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Semih Bolu

and 1 more

Background: Growth hormone (GH) release is pulsatile, and daytime GH levels are low. GH stimulation tests are therefore needed in cases requiring GH level investigation. The purpose of this study was to compare the results of L-dopa and clonidine GH stimulation tests applied in children with short stature and to identify which of these tests should be primarily selected. Methods: The records of 68 patients aged between 2.5 and 16.6 years presenting to the pediatric endocrinology clinic with short stature and undergoing GH stimulation tests between September 2016 and February 2021 were evaluated retrospectively. Cases with GH levels <10 ng/dl following the first GH stimulation test then underwent the other GH stimulation test. Thirty-four (50%) of the cases in the study consisted of individuals beginning with the clonidine test, while the other 34 (50%) started with the L-dopa test. Results: Seventeen (50%) individuals in whom clonidine was employed in the first test had low GH responses, while a low GH response was determined at the second, L-dopa test, in 15 (88.2%) of these individuals, significant variation being observed between the groups (p< 0.001). Conclusion: GH stimulation tests performed to investigate GHD are laborious and time-consuming. The first stimulation test to be applied to differentiate GHD from ISS must therefore be well selected. The clonidine stimulation test, with higher sensitivity than but similar specificity to the L-dopa test, can be employed as the first test.

Gabe O'Reilly

and 5 more

New sequencing technologies have opened the door to many new research opportunities, but these advances in data collection are not always compatible with some important methods for data analysis. Fis has been a staple calculation in the field of population genetics. Fis can be used to measure either a departure from random mating, or measure underlying selective pressures for or against heterozygote genotypes. However, when using Next Generation Sequencing (NGS) technology on multi-locus gene families it is often impossible to discern which allelic variants are present at each locus. Some important multi-locus gene families are: the major histocompatibility complex (MHC) in animals; homeobox genes in fungi; or the self-incompatibility genes in plants. This in turn makes it impossible to calculate either locus-specific expected heterozygosity, or observed heterozygosity, both of which are required to calculate Fis. Without the ability to calculate Fis from NGS of multi-locus gene families, we need a new multi-locus measure that will allow us to detect the underlining mating, and selective patterns present in such multi-locus genes. This paper provides such a novel multi-locus measure, called 1His. We demonstrate the accuracy of the 1His equation using simulated data, and two datasets taken from natural populations of dolphins and penguins. The introduction of this new measure is particularly important because of the great interest in mating patterns and selection of multi-locus gene families, such as MHC.

Fu-Yong Ye

and 5 more

Objective: To investigate the value of echocardiography in monitoring hemodynamics of postcardiotomy cardiac shock (PCS) patients before, during, and after weaning from extracorporeal membrane oxygenation (ECMO). Methods: Fifty-two patients were divided into a successful weaning group (Group A, n=23) and non-successful group (Group B, n=29). Hemodynamic parameters measured by echocardiography were collected before, during, and after ECMO. The intra-group changes and inter-group differences were analyzed. Results: In group A, the central venous pressure (CVP), proximal right ventricular outflow tract (RVOT), tricuspid annular plane systolic excursion (TAPSE), velocity of tricuspid valve (TVDV), and systolic velocity of tricuspid annulus (s‘TV) during EMCO were significantly lower than before ECMO. After ECMO, left ventricular ejection fraction (LVEF), systolic velocity of mitral annulus (s‘MV), and velocity-time integral of LV outflow tract (LVOT-VTI) were higher than pre-ECMO, and CVP, LVEF, s‘MV, LVOT-VTI, RVOT, TAPSE, TVDV and s‘TV were higher than during ECMO (all p<0.05). In group B, compared to pre-ECMO, subjects exhibited decreased CVP, RVOT, TAPSE, TVDV and s‘TV during ECMO. TAPSE, TVDV, and s‘TV were continuously lower after ECMO, while CVP and RVOT became higher after ECMO (all p<0.05). After ECMO, LVEF, s‘MV, LVOT-VTI, TAPSE, TVDV and s‘TV in group A were higher than those in group B (all p<0.05). Multiple logistic regression analysis showed that LVEF (OR=1.387, 95%CI: 1.072-1.793, p=0.013) and Tei index (OR=-0.005, 95% CI: 0.000-0.939, p=0.047) were independent factors related to the successfulness of ECMO weaning. Conclusions: Quantitative assessment of both LV and RV by echocardiography is important for ECMO weaning.

Augusto D'Onofrio

and 3 more

Introduction: Nowadays micro-invasive procedures (off-pump, beating heart) for mitral valve repair (MVRe) are abruptly expanding with the potential to be adopted as a valuable alternative to surgery. In the present manuscript, the Authors review the available technologies intended to treat mitral regurgitation (MR) through transapical approach, including annuloplasty and chordal repair options. Annuloplasty: To date, Valcare Amend is the only transapical mitral valve (MV) ring to have been implanted in patients. The device allows for stabilization of the annulus through a complete semirigid D-shaped ring. The first-in-human successful procedure was performed in 2016 by our Group and subsequent clinical experience included a total of 14 implanted patients. Currently the technology is under clinical trial evaluation to validate the efficacy and safety profile of the device. Chordal Repair: Beating heart chordal implantation via trans-apical approach is a current feasible, safe and reproducible option. Neochord DS1000 is the most widely used technology in the field, with a solid procedural experience and good results in well-selected patients. Its clinical use has been validated in Europe since 2012, while it is still under clinical investigation in the United States. Harpoon TDS-5 system is a novel technology, recently CE mark approved for clinical use. Conclusions: Transapical micro-invasive technologies are current viable therapies to treat MR in selected patients. Embracing transcatheter MVRe therapies should guide the cardiac surgeon through the new revolution of micro-invasive MV tailored repair.

Liang Yin

and 6 more

Objective To determine the predictive value of surgical Apgar score on delirium postoperatively following OPCABG. Method Intraoperative anesthesia data of patients underwent OPCABG during the period of January 2012 and December 2019 were reviewed and SAS score of each patient was calculated. Relationship between SAS score and postoperative occurrence of delirium were analyzed to determine the underlying mechanism. Results There are a total of 436 patients included with a mean age of 62.8±13.8 and 61.2±16.8 in each group. Patients in Delirium group had significantly higher incidence of heart failure (P=0.043) preoperatively in the Delirium group. No significant difference was observed referring to ASA PS III (P=0.102) and no significant difference was observed in duration of the surgery and anesthesia. Also no significant differences was observed as to dexmedetomidine and propofol use (P=0.256, P=0.278). The mean SAS score was in 4.2±0.8, 7.8±1.2 in two groups respectively (P<0.001) and 96(22.02%) postoperative delirium events were recorded. Patients in Delirium group had much more EBL (P<0.001) while LHR (P=102) showed no significant statistical difference between two groups. Univariate and multivariate regression analysis showed that the intraoperative SAS score was significant predictors of delirium following OPCABG (P<0.001; P<0.001). After adjustment for other clinical predictors, the addition of SAS also improved and the area under the curve to predict delirium was 0.934 (95%CI, 0.907-0.960, P<0.001). Conclusions Intraoperative SAS score is associated with postoperatively following OPCABG and SAS score may be a valuable component to improve preoperative risk stratification of delirium among patient under OPCABG.

Eric Jauniaux

and 2 more

Aortic balloon for the intraoperative management of placenta accreta spectrum: need for standardised methodology and safety dataIn 2003, Bell-Thomas et al (BJOG 2003;110:1120-1122) reported on the emergency use of a transfemoral aortic occlusion catheter to control massive haemorrhage in a case of caesarean hysterectomy for placenta percreta. This was only the second case published in the international literature on the use of an intra-abdominal aortic balloon occlusion (IABO) in the management of placenta accreta spectrum (PAS) (Paull et al. Anesth Intensive Care 1995;23:731-734). A non-exhaustive Pub-Med literature review of articles published in English on this the topic over the last 20 years, identifies 27 articles, 23 of which come from the Peoples Republic of China, where IABO seems to be increasingly popular in the management of PAS.In brief, IABO involves the insertion of a balloon catheter into the infrarenal abdominal aorta above the aortic bifurcation under fluoroscopy guidance. The procedure is performed in a hybrid operating room or interventional radiology (IR) suite with secondary transfer to the operating room. In all but one study (Zhu et al Biomed Res Int.2017:8604849), the balloon was inflated after delivery of the newborn.All publications so far have been retrospective and most are case-control studies, comparing the outcomes of IABO with those of routine surgical techniques with or without additional procedures such as intra-uterine tamponade. Recently, authors have also started to compare IABO with iliac artery balloon occlusion.Overall, these studies have shown that IABO is associated with reduced estimated blood loss and transfusion requirement, ICU admission and hysterectomy and suggested that IABO is more effective than iliac artery balloon occlusion, presumably as arterial occlusion is more effective.However, there is wide variation between studies in prenatal imaging and clinical selection criteria, intraoperative IR methodology and confirmation of the diagnosis of PAS at birth. For example, the pre-operative fluoroscopy time ranges between 2 and 25 minutes with fetal radiation exposure of 4 to 25 mGy; intraoperative balloon inflation/deflation time varies between 5-10/1 minutes and 45-80/10 minutes. The size of the balloon and the need for transfer between the IR room and the operative theatre is rarely described. Most studies lack histopathology confirmation of the diagnosis and/or stratification by PAS grade.Heterogeneity in methodology and design leads to a high risk of confounding, bias or chance. There is also a high risk that the relationship is not causal. One major concern is the risks-benefit ratio of the use of IABO for both mothers and fetuses, in particular if they do not have PAS. The most commonly reported post-operative complication associated with IABO are arterial thrombosis of the external iliac or the femoral artery. There are no data on the long-term follow of the children born after IABO.In 2018, the expert panel of the RCOG green top guidelines 27a (Jauniaux et al., BJOG.2019;126:e1-e48) concluded that larger studies are necessary to determine the safety and efficacy of IR before this technique can be advised in the routine management of PAS. The 10 new studies published in 2019-2010 on the use of IABO in the management of PAS are insufficient to change this statement.Word count: 499

Robert Fitt

and 1 more

Warming climates provide many species the opportunity to colonise newly-suitable regions at higher latitudes and elevations. Despite becoming warmer, higher latitudes and elevations nevertheless offer novel climatic challenges, such as greater thermal variability and altered frequency of weather events, and these challenges exert selection on expanding populations. However, high gene flow and genetic drift during the expansion phase may limit the degree to which species can adapt to novel climatic conditions at the range front. Here we examine how landscape topographic complexity influences the opportunity for local adaptation to novel conditions during a range shift. Using RAD-seq data, we investigated whether elevation, latitude, climatic niche differentiation, and gene flow across a complex landscape were associated with signatures of adaptation during recent range expansion of the damselfly Ischnura elegans in Northeast Scotland. Our data revealed two distinct routes of colonisation, with admixture between these routes resulting in increased heterozygosity and population density. Expansion rates, assessed as directional rates of gene flow, were greater between more climatically similar sites than between climatically divergent sites. Significant genetic structure and allelic turnover was found to emerge near the range front at sites characterised by high elevation, low directional gene flow, and high spatial differentiation in climate regimes. This predictive combination of factors suggests that landscape complexity may be a prerequisite for promoting differentiation of populations, and providing opportunities for local adaptation, during rapid or contemporary range shifts

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Mohammed Al-Sadawi

and 7 more

Abstract: Background: This meta-analysis assessed the relationship between Obstructive Sleep Apnea (OSA) and echocardiographic parameters of diastolic dysfunction (DD), which are used in the assessment of Heart Failure with Preserved Ejection Fraction (HFpEF). Methods: We searched the databases including Ovid MEDLINE, Ovid Embase Scopus, Web of Science, Google Scholar, and EBSCO CINAHL from inception up to December 26th, 2020. The search was not restricted to time, publication status or language. Comparisons were made between patients with OSA, diagnosed in-laboratory polysomnography (PSG) or home sleep apnea testing (HSAT), and patients without OSA in relation to established markers of diastolic dysfunction. Results: Primary search identified 2512 studies. A total of 18 studies including 2509 participants were included. The two groups were free of conventional cardiovascular risk factors. Significant structural changes were observed between the two groups. Patients with OSA exhibited greater LAVI (3.94 CI [0.8, 7.07]; p=0.000) and left ventricular mass index (11.10 CI [2.56,19.65]; p=0.000) as compared to control group. The presence of OSA was also associated with more prolonged DT (10.44 ms CI [0.71,20.16]; p=0.04), IVRT (7.85 ms CI[4.48, 11.22]; p=0.000), and lower E/A ratio (-0.62 CI [-1,-0.24]; p=0.001) suggestive of early DD. The E/e’ ratio (0.94 CI[0.44, 1.45]; p=0.000) was increased. Conclusion: An association between OSA and echocardiographic parameters of DD was detected that was independent of conventional cardiovascular risk factors. OSA may be independently associated with DD perhaps due to higher LV mass. Investigating the role of CPAP therapy in reversing or ameliorating diastolic dysfunction is recommended.

Gunter Sturm

and 38 more

Background: There is controversy whether taking β-blockers or ACE inhibitors (ACEI) is a risk factor for more severe systemic insect sting reactions (SSR) and whether it increases the number or severity of adverse events (AE) during venom immunotherapy (VIT). Methods: In this open, prospective, observational, multicenter trial, we recruited patients with a history of a SSR and indication for VIT. The primary objective of this study was to evaluate whether patients taking β-blockers or ACEI show more systemic AE during VIT compared to patients without such treatment. Results: In total, 1,425 patients were enrolled and VIT was performed in 1,342 patients. Of all patients included, 388 (27.2%) took antihypertensive (AHT) drugs (10.4% took β-blockers, 11.9% ACEI, 5.0% β-blockers and ACEI). Only 5.6% of patients under AHT treatment experienced systemic AE during VIT as compared with 7.4% of patients without these drugs (OR: 0.74, 95% CI: 0.43–1.22, p=0.25). The severity of the initial sting reaction was not affected by the intake of β-blockers or ACEI (OR: 1.14, 95% CI: 0.89–1.46, p=0.29). In total, 210 (17.7%) patients were re-stung during VIT and 191 (91.0%) tolerated the sting without systemic symptoms. Of the 19 patients with VIT treatment failure, 4 took β-blockers, none an ACEI. Conclusions: This trial provides robust evidence that taking β-blockers or ACEI does neither increase the frequency of systemic AE during VIT nor aggravate SSR. Moreover, results suggest that these drugs do not impair effectiveness of VIT. (Funded by Medical University of Graz, Austria; Clinicaltrials.gov number, NCT04269629)

Nazanin Kermani

and 12 more

Background. Patients with severe asthma may have a greater risk of dying from COVID-19 disease. Angiotensin converting enzyme-2 (ACE2) and the enzyme proteases, transmembrane protease serine 2 (TMPRSS2) and FURIN, are needed for viral attachment and invasion into host cells. Methods. We examined microarray mRNA expression of ACE2, TMPRSS2 and FURIN in sputum, bronchial brushing and bronchial biopsies of the European U-BIOPRED cohort. Clinical parameters and molecular phenotypes, including asthma severity, sputum inflammatory cells, lung functions, oral corticosteroid (OCS) use, and transcriptomic-associated clusters, were examined in relation to gene expression levels. Results. ACE2 levels were significantly increased in sputum of severe asthma compared to mild-moderate asthma. In multivariate analyses, sputum ACE2 levels were positively associated with OCS use and male gender. Sputum FURIN levels were significantly related to neutrophils (%) and the presence of severe asthma. In bronchial brushing samples, TMPRSS2 levels were positively associated with male gender and body mass index, whereas FURIN levels with male gender and blood neutrophils. In bronchial biopsies, TMPRSS2 levels were positively related to blood neutrophils. The neutrophilic molecular phenotype characterised by high inflammasome activation expressed significantly higher FURIN levels in sputum than the eosinophilic Type 2-high or the pauci-granulocytic oxidative phosphorylation phenotypes. Conclusion. Levels of ACE2 and FURIN may differ by clinical or molecular phenotypes of asthma. Sputum FURIN expression levels were strongly associated with neutrophilic inflammation and with inflammasome activation. This might indicate the potential for a greater morbidity and mortality outcome from SARS-CoV-2 infection in neutrophilic severe asthma.

Mehmet Pehlivaoğlu

and 5 more

Aim: This study evaluated the effect of intracavitary levobupivacaine infusion diluted with locally applied isotonic solution for pain control in cystoscopy. Methods: Included in this study are 100 patients who had previously undergone transurethral tumor resection for bladder tumor and were followed up by cystoscopy. The patients were randomized into five groups (n = 20). In the first, second, third, and fourth groups, 4, 6, 8, and 10 mL of levobupivacaine HCl (5.0 mg/mL) were mixed with 26, 24, 22, and 20 mL of isotonic solution, respectively. Hence, the total mixture was 30 mL for each group. The fifth group was the control group. In this group, the standard method commonly used in most clinics was utilized. That is, a gel containing Cathejell-2% lidocaine (25 mg lidocaine) was applied. Cystoscopic interventions were performed with a 17.5 Fr rigid cystoscope and 0°, 30°, and 70° lens. During cystoscopy and 30 min later, the pain status of patients was assessed using the Visual Analogue Scale (VAS), and patient satisfaction was questioned. Results: The mean VAS score during and after the cystoscopy procedure was significantly lower in the levobupivacaine groups compared to the lidocaine group. In addition, patient satisfaction in the levobupivacaine groups was significantly higher than in the lidocaine group. No drug-related side-effects were observed in all groups. Conclusion: Thus, levobupivacaine is a more effective drug than lidocaine alone to control pain during cystoscopy. The use of levobupivacaine is recommended to prevent possible complications of general anesthesia by eliminating the need for the aforementioned as well as its cost-saving advantage.

Yanhui Dong

and 4 more

Groundwater age is often used to estimate groundwater recharge through a simplified analytical approach. This estimated recharge is thought to be representative of the mean recharge between the point of entry and the sampling point. However, given the complexity in actual recharge, whether the mean recharge is reasonable is still unclear. This study examined the validity of the method to estimate long-term average groundwater recharge and the possibility of obtaining reasonable spatial recharge pattern. We first validated our model in producing reasonable age distributions using a constant flux boundary condition. We then generated different flow fields and age patterns by using various spatially-varying flux boundary conditions with different magnitudes and wavelengths. Groundwater recharge was estimated and analyzed afterwards using the method at the spatial scale. We illustrated the main findings with a field example in the end. Our results suggest that we can estimate long-term average groundwater recharge with 10% error in many parts of an aquifer. The size of these areas decreases with the increase in both the amplitude and the wavelength. The chance of obtaining a reasonable groundwater recharge is higher if an age sample is collected from the middle of an aquifer and at downstream areas. Our study also indicates that the method can also be used to estimate local groundwater recharge if age samples are collected close to the water table. However, care must be taken to determine groundwater age regardless of conditions.

Xinyi Guan

and 4 more

Adriana Bustamante

and 3 more

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