Osteoporosis is a disease that leads to a loss of bone mass and to alterations in the bone microarchitecture that occur in a site-specific manner; however it remains controversial in the jaw. The involvement of bone marrow adipose tissue (BMAT) in the bone metabolism has been suggested in several physiopathological contexts, such as in aging and osteoporosis. To test whether the BMAT content is related to mandibular bone loss, this study aimed to investigate the potential correlations between the trabecular bone microarchitecture on one hand and BMAT content and its spatial distribution in relation to bone surface on the other hand during aging and ovariectomy (OVX) during a long-term follow-up in a mature rat model. No age-related microarchitectural or BMAT changes were observed in the mandible. The OVX-induced bone loss was three-fold lower in the mandible than in the tibia and was observed only in the alveolar bone (not in the condyle). We also report a delayed increase in the mandibular BMAT content that remained 4-6-fold lower compared to tibia. This low BMAT content in the mandible was located at a distance from the trabecular bone surface (only 5% in contact with the bone surface versus 87% in the tibia). These findings highlight a specific mandibular response to OVX, in particular fewer microarchitectural alterations compared to that in the tibia. For the latter, the trabecular bone thickness and surface were correlated with the BMAT content. Oral functions may have a protective effect on the mandibular BMAT conversion in an OVX context.

New analogs of the endogenous opioid agonist endomorphin-2 (EM-2, H-Tyr-Pro-Phe-Phe-NH2) have been obtained by introducing modified tyrosines at the position 1 of the sequence. For all analogs, the cis/trans conformation ratio about the tyramine-Pro amide bond, lipophilicity, receptor affinities, and functional activities, have been determined. Among the novel derivatives, [Dmt(3'-Cl)]1EM-2 (4) stood out for its subnanomolar μ-opioid receptor affinity and potent agonist activity, superior to that of the parent peptide EM-2. Hybrid quantum mechanics/molecular mechanics docking computations supported the cis tyramine-Pro bioactive conformation, and allowed us to analyze the contribution of the substituents of the "message" tyramine to binding, highlighting the role of halogen-bonding in the higher receptor affinity of peptide 4.

Interstitial cystitis (IC), also known as painful bladder syndrome, is a debilitating chronic condition with many patients failing to respond to current treatment options. Rapid clearance, mucosal coating, and tight epithelium create strong natural barriers that reduce the effectiveness of many pharmacological interventions in the bladder. Intravesical drug delivery (IDD) is the administration of therapeutic compounds or devices to the urinary bladder via a urethral catheter. Previous work in improving IDD for IC has focused on the sustained delivery of analgesics within the bladder and other small molecule drugs which do not address underlying inflammation and bladder damage. Therapeutic glycosaminoglycans (GAG) function by restoring the mucosal barrier within the bladder, promoting healing responses, and preventing irritating solutes from reaching the bladder wall. There is an unmet medical need for a therapy that provides both acute relief of symptoms while alleviating underlying physiological sources of inflammation and promoting healing within the urothelium. Semi-synthetic glycosaminoglycan ethers (SAGE) are an emerging class of therapeutic GAG with intrinsic anti-inflammatory and analgesic properties. To reduce SAGE clearance and enhance its accumulation in the bladder, we developed a silk-elastinlike protein polymer (SELP) based system to enhance SAGE IDD. We evaluated in vitro release kinetics, rheological properties, impact on bladder function, pain response, and bladder inflammation and compared their effectiveness to other temperature-responsive polymers including Poloxamer 407 and poly(lactic-co-glycolic acid)-poly(ethylene glycol). SAGE delivered via SELP-enhanced intravesical delivery substantially improved SAGE accumulation in the urothelium, provided a sustained analgesic effect 24 h after administration, and reduced inflammation.

VNS showed time-dependent anti-seizure effect. However, the precise mechanism of VNS in acute and chronic anti-seizure effect has not been fully elucidated. Noda epileptic rat (NER) is genetic epilepsy model rat which exhibits spontaneous generalized tonic-clonic seizure (GTC) approximately once per 30 h and frequent dialeptic seizure (DS). We performed acute and chronic VNS on NER to focus on the acute and chronic anti-epileptic effect and neuronal activity change by VNS.

International resuscitation guidelines emphasize the importance of high quality chest compressions, including correct chest compression depth and rate and complete chest recoil. The aim of the study was to assess the role of the TrueCPR device in the process of teaching cardiopulmonary resuscitation in nursing students.

The occurrence of seizures during pregnancy is really a challenging situation which risks the health of both mothers and fetuses. However, new onset epilepsy is unpredictable in pregnancy, and its clinic feature is barely known. This study aimed to explore the clinical characteristics and pregnancy outcomes of new onset epilepsy during pregnancy.We screened consecutive women with epilepsy and reproductive history from June 2013 to November 2018 from 3 hospitals in West China. Detailed demographics, clinical features, neurological status, related tests, managements, seizure and pregnancy outcomes were recorded and followed-up. Within them, patients with first seizure during pregnancy and spontaneous recurrent seizures after delivery or abortion were defined as new onset epilepsy during pregnancy.We screened a total of 1041 consecutive women with epilepsy and reproductive history. Twenty-two of them (2.1%) had new onset epilepsy during pregnancy. The average age at seizure onset was 22.7 ± 3.0 years. All their first seizures occurred in pregnancy period, including 4 (18.2%) in the first trimester, ten (45.4%) in the second trimester and eight (36.4%) in the third trimester. Most patients delivered healthy babies, except one patient had to choose induced abortion because of the disappearance of fetal heart rate, one child was diagnosed with mild harelip and one was diagnosed with trisomy 21 syndrome, tetralogy of Fallot and congenital duodenal atresia. All 3 complications happened in patients with their first seizures in first trimester.Although the risk of new onset epilepsy during pregnancy was relatively low, accurate diagnosis and appropriate treatment were required to reduce the damage to both mothers and fetuses. New onset epilepsy during pregnancy mostly began in middle and late pregnancy. However, seizures occurred from early pregnancy had bad effects on the embryo or fetus.

Chronic cerebral circulation insufficiency (CCCI) is a common clinical cerebrovascular disease, especially among middle-aged and elderly patients, which seriously endangers their quality of life and physical and mental health. At present, Oral traditional Chinese patent medicine (OTCPM) is widely used in the treatment of CCCI in China, but its actual efficacy and safety lack of evidence-based evidence. Therefore, we will screen out the most effective OTCPM through a systematic review and network meta-analysis to provide a reliable theoretical basis for clinical decisions.

Pulmonary sequestrations (PS) are typically supplied by a vessel originating from thoracic aorta, or abdominal aorta. Differences in imaging features between these PS subtypes have not been described.To analyze the imaging features of PS with arterial supply from the thoracic and abdominal aorta.Retrospectively, 23 pathologically proven cases of pulmonary sequestration were analyzed and compared based on the site of feeding artery origin.In 21 cases (21/23), the PS was soft tissue density. 1 (1/23) PS was purely cystic and another heterogeneous with both cystic and solid components (1/23). In 16/23 cases, the feeding vessel(s) arose from the thoracic aorta (male:female ratio 1:7) and in 7/23 cases from the abdominal aorta (male:female ratio 4:3). Feeding vessels from the thoracic aorta were duplicated in 7/16 cases. PS location (P <.05) and size (P <.001) differed based on the origin of the feeding vessel (thoracic aorta: 14/16 left lower lobe, mean volume 962.97 mL; abdominal aorta: 3/7 left lower lobe, mean volume 1120.89 mL). The feeding arteries themselves differed in size depending on their site of origin (thoracic aorta: mean diameter 7.0mm ± 2.7 mm, mean length 44.6mm ± 10.9 mm; abdominal aorta: mean diameter 3.3mm ± 0.6 mm, mean length 103.6mm ± 34.5 mm).PS size and distribution differ depending upon the site of feeding vessel origin as does the size of the feeding vessel itself.

The number of people with diabetes and pre-diabetes is growing exponentially. Human studies have shown that zinc supplementation is beneficial for pre-diabetes. However, owing to the low quality, small sample size, and methodological heterogeneity of these studies, this conclusion is not convincing. Consequently, in order to determine whether zinc supplementation is effective and safe in pre-diabetic patients, it is necessary to conduct a meta-analysis of high-quality clinical trials.

Esophageal squamous cell carcinoma (ESCC) is a malignancy that severely threatens human health and carries a high incidence rate and a low 5-year survival rate. MicroRNAs (miRNAs) are commonly accepted as a key regulatory function in human cancer, but the potential regulatory mechanisms of miRNA-mRNA related to ESCC remain poorly understood.The GSE55857, GSE43732, and GSE6188 miRNA microarray datasets and the gene expression microarray datasets GSE70409, GSE29001, and GSE20347 were downloaded from Gene Expression Omnibus databases. The differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs) were obtained using GEO2R. Gene ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis for DEGs were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). A protein-protein interaction (PPI) network and functional modules were established using the STRING database and were visualized by Cytoscape. Kaplan-Meier analysis was constructed based on The Cancer Genome Atlas (TCGA) database.In total, 26 DEMs and 280 DEGs that consisted of 96 upregulated and 184 downregulated genes were screened out. A functional enrichment analysis showed that the DEGs were mainly enriched in the ECM-receptor interaction and cytochrome P450 metabolic pathways. In addition, MMP9, PCNA, TOP2A, MMP1, AURKA, MCM2, IVL, CYP2E1, SPRR3, FOS, FLG, TGM1, and CYP2C9 were considered to be hub genes owing to high degrees in the PPI network. MiR-183-5p was with the highest connectivity target genes in hub genes. FOS was predicted to be a common target gene of the significant DEMs. Hsa-miR-9-3p, hsa-miR-34c-3p and FOS were related to patient prognosis and higher expression of the transcripts were associated with a poor OS in patients with ESCC.Our study revealed the miRNA-mediated hub genes regulatory network as a model for predicting the molecular mechanism of ESCC. This may provide novel insights for unraveling the pathogenesis of ESCC.

Halitosis is the term used to define an unpleasant odor emanating from the mouth. However, no studies have evaluated the causes and treatment of halitosis in the population of older adults with denture.

To compare the prognosis of papillary and clear cell renal cell carcinoma (RCC) in order to determine the optimal follow-up and therapy for patients with RCC.

Anti-programmed cell death 1 (PD-1) and anti-programmed cell death ligand 1 (PD-L1) drugs treatment-related adverse events (AEs) are not uniform based on current study for patients with cancer. The study aimed to provide a complete toxicity profile and toxicity spectrum for anti-PD-1 and anti-PD-L1 drugs.

Melanoma is a malignant tumor of melanocytes that produces pigments and can occur in the whole body. It is characterized by strong invasiveness, high metastasis rate and poor prognosis, and brings heavy burden to patients and society. In order to find the most effective and safe treatment measures, in this study, a network meta-analysis (NMA) for randomized controlled trials (RCTs) of advanced melanoma treated with PD-1 inhibitors will be conducted based on the existing systematic reviews (SRs) of PD-1 inhibitor in the treatment of advanced melanoma.

Since conventional culture-based antibiotic susceptibility testing (AST) methods are too time-consuming (typically 24-72 h), rapid AST is urgently needed for preventing the increasing emergence and spread of antibiotic resistant infections. Although several phenotypic antibiotic resistance sensing modalities are able to reduce the AST time to a few hours or less, concerning the biological heterogeneity, their accuracy or limit of detection are limited by low throughput. Here, we present a rapid AST method based on whole slide imaging (WSI)-enabled high-throughput sensing antibiotic resistance at single-bacterium level. The time for determining the minimum inhibitory concentration (MIC) was theoretically shortest, which ensures that the growth of each individual cell present in a large population is inhibited. As a demonstration, our technique was able to sense the growth of at least several thousand bacteria at single-cell level. Reliable MIC of Enterobacter cloacae against gentamicin was obtained within 1 h, while the gold standard broth dilution method required at least 16 h for the same result. In addition, the application of our method prevails over other imaging-based AST approaches in allowing rapid and accurate determination of antibiotic susceptibility for phenotypically heterogeneous samples, in which the number of antibiotic resistant cells was negligible compared to that of the susceptible cells. Hence, our method shows great promise for both rapid AST determination and point-of-care testing of complex clinical bacteria isolates.

The surface modifications of titanium dental implants play important roles in the enhancement of osseointegration. The objective of the present study was to test two different implant surface treatments on a rabbit model to investigate the osseointegration. The tested surfaces were: a) acid-etched surface with sandblasting treatment (SA) and b) an oxidized implant surface (OS). The roughness was measured by an interferometeric microscope with white light and the residual stress of the surfaces was measured with X-ray residual stress Bragg-Bentano diffraction. Six New Zealand white rabbits were used for the in vivo study. Implants with the two different surfaces (SA and OS) were inserted in the femoral bone. After 12 weeks of implantation, histological and histomorphometric analyses of the blocks containing the implants and the surrounding bone were performed. All the implants were correctly implanted and no signs of infection were observed. SA and OS surfaces were both surrounded by newly formed trabeculae. Histomorphometric analysis revealed that the bone-implant contact % (BIC) was higher around the SA implants (53.49 ± 8.46) than around the OS implants (50.94 ± 16.42), although there were no significant statistical differences among them. Both implant surfaces (SA and OS) demonstrated a good bone response with significant amounts of newly formed bone along the implant surface after 12 weeks of implantation. These results confirmed the importance of the topography and physico-chemical properties of dental implants in the osseointegration.

Background: Chronic exposure to occupational stress may lead to negative health consequences. Creating less stressful work environments and making employees physically and psychologically more resilient against stress are therefore two major public health concerns. This study examined whether cardiorespiratory fitness moderated the association between occupational stress, cardiovascular risk, and mental health. Methods: Stress was assessed via the Effort-Reward Imbalance and Job Demand-Control models in 201 police officers (36% women, Mage = 38.6 years). Higher levels of blood pressure, blood lipids, blood sugar, and unfavorable body composition were considered as cardiovascular risk factors. Burnout, insomnia and overall psychological distress were used as mental health indicators. Cardiorespiratory fitness was assessed with a submaximal bicycle test. Results: High cardiorespiratory fitness levels were associated with a reduced cardiometabolic risk, whereas high stress levels were associated with better mental health. Among participants who perceived a high Effort-Reward Imbalance, those with high fitness levels showed lower overall cardiovascular risk scores than their colleagues with low fitness levels. Conclusions: Work health programs for police officers should consider the early screening of burnout, sleep disturbances, and overall mental wellbeing. To increase cardiovascular health, including fitness tests in routine health checks and promoting physical activity to further increase cardiorespiratory fitness appears worthwhile.

Mechanisms mediating mesenchymal stromal/stem cells' (MSCs) multipotency are unclear. Although the expression of the pluripotency factor OCT4 has been detected in MSCs, whether it has a functional role in adult stem cells is still controversial. We hypothesized that a physiological expression level of OCT4 is important to regulate MSCs' multipotency and trigger differentiation in response to environmental signals. Here, we specifically suppressed OCT4 in MSCs by using siRNA technology before directed differentiation. OCT4 expression levels were reduced by 82% in siOCT4-MSCs, compared with controls. Interestingly, siOCT4-MSCs also presented a hypermethylated OCT4 promoter. OCT4 silencing significantly impaired the ability of MSCs to differentiate into osteoblasts. Histologic and macroscopic analysis showed a lower degree of mineralization in siOCT4-MSCs than in controls. Moreover, OCT4 silencing prevented the up-regulation of osteoblast lineage-associated genes during differentiation. Similarly, OCT4 silencing resulted in decreased MSC differentiation potential towards the adipogenic lineage. The accumulation of lipids was reduced 3.0-fold in siOCT4-MSCs, compared with controls. The up-regulation of genes engaged in the early stages of adipogenesis was also suppressed in siOCT4-MSCs. Our findings provide evidence of a functional role for OCT4 in MSCs and indicate that a basal expression of this transcription factor is essential for their multipotent capacity.

To study the effect of early and late onset preeclampsia (EOPE, LOPE, respectively) on outcomes of late preterm infants.

Inhibition of the androgen receptor (AR) by second-generation anti-androgens is a standard treatment for metastatic castration resistant prostate cancer (mCRPC), but it inevitably leads to the development of resistance. Since the introduction of highly efficient AR signalling inhibitors, approximately 20% of mCRPC patients develop disease with AR independent resistance mechanisms. In this study, we generated two anti-androgen and castration resistant prostate cancer cell models that do not rely on AR activity for growth despite robust AR expression (AR indifferent). They are thus resistant against all modern AR signalling inhibitors. Both cell lines display cross-resistance against the chemotherapeutic drug docetaxel due to MCL1 upregulation but remain sensitive to the PARP inhibitor olaparib and the pan-BCL inhibitor obatoclax. RNA-seq analysis of the anti-androgen resistant cell lines identified hyper-activation of the E2F cell-cycle master regulator as driver of AR indifferent growth, which was caused by deregulation of cyclin D/E, E2F1, RB1, and increased Myc activity. Importantly, mCRPC tissue samples with low AR activity displayed the same alterations and increased E2F activity. In conclusion, we describe two cellular models that faithfully mimic the acquisition of a treatment induced AR independent phenotype that is cross-resistant against chemotherapy and driven by E2F hyper-activation.