scholarly journals Laminin-α4 Is Upregulated in Both Human and Murine Models of Obesity

2021 ◽  
Vol 12 ◽  
Author(s):  
Anna Goddi ◽  
Alanis Carmona ◽  
Liesl Schroedl ◽  
Jeremy M. White ◽  
Matthew J. Piron ◽  
...  

Obesity affects nearly one billion globally and can lead to life-threatening sequelae. Consequently, there is an urgent need for novel therapeutics. We have previously shown that laminin, alpha 4 (Lama4) knockout in mice leads to resistance to adipose tissue accumulation; however, the relationship between LAMA4 and obesity in humans has not been established. In this study we measured laminin-α chain and collagen mRNA expression in the subcutaneous white adipose tissue (sWAT) of mice placed on chow (RCD) or 45% high fat diet (HFD) for 8 weeks, and also in HFD mice then placed on a “weight loss” regimen (8 weeks HFD followed by 6 weeks RCD). To assess extracellular matrix (ECM) components in humans with obesity, laminin subunit alpha mRNA and protein expression was measured in sWAT biopsies of female control subjects (BMI<30) or subjects with obesity undergoing bariatric surgery at the University of Chicago Medical Center (BMI>35) both before and three months after surgery. Lama4 was significantly higher in sWAT of HFD compared to RCD mice at both the RNA and protein level (p<0.001, p<0.05 respectively). sWAT from human subjects with obesity also showed significantly higher LAMA4 mRNA (p<0.01) and LAMA4 protein expression (p<0.05) than controls. Interestingly, even though LAMA4 expression was increased in both humans and murine models of obesity, no significant difference in Lama4 or LAMA4 expression was detected following short-term weight loss in either mouse or human samples, respectively. From these results we propose a significant association between obesity and elevated LAMA4 expression in humans, as well as in mouse models of obesity. Further studies should clarify the mechanisms underlying this association to target LAMA4 effectively as a potential therapy for obesity.

Author(s):  
Matthew E Ehrlich ◽  
Heather L Turner ◽  
Lillian J Currie ◽  
Max Wintermark ◽  
Bradford B Worrall ◽  
...  

Objective: To evaluate the safety and utility of CTA acquisition during initial acute stroke evaluation. We hypothesized CTA would not increase risk of renal injury or delay therapy. Design/Methods: We performed a pilot study of CTA acquisition in the acute stroke evaluation at the University of Virginia Medical Center in the first three quarters of 2014. We extracted data from Acute Stroke Team Leader consultations with additional chart review. We collected door-to-CT read times, door-to-needle times, baseline creatinine (Cr) values on presentation, and Cr values 24-48 hours after stroke alert evaluation. Differences in means of these variables were compared between those receiving CTA versus non-contrasted head CT (NCHCT) only. Additionally, we captured CTA results immediately relevant to treatment decisions. Results: Of 289 patients, 157 had CTA completed while 132 had only NCHCT. In the CTA group, 18 patients (11.5%) were treated with IV tissue plasminogen activator (tPA) compared to 11 (8.3%) in the NCHCT group, with no significant difference between groups (p=0.377). There was no difference between mean door-to-CT-read times between the NCHCT (43.07 minutes) and CTA (41.46 minutes) groups (p=0.70). Likewise, there was no significant difference in mean door-to-needle times between the NCHCT (81.36 minutes) and CTA (68.11 minutes) groups (p=0.577). There was a difference between mean Cr values on presentation (1.39mg/dL NCHCT, 1.06mg/dL CTA; p=0.004), but there was no difference between the groups at 24-48 hours (p=0.059) and no difference between the mean change in Cr values (p=0.489). No patients developed a new requirement for hemodialysis. CTA imaging revealed 14 patients with vascular anomalies, and 53 patients with severe stenosis or occlusion of a major cervical or intracranial vessel. One patient in the CTA group and none in the NCHCT group had intravascular intervention. Conclusions: Overall, CTA during acute stroke evaluations were safe and may offer clinical utility, without delaying evaluation or therapy delivery. Additional cost of acute CTA acquisition is negligible given it replaces MRA typically performed later, following admission, as standard vessel imaging. Further prospective study is required.


SciVee ◽  
2012 ◽  
Author(s):  
Lovisa Johansson ◽  
Anders Danielsson ◽  
Hemang Parikh ◽  
Maria Klintenberg ◽  
Fredrik Norström ◽  
...  

2020 ◽  
Vol 12 (01) ◽  
pp. e63-e66
Author(s):  
Brian Michael Shafer ◽  
Thomasine Gorry ◽  
Paul Tapino ◽  
Subha Airan-Javia

Abstract Background Patient handoffs are ubiquitous in hospital settings. Historically, formal handoffs of patient information have been conducted in the inpatient setting mainly by primary teams, as opposed to medical and surgical consultants. Carelign is a software developed by the University of Pennsylvania Health System to function as an interdisciplinary, patient-centered handoff. While mainly utilized by primary teams for work management and transitions, it has been enhanced to include specialty consultant handoff functionality. Objective The aim of this study is to determine whether using Carelign for consultant handoffs improves clinical handoffs in comparison to the prior handoff system (a custom-built handoff report within the electronic health record) used by the Department of Ophthalmology at Penn Presbyterian Medical Center. Methods A 7-item questionnaire assessing the effectiveness, efficiency, accessibility, reliability, communication, and security of the handoff using a 1 to 5 scale was distributed to residents prior to and 6 months subsequent to the implementation of Carelign. Results Users reported a statistically significant increase in Health Insurance Portability and Accountability Act (HIPPA)-compliance (44 vs. 100%, p < 0.0001) and ability to communicate with primary teams (38 vs. 70%, p = 0.019) after implementation of Carelign. There was a trend toward significance with ease of accessing information after switching to Carelign (67 vs. 85%, p = 0.185). There was no statistically significant difference in effectiveness, efficiency, accessibility from home, or reliability of information on handoff after converting to the new system. Conclusion Carelign is perceived to be an effective tool that can be used by consulting providers to ensure HIPPA-compliance and the ability to communicate with primary teams without sacrificing effectiveness, efficiency, accessibility, or reliability.


2016 ◽  
Vol 51 (4) ◽  
pp. 307-314 ◽  
Author(s):  
Michelle Zaepfel ◽  
Lisa Cristofaro ◽  
Allison Trawinski ◽  
Katharine McCarthy ◽  
Elizabeth Rightmier ◽  
...  

Background: The University of Rochester (UR) Specialty Pharmacy hepatitis C patient management program offers a unique advantage of being integrated within the same health system as the University of Rochester Medical Center (URMC) Gastroenterology and Hepatology division. Objective: The primary purpose of this study was to assess treatment success through the incidence of achieving a sustained virological response (SVR) in patients served by the UR Specialty Pharmacy versus other nonintegrated pharmacies. Methods: This was a single-center retrospective cohort study in adult patients of URMC Gastroenterology and Hepatology prescribed hepatitis C treatment between January 1, 2014, and July 15, 2015. The incidence of SVR, adherence, delay in therapy initiation, early treatment discontinuation, rate of attainment of viral load measurement post–therapy completion, and predictors associated with treatment outcome were assessed. Results: A total of 414 patients were prescribed hepatitis C virus treatment during the study period; 137 did not initiate therapy. The rate of SVR was 93% among patients at the UR Specialty Pharmacy and 89% at nonintegrated pharmacies ( P = 0.357). Adherence to therapy was 100% and 97% at the UR Specialty Pharmacy and nonintegrated pharmacies, respectively ( P = 0.046). Conclusions: The UR Specialty Pharmacy was associated with a 93% SVR rate and significantly greater adherence compared with nonintegrated pharmacies. Larger studies are needed to determine if a significant difference in SVR exists between integrated and nonintegrated pharmacies. This study provides a framework for other institutions to justify developing integrated hepatitis C specialty pharmacy services and evaluate their success.


2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Renata Silvério ◽  
Fábio S. Lira ◽  
Lila M. Oyama ◽  
Cláudia M. Oller do Nascimento ◽  
José P. Otoch ◽  
...  

2017 ◽  
Author(s):  
John Eddie Ekakoro ◽  
Chika C Okafor

Background. Antimicrobial drugs in veterinary medical practice are primarily prescribed for the purposes of maintaining or improving health and increasing productivity. However, their value is being eroded by antimicrobial resistance (AMR). Indiscriminate use of antimicrobial drugs is suggested as one of the modifiable factors contributing to the development of AMR. To reduce indiscriminate use and to improve antimicrobial use, veterinary practices are encouraged to adopt good stewardship practices. Therefore, the objectives of this study were: to identify factors influencing clinician decisions to begin using antimicrobials as well as the choice of antimicrobials used at The University of Tennessee Veterinary Medical Center (UTVMC); to evaluate the practices, perceptions, opinions and concerns of veterinary clinicians at UTVMC concerning antimicrobial use, antimicrobial stewardship, and AMR. Methods. This study’s protocol was approved by the University of Tennessee Knoxville IRB for the Protection of Human Subjects in Research. Survey software was used to send a questionnaire to 121 eligible participants, where all were UTVMC faculty with clinical appointments and house officers. Cumulative logit models were fitted to investigate associations between categorical explanatory variables and ordinal response variables. Results. A response rate of 51.24% was achieved. Of the 62 respondents, 47 (75.81%) reported that bacteriological culture and antimicrobial susceptibility test results were extremely important in their antimicrobial prescription decision-making. Thirty-two (51.61%) respondents believed antimicrobials are being over-prescribed. The cephalosporin class was the most preferred antimicrobial class, while the lincosamide class was the least preferred. From the multivariable cumulative logit model, year of graduation from veterinary school (P = 0.034) and clinicians’ primary patient load (P = 0.009) were significantly associated with clinicians’ degree of concern about AMR. Conclusions and clinical relevance. The findings suggest a need for more awareness about AMR among veterinary clinicians. Improvements in antimicrobial stewardship are needed, especially among veterinary clinicians who graduated after 1999. Educational practices that target modification of antimicrobial prescription practices of veterinary clinicians would likely improve a Good Stewardship Practice (GSP) mindset. GSP is important in prolonging the efficacy of currently available antimicrobial drugs.


2021 ◽  
Author(s):  
Evan Thomas Austin ◽  
◽  
Paul Kang ◽  
Chinedu Mmeje ◽  
Joseph Mashni ◽  
...  

Purpose: The purpose of this study was to validate the second version of the Prostate Imaging Reporting and Data System (PI-RADSv2) scores in predicting positive in-bore MRI-guided targeted prostate biopsy results across different non-university related institutions. The study focuses on PI-RADS v2 scoring because during the study period, PI-RADS v2.1 had not been released. Materials and Methods: This was a retrospective review of 147 patients who underwent multiparametric magnetic resonance imaging (mpMRI) of the pelvis followed by in-bore MRI-guided targeted prostate biopsy from December 2014 to May 2018. All lesions on mpMRI were rated according to PI-RADS v2 criteria. PI-RADS v2 scores were then compared to MR-guided biopsy results and pre-biopsy PSA values. Results: Prostate Cancer (PCa) was detected in 54% (80/147) of patients, with more prostate cancer being detected with each subsequent increase in PI-RADS scores. Specifically, biopsy results in patients with PI-RADS 3, 4, and 5 lesions resulted in PCa in 25.6% (10/39), 58.1% (33/55), and 86.0% (37/43) respectively. Clinically significant PCa (Gleason score ≥7) was detected in 17.9% (7/39), 52.7% (29/55), and 72% (31/43) of cases for PI-RADS 3, 4, and 5 lesions respectively. When the PI-RADS scoring and biopsy results were compared across different institutions, there was no difference in the PI-RADS scoring of lesions or in the positive biopsy rates of the lesions. The sensitivity, specificity, PPV, and NPV for PI-RADS 3-4 lesions were also not statistically different across the institutions for detecting Gleason 7 or greater lesions. Conclusion: Our results agree with prior studies that higher PI-RADS scores are associated with the presence of clinically significant PCa and suggest prostate lesions with PI-RADS scores 3-5 have sufficient evidence to warrant targeted biopsy. The comparison of PI-RADS score across different types of non-university practices revealed no difference in scoring and biopsy outcome, suggesting that PI-RADS v2 can be easily applied outside of the university medical center setting. Clinical Relevance: PI-RADS v2 can be applied homogeneously in the non-university setting without significant difference in outcome.


1999 ◽  
Vol 37 (11) ◽  
pp. 3564-3568 ◽  
Author(s):  
Ellena M. Peterson ◽  
Audrey Nakasone ◽  
J. M. Platon-DeLeon ◽  
Y. Jang ◽  
Luis M. de la Maza ◽  
...  

Microscopic examination of respiratory specimens for acid-fast bacilli (AFB) plays a key role in the initial diagnosis of tuberculosis, monitoring of treatment, and determination of eligibility for release from isolation. The objective of this study was to compare the sensitivity obtained with smears for detection of AFB (AFB smears) made directly from respiratory specimens (direct AFB smears) to that obtained with parallel smears made from concentrates of the specimens (concentrated AFB smears). A total of 2,693 specimens were evaluated; 1,806 were from the University of California Irvine Medical Center Medical Microbiology Laboratory (UCIMC), which serves a tertiary-care hospital with outpatient clinics, and 887 were from the Microbial Disease Laboratory at the California Department of Public Health (MDL), which receives specimens from outpatient facilities and clinics on Pacific islands. Of the 353 AFB culture-positive specimens at UCIMC, there was a statistically significant difference in the sensitivity of the direct AFB smear (34%) and that of the smear made from the concentrated specimen (58%) (P < 0.05). This was also true for the 208 specimens positive for Mycobacterium tuberculosis, for which the sensitivity of the direct smear was 42% (87 of 208) and that for the smear made from the concentrated specimen was 74% (154 of 208). At MDL, where all but 1 of the 45 culture-positive specimens grew M. tuberculosis, the sensitivity of the smear made from the concentrated specimen was 93% (42 of 45) and was not significantly higher than the sensitivity of the direct smear, which was 82% (37 of 45). By combining the results from both laboratories, 42 patients from whom at least three specimens were received were culture positive for M. tuberculosis. The cumulative results for the initial three specimens from these patients showed that the direct smear detected M. tuberculosis in 81% of these patients, whereas the smear made from the concentrate detected M. tuberculosis in 91% of these patients. In summary, when all culture-positive specimens are considered, the sensitivity of the direct smear compared to that of a smear made from the concentrated specimen was significantly different overall in the two different laboratory settings. However, this difference was reduced only if the cumulative results for the initial three specimens received from patients who were culture positive for M. tuberculosiswere evaluated.


2018 ◽  
Vol 55 (1) ◽  
pp. 26-31
Author(s):  
Benjamin E. Bredhold ◽  
Shauna D. Winters ◽  
John C. Callison ◽  
Robert E. Heidel ◽  
Lauren M. Allen ◽  
...  

Background: Septic shock is a serious medical condition affecting millions of people each year and guidelines direct vasopressor use in these patients. However, there is little information as to which vasopressor should be discontinued first. Objective: The objective of this study was to assess the impact of the sequence of norepinephrine and vasopressin discontinuation on intensive care unit (ICU) length of stay. Methods: This was a single-center retrospective cohort study conducted at The University of Tennessee Medical Center in Knoxville, Tennessee. Patients included in this study were adults 18 years of age and older with a diagnosis of septic shock who received norepinephrine in combination with vasopressin. Patients were excluded if norepinephrine or vasopressin were not the last 2 vasoactive agents used or if the patient expired or care was withdrawn. Measurements and Main Results: A total of 86 patients were included in this study, with 34 patients in the norepinephrine discontinued first group (NDF) and 52 in the vasopressin discontinued first group (VDF). For the primary outcome of ICU length of stay, no statistically significant difference was found between the NDF and the VDF groups (9.38 days vs 11.07 days, P = .313). The secondary outcome of the dose of norepinephrine at which vasopressin was initiated was also found to not be significant between the NDF and VDF groups (22 µg/min vs 31.1 µg/min, P = .11). The rates of hypotension within 24 hours of discontinuation of the first agent were also not significant between the NDF and VDF groups (17% vs 31%, P = .38). Conclusions: Based on the results of this study, there was significant no difference in ICU length of stay based on the sequence of discontinuation between norepinephrine and vasopressin in patients recovering from septic shock.


2021 ◽  
Author(s):  
Zhenghua Cai ◽  
Shanshan Xu ◽  
Yifan Zhang ◽  
Yifei Yang ◽  
Jian He ◽  
...  

Abstract BackgroundTo observe body composition parameters variance in patient with periampullary neoplasmas with different clinical characteristics and assess its predictive value for postoperative complications after pancreaticoduodenectomy. MethodsIn this study, we retrospectively reviewed the clinical and image data of 144 patients with periampullary neoplasmas.The area of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and total abdominal muscle area (TAMA) were measured from preoperative CT images at the 3rd lumbar vertebra level, the TAMA was normalized to stature and termed as skeleton muscle index (SMI). The perioperative and pathological data were collected. ResultsOf the included 144 patients, 80(55.6%), 29(20.1%) and 24(16.7%) patients were classified as sarcopenia, visceral obesity and sarcopenic obesity. 84(58.3%) patients were jaundiced and 28 (19.4%),50 (34.7%),66(45.8%) patients were diagnosed with benign pancreatic tumors, pancreatic cancer and non-pancreatic cancer respectively. The incidence rate of clinical postoperative pancreatic fistula(POPF) and other major complications were 38.2% and 16%.In the univariate analysis, jaundiced patients experienced more weight loss and had higher nutrition risk score, the TAMA[103.1(61.1-176.7) vs 111.8(74.1-198.2),P=0.021] and SMI(39.2±7.0 vs 42.6±9.1,P=0.012)were lower compared with non-jaundiced group. However, no significant difference were founded between different pathological results and it was not associated with occurrence of POPF and major complications.ConclusionJaundiced patients may experience more weight loss and have lower TAMA and SMI. Body morphometric analysis of preoperative CT did not show predictive value for postoperative complications and further multicenter studies are needed.Trail registrationRegistration number:2021-437-01.


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