Publications by authors named "Sultana Razia"

85 Publications

Evaluation of pasture allowance of manganese for ruminants.

Environ Sci Pollut Res Int 2021 Jun 2. Epub 2021 Jun 2.

College of Hydrology and Water Resources, Hohai University, Nanjing, China.

The aim of this study was to access the Mn contamination in soil, forages, and animals. Heavy metal pollution is a matter of prime significance in natural environment. Through food chain, toxicity of heavy metals and their bioaccumulation potential are transferred into humans. Higher concentrations of metallic compounds are toxic to living organisms but these are essential to maintain body metabolism. Intake of food crops polluted with heavy metals is chief food chain channel for human exposure. Animals are exposed to heavy metal stress by the intake of richly contaminated food crops; those are chief part of food chain. Samples of soil, plant, animal blood, hair, and feces were collected to find contamination through wet digestion process in lab and metal analysis. Different forages were collected to study Mn content that was our major concern in this study. The present findings also emphasized on the assessment of bio-concentration factor (BCF). Other significant indices of mobility and pollution of metal were also calculated, i.e. pollution load index (PLI), daily intake of metal (DIM), health risk index (HRI), and enrichment factor (EF). The experimentation result showed different concentrations of metal in different seasons. The Mn concentration in forages was 20.01-28.29 mg/kg and in soil was 5.27-8.90 mg/kg. Soil samples showed higher level of (PLI) Pollution load index. Bio-concentration of MN was 2.59-4.21 mg/kg. It can be concluded that regular monitoring of the metal is essential to evaluate the contamination status. Mn contents were in the safe limits in soil and plants; however, its toxic level was observed in animals.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-14666-zDOI Listing
June 2021

Effects of Flower Extract and Its Active Constituent Isoorientin on Skin Moisturization via Regulating Involucrin Expression: In Vitro and Molecular Docking Studies.

Molecules 2021 04 30;26(9). Epub 2021 Apr 30.

College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon 21936, Korea.

Skin moisturization is very crucial for maintaining the flexibility, viscoelasticity, and differentiation of the epidermis and its deprivation causes several diseases from dry skin to dermatitis. , a miracle plant having diverse medicinal properties including skin moisturization effects. This study investigated for the first time the molecular mechanism targeting skin moisturization effects of the flower and its major active constituent. By treating human epidermal keratinocytes (HaCaT cells) with flower water extract (AFWE), we found that AFWE upregulated epidermal involucrin by activating the expression of protein kinase C, p38, and ERK 1/2. Additionally, it modulated filaggrin, increased aquaporin expression, and hyaluronan synthesis via a balanced regulation of HAS1 and HYAL1 protein. Similarly, it was able to protect UVB-induced photodamage. Western blot analysis, ELISA, and qRT- PCR were performed to evaluate various epidermal differentiation markers and moisturization-related factors on human epidermal keratinocytes (HaCaT cells). TLC and HPLC were used to detect and analyze the chemical constituents. Among them, we found that an active component of flower, isoorientin (IO) has a high binding affinity to all of its targeted proteins such as involucrin, PKC, P38, etc. through molecular docking assay. This study indicated that the flower and its active constituent, IO can be used as a prominent ingredient to enhance skin barrier function and improve its related pathologies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/molecules26092626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8125160PMC
April 2021

Neutropenic enterocolitis-induced sepsis and disseminated intravascular coagulation after chemotherapy: a case report.

BMC Womens Health 2021 05 3;21(1):187. Epub 2021 May 3.

Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Enyacho 89-1, Izumo, Shimane, 6938501, Japan.

Background: Neutropenic enterocolitis (NE) is a potentially life-threatening disease that primarily occurs in cancer patients treated with chemotherapy. NE has substantial morbidity and mortality, and its incidence has increased with the widespread use of chemotherapeutic agents such as taxanes, gemcitabine, and leucovorin in patients with lung, breast, gastric, and ovarian cancers. Sometimes NE can be a possible cause of death. Although, conservative approaches are often successful, there are currently no standardized treatment guidelines for NE and it is unclear when such strategies should be implemented. Therefore, we present this report to provide a greater insight into the possible treatment of NE.

Case Presentation: We report the case of a 72-year-old woman with endometrial cancer who was undergoing treatment for hypertension, obesity and diabetes mellitus. The patient initially developed paralytic ileus on the 6th postoperative day (POD) after surgery for endometrial serous carcinoma. Complete recovery was achieved after 4 days of fasting and fluid replacement therapy. On the 27th POD, she received the first cycle of combination chemotherapy consisting of paclitaxel and carboplatin. On day 5 of chemotherapy, she developed the systemic inflammatory response syndrome including febrile neutropenia and sepsis. She then developed disseminated intravascular coagulation (DIC) and septic shock. The patient was subsequently moved to the intensive care unit (ICU). Despite initiating the standard treatment for septic shock and DIC, her overall status worsened. It was assumed that gut distention had led to bowel damage, subsequently leading to bacterial translocation. Thus, she developed NE with severe DIC and septic shock. We decided to reduce the intestinal pressure using an ileus tube to suction the additional air and fluid, even though doing so had a risk of worsening her general condition. The inflammatory reaction subsided, and her general condition improved. The patient recovered after 18 days in the ICU and was discharged alive.

Conclusions: Herein, we describe a patient with suspected chemotherapy-associated NE. Our observations suggest that postoperative ileus may be one of the possible causes of NE. Patients who experience postoperative ileus must be carefully monitored while undergoing chemotherapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12905-021-01302-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091778PMC
May 2021

Transfer of metal element in soil plant chicken food chain: health risk assessment.

Environ Sci Pollut Res Int 2021 Apr 24. Epub 2021 Apr 24.

Department of Botany, University of Sargodha, Sargodha, Pakistan.

This investigation was done for the assurance of potassium amassing in four assortments of maize (grains, shoot and root), soil, and water and in seven tissues of chickens (kidney, liver, heart, bone, gizzard, breast meat). The analysis of variance showed significant differences for potassium concentration in water in all sources of water; however, the season and variety significantly influenced the quantity of potassium in cereals. The corn varieties MMRI, Sadaf, and Pearl behaved differently when treated with water from various sources. Water taken from sewage had a higher concentration of potassium compared to canal and groundwater that is why the maize plants irrigated with this water had a higher grouping. Data regarding potassium concentration in different body parts of chicken showed that season and treatment have a significant effect on the potassium concentration in chicken organs. The variety was non-significant for the potassium concentration only in the bone. Season × Variety interaction was only significant in blood, meat heart, and gizzard. Season × Treatment and Variety × Treatment interactions were significant in the heart, kidney, and gizzard. The potassium contents were higher in the chicken body parts that were reared on grains irrigated with sewage water as compared to other groups. The potassium contents were higher in the chicken meat (96.23 ± 0.00) reared on grains of the Pearl variety raised with the sewage water. In a nutshell, the irrigation of grains with sewage water led to accumulation of nutrients greater than those irrigated with ground or canal water.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-14021-2DOI Listing
April 2021

Phytochemicals against anti-diabetic complications: targeting the advanced glycation end product signaling pathway.

Arch Pharm Res 2021 Apr 9;44(4):378-401. Epub 2021 Apr 9.

College of Pharmacy, Gachon University, No. 191, Hambakmoero, Yeonsu-gu, 21936, Inchon, Korea.

The role of advanced glycation end products (AGEs) is not limited to diabetes and diabetes-related complications. There are multiple modulators, including the receptor for advanced glycation end products, high mobility group box 1, glyoxalase 1, nuclear factor-kappa B, tumor necrosis factor-α, chronic unpredictable stress, reactive oxygen species, and inflammatory cytokines, which interact with AGE signaling and control diabetes, modulating these interacting modulators. The progression of diabetes, as well as related complications, can be controlled and treated. Natural products rich in bioactive constituents can interact with AGEs and their related mediators through various signaling cascades, thereby controlling and preventing the progression of diabetes. This review provides a deeper assessment of the signaling pathway, interactions between phytochemicals and AGEs, and its mediators, to develop a multifold therapeutic approach to prevent and treat diabetes and its related complications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12272-021-01323-9DOI Listing
April 2021

Risk stratification of cardiac metastases using late gadolinium enhancement cardiovascular magnetic resonance: prognostic impact of hypo-enhancement evidenced tumor avascularity.

J Cardiovasc Magn Reson 2021 04 5;23(1):42. Epub 2021 Apr 5.

Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) is widely used to identify cardiac neoplasms, for which diagnosis is predicated on enhancement stemming from lesion vascularity: Impact of contrast-enhancement pattern on clinical outcomes is unknown. The objective of this study was to determine whether cardiac metastasis (C) enhancement pattern on LGE-CMR impacts prognosis, with focus on heterogeneous lesion enhancement as a marker of tumor avascularity.

Methods: Advanced (stage IV) systemic cancer patients with and without C matched (1:1) by cancer etiology underwent a standardized CMR protocol. C was identified via established LGE-CMR criteria based on lesion enhancement; enhancement pattern was further classified as heterogeneous (enhancing and non-enhancing components) or diffuse and assessed via quantitative (contrast-to-noise ratio (CNR); signal-to-noise ratio (SNR)) analyses. Embolic events and mortality were tested in relation to lesion location and contrast-enhancement pattern.

Results: 224 patients were studied, including 112 patients with C and unaffected (C -) controls matched for systemic cancer etiology/stage. C enhancement pattern varied (53% heterogeneous, 47% diffuse). Quantitative analyses were consistent with lesion classification; CNR was higher and SNR lower in heterogeneously enhancing C (p < 0.001)-paralleled by larger size based on linear dimensions (p < 0.05). Contrast-enhancement pattern did not vary based on lesion location (p = NS). Embolic events were similar between patients with diffuse and heterogeneous lesions (p = NS) but varied by location: Patients with right-sided lesions had threefold more pulmonary emboli (20% vs. 6%, p = 0.02); those with left-sided lesions had lower rates equivalent to controls (4% vs. 5%, p = 1.00). Mortality was higher among patients with C (hazard ratio [HR] = 1.64 [CI 1.17-2.29], p = 0.004) compared to controls, but varied by contrast-enhancement pattern: Diffusely enhancing C had equivalent mortality to controls (p = 0.21) whereas prognosis was worse with heterogeneous C (p = 0.005) and more strongly predicted by heterogeneous enhancement (HR = 1.97 [CI 1.23-3.15], p = 0.005) than lesion size (HR = 1.11 per 10 cm [CI 0.53-2.33], p = 0.79).

Conclusions: Contrast-enhancement pattern and location of C on CMR impacts prognosis. Embolic events vary by C location, with likelihood of PE greatest with right-sided lesions. Heterogeneous enhancement-a marker of tumor avascularity on LGE-CMR-is a novel marker of increased mortality risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12968-021-00727-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8020547PMC
April 2021

Ischemia-Mediated Dysfunction in Subpapillary Myocardium as a Marker of Functional Mitral Regurgitation.

JACC Cardiovasc Imaging 2021 Apr 17;14(4):826-839. Epub 2021 Mar 17.

Division of Cardiology, Weill Cornell Medicine, New York, New York, USA. Electronic address:

Objectives: The goal of this study was to test whether ischemia-mediated contractile dysfunction underlying the mitral valve affects functional mitral regurgitation (FMR) and the prognostic impact of FMR.

Background: FMR results from left ventricular (LV) remodeling, which can stem from myocardial tissue alterations. Stress cardiac magnetic resonance can assess ischemia and infarction in the left ventricle and papillary muscles; relative impact on FMR is uncertain.

Methods: Vasodilator stress cardiac magnetic resonance was performed in patients with known or suspected coronary artery disease at 7 sites. Images were centrally analyzed for MR etiology/severity, mitral apparatus remodeling, and papillary ischemia.

Results: A total of 8,631 patients (mean age 60.0 ± 14.1 years; 55% male) were studied. FMR was present in 27%, among whom 16% (n = 372) had advanced (moderate or severe) FMR. Patients with ischemia localized to subpapillary regions were more likely to have advanced FMR (p = 0.003); those with ischemia localized to other areas were not (p = 0.17). Ischemic/dysfunctional subpapillary myocardium (odds ratio: 1.24/10% subpapillary myocardium; confidence interval: 1.17 to 1.31; p < 0.001) was associated with advanced FMR controlling for infarction. Among a subgroup with (n = 372) and without (n = 744) advanced FMR matched (1:2) on infarct size/distribution, patients with advanced FMR had increased adverse mitral apparatus remodeling, paralleled by greater ischemic/dysfunctional subpapillary myocardium (p < 0.001). Although posteromedial papillary ischemia was more common with advanced FMR (p = 0.006), subpapillary ischemia with dysfunction remained associated (p < 0.001), adjusting for posteromedial papillary ischemia (p = 0.074). During follow-up (median 5.1 years), 1,473 deaths occurred in the overall cohort; advanced FMR conferred increased mortality risk (hazard ratio: 1.52; 95% confidence interval: 1.25 to 1.86; p < 0.001) controlling for left ventricular ejection fraction, infarction, and ischemia.

Conclusions: Ischemic and dysfunctional subpapillary myocardium provides a substrate for FMR, which predicts mortality independent of key mechanistic substrates.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2021.01.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8086776PMC
April 2021

Novel Echocardiographic Algorithm for Right Ventricular Mass Quantification: Cardiovascular Magnetic Resonance and Clinical Prognosis Validation.

J Am Soc Echocardiogr 2021 Mar 11. Epub 2021 Mar 11.

Division of Cardiology, Department of Medicine, Weill Cornell Medicine, New York, New York. Electronic address:

Background: Right ventricular hypertrophy (RVH) provides a key remodeling index alterable by pulmonary hypertension. Although echocardiography commonly integrates linear wall thickness and chamber dimensions to quantify left ventricular remodeling, the utility of an equivalent right ventricular (RV)-based approach is unknown.

Methods: This was a retrospective analysis of 200 patients undergoing transthoracic echocardiography and cardiac magnetic resonance (CMR) within 30 days (median = 3 days; interquartile range, 15 days), stratified by echocardiography-quantified pulmonary artery systolic pressure (<35, 35 to <55, 55 to <75, or ≥75 mm Hg). Echocardiographic assessment included RV linear dimensions in parasternal long-axis and apical four-chamber views and wall thicknesses in parasternal long-axis, four-chamber, and subcostal views. Subcostal wall thickness was integrated with chamber diameters to calculate RV mass, which was tested in relation to CMR-quantified RV mass and all-cause mortality.

Results: Echocardiography-based quantification of all linear dimensions was feasible in 95% of patients (190 of 200). RV wall thicknesses in all orientations increased in relation to pulmonary artery systolic pressure (P < .001) and was greater among patients with, versus those without, CMR-evidenced RVH (P < .001 for all). Correlations between echocardiography and CMR were greatest for RV basal diameter (r = 0.73), RV subcostal wall thickness (r = 0.71), and global RV mass (r = 0.82; P < .001 for all). Echocardiography-derived global RV mass cutoffs were established in a derivation cohort and tested in a validation cohort. Results demonstrated good sensitivity and specificity (75.5% and 74.0%, respectively) in relation to CMR-quantified RVH. During follow-up (median, 4.2 years), 18% of patients (n = 36) died. Echocardiography-evidenced RVH (hazard ratio, 1.98; 95% CI, 1.09-3.88; P = .048) conferred similar mortality risk compared with RVH on CMR (hazard ratio, 2.41; 95% CI, 1.22-4.78; P = .01).

Conclusions: Echocardiography-quantified RV parameters provide a robust index of RV afterload. Global RV mass calculated using a novel echocardiographic formula based on readily available linear indices yields good diagnostic performance for CMR-evidenced RVH and confers increased mortality risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.echo.2021.03.002DOI Listing
March 2021

Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer.

Diseases 2021 Feb 4;9(1). Epub 2021 Feb 4.

Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan.

Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes , , and ; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diseases9010014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7931088PMC
February 2021

Pregnancy by Assisted Reproductive Technology Is Associated with Shorter Telomere Length in Neonates.

Int J Mol Sci 2020 Dec 18;21(24). Epub 2020 Dec 18.

Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 693-8501, Japan.

Telomere length (TL) influences the development of lifestyle-related diseases, and neonatal TL may influence their prevalence. Various factors have been reported to affect neonatal TL. Although the fetus is exposed to multiple conditions in utero, the main factors affecting the shortening of neonatal TL are still not known. In this study, we sought to identify factors that influence fetal TL. A total of 578 mother-newborn pairs were included for TL analysis. TL was measured in genomic DNA extracted from cord blood samples using quantitative PCR. The clinical factors examined at enrollment included the following intrauterine environmental factors: maternal age, assisted reproductive technology (ART) used, body mass index (BMI), gestational diabetes mellitus (GDM), maternal stress, smoking, alcohol consumption, preterm delivery, small-for-gestational-age, neonatal sex, and placental weight. Univariate and multivariate regression analyses were used to verify the relationship between neonatal TL and these clinical factors. The median neonatal TL to single-copy gene ratio was 1.0. Pregnancy with ART was among the 11 factors associated with shorter neonatal TL. From multiple regression analysis, we determined that neonatal TL was significantly shorter for pregnancies in the ART group than in the other groups. We conclude that pregnancy with ART is associated with shorter neonatal TL.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms21249688DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7766074PMC
December 2020

Pathological findings in the endometrium after microwave endometrial ablation.

Sci Rep 2020 11 27;10(1):20766. Epub 2020 Nov 27.

Department of Obstetrics and Gynecology, Shimane University School of Medicine, Enyacho 89-1, Izumo, Shimane, 6938501, Japan.

The acceptance of MEA in Japan is well demand due to its outstanding effectiveness and safety. Infrequently, a repeat MEA or hysterectomy is needed for recurrent menorrhagia in case of failure ablation. The reasons of recurrent menorrhagia subsequent MEA treatment are unclear. The objective of current study is to identify the possible causes of menorrhagia repetition following MEA, together with the observation of histological changes in the endometrium due to this treatment compared with normal cycling endometrial tissue. A total of 170 patients, 8 (4.7%) of them carried out hysterectomy after 16.8 months (range, 2-29 months) of MEA treatment. Normal (n = 47) and MEA (n = 8) treated paraffin embedded endometrial tissue were prepared for hematoxylin and eosin (H&E) and immunostaining study to recognize the histological changes in the endometrium as a result of MEA treatment. The histological features observed increased tubal metaplasia (TM) including negative expression of the estrogen receptor (ER) and progesterone receptor (PR) in the endometrium subsequent MEA treatment. Increased TM together with the absence of ER and PR expression might be a reasonable explanation for repetition menorrhagia in cases of failure ablation. Further study is required to clarify the molecular mechanisms of tubal metaplasia and the expression loss of hormone receptor in the endometrium as a result of MEA treatment. Current studies propose that low dose estrogen-progestin may not be effective with recurrent menorrhagia patient's due to the inadequacy of hormone receptor expression in the endometrium following MEA.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41598-020-77594-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7695731PMC
November 2020

Prognostic Utility of Right Ventricular Remodeling Over Conventional Risk Stratification in Patients With COVID-19.

J Am Coll Cardiol 2020 10;76(17):1965-1977

Division of Cardiology, Weill Cornell Medicine, New York, New York; Department of Radiology, Weill Cornell Medicine, New York, New York.

Background: Coronavirus disease 2019 (COVID-19) is a growing pandemic that confers augmented risk for right ventricular (RV) dysfunction and dilation; the prognostic utility of adverse RV remodeling in COVID-19 patients is uncertain.

Objectives: The purpose of this study was to test whether adverse RV remodeling (dysfunction/dilation) predicts COVID-19 prognosis independent of clinical and biomarker risk stratification.

Methods: Consecutive COVID-19 inpatients undergoing clinical transthoracic echocardiography at 3 New York City hospitals were studied; images were analyzed by a central core laboratory blinded to clinical and biomarker data.

Results: In total, 510 patients (age 64 ± 14 years, 66% men) were studied; RV dilation and dysfunction were present in 35% and 15%, respectively. RV dysfunction increased stepwise in relation to RV chamber size (p = 0.007). During inpatient follow-up (median 20 days), 77% of patients had a study-related endpoint (death 32%, discharge 45%). RV dysfunction (hazard ratio [HR]: 2.57; 95% confidence interval [CI]: 1.49 to 4.43; p = 0.001) and dilation (HR: 1.43; 95% CI: 1.05 to 1.96; p = 0.02) each independently conferred mortality risk. Patients without adverse RV remodeling were more likely to survive to hospital discharge (HR: 1.39; 95% CI: 1.01 to 1.90; p = 0.041). RV indices provided additional risk stratification beyond biomarker strata; risk for death was greatest among patients with adverse RV remodeling and positive biomarkers and was lesser among patients with isolated biomarker elevations (p ≤ 0.001). In multivariate analysis, adverse RV remodeling conferred a >2-fold increase in mortality risk, which remained significant (p < 0.01) when controlling for age and biomarker elevations; the predictive value of adverse RV remodeling was similar irrespective of whether analyses were performed using troponin, D-dimer, or ferritin.

Conclusions: Adverse RV remodeling predicts mortality in COVID-19 independent of standard clinical and biomarker-based assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jacc.2020.08.066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7572068PMC
October 2020

Left Atrial Strain Impairment Precedes Geometric Remodeling as a Marker of Post-Myocardial Infarction Diastolic Dysfunction.

JACC Cardiovasc Imaging 2020 10 19;13(10):2099-2113. Epub 2020 Aug 19.

Greenberg Cardiology Division, Department of Medicine, Weill Cornell Medicine, New York, New York; Department of Radiology, Memorial Sloan Kettering Cancer Center, New York, New York.

Objectives: The aims of this study were to test the magnitude of agreement between echocardiography (echo)- and cardiac magnetic resonance (CMR)-derived left atrial (LA) strain and to study their relative diagnostic performance in discriminating diastolic dysfunction (DD) and predicting atrial fibrillation (AF).

Backgrounds: Peak atrial longitudinal strain (PALS) is a novel performance index. Utility of echo-quantified LA strain has yet to be prospectively tested in relation to current DD guidelines or compared to CMR.

Methods: The study population comprised 257 post-myocardial infarction (MI) patients undergoing echo and CMR, including prospective derivation (n = 157) and clinical validation (n = 100) cohorts. DD was graded on echo using established consensus guidelines blinded to strain results.

Results: PALS on both echo and CMR was nearly 2-fold lower among patients with versus no DD (p < 0.001) and was significantly different in those with mild versus no DD (p < 0.01). In contrast, LA geometric parameters including echo- and CMR-derived volumes were significantly different between advanced versus no DD groups (p < 0.001) but not between groups with mild versus no DD (all p > 0.05). Echo and CMR PALS yielded small differences irrespective of orientation and similar diagnostic performance for DD in the derivation (area under the curve [AUC]: 0.70 to 0.78) and validation (AUC: 0.75 to 0.78) cohorts. Impaired PALS on both modalities was independently associated with MI size (p < 0.001). During 4.4 ± 3.8 years of follow-up in the derivation cohort, 8% developed AF. Both 2-chamber echo- and CMR-derived PALS stratified arrhythmic risk (p = 0.004 and p = 0.02, respectively), including a 4-fold difference among patients in the lowest versus remainder of quartiles of echo-derived PALS (24% vs. 6%). Similarly, echo and CMR PALS were lower (both p < 0.05) among patients with subsequent heart failure hospitalizations.

Conclusions: Echo-derived PALS parallels results of CMR, yields incremental diagnostic utility versus LA geometry for stratifying presence and severity of DD, and improves prediction of AF and congestive heart failure after MI.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jcmg.2020.05.041DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554167PMC
October 2020

Comparison between bidirectional Stratafix barbed suture and conventional suture in laparoscopic myomectomy: a retrospective study.

BMC Womens Health 2020 08 5;20(1):164. Epub 2020 Aug 5.

Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Enyacho 89-1, Izumo, Shimane, 6938501, Japan.

Background: Laparoscopic myomectomy (LM) is one of the techniques feasible for the treatment of intramural myoma. This technique is reported to be difficult when large fibroids are involved because of excessive blood loss during surgery. Skillful and fast suturing appears to be associated with reduced blood loss during LM. In this study we compared the surgical outcomes of using bidirectional Stratafix® barbed suture versus conventional suture during LM.

Methods: This retrospective study included all patients who underwent LM for the treatment of intramural myoma in our institution between 2015 and 2020. The patients were divided into 2 groups according to the technique of suturing during LM: Group 1 comprised patients in whom Stratafix® barbed suture was used (n = 29), and group 2 comprised those in whom conventional suture was used (n = 15). Data of patient age, myoma size, the number of myoma nodes, hemoglobin levels, total operation time, total suturing time, and blood loss during surgery were compared between the 2 groups.

Results: No significant differences in age (p = 0.463) or myoma size (P = 0.373) were observed between the 2 groups. Operation time (P = 0.0104), suturing time (P = 0.007), and blood loss (P = 0.0375) during surgery were significantly less with Stratafix® barbed suture than with conventional suture. No patient required intraoperative transfusion or conversion to laparotomy.

Conclusion: The use of bidirectional barbed suture reduces operation time, suturing time, and blood loss. As these new sutures have barbs, no knot-tying is required; thus, continuous suturing becomes very simple and maintaining hemostasis is easy. Unskilled gynecological surgeons who apply this suture technique can also perform LM easily. As the bidirectional barbed suture has multiple points of fixation, this suture technique can reapproximate tissue securely, which reduces the chances of reoperation because of proper suture knotting. Therefore, bidirectional Stratafix® barbed sutures could be an optimal and efficient alternative to conventional sutures for use by gynecological surgeons in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12905-020-01030-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7405452PMC
August 2020

Chemical composition and in vitro antioxidant properties of water-soluble extracts obtained from Bangladesh vegetables.

J Food Biochem 2021 Mar 5;45(3):e13357. Epub 2020 Jul 5.

Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB, Canada.

The aim of this study was to evaluate the nutritional value and antioxidant properties of aqueous extracts of some Bangladesh vegetables using fruits of ash gourd, bitter gourd, brinjal, okra, ridge gourd, snake gourd, and leaves of Indian spinach, kangkong, and stem amaranth. Proximate composition showed that the dried extracts were composed mainly of crude protein (14.6%-46.7%) and non-fibre carbohydrates (26.4%-53.5%). With the exception of stem amaranth, all the extracts had >40% DPPH radical scavenging ability at 0.5 mg/ml. In contrast metal chelation was lower, except in Indian spinach with ~46%. The ferric reducing antioxidant power (FRAP) was highest for the kangkong (10.9 mM Fe reduced), which is similar to the 9.9 mM for butylated hydroxytoluene (BHT). All the extracts suppressed linoleic acid oxidation better than BHT within the first 5 days of the incubation period. We conclude that the Indian spinach, kangkong, and okra could be considered as the most promising sources of antioxidant compounds. PRACTICAL APPLICATIONS: Vegetables are commonly consumed as part of a regular diet but the high water and fiber contents usually mean that large quantities are required to provide long-term health benefits. Therefore, in this work, aqueous extracts of nine Bangladesh vegetables were prepared to provide a more concentrated form of nutrients and bioactive compounds. The extracts had strong nutritional value based on the high contents of crude protein, potassium, iron, and non-fibre carbohydrates. The high content of polyphenolic compounds in the extracts can also provide health benefits, which was demonstrated through strong free radical scavenging, metal chelation, ferric iron reduction, and inhibition of linoleic acid oxidation. These vegetable extracts have the potential to be used as sources of bioactive compounds to prevent or treat non-communicable diseases that are associated with high oxidative stress.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jfbc.13357DOI Listing
March 2021

Inhibitory Activities of Polyphenolic Extracts of Bangladeshi Vegetables against α-Amylase, α-Glucosidase, Pancreatic Lipase, Renin, and Angiotensin-Converting Enzyme.

Foods 2020 Jun 29;9(7). Epub 2020 Jun 29.

Department of Food and Human Nutritional Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.

The aim of the study was to determine the in vitro enzyme inhibition activities of aqueous polyphenolic extracts of nine popular Bangladeshi vegetables, namely ash gourd, bitter gourd, brinjal, Indian spinach, kangkong, okra, ridge gourd, snake gourd, and stem amaranth. Polyphenolic glycosides were the major compounds present in the extracts. Inhibition of α-amylase (up to 100% at 1 mg/mL) was stronger than α-glucosidase inhibition (up to 70.78% at 10 mg/mL). The Indian spinach extract was the strongest inhibitor of pancreatic lipase activity (IC = 276.77 µg/mL), which was significantly better than that of orlistat (381.16 µg/mL), a drug. Ash gourd (76.51%), brinjal (72.48%), and snake gourd (66.82%) extracts were the most effective inhibitors of angiotensin-converting enzyme (ACE), an enzyme whose excessive activities have been associated with hypertension. Brinjal also had a significantly higher renin-inhibitory activity than the other vegetable extracts. We conclude that the vegetable extracts may have the ability to reduce enzyme activities that have been associated with hyperglycemia, hyperlipidemia, and hypertension.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/foods9070844DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7404479PMC
June 2020

Positive Modulation of SK Channel Impedes Neuron-Specific Cytoskeletal Organization and Maturation.

Dev Neurosci 2020 24;42(1):59-71. Epub 2020 Jun 24.

Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, Louisiana, USA,

N-methyl-D-aspartate receptor (NMDAR) modulates the structural plasticity of dendritic spines by impacting cytoskeletal organization and kinase signaling. In the developing nervous system, activation of NMDAR is pertinent for neuronal migration, neurite differentiation, and cellular organization. Given that small conductance potassium channels (SK2/3) repress NMDAR ionotropic signaling, this study highlights the impact of neonatal SK channel potentiation on adult cortical and hippocampal organization. Neonatal SK channel potentiation was performed by one injection of SK2/3 agonist (CyPPA) into the pallium of mice on postnatal day 2 (P2). When the animals reached adulthood (P55), the hippocampus and cortex were examined to assess neuronal maturation, lamination, and the distribution of synaptic cytoskeletal proteins. Immunodetection of neuronal markers in the brain of P2-treated P55 mice revealed the presence of immature neurons in the upper cortical layers (layers II-IV) and CA1 (hippocampus). Also, layer-dependent cortical-cell density was attenuated due to the ectopic localization of mature (NeuN+) and immature (Doublecortin+ [DCX+]) neurons in cortical layers II-IV. Similarly, the decreased count of NeuN+ neurons in the CA1 is accompanied by an increase in the number of immature DCX+ neurons. Ectopic localization of neurons in the upper cortex and CA1 caused the dramatic expression of neuron-specific cytoskeletal proteins. In line with this, structural deformity of neuronal projections and the loss of postsynaptic densities suggests that postsynaptic integrity is compromised in the SK2/3+ brain. From these results, we deduced that SK channel activity in the developing brain likely impacts neuronal maturation through its effects on cytoskeletal formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1159/000507989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7486235PMC
June 2020

Genetic polymorphisms in DNA repair genes XRCC1 and 3 are associated with increased risk of breast cancer in Bangladeshi population.

Breast Cancer Res Treat 2020 Aug 19;182(3):739-750. Epub 2020 Jun 19.

Pharmacy Discipline, Life Science School, Khulna University, Khulna, 9208, Bangladesh.

Background: Genetic polymorphisms in DNA repair genes, XRCC1 (Arg399Gln) and XRCC3 (Thr241Met), may affect their DNA repair capacity leading to individual variation in breast cancer susceptibility among Bangladeshi females.

Methods: The case-control study comprised 121 breast cancer patients and 133 healthy controls. Genomic DNA isolated from peripheral blood was genotyped for target SNPs using PCR-RFLP method.

Results: For XRCC1, heterozygous Arg/Gln and homozygous Gln/Gln genotypes showed 1.78-fold (95% CI 1.0084 to 3.1442, p = 0.0467) and 2.41-fold (95% CI 1.0354 to 5.5914, p = 0.0413) increased risk of breast cancer, respectively, when compared with Arg/Arg genotype. The presence of any XRCC1 Gln showed association with 1.93-fold increased risk. The variant Gln allele was associated with increased risk of breast cancer (95% CI 1.1885 to 2.6805, p = 0.0052). For XRCC3, Thr/Met heterozygous and combined Thr/Met + Met/Met genotypes were associated with 1.85-fold (95% CI 1.0815 to 3.1834, p = 0.0248) and 1.89-fold (95% CI 1.1199 to 3.1908, p = 0.0171) higher risk, respectively, compared to Thr/Thr genotypes. The variant Met allele showed significant association with increased breast cancer susceptibility. Among cases genotype frequencies were significantly different in patients with age 55 or above, and with menopause and diabetes.

Conclusion: XRCC1 (Arg399Gln) and XRCC3 (Thr241Met) polymorphisms may be associated with increased breast cancer risk in Bangladeshi females.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10549-020-05738-8DOI Listing
August 2020

Mucinous borderline ovarian tumors with BRAF mutation may have low risk for progression to invasive carcinomas.

Arch Gynecol Obstet 2020 08 16;302(2):487-495. Epub 2020 Jun 16.

Department of Obstetrics and Gynecology, Shimane University School of Medicine, Enyacho 89-1, Izumo, Shimane, 6938501, Japan.

Purpose: Mucinous ovarian carcinomas (MOCs) are relatively rare. It has been proposed that a subset of mucinous cystadenomas (MCAs) may progress to mucinous borderline tumors (MBTs), and then to MOCs. KRAS is the predominantly mutated gene in MOC; however, other associated mutations and the mechanism underlying carcinogenesis in MOC remain unclear. Here, we assessed molecular genetic alterations in mucinous ovarian tumors and constructed mutation profiles.

Methods: Using the Sanger sequencing method, we assessed genetic mutations (KRAS, BRAF, TP53, and PIK3CA) in 16 cases of MOC, 10 cases of MBT, and 12 cases of MCA.

Results: Among MOC cases, the prevalence of G12D and G13D KRAS mutations was 43.8% (7/16). No MOC cases showed V600E BRAF and TP53 mutations. Among MBT cases, the prevalence of G12D KRAS mutation was 20.0% (2/10), those of TP53 and PIK3CA mutations were nil, and that of V600E BRAF mutation was 40% (4/10). None of the genetic mutations assessed were detected among MCA cases.

Conclusion: These results suggest that MBT with V600E BRAF mutation may rarely progress to MOC, while MBT with G12D or G13D KRAS mutation may more commonly progress to MOC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-020-05638-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7321901PMC
August 2020

Prognostic Value of Peripheral Blood Lymphocyte Telomere Length in Gynecologic Malignant Tumors.

Cancers (Basel) 2020 Jun 4;12(6). Epub 2020 Jun 4.

Department of Obstetrics and Gynecology, Faculty of Medicine, Shimane University, Izumo 693-8501, Japan.

Lymphocyte telomere length is strongly correlated with patient prognosis in several malignant tumor types and is thought to be related to tumor immunity. However, this correlation has not been studied in gynecological cancers. We determined the prognostic significance of peripheral blood lymphocyte telomere length in gynecologic cancers. Telomere length of lymphocytes from patients with gynecological malignant tumors (ovarian cancer (OC), = 72; cervical cancer (CC), = 63; endometrial cancer (EC), = 87) was examined by quantitative reverse-transcription PCR of isolated mononuclear cells. Kaplan-Meier and Cox proportional hazard analyses were used to determine the association between lymphocyte telomere length and clinicopathological factors. The overall survival (OS) and progression-free survival (PFS) of patients were based on the dichotomized lymphocyte telomere length using the median as a threshold (OC: 0.75, CC: 1.94, and EC: 1.09). A short telomere length was significantly correlated with residual tumors (≥1 cm) in OC and with advanced stage (III and IV) of CC. In OC and CC, patients with shorter relative lymphocyte telomere length (RLT) had significantly poorer OS and PFS than patients with longer RLT ( = 0.002, = 0.003, and = 0.001, = 0.001, respectively). However, in EC, RLT was not significantly associated with OS or PFS ( = 0.567 and = 0.304, log-rank test). Multivariate analysis showed that shorter RLT was a significant independent prognostic factor of PFS and OS for OC ( = 0.03 and = 0.04, respectively) and CC ( = 0.02 and = 0.03, respectively). Patients with OC and CC with shorter lymphocyte telomeres have significantly reduced survival; therefore, the peripheral blood lymphocyte telomere length is a prognostic biomarker in OC and CC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/cancers12061469DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7352644PMC
June 2020

High PD-1 expression level is associated with an unfavorable prognosis in patients with cervical adenocarcinoma.

Arch Gynecol Obstet 2020 07 20;302(1):209-218. Epub 2020 May 20.

Department of Obstetrics and Gynecology, Shimane University Faculty of Medicine, Enyacho 89-1, Izumo, Shimane, 6938501, Japan.

Purpose: The effectiveness of immunotherapy for cervical adenocarcinoma (CA) has not been demonstrated yet. Programmed cell death 1 (PD-1), programmed cell death-ligand 1 (PD-L1), and CD8 may be used as biomarkers of response to immune therapy in CA patients. In the present study, we aimed to investigate whether the expression levels of PD-1, PD-L1, and CD8 can predict the prognosis of patients with CA and their response to immune checkpoint inhibition therapy.

Methods: In the present study, the clinical stage for all 82 patients with cervical adenocarcinoma was classified according to the guidelines of the International Federation of Gynecology and Obstetrics (FIGO); there were 5, 48, 5, 14, 8, and 2 patients with stage IA, IB, IIA, IIB, IIIB, and IVB disease, respectively. The levels of PD-1, PD-L1, and CD8 were analyzed by the immunohistochemical analysis of the formalin-fixed paraffin-embedded tumor samples. The correlation between the expression levels and patient prognosis was analyzed using the Kaplan-Meier method and univariate and multivariate Cox proportional hazard regression models.

Results: We observed a significant inverse correlation between the expression of PD-1 and CD8 (p = 0.001, chi-square test). We also found a significant inverse correlation between the expression of PD-L1 and CD8 (p = 0.027). The overall survival and progression-free survival rates were significantly worse in patients with positive PD-1 expression (p = 0.031; p = 0.087, respectively).

Conclusion: Our results suggest that a high PD-1 expression is associated with a poor prognosis in patients with CA. Further research is necessary to identify the molecular mechanisms that mediate this association.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00404-020-05589-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7266794PMC
July 2020

Carrier Mice Exhibit Alterations in Neural pIGF-1Rβ and Related Kinase Expression.

Front Cell Neurosci 2020 5;14:94. Epub 2020 May 5.

Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.

Mutation of the gene underlies a broad range of developmental neuropsychiatric defects, including schizophrenia, depression, and bipolar disorder. The pathophysiological phenotypes linked with mutation are due to the truncation of the DISC1 primary protein structure. This leads to a defective post-synaptic scaffolding and kinase-GSK3β and Erk1/2-signaling. As a result, synaptic function and maintenance are significantly impaired in the mutant brain. Among several other pathways, GSK3β and Erk1/2 are involved in insulin-like growth factor 1 receptor (IGF-1Rβ) kinase signaling. Although mutation alters these kinases, it is unclear if the mutation impacts IGF-1R expression and activity in the brain. Here, we demonstrate that the expression of active IGF-1Rβ (pIGF-1Rβ) is altered in the hippocampus and prefrontal cortex (PFC) of mutant mice and vary with the dose of the mutation (homozygous and heterozygous). The expression of pIGF-1Rβ decreased significantly in 129S () brains. In contrast, 129S:B6 () brains were characterized by an increase in pIGF-1Rβ when compared with the C57BL/6 () level. The decrease in pIGF-1Rβ level for the 129S brains was accompanied by the loss of Akt activity (S473 pAkt) and decreased Ser9 phosphorylation of GSK3β (increased basal GSK3β). Additionally, hippocampal and cortical pErk1/2 activity increased in the 129S hippocampus and cortex. Although 129S:B6 recorded alterations in pIGF-1Rβ-pAkt-GSK3β (like 129S), there was no observable change in pErk1/2 activity for the heterozygote () mutant. In addition to GSK3β inhibition, we conclude that pIGF-1R, pAkt, and pErk1/2 are potential targets in mutant brain. On the other hand, pIGF-1R and pAkt can be further explored in brain.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fncel.2020.00094DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7214624PMC
May 2020

Development of novel machine learning model for right ventricular quantification on echocardiography-A multimodality validation study.

Echocardiography 2020 05 12;37(5):688-697. Epub 2020 May 12.

Greenberg Cardiology Division, Department of Medicine, Weill Cornell Medicine, New York, NY, USA.

Purpose: Echocardiography (echo) is widely used for right ventricular (RV) assessment. Current techniques for RV evaluation require additional imaging and manual analysis; machine learning (ML) approaches have the potential to provide efficient, fully automated quantification of RV function.

Methods: An automated ML model was developed to track the tricuspid annulus on echo using a convolutional neural network approach. The model was trained using 7791 image frames, and automated linear and circumferential indices quantifying annular displacement were generated. Automated indices were compared to an independent reference of cardiac magnetic resonance (CMR) defined RV dysfunction (RVEF < 50%).

Results: A total of 101 patients prospectively underwent echo and CMR: Fully automated annular tracking was uniformly successful; analyses entailed minimal processing time (<1 second for all) and no user editing. Findings demonstrate all automated annular shortening indices to be lower among patients with CMR-quantified RV dysfunction (all P < .001). Magnitude of ML annular displacement decreased stepwise in relation to population-based tertiles of TAPSE, with similar results when ML analyses were localized to the septal or lateral annulus (all P ≤ .001). Automated segmentation techniques provided good diagnostic performance (AUC 0.69-0.73) in relation to CMR reference and compared to conventional RV indices (TAPSE and S') with high negative predictive value (NPV 84%-87% vs 83%-88%). Reproducibility was higher for ML algorithm as compared to manual segmentation with zero inter- and intra-observer variability and ICC 1.0 (manual ICC: 0.87-0.91).

Conclusions: This study provides an initial validation of a deep learning system for RV assessment using automated tracking of the tricuspid annulus.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/echo.14674DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383774PMC
May 2020

Expression of Behavioral Phenotypes in Genetic and Environmental Mouse Models of Schizophrenia.

Front Behav Neurosci 2020 28;14:29. Epub 2020 Feb 28.

Neural Systems Laboratory, Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.

Schizophrenia is a neuropsychiatric disorder characterized by multifactorial etiology involving complex interactions among genetic and environmental factors. "Multiple-hit" models of the disorder can explain its variable incidence and prevalence in related individuals. Hence, there is a dire need to understand these interactions in the emergence of schizophrenia. To test these factors in the emergence of schizophrenia-like behaviors, we employed a genetic mouse model of the disorder (harboring the DISC1 mutation) along with various environmental insults, such as early life stress (maternal separation of pups) and/or pharmacological interventions (ketamine injections). When assessed on a battery of behavioral tests, we found that environmental interventions affect the severity of behavioral phenotypes in terms of increased negative behavior, as shown by reduced mobility in the forced swim and tail suspension tests, and changes to positive and cognitive symptoms, such as increased locomotion and disrupted PPI along with reduced working memory, respectively. Among the various interventions, the genetic mutation had the most profound effect on behavioral aberrations, followed by an environmental intervention by ketamine injections and ketamine-injected animals that were maternally separated during early postnatal days. We conclude that although environmental factors increased the prevalence of aberrant behavioral phenotypes, genetic background is still the predominant influence on phenotypic alterations in these mouse models of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnbeh.2020.00029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7058961PMC
February 2020

Prosthetic aortic graft replacement of the ascending thoracic aorta alters biomechanics of the native descending aorta as assessed by transthoracic echocardiography.

PLoS One 2020 12;15(3):e0230208. Epub 2020 Mar 12.

Department of Medicine (Cardiology), Weill Cornell Medicine, New York, New York, United States of America.

Introduction: In patients with ascending aortic (AA) aneurysms, prosthetic graft replacement yields benefit but risk for complications in the descending aorta persists. Longitudinal impact of AA grafts on native descending aortic physiology is poorly understood.

Methods: Transthoracic echocardiograms (echo) in patients undergoing AA elective surgical grafting were analyzed: Descending aortic deformation indices included global circumferential strain (GCS), time to peak (TTP) strain, and fractional area change (FAC). Computed tomography (CT) was used to assess aortic wall thickness and calcification.

Results: 46 patients undergoing AA grafting were studied; 65% had congenital or genetically-associated AA (30% bicuspid valve, 22% Marfan, 13% other): After grafting (6.4±7.5 months), native descending aortic distension increased, irrespective of whether assessed based on circumferential strain or area-based methods (both p<0.001). Increased distensibility paralleled altered kinetics, as evidenced by decreased time to peak strain (p = 0.01) and increased velocity (p = 0.002). Augmented distensibility and flow velocity occurred despite similar pre- and post-graft blood pressure and medications (all p = NS), and was independent of pre-surgical aortic regurgitation or change in left ventricular stroke volume (both p = NS). Magnitude of change in GCS and FAC was 5-10 fold greater among patients with congenital or genetically associated AA vs. degenerative AA (p<0.001), paralleling larger descending aortic size, greater wall thickness, and higher prevalence of calcific atherosclerotic plaque in the degenerative group (all p<0.05). In multivariate analysis, congenital/genetically associated AA etiology conferred a 4-fold increment in magnitude of augmented native descending aortic strain after proximal grafting (B = 4.19 [CI 1.6, 6.8]; p = 0.002) independent of age and descending aortic size.

Conclusions: Prosthetic graft replacement of the ascending aorta increases magnitude and rapidity of distal aortic distension. Graft effects are greatest with congenital or genetically associated AA, providing a potential mechanism for increased energy transmission to the native descending aorta and adverse post-surgical aortic remodeling.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0230208PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7067394PMC
June 2020

Molecular docking based virtual screening of the breast cancer target NUDT5.

Bioinformation 2019 5;15(11):784-789. Epub 2019 Dec 5.

Department of Biotechnology and Genetic Engineering, Faculty of Science, Noakhali Science and Technology University, Noakhali-3814.

Breast cancer affects one in eight women in Bangladesh and is the most common cancer among women in South Asia next to skin cancer. NUDT5 are nucleotide-metabolizing enzymes (NUDIX hydrolases) linked with the ADP ribose and 8-oxo-guanine metabolism. It is known to be associated with the hormone dependent gene regulation and proliferation in breast cancer cells. It blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in this context. We describe the structure based binding features of a lead compound (7-[[5-(3, 4-dichlorophenyl)-1,3,4-oxadiazol-2-yl]methyl]-1,3-dimethyl-8piperazin-1yl-purine-2,6-dione-CHCNO) with NUDT5 for further in vitro and in vivo validation. It is a promising inhibitor for blocking NUDT5 activity. Thus, structure based virtual screening is used to identify a potential therapeutic inhibitor for NUDT5.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.6026/97320630015784DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936656PMC
December 2019

High Frequency of Mutations in Low-Grade Serous Ovarian Carcinomas of Japanese Patients.

Diagnostics (Basel) 2019 Dec 27;10(1). Epub 2019 Dec 27.

Department of Obstetrics and Gynecology, Shimane University School of Medicine, Izumo 6938501, Japan.

The frequency of mutations associated with low-grade serous ovarian carcinoma (LGSC)/serous borderline tumors (SBTs) in Japan is unknown. We aimed to identify genetic variations in , , , and in LGSC/SBT/serous cystadenomas (SCAs) in a Japanese population. We performed a mutation analysis (by Sanger sequencing) of 33 cases of LGSC/SBT/SCA and 4 cases of LGSC with synchronous SBTs using microdissected paraffin-embedded sections. Immunohistochemistry of p53 and ARID1A was also performed. The frequency of oncogenic mutations in was 60.0% (6/10) in LGSCs, 63.6% (7/11) in SBTs, and 8.3% (1/12) in SCAs. All cases harbored wild-type . The frequency of mutations was 20.0% (2/10) in LGSCs, whereas all SBTs and SCAs harbored the wild-type allele. The frequency of mutations was 30.0% (3/10) in LGSCs, 0.0% (0/11) in SBTs, and 16.7% (2/12) in SCAs. ARID1A staining was positive in all cases. p53 staining was positive in 0% (0/10) LGSCs, 9.1% (1/11) SBTs, and 0.0% (0/12) SCAs. One LGSC case had two mutations (G1633A and G3149A) in both LGSC and SBT lesions, but a mutation was detected only in an LGSC lesion. These results suggest that, compared with the values in Western populations (16-54%), the mutation frequency in LGSCs/SBTs is lower and that of mutations in LGSCs/SBTs is much higher in Japanese populations. Therefore, the main carcinogenesis signaling pathways may be different between Japanese and Western LGSCs. Molecular therapies targeting the PIK3CA/AKT pathway may be effective in LGSCs in Japan.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics10010013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7168240PMC
December 2019

Transcatheter MitraClip repair alters mitral annular geometry - device induced annular remodeling on three-dimensional echocardiography predicts therapeutic response.

Cardiovasc Ultrasound 2019 Dec 26;17(1):31. Epub 2019 Dec 26.

Department of Medicine (Cardiology), Weill Cornell Medicine, 525 East 68th Street, New York, NY, 10021, USA.

Background: Echocardiography (echo) is widely used to guide therapeutic decision-making for patients being considered for MitraClip. Relative utility of two- (2D) and three-dimensional (3D) echo predictors of MitraClip response, and impact of MitraClip on mitral annular geometry, are uncertain.

Methods: The study population comprised patients with advanced (> moderate) MR undergoing MitraClip. Mitral annular geometry was quantified on pre-procedural 2D transthoracic echocardiography (TTE) and intra-procedural 3D transesophageal echocardiography (TEE); 3D TEE was used to measure MitraClip induced changes in annular geometry. Optimal MitraClip response was defined as ≤mild MR on follow-up (mean 2.7 ± 2.5 months) post-procedure TTE.

Results: Eighty patients with advanced MR underwent MitraClip; 41% had optimal response (≤mild MR). Responders had smaller pre-procedural global left ventricular (LV) end-diastolic size and mitral annular diameter on 2D TTE (both p ≤ 0.01), paralleling smaller annular area and circumference on 3D TEE (both p = 0.001). Mitral annular size yielded good diagnostic performance for optimal MitraClip response (AUC 0.72, p < 0.01). In multivariate analysis, sub-optimal MitraClip response was independently associated with larger pre-procedural mitral annular area on 3D TEE (OR 1.93 per cm/m [CI 1.19-3.13], p = 0.007) and global LV end-diastolic volume on 2D TTE (OR 1.29 per 10 ml/m [CI 1.02-1.63], p = 0.03). Substitution of 2D TTE derived mitral annular diameter for 3D TEE data demonstrated a lesser association between pre-procedural annular size (OR 5.36 per cm/m [CI 0.95-30.19], p = 0.06) and sub-optimal MitraClip response. Matched pre- and post-procedural TEE analyses demonstrated MitraClip to acutely decrease mitral annular area and circumference (all p < 0.001) as well as mitral tenting height, area, and volume (all p < 0.05): Magnitude of MitraClip induced reductions in mitral annular circumference on intra-procedural 3D TEE was greater among patients with, compared to those without, sub-optimal MitraClip response (>mild MR) on followup TTE (p = 0.017); greater magnitude of device-induced annular reduction remained associated with sub-optimal MitraClip response even when normalized for pre-procedure annular circumference (p = 0.028).

Conclusions: MitraClip alters mitral annular geometry as quantified by intra-procedural 3D TEE. Pre-procedural mitral annular dilation and magnitude of device-induced reduction in mitral annular size on 3D TEE are each associated with sub-optimal therapeutic response to MitraClip.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12947-019-0181-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6933704PMC
December 2019

Sarcopenic Factors May Have No Impact on Outcomes in Ovarian Cancer Patients.

Diagnostics (Basel) 2019 Nov 28;9(4). Epub 2019 Nov 28.

Department of Obstetrics and Gynecology, Shimane University, 89-1 Enya, Izumo, Shimane 693-8501, Japan.

Although the prognostic value of sarcopenic factors, such as loss of muscle mass and quality, have been widely reported in patients with cancer during the last decade, the value in those with ovarian cancer remains unclear. Therefore, this study evaluated the prognostic impact of sarcopenic factors in patients with ovarian cancer. We retrospectively evaluated the data of 94 ovarian cancer patients who underwent surgery and chemotherapy at the Shimane University Hospital between March 2006 and 2013. Preoperative computed tomography scan at the level of the third lumbar vertebra was used to evaluate skeletal muscle volume and quality based on the skeletal muscle index (SMI) and intramuscular adipose tissue content (IMAC), respectively. The impact of preoperative SMI and IMAC on outcomes was subsequently investigated. Low SMI and high IMAC were not significantly associated with disease-free survival ( = 0.329 and = 0.3370, respectively) or poor overall survival ( = 0.921 and = 0.988, respectively). Neither preoperative low muscle volume nor low muscle quality was a poor prognostic factor in ovarian cancer.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/diagnostics9040206DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6963637PMC
November 2019

SK Channel Modulates Synaptic Plasticity by Tuning CaMKIIα/β Dynamics.

Front Synaptic Neurosci 2019 31;11:18. Epub 2019 Oct 31.

Department of Comparative Biomedical Sciences, Louisiana State University School of Veterinary Medicine, Baton Rouge, LA, United States.

N-Methyl-D-Aspartate Receptor 1 (NMDAR)-linked Ca current represents a significant percentage of post-synaptic transient that modulates synaptic strength and is pertinent to dendritic spine plasticity. In the hippocampus, Ca transient produced by glutamatergic ionotropic neurotransmission facilitates Ca-Calmodulin-dependent kinase 2 (CaMKII) Thr286 phosphorylation and promote long-term potentiation (LTP) expression. At CA1 post-synaptic densities, Ca transients equally activate small conductance (SK2) channel which regulates excitability by suppressing Ca movement. Here, we demonstrate that upstream attenuation of GluN1 function in the hippocampus led to a decrease in Thr286 CaMKIIα phosphorylation, and increased SK2 expression. Consistent with the loss of GluN1 function, potentiation of SK channel in wild type hippocampus reduced CaMKIIα expression and abrogate synaptic localization of T286 pCaMKIIα. Our results demonstrate that positive modulation of SK channel at hippocampal synapses likely refine GluN1-linked plasticity by tuning dendritic localization of CaMKIIα.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fnsyn.2019.00018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834780PMC
October 2019