Notes

Global along with glucocorticoid receptor gene-specific (NR3C1) Genetic methylation examination within sufferers together with cannabinoid as well as man made cannabinoid employ condition.
Puberty is a biologically and psychologically unstable period, and pubertal changes differ by sex. However, most previous studies on pubertal timing and suicide have focused on girls. This study investigated the association between early spermarche and suicide attempts in boys.

We analyzed a nationally representative sample of Korean adolescents (The Korea Youth Risk Behavior Web-Based Survey, KYRBS) that included approximately 35,000 boys annually from 2011 to 2015. Pubertal timing in boys was defined by spermarche. Complex sampling logistic regression analyses were performed to evaluate the odds ratios (ORs) for suicide attempts between the early and average spermarche groups.

The ORs for suicide attempts in boys with early spermarche were significantly higher than those in boys with average spermarche after adjustment for age, perceived stress, depressive symptoms, and suicidal ideation. The ORs from 2011 to 2015 were as follows 1.782 (
< 0.001), 1.490 (
= 0.002), 1.693 (
< 0.001), 1.541 (
= 0.001), and 1.393 (1.024-1.895;
= 0.035), respectively.

These findings suggest that early pubertal timing is a risk factor for suicide attempts in Korean boys after adjustment for depressive symptoms, perceived stress, and suicidal ideation, which have been previously reported as risk factors for suicide attempts. Therefore, careful attention should be paid to the prevention of suicide in boys who experience early spermarche in Korea.
These findings suggest that early pubertal timing is a risk factor for suicide attempts in Korean boys after adjustment for depressive symptoms, perceived stress, and suicidal ideation, which have been previously reported as risk factors for suicide attempts. Therefore, careful attention should be paid to the prevention of suicide in boys who experience early spermarche in Korea.
Increased levels of plasma lipoproteins are among some of the modifiable risk factors for cardiovascular disease (CVD). Dietary changes and increased physical activity are the most powerful non-pharmacological interventions for achieving optimal plasma lipid levels.

To investigate the effect of an intensive short-term lifestyle intervention on plasma lipid trajectories in overweight non-diabetic females.

A total of 202 healthy overweight (body mass index (BMI) >27.5 kg/m2) females underwent an intensive short-term (ten-week) intervention (at least 4 units of one-hour exercise activity weekly at optimal energy intake) aimed at lowering body weight. Plasma lipid (total cholesterol (TC), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), and triglycerides (TG)) levels were examined at baseline and every 2 weeks over the course of the ten-week intervention.

There was a significant decrease in BMI (Δ -4.7%, p < 0.001) and body weight (Δ -4.9%, p < 0.001) after the intervention. Positive changes (decreases) in TC (Δ -8%, p < 0.001), TG (Δ -9%, p < 0.001) and LDL-C (Δ -11%, p < 0.001) were observed immediately after 2 weeks, but levels did not decrease further thereafter. In contrast, HDL-C did not increase as expected after 2 weeks of intervention, we observed a significant decrease of about 6% (p < 0.001) followed by a slow return to baseline values. But even after 10 weeks of intervention, HDL-C values had not reached the values detected at baseline.

In overweight females, HDL-C decreased after short-term intensive lifestyle intervention. To confirm the protective effect of increased physical activity, plasma lipids need to be examined over a longer time period.
In overweight females, HDL-C decreased after short-term intensive lifestyle intervention. To confirm the protective effect of increased physical activity, plasma lipids need to be examined over a longer time period.
The Sentimag hand-held probe detects the magnetic response from iron oxide particles trapped in a sentinel node.

To investigate if an electromagnetic probe can be helpful in the identification of a hook wire tip located in an occult breast lesion.

Forty-two patients undergoing lumpectomy without axillary procedure were enrolled. In all cases, suspicious non-palpable microcalcifications without mass were found, and a vacuum-assisted stereotactic biopsy was performed. On the day of surgery, a traditional localization wire (LW) was placed under imaging guidance. The Sentimag magnetometer was used to precisely detect the wire tip through the skin. Then, the skin incision was made and Sentimag was used again to guide the surgeon to the lumpectomy bed. The accuracy of excision was assessed with intra-operative specimen 3D tomosynthesis.

Median lesion size was 16 mm (range 4-38 mm) and median depth was 33 mm (range 14-78 mm). In all cases, the wire tip was successfully identified. Neither wire displacement ng targeted excision without excessive removal of breast tissue. Since it is not associated with additional costs, it may be worth considering, particularly in developing countries.
Galectin-3 is an emerging biomarker in cardiovascular disease. Myocardial galectin-3 is involved in the pathology of cardiac fibrosis; however, the role of circulating galectin-3 is not yet established.

To assess the relationships between circulating galectin-3, fibrosis and outcomes in dilated cardiomyopathy (DCM).

We included 70 patients (age 48 ±12.1 years, ejection fraction (EF) 24.4 ±7.4%) with new-onset DCM (n = 35, ≤6 months). Galectin-3 and procollagen type I and III (PICP, PINP, PIIICP, and PIIINP), transforming growth factor β (TGF-β), connective tissue growth factor (CTGF), osteopontin (OPN), matrix metalloproteinases (MMP-2 and -9), and tissue inhibitor (TIMP-1) were determined in serum at baseline and after 3 and 12 months. Patients underwent endomyocardial biopsy. The endpoint was a combination of death and urgent hospitalization at 12 months.

Galectin-3 did not correlate with biopsy-determined fibrosis. Baseline galectin-3 correlated with OPN,, TIMP-1, PIIICP, and MMP-2. In new-onset DCM, galectin-3 levels at baseline were higher than at 3 and 12 months, whereas in chronic DCM there was no difference. Galectin-3 was a predictor of the endpoint (hazard ratio (HR) = 1.115; 95% confidence interval (95% CI) = 1.009-1.231; p < 0.05). The best cut-off value was 14.54 ng/mL (area under the curve (AUC) = 0.67). Patients with galectin-3 ≥14.54 ng/mL had an increased risk of events (HR = 2.569; 95% CI = 1.098-6.009; p < 0.05).

Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.
Circulating galectin-3 is unrelated to fibrosis. Serial measurements of galectin-3 correlated with markers of fibrosis, including markers of collagen synthesis and OPN. Circulating galectin-3 was independently associated with cardiovascular (CV) outcomes in DCM.
Prediction of sudden cardiac death remains a significant challenge. There is some evidence that ventricular ectopic activity could be regarded as a predictive marker.

We carried out an analysis to explore whether premature ventricular complexes (PVCs) are a risk factor in implantable cardioverter-defibrillator (ICD) interventions.

The study method was a RR interval series analysis (n = 184) of arrhythmic events and controls from the ICD. Study group consisted of patients with a mean age of 55 ±27 years; 74% of them were male, 85% were secondary prevention patients, 62% had coronary artery disease (CAD), 15% hypertropic cardiomyopathy (HCM), 15% dilated cardiomyopathy (DCM), and 8% diseases of other etiology. The mean follow-up time was 64 months (range 3-126 months). The study population was divide into patients with at least 1 appropriate intervention ventricular tachycardia/ventricular fibrillation (VT/VF) (group A, n = 101) and controls without interventions (group B, n = 83). The number of PVC/4000 rogram called PCRR was applied for RR interval analysis. This simple method could be a predictor of PVC burden and life-threatening arrhythmias in different populations.
Significant differences were found in the characteristics of PVCs and SLS sequences between patients with appropriate ICD interventions and controls. A newly developed basic computer program called PCRR was applied for RR interval analysis. This simple method could be a predictor of PVC burden and life-threatening arrhythmias in different populations.Temporomandibular disorders (TMD) constitute a heterogeneous group of disorders concerning temporomandibular joints (TMJ) and the surrounding structures. The etiology is multifactorial, and comprises biological factors (e.g., internal derangements in TMJ), psychological factors (e.g., depression, anxiety and stress) and social factors (e.g., a learned response to pain). In accordance with the biopsychosocial model of health and illness, psychological factors are recognized as highly significant in the development of TMD. The aim of this review was to present the role of chosen mental disorders (depression, anxiety) in TMD and their significance for dental practitioners in the light of current knowledge. The PubMed, Scopus and Web of Science databases were searched for relevant studies. Finally, 22 studies were included in this review. The gathered literature shows convincing evidence that mental derangements play a significant role in TMD by influencing the onset of the disorder, the course of the condition and the patient's response to treatment. However, the precise role of each mental disorder still requires further clarification.
Heat generation is considered a decisive factor in the occurrence of bone necrosis during implant placement, which can happen when the temperature exceeds a threshold of 47°C for 1 min. The use of a surgical guide to aid implant placement has gained popularity in the last few years. Whether it increases the risk of bone necrosis is still debatable.

The aim of the present study was to compare heat generation during implant placement with and without the use of a surgical guide.

The study sample consisted of 80 measurement sites placed near 40 dental implant sockets, which were prepared on 10 bone-like dental models. These models were divided into 5 models for the conventional method group and 5 models for the surgical guide group. Each model had 4 implant sockets prepared, and then two 1-millimeter-wide holes were drilled <1 mm away from the socket on the opposite sides of the implant socket to be used as temperature measurement sites. The diameter of the drill was standardized to 2.2 mm, and 4 differ far below the threshold for bone necrosis.
Recurrent aphthous stomatitis (RAS) is one of the most common recurrent ulcerations in the oral mucosa, the etiology of which has not been elucidated; the immune system dysfunction may play an important role in the pathogenesis of RAS. The anti-inflammatory and regulatory role of vitamin D in the functioning of the immune system is well-documented.

This study aimed to evaluate and compare the serum levels of vitamin D between patients with RAS and healthy controls.

In this case-control study, 43 patients with minor RAS and 43 healthy controls were included. Two groups were matched in terms of age and sex. Blood samples were obtained from all participants. The serum levels of vitamin D were measured with the use of the enzyme-linked immunosorbent assay (ELISA) in patient and control groups. The data was analyzed using the SPSS for Windows software, v. 17.0, with the independent samples t test and the Mann-Whitney test. A p-value of <0.05 was considered statistically significant.

The mean serum level of vitamin D in the control group was significantly higher than that in the case group (22.59 ±16.06 ng/mL vs 13.19 ±8.19 ng/mL, respectively; p = 0.002).

The serum levels of vitamin D are lower in patients with RAS in comparison with healthy controls.
The serum levels of vitamin D are lower in patients with RAS in comparison with healthy controls.
Despite favorable prognoses, pediatric patients with hematologic malignancies experience significant challenges that may lead to diminished quality of life or family stress. They are less likely to receive subspecialty palliative care (PC) consultation and often undergo intensive end-of-life (EOL) care. We examined "palliative opportunities," or events when the integration of PC would have the greatest impact, present during a patient's hematologic malignancy course and relevant associations.

A single-center retrospective review was conducted on patients aged 0-18years with a hematologic malignancy who died between 1/1/12 and 11/30/17. Demographic, disease, and treatment data were collected. A priori, nine palliative opportunity categories were defined. Descriptive statistics were performed. Palliative opportunities were evaluated over temporal quartiles from diagnosis to death. Timing and rationale of pediatric PC consultation were evaluated.

Patients (n=92) had a median of 5.0 (interquartile range [IQ hematologic cancers and their caregivers.For several decades, much attention has been paid to thylakoid membranes (TMs) as photocatalysts for converting solar light to electricity. Despite extensive research, current technology provides only limited photocurrents. Here, a novel method based on TM-composite material was developed for achieving high photocurrent. When a thin film composed of TMs, osmium redox polymer (Os-RP), and indium tin oxide nanoparticles (ITOnp) was formed on a porous graphite surface, appreciable photocurrent as high as 0.5 mA cm-2 was achieved at 0.4 V vs. Ag/AgCl. Each component plays its own role in transferring electrons from TMs to the anode, resulting in sharp drop in photocurrent with missing any component. Optimization between these three components showed 1  0.5  30 (TM/Os-RP/ITOnp) was the best ratio. Action spectra confirmed that TMs was the origin of photocurrent. It was inferred from blocking experiments using 3-(3,4-dichlorophenyl)-1,1-dimethylurea as an inhibitor that about 41 % of photocurrent was transferred from QA in photosystem II to the electrode via Os-RP and ITOnp. Quantum efficiencies at 430 and 660 nm were 12.2 and 18.5 %, respectively. Turnover frequency for water oxidation depended upon the amount of the composite. A complete cell with Pt/C cathode produced Pmax of 122 μW cm-2 at 758 μA cm-2 under one sun illumination, which is the highest power density to our knowledge. This study opened a possibility of using TMs as photocatalysts for solar energy conversion.Single-cell RNA sequencing (scRNA-seq) is a technology for single-cell transcriptome analysis that can be used to characterize complex dynamics of various retinal cell types. It provides deep scrutiny into the gene expression character of diverse cell types, lending insight into all the biological processes being carried out. The scRNA-seq is an alternative to regular RNA-seq, which does not achieve cellular heterogeneity. The retina, is a part of the central nervous system (CNS) and consists of six types of neurons and several types of glial cells. Studying retinal cell heterogeneity is important for understanding retinal diseases. Currently, scRNA-seq is employed to assess retina development and retinal disease pathogenesis and has improved our understanding of the relationship between the retina, its visual pathways, and the brain. Moreover, this technology provides new ideas on the sensitivity and molecular mechanisms of cell subtypes involved in retinal-related diseases. The application of scRNA-seq technology has given us a deeper understanding of the latest advancements and challenges in retinal development and diseases. We advocate scRNA-seq as one of the important tools for developing novel therapies for retinal diseases. This article is categorized under RNA Methods > RNA Analyses in Cells RNA in Disease and Development > RNA in Development RNA in Disease and Development > RNA in Disease.
To assess effects of DF402, a bioisostere of Dimebon/Latrepirdine, on the disease progression in the transgenic model of amyotrophic lateral sclerosis (ALS) caused by expression of pathogenic truncated form of human FUS protein.

Mice received DF402 from the age of 42days and the onset of clinical signs, the disease duration and animal lifespan were monitored for experimental and control animals, and multiple parameters of their gait were assessed throughout the pre-symptomatic stage using CatWalk system followed by a bioinformatic analysis. RNA-seq was used to compare the spinal cord transcriptomes of wild-type, untreated, and DF402-treated FUS transgenic mice.

DF402 delays the onset and slows the progression of pathology. We developed a CatWalk analysis protocol that allows detection of gait changes in FUS transgenic mice and the effect of DF402 on their gait already at early pre-symptomatic stage. At this stage, a limited number of genes significantly change expression in transgenic mice and for 60% of these genes, DF402 treatment causes the reversion of the expression pattern.

DF402 slows down the disease progression in the mouse model of ALS, which is consistent with previously reported neuroprotective properties of Dimebon and its other bioisosteres. These results suggest that these structures can be considered as lead compounds for further optimization to obtain novel medicines that might be used as components of complex ALS therapy.
DF402 slows down the disease progression in the mouse model of ALS, which is consistent with previously reported neuroprotective properties of Dimebon and its other bioisosteres. These results suggest that these structures can be considered as lead compounds for further optimization to obtain novel medicines that might be used as components of complex ALS therapy.Critical-sized defects remain a significant challenge in orthopaedics. 3D printed scaffolds are a promising treatment but are still limited due to inconsistent osseous integration. The goal of the study is to understand how changing the surface roughness of 3D printed titanium either by surface treatment or artificially printing rough topography impacts the mechanical and biological properties of 3D printed titanium. Titanium tensile samples and discs were printed via laser powder bed fusion. Roughness was manipulated by post-processing printed samples or by directly printing rough features. Experimental groups in order of increasing surface roughness were Polished, Blasted, As Built, Sprouts, and Rough Sprouts. Tensile behavior of samples showed reduced strength with increasing surface roughness. MC3T3 pre-osteoblasts were seeded on discs and analyzed for cellular proliferation, differentiation, and matrix deposition at 0, 2, and 4 weeks. Printing roughness diminished mechanical properties such as tensile strength and ductility without clear benefit to cell growth. Roughness features were printed on mesoscale, unlike samples in literature in which roughness on microscale demonstrated an increase in cell activity. The data suggest that printing artificial roughness on titanium scaffold is not an effective strategy to promote osseous integration.
The impact of dental occlusion on the experiences of head and neck cancer patients and their oral, social and psychological functioning has been sparsely investigated. There is a lack of knowledge regarding the experience of tooth loss and dentures among patients treated for head and neck cancer. The aim of this study was to describe the experiences of head and neck cancer patients of prophylactic tooth extractions and temporary removable dentures, 6 months after radiotherapy treatment.

An individual interview with 25 patients 6 months after radiotherapy was subjected to a qualitative content analysis.

Two categories, Impaired oral function and Belief in the future, and seven subcategories described the patients' experiences of temporary removable dentures during the first 6 months after prophylactic tooth extractions. The temporary removable dentures affected the patients' ability to chew, swallow and speak, caused pain, and were experienced as an enemy. Despite that, the patients were hopeful and had ehabilitation phase.Glomerulonephritis is the one of the major causes of the end-stage kidney disease, whereas the pathological process of glomerulonephritis is still not completely understood. Single-cell RNA sequencing (scRNA-seq) emerges to be a powerful tool to evaluate the full heterogeneity of kidney diseases. To reveal cellular gene expression profiles of glomerulonephritis, we performed scRNA-seq of 2 human kidney transplantation donor samples, 4 human glomerulonephritis samples, 1 human malignant hypertension (MH) sample and 1 human chronic interstitial nephritis (CIN) sample, all tissues were taken from the biopsy. After filtering the cells with 10% mitochondria (MT) genes, the resulting 14 932 cells can be divided into 20 cell clusters, consistently with the previous report, in disease samples dramatic immune cells infiltration was found, among which a proximal tubule (PT) subset characterized by wnt-β catenin activation and a natural killer T (NKT) subset high expressing LTB were found. Furthermore, in the cluster of the podocyte, three glomerulonephritis related genes named FXYD5, CD74 and B2M were found. Compared with the mesangial of donor, the gene CLIC1 and RPS26 were up-regulated in mesangial of IgA nephropathy(IgAN), whereas the gene JUNB was up-regulated in podocyte of IgAN in comparison with that of donor. Meanwhile, some membranous nephropathy (MN) high expressed genes such as HLA-DRB5, HLA-DQA2, IFNG, CCL2 and NR4A2, which involve in highest enrichment pathway, display the cellular-specific expression style, whereas monocyte marker of lupus nephritis (LN) named TNFSF13B was also found and interferon alpha/beta signalling pathway was enriched in B and NKT of LN comparing with donor. By scRNA-seq, we first defined the podocyte markers of glomerulonephritis and specific markers in IgA, MN and LN were found at cellular level. Furthermore, the critical role of interferon alpha/beta signalling pathway was enriched in B and NKT of LN was declared.Interfacial cues in the tumor microenvironment direct the activity and assembly of multiple cell types. Pancreatic cancer, along with breast and prostate cancers, is enriched with cancer-associated fibroblasts (CAFs) that activate to coordinate the deposition of the extracellular matrix, which can comprise over 90% of the tumor mass. While it is clear that matrix underlies the severity of the disease, the relationship between stromal-tumor cell assembly and cell-matrix dynamics remains elusive. Micropatterned hydrogels deconstruct the interplay between matrix stiffness and geometric confinement, guiding heterotypic cell populations and matrix assembly in pancreatic cancer. Interfacial cues at the perimeter of microislands guide CAF migration and direct cancer cell assembly. Computational modeling shows curvature-stress dependent cellular localization for cancer and CAFs in coculture. Regions of convex curvature enhance edge stress that activates a myofibroblast phenotype in the CAFs with migration and increased collagen I deposition, ultimately leading to a central "corralling" of cancer cells. Inhibiting mechanotransduction pathways decreases CAF activation and the associated corralling phenotype. Together, this work reveals how interfacial biophysical cues underpin aspects of stromal desmoplasia, a hallmark of disease severity and chemoresistance in the pancreatic, breast, and prostate cancers, thereby providing a tool to expand stroma-targeting therapeutic strategies.
Recently, there has been increasing interest in providing Personal Health Budgets (PHBs) to patients with severe mental illness. However, information on implementing PHB initiatives is still limited. Aim of this observational study was to evaluate the applicability of a PHB intervention model in a sample of Italian adults with first-episode psychosis (FEP) across a 2-year follow-up period.

Participants (n = 104; 18-50 years) were recruited within the 'Parma-Early Psychosis' program and completed the brief psychiatric rating scale (BPRS), the health of nation outcome scale (HoNOS) and the global assessment of functioning (GAF). Mixed-design analysis of variance (ANOVA) and Kaplan-Maier survival analysis (as drop-out measure) were performed.

A significant effect of time on all BPRS, HoNOS and GAF scores along the follow-up was observed in both the FEP subgroups (i.e., with [n = 49] and without [n = 55] PHB intervention). Mixed-design ANOVA results showed a significant 'time x group' interaction effects on BPRS 'Disorganization', HoNOS 'Psychiatric Symptoms' and GAF scores in FEP participants with PHB. Kaplan-Meyer survival analysis showed a longer survival mean for FEP patients with PHB.

Our results support the applicability of a PHB model within an 'Early Intervention in Psychosis' program in public community mental health services.
Our results support the applicability of a PHB model within an 'Early Intervention in Psychosis' program in public community mental health services.Heterogeneous molecular catalysts have attracted considerable attention as carbon dioxide reduction reaction (CO2 RR) electrocatalysts. The π-electron system of conjugated ligands in molecular catalysts may play an important role in determining the activity. In this work, by enlarging π-conjugation through appending more aromatic substituents on the porphyrin ligand, altered π-electron system endows the as-prepared 5,10,15,20-tetrakis(4-(pyren-1-yl)phenyl)porphyrin CoII with high Faradaic efficiency (ca. 95 %) for CO production, as well as high turnover frequency (2.1 s-1 at -0.6 V vs. RHE). Density functional theory calculation further suggests that the improved electrocatalytic performance mainly originates from the higher proportion of Co d z 2 orbital and the CO2 π* orbital in the HOMO of the (Co-porphyrin-CO2 )- intermediate with larger π-conjugation, which facilitates the CO2 activation. This work provides strong evidence that π-conjugation perturbation is effective in boosting the CO2 RR.One enduring priority for ecologists has been to understand the cause(s) of variation in reproductive effort among species and localities. Avian clutch size generally increases with increasing latitude, both within and across species, but the mechanism(s) driving that pattern continue to generate hypotheses and debate. In 1961, a Ph.D. student at Oxford University, N. Philip Ashmole, proposed the influential hypothesis that clutch size varies in direct proportion to the seasonality of resources available to a population. Ashmole's hypothesis has been widely cited and discussed in the ecological literature. However, misinterpretation and confusion has been common regarding the mechanism that underlies Ashmole's hypothesis and the testable predictions it generates. We review the development of well-known hypotheses to explain clutch size variation with an emphasis on Ashmole's hypothesis. We then discuss and clarify sources of confusion about Ashmole's hypothesis in the literature, summarise existing evidence in support and refutation of the hypothesis, and suggest some under-utilised and novel approaches to test Ashmole's hypothesis and gain an improved understanding of the mechanisms responsible for variation in avian clutch size and fecundity, and life-history evolution in general.
While global longitudinal strain (GLS) is considered to be a sensitive marker of left ventricular (LV) function, it is significantly influenced by loading conditions. We hypothesized that global myocardial work index (GMWI), a novel marker of LV function, may show better correlation with load-independent markers of LV contractility in rat models of pressure-induced or volume overload-induced heart failure.

Male Wistar rats underwent either transverse aortic constriction (TAC; n=12) or aortocaval fistula creation (ACF; n=12), inducing LV pressure or volume overload, respectively. Sham procedures were performed to establish control groups (n=12/12). Echocardiographic loops were obtained to determine GLS and GMWI. Pressure-volume analysis with transient occlusion of the inferior caval vein was carried out to calculate preload recruitable stroke work (PRSW), a load-independent 'gold-standard' parameter of LV contractility. Myocardial samples were collected to assess interstitial and perivascular fibrosis areafluenced by loading conditions, GLS may not be a reliable marker of LV contractility in heart failure induced by pressure or volume overload. GMWI better reflects contractility in haemodynamic overload states, making it a more robust marker of systolic function, while GLS should be considered as an integrative marker, incorporating systolic function, haemodynamic loading state, and adverse tissue remodelling of the LV.
Being significantly influenced by loading conditions, GLS may not be a reliable marker of LV contractility in heart failure induced by pressure or volume overload. GMWI better reflects contractility in haemodynamic overload states, making it a more robust marker of systolic function, while GLS should be considered as an integrative marker, incorporating systolic function, haemodynamic loading state, and adverse tissue remodelling of the LV.An RNA structure prediction from a single-sequence RNA folding program is not evidence for an RNA whose structure is important for function. Random sequences have plausible and complex predicted structures not easily distinguishable from those of structural RNAs. How to tell when an RNA has a conserved structure is a question that requires looking at the evolutionary signature left by the conserved RNA. This question is important not just for long noncoding RNAs which usually lack an identified function, but also for RNA binding protein motifs which can be single stranded RNAs or structures. Here we review recent advances using sequence and structural analysis to determine when RNA structure is conserved or not. Although covariation measures assess structural RNA conservation, one must distinguish covariation due to RNA structure from covariation due to independent phylogenetic substitutions. We review a statistical test to measure false positives expected under the null hypothesis of phylogenetic covariation alone (specificity). We also review a complementary test that measures power, that is, expected covariation derived from sequence variation alone (sensitivity). Power in the absence of covariation signals the absence of a conserved RNA structure. We analyze artifacts that falsely identify conserved RNA structure such as the misuse of programs that do not assess significance, the use of inappropriate statistics confounded by signals other than covariation, or misalignments that induce spurious covariation. Among artifacts that obscure the signal of a conserved RNA structure, we discuss the inclusion of pseudogenes in alignments which increase power but destroy covariation. This article is categorized under RNA Structure and Dynamics > RNA Structure, Dynamics and Chemistry RNA Evolution and Genomics > Computational Analyses of RNA RNA Evolution and Genomics > RNA and Ribonucleoprotein Evolution.Dopamine transporter (DAT) and sigma-1 receptor (σ1R) are potential therapeutic targets to reduce the psychostimulant effects induced by methamphetamine (METH). Interaction of σ1R with DAT could modulate the binding of METH, but the molecular basis of the association of the two transmembrane proteins and how their interactions mediate the binding of METH to DAT or σ1R remain unclear. Here, we characterize the protein-ligand and protein-protein interactions at a molecular level by various theoretical approaches. The present results show that METH adopts a different binding pose in the binding pocket of σ1R and is more likely to act as an agonist. The relatively lower binding affinity of METH to σ1R supports the role of antagonists as inhibitors that protect against METH-induced effects. We demonstrate that σ1R could bind to Drosophila melanogaster DAT (dDAT) through interactions with either the transmembrane helix α12 or α5 of dDAT. Our results showed that the truncated σ1R displays stronger association with dDAT than the full-length σ1R. Although different helix-helix interactions between σ1R and dDAT lead to distinct effects on the dynamics of individual protein, both associations attenuate the binding affinity of METH to dDAT, particularly in the interactions with the helix α5 of dDAT. Together, the present study provides the first computational investigation on the molecular mechanism of coupling METH binding and the association of σ1R with dDAT.Lithium-sulfur (Li-S) batteries are a promising candidate for the next-generation energy storage system, yet their commercialization is primarily hindered by polysulfide shuttling and uncontrollable Li dendrite growth. Here, a protein-based Janus separator was designed and fabricated for suppressing both the shuttle effect and dendrite growth, while facilitating the Li+ transport. The Li metal-protecting layer was a protein/MoS2 nanofabric with high ionic conductivity and good Li+ affinity, thus capable of homogenizing the Li+ flux and facilitating the Li+ transport. The polysulfide-trapping layer was a conductive protein nanofabric enabling strong chemical/electrostatic interactions with polysulfides. Combination of the two layers was achieved by an integrated electrospinning method, yielding a robust and integral Janus separator. As a result, a long-lived symmetric Li|Li cell (>700 h) with stable cycling performance was demonstrated. More significantly, the resulting Li-S battery delivered greatly improved electrochemical performance, including excellent rate capacity and remarkable cycle stability (with a low decay rate of 0.063 % per cycle at 0.5 A g-1 over 500 cycles). This study demonstrates the effectiveness of the Janus separator configurations for simultaneously addressing the shuttle effect and dendrite growth issues of Li-S batteries and broadens the applications of electrospinning in electrochemistry community.Depression and anxiety are leading causes of morbidity in children and adolescents worldwide. In Pakistan, young people are exposed to many chronic adversities including violence, social and economic inequalities, and are at greater risk of developing mental health problems. Yet there is a lack of trained human resources, in-patient child and adolescent mental healthcare facilities, and training opportunities in child and adolescent psychiatry and mental health in Pakistan. Given the poor economic condition of the country, which has been made even worse by the COVID-19 pandemic, it is very unlikely that dedicated resources will be made available in near future to develop specialist child and adolescent mental health services in Pakistan. To bridge this treatment gap, we propose a multitiered, transdiagnostic, task-shifting strategy-based model for child and adolescent mental health services in Pakistan.Staphylococcus aureus is the main aetiological agent responsible for the majority of human skin infections. Of particular concern is the methicillin-resistant variety, commonly known as MRSA. The extensive use of the first-line topical antibiotic of choice, mupirocin, has inevitably resulted in the emergence of resistant strains, signalling an urgent need for the development of new antibacterials with new mechanisms of action. In this work, we describe how we designed a novel cationic nonapeptide, containing only leucine and two lysine residues, with potent anti-MRSA activity and a rapid bactericidal mode of action. Coupled to a favourable safety profile towards human skin fibroblasts, we believe nonapeptide 11 has high potential for further development as a mupirocin replacement candidate to treat skin infections caused by MRSA.Deciphering the complex cellular behaviours and advancing the biotechnology applications of filamentous fungi increase the requirement for genetically manipulating a large number of target genes. The current strategies cannot cyclically coedit multiple genes simultaneously. In this study, we firstly revealed the existence of diverse homologous recombination (HR) types in marker-free editing of filamentous fungi, and then, demonstrated that sgRNA efficiency-mediated competitive inhibition resulted in the low integration of multiple genetic sites during coediting, which are the two major obstacles to limit the efficiency of cyclically coediting of multiple genes. To overcome these obstacles, we developed a biased cutting strategy by Cas9 to greatly enhance the desired HR type and applied a new selection marker labelling strategy for multiple donor DNAs, in which only the donor DNA with the lowest sgRNA efficiency was labelled. Combined with these strategies, we successfully developed a convenient method for cyclically coediting multiple genes in different filamentous fungi. In addition, diverse HRs resulted in a useful and convenient one-step approach for gene functional study combining both gene disruption and complementation. This research provided both a useful one-step approach for gene functional study and an efficient strategy for cyclically coediting multiple genes in filamentous fungi.Increasing evidence demonstrates that mechanical forces, in addition to soluble molecules, impact cell and tissue functions in physiology and diseases. How living cells integrate mechanical signals to perform appropriate biological functions is an area of intense investigation. Here, we review the evidence of the central role of cytoskeletal prestress in mechanotransduction and mechanobiology. Elevating cytoskeletal prestress increases cell stiffness and reinforces cell stiffening, facilitates long-range cytoplasmic mechanotransduction via integrins, enables direct chromatin stretching and rapid gene expression, spurs embryonic development and stem cell differentiation, and boosts immune cell activation and killing of tumor cells whereas lowering cytoskeletal prestress maintains embryonic stem cell pluripotency, promotes tumorigenesis and metastasis of stem cell-like malignant tumor-repopulating cells, and elevates drug delivery efficiency of soft-tumor-cell-derived microparticles. The overwhelming evidence suggests that the cytoskeletal prestress is the governing principle and the cellular hallmark in mechanobiology. The application of mechanobiology to medicine (mechanomedicine) is rapidly emerging and may help advance human health and improve diagnostics, treatment, and therapeutics of diseases.
Sialocele and salivary fistula are not serious but troublesome complications after parotidectomy. Various modalities have been introduced to prevent postoperative saliva-related complications. However, clinical trials assessing the prophylactic use of botulinum toxin (BTX) for parotidectomy have not been conducted yet. Herein, we report a pilot study investigating the safety and efficacy of intraoperative BTX (iBTX) injection in partial superficial parotidectomy (PSP).

Patients with benign parotid tumour were prospectively recruited for this clinical trial from 2017 to 2019. The study participants underwent PSP with iBTX injection. We retrospectively reviewed the clinical information of all the consecutive patients who underwent PSP without iBTX from 2013 to 2019. These patients were divided into two groups the iBTX group (n=36) and the control group (n=54).

Permanent facial palsy was not observed in either group. Two patients (3.7%) had transient marginal palsy in the control group but none had it in the iBTX group. The incidence of sialocele was significantly lower in the iBTX group than in the control group (2.8% vs. 20.4%, P<.05). Although the incidence of salivary fistula was lower in the iBTX group than in the control group (0% vs. 7.4%), no significant difference was determined between the two groups (P=.147). Total drainage volume was significantly lower in the iBTX group than in the control group (55.0mL vs. 116.6mL, P<.001).

iBTX injection may be safe and effective in reducing sialocele and postoperative drainage in PSP. It might be a useful option to prevent saliva-related complications after PSP.
iBTX injection may be safe and effective in reducing sialocele and postoperative drainage in PSP. It might be a useful option to prevent saliva-related complications after PSP.
To analyse the oncological outcomes following primary Transoral Robotic Surgery (TORS) for oropharyngeal squamous cell carcinoma (OPSCC).

Observational case series.

Tertiary centre; first TORS practice to commence in the UK.

All consecutive patients undergoing primary TORS with curative intent, with or without adjuvant treatment.

Descriptive analysis of patient and tumour pathology variables. Survival outcomes Overall, Disease-Specific, Progression-Free and Locoregional control.

The cohort comprised of 120 patients undergoing TORS with minimum 12-month follow-up data and the following characteristics mean age 58years, 91 males (76%), 78 tonsil (65%) and 34 base of tongue primaries (28%), 89% HPV-related OPSCC. The surgical pathology revealed 14 (12%) with positive margins, 19 (16%) had close margins <2mm and 31% with extranodal extension. The treatment was as follows 39 (33%) treated with TORS alone, 50 (42%) received adjuvant radiotherapy and 31 (26%) received adjuvant radiotherapy with chemotherapy. There were 15 recurrences. Estimated survival for all patients at 3years (95% CI) overall 85% (78-92), disease-specific 90% (85-96), progression-free 86% (79-92) and locoregional control 90% (84-96). The equivalent survival figures for the HPV-related cases alone were as follows overall 88% (82-94), disease-specific 93% (87-98), progression-free 88% (81-95) and locoregional control 92% (87-98).

Whilst TORS has become a common practice in the management of OPSCC in the UK, these are the first reported oncological outcomes. For selected patients, TORS with or without adjuvant therapy is an appropriate treatment modality.
Whilst TORS has become a common practice in the management of OPSCC in the UK, these are the first reported oncological outcomes. For selected patients, TORS with or without adjuvant therapy is an appropriate treatment modality.Climate change globally perturbs water circulation thereby influencing ecosystems including cultivated land. Both harmful and beneficial species of insects are likely to be vulnerable to such changes in climate. As small animals with a disadvantageous surface area to body mass ratio, they face a risk of desiccation. A number of behavioural, physiological and genetic strategies are deployed to solve these problems during adaptation in various Drosophila species. Over 100 desiccation-related genes have been identified in laboratory and wild populations of the cosmopolitan fruit fly Drosophila melanogaster and its sister species in large-scale and single-gene approaches. These genes are involved in water sensing and homeostasis, and barrier formation and function via the production and composition of surface lipids and via pigmentation. Interestingly, the genetic strategy implemented in a given population appears to be unpredictable. In part, this may be due to different experimental approaches in different studnge in an insect genome. Ultimately these efforts may provide guidelines for dealing with the effects of climate-related perturbations on insect population dynamics in the future.Healthy lifestyle behaviors during the preconception period are important to optimize maternal and child outcomes, including weight. However, the majority of women do not have optimal preconception lifestyle behaviors. This systematic review explored enablers and barriers to women's preconception lifestyle behaviors using the Capability, Opportunity, Motivation, Behaviour (COM-B) model and Theoretical Domains Framework (TDF). Preconception was defined as the time before conception, capturing planned and unplanned pregnancies. Medline Complete, EMBASE, PsycINFO, and CINAHL were searched for peer-reviewed, quantitative and qualitative primary studies (English, 2006-2020) that explored enablers and barriers to lifestyle behaviors (diet, physical activity, smoking, alcohol use, supplement intake). Forty-two studies (of 3406) were included, assessing supplement use (n = 37), diet (n = 10), smoking (n = 10), alcohol use (n = 8), and physical activity (n = 5). All three COM-B components were identified only for diet and supplement use. Of the 14 TDF domains, 7 were identified knowledge, beliefs about capabilities, beliefs about consequences, goals, intentions, social support, and environmental context and resources. The presence/absence of knowledge on healthy behaviors was the most commonly assessed enabler/barrier. Future studies should explore a wider range of factors influencing preconception women's capability, opportunity, and motivation to modify their lifestyle behaviors.
To investigate macroprolactinemia caused by antipsychotics and its clinical significance.

A total of 133 patients with schizophrenia were selected, all of whom were treated with either risperidone or amisulpride alone. The levels of total prolactin (T-PRL) and macroprolactin (MPRL) were measured before treatment as well as the second, fourth, and sixth weeks of treatment.

After 2 weeks of treatment, 75.09% (100/133) of the patients met the diagnostic criteria for hyperprolactinemia, the incidence of macroprolactinemia was 43% (43/100), and MPRL levels were positively correlated T-PRL levels.

Risperidone and amisulpride caused hyperprolactinemia and macroprolactinemia; thus, detection of MPRL in the clinical setting should be performed as this phenomenon appears early in treatment (the second week) and continues, that can avoid unnecessary examination and treatment for asymptomatic patients with macroprolactinemia.
Risperidone and amisulpride caused hyperprolactinemia and macroprolactinemia; thus, detection of MPRL in the clinical setting should be performed as this phenomenon appears early in treatment (the second week) and continues, that can avoid unnecessary examination and treatment for asymptomatic patients with macroprolactinemia.
The need to adjust the indications of elective abdominal aortic aneurysm (AAA) repair among patients with a limited life-span deserves a specific evaluation for octogenarians. The aim of this study was to compare the postoperative results and the long-term survival after endovascular repair of abdominal aortic and/or iliac aneurysms (EVAR) in octogenarians compared with patients under 80 years of age.

Retrospective analysis of 241 consecutive patients who underwent an elective EVAR between 2000 and 2017. EVAR was not considered among patients with clear life-limiting conditions. Patients receiving other than commercially standard infra-renal endoprostheses were excluded.

Seventy patients (29.0%) were octogenarians. They had a lower rate of active smoking (10.0% vs. 30.4%, P < 0.001) and a higher prevalence of previous cerebrovascular disease (21.4% vs. 11.7%, P = 0.055) than younger patients. Thirty-day/in-hospital complication and mortality rates were not significantly higher among octogenarians when compared with younger patients (24.3% vs. 16.9% and 2.9% vs. 2.4%, respectively). Octogenarians had a lower long-term survival at 1, 3 and 5 years (92.6% vs. 93.3%, 67.7% vs. 78.0% and 39.3% vs. 60.6%, P = 0.039) in the bivariate analysis. However, an age ≥ 80 years per se was not an independent predictor of survival after adjustment for confounding factors.

An age above 80 years was not associated with an increased risk of postoperative complications or long-term mortality. Our results suggest that EVAR can be considered in elderly patients without a clear life-limiting condition and with a suitable aneurysm anatomy. Geriatr Gerontol Int 2021; 21 392-397.
An age above 80 years was not associated with an increased risk of postoperative complications or long-term mortality. Our results suggest that EVAR can be considered in elderly patients without a clear life-limiting condition and with a suitable aneurysm anatomy. Geriatr Gerontol Int 2021; 21 392-397.In transfusion centres, blood components are divided and stored following specific guidelines. The storage temperature and time vary among the blood cells but all of them release extracellular vesicles (EVs) under blood bank conditions. The clinical impact of such vesicles in blood components for transfusion is an object of debate, but should be considered and is being investigated. In this context, proteomics is an excellent tool to study the cargo and composition of EVs derived from red blood cells and platelets, since such vesicles are enriched in lipids and proteins. The development of quantitative mass spectrometry techniques and the evolution of bioinformatics have allowed the identification of novel EVs biomarkers for different diseases. In this context, the application of high coverage proteomic tools to the analysis of EVs in the transfusion medicine field would provide information about storage lesions and possible transfusion adverse reactions. This viewpoint article approaches the potential of proteomics to investigate the impact of EVs in blood bank transfusion components, especially red blood cells and platelets.
There is an ongoing debate regarding the optimal timing of discontinuation of antipsychotic drugs for patients with first episode psychosis. Although most guidelines recommend maintenance therapy for at least 1 or 2 years after reaching remission, study results indicate that early discontinuation may be beneficial for at least a subsample of patients. To date, little is known about which medication strategies are applied in patients recovering from a first psychotic episode. In this study, we examined the beliefs and practices of clinicians on medication discontinuation.

We performed a survey among 50 experienced Dutch psychiatrists to assess how often specific treatment strategies have been applied in the past 12 months, as well as their knowledge and expectations with respect to medication discontinuation.

Psychiatrists estimated that, after remission, they continued medication at the same dose for at least 12 months in 51.2% of cases, continued in a reduced dose in 33.8% of cases and discontinued medication in 9.1% of cases after 4.4months of remission on average. Although the medication is discontinued in only a relatively small proportion of patients, almost half of all clinicians (45.9%) used this strategy at least once in the past 12 months.

There is substantial practice variation in antipsychotic medication strategies after remission from a first psychotic episode. Future research on long-term effects of early medication discontinuation can guide clinicians in making evidence-based decisions when treating first-episode patients.
There is substantial practice variation in antipsychotic medication strategies after remission from a first psychotic episode. Future research on long-term effects of early medication discontinuation can guide clinicians in making evidence-based decisions when treating first-episode patients.
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