Commencing breastfeeding within one hour of birth is defined as early initiation of breastfeeding (EIBF). Both the mother and child benefit from EIBF. This study aims to identify the predictors of EIBF among Indonesian women. This paper analyses data from a weighted sample of 6,616 women collected at the Indonesia Demographic and Health Survey (IDHS) 2017.The frequency of EIBF is measured by the proportion of children born in the two years preceding the survey who received breastmilk within one hour of birth. https://www.selleckchem.com/products/brusatol.html The analysis uses bivariate and multivariate logistic regression for complex sample designs, adjusted for confounders to examine the relationship of EIBF with women's individual, household and community level characteristics. Overall, 57% (95% CI 54.9%-58.2%) of the children born in the two years preceding the survey had EIBF. Statistically significant (p<0.05) predictors of EIBF are women's non-working status, second or higher order of the birth of the most recent child, average or large size o. EIBF should be continuously promoted and supported particularly among mothers who do not have early skin-to-skin contact with their new-born, who have Caesarean deliveries and who have no skilled birth attendant.Obesity is a common disease over the world and is tightly associated with diabetes mellitus, cardiovascular and cancer disease. Although our previous study showed that the synthetic vanadium-protein (V-P) complex had a better effect on antioxidant and antidiabetic, the relative molecular mechanisms are still entirely unknown. Hence, we investigated the effect of the synthetic V-P complex on adipocyte differentiation (adipogenesis) using human preadipocytes to clarify its molecular mechanisms of action. The primary human preadipocytes were cultured with and without V-P complex during adipocyte differentiation. The cell proliferation, lipid accumulation, and the protein expression of transcription factors and related enzymes were determined for the differentiated human preadipocytes. In this study, the 20 μg/mL of V-P complex reduced the lipid and triglyceride (TG) content by 74.47 and 57.39% (p less then 0.05), respectively, and down-regulated the protein expressions of peroxisome proliferator-activated receptor-γ (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), sterol regulatory element-binding protein 1 (SREBP-1) and fatty acid synthase (FAS). Additionally, the V-P complex significantly up-regulated the protein levels of total β-catenin (t-β-catenin), nuclear β-catenin (n-β-catenin), phosphorylated adenosine monophosphate-activated protein kinase alpha (p-AMPKα) and liver kinase B1 (p-LKB1). These showed that the inhibitory effect of V-P complex on human adipogenesis was mediated by activating Wnt/β-catenin and LKB1/AMPK-dependent signaling pathway. Therefore, the synthetic V-P complex could be considered as a candidate for prevention and treatment of obesity.Clustering is an important technology of data mining, which plays a vital role in bioscience, social network and network analysis. As a clustering algorithm based on density and distance, density peak clustering is extensively used to solve practical problems. The algorithm assumes that the clustering center has a larger local density and is farther away from the higher density points. However, the density peak clustering algorithm is highly sensitive to density and distance and cannot accurately identify clusters in a dataset having significant differences in cluster structure. In addition, the density peak clustering algorithm's allocation strategy can easily cause attached allocation errors in data point allocation. To solve these problems, this study proposes a potential-field-diffusion-based density peak clustering. As compared to existing clustering algorithms, the advantages of the potential-field-diffusion-based density peak clustering algorithm is three-fold 1) The potential field concept is introduced in the proposed algorithm, and a density measure based on the potential field's diffusion is proposed. The cluster center can be accurately selected using this measure. 2) The potential-field-diffusion-based density peak clustering algorithm defines the judgment conditions of similar points and adopts different allocation strategies for dissimilar points to avoid attached errors in data point allocation. 3) This study conducted many experiments on synthetic and real-world datasets. Results demonstrate that the proposed potential-field-diffusion-based density peak clustering algorithm achieves excellent clustering effect and is suitable for complex datasets of different sizes, dimensions, and shapes. Besides, the proposed potential-field-diffusion-based density peak clustering algorithm shows particularly excellent performance on variable density and nonconvex datasets.Optimal breastfeeding practices can ensure healthy growth and development of infants, which in the long term can impact the country's economic development. Nevertheless, Myanmar has yet to achieve the WHO's target of 70% for early initiation of breastfeeding, and the country's target of 90% for exclusive breastfeeding. The purpose of this study was to assess the associations between early initiation of breastfeeding and exclusive breastfeeding and bio-demographic, socio-economic and behavioral factors in Myanmar. Using the 2015-2016 Myanmar Demographic and Health Survey, the analysis of early initiation of breastfeeding was based on a sample of 1,506 under-2 children and the analysis of exclusive breastfeeding was based on a sample of 376 children aged 0-5 months. Multiple logistic modeling, with heteroskedasticity-adjusted standard errors, was used. The prevalence rates of early initiation of breastfeeding and exclusive breastfeeding in the study were 67.9% and 52.2% respectively. Having a vaginal delivery (AOR = 2.5; 95% CI = 1.7-3.7) and having frequent (≥ 4) antenatal visits (AOR = 2.4; 95% CI = 1.5-3.8) were associated with higher odds of early initiation of breastfeeding. Having a postnatal checkup (AOR = 0.5; 95% CI = 0.3-0.9) and having an infant that was perceived to be small at birth (AOR = 2.5; 95% CI = 1.1-5.7, for infants perceived to be large at birth) were significantly associated with decreased odds of exclusive breastfeeding. In order to promote optimal breastfeeding practices, this study suggested that delivery and quality of health services during pregnancy need to be strengthened in Myanmar.

ost breakdown were greatly altered due to the treatment and cost for OA itself, and the treatment and cost for comorbidities. Similar studies to investigate such a trend may help predict necessary resources and social needs. Thus, further investigation utilizing other databases is needed.Drug resistance is one of the major challenges for cancer therapies. In recent years, research on disease-related molecular signaling pathways has become the key ways to understand and overcome obstacles. https://www.selleckchem.com/products/prt062607-p505-15-hcl.html Dysregulation of MALAT1 could regulate doxorubicin resistance of hepatocellular carcinoma (HCC), but how MALAT1 involving in managing doxorubicin resistance remains unclear yet. We aimed to elucidate the specific molecular mechanism of MALAT1 with doxorubicin resistance in HCC cells. Quantitative real-time polymerase chain reaction (qRT-PCR) was engaged to detect the expression levels of MALAT1, miR-3129-5p and Nova1 mRNA; MTT, western blot, flow cytometry and luciferase reporter assays were executed to identify the influence of MALAT1 on doxorubicin resistance of HCC cells. Xenograft tumor model was created to confirm the biological function of MALAT1 in doxorubicin resistance of HCC cells in vivo. MALAT1 and Nova1 were upregulated, while miR-3129-5p expression was decreased in doxorubicin-resistant HCC tissues and cells. Knockdown of MALAT1 regulated doxorubicin resistance of HCC cells through inhibiting cell proliferation, migration, invasion and promoting apoptosis, but antisense miR-3129-5p released the functional effect of MALAT1 knockdown. Nova1, as a target gene of miR-3129-5p, reversed the results of miR-3129-5p expression and enhanced doxorubicin resistance of HCC cells. Xenograft tumor model suggested that dysregulation of MALAT1 regulated tumor growth and Nova1 to mediate doxorubicin resistance of HCC cells by as a sponge for miR-3129-5p in vivo. Elevation of LncRNA MALAT1 mediated doxorubicin resistance and the progression of HCC via a MALAT1/miR-3129-5p/Nova1 axis. This study would be expected to enrich the understanding of doxorubicin resistance of HCC and provide new ideas for HCC treatment strategies.There is limited information regarding the TLR2 signaling pathway involved in Th9 cell differentiation. The role of calcitriol in regulating TLR2-mediated Th9 cell development is unknown. Thus, we aimed to unravel the TLR2 signaling pathway in Th9 cells and its regulation by calcitriol. We have used n = 5-6 animals for each murine experiment. Human studies involved five healthy volunteers. Moreover, ten healthy individuals and ten RA patients were included in the study. Murine and human Th9 cells were treated with Calcitriol (100 nM) and Pam3CSK4 (2 µg/mL). The number of IL-9+ve cells was determined by flow cytometry. Real-time PCR was used to assess the gene expression. Serum 25(OH)D3 levels were determined by HPLC. We observed that TLR2 signals via IL-33/ST2 in Th9 cells. Increased TLR2 expression associated with increased IL9 expression and augmented disease severity in RA patients. Calcitriol attenuated TLR2 signaling in murine and human Th9 cells. Low serum vitamin D3 level negatively associated with increased IL-9 and TLR2 expression and disease severity in RA patients. Our data suggest a potential role of calcitriol to ameliorate the disease severity of RA patients.COPD is an inflammatory lung disease, which is often exacerbated with microbial infections resulting in worsening of respiratory symptoms. Gallic acid (GA), a naturally occurring phenolic compound is known to possess anti-oxidant/anti-inflammatory activity. We have recently reported that GA protects against the elastase (ET) induced lung inflammation and emphysema and the present work was designed to investigate the beneficial effects of Gallic acid against ET + Lipopolysachharide (LPS) induced COPD exacerbation like condition in mice model. Our data showed that i.t. administration of LPS at 21 days after ET instillation resulted in significant infiltration of inflammatory cells particularly neutrophils (p  less then  0.0001) into the lungs along with elevated levels of pro-inflammatory cytokines like TNF-α, IL-1β and IL-6 (p  less then  0.0001). Interestingly, daily administration of GA (200 mg/Kg b. wt.) starting 7 days before ET instillation, significantly blunted the ET + LPS induced inflammation as indicated by reduced number of inflammatory cells particularly neutrophils (p  less then  0.0001) in BALF along with suppression of myeloperoxidase activity (p = 0.0009) and production of pro-inflammatory cytokines (p  less then  0.0001). Further, GA also restored the redox imbalance in the lungs towards normal. Additionally, phosphorylation of p65-NF-κB was found to be reduced (p = 0.015), which was associated with downregulation in the gene expression of IL-1β (p = 0.022) and TNF-α (p = 0.04). Conversely, GA treatment resulted in increased protein levels of Nrf2 (p = 0.021) with concomitant increase in transcription of its downstream target genes HO-1 (p = 0.033) and Prdx-1 (p = 0.006). Overall, our data show that GA effectively modulates COPD exacerbation manifestations in mice potentially by restoring redox imbalance in lungs.Despite significant progress in understanding of dye aggregation, there are still processes that need to be further explored and which can significantly affect aggregation. In this work it was shown that the aggregation of dyes is influenced not only by dye concentration, but also by solvent polarity. It was found that nature, positions and number of fluorescent peaks may be controlled by simultaneous varying of both water fraction and dye concentration. This effect is most pronounced for molecular rotors, which aggregates' geometry may be stabilized in different separate states depending on the aggregation degree. The concentration effect plays a significant role in dye aggregation and should be considered in new studies in order to prevent misinterpretation or to obtain new results in fields of molecular sensing or fine-tuning of fluorescence color. In this paper aggregation caused spectral changes are discussed in line with the dye structure preorganization as the strategy for the fine tuning of practically valuable spectral characteristics.

G175S TBK1 was unable to promote NF-κB signalling above levels observed in empty vector transfected cells. We also noted a hitherto unknown role for TBK1 as a suppressor of oxidative stress (Nrf2) signalling and show that p.G175S TBK1 expressing cells lose this inhibitory function. Our data suggest that TBK1 ALS mutations may broadly impair p62-mediated cell signalling, which ultimately may reduce neuronal survival, in addition TDP-43 was not efficiently degraded, together these effects may contribute to TBK1 mutation associated ALS and FTLD pathogenesis. The purpose of this study was to characterize health behavior profiles among active duty service members and associate these profiles with body-building and weight-loss dietary supplement (DS) use. Based on U.S. active duty service members who completed the 2011 Health-Related Behavior Survey (n=39,877), we used latent class analysis to place respondents into latent classes (using healthy/unhealthy food consumption, aerobic activity, strength training, and sleep) and examined associations between latent class and DS use. We identified seven health behavior classes that could be classified by physical activity and diet. Three classes with high activity were further characterized by healthy diet (24%); few unhealthy foods (18%); and unrestricted diet (9%). Three classes with low activity were further characterized by restricted diet (15%), healthy diet (15%), and unhealthy diet (6%). The last class (13%) reported moderate levels of all behaviors. The classes did not vary by sleep. Participant characteristics across most classes were relatively homogenous along demographics and military branch. The active classes had relatively higher usage of body-building and weight-loss DSs. Latent classes from health behavior indicators might be considered "market segments", which can be targeted with distinct messaging. Service members appear to consume DSs as part of an otherwise healthy lifestyle. Latent classes from health behavior indicators might be considered "market segments", which can be targeted with distinct messaging. Service members appear to consume DSs as part of an otherwise healthy lifestyle. The purpose of this study was to evaluate the association between psychotropic medication use during pregnancy and gestational age at delivery, after adjusting for depressive symptom and perceived stress severity. We analyzed data on singleton live births from 2914 female Pregnancy Study Online participants, aged 21 to 45, with a reported conception from 6/2013 to 6/2018. Women reported psychotropic medication use at 8 to 12weeks' and ~32weeks' gestation. We measured depressive symptoms using the Major Depressive Inventory and perceived stress using the 10-item Perceived Stress Scale. Data on gestational age at delivery were based on self-reports and/or birth certificates. We used restricted mean survival time models, stratifying by severity of depressive symptoms (Major Depression Inventory <25 vs. ≥25) and perceived stress (Perceived Stress Scale <20 vs. ≥20). Two hundred and ten (7.2%) participants reported using psychotropic medications during pregnancy. Mean gestational age at delivery among women who never used psychotropic medications was 38.2weeks (95% confidence interval 37.7, 38.7), whereas it was 37.3weeks (95% confidence interval 36.7, 37.9) among women who used psychotropic medications during pregnancy. Results were similar across strata of depressive symptoms and perceived stress. Our data indicate that the association between psychotropic medication use and gestational age at delivery is not confounded by indication. Our data indicate that the association between psychotropic medication use and gestational age at delivery is not confounded by indication. The purpose of the study was to convert waist circumference (WC) measurements obtained by the World Health Organization (WHO-WC) method to the National Heart, Lung, and Blood Institute (NHLBI-WC) method. During 2016, the National Health and Nutrition Examination Survey participants aged 20 years and older had two different WC measurements taken (n= 2405). The mean differences in the WC between the NHLBI-WC and WHO-WC measurements were calculated. Multivariable prediction models were developed to predict the NHLBI-WC from the measured WHO-WC. Sensitivity and specificity of the abdominal obesity classification (AOC) were calculated for the measured WHO-WC and the predicted NHLBI-WC. Kappa coefficients were calculated to evaluate the agreements between the AOC derived from the NHLBI-WC and from the WHO-WC and the predicted NHLBI-WC. The mean differences between the NHLBI-WC and WHO-WC were 0.8cm for males and 3.2cm for females (P≤.05). Sensitivity of the AOC for the measured WHO-WC was 93% for males and 87% for females, and the specificity of the AOC was 97% or greater for both genders. Sensitivity and specificity of the AOC for the predicted NHLBI-WC were 95% or greater for both genders. The AOC derived from the predicted NHLBI-WC had higher agreements for both genders. The prediction equations provided may be used to predict the NHLBI-WC from the WHO-WC for comparability in WC estimates across studies. The prediction equations provided may be used to predict the NHLBI-WC from the WHO-WC for comparability in WC estimates across studies. We examine whether the race and armed status interact to modify the risk of being fatally shot by police within categories of civilian age and mental illness status, and U.S. region. Data are from The Washington Post online public-use database of all U.S. https://www.selleckchem.com/products/ly333531.html police-involved shooting deaths. The sample includes black and white males with known armed status who were killed from 1/1/2015 through 12/31/2019 (n=3090). A case-only design is used to assess multiplicative interaction using adjusted logistic regression. The fully adjusted interaction estimate is null (S =0.75; 95% confidence interval [CI]=0.55-1.04). However, adjusted estimates within strata show that the risk of being armed versus unarmed when fatally shot is smaller for black than white males older than 54 years (S =0.18; 95% CI=0.06-0.65), those showing mental illness signs (S =0.50; 95% CI=0.26-0.98), and those killed in the South (S =0.52; 95% CI=0.33-0.83), and that the risk is greater in the Midwest (S =2.42; 95% CI=1.11-5.26). Notably, there is no black-white difference in armed status among younger age groups (S ≈0.

Eunkyosan (EKS), also known as the Yinqiaosan formula, is widely applied for the common cold in East Asia. Many clinical trials have reported the efficacy and safety of the EKS formula for the treatment of the common cold. This study aimed to assess the clinical evidence for and against the use of EKS formula as a treatment for the common cold. The following databases were searched from inception to the present MEDINLE, EMBASE, CENTRAL, AMED CINAHL for English articles; OASIS, the Korean Traditional Knowledge Portal, the Korean Studies Information Service System, KoreaMed, the Korean Medical Database and DBPIA); and 3 Chinese databases, including CNKI (i.e., the China Academic Journal, the China Doctoral Dissertations and Master's Theses Full-text Database, the China Proceedings of Conference Full-Text Database and the Century Journal Project), Wanfang and VIP. In addition, we searched a Japanese database and conduct non-electronic searches of conference proceedings. Prospective randomised controlled EKS alone or combined with conventional drugs. CRD42018087694. CRD42018087694.We examine the relationship between dementia and psychiatric disorder diagnoses among long-term care residents in nursing homes across the state of Rhode Island (RI), USA.Observational clinical study.Two hundred fifty-five residents with and without the diagnosis of dementia were included in this study.Prevalence analysis was used to elucidate information on psychiatric disorders in the overall cohort, and among residents with dementia. Questions from the quality of life questionnaire (EQ-5D-3L) that provides information on self-care, anxiety/depression, and resident's view of how healthy they are, were used to evaluate their association with dementia and psychiatric disorders. A logistic regression analysis was conducted to understand the relationship between dementia and mental illness diagnoses in long-term care facilities. Finally, a subgroup logistic regression analysis was performed for residents with Alzheimer disease.65.1% of all residents suffered from at least 1 psychiatric disorder. Anxiety was theip between psychiatric disorders and dementia. Coronary artery disease (CAD) is a clinically common coronary heart disease. Vitamin D might be beneficial in CAD patients through its favorable effects on inflammation biomarkers. This study will be performed to examine the effects of Vitamin D supplementation on inflammatory markers in CAD patients. We will search the electronical databases and hand-searching journals or reference lists. The study screening and data extraction will be carried out by 2 investigators independently. https://www.selleckchem.com/products/Adrucil(Fluorouracil).html The primary outcome is inflammatory biomarkers of peripheral blood. Secondary outcomes are triglyceride, total cholesterol, high-density lipoprotein cholesterol levels, low-density lipoprotein cholesterol, and blood pressure. Review Manager (RevMan, version 5.3; The Nordic Cochrane Centre, Copenhagen, Denmark http//community.cochrane.org) V.5.3 software will be used to compute the data. The results of the study will provide a reliable evidence to assess the efficacy of Vitamin D supplement on inflammation biomarkers of CAD patients. The conclusion of our systematic review will answer whether Vitamin D is an effective intervention to relieve inflammation of CAD patients. Because all of the data used in this review has been published, this review does not require ethical approval. INPLASY202060072. INPLASY202060072. Neck pain is a common musculoskeletal disorder that impacts individuals' daily life, and might sometimes lead to disability and increased medical costs. Pharmacopuncture combines acupuncture with herbal medicine, in which herbal extracts are administered on the acupoints. We designed a pragmatic randomized controlled trial (RCT) to compare the effectiveness of pharmacopuncture and physical therapy as a treatment for chronic neck pain. This study is a 2-armed, parallel, multi-center RCT. The participants will be randomly assigned to pharmacopuncture or physical therapy group to receive their respective 8-session treatments for 4 weeks. The primary outcome is the visual analogue scale of neck pain. Secondary outcomes is the Northwick Park questionnaire, visual analogue scale of radiating arm pain, numeric rating scale of the neck and arm bothersomeness, neck disability index, patient global impression of change, short form-12 health survey version 2, and 5-level EuroQol-5 dimension. This is a protocol for a pragmatic RCT that would attempt to present evidence conducive to clinical decision or policy-making by investigating the effectiveness of pharmacopuncture therapy, a widely used approach in Korean medicine clinical practice, in comparison to the standard therapy. This is a protocol for a pragmatic RCT that would attempt to present evidence conducive to clinical decision or policy-making by investigating the effectiveness of pharmacopuncture therapy, a widely used approach in Korean medicine clinical practice, in comparison to the standard therapy. This systematic review is designed to provide an assessment of the effectiveness and safety of moxibustion therapy for cervical vertigo (CV). Relevant randomized controlled trials (RCTs) will be searched from the databases of PubMed, the Cochrane Library, Embase, the China National Knowledge Infrastructure, Wanfang Database, Chinese Science and Technology Periodical Database, and Chinese Biomedical Literature Database from their inception to June 2020. Two authors will independently select studies, collect data, and assess the methodology quality by the Cochrane risk of bias tool. RevMan V.5.3 software will be used for statistical analysis. The results of this study will provide an assessment of the current state of moxibustion for CV and aim to prove the effectiveness and safety of moxibustion therapy. This systematic review will provide a credible Evidence-based for the treatment of CV with moxibustion. INPLASY202060004. INPLASY202060004. A growing number of studies have used surface-based morphometry (SBM) analyses to investigate gray matter cortical thickness (CTh) abnormalities in Parkinson disease (PD). However, the results across studies are inconsistent and have not been systematically reviewed. A clear picture of CTh alterations in PD remains lacked. Coordinate-based meta-analysis (CBMA) is a powerful tool to quantitatively integrate the results of individual voxel-based neuroimaging studies to identify the functional or structural neural substrates of particular neuropsychiatric disorders. Recently, CBMA has been updated for integrating SBM studies. The online databases PubMed, Embase, Web of Science, China National Knowledge Infrastructure (CNKI), WanFang, and SinoMed were comprehensively searched without language limitations from the database inception to February 2, 2020. We will include all SBM studies that compared regional CTh between patients with idiopathic PD and healthy control subjects at the whole-cortex level using Seed-based d Mapping with Permutation of Subject Images (SDM-PSI).

The acidity of peat-based substrates used in forest nurseries limits seedling mineral nutrition and growth as well as the activity of microorganisms. To our knowledge, no study has yet evaluated the use of granular calcite as a covering material to increase pH, calcium and CO2 concentrations in the rhizosphere and ectomycorrhizal development. The objective is to compare different covering treatments on early colonization of the roots by ectomycorrhizal fungi, as well as the growth and calcium nutrition of white spruce seedlings in the forest nursery. Three treatments were used to cover the plant cavities (Silica (29 g/cavity; control treatment), Calcite (24 g/cavity) and calcite+ (31 g/cavity)) and were distributed randomly inside each of the five complete blocks of the experimental design. The results show that calcite stimulates natural mycorrhization. Seedlings grown with calcite have significant gains for several growth and physiological variables, and that the periphery of their root plugs are more colonized by the extramatrical phase of ectomycorrhizal fungi, thus improving root-plug cohesion. The authors discuss the operational scope of the results in relation to the tolerance of seedlings to environmental stress and the improvement of their quality, both in the nursery and in reforestation sites.Curvature-induced dielectrophoresis (C-iDEP) is an established method of applying electrical energy gradients across curved microchannels to obtain a label-free manipulation of particles and cells. This method offers several advantages over the other DEP-based methods, such as increased chip area utilisation, simple fabrication, reduced susceptibility to Joule heating and reduced risk of electrolysis in the active region. Although C-iDEP systems have been extensively demonstrated to achieve focusing and separation of particles, a detailed mathematical analysis of the particle dynamics has not been reported yet. This work computationally confirms a fully analytical dimensionless study of the electric field-induced particle motion inside a circular arc microchannel, the simplest design of a C-iDEP system. Specifically, the analysis reveals that the design of a circular arc microchannel geometry for manipulating particles using an applied voltage is fully determined by three dimensionless parameters. Simple equations are established and numerically confirmed to predict the mutual relationships of the parameters for a comprehensive range of their practically relevant values, while ensuring design for safety. This work aims to serve as a starting point for microfluidics engineers and researchers to have a simple calculator-based guideline to develop C-iDEP particle manipulation systems specific to their applications.Cephalopods, an appreciated seafood product, are common hosts of marine cestodes. The aim of this work is to report visible alive plerocercoids in longfin inshore squid (Doryteuthis pealeii), a cephalopod species commercialized as fresh and whole in Italy. Seventy D. pealeii from the Northwest Atlantic (FAO area 21) were collected and visually inspected. In total, 18 plerocercoid larvae were found in the viscera of 10 host specimens (P 14.3% 95% CI 7.1-24.7; MI 1.8, MA 0.26; range 1-4) and molecularly analyzed targeting the variable D2 region of the large subunit (LSU) rRNA gene and the cytochrome c oxidase subunit I (COI) gene. The molecular characterization allowed to identify all the plerocercoids as Clistobothrium sp., a cestode of the Phyllobothriidae family with Lamnidae sharks as definitive hosts, and cephalopods as second intermediate hosts. These findings represent the first molecular record of Clistobothrium sp. in D. pealeii, thus contributing to elucidate its poorly known life cycle. Even if not affecting consumer's health, these visible parasites may represent a reason for disgust for consumers. Therefore, the results suggest that Food Business Operators should also check for the presence of these visible parasites during inspection and underline the importance of a correct consumers' education.Plants are under strong evolutionary pressure to maintain surveillance against pathogens. One major disease resistance mechanism is based on NB-LRR (NLR) proteins that specifically recognize pathogen effectors. The cluster organization of the NLR gene family could favor sequence exchange between NLR genes via recombination, favoring their evolutionary dynamics. https://www.selleckchem.com/products/gne-781.html Increasing data, based on progeny analysis, suggest the existence of a link between the perception of biotic stress and the production of genetic diversity in the offspring. This could be driven by an increased rate of meiotic recombination in infected plants, but this has never been strictly demonstrated. In order to test if pathogen infection can increase DNA recombination in pollen meiotic cells, we infected Arabidopsis Fluorescent Tagged Lines (FTL) with the virulent bacteria Pseudomonas syringae. We measured the meiotic recombination rate in two regions of chromosome 5, containing or not an NLR gene cluster. In all tested intervals, no significant difference in genetic recombination frequency between infected and control plants was observed. Although it has been reported that pathogen exposure can sometimes increase the frequency of recombinant progeny in plants, our findings suggest that meiotic recombination rate in Arabidopsis may be resilient to at least some pathogen attack. Alternative mechanisms are discussed.Agriculture has been identified as one of the most vulnerable sectors affected by climate change. In the present study, we investigate the impact of climatic change on dryland wheat yield in the northwest of Iran for the future time horizon of 2041-2070. The Just and Pope production function is applied to assess the impact of climate change on dryland wheat yield and yield risk for the period of 1991-2016. The Statistical Downscaling Model (SDSM) is used to generate climate parameters from General Circulation Model (GCM) outputs. The results show that minimum temperature is negatively related to average yield in the linear model while the relationship is positive in the non-linear model. An increase in precipitation increases the mean yield in either model. The maximum temperature has a positive effect on the mean yield in the linear model, while this impact is negative in the non-linear model. Drought has an adverse impact on yield levels in both models. The results also indicate that maximum temperature, precipitation, and drought are positively related to yield variability, but minimum temperature is negatively associated with yield variability.

Brief spells of nonpositional vertigo that recur throughout the day, phenotypically similar to vestibular paroxysmia, responded to treatment of sleep apnea, and could represent a new vestibular entity. The greatly elevated risk of migraine, Menière's disease and sudden sensorineural hearing loss are likely due to enhanced vascular risks associated with sleep apnea. https://www.selleckchem.com/products/ertugliflozin.html A history of snoring should be sought in all dizzy patients. Brief spells of nonpositional vertigo that recur throughout the day, phenotypically similar to vestibular paroxysmia, responded to treatment of sleep apnea, and could represent a new vestibular entity. The greatly elevated risk of migraine, Menière's disease and sudden sensorineural hearing loss are likely due to enhanced vascular risks associated with sleep apnea. A history of snoring should be sought in all dizzy patients. Waardenburg syndrome (WS) is a rare disorder characterized by varying combinations of sensorineural hearing loss and abnormal pigmentation of the hair and skin. WS is classified into four subtypes (WS1-WS4) based on additional symptoms. Dystopia canthorum is a hallmark of WS type 1. There are two genes linked to WS type 1, including PAX3 and EDNRB. This study aimed to investigate the genetic etiology of WS type 1 in a pair of twins from China with profound hearing loss, blond hair and eyebrows, dystopia canthorum, and brown irides. The target capture sequencing and Whole-exome sequencing were performed to detect mutations in WS-related genes. A novel de novo frameshift mutation, p.L341Rfs*18 in MITF was identified in the twins. Hearing thresholds showed substantial improvements following cochlear implantation with a pure-tone average of 30 dB in free-field conditions. The study showed the new genotype-phenotype correlations of MITF to WS type 1. Further molecular analysis is necessary to reappraise the current classification on WS. The study showed the new genotype-phenotype correlations of MITF to WS type 1. Further molecular analysis is necessary to reappraise the current classification on WS. In 2012 the first active bone conduction implant was introduced, but did not fit into the mastoids of some adults and many children. Thus, a geometry change of the transducer was proposed (BCI 602). In this study, we aimed to determine whether these changes improved the mastoid cavity fit of the implant in children and young adults. We retrospectively analyzed computed tomography scans of 151 mastoids from 81 children and adolescents (age range, 5 mo to 20 yr) and 52 control mastoids from 33 adults. After three-dimensional reconstruction of the temporal bone from computed tomography, we virtually implanted the BCI 602 into the mastoids, and compared the bone fit with that of the BCI 601. The BCI 602 could be virtually implanted in 100% of patients ≥12 years old, while the BCI 601 transducer could be completely embedded in the bone of only 70% of these mastoids. Moreover, virtual implantation of the BCI 602 was possible in 75% of children 3 to 5 years of age, while the BCI 601 did not fit in the mastoids of any patients under 5 years old without the use of lifts. Compared to the BCI 601, placement of the BCI 602 allegedly requires less bone removal. The newer BCI 602 transducer is more likely than its predecessor to be completely accommodated in the mastoid bone among all age groups and indications. Preoperative planning is still recommended to avoid exposure of delicate structures. Compared to the BCI 601, placement of the BCI 602 allegedly requires less bone removal. The newer BCI 602 transducer is more likely than its predecessor to be completely accommodated in the mastoid bone among all age groups and indications. Preoperative planning is still recommended to avoid exposure of delicate structures. Temporal bone osteoradionecrosis (TBORN) is a rare, chronic complication of head and neck radiation. Initial treatment consists of conservative management, with surgical resection of necrotic bone indicated for cases of severe, symptomatic, or progressive disease. Pentoxifylline-tocopherol (PENTO) has demonstrated usefulness for osteoradionecrosis of other head and neck subsites. Herein, we report five TBORN cases utilizing this protocol. Retrospective case series. Tertiary referral center. This case series describes five TBORN cases in which the PENTO protocol was used in conjunction with conservative management. All patients were women and average age was 61 ± 8 years. All patients received a daily dose of 800 mg of pentoxifylline and 1 g of tocopherol. Four of the five patients received systemic and/or ototopical antibiotics as an antimicrobial regimen before and/or during the PENTO protocol. Details regarding the total duration of protocol, improvement in symptoms, exposed bone and radiographic changes, and duration until first improvement of exposed bone were collected retrospectively. The average duration of PENTO protocol was 302 ± 166 days. Four of the five (80%) patients demonstrated a decrease in exposed ear canal bone. Three of the five (60%) patients had stable or improvement in otologic symptoms of TBORN. One patient progressed to diffuse TBORN. The average duration until first improvement in exposed bone was 193 ± 137 days. The PENTO protocol may be a useful adjunct to conservative measures in the management of localized TBORN. We recommend trialing the protocol for at least 12 months. The PENTO protocol may be a useful adjunct to conservative measures in the management of localized TBORN. We recommend trialing the protocol for at least 12 months. The Food and Drug Administration (FDA) has recently raised concern regarding the safety of cochlear implantation in the setting of programmable cerebrospinal fluid shunts. The purpose of this study was to evaluate the outcomes and complications of cochlear implantation in children who have a cerebrospinal fluid shunt. Retrospective chart review. Tertiary academic referral center. Twenty pediatric subjects with a cerebrospinal fluid shunt and cochlear implant (CI). Cochlear implantation in the setting of a cerebrospinal fluid shunt. Primary outcome measures included descriptive data regarding age at implantation, etiology of hearing loss, medical management, complications, and speech perception outcomes. The average age of CI candidacy was 30 months with an average 21.5 months delay to implantation. In 45% of cases the laterality of the shunt determined the ear to be implanted. Three of the subjects required a surgical intervention on the shunt before cochlear implantation. Three subjects had a concurrently programmable shunt and activated CI.

ificant differences were detected in the improvements of BCVA or CRT and injection numbers between the IVR and IVA groups treated with the TAE regimen. These results indicate that the results of the treatment with both agents with the TAE regimen were equally effective, but only 20.8% of patients completed 24 months of continuous treatment with the TAE regimen. Synopsis There are no significant differences regarding effectiveness between the IVR and IVA groups treated with the TAE regimen for DME eyes.Risperidone (RSP) is an atypical antipsychotic drug widely used to treat schizophrenia and bipolar disorder. Nanoparticles (NPs) are being developed as in vivo targeted drug delivery systems, which cross the blood-brain barrier and improve pharmacokinetics and drug effectiveness. Here, biodegradable proteinoids were synthesized by thermal step-growth polymerization from the amino acids l-glutamic acid, l-phenylalanine and l-histidine and poly (l-lactic acid). Proteinoid NPs containing RSP were then formed by self-assembly, overcoming the insolubility of the drug in water, followed by PEGylation (poly ethylene glycol (PEG) conjugation to increase the stability of the NPs in the aqueous continuous phase. These NPs are biodegradable owing to their peptide and ester moieties. They were characterized in terms of diameter, size distribution, drug loading, and long-term storage. Behavioral studies on mice found enhanced antipsychotic activity compared to free RSP.The effect of intubation timing on the prognosis of critically ill patients with coronavirus 2019 (COVID-19) is not yet well understood. We investigated whether early intubation is associated with the survival of COVID-19 patients with acute respiratory distress syndrome (ARDS). This multicenter, retrospective, observational study was done on 47 adult COVID-19 patients with ARDS who were admitted to the intensive care unit (ICU) in Daegu, Korea between February 17 and April 23, 2020. Clinical characteristics and in-hospital mortality were compared between the early intubation and initially non-intubated groups, and between the early and late intubation groups, respectively. Of the 47 patients studied, 23 (48.9%) were intubated on the day of meeting ARDS criteria (early intubation), while 24 (51.1%) were not initially intubated. Eight patients were never intubated during the in-hospital course. Median follow-up duration was 46 days, and 21 patients (44.7%) died in the hospital. No significant difference in in-hospital mortality rate was noted between the early group and initially non-intubated groups (56.5% vs. 33.3%, p = 0.110). Furthermore, the risk of in-hospital death in the early intubation group was not significantly different compared to the initially non-intubated group on multivariate adjusted analysis (p = 0.385). Results were similar between early and late intubation in the subgroup analysis of 39 patients treated with mechanical ventilation. In conclusion, in this study of critically ill COVID-19 patients with ARDS, early intubation was not associated with improved survival. This result may help in the efficient allocation of limited medical resources, such as ventilators.This study aims to investigate which maternal body mass index (BMI) categories are associated with the non-initiation or cessation of breastfeeding (BF) based on a quantitative review of the literature. We searched Ovid MEDLINE and EBSCO CINAHL for peer-reviewed articles published between 1946 (MEDLINE) or 1981 (CINAHL), and 2019. Selected studies were either cross-sectional or cohort studies, of healthy mothers and infants, that reported nutrition method (exclusive/full or any) and period (initiation/duration/cessation) of breastfeeding according to maternal BMI levels. Pairwise meta-analyses of 57 studies demonstrated that the pooled odds risks (OR) of not initiating BF among overweight and obese mothers compared to normal weight mothers were significant across 29 (OR 1.33, 95% confidence interval (CI), 1.15-1.54, I2 = 98%) and 26 studies (OR 1.61, 95% CI, 1.33-1.95, I2 = 99%), respectively; the pooled risks for BF cessation were inconsistent in overweight and obese mothers with substantial heterogeneity. However, we found that overweight mothers (n = 10, hazard ratio (HR) 1.16, 95% CI, 1.07-1.25; I2 = 23%) and obese mothers (n = 7, HR 1.45, 95% CI 1.27-1.65; I2 = 44%) were both associated with an increased risk of not continuing any BF and exclusive BF, respectively. Overweight and obese mothers may be at increased risk of not initiating or the cessation of breastfeeding. The purpose of this study was to evaluate the traits of orthorexia nervosa (ON) and its relation to body composition and anthropometric indices among elite athletes. We studied 273 (125 female, 148 male) competitive athletes. https://www.selleckchem.com/products/mv1035.html ON was assessed with the self-administered ORTO-15 questionnaire. Total body composition was determined using dual-energy X-ray absorptiometry (DXA). The ORTO-15 score was independent of sex, type of effort or age. The ORTO-15 score was related to total body mass (TBM) ( = 0.037; = 0.170), body mass index (BMI) ( = 0.022; = 0.187), bone mineral content (BMC) ( = 0.035; = 0.172), lean soft tissue ( = 0.026; = 0.182) and visceral adipose tissue (VAT) ( = 0.007; = 0.255) in the male; BMI ( = 0.045; = 0.412) and BMC ( = 0.012; = 0.506) in weight-dependent male athletes. There was no relationship between ORTO-15 score and body composition in the total study group and subgroup of female athletes. In female athletes, ON tendencies were related to the weekly training time ( = 0.039), but in sprint and high-intensity intermittent efforts subgroup exclusively. Factors related to ON tendencies concerned exclusively BMI and body composition in male, and the weekly training time in female athletes. The results from this study demonstrate that a significant percentage of athletes, irrespective of sex, age, type of sport or hours of training per week, may manifest traits of orthorexia nervosa. Factors related to ON tendencies concerned exclusively BMI and body composition in male, and the weekly training time in female athletes. The results from this study demonstrate that a significant percentage of athletes, irrespective of sex, age, type of sport or hours of training per week, may manifest traits of orthorexia nervosa.

EEA may be a cost-effective alternative to transcranial approaches for selected OGM. Charcot-Marie-Tooth (CMT) disease is diagnosed through clinical findings and genetic testing. While there are neurophysiological tools and clinical functional scales in CMT, objective disease biomarkers that can facilitate in monitoring disease progression are limited. To investigate the utility of diffusion tensor imaging (DTI) in determining the microstructural integrity of sciatic and peroneal nerves and its correlation with the MRI grading of muscle atrophy severity and clinical function in CMT as determined by the CMT neuropathy score (CMTNS). Prospective case-control. Nine CMT patients and nine age-matched controls. 3 T T -weighted in-/out-of phase spoiled gradient recalled echo (SPGR) and DTI sequences. Fractional anisotropy (FA), axial diffusivity (AD), radial diffusivity (RD), and mean diffusivity (MD) values for sciatic and peroneal nerves were obtained from DTI. Muscle atrophy was graded according to the Goutallier classification using in-/out-of phase SPGRs. DTI parameters and muscleorrelations between DTI parameters, muscle atrophy grade, and CMTNS. https://www.selleckchem.com/products/gf109203x.html Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53437-444. There were significant differences of DTI parameters between CMT and controls, with significant correlations between DTI parameters, muscle atrophy grade, and CMTNS. Level of Evidence 2 Technical Efficacy Stage 2 J. MAGN. RESON. IMAGING 2021;53437-444. Trichosporon asahii is the major causative agent of disseminated and deep-seated trichosporonosis. It is capable of forming biofilms on surfaces, leading to medical device-related infection.Trichosporon asahii may be present as yeast form, hyphae and/or arthroconidia; however, the relationship between its biofilm-forming ability and its morphological transition is unclear. We investigated whether the T.asahii morphological transition contributes to its biofilm formation. We also determined the conditions required to induce each of the morphologies. Three high- and three low-biofilm-producing strains (HBS and LBS, respectively) were selected using a biofilm formation assay, and the cell surface hydrophobicity of these six strains was measured. For each strain, the morphology was observed and the number of each morphological form (yeast form, hypha and arthroconidium) was counted to calculate the ratio. Finally, the ability of cells each morphological type to adhere to the polystyrene substrate was evaluated. The HBS exhibited abundant arthroconidia and hyphae; in contrast, the LBS produced mainly hyphae with few or no arthroconidia. The production of hyphae was increased by nitrogen-containing medium, and the production of arthroconidia was increased by nitrogen-deficient medium. Cells incubated under nitrogen-deficient conditions showed higher adherence to a polystyrene surface than those incubated in the presence of nitrogen. Arthroconidia of T.asahii play a key role in biofilm formation by promoting cellular adhesion. Arthroconidia of T. asahii play a key role in biofilm formation by promoting cellular adhesion. In recent years, methylene blue mediated-photodynamic therapy (MB-PDT) has proved to be an effective inhibitor to a variety of microorganisms, including Trichophyton rubrum, the most common dermatophyte worldwide. However, previous studies mainly focused on the spore form of Trubrum, but rarely on its hyphal form, although the latter is the main pathogenic form of Trubrum in vivo. To investigate the inhibitory effect of MB-PDT on Trubrum in different growth phases in vitro. The suspensions of spores and hyphae obtained from Trubrum (ATCC28188) were prepared, respectively, incubated with MB solution (0.15-40μg/mL) and irradiated with 635nm red light. Varied light energy and MB concentration were used. The specimen in the absence of light exposure or/and MB served as controls. MIC determination, colony counts and MTT assay were employed to evaluate the antifungal effect of MB-PDT. The MICs of MB-PDT for hyphae and spores of T. rubrum were 6.300±1.072μg/mL and 1.984±1.072μg/mL, respectively, at a fixed light dose of 60J/cm . CFU counts gave the minimum critical combinations of MB concentration and light dose to achieve 100% inhibitory rate. For hyphae, they were 5μg/mL+100J/cm or 10μg/mL+60J/cm . For spores, they were 1.25μg/mL+40J/cm or 5μg/mL+20J/cm . The outcomes of MTT assay were consistent with those of CFU counts, but less accurate. MB-PDT is a potent inhibitor to both spores and hyphae of T. rubrum in vitro, and the spores are more sensitive to it. Its antifungal efficacy is positively correlated with the concentration of MB and light dose. MB-PDT is a potent inhibitor to both spores and hyphae of T. rubrum in vitro, and the spores are more sensitive to it. Its antifungal efficacy is positively correlated with the concentration of MB and light dose. To assess changes in glucose metrics and their association with psychological distress and lifestyle changes in patients with type 1 diabetes (T1D) using flash glucose monitoring (FGM) during lockdown following severe acute respiratory syndrome coronavirus 2 outbreak. Single-centre, observational, retrospective study enrolling T1D patients who attended a remote visit on April 2020 at the Endocrinology division of the University Hospital Policlinico Consorziale, Bari, Italy. Lockdown-related changes in physical activity level and dietary habits were assessed on a semi-quantitative basis. Changes in general well-being were assessed by the General Health Questionnaire-12 items with a binary scoring system. Glucose metrics were obtained from the Libreview platform for the first 2 weeks of February 2020 (T0) and the last 2 weeks before the phone visit (T1). Out of 84 patients assessed for eligibility, 48 had sufficient FGM data to be included in the analysis. FGM data analysis revealed significant reductions in coefficient of variation, number of hypoglycaemic events, and time below range, while no changes were found in time in range, time above range, mean sensor glucose, and glucose management indicator. Moreover, the frequency of sweets consumption was inversely related to the occurrence of hypoglycaemic events during lockdown. Lockdown-related lifestyle changes, albeit unhealthy, may lead to reduction in FGM-derived measures of hypoglycaemia and glycaemic variability in patients with T1D. Lockdown-related lifestyle changes, albeit unhealthy, may lead to reduction in FGM-derived measures of hypoglycaemia and glycaemic variability in patients with T1D.

Increased inflammation can be observed in the closed eye tears of subjects with dry eye disease, and neutrophils may be a potential source of pathogenic species in dry eye disease. Further research is required to determine the diagnostic potential of closed eye tears. Increased inflammation can be observed in the closed eye tears of subjects with dry eye disease, and neutrophils may be a potential source of pathogenic species in dry eye disease. Further research is required to determine the diagnostic potential of closed eye tears.Coronavirus disease-19 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 is closely related to two other coronaviruses that caused disease epidemic breakouts in humans in the last 2 decades, namely, severe acute respiratory distress syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). The similarities have enabled the scientists to apply the basic scientific discoveries garnered from studying the structure and modus operandi of SARS-CoV and MERS-CoV to develop therapies that specifically target SARS-CoV-2 and to develop vaccines to prevent COVID-19. Targeted therapies including the use of antibodies to prevent virus entry, nucleotide analogues to prevent viral replication, and inhibitors of proteases to prevent virion formation, among others, are being tested for their clinical efficacy. https://www.selleckchem.com/products/ml355.html Likewise, complete sequencing of the SARS-CoV-2 and identification of its structural and nonstructural proteins have enabled development of RNA-, DNA-, and peptide-based vaccines as well attenuated viral vaccines to instigate the host-immune responses. The clinical impacts of the basic science discoveries are amply evident on the rapid pace of progress in developing specific antiviral therapies and vaccines against SARS-CoV-2. The progress emphasizes the merit of discovering the fundamental scientific elements, regardless of whether or not they have apparent or immediate clinical applications.This paper reports on a comprehensive in silico toxicity assessment of Salubrinal and its analogues containing a cinnamic acid residue or quinoline ring using the online servers admetSAR, ADMETlab, ProTox, ADVERPred, Pred-hERG and Vienna LiverTox. Apart from rare exceptions, in all 55 studied structures, mild or practical absence of acute toxicity was predicted for rats (III or IV toxicity class). Cardiotoxic, hepatotoxic and immunotoxic effects were predicted for Salubrinal and its analogues. We constructed models of the main predicted anti-targets hERG, BSEP, MRP3, MRP4 and AhR using the principle of homologous modeling. Molecular docking studies were carried out with the obtained models. We carried out molecular docking for all targets using AutoDock Vina, implemented in the PyRx 0.8 software package. According to the results of molecular docking, the compounds analyzed are potential moderate or weak hERG blockers. Induction of cholestasis and, as a consequence, liver damage by these drugs, directly related to inhibition of BSEP, MRP3 and MRP4, most likely will not be observed. Interaction with AhR for the studied compounds is impossible for steric reasons and, as a consequence, toxic effects on the immune and other organ systems associated with the activation of the AhR signaling pathway are excluded. To determine how foot structure and lower limb function differ between individuals with and without midfoot osteoarthritis (OA). Electronic databases were searched from inception until May 2020. To be eligible, studies needed to (1) include participants with radiographically confirmed midfoot OA, with or without midfoot symptoms, (2) include a control group of participants without radiographic midfoot OA or without midfoot symptoms, and (3) report outcomes of foot structure, alignment, range of motion or any measures of lower limb function during walking. Screening and data extraction were performed by two independent assessors, with disagreements resolved by a third independent assessor. The methodological quality of included studies was assessed using the National Institutes of Health Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies. A total of 1,550 records were screened by title and abstract and 11 met the inclusion criteria. Quantitative synthesis indicated that individuals who had midfoot OA had a more pronated foot posture, greater first ray mobility, less range of motion in the subtalar joint and first metatarsophalangeal joints, longer central metatarsals and increased peak plantar pressures, pressure time integrals and contact times in the heel and midfoot during walking. Meta-analysis could not be performed as the data were not sufficiently homogenous. There are several differences in foot structure and lower limb function between individuals with and without midfoot OA. Future research with more consistent case definitions and detailed biomechanical models would further our understanding of potential mechanisms underlying the development of midfoot OA. There are several differences in foot structure and lower limb function between individuals with and without midfoot OA. Future research with more consistent case definitions and detailed biomechanical models would further our understanding of potential mechanisms underlying the development of midfoot OA. To analyze clinical, metabolic, hormonal, and ultrasound characteristics of adolescents with polycystic ovary syndrome phenotypes. We performed a retrospective analysis of quality improvement data. We divided patients according to phenotype on the basis of clinical or biochemical diagnosis of hyperandrogenism (HA), irregular menstruation (IM), and presence or absence of polycystic ovarian morphology (PCOM) on pelvic ultrasound (PUS) images, if obtained. The 5 resulting groups were (1) HA/IM/normal PUS, n=28; (2) HA/PCOM, n=10; (3) IM/PCOM, n=18; (4) HA/IM/PCOM, n=40; and (5) HA/IM/no PUS obtained, n=80. We compared parameters between groups using the nonparametric Wilcoxon rank sum test. Boston Children's Hospital, 2012-2016. One hundred seventy-six girls and young women aged 11-25years. None. (1) Clinical, metabolic, and hormonal characteristics; and (2) PUS measurements. Groups with HA had significantly higher acne scores, Ferriman-Gallwey scores, and total and free testosterone concentrations than groups without HA.