Notes

Mixture of hepcidin using neutrophil gelatinase-associated lipocalin regarding prediction in the continuing development of sepsis-induced intense renal injury.
There was a significantly lower rate of hysterectomy in the non-praevia group. The overall estimated blood loss was significantly lower in those without praevia.

Suspected PAS without placenta praevia is at lower risk of hysterectomy and massive blood loss. The management approach can be tailored accordingly, with good operative outcomes with transverse abdominal and uterine incisions. Antenatal diagnosis can be difficult to accurately predict the degree of invasion, and a higher level of suspicion is required.
Suspected PAS without placenta praevia is at lower risk of hysterectomy and massive blood loss. The management approach can be tailored accordingly, with good operative outcomes with transverse abdominal and uterine incisions. Antenatal diagnosis can be difficult to accurately predict the degree of invasion, and a higher level of suspicion is required.The influence of reinforcement, especially fibre reinforcement in ultra-high performance concrete is strongly dependent on the bonding (adhesive, shear and friction bond) between metallic surface and cementitious matrix. As usually straight fibres are used for fibre reinforcement and, thus, no significant mechanical bonding is existent, the adhesive bond is particularly important. Previous studies stated that the adhesive bonding behaviour between metallic materials and cementitious matrix strongly depends on the chemical composition of metallic alloys. Therefore, in order to address this topic, the present study investigates the growth of C-S-H phases on stainless steel and on cold drawn steel. This growth process was realised by a surface treatment of the metallic alloys using a synthetically manufactured Tricalciumsilicate (C3 S) powder diluted in water. After defined times of the C3 S treatment the process is stopped to get a time dependent growing behaviour of the cementitious phases. Light microscopy as well as scanning electron microscopy was used in order to investigate the surfaces following the application of the C3 S. The results reveal that the growth of C-S-H phases is more dependent on the metallic surface and its topography than on the alloy composition.Novelty anticipation activates the mesolimbic system and promotes subsequent long-term memory in younger adults. Importantly, mesolimbic structures typically degenerate with age, which might reduce positive effects of novelty anticipation. Here, we used electroencephalography in combination with an established paradigm in healthy young (19-33 years old, n = 28) and older (53-84, n = 27) humans. Colored cues predicted the subsequent presentation of either a novel or previously familiarized image (75% cue validity). On the subsequent day, recognition memory for the novel images was tested. Behaviorally, novelty anticipation improved recollection-based but not familiarity-based recognition memory in both groups, and this effect was more pronounced in older subjects. Furthermore, novelty and familiarity cues increased theta (4-8 Hz) and decreased alpha/beta power (9-20 Hz); at outcome, expected novel and familiar images both increased beta power (13-25 Hz). Finally, a subsequent memory effect for expected novel images was associated with increases in beta power independent of age. Together, novelty anticipation drives hippocampus-dependent long-term recognition memory across the life span, and this effect appears to be related to neural beta oscillations.
Immune checkpoint inhibitors have improved survival in advanced stage melanoma patients. Rates of new primary melanomas (NPM) in patients with prior melanoma have been reported to be as high as 12%. Little is currently known regarding the frequency or characteristics of NPMs occurring in melanoma patients treated with immune checkpoint inhibitors.

To determine the frequency and describe clinicopathologic characteristics of NPMs diagnosed in patients during or after treatment with immune checkpoint inhibitors for metastatic melanoma.

A retrospective analysis of prospectively collected data from the Melanoma Institute Australia and Westmead Hospital Dermatology databases. Clinicopathological data for the initial primary melanoma (IPM) and NPM were compared.

Between 2013-2017, 14 NPMs in 13 patients (out of a total of 1047) treated with checkpoint inhibitors were identified. NPMs were significantly thinner than the IPM (median Breslow thickness 0.35 mm vs 2.0 mm, P = 0.0003), less likely to be ulcerated e whether the immunotherapy itself influences both their development and biology.In functional data analysis for longitudinal data, the observation process is typically assumed to be noninformative, which is often violated in real applications. Thus, methods that fail to account for the dependence between observation times and longitudinal outcomes may result in biased estimation. For longitudinal data with informative observation times, we find that under a general class of shared random effect models, a commonly used functional data method may lead to inconsistent model estimation while another functional data method results in consistent and even rate-optimal estimation. Indeed, we show that the mean function can be estimated appropriately via penalized splines and that the covariance function can be estimated appropriately via penalized tensor-product splines, both with specific choices of parameters. For the proposed method, theoretical results are provided, and simulation studies and a real data analysis are conducted to demonstrate its performance.
STriatal-Enriched protein tyrosine Phosphatase (STEP) is a brain-specific tyrosine phosphatase. Membrane-bound STEP
is the only isoform expressed in hippocampus and cortex. Genetic deletion of STEP enhances excitatory synaptic currents and long-term potentiation in the hippocampus. However, whether STEP
affects seizure susceptibility is unclear. Here we investigated the effects of STEP inhibitor TC-2153 on seizure propensity in a murine model displaying kainic acid (KA)-induced status epilepticus and its effect on hippocampal excitability.

Adult male and female C57BL/6J mice received intraperitoneal injection of either vehicle (2.8% dimethylsulfoxide [DMSO] in saline) or TC-2153 (10mg/kg) and then either saline or KA (30mg/kg) 3h later before being monitored for behavioral seizures. A subset of female mice was ovariectomized (OVX). Acute hippocampal slices from Thy1-GCaMP6s mice were treated with either DMSO or TC-2153 (10μM) for 1h, and then incubated in artificial cerebrospinal fluid (ACSF) and pota action on suppressing neuronal intrinsic excitability.
This study is the first to demonstrate that pharmacological inhibition of STEP with TC-2153 decreases seizure severity and hippocampal activity in both sexes, and dampens hippocampal neuronal excitability and Ih . We propose that the antiseizure effects of TC-2153 are mediated by its unexpected action on suppressing neuronal intrinsic excitability.Optimal treatment for resectable esophageal squamous cell carcinoma (ESCC) is controversial, especially in the context of potential benefit of combining PD-1 blockade with neoadjuvant therapy. This phase 2 study aimed to assess neoadjuvant camrelizumab plus chemotherapy in this population. Patients (clinical stage II-IVA) received two cycles of neoadjuvant chemoimmunotherapy (NIC) with camrelizumab (200 mg on day 1) plus nab-paclitaxel (260 mg/m2 in total on day 1 and day 8) and cisplatin (75 mg/m2 in total on days 1-3) of each 21-day cycle. Surgery was performed approximately 6 weeks after completion of NIC. Primary endpoint was complete pathologic response (CPR) rate in primary tumor. Secondary endpoints were objective response rate (ORR) per RECIST v1.1, 2-year progression-free survival (PFS) rate after surgery, PFS, overall survival (OS) and safety during NIC and perioperative period. Between 17 January 2020 and 8 December 2020, 56 patients were enrolled, and 51 received esophagectomy. Data cutoff date was 25 August 2021. The CPR rate was 35.3% (95% CI, 21.7%-48.9%). NIC had an ORR of 66.7% (95% CI, 40.0%-70.4%) and treatment-related adverse events (TRAEs) of low severity (grade 1-2, 75.0%; grade 3, 10.7%; grade 4-5, no). No perioperative mortality occurred. Three (5.9%) patients had tumor recurrence and one (2.0%) patient died. The 2-year PFS rate, median PFS and median OS had not been reached yet. Camrelizumab plus neoadjuvant chemotherapy in resectable ESCC demonstrates promising efficacy with acceptable toxicity, providing a feasible and effective option. Study is ongoing for long-term survival analyses.
Raspberry leaf tea (RLT) is a traditional herb purported to help with many pregnancy-related outcomes including reducing the duration of labour. No experimental data exist to support these claims.

This study aims to determine how common use and knowledge of RLT are during pregnancy. It also aims to explore whether it would be possible to recruit women for a trial of raspberry leaf in the future.

Postnatal women were asked to fill in a survey about their use of RLT during pregnancy, and their knowledge of its purported benefits. They were asked whether they would consider being part of a randomised controlled trial of raspberry leaf in the future.

One hundred and twenty-one women completed the survey. Of these, 88 (73%) were aware of herbal tea use in pregnancy and 46 (38%) reported using raspberry leaf during pregnancy. Of all women surveyed, 79% indicated they would be happy to participate in a trial of RLT in pregnancy if they were asked.

Despite no scientific evidence of the efficacy of RLT in pregnancy, 38% of women surveyed used it during pregnancy. Further studies are required to determine whether the claims made about RLT are correct. Clinicians should base their advice on available evidence.
Despite no scientific evidence of the efficacy of RLT in pregnancy, 38% of women surveyed used it during pregnancy. Further studies are required to determine whether the claims made about RLT are correct. Clinicians should base their advice on available evidence.In clinical psychopathology research, up to seven traits have been suggested as instances of antagonistic psychopathology. Those antagonistic traits, in turn, are commonly viewed as reflections of low Agreeableness as per the Big Five (BF-AG). However, specific theoretical differences between antagonistic traits suggest that other broad, basic dimensions beyond BF-AG ought to provide further points of correspondence. Specifically, whereas primarily affective antagonistic traits are closely aligned with BF-AG, primarily behavioral antagonistic traits are better aligned with Honesty-Humility (HH) from the HEXACO model and primarily cognitive antagonistic traits are better aligned with the common core of aversive traits (the Dark Factor of Personality, D). Indeed, from a theoretical perspective, D seems to be the only candidate sufficiently covering all aspects of antagonistic traits (affect, behavior, and cognition) to a comparable extent and thus affording a balanced representation of antagonistic psychopathology. We critically test these conjectures in a large and heterogeneous online sample (N = 3,396), investigating the overlap between antagonistic traits and basic personality via structural equation modeling. Results show that BF-AG, HH, and D each yield particularly strong ties to one group of antagonistic traits (affective, behavioral, and cognitive, respectively), while D offers the most balanced representation of all (groups of) antagonistic traits.
Hearing loss is a clinical symptom, frequently mentioned in the context of mitochondrial disease. With no cure available for mitochondrial disease, supportive treatment of clinical symptoms like hearing loss is of the utmost importance. The aim of this study was to summarize current knowledge on hearing loss in genetically proven mitochondrial disease in children and deduce possible and necessary consequences in patient care.

Systematic literature review, including Medline, Embase, and Cochrane library. Review protocol was established and registered prior to conduction (International prospective register of systematic reviews-PROSPERO CRD42020165356). Conduction of this review was done in accordance with MOOSE criteria.

A total of 23 articles, meeting predefined criteria and providing sufficient information on 75 individuals with childhood onset hearing loss was included for analysis. Both cochlear and retro-cochlear origin of hearing loss can be identified among different types of mitochondrial disease. Analysis was hindered by inhomogeneous reporting and methodical limitations.

Overall, the findings do not allow for a general statement on hearing loss in children with mitochondrial disease. Retro-cochlear hearing loss seems to be found more often than expected. A common feature appears to be progression of hearing loss over time. However, hearing loss in these patients shows manifold characteristics. Therefore, awareness of mitochondrial disease as a possible causative background is important for otolaryngologists. Future attempts rely on standardized reporting and long-term follow-up.

NA Laryngoscope, 2022.
NA Laryngoscope, 2022.Mandibular deviation affects the biomechanical environment of the temporomandibular joint (TMJ) and causes thinning of cartilage on the deviated side. We aimed to evaluate, using a rat model, the effect of mandibular functional deviation on the TMJ in relation to the functional roles of integrin β family members. The effects of experimental functional deviation on the TMJ of 6-week-old Sprague-Dawley female rats, randomly assigned to control (n = 42) and experimental groups (n = 42), were evaluated at 3 days and 1, 2, 4, and 8 weeks by histological staining, immunofluorescence, real-time quantitative polymerase chain reaction, and micro-computed tomography. The results showed that the experimental functional shift changed the shape of condyles, thinned the cartilage, and increased the proportion of the hypertrophic layer on the deviated sides of condyles. In addition, the extracellular matrix of the condyle cartilage exhibited degradation at 1 week and subchondral trabecular bone was lost at 4 and 8 weeks. Osteoarthritis (OA)-like changes occurred in the left and right condyles of rats in the experimental group and were aggravated over time. Integrin β family expression, especially integrin β2 , was altered from week 1, possibly related to the OA-like changes. These data may provide insight into the onset of TMJ OA.
The link between headache and epilepsy is more prominent in patients with idiopathic/genetic epilepsy (I/GE). We aimed to investigate the prevalence of headache and to cluster patients with regard to their headache and epilepsy features.

Patients aged 6-40years, with a definite diagnosis of I/GE, were consecutively enrolled. The patients were interviewed using standardized epilepsy and headache questionnaires, and their headache characteristics were investigated by experts in headache. Demographic and clinical variables were analyzed, and patients were clustered according to their epilepsy and headache characteristics using an unsupervised K-means algorithm.

Among 809 patients, 508 (62.8%) reported having any type of headache; 87.4% had interictal headache, and 41.2% had migraine. Cluster analysis revealed two distinct groups for both adults and children/adolescents. In adults, subjects having a family history of headache, ≥5headache attacks, duration of headache ≥ 24months, headaches lasting ≥1h, and vp in management and planning for future studies.
Patients with I/GE can be clustered into distinct groups according to headache features along with seizures. Our findings may help in management and planning for future studies.
The U.S. clinical research enterprise in nursing homes was unprepared to mount clinical trials in nursing homes to address urgent questions relevant to prevention and treatment during the COVID-19 pandemic. We identify priorities essential for establishing a supportive environment for future clinical trials in nursing homes.

Two cross-sectional online questionnaires were administered between January and February 2021. One was administered to nursing home providers, researchers, and policymakers; respondents rated the importance of attributes of researchers, facilities, leaders and staff for conducting clinical trials in nursing homes. Because importance may depend on trial type, respondents rated each attribute for efficacy trials (testing an intervention in ideal circumstances) and effectiveness trials (testing an intervention in "real world" circumstances). We calculated the attribute rating means and standard deviations, and used content analysis to characterize open-ended responses. The second questioin nursing homes will require a reimagining of the relationships that exist between researchers, facilities, nursing home leaders, and residents, with a research infrastructure specifically focused on supporting and fostering these connections.
Developing a robust U.S. clinical research enterprise capable of efficiently mounting future clinical trials in nursing homes will require a reimagining of the relationships that exist between researchers, facilities, nursing home leaders, and residents, with a research infrastructure specifically focused on supporting and fostering these connections.
Epithelial ovarian cancer is the sixth most common cancer worldwide 295,414 new cases were diagnosed in 2018, with 184,799 deaths. The lack of an effective screening strategy has led to the majority of women being diagnosed at an advanced stage. For these women, intravenous carboplatin combined with paclitaxel for six cycles is widely accepted as the standard first-line treatment for epithelial ovarian cancer, in combination with debulking surgery. However, there is conflicting evidence regarding the optimal dosing schedule of paclitaxel when combined with carboplatin in this setting.

To compare the efficacy and tolerability of intravenous weekly paclitaxel with that of tri-weekly paclitaxel, in combination with intravenous carboplatin, as first-line treatment for epithelial ovarian cancer (defined as epithelial ovarian, primary peritoneal and fallopian tube cancer).

We searched CENTRAL, MEDLINE, and Embase databases for relevant studies up to 15 November 2021, using keywords and MeSH terms. We additionow-certainty evidence). Our findings may not apply to women receiving bevacizumab in first-line therapy, those receiving treatment in the neo-adjuvant setting, or those with rare subtypes of clear cell or mucinous ovarian cancer.
Weekly paclitaxel combined with carboplatin for first-line treatment of epithelial ovarian cancer likely improves PFS slightly (moderate-certainty evidence) but not OS (high-certainty evidence), compared to tri-weekly paclitaxel combined with carboplatin. However, this was associated with increased risk for high-grade anaemia, treatment discontinuation, dose delays and dose omissions (high- to low-certainty evidence). Our findings may not apply to women receiving bevacizumab in first-line therapy, those receiving treatment in the neo-adjuvant setting, or those with rare subtypes of clear cell or mucinous ovarian cancer.
Although mortality in patients with acute myocardial infarction (MI) has decreased substantially over the last few decades in many countries, MI remains a major threat to public health.

To assess the number and outcomes of patients hospitalized for acute MI in Poland in 2018 as well as proportions of patients participating in cardiac rehabilitation and undergoing invasive cardiac procedures following discharge.

We used public databases. We included all patients hospitalized for acute MI in Poland in 2018 and assessed event-free survival along with uptake of invasive cardiac procedures, cardiac rehabilitation, and consultations with cardiologists.

A total of 75868 patients (mean age, 68.8 years) were hospitalized for acute MI in Poland in 2018 (the admission rate, 197.0 per 100000 inhabitants). In-hospital mortality was 8.4%, while one-year mortality was 17.3% (one-year post-discharge mortality was 9.8%). Approximately 75% and 96% of discharged patients consulted a general practitioner, whereas 12% and 62% consulted a cardiologist, 5% and 19% underwent percutaneous coronary intervention, 0.6% and 2.9% un-derwent coronary artery bypass grafting, while 0.04% and 1.9% had an implantable cardioverter defibrillator implanted within 30 days and 365 days following discharge. The participation rate in cardiac rehabilitation within the first 14 days following discharge was 11%, within the first 30 days was 19%, and within 365 days was 35%.

In-hospital and post-discharge mortality is still high in Poland. The access to cardiac consultations and cardiac rehabilitation following MI is insufficient. There is considerable potential for a further decrease in mortality in patients suffering from MI in Poland.
In-hospital and post-discharge mortality is still high in Poland. The access to cardiac consultations and cardiac rehabilitation following MI is insufficient. There is considerable potential for a further decrease in mortality in patients suffering from MI in Poland.
Arrhythmia-mediated cardiomyopathy (AMC) is an essential clinical situation which is commonly underdiagnosed. Successful arrhythmia control leads to improvement in health-related quality of life (HRQoL) and heart failure (HF) symptoms in patients with structural heart disease (SHD).

The aim of the study was to evaluate the impact of catheter ablation (CA) of persistent arrhythmia on HRQoL, biochemical and clinical parameters HF in patients with SHD and AMC.

Patients with SHD, on optimal medical treatment, with persistent arrhythmia and strong suspicion of AMC, scheduled for CA were prospectively enrolled. Study procedures included HRQoL measurement (Minnesota Living With Heart Failure Questionnaire [MLHFQ] and EuroQol Research Foundation [EQ-5D-3L] questionnaire), biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP], troponin T [TnT], matrix metaloproteinase-9 [MMP-9], soluble suppression of tumorigenesis-2 [sST2], tissue inhibitor of matrix metalloproteinase-1 [TIMP-1]), transthoracic echo with SHD and AMC.
The aims of this study were to assess long-term results after surgical AVR (sAVR) depending on the surgical technique used (ministernotomy vs. full sternotomy) and to determine in parallel, which patient- and treatment-related attributes were most associated with shorter time to the main endpoint.

Out of 2147 patients, who underwent sAVR from January 2006 to December 2017, 615 patients were treated minimally invasively (MIAVR) and 1532 patients received conventional full sternotomy aortic valve replacement (FSAVR). Multiple Cox regressive models corresponding to the four major endpoints were developed. Long-term survival and a time to re-hospitalization for acute coronary syndrome, stroke and heart failure (HF) have been analyzed, independently. Kaplan-Meier actuarial analysis was performed for univariate comparison.

The median follow-up time was 71.9 months. No significant difference in terms of long-term survival was found between MIAVR and FSAVR (hazard ratio [HR], 0.99; P = 0.91). Novel advantages oorder to reduce their high cerebrovascular risk and to limit the progression of HF. MIAVR also needs to be considered in patients with chronic lung diseases to improve their extremely poor survival prognosis.During intervertebral disc degeneration (IVDD), due to endplate calcification, diminished oxygen and nutrient concentrations and accumulated lactate are present in the microenvironment of the nucleus pulposus (NP). The disadvantages of 3D layered culture include uneven oxygen and nutrient gradients. In the present study, to mimic the in vivo microenvironment of the NP, a 5-layered 3D culture was constructed using clinical haemostatic gelatine sponges and developed as a NP degeneration (NPD) model. Subsequently, cell distribution as well as expression of NP chondrogenic markers (type II collagen and aggrecan), glycosaminoglycan (GAG) and degeneration markers [e.g. matrix metalloproteinase (MMP) 3] were measured from the top to the bottom layer. However, in a single NP-cell-loaded disc model, the chondrogenic potency in the middle or bottom layer was higher than that in the top layer. To further study the mechanism underlying the degeneration of NP cells in this NPD model, the contribution of secreted metabolites was examined. Lactate identified in the supernatant modulated GAG accumulation and MMP3 expression. Inhibition of lactate influx by the monocarboxylate transporter (MCT)-1 inhibitor, AZD3965, reversed the effect of lactate on GAG accumulation and MMP3 expression and further improved NP cell degeneration in the NPD model. Thanks to the homogenous expression of lactate in the model, it was possible to further identified that the combination of lactate and hypoxia enhanced MMP3 expression. Taken together, multilayered cell-loaded sponges, with oxygen and nutrient gradients as well as lactate accumulation, can represent a 3D multilayered NPD model for exploring potential agents for IVDD.Although indications for immune checkpoint inhibitors (ICIs) have dramatically increased in the past decade, ICIs have been associated with autoinflammatory immune-related adverse events which can resemble autoimmune diseases (ADs). Little is known about the impact of baseline AD on mortality in cancer patients treated with ICIs. Here, we identified 17,497 patients with pre-existing autoimmune diagnoses prior to treatment with anti-PD-1 or anti-PD-L1 therapy and 17,497 matched controls through the TriNetX Diamond network of over 200 million patients across the US and Europe. Using a Cox proportional hazards model, we found that patients with history of AD were not at higher risk of mortality than non-AD controls (HR, 1.03; 95% CI, 1-1.07; p = 0.05). Additionally, history of Hashimoto's disease (HR, 0.75; 95% CI, 0.62-0.90; p = 0.002) and vitiligo (HR,0.52; 95% CI, 0.34-0.81; p = 0.003) were statistically significantly associated with decreased mortality. This suggests that underlying AD need not be a contraindication to inclusion in clinical trials and administration of ICI for treatment of cancer.February is LGBT+ history month, and to celebrate, Journal of Cell Science Editorial Advisory Board member David Bryant organised a conversation with a selection of scientists to explore their experiences of being LGBT+ in academia.
Pain in childhood is prevalent and is associated with fear, particularly in the context of injuries or procedural pain, and negative emotions (e.g., sadness). Pain and fear share a bidirectional relationship, wherein fear exacerbates the experience of pain and pain increases subsequent anticipatory fear. The existing research has focused primarily on children's immediate experience of pain and fear. Research on how children remember or talk about past painful, fearful, or sad events is lacking. Parent-child reminiscing about past pain has been demonstrated to differ from reminiscing about other past negative emotional events (i.e., those involving sadness, but not fear). The present study aimed to examine differences in how parent-child dyads reminisce about past pain, fear, and sadness.

One hundred and three 4-year-old children (55% girls) and their parents (52% fathers) engaged in a narrative elicitation task in which they reminisced about unique past events involving pain, fear, and sadness. Parent-child narratives were coded using established coding schemes based on the developmental psychology literature.

Parent-child narratives about pain were characterized by fewer emotion-laden words and explanations, as well as more pain-related words compared to sadness or fearful narratives. Mothers and fathers reminisced with sons and daughters in a similar way across all types of events.

Parent-children reminiscing about past painful events differs from reminiscing about other types of distressing events (e.g., involving sadness or fear). This highlights a possibility of differential socialization of pain versus fear. Potential clinical implications of the findings are discussed.
Parent-children reminiscing about past painful events differs from reminiscing about other types of distressing events (e.g., involving sadness or fear). This highlights a possibility of differential socialization of pain versus fear. Potential clinical implications of the findings are discussed.Unlike many animals that reduce activity during fasting, northern elephant seals (NES) undergo prolonged fasting during energy-intensive life-history stages such as reproduction and molting, fueling fasting energy needs by mobilizing fat stores accrued during foraging. NES display several unique metabolic features such as high fasting metabolic rates, elevated blood lipid and high-density lipoprotein (HDL) cholesterol levels, efficient protein sparing and resistance to oxidative stress during fasting. However, the cellular mechanisms that regulate these adaptations are still not fully understood. To examine how metabolic coordination is achieved during prolonged fasting, we profiled changes in blubber, skeletal muscle and plasma proteomes of adult female NES over a 5 week fast associated with molting. We found that while blubber and muscle proteomes were remarkably stable over fasting, over 50 proteins changed in abundance in plasma, including those associated with lipid storage, mobilization, oxidation and transport. Apolipoproteins dominated the blubber, plasma and muscle proteome responses to fasting. APOA4, APOE and APOC3, which are associated with lipogenesis and triglyceride accumulation, decreased, while APOA1, APOA2 and APOM, which are associated with lipid mobilization and HDL function, increased over fasting. Our findings suggest that changes in apolipoprotein composition may underlie the maintenance of high HDL levels and, together with adipokines and hepatokines that facilitate lipid catabolism, may mediate the metabolic transitions between feeding and fasting in NES. Many of these proteins have not been previously studied in this species and provide intriguing hypotheses about metabolic regulation during prolonged fasting in mammals.Hypoxia is one of the strongest environmental drivers of cellular and physiological adaptation. Although most mammals are largely intolerant of hypoxia, some specialized species have evolved mitigative strategies to tolerate hypoxic niches. Among the most hypoxia-tolerant mammals are naked mole-rats (Heterocephalus glaber), a eusocial species of subterranean rodent native to eastern Africa. In hypoxia, naked mole-rats maintain consciousness and remain active despite a robust and rapid suppression of metabolic rate, which is mediated by numerous behavioural, physiological and cellular strategies. Conversely, hypoxia-intolerant mammals and most other hypoxia-tolerant mammals cannot achieve the same degree of metabolic savings while staying active in hypoxia and must also increase oxygen supply to tissues, and/or enter torpor. Intriguingly, recent studies suggest that naked mole-rats share many cellular strategies with non-mammalian vertebrate champions of anoxia tolerance, including the use of alternative metabolic end-products and potent pH buffering mechanisms to mitigate cellular acidification due to upregulation of anaerobic metabolic pathways, rapid mitochondrial remodelling to favour increased respiratory efficiency, and systemic shifts in energy prioritization to maintain brain function over that of other tissues. Herein, I discuss what is known regarding adaptations of naked mole-rats to a hypoxic lifestyle, and contrast strategies employed by this species to those of hypoxia-intolerant mammals, closely related African mole-rats, other well-studied hypoxia-tolerant mammals, and non-mammalian vertebrate champions of anoxia tolerance. I also discuss the neotenic theory of hypoxia tolerance - a leading theory that may explain the evolutionary origins of hypoxia tolerance in mammals - and highlight promising but underexplored avenues of hypoxia-related research in this fascinating model organism.
Food allergy is a component of the atopic march and may have effects on asthma. This study aimed to evaluate the risk factors for confirmed immunoglobulin E-mediated food allergies and their impact on the clinical picture in preschool children with asthma.

Clinical history and allergic assessment results were obtained from medical records and analyzed retrospectively. Preschool children with asthma were included in the study and the characteristics of food allergy and asthma were evaluated. The patients were grouped as those with food allergy (Group I, n = 60) and those without (Group II, n = 98).

In patients with food allergy and asthma, the number of episodes requiring systemic steroids in the last year (p = 0.002), atopic dermatitis (p = 0.001), parental atopic disease (p = 0.009) and aeroallergen sensitivity rates (p < 0.001) was higher than patients without food allergies. The use of medium or high doses of inhaled steroids to achieve asthma control was more frequent in patients with food allergies (p = 0.014). Parental history of atopic disease [p = 0.007, odds ratio (OR) 3.27, 95% confidence interval (CI) 1.37-7.77)], atopic dermatitis (p = 0.017, OR 2.80, 95% CI 1.19-6.57), starting complementary food after 6 months (p = 0.004, OR 3.9, 95% CI 1.5-10.0) and having aeroallergen sensitivity (p < 0.001, OR 6.01, 95% CI 2.21-16.29) were identified as significant risk factors for food allergy.

Asthmatic preschool children with food allergies are more likely to have a parental atopic disease, atopic dermatitis, aeroallergen sensitivity and starting complementary food after 6 months. These patients experience more asthma attacks and need higher doses of steroids.
Asthmatic preschool children with food allergies are more likely to have a parental atopic disease, atopic dermatitis, aeroallergen sensitivity and starting complementary food after 6 months. These patients experience more asthma attacks and need higher doses of steroids.
Allergic rhinitis is a common chronic childhood disease with a low diagnosis rate, causing poor quality of life, absenteeism, decreased school performance and significant healthcare cost. However, data on the prevalence of allergic rhinitis is sparse in preschoolers of rural geography, especially in developing countries.

To describe the epidemiology of allergic rhinitis in preschoolers from a rural geography of a developing country.

A population-based cross-sectional study was conducted in Anuradhapura district, Sri Lanka using the WHO-30 cluster methodology with probability proportionate to size sampling. The International Study of Asthma and Allergy in Childhood questionnaire was used to assess symptomatology.

The response rate was 91.8%, with 548 (51.7%) male and 512 (48.3%) female participants. The mean age was 4.4 (± 0.7) years. Allergic rhinitis was reported in 123 (11.6%; 95% CI 9.7-13.5), and eye symptoms were reported in 41 (3.9%; 95% CI 2.8-5.2) children. Activities of daily living were distexacerbations.PCR-based methods applied to various body fluids emerged in recent years as a promising approach for the diagnosis of mucormycosis. In this study, we set up and assess the value of a qPCR to detect a wide variety of Mucorales species in a single tube. A pair of degenerated primers targeting the rDNA operon was used in a qPCR utilizing an intercalating fluorescent dye. Analytical assessment, using a wide variety of both Mucorales strains (8 genera, 11 species) and non-Mucorales strains (9 genera, 14 species), showed 100% sensitivity and specificity rates with a limit of detection at 3 rDNA copy/qPCR reaction. Subsequently, 364 clinical specimens from 166 at-risk patients were prospectively tested with the assay. All the seven patients classified as proven/probable mucormycosis using the EORTC-MSG criteria had a positive qPCR as well as a patient with a proven uncharacterized invasive mold infection. In addition, three out of seven patients with possible mold invasive infections had at least one positive qPCR test. Sensitivity was calculated between 73.33 and 100% and specificity between 98.10 and 100%. The qPCR method proposed showed excellent performances and would be an important adjunctive tool for the difficult diagnosis of mucormycosis diagnosis.
qPCR-based diagnosis is the most reliable approach for mucormycosis. We set up a pan-Mucorales qPCR able to detect in a single reaction not less than 11 different species. Both analytical and clinical performances support its use in the clinical setting.
qPCR-based diagnosis is the most reliable approach for mucormycosis. We set up a pan-Mucorales qPCR able to detect in a single reaction not less than 11 different species. Both analytical and clinical performances support its use in the clinical setting.
In collaboration with the Office of Dietary Supplements at the National Institutes of Health, the National Institute of Standards and Technology issued a suite of botanical matrix Reference Materials (RMs) and Standard Reference Material® (SRM) for determination of isoflavones and toxic elements in kudzu dietary supplement ingredients.

RM 8650 Pueraria montana var. lobata (Kudzu) Rhizome, SRM 3268 Pueraria montana var. lobata (Kudzu) Extract, and RM 8652 Kudzu-Containing Solid Oral Dosage Form were issued with values assigned for isoflavones (puerarin, daidzin, and daidzein), toxic elements (arsenic, cadmium, and lead), and selenium.

Isoflavone values were assigned using liquid chromatography with UV absorbance or mass spectrometry detection. Element values were assigned using inductively coupled plasma mass spectrometry and results from an interlaboratory comparison exercise.

Mass fractions for puerarin were (32.2 ± 3.2) mg/g, (128 ± 13) mg/g, and (68.2 ± 6.9) mg/g in RM 8650, SRM 3268, and RM 8652, um. For the isoflavones, these new kudzu materials provide higher levels of daidzin and daidzein than existing soy-related SRMs, and they provide a value for an isoflavone not in existing SRMs (puerarin). Toxic elements in RM 8650 and SRM 3268 provide new botanical matrices for use by dietary supplement manufacturers for the verification of the safety of their raw materials.The Neosho madtom (Noturus placidus) is a small catfish, generally less than 3 inches in length, unique to the Neosho-Spring River system within the Arkansas River Basin. It was federally listed as threatened in 1990, largely due to habitat loss. For conservation efforts, we generated whole-genome sequence data from 10 Neosho madtom individuals originating from 3 geographically separated populations to evaluate genetic diversity and population structure. A Neosho madtom genome was de novo assembled, and genome size and content were assessed. Single nucleotide polymorphisms were assessed from de Bruijn graphs, and via reference alignment with both the channel catfish (Ictalurus punctatus) reference genome and Neosho madtom reference genome. Principal component analysis and structure analysis indicated weak population structure, suggesting fish from the 3 locations represent a single population. Using a novel method, genome-wide conservation and divergence between the Neosho madtom, channel catfish, and zebrafish (Danio rerio) was assessed by pairwise contig alignment, which demonstrated that genes important to embryonic development frequently had conserved sequences. This research in a threatened species with no previously published genomic resources provides novel genetic information to guide current and future conservation efforts and demonstrates that using whole-genome sequencing provides detailed information of population structure and demography using only a limited number of rare and valuable samples.
This study assesses how American life expectancy compares to other high-income countries and identifies key age groups and causes of death responsible for the U.S. life expectancy shortfall.

Data from the Human Mortality Database, World Health Organization Mortality Database, and vital statistics agencies for 18 high-income countries are used to examine trends in U.S. life expectancy gaps and how American age-specific death rates compare to other countries. Decomposition is used to estimate the contribution of 19 age groups and 16 causes to the U.S. life expectancy shortfall.

In 2018, life expectancy for American men and women was 5.18 and 5.82 years lower than the world leaders and 3.60 and 3.48 years lower than the average of the comparison countries. Americans aged 25-29 experience death rates nearly 3 times higher than their counterparts. Together, injuries (drug overdose, firearm-related deaths, motor vehicle accidents, homicide), circulatory diseases, and mental disorders/nervous system diseases (including Alzheimer's disease) account for 86% and 67% of American men's and women's life expectancy shortfall, respectively.

American life expectancy has fallen far behind its peer countries. The U.S.'s worsening mortality at the prime adult ages and eroding old-age mortality advantage drive its deteriorating performance in international comparisons.
American life expectancy has fallen far behind its peer countries. The U.S.'s worsening mortality at the prime adult ages and eroding old-age mortality advantage drive its deteriorating performance in international comparisons.Efficient plastid transformation in Arabidopsis (Arabidopsis thaliana) requires genetic lines that are hypersensitive to spectinomycin due to the absence of a chloroplast acetyl-coenzyme A carboxylase (ACCase) encoded in the acetyl-coenzyme A carboxylase 2 (ACC2) nuclear gene. To obtain plastid transformation-competent oilseed rape (Brassica napus), we inactivated all nuclear encoded, chloroplast targeted ACCase copies using CRISPR-Cas9. Brassica napus (2n = 38, AACC) is a recent interspecific hybrid of Brassica rapa (2n = 20, AA) and B. oleracea (2n = 18, CC) and is expected to have at least two ACC2 copies, one from each parent. The sequenced genome has two ACC2 copies, one that is B. rapa-like and one that is B. oleracea-like. We designed single-guide RNAs (sgRNAs) that could simultaneously inactivate both nuclear ACC2 copies. We expressed Cas9 from a chimeric egg cell promoter 1.2 (EC1.2p) known to yield homozygous or biallelic mutants in Arabidopsis in the T1 generation. To maximize the probability of functionally inactivating both orthologs in a single step, each of the two vectors carried four sgRNAs. Four T0 transgenic lines were obtained by Agrobacterium tumefaciens-mediated hypocotyl transformation. Amplicon sequencing confirmed mutations in ACC2 genes in 10 T1 progeny, in seven of which no wild-type (WT) copy remained. The B. napus T2 seedlings lacking WT ACC2 gene copies exhibited a spectinomycin hypersensitive phenotype, suggesting that they will be a useful resource for chloroplast genome transformation.In tomato (Solanum lycopersicum) and other plants, the photoreceptor UV-RESISTANCE LOCUS 8 regulates plant UV-B photomorphogenesis by modulating the transcription of many genes, the majority of which depends on the transcription factor ELONGATED HYPOCOTYL 5 (HY5). HY5 transcription is induced and then rapidly attenuated by UV-B. However, neither the transcription factors that activate HY5 transcription nor the mechanism for its attenuation during UV-B signaling is known. Here, we report that the tomato B-BOX (BBX) transcription factors SlBBX20 and SlBBX21 interact with SlHY5 and bind to the SlHY5 promoter to activate its transcription. UV-B-induced SlHY5 expression and SlHY5-controlled UV-B responses are normal in slbbx20 and slbbx21 single mutants, but strongly compromised in the slbbx20 slbbx21 double mutant. Surprisingly, UV-B responses are also compromised in lines overexpressing SlBBX20 or SlBBX21. Both SlHY5 and SlBBX20 bind to G-box1 in the SlHY5 promoter. SlHY5 outcompetes SlBBX20 for binding to the SlHY5 promoter in vitro, and inhibits the association of SlBBX20 with the SlHY5 promoter in vivo. Overexpressing 35SSlHY5-FLAG in the WT background inhibits UV-B-induced endogenous SlHY5 expression. Together, our results reveal the critical role of the SlBBX20/21-SlHY5 module in activating the expression of SlHY5, the gene product of which inhibits its own gene transcription under UV-B, forming an autoregulatory negative feedback loop that balances SlHY5 transcription in plants.Galactose is an abundant and essential sugar used for the biosynthesis of many macromolecules in different organisms, including plants. Galactose metabolism is tightly and finely controlled, since excess galactose and its derivatives are inhibitory to plant growth. In Arabidopsis (Arabidopsis thaliana), root growth and pollen germination are strongly inhibited by excess galactose. However, the mechanism of galactose-induced inhibition during pollen germination remains obscure. In this study, we characterized a plasma membrane-localized transporter, Arabidopsis Sugars Will Eventually be Exported Transporter 5, that transports glucose and galactose. SWEET5 protein levels started to accumulate at the tricellular stage of pollen development and peaked in mature pollen, before rapidly declining after pollen germinated. SWEET5 levels are responsible for the dosage-dependent sensitivity to galactose, and galactokinase is essential for these inhibitory effects during pollen germination. However, sugar measurement results indicate that galactose flux dynamics and sugar metabolism, rather than the steady-state galactose level, may explain phenotypic differences between sweet5 and Col-0 in galactose inhibition of pollen germination.Disulfiram (Antabuse®) is an alcohol use disorder medication that exhibits antifungal activity against Candida species. The purpose of this investigation was to determine if copper potentiates the antifungal effects of disulfiram based on prior observations that the combination demonstrates increased antitumor activity. Our findings revealed that copper addition conferred up to an eight-fold reduction in the minimum inhibitory concentrations (MICs) of disulfiram by broth microdilution assessment. Unexpectedly, copper was also found to nullify the fungicidal activity of disulfiram despite the significant reduction in MICs. It was therefore concluded that copper likely increased the antifungal potency of disulfiram through formation of a fungistatic chelation complex.
The effect of copper on the antifungal activity of disulfiram was evaluated against fluconazole-resistant Candida species. The study establishes that copper addition confers greater inhibition of disulfiram-treated Candida cultures, but the combination antagonizes the killing effects of disulfiram.
The effect of copper on the antifungal activity of disulfiram was evaluated against fluconazole-resistant Candida species. The study establishes that copper addition confers greater inhibition of disulfiram-treated Candida cultures, but the combination antagonizes the killing effects of disulfiram.Mediating induced abscisic acid (ABA) biosynthesis is important for enhancing plant stress tolerance. Here, we found that rice (Oryza sativa L.) osa-miR2105 (miR2105) and the Stress/ABA-activated protein kinase (OsSAPK10) coordinately regulate the rice basic region-leucine zipper transcription factor (bZIP TF; OsbZIP86) at the posttranscriptional and posttranslational levels to control drought-induced ABA biosynthesis via modulation of rice 9-cis-epoxycarotenoid dioxygenase (OsNCED3) expression. OsbZIP86 expression is regulated by miR2105-directed cleavage of the OsbZIP86 mRNA. OsbZIP86 encodes a nuclear TF that binds to the promoter of the ABA biosynthetic gene OsNCED3. OsSAPK10 can phosphorylate and activate OsbZIP86 to enhance the expression of OsNCED3. Under normal growth conditions, altered expression of miR2105 and OsbZIP86 displayed no substantial effect on rice growth. However, under drought conditions, miR2105 knockdown or OsbZIP86 overexpression transgenic rice plants showed higher ABA content, enhanced tolerance to drought, lower rates of water loss, and more stomatal closure of seedlings, compared with wild-type rice Zhonghua 11; in contrast, miR2105 overexpression, OsbZIP86 downregulation, and OsbZIP86 knockout plants displayed opposite phenotypes. Collectively, our results show that the "miR2105-(OsSAPK10)-OsbZIP86-OsNCED3" module regulates the drought-induced ABA biosynthesis without penalty on rice growth under normal conditions, suggesting candidates for improving drought tolerance in rice.In plants, the biogenesis of small interfering RNA (siRNA) requires a family of RNA-dependent RNA polymerases that convert single-stranded RNA (ssRNA) into double-stranded RNA (dsRNA), which is subsequently cleaved into defined lengths by Dicer endonucleases. Here, we determined the structure of maize (Zea mays) RNA-DEPENDENT RNA POLYMERASE 2 (ZmRDR2) in the closed and open conformations. The core catalytic region of ZmRDR2 possesses the canonical DNA-dependent RNA polymerase (DdRP) catalytic sites, pointing to a shared RNA production mechanism between DdRPs and plant RDR-family proteins. Apo-ZmRDR2 adopts a highly compact structure, representing an inactive closed conformation. By contrast, adding RNA induced a significant conformational change in the ZmRDR2 Head domain that opened the RNA binding tunnel, suggesting this is an active elongation conformation of ZmRDR2. Overall, our structural studies trapped both the active and inactive conformations of ZmRDR2, providing insights into the molecular mechanism of dsRNA synthesis during plant siRNA production.
Lung cancer is increasingly diagnosed as a second cancer. Our goal was to analyse the characteristics and outcomes of early-stage resected lung adenocarcinomas in patients with previous cancers (PC) and correlations with adenocarcinoma subtypes.

We retrospectively reviewed data of patients radically operated on for stage I-II lung adenocarcinoma in 9 thoracic surgery departments between 2014 and 2017. Overall survival (OS) and time to disease relapse were evaluated between subgroups.

We included 700 consecutive patients. PC were present in 260 (37.1%). Breast adenocarcinoma, lung cancer and prostate cancer were the most frequent (21.5%, 11.5% and 11.2%, respectively). No significant differences in OS were observed between the PC and non-PC groups (P = 0.378), with 31 and 75 deaths, respectively. Patients with PC had smaller tumours and were more likely to receive sublobar resection and to be operated on with a minimally invasive approach. Previous gastric cancer (P = 0.042) and synchronous PC (when diagredictable; however, breast and colon cancers and melanoma showed a lower incidence of solid or micropapillary patterns whereas patients with lymphomas had a higher incidence of a micropapillary pattern.
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