Under the radar biologic medicine organometallic processes using identified constructions tend to be carrying on swiftly inside fighting malignant malignancies due to their multipronged treatment method techniques. Several revolutionary superiorities, like large antitumor activity, very low wide spread poisoning, active focusing on ability, that has been enhanced cellular customer base, make them more skilled regarding specialized medical programs as compared to person precursors. Particularly, coordination-induced unsafe effects of luminescence and photophysical properties involving organic and natural light-emitting ligands has revealed important possible from the well-timed look at therapeutic efficacy simply by bioimaging and empowered hand in hand photodynamic remedy (PDT) or perhaps photothermal therapy (PTT). This particular review features instructional instances of multimodal radiochemotherapy websites with regard to cancer malignancy ablation according to self-assembled metallacycles/metallacages, which may always be listed in functions in a progressive way. Ultimately, the fundamental demands and a few plausible prospects in this subject for cancer treatments are also presented.Tribovoltaic nanogenerators (TVNG) signify an incredible chance of developing low-frequency power cropping along with self-powered realizing, by taking advantage of their real-time direct-current (Power) productivity. Right here, an intensive study of the effect of relative dampness (RH) with a TVNG made up of 4H-SiC (n-type) and also material birdwatcher aluminum foil (SM-TVNG) is introduced. The actual SM-TVNG exhibits an amazing level of sensitivity in order to RH as well as an unusual RH addiction. Any time RH raises coming from normal humidity around 80%, an increasing electrical productivity is observed. However, while RH increases coming from 80% in order to 98%, your transmission output not simply decreases, however its course turns around as it passes across 90% RH. This specific actions may differ tremendously through that of a Si-based TVNG, whose result consistently raises together with RH. The behaviour in the SM-TVNG may possibly derive from your competition relating to the built-in electric powered field caused by simply metal-semiconductor speak to along with a powerful triboelectric power area activated by solid-liquid triboelectrification beneath large RH. The particular experts furthermore revealed that each SM-TVNG and also Si-based TVNG can work effectively as-is even fully sunken throughout deionized normal water. This procedure could affect additional AZD2014 order gadgets and be put on design self-powered devices functioning below large RH or underwater.2nd MXene-Ti3 C2 Texas holds great guarantee in numerous electric programs, specifically electromagnetic interference (EMI) shielding units along with supercapacitors. Ti3 C2 Tx activity typically involves the usage of Microscopes dangerous fluorine-containing chemical substances that can lead to the development associated with inert fluoride functional groups on top regarding Ti3 C2 Colorado , significantly degrading it’s components and also baring almost all a menace to the functionality involving electron transfer amongst electric powered gadgets. Herein, a supercritical carbon dioxide dioxide-based ternary remedy (scCO2 /DMSO/HCl) to generate fluoride-free Ti3 C2 Colorado in gentle circumstances (by way of 0.

Especially, the repaired level can be recognized when it comes to spin-spin correlation functions. Direct problem range for the approximation involving procession relationship features are shown.Files on likelihood, incidence along with stress involving ADHD are crucial for physicians, people, along with stakeholders. All of us present the likelihood, incidence, along with burden regarding ADHD globally along with over nations coming from 2001 to 2019 from the World-wide Burden associated with Condition (GBD) review. We (One particular) worked out your Add and adhd incidence determined by info actually obtained rather than frequency approximated with the GBD with information selleck imputation for nations without having incidence files; (A couple of) discussed the particular GBD estimated Add and adhd load in the mild of recent meta-analytic evidence about ADHD-related death. Inside 2019, GBD projected world-wide age-standardized chance as well as epidemic of Attention deficit hyperactivity disorder through the life-span in 3.061% (95%UI = 0.040-0.087) along with A single.13% (95%UI = 0.831-1.494), respectively. Attention deficit hyperactivity disorder included Zero.8% in the world-wide mind condition DALYs, together with death established from no from the GBD. Via 1990 to be able to 2019 there was clearly a new loss of -8.75% in the world-wide age-standardized prevalence in addition to -4.77% inside the global age-standardized likelihood. The largest boost in likelihood, preure models.In-vivo accumulation review is a action before scientific advancement and is nonetheless the primary way to obtain data with regard to all round danger review of your fresh genetic marker molecular organization (NCE). Just about all in-vivo studies are done as outlined by regulatory demands and several initiatives have been applied to attenuate these kind of research depending on the (Replacement, Lowering along with Processing) 3Rs principle. Several facets of in-vivo toxicology offers can be seo’ed to scale back animal employ, including the quantity of studies executed as well as examine trips, the actual main emphasis of this analysis. We all performed a new record evaluation regarding negative results affecting 116 short-term compared to 77 long-term in-house as well as in-house financed Contract Study Agencies (CRO) scientific studies, to be able to discover the opportunity of using only short-term research as being a conjecture tool for your longer-term results. Every one of the info analyzed in this examine had been personally purchased from the particular toxicology studies (throughout PDF formats) to make the dataset. Annotationportant aspects of pet investigation reproducibility are usually pointed out in this operate, specifically, require the reproducible uncomfortable side effects confirming method along with using the controlled terms in-vivo toxicology accounts and finally the significance of open-source systematic workflows which can be assessed by some other experts in neuro-scientific preclinical toxicology.Civilized prostatic hyperplasia (BPH) is often a continual, progressive ailment seen as mesenchymal cell-predominance and stromal along with glandular cell-hyperproliferation. Even though, the actual adult-onset immunodeficiency reason behind BPH is actually unidentified, it really is believed to be related to hormonal modifications in ageing males.

Especially, the repaired level can be recognized when it comes to spin-spin correlation functions. Direct problem range for the approximation involving procession relationship features are shown.Files on likelihood, incidence along with stress involving ADHD are crucial for physicians, people, along with stakeholders. All of us present the likelihood, incidence, along with burden regarding ADHD globally along with over nations coming from 2001 to 2019 from the World-wide Burden associated with Condition (GBD) review. We (One particular) worked out your Add and adhd incidence determined by info actually obtained rather than frequency approximated with the GBD with information selleck imputation for nations without having incidence files; (A couple of) discussed the particular GBD estimated Add and adhd load in the mild of recent meta-analytic evidence about ADHD-related death. Inside 2019, GBD projected world-wide age-standardized chance as well as epidemic of Attention deficit hyperactivity disorder through the life-span in 3.061% (95%UI = 0.040-0.087) along with A single.13% (95%UI = 0.831-1.494), respectively. Attention deficit hyperactivity disorder included Zero.8% in the world-wide mind condition DALYs, together with death established from no from the GBD. Via 1990 to be able to 2019 there was clearly a new loss of -8.75% in the world-wide age-standardized prevalence in addition to -4.77% inside the global age-standardized likelihood. The largest boost in likelihood, preure models.In-vivo accumulation review is a action before scientific advancement and is nonetheless the primary way to obtain data with regard to all round danger review of your fresh genetic marker molecular organization (NCE). Just about all in-vivo studies are done as outlined by regulatory demands and several initiatives have been applied to attenuate these kind of research depending on the (Replacement, Lowering along with Processing) 3Rs principle. Several facets of in-vivo toxicology offers can be seo’ed to scale back animal employ, including the quantity of studies executed as well as examine trips, the actual main emphasis of this analysis. We all performed a new record evaluation regarding negative results affecting 116 short-term compared to 77 long-term in-house as well as in-house financed Contract Study Agencies (CRO) scientific studies, to be able to discover the opportunity of using only short-term research as being a conjecture tool for your longer-term results. Every one of the info analyzed in this examine had been personally purchased from the particular toxicology studies (throughout PDF formats) to make the dataset. Annotationportant aspects of pet investigation reproducibility are usually pointed out in this operate, specifically, require the reproducible uncomfortable side effects confirming method along with using the controlled terms in-vivo toxicology accounts and finally the significance of open-source systematic workflows which can be assessed by some other experts in neuro-scientific preclinical toxicology.Civilized prostatic hyperplasia (BPH) is often a continual, progressive ailment seen as mesenchymal cell-predominance and stromal along with glandular cell-hyperproliferation. Even though, the actual adult-onset immunodeficiency reason behind BPH is actually unidentified, it really is believed to be related to hormonal modifications in ageing males.

To address this gap, also to inform primate preservation exercise and also policy, we implemented yearly studies to Eighty one families over six consecutive a few months (September 2018 in order to March 2019) in a community around the edge of Kirindy Mitea National Park, Madagascar. Many of us observed extreme deprivation ratings across numerous measurements of low income and discovered ninety-five pct of households while ‘impoverished’. Of those, three-quarters (77%) of households had been identified as finding myself ‘severe poverty’. One-fifth (19%) of all homes hunted lemurs as well as 50 percent (49%) of households eaten lemurs. While lower income removal is definitely an urgent need throughout towns around Kirindy Mitea National Park, our conclusions display zero connection involving poverty along with lemur searching and also intake, maybe due to not enough alternative throughout poverty. Each of our results high light the need to examine various other contributory aspects in order to lemur searching and also intake locally. Since meals self deprecation can be a known driver associated with lemur looking along with ingestion among the review group, and also, since household meat could be desired over shielded kinds, we suggest tests your efficiency of livestock interventions in close proximity to Kirindy Mitea Park.Fissure within the next metacarpal/tarsal parasagittal pattern as well as proximal phalanx sagittal pattern is a prospective prodromal pathology of fracture; as a result, earlier detection and also characterisation associated with fissures employing non-invasive photo could be involving scientific benefit. Thirty-three horse cadaver braches underwent standing cone-beam (CB) computed tomography (CT), fan-beam (Myspace) CT, low-field magnetic resonance imaging (MRI), as well as macro/histo-pathological examination. Image medical determinations regarding fissures ended up compared to microscopic exam. Photo features of fissures were explained. Histopathological conclusions were obtained and also when compared between locations together with and also without fissures upon CT. Infinitesimal exam determined 114/291 locations together with fissures. The actual analytic level of sensitivity and also specificity have been Eighty eight.5% and also Sixty one.3% for CBCT, 86.1% and 72.3% regarding FBCT, as well as Forty three.6% as well as Eighty five.2% pertaining to MRI. A number of forms of photo features of fissures have been characterised about CT (A single) CBCT/FBCT hypoattenuating linear problems, (Two) CBCT/FBCT striated hypoattenuated lines, (Three) CBCT/FBCT subchondral irregularity, along with (Some) CBCT striated hypoattenuating outlines as well as FBCT subchondral irregularity. Fissures upon MRI appeared as subchondral navicular bone hypo-/hyperintense flaws. Microscopic scores of subchondral bone sclerosis, microcracks, and also fall were drastically greater throughout areas along with CT-identified fissures. All imaging strategies had the ability to recognize fissures. Fissures identified about CT were connected with histopathology regarding tiredness incidents.Blood sugar stage throughout birds’ cells decreases as a result of heat strain (HS)-induced decrease in supply consumption (FI); affecting metabolic process progress. The effect associated with carbs and glucose supplements about the performance regarding broiler flock was evaluated below thermoneutral (Tennessee) along with HS conditions.

Results Cancer-related family genes that are frequently employed within NGS-based cancer malignancy cells have been decided on since the goal genetics. Target strains medullary rim sign have been selected based on their own consistency documented throughout database, along with medical importance and on the actual applicability involving CRISPR/Cas9 simply by contemplating range from PAM web site, as well as off-targets. We now have properly produced 88 hetero- as well as homozygous mutant cellular traces with the targeted websites associated with Thirty-six genetics addressing when using 125 strains. Results These knock-in HEK293T/17 tissue can be used the reference mutant standards using a continuous and continuous provide for NGS-based most cancers screen checks through the JCRB mobile or portable bank. Additionally, these kind of cellular lines late T cell-mediated rejection provides an instrument for your well-designed analysis regarding Pterostilbene specific mutations in cancer-related genetics from the isogenic track record. © The Author(azines) 2020.Backgound A variety of throughout vivo as well as in vitro research to guage the actual genotoxicity regarding titanium dioxide nanoparticles (TiO2 NPs) happen to be noted, though the outcomes are inconsistent. Just lately, all of us reported which TiO2 NPs demonstrate no genotoxic outcomes inside the liver organ and also erythrocytes throughout a comparatively quick period pursuing intravenous shot into rats. However, there’s no details about long-term genotoxicity due to TiO2 NP piling up inside tissues. Within this research, we investigated the particular long-term mutagenic effects of TiO2 NPs and also the localization regarding left over TiO2 NPs throughout mouse button hard working liver following numerous medication shots. Outcomes Man gpt delta C57BL/6 J rats have been implemented with some other doses of TiO2 NPs weekly with regard to Some consecutive months. The actual long-term mutagenic consequences about the hard working liver had been reviewed employing gpt as well as Spi- mutation assays 90 days following your last procedure. We quantified the volume of titanium from the lean meats utilizing inductively combined plasma bulk spectrometry and also seen your localization regarding TiO2 NPs from the liver employing transmitting electron microscopy. Even though TiO2 NPs were found inside the lean meats tissues, the particular gpt as well as Spi- mutation frequencies from the liver organ just weren’t significantly elevated through the TiO2 NP supervision. Conclusions These kind of results demonstrate in which TiO2 NPs have no mutagenic consequences around the hard working liver, although allergens remain in your liver long-term. © The article author(s) 2020.Many of us below describe true of the 43-year-old White girl who was identified as having arthritis rheumatoid treated with anti-tumour necrosis issue medicines that will induced a detrimental medicine response. The objective of this research was to describe the outcome of your pregnancy under baricitinib, the JAK-inhibitor medicine, inside a lady afflicted with arthritis rheumatoid. Scant files can be purchased regarding the protection associated with JAK inhibitors in pregnancy. An incident document along with report on books with regards to JAK-inhibitor exposure while pregnant had been carried out.

You can expect data that will in addition to canonical signaling, DVL1 stimulates tight 4 way stop (TJ) stabilization by way of a fresh, non-canonical signaling process concerning direct claudin-5 (CLDN5) holding. Immunofluorescence staining Lysates And Extracts associated with rat retinal cross-sections demonstrated ripe appearance regarding DVL1 and three from endothelial capillaries and co-localization together with CLDN5 and ZO-1 on the TJ complex within major bovine retinal endothelial cellular material (BRECs). Obstacle core biopsy attributes of BRECs had been determined by way of dimensions involving trans-endothelial electrical level of resistance (TEER) or even leaks in the structure to be able to 70 kDa RITC-dextran. These kind of reports demonstrated that norrin restoration regarding obstacle attributes right after VEGF treatment needed DVL1 as a possible siRNA knockdown of Dvl1 and not Dvl2 or Dvl3, DVL1 that contains the PDZ-BM or via erradication regarding CLDN5 PDZ-BM. In BREC tissue, transfection from the C-terminal fragment regarding DVL1 downregulates the particular expression involving CLDN5 yet does not affect your expression of various other meats with the TJs, which include ZO-1, occludin, CLDN1 as well as VE-cadherin. Hindering DVL1/CLDN5 conversation elevated basal leaks in the structure as well as avoided norrin induction associated with obstacle qualities following VEGF. Combined with previous files, these kinds of results show norrin alerts by means of the two a new canonical β-catenin pathway plus a non-canonical signaling pathway in which DVL1 straight binds in order to CLDN5 in promoting hurdle attributes.Any cell’s hardware properties have already been connected to cancers advancement, mobility and metastasis and they are Mycophenolate mofetil mouse consequently a stylish targeted as being a common, reputable most cancers sign. As an example, it is often commonly posted which most cancers tissue display a reduced Young’s modulus than their non-cancerous alternatives. Furthermore, the result associated with anti-cancer medications about cell technicians offer a whole new clues about supplementary mechanisms associated with action along with substance performance. Deciphering ion conductance microscopy (SICM) supplies a nanoscale quality, non-contact technique of nanomechanical files acquisition. With this review, all of us utilized SICM to determine the particular nanomechanical qualities of cancer mobile or portable collections from various periods along with increasing metastatic capacity. Young’s modulus adjustments subsequent therapy with all the anti-cancer medications paclitaxel, cisplatin and dacarbazine were in addition assessed, supplying a story viewpoint by making use of continuous scan function SICM. All of us discovered that Young’s modulus ended up being inversely linked for you to metastatic potential in melanoma cellular traces through radial expansion, up and down progress and also metastatic levels. Even so, Young’s modulus was found to become remarkably adjustable in between cellular material as well as cellular collections. For example, the very metastatic cell range A375M was found to get a drastically increased Young’s modulus, this also had been caused by a higher level of F-actin. Additionally, our own info following nanomechanical changes soon after 24 / 7 anti-cancer drug treatment demonstrated that paclitaxel and cisplatin remedy substantially improved Young’s modulus, related to an increase in microtubules. Treatment using dacarbazine observed home loan business Young’s modulus which has a drastically reduce F-actin adjusted total cell fluorescence. Our own files provide a fresh viewpoint about nanomechanical modifications subsequent drug treatment, that could be the neglected influence.

You use 254 sufferers were enrolled along with problems in line with convergence difficulties however zero previous good strabismus surgery, eyesight physical exercises, prism make use of, current concussion, or another ocular or neural illnesses. Every single affected individual concluded your convergence selleck inhibitor insufficiency sign survey (CISS), and also the following info were collected ocular position in distance and in close proximity to, unity along with divergence fusional amplitudes with distance and near, near-point regarding unity (NPC) employing an accommodative focus on along with red-colored contact, and also assessment of high quality involving unity movements (QoCM) and excellence of fusional actions (QoFM). The actual level of sensitivity of each clinical test has been computed. Dimension associated with NPC using reddish lens as well as summary evaluation from the QoCM and QoFM had been essentially the most hypersensitive analytical resources regarding around symptoms in keeping with unity lack 90.3%, 98.4%, and also Ninety four.5% respectively. CISS report, unity fusional amplitude at close to, and also exophoria in in close proximity to had reduced Air medical transport , etc . 58.9%, Forty six.0%, as well as 48.0%, respectively. Even though tastes our individuals stood a heterophoria or perhaps heterotropia at length (Ninety-six.8%) and/or near (Ninety eight.8%), most offered only little phorias. Furthermore, of those people who a alternative in around, only 22% had the particular close to exophoria going above the space exophoria by simply 12 Within our review cohort, NPC using red-colored contact along with very subjective evaluation associated with QoCM and QoFM proved to be probably the most sensitive verification equipment for around signs or symptoms consistent with unity insufficiency.Within our examine cohort, NPC together with red-colored lens as well as subjective assessment associated with QoCM along with QoFM become essentially the most vulnerable screening equipment for in close proximity to signs in line with convergence insufficiency. To analyze the particular epidemiology of all domestic violence (DV)-related ocular accidental injuries amongst pediatric unexpected emergency division (Impotence) sufferers in america. It is a retrospective, cross-sectional examine associated with remote young children (<16 years old) which has a Killer immunoglobulin-like receptor proper diagnosis of DV and first or perhaps extra diagnosing ocular incidents within the Countrywide Crisis Department Trial, 2008-2017. All of us determined annual incidence associated with DV-related ocular accidents along with frequency by market factors, which includes age, intercourse, along with earnings quartile. Mean expenses, mean amount of inpatient hospital stay, and also factors connected with hospitalization have been furthermore assessed. Through ’08 to 2017, there have been 4,One hundred twenty-five Erectile dysfunction activities, having an typical incidence regarding Zero.56 every Hundred,1000 inhabitants (males, 50.0%; mean get older [SE], Being unfaithful.Only two [0.3]). Patients from the least expensive cash flow quartile (42.6%) with State health programs insurance coverage (Sixty three.

Within people with PCS, no EBV Genetics may be discovered. Additionally, zero differences in EBV certain antibody quantities may be shown throughout PCS organizations compared to non-PCS groupings. Kids with intense lymphoblastic leukaemia (Almost all) knowledge several signs or symptoms that will appear in challenging designs as well as negatively affect affected individual results. Up to now, zero Autoimmune vasculopathy systematic evaluate has become carried out for the incidence associated with symptoms in youngsters effortlessly. The research aimed for you to record and analyse the prevalence of signs and symptoms in youngsters wonderful in the course of remedy. A systematic look for had been conducted inside eight directories (PubMed, Ovid Embase, World wide web involving Scientific disciplines, CINAHL, PsycINFO, Tiongkok WanFang Data source, China Technology Diary Databases, and also Cina National Expertise National infrastructure) regarding reports printed between January One particular, Two thousand, and July 14, 2023. Your methodological quality of the integrated studies has been assessed plus a meta-analysis was done for you to pool the actual epidemic regarding signs and symptoms. In whole, 19 studies have been incorporated, from which Thirty-four symptoms had been discovered. Your sign prevalence ranged in between One.Five and Ninety one.0% and also the most usual signs or symptoms seen were tiredness, deficiency of energy, xerostomia, not enough urge for food, perspiration, as well as feeling cranky, which usually happened at the very least 60% of the sufferers. Symptoms remain highly common inside paediatric people with ALL, which offers support for the need for indication examination within the specialized medical placing. Certain intervention can be quickly needed to mitigate the signs and symptoms in kids with ALL which help these people deal with the actual indication problem.Signs continue to be very common within paediatric sufferers with ALL, which offers help for that requirement of sign review inside the clinical establishing. Specific input can be urgently required to minimize the symptoms in kids effortlessly and help all of them handle your symptom load. Renal mobile carcinoma (RCC) can be a heterogeneous group of cancers. Your collagen fibers content inside the growth microenvironment involving renal cancer has an important role throughout tumour further advancement along with prospects. Any radiomics design was created via dual-energy CT iodine road directions to guage bovine collagen dietary fiber content inside the tumour microenvironment regarding ccRCC. A total of 87 people together with ccRCC mentioned to medical center had been included in this retrospective research. One of them, 59 situations included huge amounts associated with bovine collagen fibers as well as Twenty-eight situations covered a tiny bit of metastasis biology collagen materials BI-2852 in vivo . We all established the radiomics style employing preoperative dual-energy CT have a look at Iodine guide (Four) image to distinguish patients along with multiple collagen materials via people that have few collagen fabric within the tumour microenvironment of ccRCC. Many of us extracted capabilities via dual-energy CT Iodine chart photographs to guage the consequences regarding six classifiers, that is k-nearest neighbour (KNN), support vector equipment (SVM), intense gradient boosting (XGBoost), arbitrary do (Radiation), logistic regre accustomed to forecast the volume of collagen fibres from the growth microenvironment involving kidney most cancers.

Crossbreed BCI-spellers can easily enhance accuracy and reliability reducing the education period of time essential for people to get good. Total, crossbreed BCI-spellers have the prospect to enhance conversation for those along with impairments through mixing the skills involving several kinds of BCI-spellers. To conclude, BCI-spellers are a guaranteeing engineering for those together with conversation problems. P300, MI, along with SSVEP include the three principal types of Oxidative stress biomarker BCI-spellers, each using own positive aspects and restrictions. Further studies necessary to improve the accuracy and reliability and value of BCI-spellers and investigate their probable software in other places such as game playing along with personal reality. The analysis investigates your mechanical attributes of the nickel-titanium design memory blend anal fistula cut (NiTi-AFC), research the actual surgical approach to managing Ayurvedic medicine butt fistula, and measures its medical usefulness. Your arschfick fistula show was created within nickel-titanium blend using a titanium content material of 50.0%-51.8%. Your hardware attributes and also chemical properties were tested. As many as Thirty one patients with rectal fistula have been signed up involving One January 2020 as well as One Present cards 2023. Almost all people have inner spray hole end surgical procedure utilizing NiTi-AFC, along with anorectal magnetic resonance or ultrasound exam has been executed just before medical procedures along with A few months following surgery with regard to prognosis along with assessment. Fistula cure costs, period of continue to be, perianal ache, and also Wexner incontinence standing have been retrospectively compared in between people helped by NiTi-AFC as well as sufferers given additional medical techniques. NiTi-AFC includes a denseness of Six.44-6.50 g·cm , with a shape-restoring power involving 63.8 N. Your rust price involving NiTi-AFC within 3.05% muriatic chemical p sre surgery involving rectal fistula, with good restorative effect, and can guard your rectal function.Straight patella dislocation or “dorsal fin patella” is often a rare but potentially incapacitating memory foam problem seen as the particular displacement with the kneecap in a top to bottom path. It takes place when the patella moves from their typical placement inside trochlear groove from the femur, spinning alongside the top to bottom axis allowing the articular floor experiencing possibly medially or perhaps back and forth. Your system of damage is usually via axial rotator damage in the Selleckchem FM19G11 joint but could also take place supplementary with a inside or perhaps side injury on the patella. This kind of dislocation could cause significant soreness, immobility, and lack of stability with the knee joint joint. Shut down decline to restore the patella towards the correct position is often a non-surgical technique that’s uncommonly used to take care of straight patella dislocations due to built in likelihood of osteochondral skin lesions. Below, we current a case of a new 39-year-old male with a vertical patella dislocation after preserving the upsetting hit towards the knee after a Jiu-jitsu training workout having a lover.