Studies have shown that fluvoxamine can be useful in preventing the spread of Covid-19 disease (in the early stages of the disease) by strengthening the body’s immune system. For this purpose, in this work, the structural and electronic properties of fluvoxamine drug were investigated using quantum theory of atom in molecule (QTAIM) and Density-functional theory (DFT) at B3LYP-DFT/6-311G+ (at presence of water as solvent and the CPCM model) computational level. Also, in order to improve the electronic/pharmaceutical properties, the effect of electron donor/acceptor groups of NO2 and NH2 on fluvoxamine was studied. According to the results, electronic properties changed significantly in the presence of the NO2 group. So that (in the presence of NO2) cohesive energy, energy gap, dipole moment, adsorption energy, antioxidant properties, and recovery time improved by 20%, 70%, 84%, 48%, 48%, and 46% respectively. Although the electronic properties were improved in the presence of the NH2 group, the effect of the NO2 functional group was more noticeable. Therefore, it is expected that the presence of the NO2 electron-acceptor electron group will improve its medicinal function by changing the electronic properties of the drug fluvoxamine.
Terrestrial resource pulses can significantly affect the community dynamics of freshwater ecosystems. Previously, its effect on the river community is considered to be stronger in summer, while weaker in winter when terrestrial invertebrates are less abundant. The movement of the terrestrial earthworms are triggered in winter, so they may be supplied to winter rivers as terrestrial resource pulse, but little is known about it. Here, we report that the massive numbers of the terrestrial earthworms were supplied intensively to an upstream of the small river in early winter. In particular, we found large numbers of Megascolecidae earthworms were supplied in an upstream of the small river in Northern Japan. Furthermore, we observed that supplied earthworms were consumed by salmonid fish species (masu salmon, white spotted char and rainbow trout) and aquatic invertebrates (gammarid amphipod, planarian flatworm and stonefly larvae). These findings suggests that the terrestrial earthworms may play a key role in ecosystem functioning in winter when severe and other resources are scarce.
Background: Acute type A aortic dissection is associated with a significant perioperative morbidity and mortality. Ascyrus Medical Dissection Stent (AMDS) is a novel bare stent graft developed to be used as an adjunct to standard surgical approach to promote true lumen expansion and therefor enhance aortic remodeling. Patients and Methods: From March 2021 to March 2022, four consecutive patients who presented with acute Debakey type I aortic dissection underwent emergent surgical repair with an inclusion (David) procedure and implantation of an AMDS. We analysed patient’s files prospectively and described the perioperative outcomes. Results: All four device implantations were successful. Overall 30-day mortality was 0 %. Malperfusion that was present in two patients pre-operatively improved after AMDS implantation. At follow up, no aortic reinterventions were needed. No aortic injury related to the device was noted. Favourable changes in aortic true lumen and false lumen dimensions were found in most of our patients but the AMDS was compressed at the isthmus in one patient. Conclusion: AMDS is a reliable and secure device. However, its benefits remain unclear when it comes to a positive remodeling and seems less likelihood comparable to a frozen elephant trunk. The main reason seems to be an insufficient radial force of the AMDS.
A 63-year-old male, with a history of coronary artery bypass grafting using bilateral internal thoracic artery grafts, underwent surgical aortic valve replacement. Avoiding the graft injury, we selected the right anterior mini-thoracotomy approach under cardiac arrest with systemic hyperkalemia with remaining bilateral internal thoracic artery grafts open. Deep hypothermia was induced to obtain more reliable myocardial protection. We believe this strategy can be considered as a therapeutic option in patients requiring aortic valve replacement but unsuitable for transcatheter aortic valve replacement.
Although the leaf-height-seed (LHS) scheme states that plant height and leaf area are closely correlated with seed mass; phylogeny, genome size, growth form, and leaf N may also explain variations in seed mass. Till now, there has been little information on the relative contributions of these factors. We compiled data consisting of 1071 plant species from the literature to quantify the relationships between seed mass, explanatory variables and phylogeny. Strong phylogenetic signals of these explanatory variables reflected inherited ancestral traits of the plant species. Without controlling phylogeny, growth form and leaf N are associated with seed mass. However, this association disappeared when accounting for phylogeny. Plant height, leaf area, and genome size showed consistent positive relationship with seed mass irrespective of phylogeny. Using partial R2s, phylogeny explained 50.89% of the variance in seed mass, much more than plant height, leaf area, genome size, leaf N, and growth form explaining only 7.39%, 0.58%, 1.85%, 0.06% and 0.09%, respectively. Our study is the first to disentangle the contributions of phylogeny and plant attributes to the variance in seed mass, providing a novel avenue for better understanding variation in traits across plant species.
Forest soil CO2 efflux (FCO2) is a crucial process in global carbon cycling; however, how FCO2 respond to disturbance regimes in different forest biomes is poorly understood. We quantified the effects of disturbance regimes on FCO2 across boreal, temperate, tropical, and Mediterranean forests based on 1240 observations from 380 studies. Globally, FCO2 was increased by 13 to 25% due to climatic perturbations such as elevated CO2 concentration, warming, and increased precipitation. FCO2 was increased by forest conversion to grassland and elevated carbon input by forest management practices but was reduced by decreased carbon input, fire, and acid rain. Disturbance also caused changes in soil temperature and water content, which in turn affected the direction and magnitude of disturbance effects on FCO2. Our results suggest that disturbance effects on FCO2 should be incorporated into earth system models to improve the projection of feedback between the terrestrial C cycle and climate change.
Although how rare species persist in communities is a major ecological question, the critical phenotypic dimension of rarity is broadly overlooked. Recent work has shown that evaluating functional distinctiveness, the average trait distance of a species to other species in a community, offers essential insights into biodiversity dynamics, ecosystem functioning, and biological conservation. However, the ecological mechanisms underlying the persistence of functionally distinct species are poorly understood. Here we propose a heterogeneous fitness landscape framework, whereby functional dimensions encompass peaks representing trait combinations that yield positive intrinsic growth rates in a community. We identify four fundamental causes leading to the persistence of functionally distinct species in a community. First, environmental heterogeneity or alternative phenotypic designs can drive positive population growth of functionally distinct species. Second, sink populations with negative growth can deviate from local fitness peaks and be functionally distinct. Third, species found at the margin of the fitness landscape can persist but be functionally distinct. Fourth, biotic interactions (either positive or negative) can dynamically alter the fitness landscape. We offer examples of these four cases and some guidelines to distinguish among them. In addition to these deterministic processes, we also explore how stochastic dispersal limitation can yield functional distinctiveness.
Published literature suggests that indigenous cultural practices, specifically traditional medicine, are commonplace among urban communities contrary to the general conception that such practices are associated to rural societies. We reviewed literature for records of herptiles sold by traditional health practitioners in urban South Africa, then used visual confirmation surveys, DNA barcoding, and folk taxonomy to identify the herptile species that were on sale. Additionally, interviews with 11 SePedi and IsiZulu speaking traditional health practitioners were used to document details of the collection and pricing of herptile specimens along with the practitioners’ views of current conservation measures aimed at traditional medicine markets. The herptile specimens sold by traditional health practitioners included endangered and non-native species. The absorbance ratios of DNA extracted from the tissue of herptiles used in traditional medicine were found to be unreliable predictors of whether those extractions would be suitable for downstream applications. From an initial set of 111 tissue samples, 81 sequencing reactions were successful and 55 of the obtained sequences had species level matches to COI reference sequences on the NCBI GenBank and/or BOLD databases. Molecular identification revealed that traditional health practitioners sometimes mislabel the species they use. The mixed methodology employed here is useful for conservation planning as it updates knowledge of animal use in indigenous remedies and can accurately identify species of high conservation priority. Furthermore, the study highlights the possibility of collaborative conservation planning with traditional health practitioners.
Objective: Although clinically widespread, scientific evidence for augmentation strategies in the treatment of severe mental illnesses is still limited. Combining different drugs increases the potential for drug-drug interactions enhancing the risk of adverse drug reactions. We aimed to unravel potential pharmacokinetic interactions between ari-piprazole and duloxetine. Methods: Plasma concentrations of aripiprazole from a large therapeutic drug monitoring da-tabase were analyzed. Two groups of 78 patients each, receiving aripiprazole as a monotherapy, or combined with duloxetine, were compared addressing a potential impact of duloxetine on the metabolism of aripiprazole being reflected in higher plasma concentrations of aripiprazole and higher dose-adjusted plasma concentra-tions (C/D). Results: Patients co-medicated with duloxetine showed significantly higher plasma concen-trations of aripiprazole (p=0.02) than in the control group by 54.2% while the dose-adjusted plasma concentrations were 45.6% higher in the co-medication group (p=0.001). Conclusions: Combining duloxetine and aripiprazole leads to significantly higher drug concentra-tions of aripiprazole, most likely via an inhibition of cytochrome P450 CYP2D6 and to a lesser extent of CYP3A4 by duloxetine. Clinicians have to consider potentially occurring adverse drug reactions caused by increased plasma levels of aripiprazole when adding duloxetine to a treatment regimen with aripiprazole.
Inclusion body myositis (IBM) is an acquired myopathy of both inflammatory and degenerative nature. Here we report a case of IBM associated with prolonged use of imatinib not reported in the literature so far. An 81 years old male with a history of gastrointestinal stromal tumor (GIST) operated 8 years ago was evaluated for the progressive loss of weight and muscle strength leading to total immobilization in 6 months. He was under imatinib for 8 years despite the remission of GIST. Physical examination disclosed diffuse loss of muscle strength, most prominently involvement of distal upper and proximal lower extremity in an asymmetrical pattern with normal serum creatinine kinase level (CK). Further investigations including bilateral thigh MRI, electromyography (EMG), and PET/CT suggested myositis and degenerative myopathy and ruled out any malignancy. Quadriceps femoris biopsy proved the diagnosis of IBM and no trigger except for imatinib was displayed. Clinical improvement in terms of wieght loss and muscle weakness was achieved after discontinuation of imatinib. Since imatinib is widely used in different conditions, it is important to be aware of even its rare adverse effects. Poor response of IBM to conventional immunosuppressive agents enhances the value of etiology identification to relieve symptoms in addition to supportive care.
Objectives: To improve PPH prediction and to compare machine learning and traditional statistical methods. Design: Cross-sectional Setting: Deliveries across US hospitals Population: Deliveries across 12 US hospitals from the 2002-2008 Consortium for Safe Labor dataset Method: We developed models using the Consortium for Safe Labor dataset. Fifty antepartum and intrapartum characteristics and hospital characteristics were included. Logistic regression, support vector machines, multi-layer perceptron, random forest, and gradient boosting were used to generate prediction models. Receiver operating characteristic area under the curve (ROC-AUC) and precision/recall area under the curve (PR-AUC) were used to compare performance. Main Outcome Measure: The primary outcome was transfusion of blood products or PPH (estimated blood loss ≥1,000mL). The secondary outcome was transfusion of any blood products. Results: Among 228,438 births, 5,760 women (3.1%) had a postpartum hemorrhage, 5,170 women (2.8%) had a transfusion, and 10,344 women (5.6%) met criteria for the transfusion-PPH composite. Models predicting transfusion-PPH composite using antepartum and intrapartum features had the best positive predictive values with the gradient boosting machine learning model performing best overall (ROC-AUC=0.833, 95% CI [0.828-0.838]; PR-AUC=0.210 95% CI [0.201-0.220]). The most predictive features in the gradient boosting model predicting transfusion-PPH composite were mode of delivery, oxytocin incremental dose for labor(mU/min), intrapartum tocolytic use, presence of anesthesia nurse, and hospital type. Conclusion: Machine learning offers higher discrimination than logistic regression in predicting PPH. The CSL dataset may not be optimal for analyzing risk due to strong subgroup effects, which decreases accuracy and limits generalizability.
Loss of consciousness during delivery by cesarean section under spinal anesthesia is a rare but potentially serious complication. We report a case of a pregnant woman with unicuspid aortic valve, which was incidentally diagnosed during an aortic valve replacement after transient loss of consciousness during cesarean section.
We present a patient who has been diagnosed with Hypereosinophilic syndrome, later determined to be chronic eosinophilic leukemia, after long-term treatment with infliximab for ulcerative colitis. Follow-up immunochemistry showed that discontinuation of infliximab improved the polyclonality of eosinophils in our patient.
Introduction: Asthma is a complex, polygenic, heterogenous inflammatory disease. Recently, we generated a list of 128 independent single nucleotide polymorphisms (SNPs) associated with asthma in genome-wide association studies. However, it is unknown if asthma SNPs are associated with specific asthma-associated traits such as high eosinophil counts, atopy, and airway obstruction, revealing molecular endotypes of this disease. Here, we aim to identify the association between asthma SNPs and asthma-associated traits and assess e-QTLs to reveal their downstream functional effects and find drug targets. Methods: Association analyses between 128 asthma SNPs and associated traits (blood eosinophil numbers, atopy, airway obstruction, airway hyperresponsiveness) were conducted using regression modelling in population-based studies (Lifelines N=32,817 / Vlagtwedde-Vlaardingen N=1,554) and an asthma cohort (Dutch Asthma GWAS N=917). Functional enrichment and pathway analysis were performed with genes linked to the significant SNPs by e-QTL analysis. Genes were investigated to generate novel drug targets. Results: We identified 69 asthma SNPs that were associated with at least one trait, with 20 SNPs being associated with multiple traits. The SNP annotated to SMAD3 was the most pleiotropic. In total, 42 SNPs were associated with eosinophil counts, 18 SNPs with airway obstruction, and 21 SNPs with atopy. We identified genetically driven pathways regulating eosinophilia, atopy and airway obstruction. The largest network of eosinophilia contained two genes ( IL4R, TSLP) targeted by drugs currently available for eosinophilic asthma. Several novel targets were identified. Conclusion: Many asthma SNPs are associated with blood eosinophil counts and genetically driven molecular pathways of asthma-associated traits were identified.
As sessile organisms, plants are constantly challenged by a dynamic growing environment. This includes fluctuations in temperature, water availability, light levels, and atmospheric conditions. In concert with changes in abiotic conditions, plants experience changes in biotic stress pressures, including plant pathogens, viruses, and herbivores. Human-induced increases in atmospheric carbon dioxide (CO 2) levels have led to alterations in plant growth environments that challenge their productivity and nutritional quality. Additionally, it is predicted that climate change will alter the prevalence and virulence of plant pathogens, further challenging plant productivity. A knowledge gap exists in the complex interplay between plant responses to biotic and abiotic stress conditions. Closing this gap is crucial for developing climate resilient crops in the future. Here, we review the physiological responses of plants to elevated CO 2, temperature, tropospheric ozone (O 3), and drought conditions, as well as the interaction of these abiotic stress factors with plant pathogen pressure. Additionally, we describe the crosstalk and trade-offs involved in plant responses to both abiotic and biotic stress, and outline targets for future work to develop a more sustainable future food supply in light of future climate change.
Long QT syndrome (LQTS) is a serious condition that can cause sudden cardiac death. Subsequently, a heterozygous mutation of KCNH2 was identified. This has led to the hypothesis that the use of maternal tacrolimus may cause LQTS or have an effect that may facilitate the early occurrence of congenital LQTS.
Fat embolism is a potentially life-threatening condition that can develop after trauma or lower limb orthopaedic surgery. Characterized as a triad of respiratory, neurological and cutaneous symptoms. High index of suspicion is important. Rapid recognition and supportive treatment are key in improving the outcome. The prognosis is usually good.
A patient with schizoaffective disorder and receiving long-term treatment with lithium developed prolonged delirium. She had recently been diagnosed with stage IIIC1 endometrial cancer and presented a deteriorating general condition. Toxic levels of lithium were measured in serum. After hemodialysis, lithium levels gradually decreased and the symptoms disappeared completely.