Stephenswiese1784

Detailed comparisons of the echinoid juvenile nervous system with those of asteroid and holothuroid juveniles moreover supported a general conservation of the main neural structures in all three species, including at the level of the appendages. Our results support the previously proposed hypotheses for the existence of two neural units in echinoderms one consisting of the basiepidermal nerve plexus to process sensory stimuli locally and one composed of the radial nerve cords and the peripheral nerves constituting a centralized control system. This study provides the basis for more in-depth comparisons of the echinoderm adult nervous system with those of other animals, in particular hemichordates and chordates, to address the long-standing controversies about deuterostome nervous system evolution.

This cross-sectional study aimed to examine the diagnostic ability of salivary matrix metalloproteinase (MMP)-9 lateral flow test (LFT) point-of-care (POC) kit and develop an algorithm for diagnosis of periodontitis.

Through Seoul National Dental Hospital, 137 participants (46 LFT negatives, 91 LFT positives) were recruited. For salivary diagnostics, 150μl of the unstimulated saliva was applied to LFT-POC kit. To make a diagnosis of periodontitis, stage II-IV in modified new international classification system was used. Covariates encompassing age, sex, smoking and obesity were evaluated through face-to-face interview. Enzyme-linked immunosorbent assay was used for quantification of salivary MMP-9. To develop a diagnostic algorithm, multivariable logistic regression analysis was used. Receiver operating characteristic curve was applied for evaluating diagnostic ability.

Diagnostic ability of salivary MMP-9 LFT-POC test was 0.82 (sensitivity of 0.92, specificity of 0.72) in total participants. Diagnostic algorithm using POC test resulted in a response equation, that is algorithm score = -3.675+2.877*LFT+0.034*age+0.121*sex+0.372*smoking+0.192*obesity. Diagnostic ability of the algorithm was 0.88 (sensitivity of 0.92, specificity of 0.85) with cut-off score of 0.589.

Salivary MMP-9 LFT-POC kit showed appropriate diagnostic ability for periodontitis and would be an efficient tool for screening of periodontitis.

Salivary MMP-9 LFT-POC kit showed appropriate diagnostic ability for periodontitis and would be an efficient tool for screening of periodontitis.

There is still limited evidence from prospective high-risk research on the evolution of specific disorders that may emerge early in the development of mood disorders. Moreover, few studies have examined the specificity of mood disorder subtypes among offspring of parents with both major subtypes of mood disorders and controls based on prospective tracking across the transition from childhood to adulthood. Our specific objectives were to (a) identify differences in patterns of psychopathological precursors among youth with (hypo)mania compared to MDD and (b) examine whether these patterns differ by subtypes of parental mood disorders.

Our data stem from a prospective cohort study of 449 directly interviewed offspring (51% female, mean age 10.1years at study intake) of 88 patients with BPD, 71 with MDD, 30 with substance use disorders and 60 medical controls. The mean duration of follow-up was 13.2years with evaluations conducted every three years.

Within the whole cohort of offspring, MDE (Hazard Ratio=4on to BPD.

Dental rehabilitation post-radiotherapy often requires the consideration of dental implants. However, these are tentatively prescribed due to the concern of hypovascularisation and possible osteoradionecrosis. Hence, the current study assessed the microvasculature of the dento-alveolar bone at implant sites taking into consideration the exact radiotherapy dose received to the region.

Bone cores were taken from nine patients during implant treatment and compared to nine control patients. Specimens were stained using CD31 and digitalised using a high-resolution scanner for qualitative and quantitative assessment of the microvasculature. Monaco

treatment planning system was used to volume the implant site providing mean dose (D

) and maximum dose (D

).

A total of 23 bone cores were retrieved for analysis. The cohort had a D

of 38.4Gy (59.6-24.3Gy). Qualitative analysis identified a clear reduction in the miniscule terminal capillaries and high incidence of obliterated lumens with increasing radiothble survival in certain oropharyngeal and nasopharyngeal cancer, dental rehabilitation via implants provides a significant clinical challenge.Most studies on the acquisition of advantageous traits in transgenic animals only focus on monogenic traits. In practical applications, transgenic animals need to possess multiple advantages. Therefore, multiple genes need to be edited simultaneously. CRISPR/Cas9 technology has been widely used in many research fields. However, few studies on endogenous gene mutation and simultaneous exogenous gene insertion performed via CRISPR/Cas9 technology are available. In this study, the CRISPR/Cas9 technology was used to achieve myostatin (MSTN) point mutation and simultaneous peroxisome proliferator-activated receptor-γ (PPARγ) site-directed knockin in the bovine genome. The feasibility of this gene editing strategy was verified on a myoblast model. The same gene editing strategy was used to construct a mutant myoblast model with MSTN mutation and simultaneous PPARγ knockin. Quantitative reverse-transcription polymerase chain reaction, immunofluorescence staining, and western blot analyses were used to detect the expression levels of MSTN and PPARγ in the mutant myoblast. Results showed that this strategy can inhibit the expression of MSTN and promote the expression of PPARγ. The cell counting kit-8 cell proliferation analysis, 5-ethynyl-2'-deoxyuridine cell proliferation analysis, myotube fusion index statistics, oil red O staining, and triglyceride content detection revealed that the proliferation, myogenic differentiation, and adipogenic transdifferentiation abilities of the mutant myoblasts were higher than those of the wild myoblasts. Finally, transgenic bovine embryos were obtained via somatic cell nuclear transfer. This study provides a breeding material and technical strategy to breed high-quality bovine and a gene editing method to realize the mutation of endogenous genes and simultaneous insertion of exogenous genes in genomes.The homeostasis of intracellular pH (pHi ) affects many cellular functions. Our previous study has established a functional and molecular model of the active pHi regulators in human induced pluripotent stem cells (hiPSCs). The aims of the present study were to further quantify passive pHi buffering power (β) and to investigate the effects of extracellular pH and Na+ -H+ exchanger 1 (NHE1) activity on pluripotency in hiPSCs. pHi was detected by microspectrofluorimetry with pH-sensitive dye-BCECF. Western blot, immunofluorescence staining, and flow cytometry were used to detect protein expression and pluripotency. Our study in hiPSCs showed that (a) the value of total (βtot ), intrinsic (βi ), and CO2 -dependent ( β C O 2 ) buffering power all increased while pHi increased; (b) during the spontaneous differentiation for 4 days, the β values of βtot and β C O 2 changed in a tendency of decrease, despite the absence of statistical significance; (c) an acidic cultured environment retained pluripotency and further upregulated expression and activity of NHE1 during spontaneous differentiation; (d) inhibition on NHE1 activity promoted the loss of pluripotency. In conclusion, we, for the first time, established a quantitative model of passive β during differentiation and demonstrated that maintenance of NHE1 at a higher level was of critical importance for pluripotency retention in hiPSCs.The amino acid sequence enriched with proline (P), glutamic acid (E), serine (S), and threonine (T) (PEST) is a signal-transducing agent providing unique features to its substrate nuclear proteins (PEST-NPs). The PEST motif is responsible for particular posttranslational modifications (PTMs). These PTMs impart distinct properties to PEST-NPs that are responsible for their activation/inhibition, intracellular localization, and stability/degradation. PEST-NPs participate in cancer metabolism, immunity, and protein transcription as oncogenes or as tumor suppressors. Gene-based therapeutics are getting the attention of researchers because of their cell specificity. PEST-NPs are good targets to explore as cancer therapeutics. Insights into PTMs of PEST-NPs demonstrate that these proteins not only interact with each other but also recruit other proteins to/from their active site to promote/inhibit tumors. Thus, the role of PEST-NPs in cancer biology is multivariate. It is hard to obtain therapeutic objectives with single gene therapy. An especially designed combination gene therapy might be a promising strategy in cancer treatment. This review highlights the multifaceted behavior of PEST-NPs in cancer biology. We have summarized a number of studies to address the influence of structure and PEST-mediated PTMs on activation, localization, stability, and protein-protein interactions of PEST-NPs. We also recommend researchers to adopt a pragmatic approach in gene-based cancer therapy.Seed size and number are central to the evolutionary fitness of plants and are also crucial for seed production of crops. However, the molecular mechanisms of seed production control are poorly understood in Brassica crops. Here, we report the gene cloning, expression analysis, and functional characterization of the EOD3/CYP78A6 gene in rapeseed. BnaEOD3 has four copies located in two subgenomes, which exhibited a steady higher expression during seed development with differential expression among copies. The targeted mutations of BnaEOD3 gene were efficiently generated by stable transformation of the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat) vector. These mutations were stably transmitted to T1 and T2 generations and a large collection of homozygous mutants with combined loss-of-function alleles across four BnaEOD3 copies were created for phenotyping. All mutant T1 lines had shorter siliques, smaller seeds, and an increased number of seeds per silique, in which the quadrable mutants showed the most significant changes in these traits. Consequently, the seed weight per plant in the quadrable mutants increased by 13.9% on average compared with that of wild type, indicating that these BnaEOD3 copies have redundant functions in seed development in rapeseed. The phenotypes of the different allelic combinations of BnaEOD3 copies also revealed gene functional differentiation among the two subgenomes. Cytological observations indicated that the BnaEOD3 could act maternally to promote cotyledon cell expansion and proliferation to regulate seed growth in rapeseed. Collectively, our findings reveal the quantitative involvement of the different BnaEOD3 copies function in seed development, but also provided valuable resources for rapeseed breeding programs.The increasing demand for rapid methods to identify both inorganic and organic gunshot residues (IGSR and OGSR) makes electrochemical methods, an attractive screening tool to modernize current practice. Our research group has previously demonstrated that electrochemical screening of GSR samples delivers a simple, inexpensive, and sensitive analytical solution that is capable of detecting IGSR and OGSR in less than 10 min per sample. In this study, we expand our previous work by increasing the number of GSR markers and applying machine learning classifiers to the interpretation of a larger population data set. Utilizing bare screen-printed carbon electrodes, the detection and resolution of seven markers (IGSR; lead, antimony, and copper, and OGSR; nitroglycerin, 2,4-dinitrotoluene, diphenylamine, and ethyl centralite) was achieved with limits of detection (LODs) below 1 µg/mL. A large population data set was obtained from 395 authentic shooter samples and 350 background samples. Various statistical methods and machine learning algorithms, including critical thresholds (CT), naïve Bayes (NB), logistic regression (LR), and neural networks (NN), were utilized to calculate the performance and error rates. Neural networks proved to be the best predictor when assessing the dichotomous question of detection of GSR on the hands of shooter versus nonshooter groups. Accuracies for the studied population were 81.8 % (CT), 88.1% (NB), 94.7% (LR), and 95.4% (NN), respectively. The ability to detect both IGSR and OGSR simultaneously provides a selective testing platform for gunshot residues that can provide a powerful field-testing technique and assist with decisions in case management.

Depression is common in people with non-communicable diseases (NCDs) such as cardiovascular disease, diabetes, cancer, and chronic respiratory conditions. The co-existence of depression and NCDs may affect health behaviours, compliance with treatment, physiological factors, and quality of life. This in turn is associated with worse outcomes for both conditions. Behavioural activation is not currently indicated for the treatment of depression in this population in the UK, but is increasingly being used to treat depression in adults.

To examine the effects of behavioural activation compared with any control group for the treatment of depression in adults with NCDs. To examine the effects of behavioural activation compared with each control group separately (no treatment, waiting list, other psychological therapy, pharmacological treatment, or any other type of treatment as usual) for the treatment of depression in adults with NCDs.

We searched CCMD-CTR, CENTRAL, Ovid MEDLINE, Embase, four other databases,iddle-income countries, for which behavioural activation may offer a feasible alternative to other treatments for depression, would be of interest.

Inappropriate prescribing of medications is common in health care, and is an important safety concern, especially for older adults, who have a high burden of comorbidity and are at greater risk for medication-related adverse events. This study aims to estimate the extent and cost of potentially inappropriate prescribing of medications to older adults in the United States.

A cross-sectional study.

Medicare Part D Prescription Drug Program data set (2014-2018).

Older adults who were enrolled in Medicare Part D Prescription Drug Program between 2014 and 2018.

Potentially inappropriate medications were identified using the 2019 American Geriatrics Society Beers Criteria®.

In 2018, 7.3 billion doses of potentially inappropriate medications were dispensed. The most common medications by number of doses dispensed were proton pump inhibitors, benzodiazepines, and tricyclic antidepressants, and the top five unique medications by reported spending were dexlansoprazole, esomeprazole, omeprazole, dronedarone, and conjugated estrogens. From 2014 to 2018, 43 billion doses of potentially inappropriate medications were dispensed, with a reported spending of $25.2 billion.

Potentially inappropriate medication use among older adults is both common and costly. Careful attention to potentially inappropriate medication use and deprescribing when clinically appropriate could reduce costs and potentially improve outcomes among older adults.

Potentially inappropriate medication use among older adults is both common and costly. Careful attention to potentially inappropriate medication use and deprescribing when clinically appropriate could reduce costs and potentially improve outcomes among older adults.

LAT4 is a broadly expressed uniporter selective for essential branched chain amino acids, methionine and phenylalanine, which are involved in epithelial transport. Its global deletion leads to an early malnutrition-like phenotype and death within 10 days after birth. Here, we tested the impact of deleting LAT4 selectively in the mouse intestine. This affected slightly the absorption of amino acids (AAs) and delayed gastrointestinal motility; however, it had no major phenotypic effect, even when combined with aromatic AA uniporter TAT1 knockout (KO). Conversely, kidney tubule-selective deletion of LAT4 led to a substantial aminoaciduria that strongly increased under a high protein diet. Combining a partial tubular LAT4 deletion with TAT1 KO implicated their synergistic action on AA reabsorption. These results show that LAT4 plays an important role for kidney AA reabsorption, but that its functional role in intestinal AA absorption is largely dispensable.

Amino acid (AA) transporter LAT4 (Slc43a2) functionsrition-like phenotype observed previously in LAT4 global KO pups is suggested to be the consequence of a combinatorial effect of LAT4 deletion in the SI, kidney and presumably other tissues.

To gain insight into veterinary nurse knowledge of pain recognition and control in rabbits.

We used a survey to establish current attitudes amongst veterinary nurses towards pain management in pet rabbits and factors that might shape those attitudes. The survey was advertised at national and international veterinary conferences, in veterinary publications and on social media.

A total of 284 questionnaires (95% from the UK) were completed and analysed. The majority of respondents (78%) nursed 1-10 rabbits per month and 5.6% of the respondents reported regularly running a rabbit clinic. The respondents were regularly involved in nursing during common procedures such as castration and ovariohysterectomy. Responsibility for post-operative pain assessment was reported to be by "nurses only" (50%), "nurses and vets" (42%) and occasionally by "vets only" (3%). The majority of respondents reported that they did not use a pain scale but often relied on behavioural indicators, while 20% used the Rabbit Grimace Scale. The majority of the respondents reported being "fairly confident" at recognising pain in rabbits.

Veterinary nurses are involved in many aspects of rabbit care, and they are generally confident at nursing this species. This survey also suggests the need for more data on the use of pain assessment tools in rabbits and the importance of teamwork between nurses and veterinarians.

Veterinary nurses are involved in many aspects of rabbit care, and they are generally confident at nursing this species. This survey also suggests the need for more data on the use of pain assessment tools in rabbits and the importance of teamwork between nurses and veterinarians.Comprehensive studies on the spatial distribution, water quality, recharge source, and hydrochemical evolution of regional groundwater form the foundation of rational utilization of groundwater resources. In this study, we investigated the water levels, hydrochemistry, and stable isotope composition of groundwater in the vicinity of the Qinghai Lake in China to reveal its recharge sources, hydrochemical evolution, and water quality. The level of groundwater relative to the level of water in the Qinghai Lake ranged from -1.27 to 122.91 m, indicating most of the groundwater to be flowing into the lake. The local evaporation line (LEL) of groundwater was simulated as δ2 H = 6.08 δ18 O-3.01. The groundwater surrounding the Qinghai Lake was primarily recharged through local precipitation at different altitudes. The hydrochemical type of most of the groundwater samples was Ca-Mg-HCO3 ; the hydrochemistry was primarily controlled by carbonate dissolution during runoff. At several locations, the ionic concentrations in groundwater exceeded the current drinking water standards making it unsuitable for drinking. The main source of nitrate in groundwater surrounding the Qinghai Lake was animal feces and sewage, suggesting that groundwater pollution should be mitigated in areas practicing animal husbandry in the Qinghai-Tibet Plateau, regardless of industrial and urbanization rates being relatively low in the region. The scientific planning, engineering, and management of livestock manure and wastewater discharge from animal husbandry practices is a crucial and is urgently required in the Tibetan Plateau.

The prognostic factors for long-term survival after curative resection of pancreatic adenocarcinoma are still poorly understood. The purpose of this study was to identify the prognostic factors of long-term survival after resection of pancreatic adenocarcinoma based on actual 5-year survival including different lymph node status classifications.

A total of 106 patients who underwent pancreatectomy were enrolled at our institution and retrospectively analyzed according to actual survival (> vs < 5 years), as well as several currently available node classifications N0/N1, N0/N1/N2, and lymph-node ratio (LNR) including multivariate logistic regression.

The actual 5-year overall survival rate of the series was 12.26%. In a univariate analysis, operative blood loss and blood transfusion, completion of adjuvant treatment, histological differentiation, perineural invasion, N0/N1, N0/N1/N2 and LNR were significant predictive factors for actual long-term survival. A multivariate analysis showed that only N0/N1 was an independent predictive factor for actual 5-year survival (OR 1.593; 0.730-1.325; p= 0.264).

The nodal involved status is the strongest independent unfavorable factor for actual long-term survival after pancreatic resection for adenocarcinoma.

The nodal involved status is the strongest independent unfavorable factor for actual long-term survival after pancreatic resection for adenocarcinoma.Appropriate waiting time for hip fracture surgery is disputed. The American Academy of Orthopaedic Surgeons recommends surgery within 48 hours of presentation, although evidence suggests that earlier surgery (within 24 hours) reduces the risks of complications and death. The authors asked (1) Do patients who receive earlier radiographic evaluation of hip fracture undergo surgery earlier? and (2) Is "surgery delay" (time from presentation to surgery) associated with postoperative opioid use, duration of hospital stay, and 30-day and 1-year mortality rates? The authors identified 511 adults 60 years or older who were admitted to their emergency department with hip fractures from 2015 through 2017. Patients were divided into 6 cohorts according to length of surgery delay and 3 cohorts according to length of radiography delay (time from presentation to first hip radiograph). The authors found that medium radiography delay (>2 to 4 hours) was associated with an additional 11 hours of surgery delay compared with short radiography delay (≤2 hours; P=.026). Longer surgery delay (>12 hours) was associated with use of 9.6 more morphine equivalents (95% confidence interval, 0.7 to 8.6) during the first 24 hours postoperatively compared with shorter surgery delay (≤12 hours). Surgery delay of greater than 36 hours was an independent risk factor for longer hospital stay (odds ratio, 2.8; 95% confidence interval, 1.7 to 4.8). Thirty-day and 1-year mortality rates were significantly higher among patients who experienced a surgery delay of greater than 36 hours compared with those who experienced a surgery delay of 36 hours or less. [Orthopedics. 2020;43(6)e609-e615.].The sweetpotato whitefly, Bemisia tabaci (Gennadius) (Hemiptera; Aleyrodidae), and greenhouse whitefly, Trialeurodes vaporariorum (Westwood) (Hemiptera Aleyrodidae), are highly problematic plant pests and virus vectors with worldwide distributions. Identification of whitefly species is typically accomplished by observation of distinct morphological characters; however, because of morphological inconsistency and indistinguishability, the discrimination of B. tabaci species variants is dependent on molecular techniques based on genetic differences. New assays were designed for the detection of B. tabaci A, B, and Q mitotype groups, and T. vaporariorum. Specific primer sets were designed for amplification of the mitochondrial cytochrome c oxidase I gene of the four targets to perform in end-point PCR, real-time PCR coupled to high-resolution melting analysis (HRM), and the isothermal helicase-dependent amplification (HDA). Primer specificities were validated using end-point PCR, then tested in HRM and HDA. Bemisia tabaci A, B, and Q mitotypes, and T. vaporariorum-targeted primer sets discriminately amplified specimens of different populations within their target whitefly group. These tests provide three novel discrimination assays for the high-consequence, exotic B. tabaci B and Q groups, along with the native B. tabaci A group and T. vaporariorum.Natural killer (NK) cell-mediated killing involves the membrane fusion of preformed lytic granules. While the roles of actin and microtubules are well accepted during this process, the function of septins, another cytoskeletal component that associates with actin and microtubules, has not been investigated. Here we show that genetic depletion or pharmacologic stabilization of the septin cytoskeleton significantly inhibited NK cell cytotoxicity. Although the stabilization of septin filaments impaired conjugate formation, depletion of septin proteins had no impact on conjugate formation, lytic granule convergence, or MTOC polarization to the cytotoxic synapse (CS). Interestingly, septins copurify and accumulate near the polarized lytic granules at the CS, where they regulate lytic granule release. Mechanistically, we find that septin 7 interacts with the SNARE protein syntaxin 11 and facilitates its interaction with syntaxin binding protein 2 to promote lytic granule fusion. Altogether, our data identify a critical role for septins in regulating the release of lytic granule contents during NK cell-mediated killing.Data from a recent epidemiological surveillance network showed a decrease in the reported number of sexually transmitted diseases (STDs) and food-borne infections. We reflect on the possible drivers and consequences of a decrease in these transmittable infectious diseases linked to human contact in relation to social distancing due to the COVID-19 pandemic in Madrid (Spain).

PAX8 is a transcription factor required for thyroid development, and its mutation causes congenital hypothyroidism (CH). More than 20 experimentally verified loss-of-function PAX8 mutations have been described, and all but one were located in the DNA-binding paired domain.

We report the identification and functional characterization of 3 novel truncating PAX8 mutations located outside the paired domain.

Three CH probands, diagnosed in the frame of newborn screening, had thyroid hypoplasia and were treated with levothyroxine. Next-generation sequencing-based mutation screening was performed. Functionality of the identified mutations were verified with Western blotting, intracellular localization assays, and transactivation assays with use of HeLa cells. Luciferase complementation assays were used to evaluate the effect of mutations on the interaction between PAX8 and its partner, NKX2-1.

Each proband had novel truncating PAX8 mutations that were I160Sfs*52, Q213Efs*27, and F342Rfs*85. Western blotting is required for the PAX8-NKX2-1 interaction.

With more countries exiting lockdown, public health safety requires screening measures at international travel entry points that can prevent the reintroduction or importation of the severe acute respiratory syndrome-related coronavirus-2. Here, we estimate the number of cases captured, quarantining days averted and secondary cases expected to occur with screening interventions.

To estimate active case exportation risk from 153 countries with recorded coronavirus disease-2019 cases and deaths, we created a simple data-driven framework to calculate the number of infectious and upcoming infectious individuals out of 100 000 000 potential travellers from each country, and assessed six importation risk reduction strategies; Strategy 1 (S1) has no screening on entry, S2 tests all travellers and isolates test-positives where those who test negative at 7days are permitted entry, S3 the equivalent but for a 14day period, S4 quarantines all travellers for 7days where all are subsequently permitted entry, S5 the equplace. If testing is not feasible, quarantining for a minimum of 14 days is recommended with strict adherence measures in place.

Obesity is a major health problem associated with severe comorbidities, including type 2 diabetes and cancer, wherein microRNAs (miRNAs) might be useful as diagnostic/prognostic tools or therapeutic targets.

To explore the differential expression pattern of miRNAs in obesity and their putative role in obesity-related comorbidities such as insulin resistance.

An Affymetrix-miRNA array was performed in plasma samples from normoweight (n = 4/body mass index < 25) and obese subjects (n = 4/body mass index > 30). The main changes were validated in 2 independent cohorts (n = 221/n = 18). Additionally, in silico approaches were performed and in vitro assays applied in tissue samples and prostate (RWPE-1) and liver (HepG2) cell-lines.

A total of 26 microRNAs were altered (P < 0.01) in plasma of obese subjects compared to controls using the Affymetrix-miRNA array. Validation in ampler cohorts revealed that miR-4454 levels were consistently higher in obesity, associated with insulin-resistance (Homeostevels were higher, associated with insulin-resistance and modulated by obesity-controlling interventions. Insulin regulated miR-4454, which, in turn may impair the cellular response to insulin, in a cell type-dependent manner (i.e., prostate gland), by modulating the splicing process.The study was conducted to determine the effects of mineral methionine hydroxy analog chelate (MMHAC) partially replacing inorganic trace minerals in sow diets on epigenetic and transcriptional changes in the muscle and jejunum of progeny. The MMHAC is zinc (Zn), manganese (Mn), and copper (Cu) chelated with methionine hydroxy analog (Zn-, Mn-, and Cu-methionine hydroxy analog chelate [MHAC]). On day 35 of gestation, 60 pregnant sows were allotted to two dietary treatments in a randomized completed block design using parity as a block 1) ITM inorganic trace minerals with zinc sulfate (ZnSO4), manganese oxide (MnO), and copper sulfate (CuSO4) and 2) CTM 50% of ITM was replaced with MMHAC (MINTREX trace minerals, Novus International Inc., St Charles, MO). Gestation and lactation diets were formulated to meet or exceed NRC requirements. On days 1 and 18 of lactation, milk samples from 16 sows per treatment were collected to measure immunoglobulins (immunoglobulin G, immunoglobulin A, and immunoglobulin M) and mi decrease mucin-2 (MUC2) mRNA (P = 0.057) and transforming growth factor-beta 1 (TGF-β1) mRNA (P = 0.057) in the jejunum of piglets on day 18 of lactation. There were, however, no changes in the amounts of tumor necrosis factor-alpha, interleukin-8, TGF-β, MUC2, and myogenic factor 6 in the tissues by MMHAC. In conclusion, maternal supplementation of MMHAC could contribute to histone acetylation and programming in the fetus, which potentially regulates intestinal health and skeletal muscle development of piglets at birth and weaning, possibly leading to enhanced growth of their piglets.

The aims of this work are to assess the clinical adverse events (AEs) of high-dose vs low-dose sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) in patients with type 2 diabetes mellitus (T2DM).

We searched MEDLINE, EMBASE, and Cochrane Library from January 1, 2006 to March 10, 2020, for identifying eligible randomized clinical trials (RCTs) that reported AEs by high-dose and low-dose SGLT2 inhibitors in T2DM patients. Random-effects models was used to obtain summary relative risks (RRs) with associated 95% CIs. Prespecified subgroup analyses according to individual SGLT2 inhibitors and follow-up duration, and leave-one-out sensitivity analysis were conducted.

A total of 51 RCTs involving 24 371 patients (12 208 received high-dose and 12 163 received low-dose SGLT2 inhibitors) were included. Overall, the heterogeneity among included studies was relatively low (I2 < 50% for each outcome). No significant differences between high-dose and low-dose SGLT2 inhibitors were observed for overall safety (including any AEs, serious AEs, AEs leading to discontinuation, and death) and specified safety (including infections and infestations, musculoskeletal disorders, gastrointestinal disorders, osmotic diuresis-related AEs, volume-related AEs, renal-related AEs, and metabolism and nutrition), except for a mild increase in risk for AEs related to study drugs (RR 1.08; 95% CI, 1.01-1.16) that mainly derived from canagliflozin (RR 1.17; 95% CI, 1.05-1.30). Subgroup analyses were consistent with the primary outcomes.

This study provided substantial evidence that AEs of SGLT2 inhibitors were not dose related.

This study provided substantial evidence that AEs of SGLT2 inhibitors were not dose related.Symbiotic nitrogen fixation carried out in legume root nodules requires transition metals. These nutrients are delivered by the host plant to the endosymbiotic nitrogen-fixing bacteria living within the nodule cells, a process in which vascular transport is essential. As members of the Yellow Stripe-Like (YSL) family of metal transporters are involved in root to shoot transport, they should also be required for root to nodule metal delivery. The genome of the model legume Medicago truncatula encodes eight YSL proteins, four of them with a high degree of similarity to Arabidopsis thaliana YSLs involved in long-distance metal trafficking. Among them, MtYSL3 is a plasma membrane protein expressed by vascular cells in roots and nodules and by cortical nodule cells. Reducing the expression level of this gene had no major effect on plant physiology when assimilable nitrogen was provided in the nutrient solution. However, nodule functioning was severely impaired, with a significant reduction of nitrogen fixation capabilities. Further, iron and zinc accumulation and distribution changed. Iron was retained in the apical region of the nodule, while zinc became strongly accumulated in the nodule veins in the ysl3 mutant. These data suggest a role for MtYSL3 in vascular delivery of iron and zinc to symbiotic nitrogen fixation.Rhagoletis mendax Curran (the blueberry maggot fly) is a major pest of wild blueberry. It is a direct pest of the fruit. Females lay eggs in fruit resulting in infestations of larvae unacceptable to most consumers. Three field perimeter interception tactics were tested for control of R. mendax in wild blueberry, Vaccinium angustifolium Aiton (Ericales Ericaceae), between 2000 and 2010. We investigated field perimeter deployment of baited, insecticide-treated, green spheres (2000-2005), baited, yellow Trécé PHEROCON AM traps (2005 and 2006), and baited, Hopper Finder, sticky barrier tape (2008-2010). Only the Hopper Finder tape provided significant reduction in R. mendax adults and fruit infestation over the 3-yr field study. However, the reduction in fruit infestation compared with control plots was only 48.2 ± 7.3%, a level of reduction in damage that would be unsuitable for many commercial wild blueberry growers as a stand-alone tactic, but could be an important reduction as part of a multiple tactic IPM strategy. In addition, we constructed an agent-based computer simulation model to assess optimal trap placement between three patterns 1) a single row of traps along field perimeter; 2) a double row of traps along the field perimeter at half the density of the single row; and 3) a grid of traps spread throughout the field but with the largest distance between traps. We found that the single row deployment pattern of traps was the best for reducing immigration of R. mendax adults into simulated fields.Diaphania hyalinata (Linnaeus, 1767) is one of the main pests of the cucurbit crops. Biological control and botanicals are used in integrated pest management (IPM), especially in agro-ecological agricultures where the use of synthetic pesticides is restricted. Toxicological effects of plant essential oils on target and nontarget organisms should be evaluated to determine its use in IPM. The toxicity of ginger, peppermint, oregano, and thyme essential oils to D. hyalinata eggs, larvae, and pupae and their selectivity to the parasitoid Trichospilus pupivorus and the LC50, LC99 and the relative selectivity index (RSI) of these botanicals were determined. The eggs of D. hyalinata were more sensitive to the botanicals applied than its larvae and pupae, with higher toxicity of oregano and thyme essential oils, followed by those of peppermint and ginger. Topical application was the least toxic method to D. hyalinata larvae. Ginger, peppermint, and thyme essential oils were more toxic by ingestion and oregano by contact to D. hyalinata larvae. The essential oil concentrations applied to D. hyalinata pupae prevent the emergence of adults of this insect with the oregano essential oil showing the greatest toxicity. Peppermint, ginger, thyme, and oregano essential oils were selective to T. pupivorus with RSI50 of 5.40, 1.38, 8.15, and 6.98 and RSI99 of 1.54, 2.53, 3.90, and 4.16 respectively. The ginger, peppermint, oregano, and thyme essential oils were toxic to immature D. hyalinata and selective to T. pupivorus females presenting potential as an alternative control in the IPM of this pest in Cucurbitaceae crops.Glochidion plants and Epicephala moths played different roles and kept the balance in the mutualism. We studied the four coexisting Epicephala species on Glochidion sphaerogynum in detail and reconstructed the phylogenic tree of 40 Gracillariidae species. The results showed that one of them (Epicephala impolliniferens) did not pollinate G. sphaerogynum, because of lacking the specialized structure of carrying pollen. These results suggested that E. impolliniferens acted as a 'cheater' in the system. The phylogenetic analyses suggested that E. impolliniferens derived from a pollinating species, and had secondarily gave up the ability to pollinate. This is a typical phenomenon of mutualism reversal. The phenomenon exhibits the co-evolutionary diversification under selection pressures.Spodoptera frugiperda (J.E. Smith) can attack cowpea plants (Vigna unguiculata [L.] Walp.) (Fabales Fabaceae) in any growth stage but attacks primarily in the first days after plant emergence, when the plants are more sensitive to defoliation. This study was carried out to evaluate the resistance to S. frugiperda in six cowpea genotypes, of which four were cultivars (BRS Tapahium, BRS Tumucumaque, Fradinho, and Miranda), and two were landraces (Juti and Nioaque), in three different experiments. In the first experiment, adult emergence, adult weight, adult longevity, larva to adult period, numbers of injured leaves per plant canopy (upper, middle, and lower), and reduction in plant dry matter were assessed. In the second experiment, the oviposition preference of S. frugiperda for the different cowpea genotypes was evaluated under free-choice conditions. In the third experiment, levels of peroxidase (POD), superoxide dismutase (SOD), and protein content in cowpea leaves were assessed. Insects fed on landrace Juti plants showed low adult emergence, yielded a lower fitness index, and caused less plant dry matter reduction. In addition, plants of landrace Juti were less preferred for oviposition. Overall, Juti plants showed higher resistance levels in all three resistance categories and higher levels of POD and SOD in S. frugiperda injured leaves, in addition to a lower protein content. Juti will be tested in field conditions, followed by molecular characterization. This will provide additional information about its potential as an S. frugiperda resistance source in plant breeding programs.The high incidence of thromboembolic disease, and in particular venous thromboembolism (VTE), has emerged as an important consideration in hospitalized and critically ill patients with coronavirus disease 2019 (COVID-19). The coagulopathy of COVID-19 is postulated to result from interactions of the inflammatory and immune systems with the coagulation system, manifesting as a cytokine storm associated with hyperinflammation and coagulation and platelet activation. Unique characteristics of VTE in hospitalized and critically ill patients with COVID-19 include the high incidence of VTE (and especially pulmonary embolism) when compared with historical controls; the finding of in situ pulmonary embolism associated with microthrombi, which suggests a thrombotic microangiopathic process in addition to classic macrovessel disease; and, most important from a clinical perspective, the unusually high rate of VTE that has been reported despite standard thromboprophylaxis. This raises the possibility that intermediate or weight-based heparin dosing may be more effective than fixed dosing for thromboprophylaxis in high-risk subsets of patients hospitalized with COVID-19. There have been several guidance statements focusing on the management of VTE in hospitalized and critically ill patients with COVID-19, including the most recent statement by the Scientific and Standardization Committee of the International Society of Thrombosis and Haemostasis, which includes comprehensive guidance on the diagnosis, prevention, and treatment of VTE in this patient population. Ongoing randomized trials that address key clinical questions, especially more intense thromboprophylactic strategies and novel antithrombotic approaches, have the potential to reduce the morbidity and mortality from VTE in hospitalized and critically ill patients with COVID-19.Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and clinically challenging hematologic malignancy with dismal outcomes. With a median age of ∼70 years, the majority of patients with BPDCN have experienced historically suboptimal responses with intensive chemotherapy regimens. The major scientific breakthrough in this field was the recognition of overexpression of a surface receptor, CD123/interleukin 3 (IL-3) receptor α, in all patients. Importantly, a novel therapeutic agent consisting of a truncated diphtheria toxin (DT) payload fused to recombinant human IL-3 was being developed, one that targeted CD123, initially known as DT-IL-3 (later known as SL401; tagraxofusp; tagraxofusp-erzs [Elzonris]). The identification of this agent, and subsequent clinical trials specifically dedicated to patients with BPDCN (including a pilot study, followed by a larger phase 1/2 multicenter study [90% overall response rate [ORR] in frontline and 67% ORR in relapsed/refractory setting]), in part led to approval of tagraxofusp-erzs on 21 December 2018. Tagraxofusp-erzs was the first agent approved for BPDCN (for patients ages 2 years and older), and importantly, established this drug as the first CD123-targeted agent ever approved. The most notable toxicity of tagraxofusp-erzs is occurrence of the capillary leak syndrome, which occurs frequently at all grades, and has also been observed to be life-threatening, appropriately leading to a US Food and Drug Administration "black box" warning in the package insert. The preclinical and clinical aspects of drug development of tagraxofusp-erzs as monotherapy leading to drug approval are reviewed herein, with discussion of future directions of this novel agent, including consideration for rational combinations in BPDCN and beyond.Adaptive immune responses are acknowledged to evolve from innate immunity. However, limited information exists regarding whether encounters between innate cells direct the generation of specialized T-cell subsets. We aim to understand how natural killer (NK) cells modulate cell-mediated immunity in humans. We found that human CD14+CD16- monocytes that differentiate into inflammatory dendritic cells (DCs) are shaped at the early stages of differentiation by cell-to-cell interactions with NK cells. Although a fraction of monocytes is eliminated by NK-cell-mediated cytotoxicity, the polarization of interferon-γ (IFN-γ) at the NKp30-stabilized synapses triggers a stable IFN-γ signature in surviving monocytes that persists after their differentiation into DCs. Notably, NK-cell-instructed DCs drive the priming of type 17 CD8+ T cells (Tc17) with the capacity to produce IFN-γ and interleukin-17A. Compared with healthy donors, this cellular network is impaired in patients with classical NK-cell deficiency driven by mutations in the GATA2 gene. Our findings reveal a previously unrecognized connection by which Tc17-mediated immunity might be regulated by NK-cell-mediated tuning of antigen-presenting cells.Myelodysplastic syndromes (MDSs) represent a heterogeneous group of hematological stem cell disorders with an increasing burden on health care systems. Evidence-based MDS guidelines and recommendations (G/Rs) are published but do not necessarily translate into better quality of care if adherence is not maintained in daily clinical practice. Guideline-based indicators (GBIs) are measurable elements for the standardized assessment of quality of care and, thus far, have not been developed for adult MDS patients. To this end, we screened relevant G/Rs published between 1999 and 2018 and aggregated all available information as candidate GBIs into a formalized handbook as the basis for the subsequent consensus rating procedure. An international multidisciplinary expert panel group (EPG) of acknowledged MDS experts (n = 17), health professionals (n = 7), and patient advocates (n = 5) was appointed. The EPG feedback rates for the first and second round were 82% (23 of 28) and 96% (26 of 27), respectively. A final set of 29 GBIs for the 3 domains of diagnosis (n = 14), therapy (n = 8), and provider/infrastructural characteristics (n = 7) achieved the predefined agreement score for selection (>70%). We identified shortcomings in standardization of patient-reported outcomes, toxicity, and geriatric assessments that need to be optimized in the future. Our GBIs represent the first comprehensive consensus on measurable elements addressing best practice performance, outcomes, and structural resources. They can be used as a standardized instrument with the goal of assessing, comparing, and fostering good quality of care within clinical development cycles in the daily care of adult MDS patients.Long-term cure of childhood Burkitt lymphoma (BL) in sub-Saharan Africa after treatment with single-agent cyclophosphamide has been documented for more than half of a century. Contemporary cure rates for the highest-risk patients with BL in high-income countries exceed 90% using intensive multiagent chemotherapy. By contrast, the majority of African children with BL still die. Data spanning 5 decades in Africa have repeatedly shown that the children most likely to achieve cure with limited cyclophosphamide regimens are those with lower-stage disease isolated to the jaw. Attempts to intensify the cyclophosphamide monotherapy backbone with the addition of vincristine, low-dose methotrexate, prednisone, doxorubicin, and/or low-dose cytarabine have not yielded significant improvement. High-dose methotrexate is a critical component in the treatment of childhood BL worldwide. Although initial efforts in Africa to incorporate high-dose methotrexate resulted in high treatment-related mortality, more recent collaborative experiences from North and West Africa, as well as Central America, demonstrate that it can be administered safely and effectively, despite limitations in supportive care resources. Recognizing the unacceptable disparity in curative outcomes for BL between the United States/Europe and equatorial Africa, there is a critical need to safely adapt contemporary treatment regimens to optimize curative outcomes amid the resource limitations in regions where BL is endemic. Here, we critically review reports of BL treatment outcomes from low- and middle-income countries, in addition to data from high-income countries that predated modern intensified regimens, to identify potential strategies to improve the therapeutic approach for children suffering from BL in sub-Saharan Africa.Although novel agents (NAs) have improved outcomes for patients with chronic lymphocytic leukemia (CLL), a subset will progress through all available NAs. Understanding outcomes for potentially curative modalities including allogeneic hematopoietic stem cell transplantation (alloHCT) following NA therapy is critical while devising treatment sequences aimed at long-term disease control. In this multicenter, retrospective cohort study, we examined 65 patients with CLL who underwent alloHCT following exposure to ≥1 NA, including baseline disease and transplant characteristics, treatment preceding alloHCT, transplant outcomes, treatment following alloHCT, and survival outcomes. Univariable and multivariable analyses evaluated associations between pre-alloHCT factors and progression-free survival (PFS). Twenty-four-month PFS, overall survival (OS), nonrelapse mortality, and relapse incidence were 63%, 81%, 13%, and 27% among patients transplanted for CLL. Day +100 cumulative incidence of grade III-IV acute graft-vs-host disease (GVHD) was 24%; moderate-severe GVHD developed in 27%. Poor-risk disease characteristics, prior NA exposure, complete vs partial remission, and transplant characteristics were not independently associated with PFS. Hematopoietic cell transplantation-specific comorbidity index independently predicts PFS. PFS and OS were not impacted by having received NAs vs both NAs and chemoimmunotherapy, 1 vs ≥2 NAs, or ibrutinib vs venetoclax as the line of therapy immediately pre-alloHCT. AlloHCT remains a viable long-term disease control strategy that overcomes adverse CLL characteristics. Prior NAs do not appear to impact the safety of alloHCT, and survival outcomes are similar regardless of number of NAs received, prior chemoimmunotherapy exposure, or NA immediately preceding alloHCT. Decisions about proceeding to alloHCT should consider comorbidities and anticipated response to remaining therapeutic options.

Levothyroxine treatment for hypothyroidism in early pregnancy has inconsistent outcomes.

This study evaluated children's cognitive function to ascertain the impact of preconception maternal hypothyroidism treatment on fetal neurodevelopment.

This prospective, single-center cohort study was conducted at a tertiary-care hospital.

Women were assigned to the before conception (BC) and after conception (AC; 8-14 gestational weeks) groups by time point of hypothyroidism diagnosis and treatment.

Levothyroxine treatment was adjusted based on results of a monthly thyroid function test.

The Gesell Development Diagnosis Scale (GDDS; Chinese version) was used to assess neurocognitive development of children at age 6, 12, and 24 months, with total score as the primary outcome.

Of the 466 participants, 187 and 279 were in the BC and AC groups, respectively. Both groups were comparable at baseline antenatal visit, except for a higher proportion of thyroid peroxidase (TPO) antibody-positive participants in the BC group (P < .