Nevertheless, the detection of specific molecular changes in known pathways enables considerations for targeted therapies.Acidosis is among the least studied secondary injury mechanisms associated with neurotrauma. Acute decreases in brain pH correlate with poor long-term outcome in patients with traumatic brain injury (TBI), however, the temporal dynamics and underlying mechanisms are unclear. As key drivers of neuroinflammation, we hypothesized that microglia directly regulate acidosis after TBI, and thereby, worsen neurological outcomes. Using a controlled cortical impact model in adult male mice we demonstrate that intracellular pH in microglia and extracellular pH surrounding the lesion site are significantly reduced for weeks after injury. Microglia proliferation and production of reactive oxygen species (ROS) were also increased during the first week, mirroring the increase in extracellular ROS levels seen around the lesion site. Microglia depletion by a colony stimulating factor 1 receptor (CSF1R) inhibitor, PLX5622, markedly decreased extracellular acidosis, ROS production, and inflammation in the brain after injury. Mechanistically, we identified that the voltage-gated proton channel Hv1 promotes oxidative burst activity and acid extrusion in microglia. Compared to wildtype controls, microglia lacking Hv1 showed reduced ability to generate ROS and extrude protons. Importantly, Hv1-deficient mice exhibited reduced pathological acidosis and inflammation after TBI, leading to long-term neuroprotection and functional recovery. Our data therefore establish the microglial Hv1 proton channel as an important link that integrates inflammation and acidosis within the injury microenvironment during head injury.

The serotonergic system is known to contribute to levodopa-derived dopamine release in advanced Parkinson’s disease.

We investigated the role of the serotonergic system in determining response to treatment in early disease and risk for complications concurrently with dopaminergic alterations.

Eighteen patients with early and stable Parkinson’s disease underwent multitracer positron emission tomography using [

C]dihydrotetrabenazine (vesicular monoamine transporter 2 marker), [

C]methylphenidate (dopamine transporter marker), [

C]-3-amino-4-(2-dimethylaminomethylphenylsulfanyl)-benzonitrile (DASB, serotonin transporter marker), and [

C]raclopride (D2 marker) to investigate relationships between striatal dopaminergic and serotonergic alterations and levodopa-induced dopamine release, related to motor response to treatment and risk for dyskinesias, using a novel joint pattern analysis.

The joint pattern analysis revealed correlated spatial patterns conceptually related to abnormal dopamine turnovherapeutic advantage in early disease. © 2020 International Parkinson and Movement Disorder Society.

Joint analysis of dopaminergic and serotonergic data identified a turnover-related dopamine release component, strongly related to motor response to levodopa in early disease and contributing to higher risk for dyskinesia. These findings suggest that the contribution of the serotonergic system to dopamine release not only increases the risk for motor complications but also fails to provide sustained therapeutic advantage in early disease. © 2020 International Parkinson and Movement Disorder Society.Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.Proximilization of frozen elephant trunk (FET) necessitates the ligation and reimplantation of the left subclavian artery (LSA), the origin of which is distal and posterior, make rerouting difficult and cumbersome. We describe a rather simple technique for subclavian artery exposure and effective anatomical reconstruction in the mediastinum coupled with hybrid FET utilization for aortic aneurysm in elective and nonelective settings. The division of the sternocleidomastoid coupled with the sandbag behind the left shoulder brings the LSA superficial enabling anastomosis without any difficulty.Several lines of evidence suggest that the aggregation and deposition of amyloid-β peptide (Aβ) initiate the pathology of Alzheimer’s disease (AD). Recently, a genome-wide association study demonstrated that a single-nucleotide polymorphism proximal to the EPHA4 gene, which encodes a receptor tyrosine kinase, is associated with AD risk. However, the molecular mechanism of EphA4 in the pathogenesis of AD, particularly in Aβ production, remains unknown. Here, we performed several pharmacological and biological experiments both in vitro and in vivo and demonstrated that EphA4 is responsible for the regulation of Aβ production. Pharmacological inhibition of EphA4 signaling and knockdown of Epha4 led to increased Aβ levels accompanied by increased expression of β-site APP cleaving enzyme 1 (BACE1), which is an enzyme responsible for Aβ production. Moreover, EPHA4 overexpression and activation of EphA4 signaling via ephrin ligands decreased Aβ levels. In particular, the sterile-alpha motif domain of EphA4 was necessary for the regulation of Aβ production. Finally, EPHA4 mRNA levels were significantly reduced in the brains of AD patients, and negatively correlated with BACE1 mRNA levels. Our results indicate a novel mechanism of Aβ regulation by EphA4, which is involved in AD pathogenesis.We aimed toevaluate the association of the exposure to environmental tobacco smoke (ETS) during pregnancy and infancy with the risk of upper respiratory tract infections (URTI) in infants based on a Chinese birth cohort study. Among 4178 infants who constituted the final study population, 46.8% experienced URTI in their first year of life. The hazard ratios (HR) and 95% confidence intervals (CI) for the risk of URTI were assessed using Cox regression models. Compared with no ETS during pregnancy, continued ETS during pregnancy was independently associated with a higher risk of URTI (HR 1.36, 95% CI 1.13, 1.63) after adjustment for potential confounders, and also associated with earlier occurrence of URTI (log-rank P = 0.002). The association remained consistent across the strata defined according to maternal age, number of siblings, sex, and breastfeeding. Exposure to ETS during infancy was associated with URTI only among infants who were breastfed for less than 12 months (P for interaction less then 0.05).Furthermore, infants exposed to ETS during both pregnancy and infancy showed the highest HR of 1.46 (95% CI 1.16, 1.85) for URTI.Efforts should be made to protect pregnant women and infants from the adverse effects of indoor and outdoor ETS.

Fine needle aspiration is a well-established technique for evaluating primary and secondary bony lesions. With use in selected cases, it achieves a diagnostic yield comparable to biopsies.

Cases of osteosarcoma (OS) with available histological follow-up were retrieved over a 10-year period. Detailed morphological evaluation was done, with special emphasis on pitfalls in the diagnosis of OS on cytology and the various variants of OS.

Of the 41 cases with available follow-up histology, 56% were correctly diagnosed as OS on cytology. The most common false-negative cytological diagnosis of OS, in 17% cases, was giant cell tumour. The possible explanations for this included low cellularity, minimal atypia, absence of typical osteoid, misinterpretation of metachromatic osteoid material as fibro-collagenous material and non-availability of radiology at time of aspiration.

A triple-phase evaluation including clinical evaluation, appropriate radiological correlation and cytology/histopathology, is important to clinch an accurate diagnosis.

A triple-phase evaluation including clinical evaluation, appropriate radiological correlation and cytology/histopathology, is important to clinch an accurate diagnosis.

Staphylococcus aureus colonization and release of enterotoxin B (SEB) has been associated with severe chronic rhinosinusitis with nasal polyps (CRSwNP). The pathogenic mechanism of SEB on epithelial barriers, however, is largely unexplored.

We investigated the effect of SEB on nasal epithelial barrier function.

SEB was apically administered to air-liquid interface (ALI) cultures of primary polyp and nasal epithelial cells of CRSwNP patients and healthy controls, respectively. Epithelial cell integrity and tight junction expression were evaluated. The involvement of Toll-like receptor 2 (TLR2) activation was studied in vitro with TLR2 monoclonal antibodies and in vivo in tlr2

knockout mice.

SEB applied to ALI cultures of polyp epithelial cells decreased epithelial cell integrity by diminishing occludin and zonula occludens (ZO)-1 protein expression. Antagonizing TLR2 prevented SEB-induced barrier disruption. SEB applied in the nose of control mice increased mucosal permeability and decreased mRNA expression of occludin and ZO-1, whereas mucosal integrity and tight junction expression remained unaltered in tlr2

mice. Furthermore, in vitro SEB stimulation resulted in epithelial production of IL-6 and IL-8, which was prevented by TLR2 antagonization.

SEB damages nasal polyp epithelial cell integrity by triggering TLR2 in CRSwNP. Our results suggest that SEB might represent a driving factor of disease exacerbation, rather than a causal factor for epithelial defects in CRSwNP. Interfering with TLR2 triggering might provide a way to avoid the pathophysiological consequences of S.aureus on inflammation in CRSwNP.

SEB damages nasal polyp epithelial cell integrity by triggering TLR2 in CRSwNP. Our results suggest that SEB might represent a driving factor of disease exacerbation, rather than a causal factor for epithelial defects in CRSwNP. Interfering with TLR2 triggering might provide a way to avoid the pathophysiological consequences of S. aureus on inflammation in CRSwNP.

In China, the prevalence of superficial fungal infections of the foot is high and recurrence is common. However, a prospective, large-scale and multicentre study on the aetiology of superficial fungal infections of the foot is still lacking.

To study the epidemiology of aetiological agents of superficial fungal infections of the foot in urban outpatients in mainland China, as well as to understand the aetiology features of the pathogenic agent.

The study was designed as a multicentre, prospective epidemiological survey. A total of 1704 subjects were enrolled from seven geographical areas in mainland China. For each subject, one mycological sample and one bacterial sample were collected. KOH wet mount examination and culture were performed at local laboratories. The bacterial results were only reported in those with positive mycology. Further morphological identification and, if necessary, molecular biological identification were conducted in a central laboratory.

Of 1704 enrolled subjects, 1327 (77.9%) subjects had positive fungal culture results. The incidence of dermatophytes, yeasts and moulds was 90.1%, 8.1% and 1.1%, respectively. The most frequently isolated aetiological agent (fungus) was Trichophyton rubrum. Moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections. The most frequently isolated bacterial genus in patients was Staphylococcus.

This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. Trubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.

This study prospectively investigated the clinical and mycological features of human dermatophytosis in mainland China. T rubrum was the most frequently isolated fungus, and moccasin form was the most commonly reported clinical diagnosis of superficial fungal infections.The genera Acremonium and Sarocladium comprise a high diversity of morphologically and genetically related fungi generally found in the environment, although a few species, mainly Sarocladium kiliense and Acremonium egyptiacum, can also be involved in many human infections. Clinical management of opportunistic infections caused by these fungi is very complex, since their correct identification is unreliable, and they generally show poor antifungal response. More than 300 clinical cases involving a broad range of Acremonium/Sarocladium infections have so far been published, and with this review we aim to compile and provide a detailed overview of the current knowledge on Acremonium/Sarocladium human infections in terms of presentation, diagnosis, treatments and prognoses. We also aim to summarise and discuss the data currently available on their antifungal susceptibility, emphasising the promising results obtained with voriconazole as well as their impact in terms of animal infections.

To evaluate the sleep quality and its association with disability, fatigue and quality of life of breast cancer survivors.

This is a cross-sectional pilot study developed with breast cancer survivors. The data collection instruments consisted of general and clinical information on the disease and the World Health Organization Disability Assessment Schedule 2.0 (WHODAS 2.0); Pittsburgh Sleep Quality Index (PSQI); Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F); and Disabilities of the arm and Shoulder (DASH). Descriptive statistical analysis, correlation tests, tests for means comparison and linear regression were performed. Cohen’s d analysed the effect size. The significance was set at p<0.05.

71,9% of women had poor sleep quality. Subjective poor sleep quality was a predictor of worse scores for fatigue (p=0.007), quality of life by FACT-G (p=0.010) and FACIT-F (p=0.004), the functional performance of upper limbs (p=0.001) and disability (p=0.003).

Breast cancer survivors with subjective poor sleep quality had more fatigue, less upper limb-related functional performance, more disability and worse quality of life.

Breast cancer survivors with subjective poor sleep quality had more fatigue, less upper limb-related functional performance, more disability and worse quality of life.Stabilization of DNA is beneficial for many applications in the fields of DNA therapeutics, diagnostics, and materials science. Now, this phenomenon is studied on heterochiral DNA, an autonomous DNA recognition system with complementary strands in α-D and β-D configuration showing parallel strand orientation. The 12-mer heterochiral duplexes were constructed from anomeric (α/β-D) oligonucleotide single-strands. Purine-2,6-diamine and 8-aza-7-deaza-7-bromopurine-2,6-diamine 2′-deoxyribonucleosides having the capability to form tridentate base pairs with dT were used to strengthen the stability of the dA-dT base pair. Tm data and thermodynamic values obtained from UV melting profiles indicated that the 8-aza-7-deaza 2′-deoxyribonucleoside decorated with a bromo substituent is so far the most efficient stabilizer for heterochiral DNA. Compared with that, the stabilizing effect of the purine-2,6-diamine 2′-deoxyribonucleoside is low. Global changes of helix structures were identified by circular dichroism (CD) spectra during melting.Photoreceptor death is an important contributor to irreversible vision loss worldwide. In this review, I outline our work examining the role that purines, such as adenosine triphosphate (ATP), have in normal retinal function and in retinal disease. Our work shows that the actions of ATP, mediated by P2X receptors, are expressed in various retinal layers including photoreceptor terminals, and when stimulated by excessive levels of ATP is associated with rapid death of neurons. Treatment with a compound that blocks the action of P2X and some P2Y receptors reduces photoreceptor death in a mouse model of retinal degeneration. Our observations not only provide a means for developing a potential treatment for reducing photoreceptor death, but also provides a novel way of studying the neural plasticity effects that develop in the inner retina following photoreceptor death. There are a range of inner retinal changes that could influence the effectiveness of retinal prostheses. Indeed, using an ATP-induced degeneration model, we established that the amount of electrical stimulation required to elicit a response in the visual cortex was affected by the level of glial scarring. However, changes in P2X7 receptor expression by OFF ganglion cells during retinal degeneration can also be exploited by photoswitches to restore light sensitivity to degenerated retinae. Finally, our work has also considered how P2X7 expression by innate immune cells, and its role as a scavenger receptor, contributes to age-related macular degeneration (AMD). Our results show that loss of P2X7 function is associated with thickening of Bruch’s membrane as well as increased risk of advanced disease in people with AMD. Overall, our work over the last 20 years highlights the importance of purinergic signalling in normal retinal function and retinal disease and suggest that developing therapies that target P2X7 function could be of benefit for these diseases.The present study examined the association between behavioural dimensions of self-regulation and respiratory sinus arrhythmia (RSA), a marker of cardiac autonomic functioning in a sample of preschool children in the United States. Sixty-six children’s emotion- and cognitive-oriented dimensions of self-regulation were examined with respect to changes in RSA (reactivity and recovery). Results showed that children’s recovery RSA, which indicates the ability to return to homeostasis, but not reactivity, was significantly associated with the cognitive-oriented self-regulation.

Pharmacists play an integral role in paediatric patient care by ensuring the safe and optimal use of medications. There are increasing demands on pharmacists’ time and challenges to meet them within allocated resources, and therefore, it is important to ensure that resources are used efficiently. Patient prioritization tools for clinical pharmacists have been proposed via many studies, but are generally adult-based and/or have not been validated to confirm their effectiveness. The aim of this study was to create, pilot and validate a patient prioritization tool to be used by pharmacists providing clinical pharmacy services to paediatric patients.

A two-phase (retrospective and prospective) observational audit of pharmacists’ interventions collected via notes made on their ward handover information sheets and patient case notes was conducted over a 2-year period in a tertiary paediatric hospital. A patient prioritization tool was created based on pharmacists’ interventions in real time. This tool could be used at the start of the working day (without the need to review the patient or their case notes) to identify patients who would benefit most from a clinical pharmacist review. The tool was validated for effectiveness and selectivity.

The tool was easy to use and effective in identifying that 43% of paediatric inpatients did not require a routine clinical pharmacist review. It had 98% specificity in identifying patients who require a pharmacist intervention. It could be easily used at the start of the day to select patients for pharmacist review.

A new patient prioritization tool has been developed and validated for identifying paediatric inpatients requiring clinical pharmacist review.

A new patient prioritization tool has been developed and validated for identifying paediatric inpatients requiring clinical pharmacist review.Atopic dermatitis (AD) is a disease that can have a high impact on quality of life, especially due to itch and skin pain. This paper utilizes expertise from members of the International Society of Atopic Dermatitis (ISAD)/Oriented Patient-Education Network in Dermatology (OPENED) task force to review the epidemiology, pathophysiology and exacerbating factors of itch and pain in atopic dermatitis. General principles of treatment are provided, as well as a more detailed evaluation of topical and systemic therapies. Educational and psychological approaches to itch and pain in atopic dermatitis are proposed, along with expert recommendations for the management of itch and pain in atopic dermatitis.

T cells from patients with primary sclerosing cholangitis (PSC) show a prominent interleukin (IL)-17 response upon stimulation with bacteria or fungi, yet the reasons for this dominant T-helper 17 (Th17) response in PSC are not clear. Here, we analyzed the potential role of monocytes in microbial recognition and in skewing the T-cell response toward Th17.

Monocytes and T cells from blood and livers of PSC patients and controls were analyzed ex vivo and in vitro using transwell experiments with cholangiocytes. Cytokine production was measured using flow cytometry, enzyme-linked immunosorbent assay, RNA in situ hybridization, and quantitative real-time PCR. Genetic polymorphisms were obtained from ImmunoChip analysis. Following ex vivo stimulation with phorbol myristate acetate/ionomycin, PSC patients showed significantly increased numbers of IL-17A-producing peripheral blood CD4

T cells compared to PBC patients and healthy controls, indicating increased Th17 differentiation in vivo. Upon stimulation withto produce chemokines mediating recruitment of Th17 cells and more monocytes into portal tracts. Taken together, these results point to a pathogenic role of monocytes in patients with PSC.

Owing to the increasing interest in public health research of antioxidant micronutrients and the inaccuracy of routine serum concentrations of the fat-soluble vitamins A (retinol) and E (DL-α-tocopherol) measurements, we developed a reliable, highly sensitive, robust and rapid method for the quantification of two clinically important lipophilic antioxidants in serum using a reverse-phase HPLC/DAD method.

Sample preparation and analytical conditions that would affect extraction efficiency and quantitative results of vitamins A and E were investigated and optimized. Vitamins A and E were extracted from serum via liquid-liquid extraction (LLE). After adequate sample preparation, the samples were injected directly into the HPLC system with diode-array detector (DAD). Chromatographic separation was completed in 7minutes for vitamins A and E. With vitamin A acetate and vitamin E acetate as internal standards, the method was applied to the measurement of vitamins A and E in human serum.

We evaluated method linrryover rate of vitamins A and E was below 1%. As for the evaluation of accuracy, the biases were <±5% by comparing with NIST standard reference material SRM 968f.

The method is a simple sample treatment procedure for the determination of fat-soluble vitamins A and E in human serum with high sensitivity and specificity. The proposed method could be recommended as a candidate reference method for the determination of serum concentrations of the fat-soluble vitamins A and E in human serum.

The method is a simple sample treatment procedure for the determination of fat-soluble vitamins A and E in human serum with high sensitivity and specificity. The proposed method could be recommended as a candidate reference method for the determination of serum concentrations of the fat-soluble vitamins A and E in human serum.Myostatin (MSTN) and myogenic differentiation antigen (MyoD) play an essential role in specification and differentiation of skeletal muscle. However, the role of stress in the regulation of MyoD and MSTN has not been fully revealed and more evidence should be provided. Here, we reported the cloning and expressional analyses of MSTN and MyoD in Large-scale Loach Paramisgurnus dabryanus (hereafter PdMSTN and PdMyoD). Injecting individuals with 0, 60, 600, and 1,200 μg/kg dexamethasone (DXM) for five consecutive days resulted in a dose-dependent change of PdMSTN and PdMyoD expression. The expression of PdMSTN was upregulated with increasing DXM concentrations, while PdMyoD expression was downregulated. The changes in the expression of these genes at different time points for 10 consecutive days were studied after individuals were treated with 600 μg/kg DXM. Compared with the control group, PdMSTN expression decreased and PdMyoD expression increased before 12 h, and both PdMSTN and PdMyoD expression levels increased at 24 h, which was significantly higher than those in control group. At a prolonged treatment of 5-10 d, expression levels of PdMSTN and PdMyoD had significantly reduced. The results indicate that both PdMyoD and PdMSTN are involved in DXM-induced stress in Large-scale Loach.Lead poisoning, mainly through incidental ingestion of lead ammunition in carcasses, is a threat to scavenging and predatory bird species worldwide. In Australia, shooting for animal control is widespread, and a range of native scavenging species are susceptible to lead exposure. However, the prevalence of lead exposure in Australia’s scavenging and predatory birds is largely unknown. We evaluated the degree to which the Tasmanian wedge-tailed eagle (Aquila audax fleayi), an endangered Australian raptor and facultative scavenger, showed evidence of lead exposure. We detected lead in 100% of femur and liver tissues of 109 eagle carcasses opportunistically collected throughout Tasmania between 1996 and 2018. Concentrations were elevated in 10% of 106 liver (>6 mg/kg dry wt) and 4% of 108 femur (>10 mg/kg dry wt) samples. We also detected lead in 96% of blood samples taken from 24 live nestlings, with 8% at elevated concentrations (>10 μg/dL). Of the liver samples with elevated lead, 73% had lead207/206 isotope ratios within the published range of lead-based bullets available in Tasmania. These first comprehensive data on lead exposure of an Australian raptor are comparable to those for raptor studies elsewhere that identify lead-based ammunition exposure as a conservation threat. Our findings highlight the importance of further research and efforts to address lead contamination throughout the Tasmanian ecosystem and in other Australian regions. Environ Toxicol Chem 2021;40219-230. © 2020 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real-world setting.

A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations.

Forty-nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was≥3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04-0.81; P=.03) in a multi-variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression-free survival (PFS) was 28.4months and median overall survival (OS) was not reached; 2-year PFS and OS were 68.6±7.5% and 90.4±4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n=517) and 2 clinical trials (n=62) meeting prespecified criteria.

Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.

Our data support favorable safety tolerability and efficacy of daratumumab among non-selective RRAL patients in a real-world setting.Iatrogenic nerve injury during surgery is a major source of concern for both patients and surgeons. This study aimed to identify the nerves most commonly injured during surgery, along with the commonly associated operative procedures. A literature search was conducted using the PubMed database to identify nerves commonly injured during surgery, along with the surgical procedure associated with the injury. The following 11 nerves, ranked in order with their associated surgical procedures, were found to be the most commonly injured (a) intercostobrachial nerve in axillary lymph node dissections and transaxillary breast augmentations, (b) vestibulocochlear nerve in cerebellopontine tumor resections and vestibular schwannoma removals, c) facial nerve in surgeries of the inner ear and cheek region, (d) long thoracic nerve in axillary lymph node dissections, (e) spinal accessory nerve in surgeries of the posterior triangle of the neck and cervical lymph node biopsies, (f) recurrent laryngeal nerve in thyroid surgeries, (g) genitofemoral nerve in inguinal hernia and varicocele surgeries, (h) sciatic nerve in acetabular fracture repairs and osteotomies, (i) median nerve in carpal tunnel release surgeries, (j) common fibular nerve in varicose vein and short saphenous vein surgeries, and (k) ulnar nerve in supracondylar fracture surgeries. Although the root cause of iatrogenic nerve injury differs for each nerve, there are four unifying factors that could potentially decrease this risk for all peripheral nerves. These four influencing factors include knowledge of potential anatomical variations, visual identification of at-risk nerves during the procedure, intraoperative nerve monitoring, and expertise of the surgeon.Emerging evidence suggests that miR-143 plays an important role in the regulation of tumor sensitivity to chemotherapeutic agents. The study explores the underlying mechanism of miR-143 in reversing cisplatin resistance in ovarian cancer. The cisplatin-resistant ovarian cancer cell line A2780/CDDP was induced and established via treating A2780 cells by gradually increasing cisplatin concentrations. The IC50 values of A2780/CDDP and A2780 to cisplatin were 218.10 ± 1.12 and 21.99 ± 1.12 μM, respectively. Quantitative real-time polymerase chain reaction (qRT-PCR) results showed that miR-143 was significantly decreased in A2780/CDDP cells compared with A2780 cells. miR-143 overexpression decreased cisplatin resistance in A2780/CDDP, and miR-143 inhibition decreased A2780 sensitivity to cisplatin. Results of qRT-PCR, Western blot analysis, and luciferase reporter assay indicated that the direct target of miR-143 was DNMT3A, which, in turn, was upregulated in A2780/CDDP. DNMT3A overexpression antagonized the sensitizing effect of miR-143 on A2780/CDDP to cisplatin. Knocking down of DNMT3A reduced cisplatin resistance in A2780/CDDP, while overexpression of DNMT3A increased cisplatin resistance in A2780. Methylation-specific polymerase chain reaction results showed that the methylation level in the promoter region of the miR-143 precursor gene was higher in A2780/CDDP cells than in A2780 cells. DNMT3A mediated the hypermethylation of the miR-143 precursor gene, resulting in miR-143 downregulation in A2780/CDDP. miR-143 inhibited cell growth of A2780/CDDP cell in nude mice. Our findings indicated the negative feedback between miR-143 and DNMT3A as a crucial epigenetic modifier of cisplatin resistance in ovarian cancer.Thymoquinone (TQ), the main active constituent of Nigella sativa seeds, has been shown to play a role in antioxidation, anti-inflammation, and antitumor. Recent studies have demonstrated that TQ contributes to the suppression of liver fibrosis. Abnormal activated epithelial-mesenchymal transition (EMT) promotes the activation of hepatic stellate cells (HSCs). However, whether the antifibrotic effects of TQ occur through inhibiting EMT is largely unknown. In this study, it was found that TQ ameliorated liver fibrosis and collagen accumulation in carbon tetrachloride (CCl4) mice. In vitro, TQ inhibited HSC activation including reduced proliferation, α-smooth muscle actin, and collagen. In addition, TQ markedly suppressed the EMT process, with enhanced E-cadherin and reduced desmin. Notably, snail family transcriptional repressor 1 (Snai1), the EMT master transcription factor, was obviously inhibited by TQ in vivo and in vitro. Further studies demonstrated that Snai1 was a target of microRNA-30a (miR-30a), which was upregulated by TQ. Interestingly, the effects of TQ on HSC activation and EMT were almost inhibited by miR-30a inhibitor. Collectively, we demonstrate that TQ inhibits HSC activation, at least in part, via regulation of miR-30a and Snai1. TQ upregulates miR-30a expression, resulting in a reduced Snai1 level as well as EMT process inactivation, which contributes to the inhibition of HSC activation. TQ may be a potential therapeutic agent for liver fibrosis.The anatomy of the hair follicle and the dynamics of its barrier provide a special space for interactions between macromolecules and the underlying tissue. Translocation across the hair follicle epithelium and immune recognition have been confirmed for proteins, nucleic acids, engineered particles, virus particles and others. Tissue responses can be modulated by pro-inflammatory stimuli as demonstrated in penetration and transcutaneous immunization studies. Even under physiological conditions, hair follicle openings are filled with exogenous material ranging from macromolecules, engineered particles to natural particles including diverse communities of microbes. The exposed position of the infundibulum suggests that local inflammatory insults could disturb the finely tuned balance and may trigger downstream responses that initiate or facilitate local outbreaks of inflammatory hair diseases typically occurring in close spatial association with the infundibulum as observed in cicatricial alopecia. The question as to how microbial colonization or deposition of contaminants on the surface of the hair follicle epithelium interact with the barrier status under the influence of individual predisposition, may help us understand local flare-ups of inflammatory hair diseases. Specifically, learning more about skin barrier alterations in the different types of inflammatory hair diseases and cross-talk with exogenous compounds could give new insights in this less explored aspect of hair follicle homeostasis. Such knowledge may not only be used to develop supportive measures to maintain a healthy scalp. It may have wider implications for our understanding on how external factors influence inflammation and immunological responses in the skin.Supravalvular pulmonary stenosis acquired as a postoperative cardiac procedure complication is relatively common. However, that occurring after a surgically created pleuro-pericardial window has not been described until now, to the best of our knowledge. We present a case of acquired supravalvular pulmonary stenosis that developed 9 years after the pleuro-pericardial window creation for pyopericardium due to a constricting pericardial band. The child underwent successful surgical relief of the stenosis along with repair of the atrial and ventricular septal defects.Equilibrium sampling based on silicone polydimethylsiloxane (PDMS) has been used to determine the concentrations of freely dissolved hydrophobic organic compounds (HOCs) and assess the thermodynamic potentials for bioaccumulation of these compounds in the aquatic environment. This allows the use of PDMS-based sampling techniques in assisting conventional sampling and extraction methods for the determination of the concentrations of HOCs in aquaculture products. The present study is an ex situ demonstration of how well PDMS can inform the tissue residues and dietary risks of legacy or current-use organic chemicals in aquaculture species from farm ponds in eastern China. For legacy contaminants such as polybrominated diphenyl ethers (PBDEs, n = 10), good agreement between the predicted concentrations based on PDMS and the measured lipid-normalized concentrations was observed for 60% of the studied biota, including both pelagic and benthic species. For pesticides currently used, such as pyrethroid (PE) (n = 4) and organophosphate pesticides (OPPs, n = 7), the measured tissue residues were consistently higher than those predicted by PDMS, possibly caused by the continuous input from the surroundings. For the organochlorine pesticides (OCPs, n = 5), the only detected chemical was also underestimated. Adjusted by ingestion rates of aquaculture products and toxicology data, the target hazard quotients of these chemicals predicted from PDMS were generally comparable to those derived from measured concentrations in tissue because of the predominance of PBDEs. Overall, PDMS-based equilibrium sampling offered an alternative approach for the prediction of tissue residues and dietary risks of PBDEs. Moreover, it should be applied with caution for PEs, OPPs, and OCPs. Improving the application of PDMS for these chemicals in farm ponds warrants future study. Environ Toxicol Chem 2021;4079-87. © 2020 SETAC.This study aims to analyze the behaviour of cardiac autonomic modulation in adolescents with a family history of hypertension along with polymorphism of the ACE gene (rs1799752). The study involved 141 adolescents, with a mean age of 14.89, divided into the following six groups offspring of normotensive parents (ONP) DD, DI and II; and offspring of hypertensive parents (OHP) DD, DI and II. Blood pressure, body composition, family history of hypertension, sleep disorder, and sexual maturation were assessed for the groups’ characterization. Afterwards, an electrocardiogram was performed, and oral mucosal cells were collected to analyze heart rate variability and genotypic research of angiotensin-converting enzyme. The main finding of this study was the decrease of vagal action in group OHP (genotype DD) relative to group ONP (genotype II) LF (%), 54.25 ± 3.14 vs 39.33 ± 3.80; HF (%), 45.74 ± 3.14 vs 60.66 ± 3.80; LF/HF, 1.48 ± 0.23 vs 0.68 ± 0.19. The results also showed changes in the variable diastolic blood pressure (DBP) in OHP (genotype DI) to ONP (genotype II) groups 72.99 ± 2.33 vs 63.27 ± 1.72; and OHP (genotype DI) to ONP (genotype DD) groups. Adolescents with genotype DD and a family history of arterial hypertension present chances in cardiac autonomic modulation, the cardiac parasympathetic modulation is lower in these adolescents in comparison to participants of ONP + II group.The biochemical properties and thermal inactivation of polyphenol oxidase (PPO) from three main planted lily cultivars in China, namely, Lilium lancifolium Thunb, Lilium brownie var. viridulum, and Lilium davidii var. unicolor cotton were evaluated. Data indicate that the PPO from three cultivars showed two optimum pH levels of 4.0 and 6.5-7.0 and temperature of 15°C and exhibited the highest affinity toward 4-methylcatechol. However, this enzyme did not exhibit monophenolase activity. Thiourea and L-cysteine were more effective than other inhibitors. The enzymatic activity of L. lancifolium Thunb PPO crude extract was higher than that of L. brownie var. viridulum and L. davidii var. unicolor cotton. For thermal inactivation, L. davidii var. unicolor cotton PPO showed the best thermal resistance at 65-75°C, and L. lancifolium Thunb showed stability at 45°C. The deactivation of the three types of PPO followed the first-order reaction kinetics, and the activation energy (Ea) was 144.28, 138.00, and 107.12 kJ/mol for L. lancifolium Thunb PPO, L. brownie var. viridulum PPO, and L. davidii var. unicolor cotton PPO, respectively. PRACTICAL APPLICATIONS Lilium is an ornamental and edible plant typically used for food and traditional Chinese medicine. Its flowers are used for decoration, and its underground bulbs are rich in various bioactive substances. Fresh lily bulbs easily turn brown and lose economic value during storage and processing. Polyphenol oxidase (PPO) is a crucial molecule involved in the enzymatic browning of fruit and vegetables. In this study, PPO was extracted from three main planted lily cultivars in China. Namely, Lilium lancifolium Thunb, Lilium brownie var. viridulum, Lilium davidii var. unicolor cotton and was partially characterized. The results are of considerable importance to further understand the PPO of lily bulbs and provide guidance for the inactivation of enzymes and the processing of lily bulb juice.Wax esters (WE) are neutral lipids formed by condensation of fatty alcohol with fatty acyl-CoA by wax synthases. They serve as carbon and energy reserves and are potential substrates for various commercial applications. Sunflower (Helianthus annuus) an edible oil seed is a source of WE, however, the gene responsible for WE formation has hitherto remained unidentified. Using an in silico approach we identified, isolated putative Sunflower wax synthase (HaWS) gene and investigated it’s potential for WE production in yeast. Heterologous expression of HaWS in Saccharomyces cerevisiae H1246 exhibited 57 kDa protein which was confirmed by immunoblotting. Recombinant yeast expressing HaWS were fed with combinations of C16, C18 fatty alcohols with 160, 180 fatty acyl CoA’s as potential substrates to validate WE formation in vivo. The yeast cells accumulated C-32 to C-36 WE. Our study reveals identification, isolation, and heterologous functional expression of WS gene from Sunflower for the first time. PRACTICAL APPLICATIONS Wax synthases (WSs) are critical enzymes for wax ester (WE) biosynthesis. WEs are high value products having several industrial applications. WE serve as substrates for lubricants, food coatings, cosmetics, and pharmaceuticals. There is a demand for alternate renewable resource of WEs. In this study, we have successfully isolated a putative wax synthase gene from Sunflower and submitted its sequence data to the GenBank (Accession number MH460820). Conserved sequence search analysis showed presence of condensation superfamily motif‒HHXXXDG, critical for WE biosynthesis. Heterologous expression of HaWS in yeast revealed synthesis of C-32 to C-36 WE. Our study demonstrates the efficacy of HaWS to accumulate specific WE of desired lengths in yeast, and thus represents an alternate source of WE for commercial applications and for biotechnological production of tailored WE in eukaryotic expression systems.The molecular structures of potassium tetrakis(hexafluoroacetylacetonato)lanthanide(III) complexes [KLn(hfa)4 ] (Ln=La, Gd, Lu; hfa=C5 HF6 O2 ,) were studied by synchronous gas-phase electron diffraction/mass spectrometry (GED/MS) supported by quantum-chemical (DFT/PBE0) calculations. The compounds sublime congruently and the vapors contain a single molecular species the heterobinuclear complex [KLn(hfa)4 ]. All molecules are of C1 symmetry with the lanthanide atom in the center of an LnO8 coordination polyhedron, while the potassium atom is coordinated by three ligands with formation of three K-O and three K-F bonds. One hfa ligand is not bonded to the potassium atom. Topological analysis of the electron-density distributions confirmed the existence of ionic-type K-O and K-F bonding. The structures of the free [KLn(hfa)4 ] molecules are compared with those of the related compounds [KDy(hfa)4 ] and [KEr(hfa)4 ] in their crystalline state. The complex nature of the chemical bonding is discussed on the basis of electron-density topology analyses.The aim of the current study was to test the validity of the Norwegian version of the Desire Thinking Questionnaire (DTQ). Three cross-sectional surveys were conducted investigating the psychometric properties of the DTQ in alcohol use (N = 588), nicotine use (N = 446) and social media use (N = 359). Principal components and confirmatory factor analyses supported the original two-factor solution consisting of verbal perseveration (VP) and imaginal prefiguration (IP); however, one item was removed to obtain good fit. Internal consistency was acceptable. Both IP and VP showed significant correlations with problem drinking, nicotine dependence and problematic social media use. Regression analyses, controlling for demographics and negative affect, found IP and VP to be significantly associated with all dependent variables. The results confirm that desire thinking is an important construct across different addictive behaviours.A triplex-PCR assay was developed and evaluated for rapid detection of methicillin-resistant Staphylococcus aureus (MRSA) recovered from various biological samples of pig. Three sets of primers were designed to target mecA, 16S rRNA and nuc genes of MRSA. The specific amplification generated three bands on agarose gel, with sizes 280 bp for mecA, 654 bp for 16S rRNA and 481 bp for nuc, respectively. A potential advantage of the PCR assay is its sensitivity with a detection limit of 102 CFU per ml of bacteria. In all, 79 MRSA isolates recovered from various samples of pigs were subjected to the amplification by the triplex-PCR assay and all the isolates yielded three bands corresponding to the three genes under this study. No false-positive amplification was observed, indicating the high specificity of the developed triplex-PCR assay. This assay will be a useful and powerful method for differentiation of MRSA from methicillin-sensitive S. aureus, coagulase-negative methicillin-resistant staphylococci and coagulase-negative methicillin-sensitive staphylococci.Aquatic systems worldwide are threatened by the anthropogenic use of synthetic chemicals, including pesticides, pharmaceuticals, and road de-icers. Exposure to contaminants can alter the behavior, morphology, and physiology of organisms if it occurs during sensitive life stages. For instance, past studies have documented feminization of male amphibians following herbicide exposure and skewed sex ratios among amphibian populations exposed to road salt. However, many of these studies lack the complexities found within natural environments, such as competition with conspecifics or threat of predation, which are also known to influence development. Thus, it is important to understand how anthropogenic and natural stressors interact to alter animal sex ratios. Given the growing concern of secondary salinization of freshwater systems, we exposed larval wood frogs (Rana sylvatica) to either road salt (sodium chloride [NaCl]) or an alternative salt mixture (NaCl, magnesium chloride [MgCl2 ], and potassium chloride [KCl]) at 3 concentrations (200, 600, and 1000 mg Cl- /L) crossed with 3 biotic stressors (no-stressor control, competition, or predator cues) to examine their potentially interactive effects on sex. Exposure to biotic stressors and NaCl did not influence wood frog sex ratios. In contrast, tadpole exposure to the intermediate salt mixture concentration significantly reduced the proportion of female frogs. Future studies are needed to determine whether such changes in sex are widespread among sensitive species with complex life cycles, and to assess the consequences of sex ratio changes on long-term population dynamics. Environ Toxicol Chem 2021;40231-235. © 2020 SETAC.

In the past, dictionary learning (DL) and sparse coding (SC) have been proposed for the regularization of image reconstruction problems. The regularization is given by a sparse approximation of all image patches using a learned dictionary, that is, an overcomplete set of basis functions learned from data. Despite its competitiveness, DL and SC require the tuning of two essential hyperparameters the sparsity level S – the number of basis functions of the dictionary, called atoms, which are used to approximate each patch, and K – the overall number of such atoms in the dictionary. These two hyperparameters usually have to be chosen a priori and are determined by repetitive and computationally expensive experiments. Furthermore, the final reported values vary depending on the specific situation. As a result, the clinical application of the method is limited, as standardized reconstruction protocols have to be used.

In this work, we use adaptive DL and propose a novel adaptive sparse coding algorithm for two-in this work we focused on 2D radial cine MR image reconstruction, we expect the method to be applicable to different imaging modalities as well.We investigated the functional morphology of lingual prey capture in the blue-tongued skink, Tiliqua scincoides, a lingual-feeding lizard nested deep within the family Scincidae, which is presumed to be dominated by jaw-feeding. We used kinematic analysis of high-speed video to characterize jaw and tongue movements during prey capture. Phylogenetically informed principal components analysis of tongue morphology showed that, compared to jaw-feeding scincids and lacertids, T. scincoides and another tongue-feeding scincid, Corucia zebrata, are distinct in ways suggesting an enhanced ability for hydrostatic shape change. Lingual feeding kinematics show substantial quantitative and qualitative variation among T. scincoides individuals. High-speed video analysis showed that T. scincoides uses significant hydrostatic elongation and deformation during protrusion, tongue-prey contact, and retraction. A key feature of lingual prey capture in T. scincoides is extensive hydrostatic deformation to increase the area of tongue-prey contact, presumably to maximize wet adhesion of the prey item. Adhesion is mechanically reinforced during tongue retraction through formation of a distinctive „saddle” in the foretongue that supports the prey item, reducing the risk of prey loss during retraction.Current evidence suggests that coronavirus disease 2019 (COVID-19), caused by severe respiratory syndrome coronavirus 2 (SARS-CoV-2), is predominantly transmitted from human-to-human. However, evidence on vertical transmission and natural passive immunity among the newborns exposed to COVID-19 is scanty and varies. This poses a challenge on preventive interventions for the newborns. We conducted a systematic review to first, determine the likelihood of vertical transmission among COVID-19 exposed infants and second, determine whether antibodies against SARS-CoV-2 were generated among COVID-19 vertically exposed but negative infants. This review registered in PROSPERO searched evidence from PubMed/MEDLINE and Google Scholar, among others. About 517 studies were pooled, where 33 articles (5.8%) met the inclusion criteria such as infection prevention and control measures at birth. A total of 205 infants born to COVID-19 positive mothers were studied. Overall, 6.3% (13/205; 95% CI 3.0%-9.7%) of the infants tested positive for COVID-19 virus at birth.