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Autoimmune pancreatitis (AIP), which is characterized by pancreatic enlargement and irregular narrowing of the main pancreatic duct, is difficult to differentiate from malignancy. The irregular narrowing of the pancreatic duct, which can be detected via endoscopic retrograde cholangiopancreatography, is a characteristic feature of AIP; however, distinguishing between localized AIP and pancreatic cancer based on pancreatic duct imaging is difficult. This study overviews the efficacy of endoscopic ultrasound (EUS)-guided pancreatic sampling for the histopathological diagnosis of AIP. Recent enhancements in needle biopsy methodologies and technologies have contributed to improvement in the diagnostic efficacy of this technique. The guidance provided in this study for the histological diagnosis of AIP is anticipated to further advance in the histopathological diagnosis of AIP using EUS-guided pancreatic sampling.Introduced species have become an increasingly common component of biological communities around the world. A central goal in invasion biology is therefore to identify the demographic and evolutionary factors that underlie successful introductions. Here we use whole genome sequences, collected from populations in the native and introduced range of the African fig fly, Zaprionus indianus, to quantify genetic relationships among them, identify potential sources of the introductions, and test for selection at different spatial scales. We find that geographically widespread populations in the western hemisphere are genetically more similar to each other than to lineages sampled across Africa, and that these populations share a mixture of alleles derived from differentiated African lineages. Using patterns of allele-sharing and demographic modelling we show that Z. indinaus have undergone a single expansion across the western hemisphere with admixture between African lineages predating this expansion. We also find support for selection that is shared across populations in the western hemisphere, and in some cases, with a subset of African populations. This suggests either that parallel selection has acted across a large part of Z. indianus's introduced range; or, more parsimoniously, that Z. indianus has experienced selection early on during (or prior-to) its expansion into the western hemisphere. We suggest that the range expansion of Z. indianus has been facilitated by admixture and selection, and that management of this invasion could focus on minimizing future admixture by controlling the movement of individuals within this region rather than between the western and eastern hemisphere.Human-induced environmental change can influence populations both at the global level through climatic warming and at the local level through habitat fragmentation. As populations become more isolated, they can suffer from high levels of inbreeding, which contributes to a reduction in fitness, termed inbreeding depression. However, it is still unclear if this increase in homozygosity also results in a corresponding increase in sensitivity to stressful conditions, which could intensify the already detrimental effects of environmental warming. Here, in a fully factorial design, we assessed the life-long impact of increased inbreeding load and elevated temperature on key life history traits in the seed beetle, Callosobruchus maculatus. We found that beetles raised at higher temperatures had far reduced fitness and survival than beetles from control temperatures. Importantly, these negative effects were exacerbated in inbred beetles as a result of increased inbreeding load, with further detrimental effects manifesting on individual eclosion probability and lifetime reproductive success. These results reveal the harmful impact that increasing temperature and likelihood of habitat fragmentation due to anthropogenetic changes in environmental conditions could have on populations of organisms worldwide.<br /><br /> Insulin-like factor 3 (INSL3) was stated to be an essential regulator in many diseases. This present study aimed to explore the underlying mechanisms of INSL3 in diabetic nephropathy (DN).<br /><br /> The serum samples were obtained from 121 DN patients, 67T2DM patients, and 44healthy controls. Twenty SD rats were used to establish the DN model in vivo. Quantitative PCR (qPCR) and Western blot were completed to analyze the INSL3 expression in cells, serum samples, and kidney of the rats. The structure of kidney was analyzed by HE staining. The diagnostic values of INSL3 in DN were determined by receiver operating characteristic (ROC) assay. Then, Spearman's correlation analysis was executed to verify the association between INSL3 and glomerular filtration rate (eGFR). Finally, the proliferation and apoptosis status of transfected cells were analyzed by MTT, flow cytometry, and Hoechst33258staining assay.<br /><br /> We found that INSL3 expression was up-regulated in DN patients and SV40-MES-13 cells. Furthermore, the correlation analysis elucidated that INSL3 expression was negatively correlated with DN diagnosis golden criterion eGFR. INSL3knockdown promoted the proliferation rate and inhibited the apoptosis rate of SV40-MES-13 cells after high-glucose treatment. Finally, the INSL3 expression and fast blood glucose were up-regulated in DN rats.<br /><br /> Collectively, this study demonstrated the clinical significance of INSL3 in diagnosing and developing DN.<br /><br />Collectively, this study demonstrated the clinical significance of INSL3 in diagnosing and developing DN.Both assortment and plasticity can facilitate social evolution, as each may generate heritable associations between the phenotypes and fitness of individuals and their social partners. However, it currently remains difficult to empirically disentangle these distinct mechanisms in the wild, particularly for complex and environmentally responsive phenotypes subject to measurement error. To address this challenge, we extend the widely used animal model to facilitate unbiased estimation of plasticity, assortment and selection on social traits, for both phenotypic and quantitative genetic (QG) analysis. Our social animal models (SAMs) estimate key evolutionary parameters for the latent reaction norms underlying repeatable patterns of phenotypic interaction across social environments. As a consequence of this approach, SAMs avoid inferential biases caused by various forms of measurement error in the raw phenotypic associations between social partners. We conducted a simulation study to demonstrate the application of SAMs and investigate their performance for both phenotypic and QG analyses. With sufficient repeated measurements, we found desirably high power, low bias and low uncertainty across model parameters using modest sample and effect sizes, leading to robust predictions of selection and adaptation. Our results suggest that SAMs will readily enhance social evolutionary research on a variety of phenotypes in the wild. We provide detailed coding tutorials and worked examples for implementing SAMs in the Stan statistical programming language.Since the late nineties, evidence has accumulated that flow-assisted basophil activation test (BAT) might be an accessible and reliable method to explore the mechanisms governing basophil degranulation and diagnostic allowing correct prediction of the clinical outcome following exposure to the offending allergen(s) and cross-reactive structures for different IgE-dependent allergies and particular forms of autoimmune urticaria. Although the BAT offers many advantages over mediator release tests, it is left with some weaknesses that hinder a wider application. It is preferable to perform the BAT analysis within 4 h of collection, and the technique does not advance diagnosis in patients with non-responsive cells. Besides, the BAT is difficult to standardize mainly because of the difficulty to perform large batch analyses that might span over several days. This article reviews the status of flow cytometric mast cell activation test (MAT) using passively sensitized mast cells (MCs) with patients' sera or plasma (henceforth indicated as passive MAT; pMAT) using both MC lines and cultured MCs in the diagnosis of IgE-dependent allergies. In addition, this paper provides guidance for generating human MCs from peripheral blood CD34+ progenitor cells (PBCMCs) and correct interpretation of flow cytometric analyses of activated and/or degranulating cells. With the recent recognition of the mas-related G protein-coupled receptor X2 (MRGPRX2) occupation as a putative mechanism of immediate drug hypersensitivity reactions (IDHRs), we also speculate how direct activation of MCs (dMAT)-that is direct activation by MRGPRX2 agonists without prior passive sensitization-could advance paradigms for this novel endotype of IDHRs.Pyroptosis and intrinsic apoptosis are two forms of regulated cell death driven by active caspases where plasma membrane permeabilization is induced by gasdermin pores. Caspase-1 induces gasdermin D pore formation during pyroptosis, whereas caspase-3 promotes gasdermin E pore formation during apoptosis. These two types of cell death are accompanied by mitochondrial outer membrane permeabilization due to BAK/BAX pore formation in the external membrane of mitochondria, and to some extent, this complex also affects the inner mitochondrial membrane facilitating mitochondrial DNA relocalization from the matrix to the cytosol. However, the detailed mechanism responsible for this process has not been investigated. Herein, we reported that gasdermin processing is required to induce mitochondrial DNA release from cells during pyroptosis and apoptosis. Gasdermin targeted at the plasma membrane promotes a fast mitochondrial collapse along with the initial accumulation of mitochondrial DNA in the cytosol and then facilitates the DNA's release from the cell when the plasma membrane ruptures. These findings demonstrate that gasdermin action has a critical effect on the plasma membrane and facilitates the release of mitochondrial DNA as a damage-associated molecular pattern.Understanding how organisms adapt to their local environment is central to evolution. With new whole-genome sequencing technologies and the explosion of data, deciphering the genomic basis of complex traits that are ecologically relevant is becoming increasingly feasible. Here, we studied the genomic basis of wing shape in two Neotropical butterflies that inhabit large geographical ranges. Heliconius butterflies at high elevations have been shown to generally have rounder wings than those in the lowlands. We reared over 1,100 butterflies from 71 broods of H. erato and H. melpomene in common-garden conditions and showed that wing aspect ratio, that is, elongatedness, is highly heritable in both species and that elevation-associated wing aspect ratio differences are maintained. Genome-wide associations with a published data set of 666 whole genomes from across a hybrid zone, uncovered a highly polygenic basis to wing aspect ratio variation in the wild. We identified several genes that have roles in wing morphogenesis or wing aspect ratio variation in Drosophila flies, making them promising candidates for future studies. There was little evidence for molecular parallelism in the two species, with only one shared candidate gene, nor for a role of the four known colour pattern loci, except for optix in H. erato. Thus, we present the first insights into the heritability and genomic basis of within-species wing aspect ratio in two Heliconius species, adding to a growing body of evidence that polygenic adaptation may underlie many ecologically relevant traits.High-throughput experimentation (HTE) methods are central to modern medicinal chemistry. While many HTE approaches to C-N and Csp2 -Csp2 bonds are available, options for Csp2 -Csp3 bonds are limited. We report here how the adaptation of nickel-catalyzed cross-electrophile coupling of aryl bromides with alkyl halides to HTE is enabled by AbbVie ChemBeads technology. By using this approach, we were able to quickly map out the reactivity space at a global level with a challenging array of 3×222 micromolar reactions. The observed hit rate (56 %) is competitive with other often-used HTE reactions and the results are scalable. A key to this level of success was the finding that bipyridine 6-carboxamidine (BpyCam), a ligand that had not previously been shown to be optimal in any reaction, is as general as the best-known ligands with complementary reactivity. Such "cryptic" catalysts may be common and modern HTE methods should facilitate the process of finding these catalysts.<br /><br /> Serum neuron-specific enolase (NSE) is an important tumor marker for small cell lung cancer and neuroblastoma. However, the test of serum NSE compromised by specimen hemolysis is presented as a falsely higher result, which seriously disturbs clinical decision. This study aimed to establish a solution integrated with laboratory information system to clear the bias from hemolysis on serum NSE test.<br /><br /> The reference range of serum hemolysis index (HI) was first established, and specimen hemolysis rate was compared between HI test and visual observation. NSE concentration in serum pool with normal HI was spiked with serial diluted lysates from red blood cells to deduce individual corrective equation. The agreement between individual corrective equation and original NSE test was assayed by Bland and Altman plots.<br /><br /> The high HI existed in 32.6% of specimens from patients. The NSE median of hemolyzed specimens was significant higher than the baseline (p=0.038), while the corrected NSE median had no difference compared with the baseline (p=0.757). The mean difference of corrected NSE and initial NSE was 1.92%, the SD of difference was 5.23%, and furthermore, the difference was independent of tendency of HI (Spearman r=-0.069, p=0.640). The 95% confidence interval of mean difference (from -8.33% to 12.17%) was less than the acceptable bias range (±20%).<br /><br /> The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.<br /><br />The agreement between individual correction equation and NSE assay was satisfied. Our automated processing algorithm for serum NSE could provide efficient management of posttest data and correct positive bias from specimen hemolysis.<br /><br /> N-nitroso compounds (NOCs) are among the most potent dietary carcinogens. N-nitrosodiethylamine (NDEA), N-nitrosodimethylamine (NDMA), and N-nitrosopiperidine (NPIP) are abundant in foods and carcinogenic to the liver. We investigated the relationship between dietary NOCs and HCC risk.<br /><br /> In this large, hospital-based, case-control study of 827 pathologically or radiologically confirmed HCC cases and 1,013 controls, NOC intake was calculated by linking food frequency questionnaire-derived dietary data with a comprehensive NOC concentration database. Multivariable-adjusted ORs and 95% CIs of HCC by quartiles of NOC consumption were estimated using logistic regression models, with the lowest quartile as the referent. We further investigated joint effects of consuming the highest quartile of NOCs that were associated with increased HCC risk and hepatitis, diabetes, or alcohol drinking on HCC risk. After adjustment for confounding factors, higher intake of NDEA from plant sources (OR<br /><br /> =1.58; 95% CI=1.03-2.41), urther prospective investigation.<br /><br /> Previous studies have demonstrated relationships between social and environmental characteristics of the drinking context and alcohol use. However, the use of event-level data to investigate individual and joint relationships between such characteristics and alcohol use remains a gap in the literature. This study aimed to examine associations between drinking context (location and social group size) and alcohol consumption, and estimate the relationship between the interaction of context and alcohol consumption.<br /><br /> Using an Internet-based cellphone-optimised assessment technique, 183 Swiss young adults (mean 23 years; range 17-37 years) completed hourly assessments from 8pm to midnight Thursday through Saturday for five consecutive weeks. Participants contributed 3454 hourly questionnaires. The number of drinks, the number of friends present and location (off-premise-home, outdoors; on-premise-bars, restaurants) were assessed based on the previous hour. Multilevel mixed-effects models were used to assess theremise locations compared to on-premise locations. Findings have implications for tailored interventions focused on reducing alcohol consumption by young adults.<br /><br /> Enlarged facial pores are one of the common skin signs of photoaging that patients seek treatment for. However, objective data and long-term assessment on the efficacy and safety of therapeutic procedures for this condition are limited.<br /><br /> To objectively evaluate the efficacy and safety of a 1064-nm picosecond laser with microlens array (MLA) for pore tightening.<br /><br /> Twenty-five patients with enlarged pores received three treatments with a 1064-nm picosecond laser coupled with MLA at 4-week intervals. Patients were evaluated using objective (measurement of pore volume using three-dimensional photography) and subjective (clinical evaluation by two blinded dermatologists) assessments at baseline and at the 1-, 3-, and 6-month follow-ups. Adverse effects were also recorded during each visit.<br /><br /> After three treatments, there was a significant reduction of pore size from baseline (p &lt; 0.001). The improvement in pore size appearance significantly continued from the 1-month to the 6-month follow-up visits (p = 0.013). The total average pore size was 1.15652 ± 0.614322 and 0.8087 ± 0.50515 at baseline and at 6 months after the final treatment, respectively, resulting in an average of 30% reduction in pore size. No cases of dyspigmentation, textural alteration, or scarring were documented.<br /><br /> Fractional 1064-nm picosecond laser appears to be effective and safe for reducing pore size in Asians with minimal transient side effects.<br /><br />Fractional 1064-nm picosecond laser appears to be effective and safe for reducing pore size in Asians with minimal transient side effects.<br /><br /> Activity of 1,2-o-dilauryl-rac-glycero-3-glutaric acid-(6'-methylresorufin) ester (DGGR) lipase is considered to be more pancreas specific than traditional lipase assays. The aim of this study was to evaluate the diagnostic performance of DGGR lipase activity for suspected acute pancreatitis in dogs and to assess its prognostic usefulness.<br /><br /> Retrospective study of case records for suspected acute pancreatitis based on clinician-stated diagnosis, point-of-care and quantitative canine pancreas-specific lipase (cPL) results and consistent ultrasonographic features. Diagnostic performance of DGGR lipase was assessed by receiver-operating characteristic curve analysis, agreement by Cohen's kappa (κ) and prognostic value by multiple regression analysis.<br /><br /> Median DGGR lipase activity was significantly (P&lt; 0.001) higher in dogs with suspected acute pancreatitis [93.7 (range, 11.0-2853.0) U/L (n=158)] compared to those with no evidence of pancreatitis [range, 20.9 (6.7-89.0) U/L (n=356)]. A DGGR lipase activity &amp; studies are required to more fully assess its value in prognostication.<br /><br /> Patients with advanced ampullary carcinoma (AC) who are unsuitable for surgery are most likely to have poor outcomes. The role of endoscopic radiofrequency ablation (RFA) in this population has not been fully defined. We aimed to assess the short- and long-term outcomes of RFA in a large cohort of AC patients.<br /><br /> In this retrospective study, data of consecutive patients with pathologically proven AC who underwent successful endobiliary RFA and/or stent placement were collected. All patients did not undergo surgical resection. The primary outcome was overall survival (OS). The secondary outcomes included clinical success and adverse events.<br /><br /> A total of 85 patients, 50 in the RFA plus stenting group and 35 in the stenting alone group, were identified. The median OS was significantly longer in the RFA group than in the stenting alone group (16.9 vs. 9.8months, P&lt;0.001). In multivariable Cox analysis, RFA (hazards ratio 0.408; 95% confidence interval 0.235-0.706; P=0.001) was the only independent OS predictor. Eight patients with stage II tumors, exclusively from the RFA group, survived for more than 3years. Clinical success was comparable between the two groups (96% vs. 100%, P=0.231). Early adverse events between the two groups were similar (10% vs. 2.9%, P=0.206); however, late biliary/pancreatic stenoses occurred in three RFA patients who were successfully managed with endoscopic interventions.<br /><br /> Endoscopic RFA appears to prolong patients' survival with acceptable safety; it may therefore be a feasible treatment option for patients with inoperable ampullary cancers.<br /><br />Endoscopic RFA appears to prolong patients' survival with acceptable safety; it may therefore be a feasible treatment option for patients with inoperable ampullary cancers.We tap into an unexplored area of preferential crystallization, being the first to develop simultaneous chiral resolution of two racemic compounds by preferential cocrystallization. We highlight how the two racemic compounds RS-mandelic acid (MAN) and RS-etiracetam (ETI) can be combined together as enantiospecific R-MAN⋅R-ETI and S-MAN⋅S-ETI cocrystals forming a stable conglomerate system and subsequently develop a cyclic preferential crystallization allowing to simultaneous resolve both compounds. The developed process leads to excellent enantiopurity both for etiracetam (ee&gt;98 %) and mandelic acid (ee≈95 %) enantiomers.Temperature-driven fluorescent NOT logic is demonstrated by exploiting predissociation in a 1,3,5-trisubstituted Δ2 -pyrazoline on its own and when grafted onto silica microparticles. Related Δ2 -pyrazolines become proton-driven YES and NOT logic gates on the basis of fluorescent photoinduced electron transfer (PET) switches. Additional PASS 1 and YES+PASS 1 logic gates on silica are also demonstrated within the same family. Beside these small-molecule systems, a polymeric molecular thermometer based on a benzofurazan-derivatized N-isopropylacrylamide copolymer is attached to silica to produce temperature-driven fluorescent YES logic.<br /><br /> Vancomycin is frequently used in paediatric hospitals. Data suggest trough levels of 10-20mg/L are needed to achieve bacterial killing. This study aimed to evaluate if commonly used dosing regimens are efficient in reaching these levels and if therapeutic drug monitoring (TDM) was appropriately used.<br /><br /> All children receiving intravenous vancomycin at the Children´s Hospital Iceland between 2012 and 2016 were included. Vancomycin trough levels were registered. Student t test, Wilcoxon test and regression models were used for statistical analysis.<br /><br /> A total of 105 children received 163 vancomycin treatments (55/105 neonates). Average daily dose in neonates was 23.4mg/kg/day and 38.4mg/kg/day for older children. No TDM was done in 58 treatments (35.6%). First trough levels were &lt;10mg/L in 52.4% and &lt;15mg/L in 92% of cases. Therapeutic levels were less likely achieved in children with malignancy (11.8%) compared with others (36.8%, p=0.09).<br /><br /> In more than half of the cases, trough drug levels were &lt;10mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use.<br /><br />In more than half of the cases, trough drug levels were less then 10 mg/L and malignancy was associated with the lowest probability of reaching therapeutic levels. This study suggests that starting doses of vancomycin in children should be higher, especially in relation to malignant diseases and supports the importance of antibiotic stewardship to ensure optimal antibiotic use.<br /><br /> To describe cochlear implantation (CI) outcomes, with speech perception, auditory, language, and parent-reported auditory and speech behaviors, in children with an enlarged vestibular aqueduct (EVA) and incomplete partition type 2 (IP-II) and compare to control children without inner ear malformations (IEMs) and to determine cerebrospinal fluid gusher rates and effect on outcomes.<br /><br /> Systematic review and meta-analysis.<br /><br /> MEDLINE, Embase, Cochrane, and CINAHL databases were searched from inception to February 2020. Studies reporting relevant outcomes in children with EVA or EVA + IP-II and controls without IEMs undergoing CI were included. Mean differences in speech perception, auditory, and language scores between cases and controls were meta-analyzed. Gusher rates were determined by proportion meta-analyses.<br /><br /> Of 214 identified articles, 42 met inclusion criteria, evaluating 775 cases and 2,191 controls. Of -cases, 578 (74.6%) had EVA and 197 (25.4%) had EVA + IP-II. Cases showed a significant improvement in speech perception, auditory and language performance, comparable to controls. Parent-reported auditory and speech production behaviors outcomes were positive among cases and comparable to controls. Pooled gusher proportions in EVA and EVA + IP-II cases were 27.7% (95% CI 17.6-39.1) and 48.6% (95% CI 28.6-69.0), respectively, with a proportion difference of 20.9% (95% CI 11.0-30.1). Gusher occurrence did not impact speech perception or language outcomes.<br /><br /> Outcomes in children with EVA or EVA + IP-II undergoing CI are favorable and largely comparable to outcomes in children with hearing loss undergoing CI without IEMs. Intraoperative gusher is more prevalent among children with EVA + IP-II as compared to iEVA. Gusher does not influence speech perception and language development outcomes.<br /><br /> NA Laryngoscope, 2021.<br /><br />NA Laryngoscope, 2021.Sulfur-doped graphitic carbon nitride (S-g-CN) has gained significant attention in recent years. Sulfur-doped graphitic carbon nitride (S-g-CN) is a promising metal-free photocatalyst because of its band orientation, natural abundance and groundwork. Improved photocatalytic activity of S-g-CN material for solar chemical production persists a hot yet challenging problem. Herein, we provide an adaptable method for the synthesis of S-g-CN nanocomposite decorated with the moiety of giant polyoxometalate (S-g-CN/Mo-368) that subsequently showed highly efficient photocatalytic activity. The as-synthesized S-g-CN/Mo-368 as a recyclable artificial photocatalyst revealed excellent activity for solar chemical production, that is nicotinamide adenine dinucleotide (NADH) regeneration under visible light. The immobilized Mo-368 on the S-g-CN surface increased the visible light adsorption capacity of the S-g-CN/Mo-368 photocatalyst. The visible light absorption activity, morphology, element compositions, particle size and zeta potential of S-g-CN powder and S-g-CN/Mo-368 were thoroughly investigated. From the application point of view, S-g-CN/Mo-368 was applied to determine the solar chemical production (i.e. NADH regeneration) under visible light with a higher yield% of about ~ 94.85%.This is the first American Association for the Study of Liver Diseases (AASLD) Practice Guidance on the management of malnutrition, frailty, and sarcopenia in patients with cirrhosis. This guidance represents the consensus of a panel of experts after a thorough review and vigorous debate of the literature published to date, incorporating clinical experience and common sense to fill in the gaps when appropriate. Our goal was to offer clinicians pragmatic recommendations that could be implemented immediately in clinical practice to target malnutrition, frailty, and sarcopenia in this population.Whereas the rising prevalence of nonalcoholic fatty liver disease (NAFLD) is closely related with the global obesity epidemic, up to 10-20% of individuals with NAFLD are lean as defined by a body mass index of less then 25 kg/m2 , or less then 23 kg/m2 in Asians. This entity designated as "lean NAFLD" is estimated to affect 8 to 10 million individuals in the United States alone. Here, we review the emerging data on the epidemiology, natural history and prognosis of lean NAFLD and put forward a diagnostic approach that combines detailed clinical phenotyping with genomic analysis. We propose two subtypes of lean NAFLD referred to as type 1 individuals with visceral adiposity and insulin resistance but normal BMI; and type 2 lean individuals with hepatic steatosis secondary to a known or unknown monogenic disease. We envision that incorporation of genomic analysis in the diagnostic algorithm of lean patients with NAFLD will elucidate the contribution of common genetic variants through the calculation of NAFLD polygenic risk score and also characterize the diverse array of rare monogenic diseases that can lead to triglyceride accumulation in the cytoplasm of hepatocytes. Collectively, the integration of a molecular diagnosis in the clinical evaluation of patients with lean NAFLD will provide an accurate diagnosis, with possible targeted therapies and may uncover novel molecular mechanisms with potential broader therapeutic implications.<br /><br /> Laryngeal squamous cell carcinoma (LSCC) has a non-negligible incidence in elderly patients. However, there is still no clear indication on the ideal treatment for early-intermediate glottic LSCC in this specific age group. Both surgical and nonsurgical approaches may be burdened by complications and sequelae that negatively impact patient's health. In this setting, carbon dioxide transoral laser microsurgery (CO<br /><br /> TOLMS) is a promising minimally invasive treatment option.<br /><br /> Retrospective case series in a single tertiary academic institution.<br /><br /> Patients who underwent CO<br /><br /> TOLMS for Tis-T3 glottic LSCC from 1997 to 2017 were reviewed. Demographic, clinical, and tumor characteristics, as well as postoperative complications were recorded. Overall (OS), disease-specific (DSS), recurrence-free (RFS), laryngo-esophageal dysfunction free survivals (LEDFS), and organ preservation (OP) were calculated.<br /><br /> A total of 134 patients (mean age, 80 ± 4 years; median, 79; range, 75-93) were included in the study. Seven lesions were classified as pTis, 65 as pT1a, 22 as pT1b, 35 as pT2, and 5 as pT3. No treatment-related death was observed. Twenty-eight (20.9%) patients reported 10 surgical and 19 medical complications. Five-year OS, DSS, RFS, LEDFS, and OP were 68.9%, 95.4%, 79.5%, 66%, and 92.5%, respectively. Age and comorbidities were associated with OS and LEDFS. Advanced T categories were negatively correlated with OS, DSS, RFS, LEDFS, and OP. Age and comorbidities were not significant risk factors for complications.<br /><br /> CO<br /><br /> TOLMS can be considered a valuable therapeutic approach for selected Tis-T3 glottic LSCC even in the elderly given its favorable oncologic outcomes and minimal aggressiveness.<br /><br /> 4 Laryngoscope, 2021.<br /><br />4 Laryngoscope, 2021.<br /><br /> Oxalic acid is a common antinutrient in the human diet, found in large quantities in spinach. However, spinach is highly regarded by vegetable producers because of its nutritional content and economic value. One of the primary purposes of spinach-breeding programs is to improve the nutritional value of spinach by adjusting oxalate accumulation. Knowledge of the biosynthetic patterns of oxalic acid, and its different forms, is important for a better understanding of this process.<br /><br /> We found three biosynthetic patterns of accumulation and concentration of oxalates. Two of them are related to the maximum type and one is related to the minimum type. We also developed a general model of variations in these compounds in the genotypes that were studied.<br /><br /> This study introduced a unique type of spinach with high oxalate accumulation, which could be particularly suitable for consumption. This had the highest ratio of insoluble oxalate to soluble oxalate. It also accumulated more ascorbic acid (AA) than other types. Our findings in this study also indicate a small role for AA as a precursor to oxalate production in spinach, possibly confirming the significant role of glyoxylate as the most critical precursor in this plant. © 2021 Society of Chemical Industry.<br /><br />This study introduced a unique type of spinach with high oxalate accumulation, which could be particularly suitable for consumption. This had the highest ratio of insoluble oxalate to soluble oxalate. It also accumulated more ascorbic acid (AA) than other types. Our findings in this study also indicate a small role for AA as a precursor to oxalate production in spinach, possibly confirming the significant role of glyoxylate as the most critical precursor in this plant. © 2021 Society of Chemical Industry.The neural tube of amniotes is formed through different mechanisms that take place in the anterior and posterior regions and involve neural plate folding or mesenchymal condensation followed by its cavitation. Meanwhile, in teleost trunk region, the neural plate forms the neural keel, while the lumen develops later. However, the data on neurulation and other morphogenetic processes in the posterior body region in Teleostei remain fragmentary. We proposed that there could be variations in the morphogenetic processes, such as cell shape changes and cell rearrangements, in the posterior region compared to the anterior one at the different stages. Here, we performed morphological and histochemical analyses of morphogenetic processes with an emphasis on neurulation in the zebrafish tail bud (TB) and posterior region. To analyze the posterior expression of sox2 and tbxta we performed whole mount in situ hybridization. We showed that the TB cells of variable shapes and orientation are tightly packed, and the neural and notochord primordia develop first. The shape of the neural primordium undergoes numerous changes as a result of cell rearrangements leading to the development of the neural rod. At the prim-6 stage, the cells of the neural primordium directly form the neural rod. The neuroepithelial cells undergo sequential shape changes. At the stage of the neural rod formation, the apical regions of triangular neuroepithelial cells of the floor plate are enriched in F-actin. The neurocoel development onset is above the apical poles of neuroepithelial cells. The expression domains of sox2 and tbxta become more restricted during the development.<br /><br /> Treatment of vascular lesions is one of the main applications of cutaneous laser technology, while the other is laser hair removal. We present here a vascular laser pumped by a commercial hair removal laser.<br /><br /> A novel 524 nm vascular laser was designed using a 755 nm hair removal laser as a pumping source. This 524 nm vascular laser was used to treat facial redness and leg telangiectasias in 24 subjects. Four treatments were administered to the face at 4-6-week intervals and final photographs were taken 8 weeks following the final treatment, while two treatments were administered to lower-extremity spider veins at 2-month intervals with follow-up photographs 3 months following the final treatment. Blinded analysis of digital images was performed by two physicians not involved in the study.<br /><br /> Blinded evaluation of digital photographs revealed an average improvement score of 3.3 ± 1.7 (mean ± SEM) on a 0-10 scale for removing facial redness (p &lt; 0.001), representing a 33% improvement. Leg veins improved an average of 51% corresponding to a score of 5.1 ± 2.0 (p &lt; 0.001). Side effects were mild and limited to erythema, purpura, edema, and one instance of mild hyperpigmentation.<br /><br /> This novel 524 nm laser is safe and effective for treating vascularity on the face and legs, and proves the ability to create a laser platform incorporating a hair removal laser which then can be used as a pumping source for the attached vascular laser module.<br /><br />This novel 524 nm laser is safe and effective for treating vascularity on the face and legs, and proves the ability to create a laser platform incorporating a hair removal laser which then can be used as a pumping source for the attached vascular laser module.<br /><br /> Non-alcoholic fatty liver disease (NAFLD) is the most common hepatic pathology in western countries and no treatment is currently available. NAFLD is characterized by the aberrant hepatocellular accumulation of fatty acids in the form of lipid droplets (LD). Recently, it was shown that liver LD degradation occurs via a process termed lipophagy; a novel form of autophagy. However, the molecular mechanisms governing liver lipophagy are elusive. Here, we aimed to ascertain the key molecular players that regulate hepatic lipophagy and their importance in NAFLD.<br /><br /> We analyzed the formation and degradation of LD in vitro (fibroblasts and primary mouse hepatocytes), in vivo and ex vivo (mouse and human liver slices) and focused on the role of the autophagy master regulator mammalian Target Of Rapamycin Complex 1 (mTORC1) and the LD coating protein Plin3 in these processes. We show that the autophagy machinery is recruited to the LD upon hepatic overload of oleic acid in all experimental settings. This led to activation of lipophagy, a process that was abolished by Plin3 knockdown using RNA interference. Furthermore, Plin3 directly interacted with the autophagy proteins Fip200 and Atg16L, suggesting that Plin3 functions as a docking protein or is involved in autophagosome formation to activate lipophagy. Finally, we show that mTORC1 phosphorylated Plin3 to promote LD degradation.<br /><br /> These results reveal that mTORC1 regulates liver lipophagy through a mechanism dependent on Plin3 phosphorylation. We propose that stimulating this pathway can enhance lipophagy in hepatocytes to help protect the liver from lipid-mediated toxicity, thus offering a new therapeutic strategy in NAFLD.<br /><br />These results reveal that mTORC1 regulates liver lipophagy through a mechanism dependent on Plin3 phosphorylation. We propose that stimulating this pathway can enhance lipophagy in hepatocytes to help protect the liver from lipid-mediated toxicity, thus offering a new therapeutic strategy in NAFLD.Response to medications, the principal treatment modality for acute and chronic diseases, is highly variable, with 40-70% of patients exhibiting lack of efficacy or adverse drug reactions. With ~ 15-30% of this variability explained by genetic variants, pharmacogenomics has become a valuable tool in our armamentarium for optimizing treatments and is poised to play an increasing role in clinical care. This review presents the progress made toward elucidating genetic underpinnings of drug response including discovery of race/ancestry-specific pharmacogenetic variants and discusses the current evidence and evidence framework for actionability. The review is framed in the context of changing demographics and evolving views related to race and ancestry. Finally, it highlights the vital role played by cohort studies in elucidating genetic differences in drug response across race and ancestry and the informal collaborations that have enabled the field to bridge the "bench to bedside" translational gap.The general expression is derived for the diffusiophoretic velocity of a spherical colloidal particle of radius a in a concentration gradient of symmetrical electrolyte. On the basis of this expression, simple approximate analytic expressions for the diffusiophoretic velocity correct up to the order of 1/κa is derived, where κ is the Debye-Hückel parameter. It is found that the approximate expression correct to order unity can be applied for κa ≥ 50 with negligible errors, while the approximate expression correct to order 1/κa can be applied for κa ≥ 20 with negligible errors.In the past decade, mRNA markers have been well demonstrated as promising molecular markers in forensic body fluid identification (BFI), and successfully used in wide applications. Several studies have assessed the performance of semen-specific mRNA markers in distinguishing semen from other common body fluids at the crime scene. Infertility has been reported as a global health problem that is affecting approximately 15% of couples worldwide. Therefore, it is important for forensic researchers to consider the impact of infertility on semen identification. This study aimed to explore the effect of semen from infertile men (hereinafter "infertile semen") on BFI and to identify semen-specific mRNAs that can efficiently and accurately distinguish normal and infertile semen samples from other body fluids. Results showed that the selected five mRNAs (KLK3, TGM4, SEMG1, PRM1, and PRM2) performed a significantly high semen specificity in normal semen. Moreover, KLK3 was slightly influenced by infertile semen samples with over 98% positive results in all semen samples. The accuracy to predict normal semen reached up to 96.6% using the discrimination function Y1 with KLK3 and PRM1. However, when the infertile semen samples were included in discrimination function (function Y2 with KLK3), the accuracy rate of semen identification (including the normal and infertile semen) was down to 89.5%. Besides, the sensitivity of multiplex assay could reach down to 50pg. Our results suggest that it is important to consider the presence of infertile semen when using mRNAs to identify semen samples, which would have a far-reaching impact in forensic identification.<br /><br /> Although germ-free mice are an indispensable tool in studying the gut microbiome and its effects on host physiology, they are phenotypically different than their conventional counterparts. While antibiotic-mediated microbiota depletion in conventional mice leads to physiologic alterations that often mimic the germ-free state, the degree to which the effects of microbial colonization on the host are reversible is unclear. The gut microbiota produce abundant short chain fatty acids (SCFAs), and previous studies have demonstrated a link between microbial-derived SCFAs and global hepatic histone acetylation in germ-free mice.<br /><br /> We demonstrate that global hepatic histone acetylation states measured by mass spectrometry remained largely unchanged despite loss of luminal and portal vein SCFAs after antibiotic-mediated microbiota depletion. In contrast to stable hepatic histone acetylation states, we see robust hepatic transcriptomic alterations after microbiota depletion. Additionally, neither dietary supplementation with supraphysiologic levels of SCFA nor the induction of hepatocyte proliferation in the absence of microbiota-derived SCFAs led to alterations in global hepatic histone acetylation.<br /><br /> These results suggest that microbiota-dependent landscaping of the hepatic epigenome through global histone acetylation is static in nature, while the hepatic transcriptome is responsive to alterations in the gut microbiota.<br /><br />These results suggest that microbiota-dependent landscaping of the hepatic epigenome through global histone acetylation is static in nature, while the hepatic transcriptome is responsive to alterations in the gut microbiota.<br /><br /> Metabolic adaptation driven by oestrogen-related receptor-α (ERRα/NR3B1) is required to meet the increased energy demand during osteoclast differentiation. Here, we hypothesize that natural product, andrographolide, acts as an ERRα inverse agonist to inhibit osteoclastogenesis.<br /><br /> Virtual docking and site-directed mutagenesis analysis were employed to study the binding mode of andrographolide to ERRα. Co-immunoprecipitation, luciferase reporter assay, real-time polymerase chain reaction (PCR) and immunoblot analyses were performed to identify andrographolide as an ERRα inverse agonist. The pharmacological effects of andrographolide in vivo were assessed in mice models of osteopenia induced by either a high-fat diet in male or ovariectomy in female mice.<br /><br /> ERRα-dependent expression of glutaminase, a rate-limiting enzyme of mitochondrial glutamine anaplerosis, is required for ex vivo bone marrow osteoclast differentiation. Andrographolide inhibited glutaminase expression induced by ERRα and co-activator peroxieoclast differentiation, implying that andrographolide may be a promising natural compound for preventing physiological and pathological bone loss.In magnetobiology, it is difficult to reproduce the nonspecific (not associated with specialized receptors) biological effects of weak magnetic fields. This means that some important characteristic of the data may be missed in standard statistical processing, where the set of measurements to be averaged belongs to the same population so that the contribution of fluctuations decreases according to the Central Limit Theorem. It has been shown that a series of measurements of a nonspecific magnetic effect contains not only the usual scatter of data around the mean but also a significant random component in the mean itself. This random component indicates that measurements belong to different statistical populations, which requires special processing. This component, otherwise called heterogeneity, is an additional characteristic that is typically overlooked, and which reduces reproducibility. The current method for studying and summarizing highly heterogeneous data is the random-effect meta-analysis of absolute values, i.e., of magnitudes, rather than the values themselves. However, this estimator-the average of absolute values-has a significant positive bias when it comes to the small effects that are characteristic of magnetobiology. To solve this problem, an improved estimator based on the folded normal distribution that gives several times less bias is proposed. We used this improved estimator to analyze the nonspecific effect of the hypomagnetic field in the Stroop test in 40 subjects and found a statistically significant meta-effect with a standardized average of magnitudes of about 0.1. It has been shown that the proposed approach can also be applied to a single study. © 2021 Bioelectromagnetics Society.In Australia, Aboriginal and Torres Strait Islander community controlled health services have been established since 1971 to provide accessible, quality and culturally-appropriate primary healthcare. The first of these services, the Aboriginal Medical Service Cooperative Redfern ('the AMS'), created its own Drug and Alcohol Unit ('the Unit') in 1999. The Unit initially prescribed opioid substitution treatment (OST) and its coordinator, Bradley Freeburn, a Bundjalung man, provided counselling. Soon afterwards, the Unit started dispensing OST. It now cares for around 150 individuals, each of whom is understood in the context of family, community and culture. The Unit is on the same site as the AMS's primary care service, specialised medical and mental health clinics, and dental clinic. This allows for integrated physical and mental health care. The Unit contributes to drug and alcohol workforce development for other AMS staff, state-wide and nationally. Several Aboriginal and Torres Strait Islander community controlled health services around Australia now offer OST prescription, and a small number administer slow-release buprenorphine. We are not aware of others that dispense Suboxone. In the USA and Canada, over the last 10 years, First Nations communities have also responded to lack of treatment access, by creating standalone OST clinics. We were not able to find examples of Māori-controlled OST clinics in Aotearoa, New Zealand. The feasibility of this model of readily accessible OST, situated within a holistic, culturally-grounded primary health-care service recommends it for consideration and evaluation, for Indigenous or non-Indigenous communities.<br /><br /> The aim of the present study was to examine the relation between adipose tissue content of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the risk of incident atrial fibrillation (AF).<br /><br /> In this case-cohort study based on data from the Danish Diet, Cancer and Health cohort, a total of 5255 incident cases of AF was identified during 16.9years of follow-up. Adipose tissue biopsies collected at baseline from all cases and from a randomly drawn subcohort of 3440 participants were determined by gas chromatography. Data were analysed using weighted Cox regression.<br /><br /> Data were available for 4741 incident cases of AF (2920 men and 1821 women). Participants in the highest vs. the lowest quintile of EPA experienced a 45% lower risk of AF (men HR 0.55 (95% CI 0.41-0.69); women HR 0.55 (0.41-0.72)). For DHA, no clear association was found in men, whereas in women, participants in the highest quintile of DHA in adipose tissue had a 30% lower risk of incident AF (HR 0.70 (0.54-0.91)) compared to participants in the lowest quintile.<br /><br /> A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.<br /><br />A monotonous inverse association was found for the content of EPA in adipose tissue and risk of AF in both men and women. The content of DHA was inversely associated with the risk of AF in women, whereas no clear association was found for men.Expanded access is a treatment use of investigational drugs, biologicals or medical devices outside of clinical trials. The purpose of our study was to assess self-reported conflicts of interest (COIs) in oncology expanded access studies. One hundred fifty-eight oncology expanded access studies published from 2013 through 2020 were included. The pharmaceutical industry funded either completely or in part 94 studies (59.49%). The authors disclosed mostly financial COIs, while the number of the reported nonfinancial conflicts was relatively small (3528 and 57 COIs, respectively). The number of articles in which at least one author had a financial COI was 118 (74.68%). The most common financial COI types included advisory board membership/consulting (1471 COIs; 41.7%), followed by honoraria (570 COIs; 16.16%) and research funding (441 COIs; 12.5%). Logistic regression was performed to identify predictors of disclosing financial COIs and positive study's conclusions. On univariate analysis, financial COIs were more likely to occur in studies with at least one center located in the United States (odds ratio [OR], 5.62; 95% confidence interval [CI], 1.57-35.98; P = .02). We also found that positive conclusions about the studied treatments were less likely in studies without industry funding (OR, 0.26; CI, 0.08-0.77; P = .01). Most of the research on COIs in oncology performed to date focused on other types of studies, especially clinical trials. To our knowledge, our study is the first to evaluate COIs in oncology expanded access studies.The host defence of insects includes a combination of cellular and humoral responses. The cellular arm of the insect innate immune system includes mechanisms that are directly mediated by haemocytes (e.g., phagocytosis, nodulation and encapsulation). In addition, melanization accompanying coagulation, clot formation and wound healing, nodulation and encapsulation processes leads to the formation of cytotoxic redox-cycling melanin precursors and reactive oxygen and nitrogen species. However, demarcation between cellular and humoral immune reactions as two distinct categories is not straightforward. This is because many humoral factors affect haemocyte functions and haemocytes themselves are an important source of many humoral molecules. There is also a considerable overlap between cellular and humoral immune functions that span from recognition of foreign intruders to clot formation. Here, we review these immune reactions starting with the cellular mechanisms that limit haemolymph loss and participate in wound healing and clot formation and advancing to cellular functions that are critical in restricting pathogen movement and replication.