BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible...BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible remodeling of the pulmonary arterial walls.Coronavirus disease 2019(COVID-19)has been associated with development of new onset PAH in the literature leading to symptoms of dyspnea,cough and fatigue that persist in spite of resolution of acute COVID-19 infection.However,the majority of these cases of COVID related PAH were diagnosed using echocardiographic data or via right heart catheterization in mechanically ventilated patients.CASE SUMMARY Our case is the first reported case of COVID related PAH diagnosed by right heart catheterization in a non-mechanically ventilated patient.Right heart catheterization has been the gold standard for diagnosis of pulmonary hypertension.Our patient had right heart catheterization four months after her initial COVID-19 infection due to persistent dyspnea.CONCLUSION This revealed new onset PAH that developed following her infection with COVID-19,an emerging sequela of the infection.展开更多
Cancer is one of the most common causes of morbidity and mortality worldwide.The high demand for specific nutrients and the sensitivity to nutritional deficiencies are newly recognized features of cancer cells.Dietary...Cancer is one of the most common causes of morbidity and mortality worldwide.The high demand for specific nutrients and the sensitivity to nutritional deficiencies are newly recognized features of cancer cells.Dietary interventions can suppress tumor demand for particular nutrients and alter certain nutrients to target a tumor's metabolic vulnerability.Cyclic fasting or fasting-mimicking diets(FMDs)are popular approaches that can reduce nutrient intake over a specific period.Accumulating evidence suggests that FMDs attenuate tumor growth by altering the energy metabolism of cancer cells.Furthermore,FMDs potentiate the sensitivity of tumors to conventional cancer treatments and limit adverse events.Recent findings also highlight the potential value of FMDs in boosting antitumor immune surveillance.However,clinical trials regarding the impact of FMDs on cancer patients remain limited and controversial.Here,we provide the latest information on the effects of FMDs on cancer progression and treatment,focusing on future clinical applications.展开更多
Obesity is a global pandemic characterized by high levels of body fat(adiposity) and derived-cytokines(i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer pro...Obesity is a global pandemic characterized by high levels of body fat(adiposity) and derived-cytokines(i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer progression. Leptin's main function is to regulate energy balance. However, obese individuals routinely develop leptin resistance, which is the consequence of the breakdown in the signaling mechanism controlling satiety resulting in the accumulation of leptin. Therefore, leptin levels are often chronically elevated in human obesity. Elevated leptin levels are related to higher incidence, increased progression and poor prognosis of several human cancers. In addition to adipose tissue, cancer cells can also secrete leptin and overexpress leptin receptors. Leptin is known to act as a mitogen, inflammatory and pro-angiogenic factor that induces cancer cell proliferation and tumor angiogenesis. Moreover, leptin signaling induces cancer stem cells, which are involved in cancer recurrence and drug resistance. A novel and complex signaling crosstalk between leptin, Notch and interleukin-1(IL-1) [Notch, IL-1 and leptin crosstalk outcome(NILCO)] seems to be an important driver of leptin-induced oncogenic actions. Leptin and NILCO signaling mediate the activation of cancer stem cells that can affect drug resistance. Thus, leptin and NILCO signaling are key links between obesity and cancer progression. This review presents updated data suggesting that adiposity affects cancer incidence, progression, and response to treatment. Here we show data supporting the oncogenic role of leptin in breast, endometrial, and pancreatic cancers.展开更多
BACKGROUND Previous studies have established a role of gout in predicting risk and prognosis of cardiovascular diseases. However, large-scale data on the impact of gout on inpatient outcomes of acute coronary syndrome...BACKGROUND Previous studies have established a role of gout in predicting risk and prognosis of cardiovascular diseases. However, large-scale data on the impact of gout on inpatient outcomes of acute coronary syndrome (ACS)-related hospitalizations and post-revascularization is inadequate. AIM To evaluate the impact of gout on in-hospital outcomes of ACS hospitalizations, subsequent healthcare burden and predictors of post-revascularization inpatient mortality. METHODS We used the national inpatient sample (2010-2014) to identify the ACS and goutrelated hospitalizations, relevant comorbidities, revascularization and postrevascularization outcomes using the ICD-9 CM codes. A multivariable analysis was performed to evaluate the predictors of post-revascularization in-hospital mortality. RESULTS We identified 3144744 ACS-related hospitalizations, of which 105198 (3.35%) also had gout. The ACS-gout cohort were more often older white males with a higher prevalence of comorbidities. Coronary artery bypass grafting was required more often in the ACS-gout cohort. Post-revascularization complications including cardiac (3.2% vs 2.9%), respiratory (3.5% vs 2.9%), and hemorrhage (3.1% vs 2.7%) were higher whereas all-cause mortality was lower (2.2% vs 3.0%) in the ACSgout cohort (P < 0.001). An older age (OR 15.63, CI: 5.51-44.39), non-elective admissions (OR 2.00, CI: 1.44-2.79), lower household income (OR 1.44, CI: 1.17- 1.78), and comorbid conditions predicted higher mortality in ACS-gout cohort undergoing revascularization (P < 0.001). Odds of post-revascularization inhospital mortality were lower in Hispanics (OR 0.45, CI: 0.31-0.67) and Asians (OR 0.65, CI: 0.45-0.94) as compared to white (P < 0.001). However, postoperative complications significantly raised mortality odds. Mean length of stay, transfer to other facilities, and hospital charges were higher in the ACS-gout cohort. CONCLUSION Although gout was not independently associated with an increased risk of postrevascularization in-hospital mortality in ACS, it did increase postrevascularization complications.展开更多
Background: Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease. The high rate of vitamin D deficiency ( 25) African Americans with elevated blood pressure (130 - 150/85 - 10...Background: Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease. The high rate of vitamin D deficiency ( 25) African Americans with elevated blood pressure (130 - 150/85 - 100 mmHg) and low serum vitamin D level (10 - 25 ng/ml). Results: There was a significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) with the intervention (p < 0.001). The increase in 25(OH)D levels was associated with a significant decrease in the serum level of intact PTH (p = 0.02), mean urinary isoprostane (p = 0.02) and adipocyte cytokine expression. Although the increase in the 25(OH)D levels was not associated with any significant change in the Pulse Wave Velocity (PWV) in the overall study sample, it was associated with a significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007). Conclusion: We concluded that vitamin D supplementation increased serum 25(OH)D levels, decreased intact PTH level and the levels of select inflammatory and oxidative stress mediators of arterial stiffness. Longer term prospective studies are warranted to evaluate the effect of high dose vitamin D supplementation on arterial stiffness.展开更多
Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with th...Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with the plasma membrane. They are composed of a lipid bilayer membrane and contain proteins, mRNA and miRNA. Exosomes are secreted by multiple cell types, including cancer cells. However, there is a relative lack of information concerning the contents of exosomes secreted by various tumor cell types. To examine exosomes in cancer, we collected blood plasma samples from patients with breast, ovarian, prostate, hepatic, gastric, colon, and pancreatic cancers. Exosomes were isolated from plasma and confirmed by AchE assay, transmission electron microscopy and expression of the CD63 exosomal marker. Expression of AFP, CA724, CA153, CEA, CA125, CA199 and PSA antigens were determined using an automated electro-chemiluminescence assay. Expression of the tumor-related chaperone protein, mortalin, was determined by Western blot analysis. Levels of exosome secretion were variable among the different tumor types. Both exosome levels and mortalin expression within tumor cell exosomes were higher than in healthy donors, except in pancreatic carcinoma, where exosomes were elevated but mortalin expression was not significantly different from healthy donors. Exosomes provide unique opportunities for the enrichment of tumor-specific materials and may be useful as biomarkers and possibly as tools of cancer therapies. Mortalin, which has been linked to cell proliferation and induction of epithelial-mesenchymal transition of cancer cells, may be useful as a prognostic biomarker and as a possible therapeutic target.展开更多
Background Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquit...Background Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquitously and abundantly in many tissues and cell types including vascular cells, the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) and upregulated during vascular lesion formation. Methods and Results We documented, by Northern blot analysis,that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats (SI-IR) compared to Wistar-Kyoto rats (WKY). In addition, we found that the expression of Angiotensin II (Ang II)type I receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC. Furthermore, Ang II potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1R signaling pathway. Conclusions OPG expression was substantially greater in SHR VSMC, suggesting that OPG may be an important determinant of vascular remodeling in SHR.展开更多
BACKGROUND The influence of opioid use disorder on implant related complications, infection and readmission rates, and total global episode-of-care costs following primary total knee arthroplasty(TKA) is limited.AIM T...BACKGROUND The influence of opioid use disorder on implant related complications, infection and readmission rates, and total global episode-of-care costs following primary total knee arthroplasty(TKA) is limited.AIM To examine whether opioid abuse in patients undergoing primary TKA.METHODS A retrospective analysis of the Medicare dataset, using the PearlDiver database,from 2005-2014 comparing outcomes in patients with opioid abusers(OUD) to non-opioid abusers(NOU) undergoing primary TKA was performed. Patient outcomes were analyzed including implant complications, readmission rates, and day-of-surgery and 90-d cost. Statistical analysis was performed with R(University of Auckland, New Zealand) calculating odds-ratio(OR) along with their respective 95% confidence interval(95%CI) and P-values.RESULTS The OUD group was at greater odds of having implant related complications overall(20.84% vs 11.25%; OR: 2.07; 95%CI: 1.93-2.23; P < 0.001). Revision(OR:2.07; 95%CI: 1.11-3.84; P < 0.001), infection(OR: 1.92; 95%CI: 1.72–2.18; P < 0.001),periprosthetic fractures(OR: 1.83; 95%CI: 1.16-4.79; P < 0.001), and 90-dreadmission rates(OR: 1.47, 95%CI: 1.35-1.61, P < 0.001) were also significantly increased. OUD patients also incurred in higher day-of-surgery and total global 90-d episode-of-care costs compared to NOU.CONCLUSION Patients with OUD show an increased risk of complications compared to the nonopioid users group. Appropriate recognition, pre-surgical optimization, and patient education are essential to mitigate these complications and improve patient outcome.展开更多
Determining the baseline utilization of best practices among clinicians, with regard to HIV care and disclosure of status to at-risk partners, is critical to addressing HIV prevention issues and disease transmission. ...Determining the baseline utilization of best practices among clinicians, with regard to HIV care and disclosure of status to at-risk partners, is critical to addressing HIV prevention issues and disease transmission. In this study, we examined clinicians' utilization of best practices for HIV/AIDS care and the disclosure of HIV status to sexual and needle-sharing partners (HSSNSP). We conducted a cross-sectional survey of 100 clinicians to assess knowledge, attitude, and behavior towards best practices for HIV care and disclosure of HSSNSP. Multiple logistic regression analysis was used to determine factors associated with the utilization of clinical best practices for HIV care and disclosure of HSSNSP. Forty eight percent of the participants revealed poor behaviors. Fifty six percent showed less positive attitudes towards clinical best practices for HIV care and disclosure of status. Less than half (32%) of the participants had earned at least 1 HIV/AIDS CME credit in the past two years. Our study showed strong associations between the utilization of best practices for HIV care and the disclosure of status, and clinician attitudes and knowledge levels. Further research that aims to improve knowledge and attitudes on clinical best practices for providing HIV/AIDS care and the disclosure of status is needed. This improvement may lead to increase in the utilization of best practices for HIV care and disclosure of status, and contribute to decreases in disease transmission rates.展开更多
The purpose of this Integrated Care Practice Change and Quality Improvement (ICPCQI) initiative was to evaluate the impact of wellness and relaxation and group psycho-education on health out-comes in an integrated car...The purpose of this Integrated Care Practice Change and Quality Improvement (ICPCQI) initiative was to evaluate the impact of wellness and relaxation and group psycho-education on health out-comes in an integrated care setting. Individuals diagnosed with mental illness and a co-occurring chronic medical condition participated in the ICPCQI initiatives which were run by peer support and wellness experts in an integrated care setting over the one-year project implementation period. Evaluation of outcome measures revealed an overall decline of 8.3% (p < 0.0001) and 7.3% (p < 0.0001) in the average systolic and diastolic blood pressure respectively. There was a 12.3% (p = 0.02) reduction on the average PHQ-9 scores. GAD-7 (p = 0.9) scores had a mean reduction of 1.5%. These preliminary results suggest that the evidence-based ICPCQI initiatives positively impact health outcomes among individuals with mental illness and chronic medical conditions.展开更多
Introduction: Adenopolyps patients have a three-fold higher risk of colon cancer over the general population, which increases to six-fold if the polyps are multiple and with lower survival among African American popul...Introduction: Adenopolyps patients have a three-fold higher risk of colon cancer over the general population, which increases to six-fold if the polyps are multiple and with lower survival among African American population. Currently, 6% of CRC can be ascribed to mutations in particular genes. Moreover, the optimal management of patients with colorectal adenopolyps depends on the accuracy of appropriate staging strategies because patients with similar colorectal adenocarcinoma architecture display heterogeneity in the course and outcome of the disease. Oxidative stress, due to an imbalance between reactive oxygen species (ROS) and antioxidant capacities as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids which promote tumor formation. Objective/Method: This study applied spectrophotometric, dinitrophenylhydrazone (DNPH) assay, two-dimensional gel electrophoresis, and western blot analyses to assess the levels of oxidatively modified proteins in 41 pairs of primary colorectal tissues including normal/surrounding, adenopolyps (tubular, tubulovillous, villous, polypvillous) and carcinoma. Analysis of variance (ANOVA) and Student’s t-tests were utilized for the resulting data set. Results: Our data showed that the levels of reactive protein carbonyl groups significantly increased as colorectal adenopolyps progresses to malignancy. No significant differences were found in the levels of carbonyl proteins between gender samples analyzed. For African American patients, there were, relative to Caucasians, 10% higher levels of reactive carbonyls in proteins of tubulovillous tissue samples展开更多
BACKGROUND The effect of posterior spinal fusion(PSF)incorporating the pelvis on an ambulatory patient’s ability to mobilize after the fusion is not well understood.AIM To see whether a posterior spinal fusion with p...BACKGROUND The effect of posterior spinal fusion(PSF)incorporating the pelvis on an ambulatory patient’s ability to mobilize after the fusion is not well understood.AIM To see whether a posterior spinal fusion with pelvic fixation using iliac or sacral alar iliac screws in ambulatory neuromuscular scoliosis(NMS)patients influences postoperative ambulatory ability.METHODS A retrospective review of all patients with NMS that underwent PSF with fixation incorporating the pelvis between January 1,2012 and February 29,2019.A total of 118 patients were eligible,including 11 ambulatory patients.The primary outcome was the maintenance of ambulatory status postoperatively.Secondary outcomes included postoperative curve magnitude,pelvic obliquity,and complications,comprising infections,instrumentation failure,and any unplanned returns to the operative room.RESULTS The ambulatory function was maintained in all 11 ambulatory NMS patients.One patient had an improvement in functional status with equipment-free ambulation postoperatively.An average postoperative follow-up was 19 mo.The overall complication rate was 19.4%(n=23)with no significant differences between the groups in infection(P=0.365),hardware failure(P=0.505),and reoperation rate(P=1.0).Ambulatory status did not affect complication rate(P=0.967).CONCLUSION Spinal fusion to the pelvis in ambulatory patients with NMS provides effective deformity correction without the reduction in ambulatory capabilities.展开更多
Mammalian collagens exhibit weak intrinsic UV fluorescence that depends on the age and previous history of the sample. Post-translational modifications result in additional fluorescent products (e.g. DOPA, dityrosine,...Mammalian collagens exhibit weak intrinsic UV fluorescence that depends on the age and previous history of the sample. Post-translational modifications result in additional fluorescent products (e.g. DOPA, dityrosine, and advanced glycation end products (AGE)). UV radiation can cause longer wavelength fluorescent oxidative bands. These alterations can assess the extent of photolysis. We describe the ground- and excited-state oxidative transformations of newly-purchased type I calf skin collagens (samples #092014 and #072012) and a 7-year-old sample (#072005). We compare the effects of UV radiation (mainly 254 nm) and age on the photochemical reaction kinetics and fluorescence spectral distribution of type I calf skin collagen at pH 7.4. The fluorescence spectra of samples #072012 and #092014 were similar but not identical to pure tyrosine, whereas #072005 indicated significant “dark” oxidation at the expense of tyrosine. Fading of oxidized product(s) at 270/360 nm is second-order. Build-up of 325/400 nm (dityrosine) fluorescence is linear with time. Rate parameters r2 and r1 were respectively proportional to second order disappearance of ground state oxidation products and the quasi–first-order photochemical formation of dityrosine. There is a reciprocal relationship between the rates of decrease in the 270/360 nm fluorescence and concomitant increase in 325/400 nm fluorescence. Their relative rates depend on the age of the collagen sample. There is a reciprocal relationship between r1 and r2. This relationship results because both ground state autoxidation and excited state photo-dimerization proceed via a common tyrosyl radical intermediate. Water of hydration appears to play a role in generating tyrosyl radical.展开更多
Recently, nitric oxide (NO) has been implicated as an epigenetic factor in keloids, a scarring disease occurring primarily in dark skinned people who have relatively high amounts of pigment melanin. In this work, we t...Recently, nitric oxide (NO) has been implicated as an epigenetic factor in keloids, a scarring disease occurring primarily in dark skinned people who have relatively high amounts of pigment melanin. In this work, we tested whether a melanin-mediated redox reaction involving adsorbed NO and O2 can couple NO oxidation with O2 reduction to form reactive oxygen species (ROS) or reactive nitrogen species (RNS) in vitro at pH 7.4. We measured the formation of reactive species that oxidize dihydrorhodamine123 (DHR) to fluorescent rhodamine123 in the presence and absence of sepia melanin. In separate experiments, we monitored NO concentration with 4,5-diaminofluorescein (DAF) by measuring the highly fluorescent NO-adduct, DAF-2T. We attempted to detect peroxynitrite with 5 μM 3-methyl-1,2-cyclopentanedione (MCP), a selective scavenger of peroxynitrite (IC50 = 3.6 μM for ONOO- vs. 63.8 μM and >> 100 μM for NO and O2- respectively). However, MCP itself oxidized DHR. We found that in the absence of NO, melanin itself oxidizes DHR, with no loss of DAF-fluorescence (i.e. no net consumption of NO). In the presence of NO, there was a ~ 57% loss of DAF fluorescence, indicating that NOx is formed at the expense of NO. The data provided good fit (r2 = 0.94) to a Langmuir adsorption isotherm, with pseudo first order rate k' = 8.2 × 107) s-1 and adsorption coefficient Kad = 4.04 M-1. Both of these parameters are consistent with a facile chemisorption reaction between NO and O2 on the melanin surface. Possible reactions are a) NO and O2- → ONOO- and/or b) 2NO + O2 → 2NO2. The latter reaction is disfavored in solution but is significantly accelerated on the melanin surface via an entropy effect.展开更多
The benzenearsonate, Roxarsone, has been used since 1944 as an antimicrobial, growth-promoting poultry feed additive. USGS and EPA report that Roxarsone (4-hydroxy-3-nitrobenzenearsonate) and metabolites, including AH...The benzenearsonate, Roxarsone, has been used since 1944 as an antimicrobial, growth-promoting poultry feed additive. USGS and EPA report that Roxarsone (4-hydroxy-3-nitrobenzenearsonate) and metabolites, including AHBA (3-amino-4-hydroxybenzenearsonate), contaminate waterways at greater than 1100 tons annually. To assess human impact of these organic arsenic water contaminants, it was important to study their potential absorption. The human adenocarcinoma cell line, Caco-2, is a model for intestinal absorption. We found proliferative effects on Caco-2 cells at micromolar levels of these compounds, as monitored by [3H]-thymidine incorporation into DNA. Flow cytometry cell cycle analysis confirmed accumulation in S phase from 21% (control) to 36% (24 hour exposure to 10 μM AHBA). Confluent Caco-2 cells grown on collagen-coated Transwell plates were dosed on the apical side. After exposure, media from apical and basolateral sides were collected separately. Following removal of FBS by 30K centrifugal filtration, the benzenearsonates in the collected media were analyzed by HPLC. Analyses were at wavelengths in the ultraviolet/visible range where the absorbance values were linear with respect to concentration. Concentrations were calculated by comparison with analytically-prepared commercial standards. Results from cells dosed at 10 μM for 24 hours with AHBA, Roxarsone, or Acetarsone indicated 6%-29% permeation occurring from apical to basolateral side, modeling absorption across intestinal epithelium to the circulatory system. Benzenearsonate feed additives are frequently applied in combination with antibiotics, raising additional health concerns. We conclude that micromolar levels of these benzenearsonates are adequate to stimulate Caco-2 cell proliferation.展开更多
As breast cancer relative survival continues to increase, many breast cancer patients face many issues, including recurrence of cancer and cancer-related side effects that impact several aspects of their quality of li...As breast cancer relative survival continues to increase, many breast cancer patients face many issues, including recurrence of cancer and cancer-related side effects that impact several aspects of their quality of life. With breast cancer patients living longer, there is more of a concern for negative breast cancer outcomes. Although physical activity is an affordable and relatively convenient way to improve breast cancer outcomes, only about one-third of breast cancer survivors engage in the recommended level of physical activity. This article reviews articles published to date to examine whether home-based physical activity interventions are effective in improving physical activity and other outcomes among breast cancer survivors who have completed primary therapy for the disease. The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from 1980 through February 28, 2019 were identified. A total of 360 article citations were identified in PubMed and non-duplicates in CINAHL. After screening the abstracts or full texts of these articles and reviewing the references of previous review articles, 20 studies that met the eligibility criteria. Three of the studies were pre-/post-test trials and 17 were randomized controlled trials. Home-based exercise programs are effective in improving physical activity among breast cancer survivors who have completed primary therapy for the disease. Home-based exercise programs such as walking programs offer a convenient and affordable option for women who wish to increase their physical activity and maintain a healthy lifestyle.展开更多
The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, providing not only essential physical scaffolding for the cellular constituents and initiating crucial biochemical an...The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, providing not only essential physical scaffolding for the cellular constituents and initiating crucial biochemical and biomechanical cues, required for tissue morphogenesis, differentiation and homeostasis. Roughly divided into two groups, these are 1) the main fibrous ECM proteins: collagens, elastins, fibronectins and laminins. 2) Classification of proteoglycans (PGs) is based on their location and binding. Although many different molecular interactions are possible, they depend on the cells’ condition (i.e. “Normal”, Aged, Wounded/Fibrotic, and cancerous). There is little or no data that addresses the influence of the surrounding ECM on dityrosine formation. As a simpler model, we have replaced total PG with hyaluronan (HA) and have used purified calf-skin collagen tyrosine, which forms dityrosine (A2) under 254 nm UV in buffered solution and (near) physiological temperatures. Our results reveal a complicated temperature dependence involving factors relating to collagen HA structure, and collagen’s photochemical activation parameters.展开更多
文摘BACKGROUND Pulmonary arterial hypertension(PAH)is a disease of the arterioles resulting in an increased resistance in pulmonary circulation with associated high pressures in the pulmonary arteries,causing irreversible remodeling of the pulmonary arterial walls.Coronavirus disease 2019(COVID-19)has been associated with development of new onset PAH in the literature leading to symptoms of dyspnea,cough and fatigue that persist in spite of resolution of acute COVID-19 infection.However,the majority of these cases of COVID related PAH were diagnosed using echocardiographic data or via right heart catheterization in mechanically ventilated patients.CASE SUMMARY Our case is the first reported case of COVID related PAH diagnosed by right heart catheterization in a non-mechanically ventilated patient.Right heart catheterization has been the gold standard for diagnosis of pulmonary hypertension.Our patient had right heart catheterization four months after her initial COVID-19 infection due to persistent dyspnea.CONCLUSION This revealed new onset PAH that developed following her infection with COVID-19,an emerging sequela of the infection.
基金supported by the National Natural Science Foundation of China(No.82172704).
文摘Cancer is one of the most common causes of morbidity and mortality worldwide.The high demand for specific nutrients and the sensitivity to nutritional deficiencies are newly recognized features of cancer cells.Dietary interventions can suppress tumor demand for particular nutrients and alter certain nutrients to target a tumor's metabolic vulnerability.Cyclic fasting or fasting-mimicking diets(FMDs)are popular approaches that can reduce nutrient intake over a specific period.Accumulating evidence suggests that FMDs attenuate tumor growth by altering the energy metabolism of cancer cells.Furthermore,FMDs potentiate the sensitivity of tumors to conventional cancer treatments and limit adverse events.Recent findings also highlight the potential value of FMDs in boosting antitumor immune surveillance.However,clinical trials regarding the impact of FMDs on cancer patients remain limited and controversial.Here,we provide the latest information on the effects of FMDs on cancer progression and treatment,focusing on future clinical applications.
基金We thank members of our group for insightful discussion during the course of this study.This work was supported by grants from Chinese Academy of Science(KSCX1-YW-R65,KSCX2-YW-H10)National Basic Research Program of China(2002CB713700)+4 种基金Hi-Tech Research and Development Program of China(2001AA215331)Chinese Minister of Education(20020358051 to XY,PCSIRT0413 to XD)National Natural Science Foundation of China(39925018,30270293 to XY,30500183 to XD,30600222 to JY)National Institutes of Health(USA)(DK56292,CA92080)to XY(a Georgia Cancer Coalition Eminent Scholar)JY was supported by China Postdoctor(2005037560).
基金Supported by The National Cancer Institute at the National Institutes of Health(NIH 1R41 CA183399-01A1,5U54 CA118638 Pilot Project Award and UAB/UMN SPORE in Pancreatic Cancer)the Congressionally Directed Medical Research Programs--Department of Defense(CDMRP DOD W81XWH-13-1-0382)to Gonzalez-Perez RR+1 种基金and NCI S21 MD000101,5G12 MD0076021,G12 RR026250-03,NIH RR03034 and 1C06 RR18386 to Morehouse School of Medicinethe National Center for Advancing Translational Sciences of the NIH Award 5T32HL103104-04(MPI)to Daley-Brown D
文摘Obesity is a global pandemic characterized by high levels of body fat(adiposity) and derived-cytokines(i.e., leptin). Research shows that adiposity and leptin provide insight on the link between obesity and cancer progression. Leptin's main function is to regulate energy balance. However, obese individuals routinely develop leptin resistance, which is the consequence of the breakdown in the signaling mechanism controlling satiety resulting in the accumulation of leptin. Therefore, leptin levels are often chronically elevated in human obesity. Elevated leptin levels are related to higher incidence, increased progression and poor prognosis of several human cancers. In addition to adipose tissue, cancer cells can also secrete leptin and overexpress leptin receptors. Leptin is known to act as a mitogen, inflammatory and pro-angiogenic factor that induces cancer cell proliferation and tumor angiogenesis. Moreover, leptin signaling induces cancer stem cells, which are involved in cancer recurrence and drug resistance. A novel and complex signaling crosstalk between leptin, Notch and interleukin-1(IL-1) [Notch, IL-1 and leptin crosstalk outcome(NILCO)] seems to be an important driver of leptin-induced oncogenic actions. Leptin and NILCO signaling mediate the activation of cancer stem cells that can affect drug resistance. Thus, leptin and NILCO signaling are key links between obesity and cancer progression. This review presents updated data suggesting that adiposity affects cancer incidence, progression, and response to treatment. Here we show data supporting the oncogenic role of leptin in breast, endometrial, and pancreatic cancers.
基金National Natural Science Foundation of China （39925018, 90508002 , 30121001） Chinese Academy of Science （KSCX 1-R65 and RSCX2-H10）+2 种基金 National Basic Research Program of China （973 project, 2002CB713700） American Cancer Society （RPG-99-173-01） a Gcc Breast Cancer Research award and National Institutes of Health grants DK56292 and CA89019 to XY （a GCC Eminent Scholar） and NS36194 （JW）.
文摘BACKGROUND Previous studies have established a role of gout in predicting risk and prognosis of cardiovascular diseases. However, large-scale data on the impact of gout on inpatient outcomes of acute coronary syndrome (ACS)-related hospitalizations and post-revascularization is inadequate. AIM To evaluate the impact of gout on in-hospital outcomes of ACS hospitalizations, subsequent healthcare burden and predictors of post-revascularization inpatient mortality. METHODS We used the national inpatient sample (2010-2014) to identify the ACS and goutrelated hospitalizations, relevant comorbidities, revascularization and postrevascularization outcomes using the ICD-9 CM codes. A multivariable analysis was performed to evaluate the predictors of post-revascularization in-hospital mortality. RESULTS We identified 3144744 ACS-related hospitalizations, of which 105198 (3.35%) also had gout. The ACS-gout cohort were more often older white males with a higher prevalence of comorbidities. Coronary artery bypass grafting was required more often in the ACS-gout cohort. Post-revascularization complications including cardiac (3.2% vs 2.9%), respiratory (3.5% vs 2.9%), and hemorrhage (3.1% vs 2.7%) were higher whereas all-cause mortality was lower (2.2% vs 3.0%) in the ACSgout cohort (P < 0.001). An older age (OR 15.63, CI: 5.51-44.39), non-elective admissions (OR 2.00, CI: 1.44-2.79), lower household income (OR 1.44, CI: 1.17- 1.78), and comorbid conditions predicted higher mortality in ACS-gout cohort undergoing revascularization (P < 0.001). Odds of post-revascularization inhospital mortality were lower in Hispanics (OR 0.45, CI: 0.31-0.67) and Asians (OR 0.65, CI: 0.45-0.94) as compared to white (P < 0.001). However, postoperative complications significantly raised mortality odds. Mean length of stay, transfer to other facilities, and hospital charges were higher in the ACS-gout cohort. CONCLUSION Although gout was not independently associated with an increased risk of postrevascularization in-hospital mortality in ACS, it did increase postrevascularization complications.
文摘Background: Vitamin D deficiency has been implicated as a potential risk factor for cardiovascular disease. The high rate of vitamin D deficiency ( 25) African Americans with elevated blood pressure (130 - 150/85 - 100 mmHg) and low serum vitamin D level (10 - 25 ng/ml). Results: There was a significant increase in the serum 25(OH)D levels to a mean level of 34.5 ng/ml (SD = 7.1) with the intervention (p < 0.001). The increase in 25(OH)D levels was associated with a significant decrease in the serum level of intact PTH (p = 0.02), mean urinary isoprostane (p = 0.02) and adipocyte cytokine expression. Although the increase in the 25(OH)D levels was not associated with any significant change in the Pulse Wave Velocity (PWV) in the overall study sample, it was associated with a significant decrease in the augmentation index among the participants with the highest tertile of urinary isoprostane (p = 0.007). Conclusion: We concluded that vitamin D supplementation increased serum 25(OH)D levels, decreased intact PTH level and the levels of select inflammatory and oxidative stress mediators of arterial stiffness. Longer term prospective studies are warranted to evaluate the effect of high dose vitamin D supplementation on arterial stiffness.
文摘Detection of circulating tumor-specific DNA, RNA or proteins can be difficult due to relative scarcity. Exosomes are extracellular vesicles, 30 - 150 nm in diameter derived from fusion of multivesicular bodies with the plasma membrane. They are composed of a lipid bilayer membrane and contain proteins, mRNA and miRNA. Exosomes are secreted by multiple cell types, including cancer cells. However, there is a relative lack of information concerning the contents of exosomes secreted by various tumor cell types. To examine exosomes in cancer, we collected blood plasma samples from patients with breast, ovarian, prostate, hepatic, gastric, colon, and pancreatic cancers. Exosomes were isolated from plasma and confirmed by AchE assay, transmission electron microscopy and expression of the CD63 exosomal marker. Expression of AFP, CA724, CA153, CEA, CA125, CA199 and PSA antigens were determined using an automated electro-chemiluminescence assay. Expression of the tumor-related chaperone protein, mortalin, was determined by Western blot analysis. Levels of exosome secretion were variable among the different tumor types. Both exosome levels and mortalin expression within tumor cell exosomes were higher than in healthy donors, except in pancreatic carcinoma, where exosomes were elevated but mortalin expression was not significantly different from healthy donors. Exosomes provide unique opportunities for the enrichment of tumor-specific materials and may be useful as biomarkers and possibly as tools of cancer therapies. Mortalin, which has been linked to cell proliferation and induction of epithelial-mesenchymal transition of cancer cells, may be useful as a prognostic biomarker and as a possible therapeutic target.
文摘Background Osteoprotegerin (OPG) is a secreted protein of the tumor necrosis factor receptor family, which regulates bone mass by inhibiting osteoclast differentiation and activation. Although OPG is expressed ubiquitously and abundantly in many tissues and cell types including vascular cells, the role of OPG in other tissues is unknown.Our previous studies demonstrated that OPG was highly expressed in vascular smooth muscle cells (VSMC) and upregulated during vascular lesion formation. Methods and Results We documented, by Northern blot analysis,that the expression of OPG was more prevalent in the aorta and cultured VSMC from spontaneously hypertensive rats (SI-IR) compared to Wistar-Kyoto rats (WKY). In addition, we found that the expression of Angiotensin II (Ang II)type I receptor (AT1R) in SHR VSMC was at significantly increased levels than in WKY VSMC. Furthermore, Ang II potently induced the expression of OPG in VSMC in a time- and dose-dependent manner through the AT1R signaling pathway. Conclusions OPG expression was substantially greater in SHR VSMC, suggesting that OPG may be an important determinant of vascular remodeling in SHR.
文摘BACKGROUND The influence of opioid use disorder on implant related complications, infection and readmission rates, and total global episode-of-care costs following primary total knee arthroplasty(TKA) is limited.AIM To examine whether opioid abuse in patients undergoing primary TKA.METHODS A retrospective analysis of the Medicare dataset, using the PearlDiver database,from 2005-2014 comparing outcomes in patients with opioid abusers(OUD) to non-opioid abusers(NOU) undergoing primary TKA was performed. Patient outcomes were analyzed including implant complications, readmission rates, and day-of-surgery and 90-d cost. Statistical analysis was performed with R(University of Auckland, New Zealand) calculating odds-ratio(OR) along with their respective 95% confidence interval(95%CI) and P-values.RESULTS The OUD group was at greater odds of having implant related complications overall(20.84% vs 11.25%; OR: 2.07; 95%CI: 1.93-2.23; P < 0.001). Revision(OR:2.07; 95%CI: 1.11-3.84; P < 0.001), infection(OR: 1.92; 95%CI: 1.72–2.18; P < 0.001),periprosthetic fractures(OR: 1.83; 95%CI: 1.16-4.79; P < 0.001), and 90-dreadmission rates(OR: 1.47, 95%CI: 1.35-1.61, P < 0.001) were also significantly increased. OUD patients also incurred in higher day-of-surgery and total global 90-d episode-of-care costs compared to NOU.CONCLUSION Patients with OUD show an increased risk of complications compared to the nonopioid users group. Appropriate recognition, pre-surgical optimization, and patient education are essential to mitigate these complications and improve patient outcome.
文摘Determining the baseline utilization of best practices among clinicians, with regard to HIV care and disclosure of status to at-risk partners, is critical to addressing HIV prevention issues and disease transmission. In this study, we examined clinicians' utilization of best practices for HIV/AIDS care and the disclosure of HIV status to sexual and needle-sharing partners (HSSNSP). We conducted a cross-sectional survey of 100 clinicians to assess knowledge, attitude, and behavior towards best practices for HIV care and disclosure of HSSNSP. Multiple logistic regression analysis was used to determine factors associated with the utilization of clinical best practices for HIV care and disclosure of HSSNSP. Forty eight percent of the participants revealed poor behaviors. Fifty six percent showed less positive attitudes towards clinical best practices for HIV care and disclosure of status. Less than half (32%) of the participants had earned at least 1 HIV/AIDS CME credit in the past two years. Our study showed strong associations between the utilization of best practices for HIV care and the disclosure of status, and clinician attitudes and knowledge levels. Further research that aims to improve knowledge and attitudes on clinical best practices for providing HIV/AIDS care and the disclosure of status is needed. This improvement may lead to increase in the utilization of best practices for HIV care and disclosure of status, and contribute to decreases in disease transmission rates.
文摘The purpose of this Integrated Care Practice Change and Quality Improvement (ICPCQI) initiative was to evaluate the impact of wellness and relaxation and group psycho-education on health out-comes in an integrated care setting. Individuals diagnosed with mental illness and a co-occurring chronic medical condition participated in the ICPCQI initiatives which were run by peer support and wellness experts in an integrated care setting over the one-year project implementation period. Evaluation of outcome measures revealed an overall decline of 8.3% (p < 0.0001) and 7.3% (p < 0.0001) in the average systolic and diastolic blood pressure respectively. There was a 12.3% (p = 0.02) reduction on the average PHQ-9 scores. GAD-7 (p = 0.9) scores had a mean reduction of 1.5%. These preliminary results suggest that the evidence-based ICPCQI initiatives positively impact health outcomes among individuals with mental illness and chronic medical conditions.
文摘Introduction: Adenopolyps patients have a three-fold higher risk of colon cancer over the general population, which increases to six-fold if the polyps are multiple and with lower survival among African American population. Currently, 6% of CRC can be ascribed to mutations in particular genes. Moreover, the optimal management of patients with colorectal adenopolyps depends on the accuracy of appropriate staging strategies because patients with similar colorectal adenocarcinoma architecture display heterogeneity in the course and outcome of the disease. Oxidative stress, due to an imbalance between reactive oxygen species (ROS) and antioxidant capacities as well as a disruption of redox signaling, causes a wide range of damage to DNA, proteins, and lipids which promote tumor formation. Objective/Method: This study applied spectrophotometric, dinitrophenylhydrazone (DNPH) assay, two-dimensional gel electrophoresis, and western blot analyses to assess the levels of oxidatively modified proteins in 41 pairs of primary colorectal tissues including normal/surrounding, adenopolyps (tubular, tubulovillous, villous, polypvillous) and carcinoma. Analysis of variance (ANOVA) and Student’s t-tests were utilized for the resulting data set. Results: Our data showed that the levels of reactive protein carbonyl groups significantly increased as colorectal adenopolyps progresses to malignancy. No significant differences were found in the levels of carbonyl proteins between gender samples analyzed. For African American patients, there were, relative to Caucasians, 10% higher levels of reactive carbonyls in proteins of tubulovillous tissue samples
文摘BACKGROUND The effect of posterior spinal fusion(PSF)incorporating the pelvis on an ambulatory patient’s ability to mobilize after the fusion is not well understood.AIM To see whether a posterior spinal fusion with pelvic fixation using iliac or sacral alar iliac screws in ambulatory neuromuscular scoliosis(NMS)patients influences postoperative ambulatory ability.METHODS A retrospective review of all patients with NMS that underwent PSF with fixation incorporating the pelvis between January 1,2012 and February 29,2019.A total of 118 patients were eligible,including 11 ambulatory patients.The primary outcome was the maintenance of ambulatory status postoperatively.Secondary outcomes included postoperative curve magnitude,pelvic obliquity,and complications,comprising infections,instrumentation failure,and any unplanned returns to the operative room.RESULTS The ambulatory function was maintained in all 11 ambulatory NMS patients.One patient had an improvement in functional status with equipment-free ambulation postoperatively.An average postoperative follow-up was 19 mo.The overall complication rate was 19.4%(n=23)with no significant differences between the groups in infection(P=0.365),hardware failure(P=0.505),and reoperation rate(P=1.0).Ambulatory status did not affect complication rate(P=0.967).CONCLUSION Spinal fusion to the pelvis in ambulatory patients with NMS provides effective deformity correction without the reduction in ambulatory capabilities.
文摘Mammalian collagens exhibit weak intrinsic UV fluorescence that depends on the age and previous history of the sample. Post-translational modifications result in additional fluorescent products (e.g. DOPA, dityrosine, and advanced glycation end products (AGE)). UV radiation can cause longer wavelength fluorescent oxidative bands. These alterations can assess the extent of photolysis. We describe the ground- and excited-state oxidative transformations of newly-purchased type I calf skin collagens (samples #092014 and #072012) and a 7-year-old sample (#072005). We compare the effects of UV radiation (mainly 254 nm) and age on the photochemical reaction kinetics and fluorescence spectral distribution of type I calf skin collagen at pH 7.4. The fluorescence spectra of samples #072012 and #092014 were similar but not identical to pure tyrosine, whereas #072005 indicated significant “dark” oxidation at the expense of tyrosine. Fading of oxidized product(s) at 270/360 nm is second-order. Build-up of 325/400 nm (dityrosine) fluorescence is linear with time. Rate parameters r2 and r1 were respectively proportional to second order disappearance of ground state oxidation products and the quasi–first-order photochemical formation of dityrosine. There is a reciprocal relationship between the rates of decrease in the 270/360 nm fluorescence and concomitant increase in 325/400 nm fluorescence. Their relative rates depend on the age of the collagen sample. There is a reciprocal relationship between r1 and r2. This relationship results because both ground state autoxidation and excited state photo-dimerization proceed via a common tyrosyl radical intermediate. Water of hydration appears to play a role in generating tyrosyl radical.
文摘Recently, nitric oxide (NO) has been implicated as an epigenetic factor in keloids, a scarring disease occurring primarily in dark skinned people who have relatively high amounts of pigment melanin. In this work, we tested whether a melanin-mediated redox reaction involving adsorbed NO and O2 can couple NO oxidation with O2 reduction to form reactive oxygen species (ROS) or reactive nitrogen species (RNS) in vitro at pH 7.4. We measured the formation of reactive species that oxidize dihydrorhodamine123 (DHR) to fluorescent rhodamine123 in the presence and absence of sepia melanin. In separate experiments, we monitored NO concentration with 4,5-diaminofluorescein (DAF) by measuring the highly fluorescent NO-adduct, DAF-2T. We attempted to detect peroxynitrite with 5 μM 3-methyl-1,2-cyclopentanedione (MCP), a selective scavenger of peroxynitrite (IC50 = 3.6 μM for ONOO- vs. 63.8 μM and >> 100 μM for NO and O2- respectively). However, MCP itself oxidized DHR. We found that in the absence of NO, melanin itself oxidizes DHR, with no loss of DAF-fluorescence (i.e. no net consumption of NO). In the presence of NO, there was a ~ 57% loss of DAF fluorescence, indicating that NOx is formed at the expense of NO. The data provided good fit (r2 = 0.94) to a Langmuir adsorption isotherm, with pseudo first order rate k' = 8.2 × 107) s-1 and adsorption coefficient Kad = 4.04 M-1. Both of these parameters are consistent with a facile chemisorption reaction between NO and O2 on the melanin surface. Possible reactions are a) NO and O2- → ONOO- and/or b) 2NO + O2 → 2NO2. The latter reaction is disfavored in solution but is significantly accelerated on the melanin surface via an entropy effect.
文摘The benzenearsonate, Roxarsone, has been used since 1944 as an antimicrobial, growth-promoting poultry feed additive. USGS and EPA report that Roxarsone (4-hydroxy-3-nitrobenzenearsonate) and metabolites, including AHBA (3-amino-4-hydroxybenzenearsonate), contaminate waterways at greater than 1100 tons annually. To assess human impact of these organic arsenic water contaminants, it was important to study their potential absorption. The human adenocarcinoma cell line, Caco-2, is a model for intestinal absorption. We found proliferative effects on Caco-2 cells at micromolar levels of these compounds, as monitored by [3H]-thymidine incorporation into DNA. Flow cytometry cell cycle analysis confirmed accumulation in S phase from 21% (control) to 36% (24 hour exposure to 10 μM AHBA). Confluent Caco-2 cells grown on collagen-coated Transwell plates were dosed on the apical side. After exposure, media from apical and basolateral sides were collected separately. Following removal of FBS by 30K centrifugal filtration, the benzenearsonates in the collected media were analyzed by HPLC. Analyses were at wavelengths in the ultraviolet/visible range where the absorbance values were linear with respect to concentration. Concentrations were calculated by comparison with analytically-prepared commercial standards. Results from cells dosed at 10 μM for 24 hours with AHBA, Roxarsone, or Acetarsone indicated 6%-29% permeation occurring from apical to basolateral side, modeling absorption across intestinal epithelium to the circulatory system. Benzenearsonate feed additives are frequently applied in combination with antibiotics, raising additional health concerns. We conclude that micromolar levels of these benzenearsonates are adequate to stimulate Caco-2 cell proliferation.
文摘As breast cancer relative survival continues to increase, many breast cancer patients face many issues, including recurrence of cancer and cancer-related side effects that impact several aspects of their quality of life. With breast cancer patients living longer, there is more of a concern for negative breast cancer outcomes. Although physical activity is an affordable and relatively convenient way to improve breast cancer outcomes, only about one-third of breast cancer survivors engage in the recommended level of physical activity. This article reviews articles published to date to examine whether home-based physical activity interventions are effective in improving physical activity and other outcomes among breast cancer survivors who have completed primary therapy for the disease. The present review is based upon bibliographic searches in PubMed and CINAHL and relevant search terms. Articles published in English from 1980 through February 28, 2019 were identified. A total of 360 article citations were identified in PubMed and non-duplicates in CINAHL. After screening the abstracts or full texts of these articles and reviewing the references of previous review articles, 20 studies that met the eligibility criteria. Three of the studies were pre-/post-test trials and 17 were randomized controlled trials. Home-based exercise programs are effective in improving physical activity among breast cancer survivors who have completed primary therapy for the disease. Home-based exercise programs such as walking programs offer a convenient and affordable option for women who wish to increase their physical activity and maintain a healthy lifestyle.
文摘The extracellular matrix (ECM) is the non-cellular component present within all tissues and organs, providing not only essential physical scaffolding for the cellular constituents and initiating crucial biochemical and biomechanical cues, required for tissue morphogenesis, differentiation and homeostasis. Roughly divided into two groups, these are 1) the main fibrous ECM proteins: collagens, elastins, fibronectins and laminins. 2) Classification of proteoglycans (PGs) is based on their location and binding. Although many different molecular interactions are possible, they depend on the cells’ condition (i.e. “Normal”, Aged, Wounded/Fibrotic, and cancerous). There is little or no data that addresses the influence of the surrounding ECM on dityrosine formation. As a simpler model, we have replaced total PG with hyaluronan (HA) and have used purified calf-skin collagen tyrosine, which forms dityrosine (A2) under 254 nm UV in buffered solution and (near) physiological temperatures. Our results reveal a complicated temperature dependence involving factors relating to collagen HA structure, and collagen’s photochemical activation parameters.
