Restrictive cardiomyopathy secondary to cardiac amyloidosis is an underdiagnosed, but treatable, cause of heart failure involving an extracellular deposition of misfolded protein. Hereby, we report a case of female patient with heart failure and nephrotic syndrome. The case underscores the importance of a timely diagnosis.

The guided image filter (GIF) provides a useful tool for image processing. However, few works have tried to use GIF for vessel enhancement on medical images. This letter presents an efficient GIF based method for vessel enhancement, in which a weighted GIF (WGIF) is introduced by incorporating a contrast-aware weighting into GIF. The WGIF has the adaptive property, which enables it to achieve better performance in noise reduction and edge preservation. In addition, we assemble the multiscale vesselness measurement with the WGIF to produce stronger enhancement results on small and thin vessel structures. The proposed method achieves excellent results that illustrate its effectiveness.

Sublingual buprenorphine is used in the treatment of opioid use disorder (OUD) and neonatal opioid withdrawal syndrome (NOWS). The aim of this study was to develop a full physiologically-based pharmacokinetic (PBPK) model that can adequately describe dose- and formulation-dependent bioavailability of buprenorphine. Simcyp (v21.0) was used for model construction. Linear regression modeling was explored to describe sublingual absorption of buprenorphine across dose. Published clinical trial data not used in model development were used for validation. The PBPK model’s predictive performance was deemed adequate if the geometric means of ratios between predicted and observed (P/O ratios) area under the curve (AUC), apparent clearance (CL/F), peak concentration (Cmax), and time to reach Cmax (Tmax) fell within the 1.25-fold prediction error range. Sublingual buprenorphine absorption was best described by a regression model with logarithmically transformed dose. By integrating this nonlinear absorption profile, the PBPK model adequately predicted buprenorphine pharmacokinetics (PK) following administration of sublingual tablets and solution across a dose range of 2–32 mg, with geometric mean (95% confidence interval) P/O ratios for AUC, CL/F, Cmax, and Tmax equaling 0.99 (0.86–1.12), 1.04 (0.92–1.18), 1.24 (1.09–1.40), and 1.07 (0.95–1.20), respectively. In conclusion, a fully validated PBPK model was developed that adequately predicts dose- and formulation-dependent buprenorphine PK following sublingual administration. The model forms the foundation on which a fetomaternal PBPK model for buprenorphine can be built. Fetomaternal PBPK modeling will allow conceptualization of prenatal buprenorphine exposure and investigation of its influence on postnatal NOWS severity.

We report a case of intoxication by metoclopramide, an antiemetic neuroleptic, in a breastfed child, causing an extrapyramidal syndrome. A 21-week-old breastfed child was brought to the pediatric neurology consultation following two episodes of unexplained dystonia. The anamnesis revealed that the mother had taken a rectal suppository of metoclopramide (10 mg) 48 hours before the first episode. The father was also treated by paracetamol codeine for capsulitis and the child had received paracetamol for teething. Blood toxicology analyses were performed at the first episode. A 3-cm strand of brown hair was collected during the consultation, one month after the second episode. The child had no further episodes of dystonia since the second event. The child’s blood toxicology analysis revealed the presence of metoclopramide at a concentration of 8 ng/mL. Hair analysis revealed metoclopramide at a relatively high concentration, with paracetamol, lidocaine, diazepam and nordazepam, and codeine. The presence of diazepam can be explained by medical care. The low concentration of codeine without its metabolite morphine, may suggest an external contamination by the environment, contact with people who had consumed this molecule, especially the child’s father. The interpretation of hair analysis in infants remains nevertheless delicate to discriminate consumption from environmental contamination. The presence of metoclopramide in the blood and hair is compatible with a passage of breast milk to the child. According to the literature, less than 5% of the maternal dose is found in the child. No case of intoxication through breast milk has been described, to our knowledge.

In this paper, three Iridium(III) complexes, Ir(dnfppy)2(Cl/Pyrrole), Ir(dfppy)2(dpp) and Ir(tfmqz)2(sdpp), have been designed and synthesized. They emitted deep-blue, blue or red photoluminescence with high quantum yields, for ((Ir(dnfppy)2(Cl/Pyrrole): λmax = 447 nm, F = 62.4%; Ir(dfppy)2(dpp): λmax = 467 nm, F = 25%; Ir(tfmqz)2(sdpp): λmax = 609 nm, F = 73.7%), respectively. Two pairs of enantiomers of Ir(dfppy)2(dpp) and Ir(tfmqz)2(sdpp) have been separated by column chromatography. The maximum external quantum efficiency (EQEmax) of OLEDs based on Ir(tfmpqz)2(sddp) was 13.8%, showing a relatively low efficiency roll-off with the EQE of 10.7% at 5000 cd/m2.

Guillain- Barre Syndrome (GBS), an autoimmune neurological disease of peripheral nerves has been causally associated with COVID-19 vaccination in adults. However, no such report has been published so far in children. We describe a 13-year old female child who presented to emergency department with complaints of bilateral upper limb, lower limb and truncal weakness over three days following first dose of recombinant protein subunit COVID-19 vaccine (Corbevax). Clinical examination and nerve conduction studies showed pure motor axonal polyneuropathy with absent compound muscle action potential (CMAP) in all sampled nerves of upper and lower limbs which was consistent with the diagnosis of GBS after ruling out possible alternative aetiologies. A temporal association between first dose of protein subunit COVID-19 vaccine administered a day prior and symptom onset was noted. The causality assessment using World Health Organization (WHO) tool for adverse event following immunization (AEFI) assessment indicated vaccine-product related reaction categorized as A1. Patient’s clinical condition improved after seven sessions of plasmapheresis. The purpose of this report is to create awareness among the health care professionals about COVID-19 vaccine induced GBS in children as early diagnosis and management can be critical in avoiding complications and improving patient outcomes.

A novel double mutation, c.1448T>A (p.L483P, rs421016) in GBA and c.691T>C (p.S231P, rs201332859) in LRRK2 was identified in a 69-year-old man with Parkinsonism who first developed bradykinesia and rigidity in neck at one month after acute hypoxia insult during mountaineering.

FAR1-related phenotypes caused by FAR1 gene encodes the peroxisomal protein, fatty acyl-CoA reductase 1 (FAR1), which is required to reduce fatty acids to fatty alcohols used to form ether-linked alkyl bonds. Biallelic loss of function variants have been associated with severe psychomotor developmental delayed, seizures, cataracts, growth retardation with microcephaly,

Positive interactions have been hypothesized to influence plant community dynamics and species invasions. However, their prevalence and importance relative to negative interactions remain unclear, but are fundamentally important for both theoretical and applied ecology. We examined pairwise biotic interactions using over 50 years of successional data to assess the prevalence of positive interactions and their effects on each focal species (either native or exotic). We found that positive interactions were widespread and the relative frequency of positive and negative interactions varied with establishment stage and between native and exotic species. Specifically, positive interactions were more frequent during early establishment and less frequent at later stages. Positive interactions involving native species were more frequent and stronger than those between exotic species, reducing the impact of invasional meltdown on succession. Our study highlights the role of positive native interactions in shielding communities from biological invasion and enhancing the potential for long-term resilience.

Up to ten males have been reported to sire clutches of crocodilian eggs but review of the underlying study designs raised questions of potential upward bias of inferred sire numbers. To test this premise, different scenarios were explored using a published dataset of 16 known single-sire saltwater crocodile pairs and their offspring which were originally confirmed using an 11 loci microsatellite panel in CERVUS. Varying the number of microsatellites, omitting one or both parental genotypes and using different parentage analysis techniques revealed that total allele number, rather than number of loci, determined inferred sire accuracy in two opposing ways. Using the single-locus minimum method and GERUD, which both require prior knowledge of family groupings (ie nests), fewer alleles (and loci) accurately inferred only one father. In contrast, CERVUS and COLONY required all 11 loci (65 alleles) and both parental genotypes to (a) assign correct family groups and (b) infer the correct sire number, except in one family where two sires were equally assigned based on their number of homozygous loci. When less genotype information was provided, CERVUS and COLONY inferred up to six and seven sires, respectively. Consequently, crocodilian maternal genotypes should at least be obtained either directly (blood, tissue) or indirectly (eggshells, eDNA) in addition to a representative population sample of adult genotypes before embarking on multiple paternity determination. Running different scenarios using different analytical methods and reporting on the lowest number of inferred sires is encouraged remembering these sires are hypothetical until proven by true genotype.

Decomposition of taxonomic, phylogenetic, and functional beta diversity into their turnover and nestedness component could provide novel insight for biodiversity conservation, e.g., provide implications for the Single Large Or Several Small reserves debate (SLOSS debate). This study applied this beta diversity decomposition in wetland bird communities in North China, aiming to propose scientific and comprehensive suggestions for bird diversity conservation in this region. Paired t test was used to compare the differences between taxonomic, phylogenetic, functional turnover and their nestedness component. In addition, spearman correlation analysis was used to assess the associations between each explanatory variable and each beta diversity index. The results showed that taxonomic and phylogenetic beta diversity among wetland bird communities in North China was dominated by turnover, while functional beta diversity was dominated by nestedness. Importantly, the phylogenetic and functional results showed similar patterns even after control the effects of taxonomic beta diversity. In addition, the taxonomic and phylogenetic turnover was more associated with both climate variables and spatial distances than other component. The contrasting patterns between taxonomic, phylogenetic decomposition and functional decomposition of wetland bird communities in North China indicate that distinctive conservation strategies should be considered for different biodiversity dimensions. Specifically, the conservation of taxonomic and phylogenetic bird diversity in this region should focus on multiple wetlands, while the conservation of bird functional diversity should focus on single wetland with high functional diversity.

Background and Purpose: The opioid epidemic remains one of the most pressing public health crises facing the United States. Rising rates of opioid-involved overdose deaths are presently driven primarily by fentanyl and related synthetic opioid agonists that are resistant to reversal by naloxone and increasingly used as adulterants or clandestine substitutes in illicitly produced opioids, sedatives, and psychostimulants. Deaths involving opioids typically result from lethal respiratory depression and it is currently unknown whether co-use of psychostimulants with opioids affects respiratory toxicity. Considering psychostimulant overdoses have increased over 3-fold since 2013, and half of those co-involved opioids, this is a cardinal question. Experimental Approach: Naloxone, d-amphetamine (AMPH), and (+/-)-methamphetamine (METH), were evaluated for their effects on basal and fentanyl-depressed respiration. Minute volume (MVb) was measured in awake, freely moving mice via whole-body plethysmography to quantify fentanyl-induced respiratory depression and its modulation by dose ranges of each test drug. Key Results: Naloxone reversed respiratory depression induced by fentanyl only at the highest dose tested (10 mg•kg-1). Both AMPH and METH exhibited bidirectional effects on MVb under basal conditions, producing depressions then elevations of respiration as dose increased. Under depressed conditions the bidirectional effects of AMPH and METH on respiration were exaggerated, exacerbating and then reversing fentanyl-induced depression as dose increased. Conclusions and Implications: These results indicate that co-use of amphetamines with fentanyl may worsen respiratory depression, but conversely, monoaminergic components of the amphetamines may possibly be exploited to mitigate fentanyl overdose.

This article introduces current status of COVID-19 and its side-effects, and reviews emerging protective measures and strategies from lifestyle to traditional Chinese medicine (TCM) for fighting against the SARS-CoV-2 and its major variants (Delta and Omicron) as well as the global COVID-19 pandemic, which include “Carassius auratus lifestyle” for high effective isolation, social and high-tech related medical strategies, traditional Chinese herbs “Bark-Flower-Fruit-Grass-Leaf-Nucleolus-Root (BFFGLNR)”, as well the combination of Chinese and western medicine. As a choice, little is known whether Chinese acupuncture is an effective method for confirmed and suspected COVID-19 patients, which include imported and asymptomatic cases. Definitely, acupuncture is effective for the recovery of COVID-19 cases. However, its effects and related mechanisms need further animal experiments and clinical trials to confirm and disclose. In conclusion, these emerging protective measures and strategies for COVID-19 will help to effectively combat the SARS-CoV-2 and its variants during the pandemic and post-COVID-19 era.

Biomonitoring surveys from environmental DNA make use of metabarcoding tools to describe the community composition. These studies match their sequencing results against public genomic databases to identify the species. However, mitochondrial genomic reference data are yet incomplete, only a few genes may be available, or the suitability of existing sequence data is suboptimal for species level resolution. Here we present a dedicated and cost-effective workflow with no DNA amplification for generating complete fish mitogenomes for the purpose of strengthening fish mitochondrial databases. Two different long-fragment sequencing approaches using Oxford Nanopore sequencing coupled with mitochondrial DNA enrichment were used. One where the enrichment is achieved by preferential isolation of mitochondria followed by DNA extraction and nuclear DNA depletion (‘mitoenrichment’). A second enrichment approach takes advantage of the CRISPR-Cas9 targeted scission on previously dephosphorylated DNA (‘targeted mitosequencing’). The sequencing results varied between tissue, species, and integrity of the DNA. The mitoenrichment method yielded 0.17-12.33 % of sequences on target and a mean coverage ranging from 74.9-805-fold. The targeted mitosequencing experiment from native genomic DNA yielded 1.83-55 % of sequences on target and a 38-2123-fold mean coverage. This helped complete the mitogenome of species with homopolymeric regions, tandem repeats and gene rearrangements. We demonstrate that deep sequencing of long fragments of native fish DNA is possible, can be achieved with low computational resources in a cost-effective manner, exceeding the widespread genome skimming approach, and allowing the discovery of mitogenomes of non-model or understudied fish taxa to a broad range of laboratories worldwide.

Invasive species are among the most important, growing threats to food security and agricultural systems. The Mediterranean fruit fly Ceratitis capitata is one of the most damaging representatives of a group of rapidly expanding species in the family Tephritidae due to their wide host range and high invasiveness. Here, we used restriction site-associated DNA sequencing (RADseq) to investigate population genomic structure and phylogeographic history of medflies collected from six sampling sites, including Africa (South Africa), the Mediterranean (Spain, Greece), Latin America (Guatemala, Brazil) and Australia. A total of 1,907 single nucleotide polymorphisms (SNPs) showed two genetic clusters separating native and introduced ranges, consistent with previous findings. In the introduced range, all individuals were assigned to one genetic cluster except for those in Brazil, which showed introgression of a genetic cluster that also appeared exclusively in South Africa and could not be previously identified using microsatellite markers. Moreover, the microbiome variations in medfly populations from selected sampling sites was assessed by amplicon sequencing of the 16S ribosomal RNA (V4 region). No strong patterns of microbiome variation were detected across geographic regions or host plants, except for the differentiation of the Brazilian specimens which showed increased diversity and unique composition of its microbiome compared to other sampling sites. The unique SNP patterns in the Brazilian specimens could point to a direct migration route from Africa with subsequent adaptation of the microbiota to the specific conditions present in Brazil. These findings significantly improve our understanding of the evolutionary history of global medfly invasions and adaptation to newly colonised environments.

Background: Aortic regurgitation (AR) is a common cardiovascular complication in patients with Takayasu arteritis (TAK), and complication after aortic valve surgery (AVS) is not rare. This study aimed to identify the long-term postoperative outcomes for significant AR in patients with TAK compared with those in patients without TAK. Methods: We included 35 patients with TAK with moderate-to-severe AR who underwent AVS and compared their postoperative outcomes with those of 105 age- and operation period-matched patients with severe AR but without TAK. The risk factors for poor outcomes (all-cause death and major adverse cardiac and cerebrovascular events [MACCE]) in patients with TAK were analyzed using multivariate Cox regression. Results: The 10-year overall survival rate was 70.5% in patients with TAK and 89.4% in those without TAK (p = 0.048). The MACCE and reoperation rates were significantly higher in patients with TAK (10-year freedom from MACCE, 58.2% vs. 86.4% [p < 0.001]; 10-year freedom from reoperation, 64.5% vs. 98.3% [p < 0.001]). Eighteen of the 35 patients with TAK (51.4%) had poor outcomes, and multivariate analysis revealed that significant coronary artery involvement (hazard ratio [HR], 4.178; 95% confidence interval [CI], 1.222–14.282; p = 0.023) and decreased estimated glomerular filtration rate (HR, 0.968; 95% CI, 0.947–0.989; p = 0.003) were associated with poor outcomes. Conclusion: The long-term postoperative outcomes for AR were poorer in patients with TAK than in those without TAK. The poor outcomes in patients with TAK were associated with coronary artery involvement and decreased renal function.

Simultaneous exposure to multiple stressors potentially complicates enormously the challenge of predicting ecological responses to global environmental change. Here, we show that, though the contributions of individual species and functional groups to ecosystem stability may vary under different disturbance types, their contributions to stability under combined stressors can nonetheless frequently be predicted from their contributions under the individual disturbances acting in isolation. By disturbing natural rocky shore communities experimentally with nutrients and sediments and simultaneously simulating extinction of predatory whelks and grazing consumers both separately and in combination, we found that trophic position does not, however, appear to be a useful general predictor of species contributions to stability. We conclude that quantifying contributions of key species and functional groups to stability across a range of environmental contexts may provide a pathway towards predicting the multifaceted responses of ecosystems to distinct combinations of stressors acting simultaneously.

Management of aortic arch pathologies remains challenging. Open total arch replacements have been associated with significant morbidity and mortality owing to the need for cardiopulmonary bypass and circulatory arrest. On the other hand, aortic arch branched stent grafts are not widely available. In this context, hybrid techniques combining open arch debranching with endovascular graft placement have been identified as an attractive option in select patients. However, there still is a paucity of literature on their application and outcomes. A case is presented of an elderly frail patient diagnosed with a pseudoaneurysm of the aortic arch and who was successfully treated by an off-pump arch debranching followed by endovascular arch repair. This case highlights (i) the feasibility of hybrid debranching techniques, (ii) their technical challenges, and (iii) the need for long-term follow-up data.

In this paper, being investigated an initial - boundary value problem for a one - dimensional wave equation with a nonlinear source of variable order and nonlinear dissipation at the boundary. The existence of a local solution of the problem under consideration is proved. Then the question of the absence of global solutions is investigated. Depending on the relationship between the order of growth of the nonlinear source and the nonlinear boundary dissipation, different results are obtained on the blow - up of weak solutions in a finite time interval.

This article concerns the large deviations regime and the consequent solution of the Kramers problem for a two-time scale stochastic system driven by a common jump noise signal perturbed in small intensity epsilon > 0 and with accelerated jumps by intensity 1/epsilon. We establish Freidlin-Wentzell estimates for the slow process of the multiscale system in the small noise limit epsilon tend to 0 using the weak convergence approach to large deviations theory. The core of our proof is the reduction of the large deviations principle to the establishment of a stochastic averaging principle for auxiliary controlled processes. As consequence we solve the first exit time/ exit locus problem from a bounded domain containing the stable state of the averaged dynamics for the family of the slow processes in the small noise limit.

Phage display technology is commonly applied for high-throughput screening of single-domain antibodies (sdAbs), and the problem of non-specific adsorption caused by carrier proteins is often faced during the biopanning of single-domain antibodies against haptens. Therefore, an enrofloxacin (ENR)-functionalized cryogels was prepared for application in the biopanning of ENR-specific phages, which was prepared by the ethylenediamine (EDA) and carbodiimide methods. To improve the efficiency of biopanning, double blocking, a wash solution flow rate of 1 ml/min and phage pre-incubation were applied to the biopanning process through single-factor experiments. The results of flat colony counting showed that the phage output of AG-ENR cryogels was 15 times higher than the phage output of AG cryogels for the same input amount. And 7 complete sequences of ENR-specific shark sdAbs were obtained by monoclonal phage ELISA and sequence alignment. All these results indicated that AG-ENR cryogels can improve the efficiency of hapten-specific phages biopanning and this study provided a novel and efficient method for phage biopanning for single-domain antibody to haptens.

Introduction: This paper will demonstrate the possibility of the existence of dark matter from astronomy, astrophysics, theoretical physics and give a new possibility that can explain the excessively fast orbiting of the outer stars of the Milky Way and other galaxy clusters. Explain the model. Hint: The text description of this article is a little more than a computational argument argument.

Leaf anatomical traits can reflect plant adaptation to environmental changes. However, whether the trade-offs among leaf anatomical traits can reflect the strategies spectrum of plant response to environmental changes and the strategic spectrum will shift with altitudes are not clear. In this study, 286 plant species from 19 altitudinal gradients from 1050 m to 3070 m on the eastern Tibetan Plateau were selected and 16 anatomical characters of blade, mesophyll and midrib were measured. The strategic and strategic spectra of leaf anatomical trait formation were by principal components analysis, followed by generalized additive models of the strategic spectra with shift in elevation to test the shift of strategy spectra along altitudes. Our results showed that the midrib xylem thickness of woody increased with increasing altitude, while other traits decreased; the upper and lower epidermis width, midrib parenchyma cell thickness and midrib lower epidermis cell thickness of herb increased with increasing altitudes, while other traits decreased. Blade strategic spectrum (BES), blade and mesophyll strategic spectrum (BMSS) and midrib strategic spectrum (MSS) were formed in the tissue of leaves, and the score of principal component one (PC1) was not significant between herbs and woody plants ( P>0.05).  There were mainly formed the spectrum of conservation and support strategies and the spectrum of resource acquisition and consumption, etc. With increasing altitudes, the habitat tended to become unsuitable for plant growth and the resources available to plants are reduced, plants shift from a “invest-fast-reap” acquisition strategy to a “invest-slow-reap” conservative strategy.

A document by Manuel Martinez Gomez . Click on the document to view its contents.