Cardenasalmeida5906

1% and 31.3%, respectively). Univariate and multivariate logistic regression analyses revealed that stimulant in drug action, and "B" (blood and blood forming organs), "G" (genito-urinary system and sex), and "J" (anti-infectives for systemic use) in drug application were statistically associated with high approval success rates. We found several parameters and their combinations that affected drug approval success rates. Our results could assist pharmaceutical companies in evaluating the probability of success of their drug candidates and, thus, in efficiently conducting the clinical development process.The liver is the only visceral organ in the body with a tremendous capacity to regenerate in response to insults that induce inflammation, cell death, and injury. Liver regeneration is a complicated process involving a well-orchestrated activation of non-parenchymal cells in the injured area and proliferation of undamaged hepatocytes. Furthermore, the liver has a Hepatostat, defined as adjustment of its volume to that required for homeostasis. Understanding the mechanisms that control different steps of liver regeneration is critical to informing therapies for liver repair, to help patients with liver disease. The Hippo signaling pathway is well known for playing an essential role in the control and regulation of liver size, regeneration, stem cell self-renewal, and liver cancer. Thus, the Hippo pathway regulates dynamic cell fates in liver, and in absence of its downstream effectors YAP and TAZ, liver regeneration is severely impaired, and the proliferative expansion of liver cells blocked. We will mainly review upstream mechanisms activating the Hippo signaling pathway following partial hepatectomy in mouse model and patients, its roles during different steps of liver regeneration, metabolism, and cancer. We will also discuss how targeting the Hippo signaling cascade might improve liver regeneration and suppress liver tumorigenesis.The hydroxide ion concentration dependence of the methanol oxidation reaction at Pt was studied using microelectrode voltammetry and rotating disk electrode voltammetry. Both methods suggest that the rate of methanol oxidation is limited by hydroxide mass transport at low hydroxide concentrations, while it is inhibited by hydroxide adsorption at high concentrations. It was possible to shift from the transport-limited regime to the inhibitory regime by varying the bulk concentration of hydroxide or by varying mass transport to the electrode. Rotating ring-disk electrode voltammetry was employed to qualitatively assess changes in the diffusion layer pH. The results indicated a decrease in the surface pH during methanol oxidation, as expected, but also that the pH reached a steady state during hydroxide transport limited methanol oxidation.Ninety wild Atlantic salmon, Salmo salar L., (1.5-10.3 kg) were caught in the Namsen Fjord near the mouth of River Namsen, mid-Norway, and examined for the presence and distribution of Anisakis simplex (Rudolphi, 1809 det. Krabbe, 1878) larvae by digestion of the viscera and muscles in a pepsin/HCl solution. All salmon were migrating spawners after 1-4 years of feeding in the Atlantic Ocean. All 90 Atlantic salmon had A. simplex larvae in the viscera, and all, except two, had A. simplex larvae in the musculature. The number of A. simplex larvae in each fish varied between 3 and 181, and the total mean number of nematode larvae was 44.5. The intensity of A. simplex larvae was positively correlated with increasing weight and sea age of the host. However, the proportion of larvae in the muscle fillets decreased with increasing host weight and sea age. Atlantic salmon females had more A. simplex larvae than males. In all the fish examined, 70.2% of the A. simplex larvae were found in the viscera and 29.8% in the musculature. The majority (93%) of the larvae in the musculature occurred in the hypaxial sections anterior to the anus. As A. simplex larvae commonly occur in the musculature of wild Atlantic salmon, consumption of unfrozen, raw or semi-raw musculature represents a risk for humans developing anisakiasis.Despite the increasing incidence of hepatocellular carcinoma (HCC) worldwide, current pharmacological treatments are still unsatisfactory. We have previously shown that lysophosphatidic acid receptor 6 (LPAR6) supports HCC growth and that 9-xanthenylacetic acid (XAA) acts as an LPAR6 antagonist inhibiting HCC growth without toxicity. Here, we synthesized four novel XAA derivatives, (±)-2-(9H-xanthen-9-yl)propanoic acid (compound 4 - MC9), (±)-2-(9H-xanthen-9-yl)butanoic acid (compound 5 - MC6), (±)-2-(9H-xanthen-9-yl)hexanoic acid (compound 7 - MC11), and (±)-2-(9H-xanthen-9-yl)octanoic acid (compound 8 - MC12, sodium salt) by introducing alkyl groups of increasing length at the acetic α-carbon atom. Two of these compounds were characterized by X-ray powder diffraction and quantum mechanical calculations, while molecular docking simulations suggested their enantioselectivity for LPAR6. Biological data showed anti-HCC activity for all XAA derivatives, with the maximum effect observed for MC11. Our findings support the view that increasing the length of the alkyl group improves the inhibitory action of XAA and that enantioselectivity can be exploited for designing novel and more effective XAA-based LPAR6 antagonists.

This study aimed to investigate the beneficial effects of synchronized intermittent mandatory ventilation (SIMV) with heliox in newborn infants with meconium aspiration syndrome (MAS).

Seventy-one newborn infants with MAS in the neonatal intensive care unit (NICU) of Daping Hospital of Army Medical University were enrolled in the trial. Infants treated with SIMV were randomized and divided into the heliox group (n = 35) and control group (n = 36). The heliox group received heliox for 6 h followed by air-oxygen mixed gas, and the control group received air-oxygen mixed gas. The primary outcome measures were PaO

/FiO

(P/F) and the extubation time. The secondary outcome measures were the incidence of mechanical ventilation complications, hospital length of stay in the NICU, blood gas analysis, and inflammation markers.

The P/F in the heliox group was significantly better than that in the control group (p < .001). The extubation time and hospital length of stay in the NICU in the heliox group were shorter than those in the control group (p < .001). The inflammation markers at 6 h and myocardial injury markers at 24 h were decreased compared with those at 0 h, and those in the heliox group were more significantly decreased than those in the control group ([interleukin IL-6/IL-8/tumor necrosis factor α] p < .001, [C-reaction protein] p = .012; [creatine kinase] p < .001, [CK-MB] p = .041).

Heliox appears to be more effective in reducing the length of ventilation and increasing carbon dioxide eliminations than an air-oxygen mixture in infants with MAS under the support of SIMV.

Heliox appears to be more effective in reducing the length of ventilation and increasing carbon dioxide eliminations than an air-oxygen mixture in infants with MAS under the support of SIMV.A bowl-shaped nitrogen-doped nanographene composed of a pyrrolo[3,2-b]pyrrole core substituted with six arene rings circularly bonded with one another has been prepared via a concise synthetic strategy encompassing the multicomponent tetraarylpyrrolopyrrole (TAPP) synthesis, the Scholl reaction, and intramolecular direct arylation. This synthesis represents the first case of programmed sequential intramolecular direct arylation reactions utilizing the different reactivity of C-Br and C-Cl bonds. The target compound contains two central pentagons confined between two adjacent heptagons-the inverse Stone-Thrower-Wales topology. The presence of both five- and seven-membered rings in the final structure is responsible for interesting properties such as a perpendicularly aligned dipole moment, absorption and fluorescence in the orange-red region, weak emission originating from the charge-transfer character of a low-energy absorption band, and a high lying HOMO. In the solid state slipped convex-to-convex π-π stacking dominates.The development of coronavirus disease 2019 (COVID-19) vaccines has proceeded at an unprecedented pace, with numerous trials conducted simultaneously across the world as a result of massive technological and financial resource expenditures. With multiple vaccines having now received regulatory approval, public health efforts to promote widespread vaccine dissemination are currently underway. There has been particular emphasis placed on vaccination of older populations, the age group in which COVID-19 infection has been most lethal. However, such widespread vaccination approaches have necessarily raised important questions related to potential interactions with underlying diseases and concomitant treatments among persons to be vaccinated. Osteoporosis is a chronic condition marked by reduced bone strength and an associated increased risk for fracture that generally requires sustained medical intervention(s). Osteoporosis is neither associated with a higher risk of COVID-19 infection nor by more pronounced disease severity following infection, such that individuals with osteoporosis need not be more highly prioritized for COVID-19 vaccination. Osteoporosis therapies do not interfere with the efficacy or side effect profiles of COVID-19 vaccines and should not be stopped or indefinitely delayed because of vaccination. Depending on the specific drug profile within an anti-osteoporosis medication category, minor adjustments to the timing of drug administration may be considered with respect to the patient's COVID-19 vaccination schedule. Herein we provide practical recommendations for the care of patients requiring treatment for osteoporosis in the setting of COVID-19 vaccination. © 2021 American Society for Bone and Mineral Research (ASBMR).Stimuli-responsive chromic materials such as photochromics, hydrochromics, thermochromics, and electrochromics have a long history of capturing the attention of scientists due to their potential industrial applications and novelty in popular culture. However, hybrid chromic materials that combine two or more stimuli-triggered color changing properties are not so well known. Herein, we report a design strategy that has led to a series of emissive 1,8-naphthalimide-viologen dyads which exhibit unusual dual photochromic and hydrochromic switching behavior in the solid-state when embedded in a cellulose matrix. This behavior manifests as reversible solid state fluorescence hydrochromism upon changes in atmospheric relative humidity (RH), and reversible solid state photochromism upon generation of a cellulose-stabilized viologen radical cation. In this design strategy, the bipyridinium unit serves as both a water-sensitive receptor for the hydrochromic fluorophore-receptor system, and a photochromic group, capable of eliciting its own visible colorimetric response, generating a fluorescence quenching radical cation with prolonged exposure to ultraviolet (UV) light. These dyes can be inkjet-printed onto cellulose paper or drop-cast as cellulose powder-based films and can be unidirectionally cycled between three different states which can be characteristically visualized under UV light or visible light. The material's photochromism, hydrochromism, and underlying mechanism of action was investigated using computational analysis, dynamic vapor sorption/desorption isotherms, electron paramagnetic resonance spectroscopy, and variable humidity UV-Vis adsorption and fluorescence spectroscopies.SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) is an emerging respiratory pathogen that has rapidly spread in human populations. Severe forms of infection associate cytokine release syndrome and acute lung injury due to hyperinflammatory responses even though virus clearance is achieved. Key components of inflammation include immune cell recruitment in infected tissues, a step which is under the control of endothelial cells. Here, we review endothelial cell responses in inflammation and infection due to SARS-CoV-2 together with phenotypic and functional alterations of monocytes, T and B lymphocytes with which they interact. We surmise that endothelial cells function as an integrative and active platform for the various cells recruited, where fine tuning of immune responses takes place and which provides opportunities for therapeutic intervention.Virtually inert sulfur hexafluoride becomes a precious pentafluorosulfanylation agent, if properly activated by photoredox catalysis, to access α-fluoro and α-alkoxy SF5 -compounds. This advanced protocol converts SF6 in the presence of alkynols as bifunctional C-C- and C-O-bond forming reagents directly into pentafluorosulfanylated oxygen-containing heterocycles in a single step from α-substituted alkenes. The proposed mechanism is supported by theoretical calculations and gives insights not only in the pentafluorosulfanylation step but also into formation of the carbon-carbon bond and is in full agreement with Baldwin's cyclization rules. The key step is a radical type 5-, 6- respectively 7-exo-dig-cyclization. The synthesized oxaheterocycles cannot be simply prepared by other synthetic methods, show a high level of structural complexity and significantly expand the scope of pentafluorosulfanylated building blocks valuable for medicinal and material chemistry.High fracture rate and high circulating levels of the Wnt inhibitor, sclerostin, have been reported in diabetic patients. We studied the effects of Wnt signaling activation on bone health in a mouse model of insulin-deficient diabetes. We introduced the sclerostin-resistant Lrp5A214V mutation, associated with high bone mass, in mice carrying the Ins2Akita mutation (Akita), which results in loss of beta cells, insulin deficiency, and diabetes in males. Akita mice accrue less trabecular bone mass with age relative to wild type (WT). Double heterozygous Lrp5A214V /Akita mutants have high trabecular bone mass and cortical thickness relative to WT animals, as do Lrp5A214V single mutants. Likewise, the Lrp5A214V mutation prevents deterioration of biomechanical properties occurring in Akita mice. Notably, Lrp5A214V /Akita mice develop fasting hyperglycemia and glucose intolerance with a delay relative to Akita mice (7 to 8 vs. 5 to 6 weeks, respectively), despite lack of insulin production in both groups by 6 weeks of age. Although insulin sensitivity is partially preserved in double heterozygous Lrp5A214V /Akita relative to Akita mutants up to 30 weeks of age, insulin-dependent phosphorylated protein kinase B (pAKT) activation in vitro is not altered by the Lrp5A214V mutation. Although white adipose tissue depots are equally reduced in both compound and Akita mice, the Lrp5A214V mutation prevents brown adipose tissue whitening that occurs in Akita mice. Thus, hyperactivation of Lrp5-dependent signaling fully protects bone mass and strength in prolonged hyperglycemia and improves peripheral glucose metabolism in an insulin independent manner. Wnt signaling activation represents an ideal therapeutic approach for diabetic patients at high risk of fracture. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).A modified synthetic pathway towards perylene-perylene dimers and a facile purification method to obtain the regioisomerically pure syn- and anti-isomers are reported. In addition, a novel perylene-naphthalene heterodimer with 30 conjugated π-electron pairs was designed and synthesized on the basis of a previously described precursor and the resulting regioisomers were separated from each other. Thereby, the opto-electronic properties of the linearly elongated chromophores could be investigated regarding the differences in length of their aromatic system and the configuration of the isomers. Further tuning of their energy gaps was realized via protonation and methylation of the dibenzimidazole-bridging unit. Extraordinary red-shifts of the absorption maxima of 62 nm for the methylated and 92 nm for the protonated perylene-perylene anti-isomer could be achieved. Moreover, the maxima for the syn-isomer could be shifted bathochromically by 87 and 113 nm, respectively.

Asthma is a chronic disease, of high prevalence, with important morbidity and that can lead to death in childhood. The use of intravenous magnesium sulfate has been indicated in cases refractory to the initial management with inhaled bronchodilators and corticosteroids.

To evaluate the use of magnesium sulfate in continuous infusion (50 mg/kg/h in 4 h) in children with severe acute asthma in a pediatric emergency room.

Ten-bed general pediatric emergency room, university hospital, tertiary, in southern Brazil.

All children over 2 years old with severe acute asthma refractory to the initial treatment who received a continuous infusion of magnesium sulfate at a dose of 50 mg/kg/h in 4 h, from April 2017 to October 2019.

Based on this study, the use of continuous intravenous magnesium sulfate proved to be well tolerated, leading to improved respiratory status, and can be considered as a satisfactory adjunctive therapy in the management of severe acute asthma.

Based on this study, the use of continuous intravenous magnesium sulfate proved to be well tolerated, leading to improved respiratory status, and can be considered as a satisfactory adjunctive therapy in the management of severe acute asthma.

Difficulties with sexual desire and arousal are common in women, but most lack access to effective treatment such as cognitive-behavioral therapy (CBT). eSense is a recently created online CBT intervention for sexual difficulties with promising evidence of usability. The current study assessed the feasibility of women completing the full eSense CBT program without guidance.

Eleven women with Sexual Interest/Arousal Disorder completed eSense and provided feedback via semi-structured interviews.

Participants reported high satisfaction with eSense's functionality, improved knowledge about sexuality, greater awareness of their thought patterns, and better perspective around their sexual difficulties. Despite some difficulty completing homework, participants exhibited statistically significant pre-post improvements in sexual desire (d = 1.04), sexual arousal (d = 1.83), sexual satisfaction (d = 1.35), and sexual distress (d = 1.79).

The findings add to the growing evidence that self-guided online interventions are feasible and potentially efficacious in treating female sexual dysfunction.

The findings add to the growing evidence that self-guided online interventions are feasible and potentially efficacious in treating female sexual dysfunction.Dual-energy X-ray absorptiometry (DXA)-derived appendicular lean mass/height2 (ALM/ht2 ) is the most commonly used estimate of muscle mass in the assessment of sarcopenia, but its predictive value for fracture is substantially attenuated by femoral neck (fn) bone mineral density (BMD). We investigated predictive value of 11 sarcopenia definitions for incident fracture, independent of fnBMD, fracture risk assessment tool (FRAX® ) probability, and prior falls, using an extension of Poisson regression in US, Sweden, and Hong Kong Osteoporois Fractures in Men Study (MrOS) cohorts. Definitions tested were those of Baumgartner and Delmonico (ALM/ht2 only), Morley, the International Working Group on Sarcopenia, European Working Group on Sarcopenia in Older People (EWGSOP1 and 2), Asian Working Group on Sarcopenia, Foundation for the National Institutes of Health (FNIH) 1 and 2 (using ALM/body mass index [BMI], incorporating muscle strength and/or physical performance measures plus ALM/ht2 ), and Sarcopenia Definitioed only modestly influenced by inclusion of fnBMD. In conclusion, the predictive value for fracture of sarcopenia definitions based on ALM is reduced by adjustment for fnBMD but strengthened by additional inclusion of physical performance measures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..Systemic chemotherapy improves the survival of patients who undergo pancreatectomy, but whether chemotherapy should be delivered before or after surgery remains debated. At The University of Texas MD Anderson Cancer Center, localized pancreatic ductal adenocarcinoma (PDAC) has been preferentially treated with preoperative therapy-a practice supported by a robust history of institutional and national trials. In the following review, we discuss the historical use of perioperative therapy, our experience with it at MD Anderson Cancer Center and internationally, and the future of treatment and trials for PDAC.Adjuvant therapy for pancreatic cancer has undergone a paradigm shift in the last 30 years. Before the 1990s, surgery was the main treatment with high morbidity and minimal long-term survival. In the mid-1980s, GITSG showed a doubling of overall survival from 11 to 20 months with 5-fluorouracil-based chemoradiation and now the PRODIGE trial showed the benefit of FOLFIRINOX with the longest overall survival to date approaching 5 years. Further investigation on the agents, duration and sequencing of therapy remains ongoing.While the use of neoadjuvant therapy is well-accepted in the treatment of borderline resectable and locally advanced pancreatic cancers, the benefit of neoadjuvant chemotherapy in patients with resectable disease has been a topic of debate. Recently, key trials evaluating neoadjuvant chemotherapy for resectable pancreatic cancer have reported results. This review describes key clinical trials evaluating the use of preoperative therapy in patients with technically resectable pancreatic cancer with a focus on their contribution to the available evidence.For patients with localized pancreatic cancer, neoadjuvant therapy (NT) is increasingly delivered before surgery to maximize the receipt of multimodality therapy and the odds of a margin-negative resection. Three decades of refining the use of NT have led to its acceptance as a valid treatment approach for pancreatic adenocarcinoma. In this review, we discuss the rationale for and recent global trends in the utilization of NT for patients with pancreatic cancer.Treatment of localized pancreatic cancer has also evolved to prioritize preoperative (neoadjuvant) multimodality therapy over a surgery-first approach. Given the complexities of pancreatic cancer staging and the challenge of delivering multiple treatment modalities (chemotherapy, radiation therapy, and surgery), an experienced and highly integrated multidisciplinary team is necessary to achieve the best outcomes. In this review, we will discuss our institutional experience with neoadjuvant therapy, guiding principles for treatment, and outline the landscape for future investigations.Surgery remains the only curative intent treatment modality for localized pancreatic adenocarcinoma. Even in those who can undergo successful margin negative resection, the ability to deliver adjuvant chemotherapy is suboptimal for various reasons, resulting in poor outcomes. The delivery of "standard of care" intensive modern neoadjuvant therapies can be challenging in low to-middle-income countries (LMICs) with limited resource. This article reviews the constraints in delivering neoadjuvant therapies in LMICs and strategies to improve its implementation.Surgical site infection after pancreaticoduodenectomy is often caused by pathogens resistant to standard prophylactic antibiotics, suggesting that broad-spectrum antibiotics may be more effective prophylactic agents. This article describes the rationale and methodology underlying a multicenter randomized trial evaluating piperacillin-tazobactam compared with cefoxitin for surgical site infection prevention following pancreaticoduodenectomy. As the first US randomized surgical trial to utilize a clinical registry for data collection, this study serves as proof of concept for registry-based clinical trials.Despite overall advances in cancer therapy, patients with pancreatic ductal adenocarcinoma continue to have a poor prognosis. While adjuvant therapy is still considered standard, there is mounting evidence that neoadjuvant therapy confers similar benefits in patients with locally advanced disease. The primary measures of response are radiographic, biochemical, margin status, and pathologic. Given overall low response rates and the need for new treatment strategies, standard metrics remain important to the investigation of new systemic agents.The management of pancreatic adenocarcinoma remains an area of controversy and ongoing discovery. Despite advances in surgical and radiation techniques, as well as chemotherapeutic agents, outcomes of patients diagnosed with this devastating malignancy remain poor. This article aims to review the available literature evaluating the efficacy of adjuvant, neoadjuvant, and definitive radiation therapy. We will also highlight areas of ongoing research efforts being carried out to improve outcomes in this patient population.The annual incidence of pancreatic cancer is nearly 50,000 patients. The 5-year overall survival is only 9%, and there remains a great need for better therapy. A subset of these patients presents with locally advanced disease. Multidisciplinary therapy has evolved to include some combination of systemic chemotherapy, locoregional radiation, and surgery in select patients with excellent biology. This review will address the thoughtful evidence-based and individualized approach to these patients.Metastatic pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related mortality in 2021. Cytotoxic therapies are the therapeutic mainstay for PDAC. The recent approval of olaparib as maintenance therapy for germline BRCA1/2-mutated PDAC and pembrolizumab for mismatch repair deficient PDAC represent molecularly targeted approaches for this disease. Investigational therapeutic strategies include targeting the stroma, metabolism, tumor microenvironment, and the immune system, and selected approaches are reviewed herein.Computed tomography (CT) is increasingly available to evaluate dogs with suspected adrenal disease, however, published studies describing the reproducibility of CT methods for quantifying adrenal gland (AG) measurements are lacking. This prospective, pilot, observer agreement study aimed to evaluate reproducibility and repeatability of two different methods of measurement of AGs on CT to establish a usable technique and define standard reference ranges. Multiplanar reformatted (MPR) CT images of both AGs of six large breed dogs were obtained with the MPR axis parallel to the spine and parallel to the long axis of the AG. Ten measurements were performed maximal length and diameter at cranial and caudal poles on dorsal, sagittal, and transverse images; and minimal diameter of cranial and caudal poles on transverse images. Three observers with different levels of experience repeated these measurements three times for each dog. Intra- and interobserver variability were calculated through intraclass correlation coefficient (ICC). The differences in time to perform measurements between the two methods were tested with Student's t-test. Regardless of the measurement method used, length of AGs on dorsal and sagittal MPR images had the lowest intra- and inter-observer variability (ICC = 0.93-0.99), diameter of caudal pole on transverse plane showed low intra- and interobserver variability (ICC = 0.77-0.80) and diameter of cranial pole had the highest variability (ICC = 0.12-0.61). Although length was the less variable measurement, its use may be unrealistic in daily practice. Interestingly measurement of caudal pole on transverse plane was characterized by low intra- and interobserver variability. No difference in time performing the measurements was noted between the two methods.

Advances in the care of soft-tissue tumors, including imaging capabilities and adjuvant radiation therapy, have broadened the indications and opportunities to pursue surgical limb salvage. However, peripheral nerve involvement and femoral nerve resection can still result in devastating functional outcomes. Nerve transfers offer a versatile solution to restore nerve function following tumor resection.

Two cases were identified by retrospective review. Patient and disease characteristics were gathered. Preoperative and postoperative motor function were assessed using the Medical Research Council Muscle Scale. Patient-reported pain levels were assessed using the numeric rating scale.

Nerve transfers from the obturator and sciatic nerve were employed to restore knee extension. Follow up for Case 1 was 24 months, 8 months for Case 2. In both patients, knee extension and stabilization of gait without bracing was restored. Patient also demonstrated 0/10 pain (an average improvement of 5 points) with decreased neuromodulator and pain medication use.

Nerve transfers can restore function and provide pain control benefits and ideally are performed at the time of tumor extirpation. This collaboration between oncologic and nerve surgeons will ultimately result in improved functional recovery and patient outcomes.

Nerve transfers can restore function and provide pain control benefits and ideally are performed at the time of tumor extirpation. This collaboration between oncologic and nerve surgeons will ultimately result in improved functional recovery and patient outcomes.Improved nitrogen (N) use is key to future food security and environmental sustainability. While many regions still experience N shortages, agriculture is the leading global emitter of N2 O due to losses exacerbated by N surpluses in other regions. In order to sustainably maintain or increase food production, farmers and their advisors need a comprehensive and actionable understanding of how nutrient management affects both yield and N2 O emissions, particularly in tropical and subtropical agroecosystems. We performed a meta-analysis to determine the effect of N management and other factors on N2 O emissions, plant N uptake, and yield. Our analysis demonstrates that performance indicators-partial N balance and partial factor productivity-predicted N2 O emissions as well as or better than N rate. While we observed consistent production and environmental benefits with enhanced-efficiency fertilizers, we noted potential trade-offs between yield and N2 O emissions for fertilizer placement. Furthermore, we observed confounding effects due to management dynamics that co-vary with nutrient application practices, thus challenging the interpretation of the effect of specific practices such as fertilization frequency. Therefore, rather than providing universally prescriptive management for N2 O emission reduction, our evidence supports mitigation strategies based upon tailored nutrient management approaches that keep N balances within safe limits, so as to minimize N2 O emissions while still achieving high crop yields. The limited evidence available suggests that these relationships hold for temperate, tropical, and subtropical regions, but given the potential for expansion of N use in crop production, further N2 O data collection should be prioritized in under-represented regions such as Sub-Saharan Africa.

There isgreat global variation in the sleeping arrangements for healthy newborn infants. Bed sharingis a type of sleeping practice in which the sleeping surface (e.g. bed, couch or armchair, or some other sleeping surface) is shared between the infant and another person. The possible physiological benefits include better oxygen and cardiopulmonary stability, fewer crying episodes, less risk of hypothermia, and a longer duration of breastfeeding. On the other hand, the most important harmful effect of bed sharing is that it may increase the risk of sudden infant death syndrome (SIDS). Studies have found conflicting evidence regarding the safety and efficacy of bed sharing during infancy.

To evaluate the efficacy and safety of bed sharing, started during the neonatal period, on breastfeeding status (exclusive and total duration of breastfeeding), incidence of SIDS, rates of hypothermia, neonatal and infant mortality, and long-term neurodevelopmental outcomes.

We used the standard search strategy of Cochras) and safety. Future studies should assess outcomes such as breastfeeding status and risk of SIDS. They should also include neonates from high-income countries and low- and middle-income countries, especially those countries where bed sharing is more prevalent because of cultural practices (e.g. Asian countries).Pathogens adapted to sub-lethal acidic conditions could increase the virulence and survival ability under lethal conditions. In the aquaculture industry, feed acidifiers have been used to increase the growth of aquatic animals. However, there is limited study on the effects of acidic condition on the virulence and survival of pathogens in aquaculture. In this study, we investigated the survival ability of Vibrio parahaemolyticus at lethal acidic pH (4.0) after adapted the bacteria to sub-lethal acidic pH (5.5) for 1 hr. Our results indicated that the adapted strain increased the survival ability at lethal acidic pH invoked by an inorganic (HCl) or organic (citric) acid. RNA-sequencing (RNA-seq) results revealed that 321 genes were differentially expressed at the sub-lethal acidic pH including cadC, cadBA and groES/groEL relating to acid tolerance response (ATR), as well as genes relating to outer membrane, heat-shock proteins, phosphotransferase system and flagella system. Quantitative real-time polymerase chain reaction (qRT-PCR) confirmed that cadC and cadBA were upregulated under sub-lethal acidic conditions. The CadC protein could directly regulate the expression of cadBA to modulate the ATR in V. parahaemolyticus. RNA-seq data also indicated that 113 genes in the CadC-dependent way and 208 genes in the CadC-independent way were differentially expressed, which were related to the regulation of ATR. Finally, the motility and cytotoxicity of the sub-lethal acidic adapted wild type (WT) were significantly increased compared with the unadapted strain. Our results demonstrated that the dietary acidifiers may increase the virulence and survival of V. parahaemolyticus in aquaculture.

Intensive care unit-acquired weakness (ICUAW) is a severe neuromuscular complication of critical illness. Serum lactate is a useful biomarker in critically ill patients. The relationship between serum lactate level and ICUAW remains controversial. This study evaluated whether hyperlactacidemia (lactate level >2 mmol/L) was an independent risk factor for ICUAW in critically ill adult patients.

An observational cohort study was performed in a general multidisciplinary intensive care unit (ICU). Sixty-eight consecutive adult critically ill patients without preexisting neuromuscular disease or a poor pre-ICU functional status whose length of ICU stay was 7 or more days were evaluated. Patients were screened daily for signs of awakening. Muscle strength assessment using the Medical Research Council score was performed on the first day a patient was considered awake. Patients with clinical muscle weakness were considered to have ICUAW.

Among the 68 patients who achieved a satisfactory state of consciousness, the diagnosis of ICUAW was made in 30 patients (44.1%). After multivariate analysis, hyperlactacidemia (P=.02), Acute Physiology and Chronic Health Evaluation II score (P=.04), duration of mechanical ventilation (P=.02), and the use of norepinephrine (P=.04) were found to be significantly associated with the development of ICUAW in critically ill patients.

This study shows a number of risk factors to be significantly associated with the development of ICUAW in critically ill adults. These factors should be considered when building early prediction models or designing prevention strategies for ICUAW in future studies.

This study shows a number of risk factors to be significantly associated with the development of ICUAW in critically ill adults. These factors should be considered when building early prediction models or designing prevention strategies for ICUAW in future studies.Programming magnetic fields with microscale control can enable automation at the scale of single cells ≈10 µm. Most magnetic materials provide a consistent magnetic field over time but the direction or field strength at the microscale is not easily modulated. However, magnetostrictive materials, when coupled with ferroelectric material (i.e., strain-mediated multiferroics), can undergo magnetization reorientation due to voltage-induced strain, promising refined control of magnetization at the micrometer-scale. This work demonstrates the largest single-domain microstructures (20 µm) of Terfenol-D (Tb0.3 Dy0.7 Fe1.92 ), a material that has the highest magnetostrictive strain of any known soft magnetoelastic material. These Terfenol-D microstructures enable controlled localization of magnetic beads with sub-micrometer precision. Magnetically labeled cells are captured by the field gradients generated from the single-domain microstructures without an external magnetic field. The magnetic state on these microstructures is switched through voltage-induced strain, as a result of the strain-mediated converse magnetoelectric effect, to release individual cells using a multiferroic approach. These electronically addressable micromagnets pave the way for parallelized multiferroics-based single-cell sorting under digital control for biotechnology applications.Leaf angle and leaf orientation value (LOV) are critical agronomic traits for maize plant architecture. The functions of NUCLEAR FACTOR Y (NF-Y) members in regulating plant architecture have not been reported yet. Here, we identified a regulator of maize plant architecture, NF-Y subunit C13 (ZmNF-YC13). ZmNF-YC13 was highly expressed in the leaf base zone of maize plants. ZmNF-YC13 overexpressing plants showed upright leaves with narrow leaf angle and larger LOV, while ZmNF-YC13 knockout plants had larger leaf angle and smaller LOV compared with wild-type plants. The changes in plant architecture were due to the changes in the expression of cytochrome P450 family members. ZmNF-YC13 interacts with two NF-Y subunit B members (ZmNF-YB9 and ZmNF-YB10) of the LEAFY COTYLEDON1 sub-family, and further recruits NF-Y subunit A (ZmNF-YA3) to form two NF-Y complexes. The two complexes can both activate the promoters of transcriptional repressors (ZmWRKY76 and ZmBT2), and the promoters of PLASTOCHRON group genes can be repressed by ZmWRKY76 and ZmBT2 in maize protoplasts. We propose that ZmNF-YC13 functions as a transcriptional regulator and, together with ZmNF-YBs and ZmNF-YA3, affects plant architecture by regulating the expression of ZmWRKY76 and ZmBT2, which repress the expression of cytochrome P450 family members in PLASTOCHRON branch.

Depression is common in patients with cardiac disease. The importance of preoperative depression for development of postoperative delirium (POD) following cardiac surgery is not well known. The aim is to provide a summary estimate of depression as a predictor of POD following cardiac surgery.

Systematic search of MEDLINE, EMBASE, Cochrane Library, Web of Science Core Collection and Psycinfo (Ovid) was performed from inception to October 2019, including cohort studies reporting odds ratios (ORs) and 95% confidence intervals (CIs) for POD following cardiac surgery in patients with preoperative depression compared to patients without depression. ORs and 95% CIs for POD were calculated using random-effects meta-analyses. Subgroup and sensitivity analyses were performed.

Seven studies were included with a combined study population of 2066 patients. The pooled prevalence of POD in the combined study population was 26% and preoperative depression was present in ∼9% of the total study population. All studies showed a positive association between preoperative depression and POD; and in 5 studies, the association was statistically significant. Patients with depression had a pooled OR of 2.31 (95% CI 1.37-3.90) for POD.

This systematic review and meta-analysis confirm the findings that the previous association between preoperative depression and increased risk for developing POD reported for other patient groups is found also in cardiac surgery. Depression screening prior to cardiac surgery may be effective in identifying patients at higher risk for POD.

This systematic review and meta-analysis confirm the findings that the previous association between preoperative depression and increased risk for developing POD reported for other patient groups is found also in cardiac surgery. Depression screening prior to cardiac surgery may be effective in identifying patients at higher risk for POD.

The inflammatory response after surgery is associated with patient prognosis. Patients who undergo thoracic surgery exhibit a profound systemic inflammatory response due to the surgical procedures used and application of one-lung ventilation. The aim of this study was to compare perioperative inflammatory changes in patients after intubated and non-intubated thoracic surgery for primary lung cancer resection.

This prospective randomized controlled study included forty patients who underwent surgical resection for stage I non-small-cell lung cancer. Blood samples for cytokine analysis were collected just before induction, at 1 and 24 h after surgery. Levels of the pro-inflammatory cytokine and anti-inflammatory cytokines were measured using quantitative sandwich enzyme immunoassay kits.

The basal values of cytokines were comparable between 2 groups. Within each group, the postoperative levels of interleukin (IL)-1, IL-6 and tumour necrosis factor-α increased, while those of IL-4 and IL-10 did not change significantly. The levels of IL-6 and tumour necrosis factor-α were significantly lower in group NI at 1 and 24 h postoperatively. Other cytokines did not differ in both groups during postoperative period. The IL-6/IL-10 ratio at 1 h after surgery was lower in non-intubated patients than in intubated patients, but there was no difference at 24 h after surgery.

Non-intubated thoracic surgery may attenuate the early inflammatory cytokine changes following major resection for primary lung cancer compared with intubated conventional surgery.

ClinicalTrials.gov registry number NCT04007354.

ClinicalTrials.gov registry number NCT04007354.

To compare patient-reported outcome measures of minimally invasive (MI) to sternotomy (ST) mitral valve repair.

We included all patients undergoing isolated mitral valve surgery via either a right mini-thoracotomy (MI) or ST over a 36-month period. Patients were asked to complete a modified Composite Physical Function questionnaire. Intraoperative and postoperative outcomes, and patient-reported outcome measures were compared between 2 propensity-matched groups (n = 47/group), assessing 3 domains 'Recovery Time', 'Postoperative Pain' (at day 2 and 1, 3, 6 and 12 weeks) and 'Treatment Satisfaction'. Composite scores for each domain were subsequently constructed and multivariable analysis was used to determine whether surgical approach was associated with domain scores.

The response rate was 79%. There was no mortality in either group. In the matched groups, operative times were longer in the MI group (P < 0.001), but postoperative outcomes were similar. Composite scores for Recovery Time [ST 51.7 (31.8-62.1) vs MI 61.7 (43.1-73.9), P = 0.03] and Pain [ST 65.7 (40.1-83.1) vs MI 79.1 (65.5-89.5), P = 0.02] significantly favoured the MI group. Scores in the Treatment Satisfaction domain were high for both surgical approaches [ST 100 (82.5-100) vs MI 100 (95.0-100), P = 0.15]. The strongest independent predictor of both faster recovery parameter estimate 12.0 [95% confidence interval (CI) 5.7-18.3, P < 0.001] and less pain parameter estimate 7.6 (95% CI 0.7-14.5, P = 0.03) was MI surgery.

MI surgery was associated with faster recovery and less pain; treatment satisfaction and safety profiles were similar.

MI surgery was associated with faster recovery and less pain; treatment satisfaction and safety profiles were similar.

We herein report a single-centre experience with the SAPIEN 3 Ultra balloon-expandable transcatheter aortic valve implantation (TAVI) system.

Between March 2019 and January 2020, a total of 79 consecutive patients received transfemoral TAVI using the SAPIEN 3 Ultra device. Data were retrospectively analysed according to updated Valve Academic Research Consortium-2 definitions. Detailed analysis of multislice computed tomography data was conducted to identify potential predictors for permanent pacemaker (PPM) implantation and residual paravalvular leakage (PVL) post TAVI.

Device success and early safety were 97.5% (77/79) and 94.9% (75/79) with resulting transvalvular peak/mean pressure gradients of 21.1 ± 8.2/10.9 ± 4.4 and PVL >mild in 0/79 patients (0%). Mild PVL was seen in 18.9% (15/79) of cases. Thirty-day mortality was 2.5% (2/79). The Valve Academic Research Consortium-2 adjudicated clinical end points disabling stroke, acute kidney injury and myocardial infarction occurred in 1.3% (1/79), 5.1 valve in TAVI procedures.

Approved pharmacological treatments for smoking cessation are modestly effective, underscoring the need for improved pharmacotherapies. Glucagon-like peptide-1 receptor (GLP-1R) agonists attenuate the rewarding effects of nicotine in preclinical studies. We examined the efficacy of extended-release exenatide, a GLP-1R agonist, combined with nicotine replacement therapy (NRT, patch) for smoking cessation, craving and withdrawal symptoms, with post-cessation body weight as secondary outcome.

Eighty-four prediabetic and/or overweight smokers were randomized (11) to once-weekly placebo or exenatide, 2mg, subcutaneously. All participants received NRT (21mg) and brief smoking cessation counseling. Seven-day point prevalence abstinence (expired CO level ≤5 ppm), craving, withdrawal and post-cessation body weight were assessed following 6 weeks of treatment. A Bayesian approach for analyzing generalized linear models yielded posterior probabilities (PP) to quantify the evidence favoring hypothesized effects of trtor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

Despite considerable progress in tobacco control, cigarette smoking remains the leading cause of preventable disease, disability, and death. In this pilot study, we showed that extended-release exenatide, a glucagon-like peptide-1 receptor agonist, added to the nicotine patch, improved abstinence and mitigated post-cessation body weight gain compared to patch alone. Further research is needed to confirm these initial positive results.

The SureFast® SARS-CoV-2 PLUS Test is a reverse transcription qPCR (RT-qPCR) assay for the direct, qualitative detection of novel coronavirus (SARS-CoV-2) RNA from stainless steel environmental sample swabs.

To validate the SureFast® SARS-CoV-2 PLUS Kit as part of the AOAC Research Institute's Emergency Response Validation Performance Tested Method SM program.

The SureFast® SARS-CoV-2 PLUS Kit was evaluated for specificity using in silico analysis of 15,764 SARS-CoV-2 sequences and 65 exclusivity organisms (both near neighbors and background organisms) using the ThermoBLAST program. The candidate method was evaluated in an unpaired study design for one environmental surface (stainless steel) and compared to the U.S. Centers for Disease Control and Prevention 2019-Novel Coronavirus (2019-nCoV) Real-Time RT-PCR Diagnostic Panel, Instructions for Use (Revision 4, Effective 6/12/2020).

Results of the in silico analysis demonstrated 99.99% selectivity of the method in being able to detect target sequences of the known CoV-2 genomes and discriminate them from near neighbors. In the matrix study, the candidate method demonstrated statistically significant better recovery of the target analyte than the PCR detection reference method.

The SureFast® SARS-CoV-2 PLUS Kit is a rapid and accurate method that can be utilized by food producers to detect the causative agent of COVID-19 on stainless steel contact surfaces.

SureFast® SARS-CoV-2 PLUS test method is highly specific for primer/probe binding to the E target genome region for the SARS-CoV-2 virus, 99.99% binding specificity using in silico analysis.

SureFast® SARS-CoV-2 PLUS test method is highly specific for primer/probe binding to the E target genome region for the SARS-CoV-2 virus, 99.99% binding specificity using in silico analysis.Lockdowns have been widespread used to limit social interaction and bend the epidemic curve. However, their intensity and geographical delimitation have been variable across different countries. Madrid (Spain) implemented perimeter lockdowns in September with the purpose of bending the COVID-19 curve. In this paper we compared, using join point regressions, the evolution of COVID-19 cases in those areas where this intervention was implemented and those where it was not. According to our analysis, the decrease in the epidemic curve started before the impact of the perimeter lockdown could be reflected.Magnesium (Mg) and calcium (Ca) are essential mineral nutrients poorly supplied in many human food systems. In grazing livestock, Mg and Ca deficiencies are costly welfare issues. Here, we report a Brassica rapa loss-of-function schengen3 (sgn3) mutant, braA.sgn3.a-1, which accumulates twice as much Mg and a third more Ca in its leaves. We mapped braA.sgn3.a to a single recessive locus using a forward ionomic screen of chemically mutagenised lines with subsequent backcrossing and Linked-Read sequencing of second back-crossed, second filial generation (BC2F2) segregants. Confocal imaging revealed a disrupted root endodermal diffusion barrier, consistent with SGN3 encoding a receptor-like kinase required for normal formation of Casparian strips, as reported in thale cress (Arabidopsis thaliana). Analysis of the spatial distribution of elements showed elevated extracellular Mg concentrations in leaves of braA.sgn3.a-1, hypothesised to result from preferential export of excessive Mg from cells to ensure suitable cellular concentrations. This work confirms a conserved role of SGN3 in controlling nutrient homeostasis in B. rapa, and reveals mechanisms by which plants are able to deal with perturbed shoot element concentrations resulting from a "leaky" root endodermal barrier. Characterisation of variation in leaf Mg and Ca accumulation across a mutagenised population of B. rapa shows promise for using such populations in breeding programmes to increase edible concentrations of essential human and animal nutrients.