monocytogenes, or Salmonella) at lower (L. monocytogenes in 8 of 12 replicates (P = 0.001 to P = 0.028). Analysis of variance confirmed significant increases for L. monocytogenes at both initial levels in week 2. No evidence of growth was documented over 14 days for the three pathogens predominantly associated with raw milk outbreaks in the US (Campylobacter, E. coli O157:H7, and Salmonella). Further research is needed to characterize parameters for pathogen growth and decline to support re-assessment of risks that were based on incorrect assumptions about interactions of pathogens with the raw milk microbiota.by Peter T. Tanksley, Matthew W. Logan, J. C. Barnes
History of incarceration is associated with an excess of morbidity and mortality. While the incarceration experience itself comes with substantive health risks (e.g., injury, psychological stress, exposure to infectious disease), most individuals eventually return from prison to the general population where they will be diagnosed with the same age-related conditions that drive mortality in the non-incarcerated population but at exaggerated rates. However, the interplay between history of incarceration as a risk factor and more traditional risk factors for age-related diseases (e.g., genetic risk factors) has not been studied. Here, we focus on cognitive impairment, a hallmark of neurodegenerative conditions like Alzheimer’s disease, as an age-related state that may be uniquely impacted by the confluence of environmental stressors (e.g., incarceration) and genetic risk factors. Using data from the Health and Retirement Study, we found that incarceration and APOE-ε4 genotype (i.e., the chief genetic risk factor for Alzheimer’s disease) both constituted substantive risk factors for cognitive impairment in terms of overall risk and earlier onset. The observed effects were mutually independent, however, suggesting that the risk conveyed by incarceration and APOE-ε4 genotype operate across different risk pathways. Our results have implications for the study of criminal-legal contact as a public health risk factor for age-related, neurodegenerative conditions.by Bennet S. Cho, Scott C. Fligor, Gillian L. Fell, Jordan D. Secor, Savas T. Tsikis, Amy Pan, Lumeng J. Yu, Victoria H. Ko, Duy T. Dao, Lorenzo Anez-Bustillos, Thomas I. Hirsch, Jenny Lund, Arild C. Rustan, David A. Fraser, Kathleen M. Gura, Mark Puder
BackgroundParenteral (intravenous) nutrition is lifesaving for patients with intestinal failure, but long-term use of parenteral nutrition often leads to liver disease. SEFA-6179 is a synthetic medium-chain fatty acid analogue designed to target multiple fatty acid receptors regulating metabolic and inflammatory pathways. We hypothesized that SEFA-6179 would prevent hepatosteatosis and lipotoxicity in a murine model of parenteral nutrition-induced hepatosteatosis.
MethodsTwo in vivo experiments were conducted. In the first experiment, six-week-old male mice were provided an ad lib fat-free high carbohydrate diet (HCD) for 19 days with orogastric gavage of either fish oil, medium-chain triglycerides, or SEFA-6179 at a low (0.3mmol/kg) or high dose (0.6mmol/kg). In the second experiment, six-week-old mice were provided an ad lib fat-free high carbohydrate diet for 19 days with every other day tail vein injection of saline, soybean oil lipid emulsion, or fish oil lipid emulsion. Mice then received every other day orogastric gavage of medium-chain triglyceride vehicle or SEFA-6179 (0.6mmol/kg). Hepatosteatosis was assessed by a blinded pathologist using an established rodent steatosis score. Hepatic lipid metabolites were assessed using ultra-high-performance liquid chromatography-mass spectrometry. Effects of SEFA-6179 on fatty acid oxidation, lipogenesis, and fatty acid uptake in human liver cells were assessed in vitro.
ResultsIn the first experiment, mice receiving the HCD with either saline or medium-chain triglyceride treatment developed macrovesicular steatosis, while mice receiving fish oil or SEFA-6179 retained normal liver histology. In the second experiment, mice receiving a high carbohydrate diet with intravenous saline or soybean oil lipid emulsion, along with medium chain triglyceride vehicle treatment, developed macrovescular steatosis. Treatment with SEFA-6179 prevented steatosis. In each experiment, SEFA-6179 treatment decreased arachidonic acid metabolites as well as key molecules (diacylglycerol, ceramides) involved in lipotoxicity. SEFA-6179 increased both β- and complete fatty oxidation in human liver cells, while having no impact on lipogenesis or fatty acid uptake.
ConclusionsSEFA-6179 treatment prevented hepatosteatosis and decreased toxic lipid metabolites in a murine model of parenteral nutrition-induced hepatosteatosis. An increase in both β- and complete hepatic fatty acid oxidation may underlie the reduction in steatosis.
by Bhagvat J. Maheta, Nainwant K. Singh, Karl A. Lorenz, Sarina Fereydooni, Sydney M. Dy, Hong-nei Wong, Jonathan Bergman, John T. Leppert, Karleen F. Giannitrapani
IntroductionInterdisciplinary teams are often leveraged to improve quality of cancer care in the perioperative period. We aimed to identify the team structures and processes in interdisciplinary interventions that improve perioperative patient-reported outcomes for patients with cancer.
MethodsWe searched PubMed, EMBASE, and CINAHL for randomized control trials published at any time and screened 7,195 articles. To be included in our review, studies needed to report patient-reported outcomes, have interventions that occur in the perioperative period, include surgical cancer treatment, and include at least one non physician intervention clinical team member: advanced practice providers, including nurse practitioners and physician assistants, clinical nurse specialists, and registered nurses. We narratively synthesized intervention components, specifically roles assumed by intervention clinical team members and interdisciplinary team processes, to compare interventions that improved patient-reported outcomes, based on minimal clinically important difference and statistical significance.
ResultsWe included 34 studies with a total of 4,722 participants, of which 31 reported a clinically meaningful improvement in at least one patient-reported outcome. No included studies had an overall high risk of bias. The common clinical team member roles featured patient education regarding diagnosis, treatment, coping, and pain/symptom management as well as postoperative follow up regarding problems after surgery, resource dissemination, and care planning. Other intervention components included six or more months of continuous clinical team member contact with the patient and involvement of the patient’s caregiver.
ConclusionsFuture interventions might prioritize supporting clinical team members roles to include patient education, caregiver engagement, and clinical follow-up.
by Andrew J. Strick, Logan T. Markwell, Hubert Makaruk, Jared M. Porter
Prior research has questioned the appropriateness of internal focus instructions or the juxtaposition to external and control conditions. Moreover, there has been a lack of research conducted to test a variety of internal conditions on motor performance. The purpose of the present study was to address those critiques and add to the attentional focus literature by varying the location of an internal focus while performing a standing long jump. Participants performed a standing long jump during five separate conditions (internal focus: toes, knees, hips, arms; and control). The analysis revealed that all internal focus conditions performed worse than the control condition. Furthermore, the only difference between internal conditions was found between arms and knees, where the knee condition resulted in a significantly shorter jump distance relative to the arms. Regardless of the location specified, all internal focus conditions led to detriments in jump performance when compared to the control condition. These findings add to a large body of work demonstrating the importance of instructional content on motor performance.
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