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Dillon Adam

and 5 more

Jan Mir

and 1 more

Nitric oxide (NO) along with Carbon monoxide (CO) and Hydrogen Sulphide (H2S) are biologically significant gaseous molecules generally called as “gasotransmitters”. At a concentration higher or lower than optimum value may result in toxicity or malfunctioning of mammalian tissues. Soon after the acknowledgment of NO as multifunctional bio-signalling molecule in 1987, many interesting implications of this field emerged out. Meanwhile, several studies have proven the NO-biosynthetic pathway responsible for normal functioning of eye. High intraocular pressure (IOP) has been suggested as the main risk factor in this context and collaborative approach with nitric oxide releasers is said to control IOP and hence the relation with glaucoma. Similar miracles were reflected from several other naturally produced gaseous molecules,viz., CO and H2S after year 1990. The biological roles of both these molecules are now widely accepted and in the current era investigations focused mainly with development of efficient CO and H2S releasing compounds. CO and H2S donors are also said to help in normalising IOP like NO. Therefore the trio-gasotransmitters have collective relation with the ophthalmic homeostasis in association with nervous control. On one hand, the antimicrobial efficiency of these three molecules is widely known and on the other hand, their collaborative key-role in ocular nerve functioning makes it remarkable to state here that their donors are supposed to act as a shield for both the infectious as well as the non-infectious eye defects.

David Niedrig

and 8 more

Background and Purpose: There is an increasing number of evidence-based indications for pharmacogenetic (PGx) tests and a growing demand for PGx screening. We aimed to evaluate clinical relevance of a 16-gene panel test for PGx-guided pharmacotherapy. Experimental Approach: Observational cohort study of subjects tested with a PGx panel for variants of ABCB1, COMT, CYP1A2, CYP2B6, CYP3A4, CYP3A5, CYP2C9, CYP2C19, CYP2D6, CYP4F2, DPYD, OPRM1, POR, SLCO1B1, TPMT and VKORC1. Specialized clinical pharmacology consultations with PGx-guided pharmacotherapy management were supported by the PGx expert system SONOGEN XP. Study outcomes were PGx-based changes and recommendations regarding current and potential future medication. Key Results: PGx-testing was triggered by specific drug-gene pairs in 102 subjects, whereas screening was performed in 33. Based on PHARMGKB expert guidelines the 16-gene panel identified at least one “actionable” variant relevant for current or potential future medication in all 135 (100%) tested patients. Drugs that triggered PGx-testing were clopidogrel in 60, tamoxifen in 15, polypsychopharmacotherapy in 9, opioids in 7, and other in 11 patients. Among those, PGx variants resulted in clinical recommendations to change PGx-triggering drugs in 33 (32.4 %), and other current pharmacotherapy in 23 (22.5%). Conclusion and Implications: The 16-gene PGx panel detected clinically relevant variants in a high proportion of tested patients, and SONOGEN XP supported their interpretation based on latest evidence. Additional costs of panel vs. single gene tests are moderate, and the efficiency of PGx panel testing challenges traditional cost-benefit calculations for single drug-gene pairs. However, PGx-guided pharmacotherapy requires specialized consultations with interdisciplinary collaborations.

Wei Quan

and 18 more

KAI WANG

and 3 more

Afforestation is among the most effective means of preventing and controlling desertification. Silver poplar (Populus alba) is commonly planted tree species for afforestation of the Horqin Sandy Land of China. However, this species has exhibited some drawbacks such as top shoot dieback, premature senescence and mortality, and soil and ecosystems degradation. In contrast, Siberian elm (Ulmus pumila) rarely experiences these problems in the same regions. Ecological stoichiometry plays a vital role in exploring ecological processes and nutrient cycle relationships in plant–litter–soil systems. We measured C, N, and P concentrations in leaves, branches, roots, litter, and soils and analyzed N and P resorption efficiencies, and stoichiometric homeostasis in elm and poplar plantations in the Horqin Sandy Land. The results showed that soil C and N concentrations, C:P, and N:P were greater in the elm plantation than in the poplar plantation. The plant N concentrations, C:P, and N:P and litter N and P concentrations were greater, whereas N and P resorption efficiencies were lower, in the elm plantation than in the poplar plantation. Generally, elm exhibited greater homeostasis than poplar. These findings indicate that poplar exhibited more developed internal nutrient conservation and allocation strategies but poor nutrient accumulation in soil, which may contribute to degradation of poplar plantation. In contrast, elm tended to return more nutrients to the soil. Therefore, compared with poplar, elm may be a more suitable afforestation tree species for the Horqin Sandy Land, where it may promote the accumulation of soil nutrients and enhance ecosystem stability.

Carina Vedeler

and 4 more

Objective To explore and describe what women who have given birth in Norway emphasise as important aspects of care during childbirth. Design The study is based on data from the Babies Born Better survey, version 2, a mixed-method online survey. Setting The maternity care system in Norway. Study population Women who gave birth in Norway between 2013 and 2018. Method Descriptive statistics were used to describe sample characteristics and to compare data from the B3 survey with national data from the MBRN, using SPSS® software (version 20). The open-ended questions were analysed with an inductive thematic analysis, using NVIVO 12® software. Main outcome measures Themes developed from two open-ended questions. Results The final sample included 8,401 women. There were no important differences between the sample population and the national population with respect to maternal age, marital status, parity, mode of birth and place of birth, except for the proportion of planned homebirths. Four themes and one overarching theme were identified; Compassionate and Respectful Care, A Family Focus, Continuity and Consistency, and Sense of Security, and the overarching theme Coherence in Childbearing. Conclusions Socio-cultural and psychological aspects of care are significant for women in childbirth, alongside physical and clinical factors. Caring for the woman implies caring for her partner and having a baby is about ‘becoming a family or expanding the family’. Childbirth is a continuous experience in women’s lives and continuity and consistency are important for women to maintain and promote a coherent experience.

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The sinoatrial node in medication-resistant inappropriate sinus tachycardia: to modify or to ablate?Khalil El Gharib1*1Hôtel-Dieu de France, Beirut, Lebanon*Author for correspondence: khalil.gharib@outlook.comKEYWORDS: IST, sinus node modification, sinus node ablation, radiofrequency ablation, surgical ablationNo conflict of interest to discloseFunding: noneInappropriate sinus tachycardia (IST) is defined as a resting heart rate >100 beats per minute (with a mean heart rate >90 beats per minute over 24 hours) associated with highly symptomatic palpitations(1). The syndrome is associated neither with structural heart disease nor with any secondary cause of sinus tachycardia(2) and evidence suggests that enhanced intrinsic automaticity of the sinoatrial node, which can be due to anti-β-adrenergic antibodies, is behind its genesis(3). However, it is benign in terms of clinical outcomes and echocardiographic evidence of ventricular dysfunction(4), being rarely associated with tachycardia-induced cardiomyopathy(3).Patients with IST are essentially treated with ß-blockers to alleviate their symptoms(5). Ivabradine, a drug that inhibits funny calcium channels, particularly abundant in the SA node, showed modest benefit, receiving class IIa recommen­dation in the treatment of IST(4). But, the duration of medical therapy might be indefinite, and, a considerable number of patients would respond inadequately, or have no response, even after prolonged therapy(5). Historically, such patients would have subtotal right atrial excision, atrioventricular junctional ablation with permanent pacemaker implantation, or chemical occlusion of the sinus node artery(6). These options are considered today unacceptable in this setting, and other therapeutic approaches should be unveiled when resistance to medical treatment appears.Electrophysiological study was initially purely diagnostic, but recent advances in technology have allowed us to intervene(7); patients with ventricular and supraventricular tachyarrhythmias are successfully treated with percutaneous catheter procedures. Of these, SA node ablation/ modification has been proposed as alternative approaches in IST that is not responding to medical treatment; trials reported auspicious results, highlighted here.Electrophysiologic mapping to the site of the earliest endocardial activation during either spontaneous sinus tachycardia or isoproterenol-induced sinus tachycardia has rendered these procedures feasible(8). Additionally, combination with intracardiac echocardiography permitted a more accurate electrophysiologic and anatomic localization of the sinoatrial node(9).Sinus node modification is not a focal ablation, but requires complete abolition of the cranial portion of the SA node complex, the one that exhibits the most of the autonomic activity(9). It is defined as successful when the heart rate decreases by 30 beats per minute (bpm) during isoproterenol infusion(8). Short-term success was also defined by other investigators when there was a reduction of the baseline sinus rate to less than 90 bpm and the sinus rate during isoproterenol infusion by more than 20% or by 25%(8). The acute success rate for modification has been varying between 76 and 100 % across trials, while long-term clinical outcomes are modest at best, with reported freedom from IST ranging from 23 to 85%(10).Complications specific to SA node modification include superior vena cava (SVC) syndrome, diaphragmatic paralysis, and sinus node dysfunction(10). And while modification with conventional methods has its setbacks, modification using laser energy can be considered in the setting of IST. This modality creates clear-cut homogenous transmural lesions of the myocardium that comprises the scattered “functional” SA node(11). The burnt myocardium will then heal into a dense fibrous scar, decreasing potential amplitudes. And when adapting laser energy settings to the thickness of the myocardial wall, collateral dam­ages such as esophageal fistulae, lung burns, and phrenic nerve palsy will be avoided(11); thus, this technique may prove itself as a new intriguing alternative for the safe and effective treatment of IST.SA node modification is apt in achieving acute reductions in postprocedural heart rate. However, and as aforementioned, success rates are suboptimal in terms of symptomatic control with a significant recurrence rate(12). Catheter ablation aiming at either total exclusion and obliteration of the SA node has been described and performed, success being defined as a slowing of >50% from the baseline rate of tachycardia along with a junctional escape rhythm(12). With radiofrequency (RF) applications, the earliest local atrial activation time would shift from a cranial location to a more caudal one, usually at the mid-lateral right atrium(5). Reviews have reported that acute success rates were consistently to be as high as 88.9%, with an overall frequency of recurrence of 19.6%, the latter occurring within a wide range of post-ablation intervals, anywhere from a few weeks to several months after the procedure(12). Additionally, Takemoto and colleagues documented a significant drop in B-type natriuretic peptide levels, 6 to 12 months after ablation, suggesting fewer stretching shears on cardiac muscle.Two types of response of the sinus tachycardia to RFA were observed across studies, whether a step-wise reduction in sinus rate accompanying migration of the site of earliest atrial activation in a cranial-caudal direction along the lateral right atrial wall, or an abrupt drop in heart rate in response to RFA at a focal site of earliest atrial activation(13).However, RFA of inappropriate sinus tachycardia requires a large number of applications of radiofrequency energy and is, as in SA node modification, associated with a high recurrence rate(13). Complete remission is achieved only in approximately 50% of patients in some studies(14); longer history of IST and those reporting near syncope/syncope having a higher probability of recurrence(15).While other studies have shown that RF ablation of the SA node can achieve even longer-term reductions in the sinus rate and relief of symptoms in two-thirds of patients with drug-refractory, inappropriate sinus tachycardia(13), aiming specific sites related to the SA node should be elaborated, for better and optimal outcomes Killu and colleagues created a lesion in the arcuate ridge resulting in complete abolition of the tachycardia, since arrhythmias arising in this region may exhibit both electrocardiographic and clinical similarities to IST(16). This has led to consider ablation of the arcuate ridge as a treatment of refractory IST, necessitating larger trials to confirm its potential role.Phrenic nerve injury is a severe and dreaded complication of SN ablation(12). Pericarditis, right diaphragmatic paralysis, and SVC syndrome are other undesirable side effects of the procedures, variously reported in studies. but a common complication was observed in them all, atrial tachyarrhythmias(12). It has been hypothesized that myocardial pathology, such as inflammation and fibrosis, considered iatrogenic due to the ablation procedures, may be promoting arrhythmias both in the region of the SA node, as well as in remote locations(12). Through multivariable analysis, higher resting heart rates post-ablation and smaller cranial-to-caudal shifts have been defined as predictors of atrial arrhythmias(15). In conclusion, catheter ablation could be considered an effective treatment for highly symptomatic, drug-refractory patients, even for those who did not respond to SA node modification(5).The sinus node is located close to the epicardial surface and catheter-based ablations do not always make full-thickness lesions across the atrial muscle, leading to failure of the ablation(17), besides the numerous trabeculae and the widely variable anatomy.Surgical ablation is not a first-line or routine management strategy for IST, but it has been proposed when IST resists or recurs after SN modification/ endocardial ablation(17). Effectively, in several studies, epicardial lesions, through a single small incision in one of the intercostal spaces, successfully slowed heart rate and shifted activation to a more caudal location, and surprisingly, subsequent endocardial lesions led to an even greater drop in heart rate and more caudal site of earliest activation(18). These outcomes were again replicated when using minimally invasive thoracoscopic ablation of the epicardial site of the SA node, concluding of the promising efficacy and the safety of this approach, since it preserves the phrenic nerve(17), although continued follow-up after surgery is required.Medication-resistant IST remains a medical challenge for physicians and cardiologists; and in the era of great advances in interventional cardiology, its treatment remains debatable. Sinus node modification/ ablation is not recommended as first-line therapy in IST, this procedure should be considered only in drug-refractory patients who have severe symptoms(13). Although the number of patients in the available studies is generally small, both procedures have documented an encouraging success rate in the short-term, while being less impressive in the long-term. It has been hypothesized that this discrepancy is due to the relatively large potential area of atrial pacemaker cells(18); modification or ablation may fail to ablate or isolate all the pathways that comprise the functional SA node because they often target the anatomic part and the area of earliest atrial activation(19). Others have explained that the long-term slowing in rhythm fails because these procedures inconsistently produce transmural lesions in the right atrium. Surgical treatment of IST has proposed a solution to the latter conflict when isolating the SA node with a wide cuff of surrounding atrial muscle(19). And with the advent of bipolar RF clamps and minimally invasive cardiac surgical techniques with thoracoscopic guidance, this approach appears more appealing than before, especially when combined with endocardial ablation(19). But again, current data specifies employing these techniques in highly selected cases.

Jerome FERRARA

and 10 more

Background: There is insufficient evidence regarding the comparison of Rapid Deployment aortic valve replacement(RDAVR) to TAVR in intermediate-risk patients with severe symptomatic aortic stenosis(AS) Aims: We compare the 2-years outcomes between RDAVR with INTUITY and TAVR with SAPIEN 3 in intermediate-risk patients with AS. Methods: Inclusion criteria: severe AS implanted with RDAVR or TAVR; EUROSCORE II ≥ 4% and clinical evaluation by Heart Team. Regression adjustment for the propensity score was used to compare RDAVR with TAVR(1:1). Primary endpoint: composite criterion of death, disabling stroke or rehospitalization. Secondary endpoints: occurrence of major bleeding post-operative complications, paravalvular regurgitation (PVR)≥2 and patient-prosthesis mismatch(PPM) at 1 month and pacemaker implantation at 2 years. Results: A total of 152 patients were included from 2012 to 2018: 48 in the RDAVR group and 104 in the TAVR group. Mean age was 82.7±6, 51.3% were female, mean Euroscore II was 6.03±1.6% and mean baseline LVEF was 56±13%,mean indexed iEOA was 0.41±0.1cm/m2, mean gradient was 51.7±14.7mmHg. Patients with RDAVR were younger(79.5±6vs82.6±6,p=0.01), at higher risk (EUROSCORE2 6,61±1,8%vs5,63±1,5%, p=0.005), combined surgery was performed in 28 patients(58.3%). Twenty-two patients(45.99%) met the primary outcome in the RDAVR group and 32 patients(66.67%) in the TAVR group. By 1:1propensity score matching analysis, there was a significant difference between both groups in favor of RDAVR(HR=0.58[95%CI:0.34;1.00],p=0.04). No difference were observed in PPM occurrence(0.83;[0.35-1.94];p=0.67),major bleeding events(1.33;[0.47-3.93];p=0.59),PVR≥2(0.33[0-6.28],p=0.46), and pacemaker implantation (0.84[0.25-2.84],p=0.77).Conclusion: RDAVR is associated with better 2-years outcomes than TAVR in intermediate-risk patients with severe symptomatic AS.

Francesca Mori

and 10 more

Hakan Celikhisar

and 2 more

Abstract Objective: To evaluate whether smoking cessation has an effect on female sexual function and quality of life. Methodology: After approval by the local ethics committee, smoking and non-smoking female participants were included in the study and all participants filled the female sexual function index (FSFI) and the short form 36 (SF-36). The same questionnaires were filled again at the 9th month control after smoking cessation. The scores of these questionnaires were compared between the groups. In addition, the FSFI and SF-36 scores of the participants in the smoking group were also compared with the scores at the 9th month after smoking cessation. Results: The rate of FSD was significantly higher in the smoking group when compared with control group (86.0% vs 32.5%; p<0,001). The FSFI total and sub domains score was significantly lower in the smoking group when compared control group [21.5 (min:14.4-max:28.69) and 28.9 (min:17.7-max:32.8); p<0.001 respectively]. The rate of FSD was significantly decreased after nine months smoking cessation (86% to 35.1%; p<0.001). After smoking cessation significant improvements on FSFI total and sub-domain scores and SF-36 sub-domain scores were determined. Conclusion: In this study, it was shown that smoking negatively affected FSD and QOL when compared to healthy non-smoking women, and smoking cessation caused significant improvements in FSFI and SF-36 scores in these women after 9 months. Keywords: female sexual dysfunction, female sexual function index, smoking cessation, the Short Form 36, quality of life.

Carola Sauter-Louis

and 20 more

African swine fever (ASF) has spread across many countries in Europe since the introduction into Georgia in 2007. We report here on the first cases of ASF in wild boar detected in Germany close to the border with Poland. In addition to the constant risk of ASF virus (ASFV) spread through human activities, movements of infected wild boar also represent a route of introduction. Since ASF emerged in Western Poland in November 2019, surveillance efforts, in particular examination of wild boar found dead, were intensified in the regions of Germany bordering with Poland. The first case of ASF in wild boar in Germany was therefore detected by passive surveillance and confirmed on 10th September 2020. By 24th September 2020, 32 cases were recorded. Testing of samples from tissues of carcasses in different stages of decomposition yielded cycle threshold values from 18 to 36 in the OIE-recommended PCR which were comparable between the regional and national reference laboratory. Blood swabs yielded reliable results, indicating that the method is suitable also under outbreak conditions. Phylogenetic analysis of the ASFV whole-genome sequence generated from material of the first carcass detected in Germany, revealed that it groups with ASFV genotype II including all sequences from Eastern Europe, Asia and Belgium. However, some genetic markers including a 14 bp tandem repeat duplication in the O174L gene were confirmed that have so far been detected only in sequences from Poland (including Western Poland). Epidemiological investigations that include estimated postmortem intervals of wild boar carcasses of infected animals suggest that ASFV had been introduced into Germany in the first half of July 2020 or even earlier.

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